Self-Monitoring of Blood Glucose in Type 2 Diabetes: Systematic Review

ReferencesHealth Technology Assessment 2010; Vol. 14: No. 12 Health Technology Assessment 2010; Vol. 14: No. 12 AppendixAbstract 1 Search strategy and flow of studies List of abbreviations Appendix 2 ExecutiveCharacteristics summary of systematic reviews Background AppendixMain question 3 MethodsCharacteristics of RCTS Results AppendixConclusions 4 Results of RCTs (included in reviews and additional) Self-monitoring of blood glucose in type 2 Chapter 1 AppendixIntroduction 5 diabetes: systematic review BackgroundObservational and non-randomised studies (included in reviews and new) Questions for this review Appendix 6 ChapterCharacteristics 2 and results ofClinical qualitative effectiveness studies of C Clar, K Barnard, E Cummins, P Royle self-blood glucose monitoring HealthMethods Technology Assessment reports published to date and N Waugh for the Aberdeen Health Results Health Technology Assessment Technology Assessment Group Chapterprogramme 3 Self-monitoring of blood glucose: economic literature review Cost studies Quality of life Cost-effectiveness Summary

Chapter 4 Discussion Problems with the evidence base Other reviews Research needs Current or planned research Conclusions

Acknowledgements Contributions of authors About the Aberdeen HTA group

March 2010 DOI: 10.3310/hta14120

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C Clar,1 K Barnard,2 E Cummins,3 P Royle4 and N Waugh5* for the Aberdeen Health Technology Assessment Group

1Researcher in Systematic Reviews, Berlin, Germany 2Health Psychologist, University of Southampton, Southampton, UK 3Health Economist, McMaster Development Consultants, Glasgow, UK 4Research Fellow, University of Aberdeen, Aberdeen, UK 5Professor of Public Health, Department of Public Health, Medical School Buildings, Foresterhill, Aberdeen, UK

*Corresponding author

Declared competing interests of the authors: none

Published March 2010 DOI: 10.3310/hta14120

This report should be referenced as follows:

Clar C, Barnard K, Cummins E, Royle P, Waugh N. Self-monitoring of blood glucose in type 2 diabetes: systematic review. Health Technol Assess 2010;14(12).

Health Technology Assessment is indexed and abstracted in Index Medicus/MEDLINE, Excerpta Medica/EMBASE, Science Citation Index Expanded (SciSearch) and Current Contents/Clinical Medicine. NIHR Health Technology Assessment programme

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The research reported in this issue of the journal was commissioned by the HTA programme on behalf of the Department of Health as project number 09/19/01. The contractual start date was in February 2009. The draft report began editorial review in August 2009 and was accepted for publication in December 2009. As the funder, by devising a commissioning brief, the HTA programme specified the research question and study design. The authors have been wholly responsible for all data collection, analysis and interpretation, and for writing up their work. The HTA editors and publisher have tried to ensure the accuracy of the authors’ report and would like to thank the referees for their constructive comments on the draft document. However, they do not accept liability for damages or losses arising from material published in this report. The views expressed in this publication are those of the authors and not necessarily those of the HTA programme or the Department of Health. Editor-in-Chief: Professor Tom Walley CBE Series Editors: Dr Martin Ashton-Key, Dr Aileen Clarke, Professor Chris Hyde, Dr Tom Marshall, Dr John Powell, Dr Rob Riemsma and Professor Ken Stein ISSN 1366-5278 © 2010 Queen’s Printer and Controller of HMSO This journal may be freely reproduced for the purposes of private research and study and may be included in professional journals provided that suitable acknowledgement is made and the reproduction is not associated with any form of advertising. Applications for commercial reproduction should be addressed to: NETSCC, Health Technology Assessment, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK. Published by Prepress Projects Ltd, Perth, Scotland (www.prepress-projects.co.uk), on behalf of NETSCC, HTA. Printed on acid-free paper in the UK by Henry Ling Ltd, The Dorset Press, Dorchester. G DOI: 10.3310/hta14120 Health Technology Assessment 2010; Vol. 14: No. 12

Abstract Self-monitoring of blood glucose in type 2 diabetes: systematic review C Clar,1 K Barnard,2 E Cummins,3 P Royle4 and N Waugh5* for the Aberdeen Health Technology Assessment Group

Objectives: To examine whether or not self- SMBG, and more intensive SMBG versus no SMBG. monitoring of blood glucose (SMBG) is worthwhile, in Available qualitative data gained from in-depth interview terms of glycaemic control, hypoglycaemia, quality of life studies, repeated interviews, and questionnaire and (QoL) and cost per quality-adjusted life-year (QALY), survey data were summarised. in people with type 2 diabetes (T2DM) who were not Results: The review identified 30 RCTs, although few treated with insulin or who were on basal insulin in were of high quality. Ten trials comparing SMBG with combination with oral agents. no SMBG showed statistically significant reduction in

Data sources: Literature searched included systematic HbA1C of 0.21%, which may not be considered clinically reviews published since 1996, and a systematic review significant. A similar, though not statistically significant and meta-analyses of randomised controlled trials difference, was shown where SMBG with education was (RCTs) identified from the reviews, and from searches compared to SMBG without education or feedback. for more recent trials, along with review of qualitative RCTs showed no consistent effect on hypoglycaemic and economic studies. Search strategies were limited episodes and no impact on medication changes. Review to the English language and to articles published since of cost-effectiveness studies showed that costs of SMBG 1996, and included: databases searched from 1996 to per annum vary considerably (£10–259). Although April 2009 – The Cochrane Library, MEDLINE, EMBASE, some studies assert that SMBG may lead to savings in PsycINFO, Web of Science – limited to meeting health-care costs which may offset the costs of testing, abstracts; and websites. the best analysis to date (DiGEM – Diabetes Glycaemic Review methods: The intervention was self- Education and Monitoring) concluded that SMBG was testing of blood glucose with a meter and test strips. not cost-effective. Qualitative studies revealed that Studies included adult patients with T2DM on any there was a lack of education in how to interpret and oral treatment or combination of regimens, including use the data from SMBG, and that failure to act on the lifestyle, oral agents or once-daily basal insulin. Existing results was common. systematic reviews of SMBG were summarised and Conclusions: The evidence suggested that SMBG is results compared. Evidence synthesis of all of the of limited clinical effectiveness in improving glycaemic studies meeting the inclusion criteria was carried control in people with T2DM on oral agents, or diet out using a narrative review. Data were analysed by alone, and is therefore unlikely to be cost-effective. outcome and subgroups. HbA1c data from RCTs were SMBG may lead to improved glycaemic control only summarised using a meta-analysis. Heterogeneity was in the context of appropriate education – both for calculated using the chi-squared and I2 methods. The patients and health-care professionals – on how to following analyses were carried out: SMBG compared respond to the data, in terms of lifestyle and treatment to self-monitoring of urine glucose, SMBG versus no adjustment. Also, SMBG may be more effective if SMBG, more intensive SMBG versus less intensive patients are able to self-adjust drug treatment. Further iii

research is required on the type of education and frequency of SMBG, and the circumstances under which feedback that are most helpful, characteristics of SMBG causes anxiety and/or depression. patients benefiting most from SMBG, optimal timing and

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Contents

List of abbreviations ...... vii Acknowledgements ...... 47

Executive summary ...... ix References ...... 49

1 Introduction ...... 1 Appendix 1 Search strategy and flow Background ...... 1 of studies ...... 57 Questions for this review ...... 3 Appendix 2 Characteristics of systematic 2 Clinical effectiveness of reviews ...... 59 self-blood glucose monitoring ...... 5 Methods ...... 5 Appendix 3 Characteristics of RCTS ...... 67 Results ...... 7 Appendix 4 Results of RCTs (included 3 Self-monitoring of blood glucose: in reviews and additional) ...... 85 economic literature review ...... 31 Cost studies ...... 31 Appendix 5 Observational and non- Quality of life ...... 32 randomised studies (included in reviews Cost-effectiveness ...... 33 and new) ...... 97 Summary ...... 36 Appendix 6 Characteristics and results 4 Discussion ...... 39 of qualitative studies ...... 111 Problems with the evidence base ...... 39 Other reviews ...... 42 Health Technology Assessment reports Research needs ...... 42 published to date ...... 115 Current or planned research ...... 44 Conclusions ...... 45 Health Technology Assessment programme ...... 137

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List of abbreviations

ADA American Diabetes Association ICER incremental cost-effectiveness AHRQ Agency for Healthcare Research ratio and Quality IQWiG Institut für Qualität BG blood glucose und Wirtschaftlickeit im Gesundheitswesen BMI body mass index LDL low-density lipoprotein CHF Swiss franc MHRA Medicines and Healthcare DiGEM Diabetes Glycaemic Education Products Regulatory Agency and Monitoring NICE National Institute for Health and DTSQ Diabetes Treatment Satisfaction Clinical Excellence Questionnaire NIH National Institutes of Health EASD European Association for the Study of Diabetes NR not reported ESMON Efficacy of Self-MONitoring of NS not significant blood glucose in newly diagnosed OHA oral hypoglycaemic agent type 2 diabetes trial PTC Pathways To Change EQ-5D EuroQol-5D questionnaire QALY quality-adjusted life-year FBG fasting blood glucose QoL quality of life FDA US Food and Drug RCT randomised controlled trial Administration SF-36 Short Form-36 FPG fasting plasma glucose SMBG self-monitoring of blood glucose GPs general practitioners SMUG self-monitoring of urine glucose HbA1c glycosylated/glycated haemoglobin T1DM type 1 diabetes HCPs health-care professionals T2DM type 2 diabetes HDL high-density lipoprotein UKPDS UK Prospective Diabetes Study HTA Health Technology Assessment

All abbreviations that have been used in this report are listed here unless the abbreviation is well known (e.g. NHS), or it has been used only once, or it is a non-standard abbreviation used only in figures/tables/appendices, in which case the abbreviation is defined in the figure legend or in the notes at the end of the table.

vii

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Executive summary

Background relevant outcomes, and cost per quality-adjusted life-year (QALY)? The prevalence of type 2 diabetes (T2DM) has been rising in the UK, and around 4% of the population now have the condition. Methods

Good control of blood glucose level is important in Review of systematic reviews published since 1996, preventing or delaying the complications of T2DM, and a systematic review and meta-analyses of such as heart disease, peripheral vascular disease, randomised controlled trials (RCTs) identified from visual loss and renal failure. the reviews, and from searches for more recent trials. Review of qualitative and economic studies. However, many people with T2DM do not have good control of their blood glucose. Search strategy

The usual method for monitoring glycaemic • Electronic databases: including The Cochrane control is by measuring glycated haemoglobin, or Library [all sections] (Issue 2, 2009),

HbA1c, which gives an average of the blood glucose MEDLINE (1996–April 2009), EMBASE over 3 months. If it is high then control needs to be (1996–April 2009), PsycINFO (1996–April improved. The National Institute for Health and 2009), Web of Science – limited to meeting Clinical Excellence (NICE) recommends that most abstracts (1996–April 2009). people with T2DM should aim to keep their HbA1c • Websites of the European Association for level at 6.5% or under, though targets should be the Study of Diabetes (EASD), the American tailored to the individual. Diabetes Association (ADA) and Diabetes UK searched for meeting abstracts in April 2009.

However, HbA1c level does not tell patients what • Websites of the US Food and Drug their blood glucose is doing on a day-to-day basis. Administration (FDA), the Medicines and Self-monitoring by testing for urinary glucose is Healthcare Products Regulatory Agency one way of checking when blood glucose is high, (MHRA), Self-Monitoring of Blood Glucose but is only a rough guide. A more accurate measure (SMBG) International Working Group, Current can be obtained by blood testing, which is done by Controlled Trials, and ClinicalTrials.gov pricking the skin to get a drop of blood, putting • Contact with experts in the field. that blood on a testing strip, and reading the result • Scrutiny of bibliographies of retrieved papers. with a small meter. This can be done at different times of day, before or after meals, or before or The searches were limited to the English language after physical activity. and to articles published since 1996, due to the number of recent good quality systematic reviews Meters are cheap (about £14), and the NHS and in order to reflect current meter technologies. requires manufacturers to provide them free of The search strategy did not include limits for charge if needed, so the main cost is the test strips, study design, as all types of studies were screened at about £14 for a pack of 50. manually for potential inclusion.

Main question Results Systematic reviews Is self-monitoring of blood glucose worthwhile in people with T2DM who are not treated with insulin We found 11 systematic reviews published in the or who are on only basal insulin in combination last 10 years, most in the last few years. Most were with oral agents, in terms of glycaemic control, of good quality. They contained from three to 13 hypoglycaemia, quality of life (QoL) and other RCTs out of a total of 20. Their conclusions on ix

glycaemic control varied, with some saying there adverse effect on anxiety and/or depression. Results was no benefit, others saying there was benefit, and from other studies were less clear cut. some saying that there was no conclusive evidence of benefit. Much of the apparent disagreement may Observational studies arise from the level of HbA1c that was considered to prove benefit, since the differences in meta-analysis There were 36 relevant observational studies. were often of the order of 0.2%, which can be These are more prone to bias, from confounding statistically significant, but not clinically important. factors, and association does not necessarily mean

There was some evidence that studies in which cause. Eighteen showed no difference in HbA1c patients were given feedback in response to SMBG level, 12 showed a reduction (but often very small),

values and/or in which SMBG results were used to and some showed an increase in HbA1c level on modify therapeutic regimens were more effective SMBG, which may be because SMBG was started as than those without feedback or use of SMBG for a result of poor glycaemic control. therapy modification. Effects also tended to be

larger for patients with higher baseline HbA1c Qualitative studies values. The qualitative studies had some fairly consistent Randomised controlled trials messages:

We found 26 RCTs, ranging in size from under • There was a lack of education in how to 30 to over 800 patients, and in duration from 12 interpret and use the data from SMBG. weeks to 30 months. Only four trials scored highly • In some patients, SMBG caused adverse on quality assessment. Components of the SMBG psychological effects, including depression and interventions were not well described in many self-chastisement, whereas others found it a cases. Half of the trials reported a reduction in useful tool for reassurance, assessing effects of

HbA1c level, and all those that did find favourable behaviour and empowerment. results included an educational component and/or • There was a lack of education in how to feedback. interpret and use the data from SMBG. • There was a lack of interest in the results from Ten trials compared ‘simple’ SMBG with no SMBG, health-care professionals (HCPs).

and found a reduction in HbA1c level of 0.21%, • Failure to act on the results was common. which was statistically significant but of doubtful clinical significance. Four trials of ‘enhanced’ The cost-effectiveness literature SMBG (for example with education, feedback, etc.)

showed a bigger reduction in HbA1c level – 0.52% There was a mixture of studies: some just about compared with no-SMBG. When SMBG enhanced costs, some looking at possible savings and others with an educational or feedback component was at cost-effectiveness. Some were funded by the compared to simple SMBG (five trials), there was manufacturers of testing strips and meters; these

an HbA1c reduction of 0.2%, however, this was not tended to be more favourable by making more

statistically significant. generous assumptions on the effect on HbA1c level.

Three RCTs showed no difference between SMBG The cost of SMBG in people with T2DM in and urine testing. England is uncertain, but probably around £30M per year, of which at least half could be saved by Differences in the frequency of hypoglycaemic adhering to previous guidelines and by applying episodes were inconsistent. There was no difference the findings of DiGEM in the sulphonylurea-only in weight or body mass index (BMI). There was group. no increase in medication changes with SMBG

versus no SMBG, which may explain why HbA1c The reported costs per annum of SMBG vary is not improved. Few studies examined quality of amongst studies from £10 to £259, the lowest being life (QoL), but the two best ones for this outcome an estimate about £10 per year for infrequent [both from the UK, DiGEM (Diabetes Glycaemic testers on diet alone. Education and Monitoring) and ESMON (Efficacy of Self MONitoring of blood glucose in newly Several studies asserted that SMBG can lead to diagnosed type 2 diabetes trial)] reported a net savings that offset testing costs, and some estimated x DOI: 10.3310/hta14120 Health Technology Assessment 2010; Vol. 14: No. 12

that SMBG could lead to savings from reduced glycaemic control in people with T2DM on oral costs in other health care. These studies tended to agents, or diet alone, and is therefore unlikely to be have more optimistic assumptions. cost-effective. There were insufficient data for those on a single basal insulin to reach any conclusion. However, most of these studies failed to allow No data are available on the possible benefits of for the potentially negative impact of SMBG on SMBG in selected patient subgroups. SMBG can aspects of QoL. be expected to lead to improved glycaemic control only in the context of appropriate education – both The cost-effectiveness analyses vary in their for patients and HCPs – on how to respond to assumptions, with those funded by industry the readings, in terms of lifestyle and treatment producing lower incremental cost-effectiveness adjustment. It may be more effective if patients are ratios (ICERs). The best analysis to date was that able to self-adjust drug treatment. from the DiGEM trial (funded by the UK Health Technology Assessment programme), which, after In the authors’ opinion, at a time when funds are taking into account all costs, gains and disutilities, scarce, the case for investment in blood glucose concluded that SMBG was not cost-effective. monitoring in T2DM, in patients who are not treated with insulin, is not proven. Further research is required on the type of education and feedback Conclusions that are most helpful, characteristics of patients benefiting most from SMBG, optimal timing and The current evidence suggests that SMBG is frequency of SMBG, and the circumstances under of limited clinical effectiveness in improving which SMBG causes anxiety and/or depression.

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Chapter 1 Introduction

Background Each step in the treatment pathway is triggered Type 2 diabetes and its by rising blood glucose levels. The National Institute for Health and Clinical Excellence (NICE) treatment guideline CG661 recommends that the target

Type 2 diabetes (T2DM) is usually seen in people should usually be a glycated haemoglobin (HbA1c) who are overweight or obese, and the prevalence level of 6.5% or less. HbA1c is a blood test, taken by is increasing. In most patients it is a progressive a doctor or nurse, and measured in a laboratory, disease, in the sense that treatment starts with and gives average blood glucose levels over the past diet and other lifestyle measures, such as physical 2–3 months. The HbA1c test measures the amount activity, but that tablet therapy is soon required, of glucose attached to the haemoglobin molecule. and progression to needing insulin is common as time passes. This is not invariable, in that some If not well controlled, diabetes will increase the people manage to lose weight and be physically risk of heart disease, blindness, renal failure, active and may not progress to needing intensified amputation and other complications, so patients treatment. need to keep their blood glucose under as good control as possible. To do so, they need to know

The problems underlying progression of disease what it is. They will usually have their HbA1c level are twofold. Firstly, overweight and obesity measured at intervals, which will let them know make the body less sensitive to insulin (‘insulin if control is poor. However, HbA1c level, being an resistance’), so that the pancreas needs to produce average, will not explain why control is poor. Blood more to keep blood glucose levels normal. glucose can fluctuate from hour to hour, and blood Secondly, there is progressive failure of the function glucose testing with meters and strips can identify of the beta cells in the pancreas, so that insulin the times when blood glucose is too high. It can production cannot be maintained. By the time also be used to check on when the level might be someone is diagnosed with T2DM, they have going too low – hypoglycaemia or hypoglycaemic usually lost about half of their beta-cell capacity. episodes.

Progression may mean that patients go through the Self-monitoring of blood glucose following treatment stages: Nowadays, patients can measure their blood • Diet and physical activity, aiming to achieve glucose level by putting a drop of blood on to a weight loss and reduce insulin needs and test strip, and using a meter to read colour changes resistance. in that. This is painful as patients are required to • Treatment with a single oral drug, usually prick their finger with a lancet to obtain a blood metformin. sample. The strips are cumulatively expensive, • Treatment with two oral drugs, usually by with the average cost2 being £14.57 for a 50-strip adding a sulphonylurea to the metformin. pack. The meters are inexpensive at an average • Treatment with three oral drugs. cost of £14.68 (2009 price) [and the NHS requires • The addition of insulin, usually with a once- manufacturers to provide them free of charge for daily long-acting (‘basal’) insulin, taken along distribution to patients as considered appropriate with metformin and a perhaps reduced dose of by health-care professionals (HCPs)]. Knowledge of sulphonylurea. high blood glucose levels may cause anxiety, and • When that fails, moving to more complex fear of the long-term complications. However, it insulin regimens, such as adding short- can also give patients information that they can use acting insulin at mealtimes, or twice-daily to improve control of their blood glucose. They can mixed insulins, with the sulphonylurea being also measure the amount of glucose in their urine, discontinued. which is a guide to blood glucose level. Urine

glucose tests only detect glucose in the urine once it still remains a controversial area. So, the first blood levels are above the renal threshold (around question may be – why is there still a question? 10 mmol/l), so hypoglycaemia cannot be detected. Similarly, urine tests cannot detect the degree of There are (at least) five possible answers to that. hyperglycaemia. Firstly, the evidence is to some extent conflicting, A number of assumptions are made when with different types of study design giving different proposing self-monitoring of blood glucose results. There is also the issue of what harm it may (SMBG) as an effective tool for blood glucose do. Studies have shown that SMBG can increase control, as outlined by McAndrew et al. (2007).3 anxiety. The authors suggest that the efficacy of SMBG would depend on whether the interventions Secondly, as with other diagnostic interventions, created a patient-centred behavioural control there is a hierarchy of questions; system that would address the patient’s skills in: • The technical level – does it accurately measure • taking a blood glucose reading what it is supposed to? • interpreting the reading as a target for action • The treatment level – does SMBG lead to • perceiving linkages between specific behaviours changes in treatment? (diet, exercise) and the reading (i.e. which • The outcomes level – does SMBG reduce the behaviours lower an above-target reading and risk of heart disease, visual loss, etc.? which raise a below-target reading) – ideally, the linkage would also act as a motivator to Thirdly, SMBG is not an end in itself, but only an change behaviour aid to management, and another question is ‘who • implementing action plans (i.e. behavioural uses the results?’. Do the patients record the results and treatment adjustments) in response to and bring them to the clinic or surgery to discuss SMBG the implications, so that the doctor or nurse can • giving less weight to subjective symptoms that adjust treatment accordingly? Or do the patients are the basis for commonsense decisions that use the information themselves and self-adjust diet, one is sick or well, as these cues are invalid or doses of oral drugs or insulin? guides for the regulation of blood glucose levels Fourthly, if patients are going to self-adjust • incorporating the behavioural system into the management, are they given sufficient education patient’s ongoing daily behavioural patterns to with which to do that? eventually become automatic • viewing difficulties in achieving control as Fifthly, knowledge alone does not always lead issues of adjusting the behavioural treatment, to action. Education might have two strands – not deficits in personal motivation or knowledge of how to adjust treatment, but also competence for self-management. ‘motivational knowledge’ that makes people understand the importance of good control. Table 1 suggests possible facilitators and barriers to SMBG as an effective diabetes management tool. Also, is there a relationship between adherence to medication, and likelihood of SMBG improving

The volume and costs of prescriptions for blood HbA1c level? If people are not adhering to a diet, glucose monitoring in England has risen steadily exercise regimen or oral medication as prescribed over the last 6 years. The last figures available4 are (one study reported that only 35% of people for the quarter July–September 2008, when the adhere to any medication regimen on average6) cost was £34M, which gives a projected annual cost then what effect will SMBG have on patient of almost £140M. This compares with ~£107M in perception of disease severity and/or importance 2002.5 However, one would expect that much of of adherence generally? Some patients report in this will be for people with type 1 diabetes (T1DM). the qualitative studies7–9 that low SMBG readings give them the impression that they are fine. What The SMBG controversy impact does this have on adherence to therapy, diet and exercise? It is also not clear whether patients There have been several recent trials and are instructed to monitor because they were in poor systematic reviews to evaluate the clinical control initially or because they are given a tool to effectiveness and cost-effectiveness of SMBG, but assist self-management. 2 DOI: 10.3310/hta14120 Health Technology Assessment 2010; Vol. 14: No. 12

TABLE 1 Facilitators and barriers to SMBG

Consequences

Facilitators Barriers Patients Health-care providers Instruction in SMBG use Negative message: internal Direct feedback of effects of Readings facilitate Accuracy checks and (failure of self) or external certain lifestyle behaviours individualised treatment adherence checks Lack of instruction/education on glucose values – learning of patient/treatment – lack of understanding effects of physiological adjustments Integrated into patient consequences of, for education so that patients Lack of integration into example, eating certain foods can understand and use management Improved short- and long- SMBG information in a wider People don’t like pricking context term clinical outcomes if fingers – and ‘dose’ of SMBG readings are adequately acted Positive messages may be inappropriate cost upon Made easy for patient – ease Improved control/ of access and convenient empowerment – patients regimen have more possibilities to Feedback on self-monitoring make changes to influence and clear messages regarding disease positively treatment/behaviour changes as a consequence of readings

The NICE clinical guideline1 on the management – but did not mention that it was funded by the of T2DM, which was written before the two recent manufacturers of meters. As discussed in Chapter trials [DiGEM10–12 (Diabetes Glycaemic Education 3, it may be unduly favourable to SMBG. The cost- and Monitoring) and ESMON13 (Efficacy of Self effectiveness results from the DiGEM trial came MONitoring of blood glucose in newly diagnosed out too late to be included in the NICE review. It type 2 diabetes trial)] had reported, supported is not clear why other economics studies were not SMBG in certain circumstances. It recommended included. that SMGB should be available to newly diagnosed patients (recommendation 22), and to those on The guideline commented that past research insulin and oral agents (recommendation 23). had failed ‘to address the complicated issue of its integration into patient education and self- The evidence base for these recommendations management behaviours’. was based mainly on two observational studies, from the Kaiser Permanente14 study and the ROSSO (RetrOlective Study: Self-monitoring Questions for this review of blood glucose and Outcome in patients with Primary question type 2 diabetes) study.15 Two other observational studies by Wen et al.16 and Davis et al.17–19 were also Is SMBG worthwhile in patients, or selected mentioned, as were two randomised controlled patients, with T2DM: trials (RCTs).20,21 The evidence cut-off date was before the DiGEM study was published, and well • on diet alone before the ESMON one. However, the NICE • on metformin monotherapy Guideline Development Group was clearly aware • on combination oral therapy of the DiGEM study, and discounted it because • on combinations of oral therapy and basal ‘a study which viewed self-monitoring as a stand- insulin? alone intervention, and not as an element of a full educational programme, could not properly inform By ‘worthwhile’, we mean whether it provides the appropriate use of self-monitoring’. This seems clinical benefits, such as improved glycaemic curious, as the third arm of the DIGEM study control, fewer hypoglycaemic episodes or quality of included patient education and motivation. life (QoL), at a cost that makes it cost-effective.

The NICE evidence review mentions only one For the purposes of this review, we have assumed economic study of SMBG – that by Palmer et al.22 that, in line with NICE guidance,9 SMBG is

worthwhile in those on more complicated insulin • What education is required to enable the regimens, such as basal + mealtimes or twice-daily patients, and their HCPs, to use the SMBG mixed insulin, and the evidence on that was not results to improve their diabetes control? examined. • How do we motivate those groups of patients that could benefit from SMBG to use it to Additional questions improve their diabetes control? • For those patients for whom SMBG is shown • Which sub-groups of patients benefit most from to be worthwhile, a subsidiary question might SMBG? be how to best deliver SMBG (in terms of • Which are harmed? frequency and quality of testing, education, use of results, costs)?

4 DOI: 10.3310/hta14120 Health Technology Assessment 2010; Vol. 14: No. 12

Chapter 2 Clinical effectiveness of self-blood glucose monitoring

Methods • Exclusion criteria: –– pregnant women with diabetes A protocol was produced and approved by the –– studies in which some patients had T1DM Health Technology Assessment (HTA) programme and results were not given separately before the start of this review. It is available on –– studies in people on complex insulin the HTA programme website (www.ncchta.org/ regimens. protocols/200900190001). Place of self-monitoring of blood glucose Criteria considered for Evidence from existing reviews suggests that not all synthesis of evidence of clinical groups of patients benefit. effectiveness Intervention Patients could be grouped by: Self-testing of blood glucose with a meter and test • type of treatment, i.e. diet alone, strips. metformin monotherapy, dual therapy (metformin + sulphonylurea), triple oral Relevant comparators therapy, the combination of once-daily basal The comparators were: insulin + oral therapy

• baseline HbA1c level • self-monitoring of urine glucose (SMUG) • duration of diabetes

• monitoring with HbA1c • age • a combination of the above • patient preference (patients who feel that • comparisons of SMBG of different intensities SMBG will benefit and empower them might (either in terms of frequency or additional do better than patients who are reluctant to use education, feedback or similar). SMBG – determined by patient self-report) • previous use of SMBG A review of the evidence for clinical effectiveness • levels of education was undertaken systematically following the • motivation for self-care (e.g. as determined general principles recommended in the using instruments related to an information- QUOROM (Quality of Reporting of Meta-analyses) motivation-behavioural skills model of diabetes statement.23 self-care).

Population Outcomes

• Inclusion criteria: • HbA1c level. –– studies including adult patients with T2DM • Hypoglycaemia. on any oral treatment or combination of • Quality of life, anxiety, depression. regimens, including lifestyle, oral agents or • Costs. once-daily basal insulin • Treatment satisfaction. –– minimum duration of study was 12 weeks • Weight. (as it may take longer for people using • Treatment change in response to measurement SMBG to assess the effects of changes and (insulin dose, oral drug use, diet, exercise). fine tune their treatment, a trial giving • Lipids (patients who adjust their diet in order a positive result at 12 weeks would give to control hyperglycaemia may improve useful information. However, a negative cholesterol levels as a by-product). result at 12 weeks would not be regarded as • Blood pressure. proof that SMBG was ineffective)

• In theory, complications such as retinopathy • scrutiny of bibliographies of retrieved papers. would be reported, but, realistically, very few studies would be long enough. The searches were limited to the English language and to articles published since 1996 (due to the Technical issues related to SMBG were considered, number of recent good quality systematic reviews) but based only on reports in existing systematic and in order to reflect current meter technologies. reviews. The search strategy did not include limits for Study type study design, as all types of studies were screened • Inclusion criteria: manually for potential inclusion. Selection was –– For the review of clinical effectiveness, only carried out independently by two reviewers. systematic reviews and RCTs were included. –– Large observational studies (500 A separate search strategy for cost-effectiveness participants or more) of adequate duration studies was performed and comprised searches and published as full text articles were of the following electronic databases: MEDLINE included for information on adverse (1996–June 2009), EMBASE (1996–June 2009), events, longer-term outcomes (e.g. Web of Science with Conference Proceedings – cardiovascular events, retinopathy) and limited to meeting abstracts (1996–June 2009), qualitative issues (motivation, adherence Cochrane Library (Issue 2, 2009). and QoL, patient preferences). –– Editorials, letters in journals, and small Appendix 1 gives details of the search strategies observational studies would be discussed and flow of studies. if they threw light on the reasons for controversy. Quality assessment strategy –– Titles and abstracts were examined for inclusion by two reviewers independently. Consideration of study quality for systematic Disagreement was resolved by consensus. reviews and trials included the following factors • Exclusion criteria: [based on key criteria of the QUOROM and –– non-English language papers CONSORT (Consolidated Standards of Reporting –– papers published pre-1996 Trials) statements]. –– reports published as meeting abstracts only, where insufficient methodological Systematic reviews details were reported to allow critical • Were inclusion/exclusion criteria that addressed appraisal of study quality. the review question reported? • Were details of the literature search given? Search strategy • Was study selection described and study flow shown? The search strategy comprised the following • Was data extraction described? searches: • Was the validity of the included studies assessed? • electronic databases: including The Cochrane • Were sufficient details about the individual Library (all sections) (Issue 2, 2009), included studies presented (characteristics, MEDLINE (1996–April 2009), EMBASE quality and results)? (1996–April 2009), PsycINFO (1996–April • Was the statistical analysis appropriate? 2009), Web of Science – limited to meeting abstracts (1996–April 2009) Quality was rated as ‘high’ if no more than one of • websites of the European Association for the the quality criteria was not clearly fulfilled. Quality Study of Diabetes (EASD), American Diabetes was rated as ‘moderate’ if two of the quality criteria Association (ADA) and Diabetes UK searched were not clearly fulfilled (or three including study for meeting abstracts in April 2009. flow), and as ‘poor’ if more than two quality criteria • websites of the US Food and Drug were not fulfilled. Administration (FDA), Medicines and Healthcare Products Regulatory Agency Randomised controlled trials (MHRA), SMBG International Working Group, • Adequate description of trial design and Current Controlled Trials, ClinicalTrials.gov participants. • contact with experts in the field • Method of randomisation. 6 DOI: 10.3310/hta14120 Health Technology Assessment 2010; Vol. 14: No. 12

• Allocation concealment. • Did patients receive education about SMBG: • Blinding of outcome assessment. –– about how to do SMBG (use of equipment, • Adequate power. etc.) • Numbers of participants randomised, excluded –– about how to interpret results and how to and lost to follow-up reported. respond • Intention-to-treat analysis performed, methods –– who carried out the education? for handling missing data given. • Were the accuracy and frequency of monitoring • Appropriateness of statistical analysis. (i.e. adherence) checked? (and by whom?) • Baseline characteristics similar. • How the monitoring results were used: • Funding of study. –– for behaviour change by the patient –– for treatment (medication) adjustment by Quality was rated as ‘high’ if no more than one the patient of the quality criteria was not clearly fulfilled. –– for treatment (medication) adjustment by a Quality was rated as ‘moderate’ if two or three of doctor (or nurse) the quality criteria were not clearly fulfilled, and as –– was feedback on monitoring results given? ‘poor’ if more than three quality criteria were not (if so, what kind?) fulfilled. • What message did the patients receive? –– For example, that monitoring helped Methods of analysis/synthesis people gain control of their disease and that there was no reason to feel guilty Initially, existing systematic reviews of SMBG were about off-range values or that off-range summarised and results compared. Reasons for values were a bad thing differences between the reviews were investigated –– Did patients get the impression that their and possible reasons for conflicting results were doctor/nurse thought monitoring was a investigated in a narrative review. Any RCTs and good thing and took note of the values? observational studies that were not included in the • How does benefit of SMBG vary by: existing systematic reviews were data extracted and –– starting HbA1c level (or stable/well included. Details of any RCTs and observational controlled versus poor control) studies included in the reviews were tabulated as far –– frequency of monitoring as reported in the reviews. Where there were doubts –– (type of) education regarding the accuracy of the information in the –– susceptibility to (unnoticed) hypoglycaemia reviews or where there was missing information, –– treatment (sulphonylureas versus other) data were verified using the original papers. –– age –– time point during the course of the disease Evidence synthesis of all of the studies meeting our (e.g. after diagnosis, during treatment inclusion criteria was carried out using a narrative change, at other times)? review. Data were to be analysed by outcome and subgroups as outlined above. HbA1c data from RCTs were summarised using a meta-analysis Results (weighted mean differences, random effects model, Functionality issues inverse variance method). Heterogeneity was calculated using the chi-squared and I2 methods. Technical issues were discussed in the HTA report by Coster et al.:24 The following analyses were carried out: SMBG compared to SMUG, SMBG versus no SMBG (in • They evaluated a sample of studies on device studies, where different intensities of SMBG were validation, which suggested that issues of compared to no SMBG, this comparison included observer training, interdevice variability, effects the less intensive SMBG intervention), more of long-term use and patient acceptability were intensive SMBG (e.g. more frequent, enhanced not usually addressed. by special education elements, etc.) versus less • Some evidence [Brunner et al. (1998)]25 intensive SMBG, and more intensive SMBG versus suggests that meter performance may be less no SMBG. satisfactory in the low glycaemic range and that there is some variation in the size and direction Relevant studies were examined with respect to the of measurement bias in different parts of the following aspects: glycaemic range.

• Development of memory meters showed that reviews, and Table 5 shows the results of any meta- patients often make incomplete and incorrect analyses reported in the reviews. recordings of blood glucose values in their diary records; sources of inaccurate readings Only two reviews were not of high or moderate include rounding values to the nearest whole quality.28,30 Six reviews24,29,31,34,36,38 included a meta- number, omission of outlying values, reporting analysis of RCTs, of which several performed results when no test was recorded by the meter; subgroup analyses, for example based on trial over- and under-reporting often occurred duration of whether patients received feedback on together and was associated with higher their SMBG results or not. Most reviews focused on

HbA1c values and poor testing technique; T2DM, with some excluding trials in insulin-treated occurrence of hypo- and hyperglycaemia was patients. The trials included mostly compared often obscured; informing patients of memory SMBG with no SMBG. Three trials40,47,56 compared function of the meter led to correct readings.26 SMBG with SMUG (urine monitoring), and nine • In some patients readings may be inaccurate trials10,11,42–44,46,50,55,59–61 compared a more intensive because wide variations in blood glucose values SMBG intervention with a less intensive one. between readings go unnoticed. • Evidence that more accurate blood glucose The systematic reviews provided evidence both readings may be obtained if patients are given in support of the benefits of SMBG and evidence sufficient training – need for formal training that it can be associated with increased anxiety and and updating of skills in the use of meters, levels of depression in users. However, the size of especially in people with special needs. benefit was often very small and below the change

• Further work should be done to develop in HbA1c level that is usually considered clinically standard packages to train patients in the use significant (0.5% – although this is a somewhat of self-monitoring devices and to provide them arbitrary figure). There is a lack of evidence on why with the information needed to adjust their SMBG clearly does not work for some patients, and therapy in accordance with self-monitoring on which patients are most likely to benefit from results. the technology. Results are presented addressing

outcome measures such as HbA1c level, rather than No more recent systematic reviews were found. exploring issues predicting success or failure, and There is some indication that devices are becoming there is little exploration of either accuracy of more reliable.27 results or whether behaviour/therapy changes are made based on those results. Furthermore, there is Systematic reviews and included little evidence in the literature regarding the way RCTs in which HCPs collaborate with patients regarding how to interpret and act on readings. There were 112,24,28–38 mostly high-quality reviews. The number of RCTs included ranged from 3 to 13 Mixed results were reported among systematic

out of a total of 20 referenced RCTs (of which two reviews in terms of improvements in HbA1c level were not strictly RCTs), as shown in Table 2. Our with SMBG compared to no monitoring. Five searches identified six additional RCTs (also shown reviews include a meta-analysis,24,29,31,34,37 with in Table 2), of which two were published as abstracts the newer ones all showing some significant 42,53 only. reduction of HbA1c level in the SMBG groups versus control (between –0.21% and –0.42%). Four of the reviews also included a range of 6–18 Towfigh et al. (2008),35 however, found only a short-

non-randomised/observational studies. [Agency for term significant reduction of HbA1c at 6 months Healthcare Research and Quality (AHRQ; 2007),28 but this was not sustained after a year or more. McAndrew et al. (2007),2 McGeoch et al. (2007)32 The Bayesian meta-analysis (including indirect and St John et al. (2009)38]. Appendix 2 gives the comparisons) by Jansen et al. (2006)31 found a characteristics of the systematic reviews. reduction of –1.13% with SMBG plus feedback given to patients versus no self-monitoring. This Table 3 shows 31 observational or difference is much larger than those from other pseudoexperimental studies included in four of the reviews, and may be due to the use of indirect systematic reviews,2,28,32,38 and another five relevant comparisons. Poolsup et al. (2008)33 found a 67,82,88,92,94 studies were identified which were not significant difference in HbA1c level overall (–0.24% included in any of the reviews (three published as SMBG versus no SMBG), but, when comparing abstracts only). Table 4 shows the conclusions of the trials where SMBG results were used to modify 8

DOI: 10.3310/hta14120 Health Technology Assessment 2010; Vol. 14: No. 12 Additional

Yes Yes Yes Yes Yes Yes

(2009)

38 St John John St

Yes Yes Yes Yes Yes Yes Yes

(2008)

35 Towfigh Towfigh

Yes Yes Yes Yes Yes Yes Yes Yes Yes

(2008)

33 Poolsup Poolsup

Yes Yes Yes Yes Yes Yes Yes

(2007)

32 McGeoch McGeoch

Yes Yes Yes

(2007)

2 McAndrew McAndrew

Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes

(2006)

31 Jansen Jansen

Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes

(2005)

36,37 Welschen Welschen

Yes Yes Yes Yes Yes Yes

(2005)

34,39 Sarol Sarol

Yes Yes Yes Yes Yes Yes Yes Yes

HTA)

24,29

(NHS (NHS

(2000) (2000) Coster Coster

Yes Yes Yes Yes Yes Yes Yes Yes

(1997)

30 Faas Faas

Yes Yes Yes Yes Yes Yes

(2007)

28 AHRQ AHRQ Systematic reviews Yes Yes Yes Yes (but judged to be Yes non-randomised) (but judged to be Yes non-randomised) Yes 59,60 57 47 (abstract) 61 20 45 48 42 51 13 41 10,11 54 58 62 49 43 55 63 52 46 40 56 50 (abstract) 44 53 Randomised controlled trials reviews) (plus additional RCTs not includedRandomised controlled (RCTs) – included in previous in reviews Agency for Healthcare Research and Quality. Research Healthcare Agency for

Estey (1990) Estey Jaber (1996) Seaton (1996) Brown (2002) Brown Johnson (2006) Johnson Miles (1997) Davidson (2005) Davidson (2003) Jones (2003) Joy (2002) Schwedes Cho (2006) Muchmore (1994) Muchmore Wing (1986) Fontbonne (1989) Fontbonne AHRQ, Farmer (2007) (2003) Guerci Barnett (2008) O’Kane (2008) Kibriya (1999) RCTs Allen (1990) Gallichan (1994) Scherbaum (2008) Kwon (2004) Kwon (2006) Moreland Bonomo (2006) Rutten (1990)

TABLE 2 TABLE 9

TABLE 3 Observational/pseudoexperimental studies included in reviews in T2DM

Systematic reviews

AHRQ McGeoch McAndrew St John Observational study (2007)a,28 (2007)32 (2007)2 (2009)38 Additional Bajakowska- Yes Fiedziukiewicz (2008)64 Banister (2004)65 Yes Blonde (2002)66 Yes Yes Capelson (2006)67 Yes (abstract) Chan (2000)68 Yes Davis (2006)18,19 Yes Yes Evans (1999)69 Yes Franciosi (2001)70 Yes Yes Franciosi (2005)71 Yes Yes Yes Hanninen (2001)72 Yes Harris (2001)73 Yes Yes Yes Jaworska (2004)74 Yes Karter (2001)75 Yes Yes Yes Karter (2005)76 Yes Karter (2006)14 Yes Yes Klein (1993)77 Yes Martin (2006)15,78 Yes Meier (2002)79 Yes Yes Yes Mitchell (2004)80 Yes Murata (2003)81 Yes Murata (2009)82 Yes Newman (1990)83 Yes Oki (1997)84 Yes Ozmen (2003)85 Yes Patrick (1994)86 Yes Rindone (1997)87 Yes Yes Yes Roblin (2001)88 (abstract) Yes Rost (1990)89 Yes Schiel (1999)90 Yes Schütt (2006)91 Yes Yes Secnik (2007)92 Yes Soumerai (2004)93 Yes Yes Yes Stiptzarov (2003)94 Yes (abstract) Tengblad (2007)95 Yes Wen (2004)16 Yes Yes Wieland (1997)96 Yes Yes

AHRQ, Agency for Healthcare Research and Quality. a Classified two of the RCTs as non-randomised and included one study not relevant to this review, so only three out of six studies are shown in the table.

10 DOI: 10.3310/hta14120 Health Technology Assessment 2010; Vol. 14: No. 12

therapeutic regimens with those that did not, • SMBG accuracy checks were not carried out only the results for the former were statistically in the majority of trials therefore it cannot significant and the difference (–0.27%) was not be known whether readings represented clinically significant. There was no significant an accurate reflection of blood glucose. difference between SMBG and urine monitoring. Furthermore, McGeoch et al. (2007)32 raises Some of the reviews reported results on weight questions about whether some participants are and showed that there was no significant effect of sufficiently literate and numerate to be able to SMBG versus no monitoring on weight. take advantage of the intervention. • Only a very limited range of outcomes was

Reviews tended to focus on comparisons between reported – mainly HbA1c level, with few

SMBG and no SMBG and on trials reporting HbA1c reviews reporting weight, hypoglycaemia, level as an outcome. There was less consideration QoL or adverse effects. Behaviour change was of studies looking at different modes of using acknowledged; however, the extent to which SMBG, for example frequency, duration of behaviour was adjusted or specific adjustments monitoring, purpose, etc. This could potentially remains unclear. highlight why some of the important components • Many included trials were of poor quality, i.e. of a successful SMBG intervention are not fully sample sizes were often small and many trials explored. Features predicting success/failure had short follow-up times. Randomisation include: techniques were not described in many studies.24,29,34 The study by Worth et al.,97 • The SMBG regimens used in the trials were as reported in a review by Coster et al.,24,29 very different, ranging from 6 times per day for suggests that the main benefit of self- 6 days per week, to less frequent regimens or monitoring was an educational modality, no fixed regimen, i.e. at patient’s discretion. leading to increased contact time with diabetes • Most trials did not give any details on changes care staff and greater motivation. Any effects made to therapy or lifestyle based on SMBG were short-lived and future research should results;32 in some trials, therapy changes were focus on long-term results. made by physician/nurse but the patient was not allowed to change anything. No trials None of the systematic reviews addressed variations reported patients being actively encouraged in benefit from SMBG by frequency of monitoring, to make behaviour/lifestyle changes based on type of education, susceptibility to hypoglycaemia,

results of SMBG. treatment, age, starting HbA1c level or time points • No feedback on results was given to patients. during the course of diabetes (for example after There appears to be difference in expectation diagnosis, during treatment change, etc.). One between HCPs and patients, in that patients review noted that SMBG had no clear benefit on

expect HCPs to make decisions based on the HbA1c level in a number of observational studies readings they provide, whereas HCPs see but did have some in RCTs.2 Furthermore, in SMBG as a tool for patients to make behaviour/ one study,40 reported in a review by McAndrew lifestyle changes. et al.,2 there was a trend towards younger and • SMBG readings were taken at inappropriate better-educated participants improving more with times and so it was impossible to gain SMBG. The prevalence of T2DM in ever younger meaningful results.38 patients needs to be explored in terms of use and • Efficacy of SMBG may be lower when baseline effectiveness of SMBG because if there are no

HbA1c level is higher, i.e. SMBG may be least apparent benefits, yet individuals are encouraged effective for those who need it most.35 This to continue testing, the long-term financial costs could be because at higher levels they have are going to be enormous. little scope to alter treatment or perhaps because those with higher levels are less willing Self-monitoring of blood glucose does not improve to self manage. glycaemic control in isolation,34 but proper • While several trials included an educational/ use of SMBG data can guide clinical decisions counselling component, this was not and improve control if results are used only to widespread across all trials and the detail of modify behaviour, diet, exercise and medications. education was not provided. In some cases, Optimal and realistic testing frequencies need to interventions were incomparable between be explored, i.e. is it achievable by patients, do cohorts, thus contributing to possible patients need to perform SBMG indefinitely or confounding variables. would time-limited periods be sufficient to address 11

© 2010 Queen’s Printer and Controller of HMSO. All rights reserved. Clinical effectiveness of self-blood glucose monitoring DOI: 10.3310/hta14120 Health Technology Assessment 2010; Vol. 14: No. 12 Attention of doctors and nurses and patient Attention of doctors and nurses results contributed to positive education could have with coping of patients and physicians Effective changes in combination with SMBG is most lifestyle strategy promising practice is that SMBG should Recommendation for control be used in patients with poor glycaemia despite optimal treatment a limited range of outcomes – Studies reviewed not fully issues of QoL and patient satisfaction were be psychological benefits not may there evaluated; evaluated of be beneficial in some groups Self-monitoring may patients or under certain conditions of use monitor interventions, to standardise A failure utilisation of for protocols and provide adherence contributed to the self-monitoring data might have reviewed findings of the trials negative leading to be educational modality, Main benefit may contact time increased current regimen include: Factors influencing SMBG risk of medication regimen, control, of glycaemic level patient motivation and attitudes hypoglycaemia, or more four range from Ideal testing regimens (not times per week on insulin to a few tests daily specified) • • • • • • • • • Comments SMBG intervention should be patients not stimulating comprehensive, but also combine SMBG, to perform only changes of lifestyle it with a programme preferably protocols, SMBG should have regimen with a semi-fixed on the feedback should give Caregiver glucose levels self-measured patient’s RCT needed to assess issues of with adherence patient training, for use of protocols recommendations, trial should modification of therapy; for after stratifying sufficient power have type (including age, important risk groups range of outcomes should of treatment); including symptom severity, be evaluated, changes in therapy satisfaction with care, hypoglycaemia and clinical outcomes, SMBG RCT needed to study discontinuing of patients (e.g. groups in well-defined T2DM) patients with stable to identify subset of required Research patients willing and able to effectively adjustments carry out treatment cost–benefit Optimal testing frequencies, of SMBG and QoL as an outcome should also be explored • • • • • • • Recommendations for research Recommendations for : not reported : not reported : : efficacy of SMBG in non-insulin dependent patients with T2DM efficacy of SMBG in non-insulin dependent patients with : that SMBG or SMUG improves to show is no evidence there : in the short term and when integrated with educational advice, : 1c 1c 1c is questionable not reported (frequencyHypoglycaemia and severity) : – self-efficacy? of empowerment not reported QoL/measure oral drug (insulin dose, to measurements change in response Treatment not reported etc.): dose, not etc.): exercise (diet, to measurements Behaviour change in response reported limited evidence : Weight Hospital admissions not reported Cost s: is no evidence there using GHb or FPG; measured glucose control than urine glucose effective that glucose monitoring is more glucose control monitoring in improving trials by not reported and severity): (frequency Hypoglycaemia – self-efficacy? of empowerment patients’ perceptions QoL/measure studied and nor rigorously neither completely of monitoring were some by urine testing is preferred further is need in this area; work patients oral drug (insulin dose, to measurements change in response Treatment not reported etc.): dose, not etc.): exercise, (diet, to measurements Behaviour change in response reported or SMUG of SMBG vs control no significant effect : Weight Hospital admissions than blood testing urine testing is less costly Costs : and were statistical power had low the studies reviewed : General changes relevant small but clinically reported and conducted; poorly been detectable might not have contribute to improving may therapy SMBG as an adjunct to standard T2DM; patients with among non-insulin-requiring control glycaemic use proper in isolation; control glycaemic SMBG does not improve only control of SMBG data can guide clinical decisions and improve and exercise diet, used to modify behaviour, are if SMBG results medications Conclusions (medical effectiveness) HbA HbA HbA Conclusions of the systematic reviews and recommendations 30 34,39 29 Coster (2000) (NHS HTA) Sarol (2005) Study Faas (1997)

12 4 TABLE 13

© 2010 Queen’s Printer and Controller of HMSO. All rights reserved. Clinical effectiveness of self-blood glucose monitoring DOI: 10.3310/hta14120 Health Technology Assessment 2010; Vol. 14: No. 12 continued level showed a showed level 1c level 1c level improvement level 1c level through direct and indirect and indirect direct through level 1c level 1c greater final reduction in HbA final greater Studies with higher baseline HbA Only assesses HbA Only Generalisability: patients were generally younger than younger generally patients were Generalisability: the typical patient population and comorbidities were not reported comparisons (Bayesian meta-analysis) comparisons (Bayesian or physicians nurses Further from FU and feedback of SMBG use important for results regarding control glycaemic compliance and to improve Diabetes duration at start of studies was different, Diabetes duration at start of studies was different, in results, contributed to differences have which may short duration of diabetes was associated with i.e. of HbA higher likelihood No standard instructions were given to the patients given instructions were No standard and medication to adjust to adjust their behaviour their glucose values Studies very different in how frequently and on which frequently in how Studies very different SMBG was performed days patients or clinicians how As studies did not report do results or treatments, changed their behaviour in improved use of SMBG resulted not explain how HbA • • • • Comments • • • • values should be evaluated 1c Studies with final end points (e.g. Studies with final end points (e.g. and patient QoL/ events) cardiovascular satisfaction required More trial evidence needed in a large trial evidence More SMBG of patients performing group testing frequency to standard according interventioncontrol both and instructions; the same standard should receive group to change diet, programme treatment with preferably and medication, lifestyle with responsibility diabetes nurse dietitian; SMBG instruction should supervisefor a long-term FU needed; the SMBG group; range of outcomes should be investigated, including patient satisfaction and QoL, based on subgroups hypoglycaemia; diabetes duration and baseline patient age, HbA Recommendations for research Recommendations for • •

1c in T2DM – regular T2DM – regular in 1c ; no conclusions regarding the no conclusions regarding ; 1c with SMBG; but overall studies are studies are but overall with SMBG; 1c 1c : not reported : : not reported : : not reported : : SMGB might be effective in improving glycaemic control in control glycaemic in improving SMGB might be effective : HbA in reducing SMBG is effective : non- clinically suggest small but possibly the studies may : 1c 1c 1c patients with T2DM not using insulin; meta-analysis resulted in a resulted meta-analysis T2DM not using insulin; patients with reduction of HbA relevant significant and clinically statistically reductions in HbA significant Conclusions (medical effectiveness) HbA HbA HbA cohort studies investigating three considered : Hypoglycaemia and insulin treated but all patients were SMBG and hypoglycaemia, of SMBG on T1DM – effect patients with were large proportions unclear hypoglycaemia reported – self-efficacy? not of empowerment QoL/measure not reported : to measurements change in response Treatment not reported : Weight Hospital admissions : not reported Costs : inconclusive; uncontrolled and cohort studies agreed with RCTs and cohort studies agreed uncontrolled inconclusive; reductions in HbA in finding small frequency of SMBG and HbA frequency feedback is important; SMBG is likely to be more effective than SMUG effective to be more SMBG is likely is important; feedback not reported and severity): (frequency Hypoglycaemia – self-efficacy? of empowerment not reported QoL/measure oral drug (insulin dose, to measurements change in response Treatment not reported etc.): dose, not etc.): exercise, (diet, to measurements Behaviour change in response reported not reported : Weight Hospital admissions : not reported Costs : (–0.39%) not reported and severity): (frequency Hypoglycaemia – self-efficacy? in of empowerment not enough information QoL/measure results conclusive trials for not etc.): exercise, (diet, to measurements Behaviour change in response reported not reported : Weight Hospital admissions : not reported Costs : 36,37 31 28 Study Welschen (2005) AHRQ (2007) 12 Jansen (2006) 13

© 2010 Queen’s Printer and Controller of HMSO. All rights reserved. Clinical effectiveness of self-blood glucose monitoring DOI: 10.3310/hta14120 Health Technology Assessment 2010; Vol. 14: No. 12 level is above 8% is above level 1c their baseline Hba they are properly educated in the use of SMBG and properly are they action based on the results appropriate to take how numerate to take literate and sufficiently are they advantage of the intervention better metabolic to the need for receptive are they the necessary motivated to make and are control changes such as new special circumstances, are there initiation or change in medication, diagnosis, of lack of awareness gestational diabetes, illness, hypoglycaemia know how to take a reading to take how know target is above/below understand when reading and readings deviant see the connection between prior behaviour glucose and implement an action plan to control have levels less and give on SMBG readings heavily more rely of well-being feelings to subjective weight the patient simple action plans that will allow create patterns life to integrate them into his/her ongoing in a non-judgemental glucose readings evaluate framework None of the studies examined how SMBG is used to None of the studies examined how (which is also dependent on modify patients’ lifestyles provided, context of carrying out SMBG and incentives addresses none of the evidence strips/monitors); free e.g. to when SMBG in terms of consistent guidance relating and act on to interpret and how to monitor, and how monitoring is meaningless unless frequent the results; long-term diabetes acted upon to prevent are the results complications benefits not be whether SMBG confers Question may and how which particular but for patients, on average, be identified? can they justified in all not be helpful or economically SMBG may benefit if: that individuals would but it seems likely cases, • Comments • • • • Steps required for SMBG to be effective – patients must: SMBG to be effective for Steps required • • • • • • • level level 1c or better at the level of the individual or better at the level patient and should qualitatively Trials SMBG is how record quantitatively taught to individuals and used modify behaviour Concur with the view that larger, long- that larger, Concur with the view duration trials with patient-centred should needed but analysis outcomes are out based on initial HbA be carried • Recommendations for research Recommendations for • levels 1c : not reported : : not reported : : SMBG may be effective in controlling glucose for patients with glucose for in controlling be effective SMBG may : conclusive neither RCTs nor observational studies provided : 1c 1c T2DM not reported : Hypoglycaemia – self-efficacy? SMBG to of empowerment One study found QoL/measure but QoL unchanged in another be associated with higher depression in one trial in the SMBG group studies and improved two not reported : to measurements change in response Treatment not reported : Weight Hospital admissions not reported Costs : larger observational studies showed or against SMBG; for evidence in patients with higher initial HbA better results Conclusions (medical effectiveness) HbA HbA : not reported : Hypoglycaemia – self-efficacy? of empowerment not reported QoL/measure not reported : to measurements change in response Treatment not reported : Weight Hospital admissions : not reported Costs : T2DM than 60% of patients with data suggests that fewer SMBG use : agents practice SMBG on a regular using diet and/or hypoglycaemic basis observational had study with the longest FU (6.5 years) Other : than in mortality and morbidity in SMBG group lower significantly non-SMBG group Conclusions and recommendations of systematic reviews (continued) Conclusions of systematic reviews and recommendations 2 32 Study McAndrew (2007) McGeoch (2007)

14 4 TABLE 15

1c level is above 8% is above level 1c their baseline Hba they are properly educated in the use of SMBG and properly are they action based on the results appropriate to take how numerate to take literate and sufficiently are they advantage of the intervention better metabolic to the need for receptive are they the necessary motivated to make and are control changes such as new special circumstances, are there initiation or change in medication, diagnosis, of lack of awareness gestational diabetes, illness, hypoglycaemia know how to take a reading to take how know target is above/below understand when reading and readings deviant see the connection between prior behaviour glucose and implement an action plan to control have levels less and give on SMBG readings heavily more rely of well-being feelings to subjective weight the patient simple action plans that will allow create patterns life to integrate them into his/her ongoing in a non-judgemental glucose readings evaluate framework level is higher – meaning that SMBG may be least is higher – meaning that SMBG may level the patients who need it most for effective SMBG is an intervention of modest efficacy At best, in patients not taking insulin Periodic checking of glucose meter user’s technique checking of glucose meter user’s Periodic is important in some adherence of trials included low Problems training or use of a protocol lack of standard studies; use of SMBG techniques to guide the proper no feedback on results no feedback not taught self-management skills needed to lower BG values times BG at wrong measured rather what patient does with per se, not results in to measure that influences outcome (hard results an RCT) Comments on education provided: large variation in education package provided Efficacy of SMBG may be lower as the baseline HbA be lower Efficacy of SMBG may None of the studies examined how SMBG is used to None of the studies examined how (which is also dependent on modify patients’ lifestyles provided, context of carrying out SMBG and incentives addresses none of the evidence strips/monitors); free e.g. to when SMBG in terms of consistent guidance relating and act on to interpret and how to monitor, and how monitoring is meaningless unless frequent the results; long-term diabetes acted upon to prevent are the results complications benefits not be whether SMBG confers Question may and how which particular but for patients, on average, be identified? can they justified in all not be helpful or economically SMBG may benefit if: that individuals would but it seems likely cases, • Comments • • • • Steps required for SMBG to be effective – patients must: SMBG to be effective for Steps required • • • • • • • • • • Comments on potential modifiers: • • • • • • Comments • level level at 1c 1c or better at the level of the individual or better at the level patient and should qualitatively Trials SMBG is how record quantitatively taught to individuals and used modify behaviour Concur with the view that larger, long- that larger, Concur with the view duration trials with patient-centred should needed but analysis outcomes are out based on initial HbA be carried baseline; goal of glycaemic control should control of glycaemic goal baseline; users vs ongoing in new effect be defined; should be evaluated Further studies needed that could from in the process, determine where of SMBG and interpretation performance to self- of the result and application education and improved management, the greatest produce motivation would gains Large, high-quality RCTs in patients Large, T2DM are with non-insulin-dependent protocols including standard warranted, of SMBG testing, use and frequency for assessment of accuracy the glucose patient meter and user technique, to self-monitor glucose, education of how and the SMBG results, to interpret how to adjust to use the SMBG results how and/or medications to diet, lifestyle, of SMBG effect diabetes control; improve of in subgroups should also be evaluated of Hba patients with various levels • Recommendations for research Recommendations for • Recommendations for research Recommendations for • • at in 1c 1c levels 1c 1c : not reported : : not reported : : not reported : : not reported : , especially when used to adjust therapeutic regimens when used to adjust therapeutic especially , : SMBG may be effective in controlling glucose for patients with glucose for in controlling be effective SMBG may : conclusive neither RCTs nor observational studies provided : : The evidence suggests that SMBG is beneficial in improving suggests that SMBG is beneficial in improving The evidence : in HbA significant improvement modest but statistically : in HbA significant improvement modest but statistically : 1c 1c 1c 1c 1c 1c T2DM not reported : Hypoglycaemia – self-efficacy? SMBG to of empowerment One study found QoL/measure but QoL unchanged in another be associated with higher depression in one trial in the SMBG group studies and improved two not reported : to measurements change in response Treatment not reported : Weight Hospital admissions not reported Costs : larger observational studies showed or against SMBG; for evidence in patients with higher initial HbA better results Conclusions (medical effectiveness) HbA HbA : not reported : Hypoglycaemia – self-efficacy? of empowerment not reported QoL/measure not reported : to measurements change in response Treatment not reported : Weight Hospital admissions : not reported Costs : T2DM than 60% of patients with data suggests that fewer SMBG use : agents practice SMBG on a regular using diet and/or hypoglycaemic basis observational had study with the longest FU (6.5 years) Other : than in mortality and morbidity in SMBG group lower significantly non-SMBG group HbA Conclusions (medical effectiveness) HbA HbA trials suggests that SMBG of three limited evidence : Hypoglycaemia hypoglycaemia of recognised the frequency increase may – self-efficacy? of empowerment not reported QoL/measure not reported : to measurements change in response Treatment not reported hospital admissions: not reported : Weight not reported Costs : HbA 6 months in patients with T2DM not requiring insulin when SMBG T2DM not requiring 6 months in patients with 95% CI –0.38 to to management (–0.21%, added and education were suggested that meta-regression not significant; 12-month result –0.04); with higher baseline HbA be lower may effects up insulin when using SMBG for T2DM not requiring patients with finding –0.22% (95% CI –0.34 to –0.11)); RCTs, to 12 months (seven consistent with most observational treated studies of similarly patients not reported : Hypoglycaemia – self-efficacy? of empowerment not reported QoL/measure not reported : to measurements change in response Treatment not reported : Weight Hospital admissions : not reported Costs : : not reported Costs : : not reported : Hypoglycaemia – self-efficacy? of empowerment not reported QoL/measure not reported : to measurements change in response Treatment not reported : Weight Hospital admissions 2 32 33 35 38 Study McAndrew (2007) McGeoch (2007) St John St John (2009) Towfigh Towfigh (2008) Study Poolsup (2008) 14 haemoglobin. glycosylated GHb, follow-up; FU, fasting plasma glucose; FPG, blood glucose; BG, 15

TABLE 5 Results of meta-analyses in the reviews

Results of meta-analysis (for SBMG minus Outcome comparator, so negative value = better on SMBG)

Coster (2000)29

HbA1c Effect of blood or urine monitoring on GHb vs control –0.25% (95% CI –0.61 to 0.10; p = NS) (four studies) SMBG vs SMUG –0.03% (95% CI –0.52 to 0.47; p = NS) Weight Effect of blood or urine monitoring on weight vs control –0.28 kg (95% CI –1.48 to 0.98; p = NS) (four studies) SMBG vs SMUG 0.36 kg (95% CI –1.93 to 2.65; p = NS) Sarol (2005)34,39

HbA1c SMBG vs non-SMBG (random effects) –0.42% (95% CI –0.63 to –0.21; p < 0.05) (eight studies) Welschen (2005)36,37

HbA1c SMBG vs control –0.39% (95% CI –0.56 to –0.21; p < 0.05) (five studies) SMBG vs SMUG –0.17% (95% CI –0.96 to 0.61; p = NS) (two studies) Jansen (2006)31

HbA1c (adjusted for baseline HbA1c to all T2DM patients) No self-monitoring –0.47% (95% CrI: –0.66 to –0.28) SMUG –0.61% (95% CrI: –1.20 to –0.05) SMBG –0.87% (95% CrI: –1.14 to –0.58) SMUG vs control –0.19% (95% CrI: –0.80 to 0.44; Pr = 74%) SMBG vs control –0.41% (95% CrI: –0.72 to –0.06; Pr = 98%) SMBG + FB vs control –1.13% (95% CrI: –1.87 to –0.35; Pr = 99%) SMBG vs SMUG –0.21% (95% CrI: –0.82 to 0.39; Pr = 78%) SMBG + FB vs SMUG –0.95% (95% CrI: –1.78 to –0.09; Pr = 98%) SMBG + FB vs SMBG –0.73% (95% CrI: –1.41 to –0.04; Pr = 98%) Subgroups Results similar for non-insulin-requiring patients with T2DM Poolsup (2008)33

HbA1c SMBG vs no SMBG –0.24% (95% CI –0.37 to –0.12; p = 0.0002) (seven trials) SMBG vs no SMBG – SMBG results used to modify therapy –0.27% (95% CI –0.41 to –0.14; p = 0.0001) (six trials) SMBG vs no SMBG – SMBG results not used to modify –0.12% (95% CI –0.32 to 0.08; p = NS) (six trials) therapy Towfigh (2008)35

HbA1c SMBG vs no SMBG ≥ 1 year –0.16% (95% CI –0.38 to 0.05; p = NS) (five trials) SMBG vs no SMBG 6 months –0.21% (95% CI –0.38 to –0.04; p < 0.05) (six trials) St John (2009)38

HbA1c SMBG vs no SMBG –0.22% (95% CI –0.34 to –0.11; p < 0.05) (seven trials) SMBG vs no SMBG to duration < 1 year –0.26% (95% CI –0.40 to –0.11; p = 0.001) (five trials) SMBG vs no SMBG to duration ≥ 1 year –0.17% (95% CI –0.36 to +0.02; p = 0.072) (two trials – DiGEM to ESMON)

CI, confidence interval; CrI, credible interval; FB, feedback; GHb, glycosylated haemoglobin; NS, not significant; Pr, probability 16 that first intervention results in greater reductions than second intervention. DOI: 10.3310/hta14120 Health Technology Assessment 2010; Vol. 14: No. 12

specific questions? One could suggest that testing had substantial losses to follow-up. Additionally, 6 days per week before and after meals places an important aspects of the SMBG intervention unnecessary burden on patients who are treated were not clearly described by many of the trials using diet and exercise alone. (e.g. what kind of instructions and education was received, how and if feedback was given, whether Randomised controlled trials SMBG technique was checked, whether monitoring frequency was checked (and how frequently people Appendix 3 shows details of the 26 relevant RCTs were monitored, etc.). identified from the reviews and from our additional searches. Two of the high-quality trials, O’Kane et al. (2008 – ESMON)13 and Barnett et al. (2008 – DINAMIC; Trial duration/follow-up ranged from 12 weeks to Diamicron MR in NIDDM: assessing management 30 months. Participant numbers varied from less and improving control),41 have been criticised than 30 to over 800, with over 100 participants on the grounds that they were both in recently in the majority of trials. Some trials included diagnosed patients whose control was poor, and only non-insulin-treated patients, whereas was going to improve with treatment and intensive others specified no medication restrictions. education whether SMBG was used or not.98 In

Trials generally provided no details of oral the control groups, HbA1c level improved from anti-hyperglycaemic treatment received and 8.6% to 6.9% (ESMON) and from 8.1% to 7.2% no details of subgroups of patients (e.g. those (DINAMIC), hence leaving little scope to show taking sulphonylureas or those susceptible to benefit from SMBG. hypoglycaemia), therefore separate assessments by treatment type could not be carried out. A The DiGEM trial has been criticised on similar few trials included small numbers of patients grounds because control was quite good at baseline also taking insulin, but no details were provided (mean HbA1c level = 7.5%), making further of subgroups taking insulin. Primary outcome improvements difficult.98 measures were mainly HbA1c level, but trials also assessed a range of additional outcomes such as Table 6 presents an attempt to classify the studies by

HbA1c level fluctuations, fasting plasma glucose the moderators we identified as being potentially (FPG), fructosamine, episodes of hypoglycaemia, important. Overall, less than half the studies found weight/body mass index (BMI), diabetes self-care better HbA1c values in the intervention group activities, adverse effects, frequency of SMBG, QoL, than in the control group. All the studies that did medication use, health-care utilisation and lipid find more favourable results for the intervention parameters. included an education component and/or feedback on SMBG results. No adequate data for meta-analysis were available for outcomes other than HbA1c level, and no data The following figures (Figures 1–4) show the results on relevant subgroups could be identified (neither of our meta-analyses. In total, 10 RCTs were for narrative nor for statistical analysis). included in the meta-analysis of (‘simple’) SMBG versus no SMBG. Overall, there was a small but

Due to the limitations of the data, most of significant reduction of HbA1c level with SMBG the original questions of this review could not of –0.21% (95% CI –0.31 to –0.10, p < 0.0001, no be answered, as not enough data on relevant significant heterogeneity). None of the studies subgroups by treatment or patient characteristics comparing SMBG with SMUG (three RCTs) were presented. found a significant difference, and there was no significant difference overall (–0.06%, 95% CI Most trials had serious quality deficits (see –0.69 to 0.56, no significant heterogeneity). Appendix 3). Only four of the trials [Barnett et al. (2008),41 Farmer et al. (2007)10 (DiGEM), O’Kane For the meta-analysis of ‘enhanced’ SMBG versus et al. (2008)13 (ESMON) and Scherbaum et al. ‘simple’ SMBG, ‘enhanced’ SMBG was subdivided (2008)60] could clearly be classified as high quality, into those studies with a component of education while more than half of the studies were classified and/or feedback and those using other methods as clearly being of poor quality. Randomisation and (higher versus lower frequency of monitoring, allocation concealment was often not described, free provision of strips versus no free provisions sample sizes were often small, and some trials of strips). HbA1c level reduction when comparing

1c results Hba NS SMBG better More frequent better Unclear SMBG better NS NS NS NS NS SMBG better SMBG better NS Diabetes duration 8 3 11 NR 7 6 NR 3 12.5 NR 8 6.8 8 Treatment Diet, oral Diet, MET/ Diet, SU oral Diet, Oral oral, Diet, insulin MET/SU oral Diet, oral Diet, oral Diet, oral Diet, MET/SU Unclear oral Diet, Age 58 56 65 NR 53 50 55 66 55 64 62 62 68

1c Starting HbA level 12 8 8 12 7.6 8.5 6.2 7.5 8.3 NR 9 9.5 7.4 SMBG regimen Moderate Moderate Infrequent Unclear Unclear Frequent Unclear Moderate Moderate Unclear Frequent Moderate Frequent Treatment Treatment adjustment Doctor No Yes Unclear Yes Doctor/nurse Unclear Patient (intensive) Doctor Unclear Doctor Doctor? No Feedback Feedback given Yes Unclear Unclear Unclear Yes Unclear Yes Yes Yes No Unclear Unclear No Education/ counselling Yes (both) Yes (both) Yes Yes (only Yes intervention) Yes (both) Yes (both) Yes Yes Limited No No (only Yes intervention) No SMBG instruction Yes Yes No Yes Unclear Unclear Yes No Yes Yes Yes Yes Yes feedback vs feedback + Comparison SMBG no feedback SMBG vs SMUG SMBG vs no once SMBG profile per month vs more detailed SMBG weeks every 2 profile SMBG plus education vs no SMBG Internet vs non- internet SMBG SMBG vs no SMBG vs SMBG intensive SMBG less intensive vs no SMBG SMBG vs SMUG no SMBG SMBG vs SMUG SMBG vs no SMBG plus education vs no SMBG blood glucose Free meter plus testing blood strips vs free glucose meter Intervention components – RCTs 40 41 42 43 44 45 46 10 47 48 49 50 51 Study Allen (1990) Barnett (2008) Bonomo (2006) Brown (2002) Cho (2006) Davidson (2005) Estey (1990) Farmer (2007) Fontbonne (1989) Gallichan (1994) Guerci (2003) Jaber (1996) Johnson (2006)

18 6 TABLE 19

1c results Hba NS NS SMBG better (?) SMBG better NS NS NS NS SMBG better NS SMBG better Unclear NS Diabetes duration 10.5 NR NR 5.6 0 10 5.5 0 8.8 8 5.3 NR NR Treatment Oral, insulin Oral, insulin Oral, (?) insulin Oral, NR insulin Oral, insulin Oral, NR oral Diet, oral Diet, MET/ Diet, SU oral Diet, Oral oral, Diet, insulin Age 55 NR 50 54 65 48 59 60 63 62 60 NR 54

1c Starting HbA level 8.5 8.4 NR 7.3 10.3 9 10.4 8.7 9.3 7.2 8.5 NR 10.5 SMBG regimen Unclear Frequent Infrequent Moderate Frequent NR Frequent/moderate Moderate/frequent Infrequent Moderate/ infrequent Moderate NR Frequent Treatment Treatment adjustment Unclear Doctor Patient Patient Unclear Unclear Doctor Patient/doctor? Doctor Doctor Unclear Doctor Doctor Feedback Feedback given Unclear NR Unclear Yes Unclear Unclear Yes Yes Yes Yes Unclear NR Yes Education/ counselling Yes NR (both) Yes (only Yes intervention) (both) Yes (all) Yes (both) Yes (both) Yes No No in (different Yes groups) two NR (both) Yes SMBG instruction No NR Yes Unclear Unclear Yes Yes Yes Yes Unclear Yes NR Yes manual manual + Comparison PTC plus SMBG vs PTC vs SMBG control SMBG vs Preprandial postprandial SMBG SMBG vs no Internet vs non- internet SMBG SMBG vs SMUG BG meter vs BG meter no SMBG SMBG vs no SMBG vs no SMBG vs no High SMBG vs low SMBG vs no SMBG vs no SMBG vs no SMBG vs no 53 52 54 55 56 20 57 13 58 60 61 62 63 Study Jones Jones (2003) Joy (2003) Joy Kibriya (1999) Kwon (2004) Miles (1997) Moreland (2006) Muchmore (1994) O’Kane (2008) Rutten (1990) Scherbaum (2008) Schwedes (2002) Seaton (1996) Wing (1986) not NR, metformin/sulphonylurea; MET/SU, times per week; several ‘moderate’, times per week; than several fewer ‘infrequent’, times each day; each day/several ‘Frequent’, blood glucose; BG, to change. pathways PTC, not significant; NS, reported; 18 19

© 2010 Queen’s Printer and Controller of HMSO. All rights reserved. Clinical effectiveness of self-blood glucose monitoring DOI: 10.3310/hta14120 Health Technology Assessment 2010; Vol. 14: No. 12 2 2 CI CI Favours no SMBG ence 0 1 95% ence 95% Favours SMUG differ differ 0 1 –1 , Random , , Random , , , Mean , , Mean IV IV –1 –2 Favours SMBG Favours SMBG –2 CI CI 0.10) – 0.08) 0.07) 0.56) 2.17) 0.68) 0.20) 0.24) − 0.73) 0.03) 0.71) − 0.55) 1.05) 0.98) 0.30) ence 95% ence 95% to to to to to to to to to to to to to to to differ differ 0.31 0.69 0.48 0.77 1.46 0.75 2.41 0.64 0.75 0.52 0.45 0.43 0.70 0.30 – − − − − ( – ( ( ( − ( − ( − ( ( − ( ( − ( − ( − ( − 1.45 ( − ( , Random , , Random , , , Mean , , Mean 0.10 0.70 IV 0.20 0.10 0.30 0.21 0.25 0.14 0.00 0.06 IV − 0.63 − 0.01 − 0.85 − − − − 0.21 – − − 0.20 – 1.9% 0.4% 1.5% 5.7% 2.5% 0.7% eight eight 21.2% 34.8% 12.1% 19.0% 50.3% 15.0% 34.7% . W 100.0% W 100.0% 1c . 1c 32 11 68 88 83 45 25 344 299 152 otal otal 82 27 72 T 1147 T 181 SMBG SMUG No SD SD 1.7 2.6 2.5 1.4 1.85 2.1 2.5 1.22 1.2 1.14 1.5 1.2 2.2 36% 0%

= = 2 2 I I

8.4 7.12 9.6 7.7 7.2 6.9 9.4 7.8 7.49 Mean Mean 10.4 8.7 9.7 8.47 0.21); 0.88);

= = p p 32 12 25 68 96 66 43 ( ( 345 150 311 otal otal 68 27 68 2 9 T 1148 T 163

= = 0.84) 0.0001)

df df = < p p SD SD 2.9 2.5 1.9 1.6 1.08 0.88 1.66 2.3 2.5 0.97 0.8 1.49 1.6 ( ( , 3.14 , , 4.44 , SMBG SMBG

= = 0.20 3.94 2 2

χ χ = = 7.84 8.8 8.1 7.11 7.28 8.75 7.84 6.95 6.9 9.2 7.7 z z Mean 10.4

Mean 10.2 ; 0.11 ; ; 0.00 ;

57 = = 47 47 2 2 45 effect: effect: τ τ 13 41 10,11 54 58 49 CI) CI) 63 1994) 1989) 1989) 40 56 ( ( 2005) ( Self-monitoring of blood glucose (SMBG) versus no SMBG – HbA Self-monitoring of blood glucose (SMBG) versus SMUG – HbA 2008) 2008) 2007) 1999) re ( overall overall overall overall 2003) 1990) ( ( ( ( ( ( or or 1986) 1990) 1997) (95% (95% oup oup ( ( ( : ogeneity : : ogeneity : for for for for vidson otal otal est est ontbonne ontbonne T Barnett i Gue rc Wing F Heter Kibriya Study subgr Muchmo F O’Kane T Da Farmer Study subgr T Miles T Heter Rutten Allen FIGURE 1 20 FIGURE 2 21

© 2010 Queen’s Printer and Controller of HMSO. All rights reserved. Clinical effectiveness of self-blood glucose monitoring DOI: 10.3310/hta14120 Health Technology Assessment 2010; Vol. 14: No. 12 2 4 1 Favours no SMBG CI Favours simple SMBG CI 0 2 ence 95% ence 0 95% differ differ , Random , –2 , Random , , , Mean , , Mean IV IV –1 –4 Favours enhanced SMBG Favours enhanced SMBG –2 CI 0.03) 0.41) CI − 0.21) 0.44) 0.30) 0.53) 0.06) 0.08) 0.48) 0.06) ence 95% to to – 0.08) to to to to to to to − 0.75) − 0.03) 0.12) ence 95% to to to to to differ 0.44 0.01 1.19 0.84 0.14 0.13 0.42 0.64 0.08 − − − − − − differ ( – ( – ( ( ( ( ( ( ( − 0.98 3.35 0.71 1.42 0.38 , Random , − − ( – ( ( − ( − ( , , Mean , Random , 0.70 0.20 0.08 0.20 0.18 0.28 0.20 0.20 0.20 IV , , − − − − Mean – 0.52 2.05 IV 0.75 0.13 – − − 0.34 − − . eight 1c 14.4% 10.0% 28.3% 41.3% 27.3% 20.0% 58.7% W 100.0% 100.0% 9.7% eight 32.3% 21.9% 36.1% W 100.0% otal 40 25 96 50 150 131 100 T 361 231 otal 22 T 110 125 152 409 SMBG SD Nothing 1.3 1.5 0.88 1.2 1.05 0.92 1 71% SD 1.52 2.85 1.2 2.61 58% 0%

= = = 2 I 2 2

I I .

Mean 7.4 5.8 7.28 7.1 7.78 7.22 6.9 1c 7.81 7.49 9.65 0.01); Mean 11.64 0.05); 1.00);

= = = p otal 40 28 51 ( p p 151 131 177 102 T ( ( 447 233 3

otal 1 4 17

= T 113 126 151 407 = = plus 0.03) 0.06) 0.09) df

df df = = = SD plus 0.9 0.7 1.05 1.5 0.73 0.93 1 p p p ( ( ( SD 1.27 2.56 1.05 1.48 , 10.47 , , 0.00 , , 9.62 , SMBG

= = = strips) 2.20 1.68 1.85 2 2 2 SMBG

χ χ χ = = = Mean 6.7 5.6 7.36 7.3 7.6 6.94 7.1 ee z z z fr 7.47 7.36 7.6

Mean / 10.89 ; 0.14 ; ; 0.04 ; 0.00 ;

59,60 = = = 61 CI) CI) 2 2 2 effect: effect: effect: 42 τ τ τ 51 10,11 10,1 1 43 feedback 55 CI) 2008) 46 / 50 ( 44 2002) equency (95% (95% ( 2006) 2006) Enhanced/more frequent SMBG versus frequent SMBG – HbA Enhanced/more only/less frequent Enhanced SMBG versus no SMBG – HbA ( 2007) 2007) ( overall overall overall overall overall 2002) ( ( (fr 2004) ( or or 1990) 1996) ( (95% oup oup 2006) : ogeneity : : ogeneity : : ogeneity : ( edes ( for for for for for on own own otal est est est ohnson Other J Est ey ( Schw Farmer Subtotal T Study subgr Farmer Study subgr T T Kw Scherbaum Cho Subtotal Br T Heter Jaber Bonomo Education Heter Heter FIGURE 3 20 FIGURE 4 21

SMBG with an educational/feedback component for the limited effectiveness of SMBG). Only two with ‘simple’ SMBG was in the same order of studies reported on behaviour changes (diet or magnitude as when comparing ‘simple’ SMBG with physical activity) and one found improved dietary no SMBG; however, the difference was not quite adherence in the SMBG group compared to the significant: –0.2% (95% CI –0.44 to 0.03; p = 0.09), control group. with significant heterogeneity. There was no

significant effect of providing free strips on HbA1c, Seven studies reported on outcomes such as or of decreasing the frequency of monitoring. QoL, well-being, treatment satisfaction and For comparisons between enhanced SMBG and depression.10,13,20,56,57,61,63 For most measures, there no SMBG (four RCTs), there was a significant was no significant difference between SMBG and difference in favour of enhanced SMBG of –0.52% no SMBG. However, both the DiGEM10 trial and (95% CI –0.98 to –0.06; p = 0.03). All studies in the ESMON13 trial reported increased depression this group included some education or feedback in the SMBG group (more intensive SMBG group component in the SMBG group only. There was for the DiGEM trial). The DiGEM trial found no significant heterogeneity, which was clearly due to significant difference between comparison groups an outlier study.50 for mobility, self-care, usual activities and pain; the ESMON trial found no significant differences for Figures 5–7 show some crude analyses of changes in anxiety (p = 0.07), positive well-being and energy.

HbA1c level dependent on baseline HbA1c level for On the other hand, two trials specifically including all trials considered together. The graphs suggest education/counselling components emphasising that while both control groups and intervention a positive attitude to SMBG20,61 found improved

groups showed a decrease in HbA1c level, which outcomes for negative affect with respect to SMBG

was larger with high baseline HbA1c values than and depression. In one study of SMBG versus

with low baseline HbA1c values (Figures 6 and 7), the SMUG, 70% of patients preferred SMUG to SMBG difference between the change in the control group for ease of use (versus 15% preferring SMBG), and the change in the intervention group also 44% preferred SMUG for acceptability (versus

increased with higher baseline HbA1c values 31% for SMBG), but 76% preferred SMBG for (Figure 5). perceived accuracy (versus 11% SMUG) and 49% for usefulness (versus 21% SMUG). Details of other outcomes reported by the RCTs are shown in Appendix 4. Observational and non- randomised experimental Hypoglycaemic events were reported by six studies RCTs.10,13,41,49,54,60 Results for this outcome were inconsistent, although there was a suggestion that Appendix 5 shows details of the 36 observational occurrence of (mild or moderate) hypoglycaemia and non-randomised studies identified (details was increased with more frequent self-monitoring. for studies in reviews as far as provided by the reviews). Most studies only provided very limited Thirteen RCTs reported on weight or BMI and details on SMBG methods and participants. Most none found a significant difference between the studies examined the relationship between SMBG

intervention groups. Results on lipid parameters use and HbA1c level. An overview of the relevant were reported by six RCTs and were inconsistent, parameters examined by the observational and with most studies finding no significant difference non-randomised experimental studies is shown in between groups. Similarly, no difference was found Table 7. by a small number of studies reporting on blood pressure. Eighteen studies found no favourable changes in

HbA1c level with SMBG, while 12 studies found a

SMBG adherence was reported by eight RCTs. In positive effect of SMBG on HbA1c level, whereas most studies using a form of enhanced SMBG, another six showed favourable effects of SMBG on

adherence was greater in enhanced group – only HbA1c level, depending on treatment (especially 10 the DiGEM trial reported reduced SMBG in insulin-treated patients) or entry HbA1c level

adherence in the more intensive group. (especially with higher entry HbA1c level). Two studies reported on mortality and morbidity, with Data on medication changes were provided by the ROSSO Study15,78,99 (Germany) finding that seven RCTs.10,45,49,55,61,63 None found a significant SMBG was associated with lower morbidity and difference between groups (which could be a reason mortality, while the Fremantle Diabetes Study17,19 22 DOI: 10.3310/hta14120 Health Technology Assessment 2010; Vol. 14: No. 12

1.0

0.5

0.0

–0.5 Change in HbA1c –1.0

–1.5

–2.0 r = 0.64, slope = –0.13

–2.5 6 8 10 12 Mean baseline HbA1c (%)

FIGURE 5 Treatment difference as a function of mean baseline HbA1c.

1.0

0.5

0.0

–0.5 Change in HbA1c –1.0

–1.5

–2.0 r = 0.64, slope = –0.13

–2.5 6 8 10 12 Mean baseline HbA1c (%)

FIGURE 6 Change from baseline as a function of baseline HbA1c (control group). Title: 09-19-01 Proof Stage: 2 Figure Number: 00.01.ai

Cactus Design and Illustration Ltd 23

Title: 09-19-01 Proof Stage: 2 Figure Number: 00.01.ai

Cactus Design and Illustration Ltd Clinical effectiveness of self-blood glucose monitoring

1.0

0.5

0.0

–0.5 Change in HbA1c –1.0

–1.5

–2.0 r = 0.89, slope = –0.19

–2.5 6 8 10 12 Intervention baseline HbA1c (%)

FIGURE 7 Change from baseline as a function of baseline HbA1c (intervention group).

(USA) found no changes in mortality in relation to self-management as a result of SMBG. Negative to SMBG, but SMBG use was associated with less results showed increased levels of depression retinopathy. These associations may be due to and anxiety compared with patients who do not confounding factors – those who perform SMBG self-monitor, few patients use SMBG to guide may be more motivated to self-manage in other and maintain change to behaviour or lifestyle; ways. negative impact on patients’ self-management when readings are counterintuitive and lack of Qualitative studies education on how to interpret and act on out of target readings. A summary of messages regarding A summary of studies including qualitative data in advantages of SMBG and barriers to benefit of terms of study design, participants and brief results SMBG is shown in Table 8. is presented in Appendix 6. Six qualitative studies were identified: Belsey et al. (2009),100 DiGEM RCT Results from published qualitative studies have questionnaire and qualitative components,10,11 identified a number of reasons why SMBG may Lawton et al. (2004),6 Peel et al. (2004),101 Peel et not be helping some individuals. Increased anxiety al. (2007)102 and Zgibor and Simmons (2001).103 and depression have been reported,71,100 with These reported results from in-depth interview individuals reporting feelings of obsession about studies, repeated interviews, questionnaire and results, paranoia, pain/discomfort, contradictory survey data. Numbers of participants ranged from information, lack of knowledge/understanding of Title: 09-19-01 Proof Stage: 2 Figure Number: 00.03.ai n = 18 to n = 40 for interview studies, to n = 323 what results mean, monitoring fatigue, increased Cactus Designto n = and 40,651 Illustration patient Ltd records examined for survey worry, distress and anxiety and self-blame and and questionnaire data. Key positive results abandonment of regimen resulting in adverse showed increased awareness of diabetes and help effects on adherence, for example nihilistic with establishing relationship between physical attitudes.101 Peel et al. (2007)102 reported that symptoms and blood glucose readings; increased reasons for discontinuation of SBMG included empowerment to take more control over their self-chastisement, with SMBG seen as a proxy health care; and the ability to use SMBG to assess measure for ‘good and bad’ behaviour rather than effects of behaviour and promotion of adherence an aid to better diabetes self-management. Women

24 DOI: 10.3310/hta14120 Health Technology Assessment 2010; Vol. 14: No. 12

were particularly like to chastise themselves when decision-making.102 Many were disappointed readings were high, indicating specific gender with HCPs’ disinterest in the results.101 Song and differences. Lipman (2008)8 reported that a patient who uses SMBG on a regular basis may believe the number Lack of education in how to interpret blood glucose on the glucose meter reflects ‘the truth’, even results and what to do with that information, for although it may not be consistent with what his/ example how to respond to high readings, was her body is telling him/her. This is particularly reported in a number of studies.18,100,102,104 Peel worrying in view of the lack of checking/calibrating et al. (2007)102 reported a lack of explicit and of meters,104 which may result in inappropriate unified messages from health-care teams about reliance on inaccurate results. Alternatively, other if, when, and how, to self-monitor. None of the patients may not believe the number because participants in this study reported receiving they feel fine. Incorrectly interpreting a lack of ongoing education about SMBG. It is unclear symptoms (incorrect because blood glucose has whether practice nurses provide sufficient (or any) to be well above normal to cause symptoms) as training to patients, or indeed help patients to meaning that all is well could lead to SMBG results interpret results, and this is an area that requires being ignored. further investigation. Anecdotal evidence suggests that practice nurses are unclear themselves about There was a lack of data in the studies (qualitative, how to interpret blood glucose readings and systematic review or economic) about whether how to use that information to direct behaviour SMBG benefits vary by frequency of monitoring, changes. There is certainly a theme running type of education, susceptibility to hypoglycaemia, through the qualitative literature that HCPs are treatment, age, starting HbA1c level or time disinterested in the results that patients take to points during the course of diabetes, for example them, resulting in disappointment and disinterest after diagnosis, during treatment change, etc. ultimately by patients. This may reflect a mismatch What was evident was that older and less well- in expectations, with the professionals expecting educated patients were most interested in HCP patients to use SMBG to self-manage, and patients attitudes to readings102 and that longer diabetes expecting the professionals to use the results to duration was associated with less SMBG. 18 Evans adjust treatment. et al. (1999)69 reported a decreasing uptake of test strips which was associated with age, and Individuals who simply purchase a blood glucose Belsey et al. (2009)100 reported that participants meter (which are widely available for sale in on diet and exercise did least testing, with testing pharmacies, with basic instruction only on how to increasing as therapy intensifies. None of the use the machine) will have received no education studies reported monitoring results being used at all unless they have sought it from a HCP. There for treatment adjustment by the HCP, whilst Peel is perhaps an important role for pharmacists to et al. (2007)102 were alone in reporting that most ensure that anybody purchasing such a device is participants could counteract hypoglycaemia offered appropriate training on both how to use but not hyperglycaemia. Furthermore, they it and how to interpret the results. However, that reported that inexplicable readings promoted assumes that the pharmacists have the necessary nihilistic attitudes, whilst Lawton et al. (2004)6 knowledge to do the training, or the ability to reported that consistently normal results on self- arrange for others to do it. monitoring of urine were interpreted as successful diabetes management/compliance. Highest SMBG Failure to use SMBG to alter treatment dose or frequency was reportedly conducted by participants behaviour was reported.100,102,104 In the UK, few who had attended diabetes education.18 patients use SMBG to guide and maintain changes to their behaviour and lifestyle,100 and this appears Interestingly, Peel et al. (2007)102 reported that to be due, in part, to lack of education about participants felt they were monitoring for the interpreting and acting upon results. Indeed, some benefit of their HCP, rather than their own participants reported that reasons for continuing benefit, despite the HCPs showing no interest with SMBG included curiosity and reassurance102 in the readings. There is a clear incongruence rather than to guide diabetes self-care behaviours. between patient expectations of HCPs and vice Some individuals found that SMBG promoted versa. In fact, how the monitoring results were a focus on the ‘here and now’, which could be used for treatment adjustment by patients was not detrimental to long-term health behaviours and addressed in any of the qualitative studies. HCPs

© 2010 Queen’s Printer and Controller of HMSO. All rights reserved. Clinical effectiveness of self-blood glucose monitoring DOI: 10.3310/hta14120 Health Technology Assessment 2010; Vol. 14: No. 12 with more with more 1c under 7% with after SMBG 1c 1c with more SMBG with more 1c : NS : reduced : NS : frequent with more 0.7% lower NS : lower SMBG, higher with more NS : NS : SMBG higher with more NS : NS : SMBG in with more 0.6% lower NS : NS : 1c 1c 1c 1c 1c 1c 1c 1c 1c 1c 1c 1c 1c 1c SMBG Results No change in HbA SMBG when insulin could be adjusted NS Mortality: less retinopathy SMBG: those on oral drugs HbA HbA Higher % with HbA HbA HbA HbA HbA HbA HbA HbA HbA HbA HbA under 7% HbA 5% more HbA Lower HbA HbA more frequent SMBG frequent more reduction 10 Diabetes duration NR 11 NR NR 21 NR NR NR 9.1 NR NR NR NR 0 to > NR NR NR NR Treatment Diet, oral Diet, Oral, insulin Oral, Unclear oral, Diet, insulin Insulin NR Insulin oral, Diet, insulin oral Diet, oral, Diet, insulin oral, Diet, insulin oral, Diet, insulin oral, Diet, insulin oral, Diet, insulin oral, Diet, insulin oral, Diet, insulin oral, Diet, insulin oral Diet, Age 64 63 49 35–65 80 53 NR 63 62 65 63 63 62 60 60 60 62 64 1c Starting HbA NR 7.5 9.7 NR 7.6 NR NR 7.3 7–7.3 7.4 NR 7.6 NR 8.4 9.9 6.4 NR NR Education/ counselling NR Yes Yes NR NR NR NR NR NR NR NR NR NR NR NR NR NR NR SMBG method NR Reported Reported NR NR NR NR NR NR NR NR NR NR NR NR NR NR NR 1c 1c 1c 1c 1c 1c 1c 1c 1c 1c 1c 1c 1c 1c 1c 1c 1c Focus Association between SMBG Association between use and HbA SMBG Association between use and HbA SMBG Association between use and HbA SMBG Association between use and HbA SMBG Association between use and HbA SMBG Association between use and HbA SMBG Association between use and HbA SMBG Association between use and HbA SMBG Association between use and HbA SMBG Association between use and HbA SMBG Association between use and HbA SMBG Association between use and HbA SMBG Association between use and HbA SMBG Association between use and HbA SMBG Association between use and HbA Reduced access test strips SMBG Association between use and HbA Association between SMBG Association between use and HbA ] 64 17,19 72 67 70 71 74 65 80 66 75 76 14 73 79 69 68 77 Intervention components – observational studies and non-randomised Study Karter (2006) Klein (1993) Bajkowska- (2008) Fiedziukiewicz Banister (2004) Blonde (2002) Chan (2000) Evans (1999) Franciosi (2001) Franciosi (2005) Diabetes Fremantle (2007) [Davis Study Hanninen (2001) (2001) Harris (2004) Jaworska Karter (2001) Karter (2005) Meier (2002) Capelson (2006) Capelson Mitchell (2004)

26 7 TABLE 27

© 2010 Queen’s Printer and Controller of HMSO. All rights reserved. Clinical effectiveness of self-blood glucose monitoring DOI: 10.3310/hta14120 Health Technology Assessment 2010; Vol. 14: No. 12 ) 1c 1c with 1c (by 0.3%) with more 0.3%) with more (by with SMBG in insulin- with SMBG SMBG with more SMBG with more in SMBG only with more SMBG only with more SMBG with more 1c 1c 1c 1c 1c 1c 1c 1c NS overall, lower HbA lower NS overall, NS : NS : 1.9% with SMBG by reduced NS : NS : NS : NS : NS : 1c 1c 1c 1c 1c 1c 1c 1c 1c HbA SMBG (depending on entry HbA but not non-insulin treated treated not with oral patients, insulin-treated those with higher initial HbA for Results Lower HbA Lower HbA HbA Lower Lower HbA Lower Morbidity and mortality lower with Morbidity and mortality lower SMBG Lower HbA Lower HbA HbA HbA HbA HbA Lower HbA Lower HbA Lower HbA Lower HbA HbA more SMBG in specified treatment SMBG in specified treatment more groups HbA 4 Diabetes duration NR NR NR NR 0 0 NR NR 8.6 NR 12 NR 10 NR > 87%, NR NR NR Treatment Insulin Sulphonylurea insulin Oral, Oral, insulin Oral, Diet, oral, oral, Diet, insulin Oral, insulin Oral, Diet, oral, oral, Diet, insulin oral, Diet, insulin oral, Diet, insulin Sulphonylurea oral, Diet, insulin Insulin oral, Diet, insulin NR oral, Diet, insulin Oral Sulphonylurea Oral 65 Age 48 68 20 to > 56 63 56 60 56 58 65 53 NR NR 65 69 63 39–89 59 1c Starting HbA 8.1 8.1 NR 8.4 7.7 NR NR NR 9.1 NR NR NR 7.6 NR 5.4–6.9 7.2 7.9 NR Education/ counselling NR NR NR NR NR NR NR NR NR NR NR NR NR NR NR NR NR NR SMBG method NR NR NR NR NR NR NR NR Yes NR NR NR NR NR NR NR NR NR and 1c 1c in insulin 1c 1c 1c 1c 1c 1c 1c 1c 1c 1c 1c Focus Intensified SMBG Association between SMBG use and HbA SMBG Association between use and HbA SMBG Association between use and HbA SMBG Association between use and HbA SMBG/ Association between SMUG use and HbA Access strips vs no access SMBG Association between use and HbA SMBG Association between use and HbA SMBG Association between use and HbA SMBG Association between use and HbA blood glucose Access-free monitors blood glucose Access-free monitors SMBG Association between use and HbA SMBG Association between use and HbA SMBG Association between use and HbA SMBG Association between use and HbA Association between SMBG Association between use and morbidity/mortality users and non-insulin medication change 94 93 83 95 96 87 85 81 82 86 88 92 91 90 16 89 84 ] 15 Murata (2009) Study (2003) Stiptzarov ROSSO study [Martin ROSSO (2006) Schiel (1999) Schütt (2006) Secnik (2007) Soumerai (2004) (2007) Tengblad Murata (2003) Oki (1997) Ozmen (2003) Patrick (1994) Rindone (1997) Roblin (2001) (2004) Wen Wieland (1997) not significant. NS, not reported; NR, Rost (1990) 26 (1990) Newman 27

TABLE 8 Summary of messages from qualitative studies

Perceived advantages Barriers Reassurance when blood glucose levels were normal People tended not to act on their SMBG results Patients felt they could use SMBG to assess effects of SMBG associated with increased levels of depression and behaviour anxiety compared with patients who do not self-monitor Participants felt empowered to take more control over their SMBG as threat – constant reminder of illness health care and ability to contribute to physician’s evaluation Feeling of failure, self-blame when blood glucose levels were of their status abnormal Convenience of taking measurements Health professionals were often perceived to show no interest in meter readings – lack of feedback Lack of specific instructions and education received

have an expectation that individuals are using not be sufficiently clear. For example, the NICE SMBG as an aid to improved self-management of guideline CG669 says SMBG ‘should be available diabetes. If this assumption is not challenged then to those on oral glucose-lowering medications to patients are needlessly burdened with an additional provide information on hypoglycaemia’ but that is (not to mention painful) diabetes-related task for not relevant to those on metformin alone (because apparently no benefit. With the NHS spending metformin does not cause hypoglycaemia). It also almost as much on blood glucose testing materials says that SMBG should be available to those on as on oral hypoglycaemic agents,105 and 69% of insulin treatment but does not say whether this participants on oral hypoglycaemic agents taking should apply to those on a small once-daily dose of no action at all if a reading was beyond their target basal insulin. If individuals are not benefiting from range, it is clear that patient education needs to be SMBG, and indeed it is detrimental to their overall improved. Furthermore, the behaviours of HCPs health, there is a clear need to cease SMBG. There in relation to how they issue blood glucose meters is also a passionate argument from patient groups and help patients interpret the results, should be and the pharmaceutical industry that SMBG for examined. individuals with T2DM should not be withdrawn. O’Kane and Pickup (2009)106 perhaps aptly The simple act of how and whether a blood glucose declared that ‘present widespread use of SMBG in meter was issued at all to a patient was associated T2DM is a good example of a monitoring test that with whether individuals felt their HCP was taking was adopted in advance of robust evidence of its their diabetes seriously enough.6 Failure to receive clinical efficacy’. Thus identification of potential a blood glucose meter was associated with increased subgroups of those patients who would receive the anxiety and undermining of confidence in HCPs. most benefit from SMBG should be identified, perhaps by some qualitative work to identify The mode of obtaining meters or amounts of characteristics of those most likely to benefit education received did not appear to differentially (which may be about patient attributes rather than impact on patients’ views of glucose monitoring treatment) followed by a RCT. according to Peel et al. (2004).101 Whether a patient had well-controlled diabetes or not affected Most studies, including 18 out of the 36 satisfaction with SMBG, that is patients with observational studies, report that SMBG does

well-controlled diabetes viewed SMBG positively, not improve HbA1c level for most patients on whereas poorly controlled patients voiced more diet and lifestyle change or oral hypoglycaemic concerns and experienced monitoring fatigue.102 agent (OHA) alone. There are repetitive themes throughout the literature on why SMBG is At a workshop at the Spring 2009 Diabetes UK ineffective for many individuals. These include conference (attended by two authors of this lack of education, lack of interest from HCPs report), some patients and industry representatives in results, failure to make behaviour/lifestyle or said that some general practitioners (GPs) were therapy changes based on readings, failure to now rationing test strips for individuals with understand exactly what SMBG is (i.e. a tool to aid diabetes, presumably because of rising costs and diabetes self-management), failure to calibrate or doubt about effectiveness. This can appear to check accuracy of readings and failure to identify be contrary to current guidelines, but these may patients most likely to benefit from the technology. 28 DOI: 10.3310/hta14120 Health Technology Assessment 2010; Vol. 14: No. 12

Consideration needs to be given to identifying HCPs’ responsibilities include helping patients those patients who would benefit from SMBG both make informed decisions about diabetes and biomedically in terms of glycaemic control and its self-management in the context of their own psychosocially in terms of improved QoL. However, lives so that they are empowered to engage the key may be to not only identify these patients, more effectively in self-care behaviours. but also have a supportive HCP who supports them • One of the biggest barriers to behaviour in self-management and the best use of SMBG change is fear of failure, which grows each time data. we try unsuccessfully to achieve a goal. Being overwhelmed with information, but not given Funnel and Anderson (2004)107 developed the tools to interpret it, can add to the burden, the empowerment philosophy within which not reduce it. Emotions are important driving approaches to education incorporate interactive forces that require exploration. teaching strategies that are designed to involve • Patients are already motivated to accomplish patients in problem-solving and address their their own goals – their behaviours are often cultural and psychosocial needs. Key tenets of the not irrational to them and underlying health empowerment philosophy include: beliefs should be explored. Collaboration between patients and HCPs is required to set • Empowering people with diabetes to make self- goals and achieve targets. directed behaviour change. • Treatment needs to be personally meaningful • It is not the HCP’s job to get patients to do to patients – i.e. what does it mean to me? what they consider ‘the right thing’, rather What difference will doing this test make?

DOI: 10.3310/hta14120 Health Technology Assessment 2010; Vol. 14: No. 12

Chapter 3 Self-monitoring of blood glucose: economic literature review

n this literature review, a base year of 2008 has These costs were extrapolated to the UK as a whole Ibeen applied for costs and prices, with sums by applying disease prevalence data of 3.7% to converted being reported in square brackets: give an annual average cost per patient of £73.64 [£XX]. Where papers used an alternative base year, [£76.10] and a total UK cost of £165M [£171M]. the Health and Community Services price index The cost for England alone in 2006–7 was estimated as reported within the Personal Social Services to be £138M. The authors noted that what they Research Unit (PSSRU) Costs of Health and Social describe as the UK consensus recommendations Care108 has been applied. Where costs and prices on monitoring, suggest that those using diet were reported in a foreign currency these were and exercise alone, or monotherapy metformin, converted to pounds sterling using the exchange monotherapy glitazone or metformin plus rate prevailing on 5 April at the end of the base glitazone, should not be using SMBG. This resulted year of the paper, the Health and Community in an estimate of £13.42M [£13.87M] being spent Services price index being subsequently applied to unnecessarily on SMBG among these patients, the resultant pounds sterling amount if required. which was only partially offset by a £610K [£630K] Where the base year was not stated within the underspend among sulphonylurea monotherapy paper it was assumed to be the publication year. patients. In contrast, multiple oral agent patients were typically estimated as underutilising SMBG to the extent of £2.56M [£2.65M] per annum. Those Cost studies using insulin plus an oral therapy were estimating Cost studies: full papers as overutilising SMBG by £6.7M [£6.92M] per annum, to yield an estimate of the total overspend Belsey et al. (2009)100 undertook a retrospective of £17.02M [£17.59M]. analysis of the IMS Disease Analyzer database of 40,651 patient records between March 2007 and The authors acknowledged that individual February 2008. They identified those with T2DM circumstances will in some cases have correctly who had received one or more prescriptions for over-ridden the consensus guidelines and that, as a oral glucose lowering drugs or insulin or had a consequence, the estimated overspend will to some clinical diagnosis of diabetes in the preceding extent be an overestimate. However, they also note 12 months. Among these patients 12.9% were that the DiGEM trial showed no benefit to those on estimated to be using diet and exercise alone, sulphonylurea alone, and avoiding SMBG in this 34.1% were estimated to be on a single oral agent, group could double the potential savings. 26.0% on multiple oral therapy, and 27% on oral therapy plus insulin. Weber et al. (2007)109 used the results of the German ROSSO15 longitudinal observational Coprescription of test strips averaged 54%, but study of SMBG versus non-SMBG between two varied from a low of 26% among those on diet groups of patients with T2DM: those using only and exercise, between 36% and 44% among those oral drugs and those using oral drugs plus insulin. on one oral agent, between 48% and 60% among The ROSSO results included long-term outcomes those on multiple oral therapy, and between 87% in terms of micro- and macrovascular event rates and 89% for those receiving insulin. Given these over an average follow-up period of 6.5 years, rates of use, the annual average cost of tests strips which Weber et al. reported as being 7.2% among was £9.83 [£10.16] for those on diet and exercise; the SMBG group and 10.4% in the control group between £15.95 [£16.48] and £23.50 [£24.28] (p = 0.002). Similarly, fatal event rates were lower for those on one oral therapy; between £23.87 among the SMBG group at 2.7% compared with [£24.67] and £37.91 [£39.18] for those on multiple 4.6% with a p-value of 0.004. These event rates oral therapy; and between £135.83 [£140.36] and were associated with Swiss unit costs to determine £191.18 [£197.56] for those on insulin. the average cost per patient. 31

Self-monitoring of blood glucose was associated Cost studies: abstracts with an additional average annual direct cost Neeser et al. (2006)111 also report the results of for test strips and lancets of CHF90 (90 Swiss the ROSSO15 study, but on the grounds of one francs) [£39] among those using oral agents and group being 3.5 years older on average than the CHF130 [£56] among those using oral agents in other group, they undertook a matched-pairs combination with insulin. But these additional analysis based on age, gender, smoking status and direct costs were more than offset by the costs of blood glucose level at diagnosis. This resulted reduced events with the total average annual costs in 813 matched pairs being available for the of CHF5140 [£2219] among SMBG users compared comparison of SMBG with no-SMBG, with costs with CHF5654 [£2441] for non-users among the of 18 complications of diabetes being estimated oral agents group, and CHF8254 [£3564] among in addition to the costs of SMBG. Among those SMBG users compared with CHF11,776 [£5084] treating their diabetes with oral antidiabetic drugs for non-users among the oral agents-plus-insulin alone, Neeser et al. estimated that SMBG led a group. However, the generalisability of the study reduction of €214 [£162] per year, but this was not is limited by the ROSSO source data being drawn statistically significant. Among those using insulin from a longitudinal retrospective study, not a in combination with oral antidiabetic drugs, SMBG randomised trial. Tiley110 noted that SMBG could was found to cause a significant reduction in costs not be considered to be the sole source of the risk of €1727 [£1310] per year. However, the caveats of reduction. Other interventions would also have Tiley (2002)110 still apply: the care for the SMBG ‘played a part in the outcome; these including group differed in other ways. regular educational input, regular screening and more regular dietary advice and medical consultation’ among the SMBG group. Quality of life Quality of life: full papers Meier et al. (2002)79 undertook a study of the effect 11 of the frequency of SMBG on costs and HbA1c levels Farmer et al. (2009) reported the utility estimates among a sample of patients with T2DM in the US derived from UK DiGEM10 trial. Within the trial Veterans Affairs study, who were being controlled period the QoL values, derived from the completed on either diet or oral antidiabetic drugs. A cases’ EuroQol-5D (EQ-5D) questionnaire data, retrospective analysis of prescription data provided showed no change between baseline and 12 months the estimate of the pre-baseline frequency of for the control group, the average increasing by SMBG, given an assumption of no wastage of test an insignificant 0.002 (95% CI –0.034 to 0.038). strips. A policy of reduced SMBG frequency was There was some evidence of a fall among the less implemented by letter and by reducing the number intensive SMBG group, –0.037 between baseline of test strips per prescription. and 12 months, which, given a 95% CI of –0.080 to 0.005, was of borderline significance. The more The authors found that the frequency of SMBG intensive SMBG group recorded a larger fall of among those on oral agents was 1.36 strips per day, –0.056, which, given a 95% CI of –0.099 to –0.013,

with an average HbA1c level of 7.83%. Subsequent achieved significance. The differences between to implementation an average 0.74 strips were low-intensity SMBG and standardised care, and being used, with a non-statistically significant between more intensive SMBG and standardised

change in average HbA1c level to 7.86%. Among care, exhibited a similar pattern, though neither those being controlled on diet the average test quite reached statistical significance given frequency dropped from 1.07 strips per day to 0.51 respective central estimates and 95% CIs of –0.040

strips per day, with HbA1c level again showing a (–0.094 to 0.015) and –0.053 (–0.109 to 0.004), non-significant change from 6.85% to 6.78%. The respectively. QoL values were also imputed for the authors had to cope with a change of laboratory full data set. These showed a similar pattern to that analyser between baseline and end of study, and reported above, the main difference of note being used several methods to overcome this, which is that the difference between more intensive SMBG slightly confusing. Despite these difficulties, the and standardised care was estimated to reach authors concluded that reduced SMBG could statistical significance given a central estimate result in an average annual saving per patient of and 95% confidence interval of –0.072 (–0.127 to US$76.44 [£66.38] without affecting glycaemic –0.017). So SMBG may slightly reduce the QoL. control.

32 DOI: 10.3310/hta14120 Health Technology Assessment 2010; Vol. 14: No. 12

The 2005 Cochrane review of SMBG37 in patients • standardised usual care, through which there with T2DM not using insulin found two relevant was no impact on HbA1c level. papers57,61 for assessing the QoL impacts of SMBG. Muchmore et al. (1994)57 was reported as finding This analysis used only the results of the DiGEM identical results for QoL for those using SMBG trial, and the alternative of SMUG was not compared with the control group across the considered. Note that in addition to the HbA1c dimensions assessed: satisfaction, impact and worry changes, clinical effects also were observed in (social/vocational and diabetes related). Paralleling terms of blood pressure and cholesterol. The direct this, Schwedes et al. (2002)61 found that well-being QoL effects of SMBG are reported in the previous and treatment satisfaction improved by the same section. amount across both groups. Neither study found any statistically significant difference between the The direct impact of SMBG on QoL was estimated two groups in terms of QoL. through the baseline and 12-month EQ-5D responses, through the application of the standard Franciosi et al. (2001)70 reported the results of a UK tariff. Given the 12 months’ clinical results prospective study of 3567 Italian outpatients with from the DiGEM trial, the risk factors for the T2DM, among whom there were 2855 patients complications of diabetes were extrapolated to with data on SMBG: 17% tested more than once lifetime costs, life expectancy and quality-adjusted per day, 31% tested more than once per week, life expectancy using the UK Prospective Diabetes 14% tested less than once per week and 38% Study (UKPDS) Outcomes Model.112 Future health did not perform SMBG. Among those not using effects and costs were discounted at 3.5%. insulin, and adjusting for baseline characteristics, SMBG of at least once per day was significantly The modelling assumed that patients were initially associated with higher levels of distress, worries controlling their diabetes through diet alone and depressive symptoms, and SMBG of at least or oral drug therapy. As the disease progresses once per week was still significantly associated with and control worsens, patients will intensify their higher levels of distress and worries. In contrast, therapy, moving from controlling their diabetes there was no association between QoL and SMBG using diet alone, to oral drug therapy, to basal among patients using insulin, with the exception insulin-plus-oral drug therapy to basal/bolus of stress, which was lower for those patients insulin-plus-oral drug therapy. It is unclear if, or performing SMBG at least once per week. how, these intensifications of therapy have been incorporated within the modelling. Could these differences relate to ability to self- adjust medication? People on insulin are able to, During the 12 months’ period of the DiGEM trial and indeed are encouraged to, adjust insulin dose a resource use questionnaire was also administered, according to blood glucose levels. However, those which, together with patients’ SMBG diaries on oral agents are presumably dependent on their and nurse notes, provided data on the within doctors to change prescribed doses. trial resource utilisation – including nurse visits, medications, primary care, hospital care, and auxiliary medical resource use such as podiatry, Cost-effectiveness optician and dietitian services. Where information Cost-effectiveness: full papers was missing on SMBG and medication use, the last value carried forward technique was used, which Farmer et al. (2009)11 undertook a cost–utility could be misleading because those who do not study using the results of the UK DiGEM trial, return may have altered their behaviour. SMBG was comparing the costs and effects among the typically associated with longer nurse visits than DiGEM10 trial population of patients with T2DM standardised care, with the more intensive SMBG being controlled through either diet or oral drug typically also being associated with longer nurse therapy. This was an update of the Simon et al. visits than less intensive SMBG. (2008)12 paper, and, in line with this, considered the three comparators of: Resource use was valued by applying unit costs reported in the NHS reference costs 2005–06;113 the • more intensive SMBG, through which the Annual financial returns of NHS trusts 2003–2004;114

average HbA1c level fall was –0.17% and the PSSRU Costs of Health and Social Care • less intensive SMBG, through which the 2002,115 with these being inflated to 2005–6 costs

average HbA1c level fall was –0.14% using the Department of Health Pay and Prices Inflation Indices.113 33

Within the trial period, standardised care was Clinical effectiveness estimates in terms of the

estimated to cost £89 [£95] compared with £181 HbA1c effect were drawn from the large 3-year [£193] for the less intensive SMBG and £173 Kaiser Permanente Healthcare Group observational

[£184] for the more intensive SMBG, giving cost study among 30,000 patients, with the HbA1c increases of £92 [£98] and £84 [£90] for the SMBG changes reported above relating to a subset of groups, respectively. Given parallel QoL losses of around 16,000 new users of SMBG as reported in –0.008 quality-adjusted life-years (QALYs) and Karter et al. (2001).75 –0.036 QALYs from less intensive SMBG and more intensive SMBG, respectively, compared with Medicare reimbursement unit costs were applied, standardised care, the within trial comparison with QoL values being drawn from the UKPDS estimated that standardised care dominated SMBG. study, but, crucially, it was assumed that there was no disutility associated with SMBG use. The above values are as per those reported in 12 the Simon et al. (2009) paper, with Farmer et al. The changes in HbA1c level were assumed to be (2008)11 extending this through extrapolating the maintained for the duration of the modelling. long-term effects by using the UKPDS Outcomes Patients had an average age of 63 years, with the Model.112 This marginally improved the situation model time horizon of 40 years consequently, and for the SMBG: for the less intensive SMBG, the effectively, being a lifetime horizon. Costs were lifetime patient loss was estimated to be –0.004 inflated to 2006 prices, with costs and benefits QALYs, while the additional lifetime cost was being discounted at 3%. It was assumed that after 5 £59 [£63]; and, for the more intensive SMBG years patients would switch to insulin. the lifetime patient loss was estimated as –0.020 QALYs, while the additional lifetime cost was £56 For the comparison of ‘once-daily SMBG’ with ‘no [£60]. This did not change the overall conclusion SMBG’, the central estimate was that an additional that standardised care was both more effective and 0.103 QALYs would accrue at an additional cost less costly than SMBG, and so dominated SMBG. of US$808 [£493] to yield a cost-effectiveness estimate of US$7856 [£4789] per QALY. For the Similarly, a probabilistic analysis estimated that comparison of ‘three-times-daily SMBG’ with ‘no while the probability of SMBG being cost-effective SMBG’ the central estimate was that an additional would rise as the willingness to pay increased 0.327 QALYs would accrue at an additional cost to around £10K per QALY, any increases in the of US$2161 [£1317] to yield a cost-effectiveness probability of SMBG being cost-effective as the estimate of US$6601 [£4024] per QALY. willingness to pay increased further were limited. At a willingness to pay of £30K per QALY, the Results were particularly sensitive to the time probability of less intensive SMBG was a little horizon assumed. Reducing this to 5 years resulted under 40% and the probability of more intensive in cost-effectiveness estimates for ‘once-daily SMBG was around 15%, these probabilities showing SMBG’ and ‘three-times-daily SMBG’ compared little change as the willingness to pay was increase with ‘no SMBG’ of $23,380 [£14,253] per QALY to £50K per QALY. and $29,137 [£17,762] per QALY, respectively.

Tunis and Minshall (2008),116 in a study funded by The Tunis and Minshall (2008)116 study needs to LifeScan, a major manufacturer of glucose testing be interpreted with caution due to the clinical data material, modelled the cost–utility of SMBG among being from an observational study, the observed

patients with T2DM using oral antidiabetic drugs differences in HbA1c level during the study being within the US Medicare setting, using the CORE assumed to be maintained over the lifetime Diabetes Model.117 This compared: of the patient, and, most obviously, due to the assumption of SMBG not in itself being associated • three-times-daily SMBG, through which with any disutility. Aspinall and Glassman (2008)118

average HbA1c level was assumed to fall by expressed additional concerns in a letter to the 1.02% editors that not all patients would commence

• once daily SMBG, through which average SMBG at the average HbA1c value assumed by

HbA1c level fell by 0.32% Tunis and Minshall, and that the effect of SMBG

• no SMBG, through which average HbA1c level would be, in all likelihood, different for different

rose by 0.13%. baseline levels of HbA1c. Note also that an abstract

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of a cost-effectiveness study, undertaken by Tunis,119 effectiveness estimates for SMBG compared with of SMBG among patients with T2DM, using the non-SMBG of: same clinical data source as her 2008116 paper, reported a considerably worse cost-effectiveness • £15,515 [£17,760] per QALY for those on diet ratio than those reported above. and exercise • £4508 [£5160] per QALY for those on oral Palmer et al. (2006),22 also funded by LifeScan, antidiabetic drugs modelled the cost–utility of SMBG among patients • £4593 [£5257] per QALY for those on insulin. with T2DM controlling their diabetes with diet and exercise, or with oral antidiabetic drugs, or with As in the Tunis and Minshall (2008) paper,116 insulin. This compared SMBG with non-SMBG Palmer et al. (2006)22 found results to be sensitive among the three patient groups, with assumptions to a shorter time horizon. Reducing this to 10 on HbA1c level as follows: years resulted in estimates of cost-effectiveness of £74,528 [£85,311] per QALY for those on diet and • for those on: exercise; £33,742 [£38,624] per QALY for those on –– diet and exercise – SMBG resulted in a fall oral antidiabetic drugs; and £11,082 [£12,685] per of 0.3% QALY for those on insulin. An assumption of the

–– oral antidiabetic drugs – SMBG resulted in HbA1c benefit only lasting for 5 years also worsened a fall of 0.4% cost-effectiveness ratios among the three patient –– insulin – SMBG resulted in a fall of 0.6%. groups: £25,802 [£29,535] per QALY; £9141 [£10,464] per QALY; and, £9909 [£11,342] per These clinical effectiveness estimates were drawn QALY, respectively. from the Karter et al. (2001)75 study, as reported above for the Tunis and Minshall (2008) paper,116 Applying the disutility of taking insulin to SMBG though within an alternative patient grouping. reduced the anticipated gains from SMBG. This Palmer et al. (2006)22 also assumed that only 78% particularly affected the diet and exercise group, of patients would adhere to SMBG. The 22% not among whom the anticipated gain fell from 0.165 adhering to SMBG were assumed to be identical to to 0.077 QALYs, resulting in a cost-effectiveness the non-SMBG in terms of both costs and effects, estimate of £34,259 [£39,216] per QALY. The and, as a consequence, the main effect of the effect, while still large, was less dramatic for those inclusion of non-adherence is simply to dilute the taking oral antidiabetic drugs and those taking SMBG arm. insulin, with the QALY gains falling from 0.225 to 0.140 QALYs and from 0.255 QALYs to 0.172 The analysis was undertaken using the CORE QALYs, respectively. As a consequence, their model in the UK setting in terms of costs, with a respective cost-effectiveness estimates worsened to base year of 2004. A lifetime horizon was adopted £6985 [£7996] and £6586 [£7539] per QALY. with costs and benefits being discounted at 3.5%. Cost-effectiveness: abstracts In common with Tunis and Minshall (2008),116 Palmer et al. (2006)22 also assumed that the Tunis (2009)119 reported the results of further benefit in terms of improved HbA1c level would be cost-effectiveness modelling using data from the maintained over patient lifetime and that there Kaiser Permanente Healthcare Group observational was no direct disutility from SMBG, although a study as for her 2008 paper.116 Compared with ‘no sensitivity analysis was undertaken equalising this SMBG’, the results were as follows, the first and to the disutility from taking insulin. third being roughly one-half to one-third of the estimated gains of her 2008 paper.116 The additional annual ongoing cost of SMBG varied between the patient groups, being £124 • Once-daily SMBG led to an additional 0.047 [£142] for those on diet and exercise, £247 [£283] QALYs. for those on oral agents and £371 [£425] for those • Twice-daily SMBG led to an additional 0.116 on insulin. The respective average lifetime patient QALYs. gains were estimated as being 0.165 QALYs, • Three-times daily SMBG led to an additional 0.225 QALYs and 0.255 QALYs, respectively, 0.132 QALYs. while the respective additional lifetime costs were estimated to be £2564 [£2934], £1013 [£1160] and The difference may be because the 2008 study was £1171 [£1340], respectively. This resulted in cost- of new users. As a consequence, cost-effectiveness 35

estimates worsened considerably to US$26,206 [£24,084], respectively. The authors regarded this [£17,706] per QALY, US$18,572 [£12,548] per as being cost-effective. QALY and US$25,436 [£17,186] per QALY, respectively. In an earlier abstract, Weber et al. (2006)123 report the outcome of a Markov model looking at the Mataveli et al. (2008),120 in an abstract with few cost-effectiveness of SMBG among patients with details, reported the results of a cost-effectiveness T2DM not using insulin. The impact of SMBG

analysis of SMBG among patients with T2DM was limited to the change in HbA1c level reported using oral glucose lowering drugs within the in the Sarol meta-analysis.34 Given a frequency

Brazilian setting. It was reported that daily use of of seven times per week, the impact on HbA1c

SMBG was associated with a fall in HbA1c level of level was reported as an improvement of 0.42%. 0.6%, though details are sparse and other changes This led to an estimate of the cost-effectiveness of may have occurred. Over a 3-year period, once- SMBG alongside metformin treatment of €28,171 daily SMBG was estimated to result in average cost [£21,074] per life-year gained and alongside savings across three Brazilian health maintenance sulphonylurea of €27,062 [£20,245] per life- organisations: R$3499 (Brazilian real) [£954], year gained. Applying the upper and lower 95% R$884 [£258] and R$649 [£190]. The source of confidence limits reported in Sarolet al.34,39 resulted funds is not given, but one author is from LifeScan. in cost-effectiveness estimates of €63,404 [£47,433] per life-year gained and €19,351 [£14,477] per Erny-Albrecht et al. (2007)121 reported the outcome life-year gained, respectively. of modelling of the cost-effectiveness of SMBG using the Kaiser Permanente Healthcare Group Neeser et al. (2006),124 in a letter, reported observational study. The estimated patient impacts undertaking a Markov modelling exercise of the of this modelling fell between those of the Tunis cost-effectiveness within the German health-care 116 and Minshall (2008) full paper and the Tunis system using a 0.39% HbA1c level reduction from (2009)119 abstract above. Compared to ‘no SMBG’: SMBG among non-insulin-using patients with T2DM, the reduction being derived from the • Once-daily SMBG led to an additional 0.083 Welschen et al. (2005)36 meta-analysis. No other QALYs. details are provided as to the modelling inputs or • Twice-daily SMBG led to an additional 0.216 the model used, but they report an anticipated QALYs. 0.083 years’ additional life expectancy and a cost • Three-times-daily SMBG led to an additional per life-year of ~€31,000 [£23,191]. Davidson 0.270 QALYs. (2006),125 in a response to this, highlighted the anticipated gain estimated by Neeser et al. (2006)124 Given these estimates, the respective cost- being only 30 days, and that the estimate of a

effectiveness estimates were US$6530 [£3424] per reduction in HbA1c level was significant in only two QALY, US$5997 [£3145] per QALY and US$7784 out of the six trials within the meta-analysis. [£4082] per QALY, respectively. The source of funding is not given but, from the authorship, it is likely to have been industry funded. Summary

Weber et al. (2007)122 also reported the outcomes of Reviewing cost-effectiveness was complicated by: modelling using the Kaiser Permanente Healthcare Group observational study. Few details were • a lack of clarity as to the assumed duration provided but the additional cost of treatment in of therapies and when or if intensification of the SMBG group was estimated as being €1524 therapy, such as switching to insulin, had been [£1073] for testing of between every 2 days and allowed for once daily, and as being €3273 [£2304] for testing • a lack of clarity as to the assumed duration of

of between 2.5 and 3-times-daily. Additional an effect upon HbA1c level, though it appears life expectancies of 0.021 years and 0.222 were likely that this was assumed to be lifetime, estimated, resulting in cost-effectiveness ratios regardless of any intensification of therapy of €70,199 [£49,419] and €14,710 [£10,356], • with the exception of Farmer et al.,10,11 typically respectively. Further modelling estimated the cost- assuming no direct QoL decrement from effectiveness of testing between once and twice SMBG among those controlling their diabetes daily as between €33,607 [£23,659] and €34,211 with diet or oral medication.

36 DOI: 10.3310/hta14120 Health Technology Assessment 2010; Vol. 14: No. 12

The cost of SMBG in people with T2DM in Meier et al. (2002)79 estimate savings to be £66 per England is probably around £38M per year,100 of annum. which about £17M could be saved by adhering to previous guidelines, and another similar However, most of these studies fail to allow for the amount by applying the findings of DiGEM in the negative impact of SMBG on QoL, as reported by sulphonylurea-only group. the DiGEM10 group and Franciosi et al. (2001).70

The reported costs per annum of SMBG vary The cost-effectiveness analyses vary in their amongst studies, the lowest being the estimate by assumptions, with those funded by industry being 100 Belsey et al. (2009) of about £10 per year for more optimistic in the size of gains in HbA1c level, infrequent testers on diet alone, to £259 in the and hence producing lower incremental cost- Palmer et al. (2006) study.22 effectiveness ratios (ICERs). The best analysis to date is that of Farmer et al. (2009)11 (funded by the Several studies assert that SMBG can lead to UK Health Technology Assessment programme), savings that offset testing costs, for example Weber which, after taking into account all costs, gains and et al. (2007)122 estimate the additional costs to be disutilities, concluded that SMBG was not cost- £39 annually but that taking avoided events into effective. account gives an average annual saving of £222.

DOI: 10.3310/hta14120 Health Technology Assessment 2010; Vol. 14: No. 12

Chapter 4 Discussion

Problems with the evidence • There is also lack of agreement on what is a clinically significant difference in HbA level. base 1c The consensus seems to be 0.5% or more but Some of the reasons for the controversy around the that appears to be an arbitrary number. value of SMBG in people with T2DM are apparent • Differences in the use made of the data from from the literature. They include: SMBG. In some studies, no action was taken based on the results, so no benefit was likely. • The evidence base did not allow us to answer In others, drug treatment could be changed by our original primary or additional questions; doctors but not by patients. In some studies, the studies did not provide information patients were encouraged to adjust treatment on patient outcomes by treatment received themselves. However, there was little evidence (i.e. diet alone, metformin monotherapy, for adjustment in what was most under their combination oral therapy, or combinations of control – diet and exercise. There appears to oral therapy and insulin), with most studies not be a disconnection between SMBG and diet/ even providing a breakdown of the treatment exercise, in that neither patients nor HCPs are patients were taking. Similarly, none of the actively checking SMBG in response to specific studies provided enough information for behaviour changes, such as a diet or starting making a judgement on any subgroups of an exercise regime. It’s almost as if patients patients that might benefit most, or that might don’t regard lifestyle change as an appropriate be harmed. We also did not find any studies remedy. Kempf et al. (2008)126 suggest that that investigated in detail the different aspects ‘appropriate use of SMBG data by the patient of education in relation to SMBG. may be improved by practical lessons that allow • Most, if not all, RCTs have treated SMBG – the patient to recognise the impact of high which, in the first instance, is a diagnostic tool versus low glycaemic meals and of moderate – as an intervention in its own right, rather physical activity such as 30 minutes of brisk than acknowledging that in order to be able walking’. to have a benefit on patient outcomes. SMBG • Some of the observational studies had too needs to be linked to appropriate education, many confounders to provide useful data. For

feedback, treatment and behaviour adjustment, example, some reported higher HbA1c level as well as to an analysis of the types of patients in those undertaking SMBG but that may and situations for which SMBG might be most be because poor control was the reason for helpful. In some studies there appeared to be a starting SMBG. In others, SMBG appeared to lack of provision of education and/or feedback, improve control but the improvements may and in others there was a lack of detail about have been in adherence to other aspects of self- what education was offered. Most other care. potential modifiers of SMBG benefit were not • Some studies reported the results of SMBG assessed at all. where there was no education to empower • Differences in conclusions of the systematic patients in altering treatment. Some implied reviews, with some reporting that results are that SMBG was carried out to inform the inconclusive, while others reported that SMBG doctor or nurse, rather than the patient.

improves HbA1c level. However, it is notable • The baseline HbA1c level may be relevant. that the latter usually find small differences It was sometimes too low to expect

in HbA1c level ranging from improvements of much improvement (but there could be 0.16%35–0.42%.34 It is also noteworthy that the improvements in other areas such as effects sizes are smaller in the later reviews with hypoglycaemic episodes). A simple regression more trials – for example 0.24%,33 0.16%35 and analysis suggested that effects of SMBG were 38 34 37 0.22% compared with 0.42%, 0.39% and larger in patients with higher baseline HbA1c 0.41%.31 values.

Some common themes emerged. Use of SMBG in In the trial by Schwedes et al.,21,61 SMBG use in T2DM is clearly an international issue, with studies patients with T2DM (on diet and/or oral treatment) from the UK, Italy, New Zealand and Australia. was combined with a short counselling algorithm focusing on promotion of self-perception (diary It may be that better targeted selection of patients entries of eating, well-being and SMBG readings), for SMBG is required. McGeoch et al. (2007)32 self-reflection (what worked/did not work in concluded that SMBG may not be helpful or experience with SMBG, what facilitated SMBG), economically justified in all cases, but that and enhancement of self-regulation (ideas of individuals would benefit if: how to use diary entries and SMBG to improve glycaemic control, assessment of probability of

• their baseline HbA1c level is above 8% achieving goals). Compared with the non-SMBG • they are properly educated in the use of SMBG control group, patients in the intervention group

and how to take appropriate action based on had a 0.46% greater reduction in HbA1c level, and the results depression was significantly reduced (no significant • they are sufficiently literate and numerate to difference in treatment satisfaction, general well- take advantage of the intervention being, anxiety, energy or positive well-being). • they are receptive to the need for better This is in contrast with the results of the DiGEM metabolic control and are motivated to make and ESMON trials, which used more traditional the necessary changes educational strategies. It has been argued that the • there are special circumstances – such as new additional counselling strategy used in the SMBG diagnosis, initiation or change in medication, group (but not in the control group) in the trial by illness, gestational diabetes and lack of Schwedes et al. meant that the effect of SMBG per awareness of hypoglycaemia. se could not be distinguished from the effect of the counselling – but then as a diagnostic test rather Davidson (2005)127 commented that possible than an intervention, SMBG cannot be expected explanations for lack of effect of SMBG in patients to have a benefit without giving patients and HCPs include: optimal help in using the results.

• patients receive little or no feedback on their Thus, education is required not only for patients, results but also for professionals such as practice nurses so • they are not taught the self-management skills that they can advise on treatment changes – though to lower blood glucose this might require a change in prescription that the • (in his experience) the vast majority of patients nurse could organise rather than provide. However, monitor fasting or preprandial BG values, if the prescription was dietary, the nurse or the which neither serves to educate or motivate. practice might not have access to sufficient dietetic help. The type of education offered also seems to be of importance, with education emphasising a positive Another issue is that there seems to be an attitude and enhanced self-efficacy possibly being assumption across the literature that it is simply more effective than simple ‘information-based’ a case of ‘to test or not to test’, i.e. that SMBG education. In one trial of both T1DM patients is ongoing rather than episodic. There was little and T2DM patients,20 recruits in the intervention reference in the literature to suggest that HCPs arm were given the Blood sugar monitoring owner’s are engaging patients in short bursts of targeted manual, devised by Laffel et al. (available at testing, for example to assess the effects of lifestyle US$5.25 from Joslin Diabetes Center, Boston, changes (weight change, exercise, dietary changes, Massachusetts, USA),128 which emphasises a etc.). Such an episodic approach might be more positive attitude. The control group was given effective and less costly. Testing could be at greater meters, strips and instructions in use. While intensity initially, with routine testing then stopped

there was no significant difference in absolute pending HbA1c results. It is also unclear whether

HbA1c levels at the end of the 6-month trial (the patients achieving ‘good’ diabetes control without difference was only 0.09%), significantly more SMBG might be actively discouraged from taking patients in the intervention group managed to on the additional burden of it.

improve their HbA1c values (61% versus 44%) and fewer participants had a negative affect regarding Selection might also be better if based more on SMBG than patients who were not receiving the patients’ personalities (some want to take control manual (38% versus 65%). 40 DOI: 10.3310/hta14120 Health Technology Assessment 2010; Vol. 14: No. 12

themselves, some do not) than on treatment group. qualitative evidence – that depression and anxiety It would be useful to split the insulin-treated group are due to the constant reminder of illness when into those on single basal injections per day from monitoring (and this may be especially true in those on more complex regimens. newly diagnosed patients, such as those in the ESMON trial, who may not yet have adapted to the There may also be unrealistic expectations of disease). On the other hand, if the aim is increased the value of SMBG, for example stimulated self-efficacy then avoidance is probably not an by advertising to HCPs and patients. Being a appropriate strategy. In a study of 292 insulin- diagnostic tool, SMBG is only ever going to be treated patients who had either T1DM or T2DM as good as the context in which it is used and the (48% T2DM) in the Netherlands, the coping style actions taken in response to the readings. of diabetes avoidance was significantly associated with less frequent SMBG and perceiving SMBG There are psychological disbenefits from SMBG as as a burden. Participants with a low level of self- used in current practice – anxiety, depression and efficacy perceived all types of self-management self-chastisement. Adverse effects on QoL were not activities as a burden. As also suggested by the only seen in clinical trials, but also in a large Italian data from the RCT by Schwedes et al. described observational study on SMBG in T2DM (2855 above,21,61 increased self-efficacy may therefore lead respondents, of whom 2254 were not on insulin).70 to feeling more in control, less burdened and less There was no association of SMBG frequency with depressed.131

HbA1c level in non-insulin-treated patients, but QoL (including diabetes-related distress, diabetes Clear, specific guidelines on who should use SMBG, health distress, diabetes-related worries and and how frequently, are required – repeatedly depressive symptoms) was significantly decreased articles cite ambiguity around current guidance for in those who were monitoring once or more per T2DM. Further research needs to address these day (no significant difference for those monitoring factors, rather than just asking whether SMBG is less frequently). The authors suggest that the useful per se. correlation with poorer psychological well-being could be related to the feeling of powerlessness The economics of SMBG caused by unsatisfactory results that patients are not able to improve, and they call for education Belsey et al. (2009)100 estimated that in the UK and better guidance on how to use the results for SMBG varies from a low of 26% among those treatment adjustment and/or behaviour change. controlling their diabetes through diet and exercise In a recent study from the USA of attitudes and alone, at an average annual cost of £10, rising as behaviours in 253 people with T2DM the following oral agents are added to peak at between 87% and factors were found to be significant barriers for 89% for those using insulin, at an average annual

SMBG, and were associated with higher HbA1c cost of between £140 and £198. Given this, the levels: ‘costs too much’, ‘hassle’, ‘depression annual overall UK cost of SMBG was estimated interferes’, ‘don’t understand’, ‘don’t like’, ‘it hurts’ as £171M, of which the authors estimated around and ‘don’t know how to use the results’.129 £13M was unnecessary, given current guidelines. These results can be coupled with those of the The invasiveness of the SMBG procedure may US Veterans Affairs study of Meier et al. (2002),79 also contribute to anxiety, as suggested by another within which a policy of reducing test strip usage American study of 339 diabetes patients (69.5% found that those using diet and exercise alone T2DM, 51.2% on diet and/or oral agents only), could approximately halve test strip usage, to one which showed that anxiety associated with SMBG every other day with no impact upon HbA1c level. invasiveness contributes to perceived burden and Similar results were reported for those using oral is negatively correlated with adherence to SMBG agents, though test strip usage was higher after the recommendations.130 reduction, at around five per week.

The question is whether the conclusion should Whether SMBG is cost-effective given its direct cost be that because of these potential psychological and its direct QoL impacts is not clear from the disbenefits SMBG should not be used at all or current literature. Farmer et al.10,11 undertook what whether these effects are just a warning sign that appears to be the most comprehensive study of the it should be used differently than used at present. cost-effectiveness of SMBG in the UK setting. This

There is a possibility – supported by some of the applied the direct QoL effects and HbA1c levels

effects of SMBG from the DiGEM study, assessing The findings of the IQWiG report are summarised cost-effectiveness within the trial period and in Box 1. The report placed most importance also extrapolating beyond this using the UKPDS on assessment of hypoglycaemia. There was Outcomes Model. Within the trial period, SMBG little emphasis on the issues of education and was estimated to result in additional costs and adjustment of therapy (other than using this as an QALY losses and so be dominated by standard care. outcome, but not in the sense of arguing that this is Extrapolation using the UKPDS Outcomes Model what should follow the SMBG measurement), and reduced both the additional costs and the QALY no discussion of behaviour changes. losses, due to some avoidance of downstream complications, but this did not affect the conclusion A review by O’Kane and Pickup (2009)106 comes to that SMBG was dominated by standard care. a similar conclusion as our review and ends with But the overall effects were small and subject to the comment that ‘The widespread use of SMBG considerable uncertainty. (particularly in type-2 patients) is a good example of self-monitoring that was adopted in advance Other cost-effectiveness studies typically found of robust evidence of it clinical efficacy’. Their

minor QALY gains due to improvements in HbA1c review provides a useful history of SMBG and the level. This was typically at some additional cost, technical aspects. though some studies suggested the possibility of downstream cost savings outweighing the initial One issue raised by O’Kane and Pickup (2009)106 costs of SMBG. A key aspect of these studies was is that most previous RCTs have excluded patients that SMBG was assumed not to be associated with who are already monitoring their blood glucose, any direct QoL loss, which appears unrealistic. and that this may cause a bias in that the excluded There is the clear potential for the immediate people may be the most successful. direct QoL loss from SMBG to outweigh any downstream benefit in terms of reduced The International Diabetes Federation issued complications if the immediate impact of SMBG its guidelines on SMBG in non-insulin-treated

upon HbA1c level is minor or not sustained. diabetes at the World Diabetes Congress in October 2009.98 The summary noted ‘further studies are needed to better assess the benefits, Other reviews optimal use and cost-effectiveness of SMBG’. The recommendations are given in Box 2. The IQWiG preliminary report on SMUG and SMBG in T2DM. Research needs The German equivalent of NICE, the Institut für Qualität und Wirtschaftlichkeit im The top priority for research is to determine Gesundheitswesen (IQWiG), produced a report whether SMBG is ineffective in T2DM, or whether (in German, and not included in our clinical we have just not used it effectively in appropriately effectiveness partly because of language and partly selected and empowered patients. Perhaps there because the preliminary report was published has been too much focus on the technology end of after ours was completed) assessing the effects the technology–human interface and not enough of SMBG or SMUG as an integral part of any on the human end. management strategy aimed at lowering blood glucose, compared with a strategy without self- Research is required to: measurement of glucose, or the comparison of a strategy involving SMBG with one involving SMUG • determine characteristics of patients benefiting in patients with T2DM who were not treated with most from SMBG, in terms of psychological insulin, with respect to patient-related outcomes.132 attributes, preferences, underlying treatment,

Studies were included only if they also considered baseline HbA1c level, duration of diabetes, outcomes such as hypoglycaemia, QoL, mortality, age, level of education, previous use of SMBG,

diabetes-related morbidity, etc., but HbA1c level motivation for self-care, etc. was also recorded. RCTs were considered, as well • determine the optimal duration and frequency as epidemiological studies assessing mortality and of SMBG for such individuals; specific time morbidity. Minimum study duration was 6 months. periods may occur at diagnosis, onset of Only full publications were included. behaviour change regimen (such as diet

42 DOI: 10.3310/hta14120 Health Technology Assessment 2010; Vol. 14: No. 12

BOX 1 The IQWiG report

The IQWiG report findings and conclusions were as follows: The search identified 15 relevant papers describing 11 studies. However, five studies were excluded for the following rea-

sons: three did not report relevant outcome measures other than HbA1c level (Allen 1990, Davidson 2005, Gallichan 1994) and two included relevant subgroups but the authors did not send the required data (Oria-Pino 2006, Wong 1986). The following five studies were included in the analysis: Guerci 2003, DiGEM 2007, Barnett 2008, ESMON 2008, Scherbaum 2008 and Schwedes 2002. Three studies were classified as having a low risk of bias, two as having a high risk of bias.

Data on hypoglycaemia were insufficiently reported: three studies reported data on severe hypoglycaemia but these were

very rare. There was a statistically significant difference in HbA1c level in favour of SMBG (–0.23%), but this was judged not to be relevant as it was within the non-inferiority interval of 0.4%. There was no significant difference in therapy changes. Only one study reported other adverse events, and there was no significant difference between groups. There was no evidence of harm of SMBG compared with interventions without SMBG, but data were insufficient.

Four out of five studies reported on body weight and tended to show a slight reduction with SMBG, but overall the difference was non-significant.

Three studies reported on health-related QoL. The risk of bias for this measure was judged to be high for all three studies. In the DiGEM study, there was no significant difference for the W-BQ12 measure, and results on the EQ-5D were partially contradictory and could not be used. The ESMON study found increased depression in SMBG patients, whereas Schwedes 2002 found reduced depression in patients performing SMBG. Overall, there was no evidence for benefit or harm based in health-related QoL.

Three studies reported on patient satisfaction and there was no significant difference between groups. Two epidemiological studies were identified that reported on diabetes-related mortality and morbidity (ROSSO study and Fremantle diabetes study), but gave contradictory results.

Overall, there was no evidence for a benefit of self-measurement of blood or urinary glucose in patients with T2DM who were not being treated with insulin. There were no relevant and sufficiently clearly reported studies on measurement of urinary glucose. There was no evidence that measurement frequency had an influence on results. Epidemiological studies showed no evidence of an association between SMBG or SMUG and morbidity and mortality.

BOX 2 International Diabetes Federation recommendations (abbreviated)

SMBG should be used only when individuals with diabetes and/or their health-care providers have the knowledge, skills and willingness to incorporate SMBG monitoring and therapy adjustment into their diabetes care plans in order to attain agreed treatment goals

SMBG should be considered at the time of diagnosis to enhance the understanding of diabetes as part of individuals’ education and to facilitate timely treatment initiation and titration optimisation

SMBG should also be considered as part of ongoing diabetes self-management education to assist people with diabetes to better understand their disease and provide a means to actively and effectively participate in its control and treatment, modifying behavioural and pharmacological interventions as needed, in consultation with their health-care provider

SMBG protocols (intensity and frequency) should be individualised to address each individual’s specific educational/behavioural/clinical requirements (to identify/prevent/manage acute hyper- and hypoglycaemia) and provider requirements for data on glycaemic patterns and to monitor the impact of therapeutic decisions

The purpose(s) of performing SMBG and using SMBG data should be agreed between the person with diabetes and the health-care provider

or exercise programme) or on progression Current or planned of disease, for example when HbA level 1c research exceeds target on two or more consecutive measurements; there may be a particular The Self Monitoring of Blood Glucose Trialists benefit in patients on combination oral therapy Collaboration is going to carry out an individual who are being considered for the addition patient-based meta-analysis,134 which will, amongst of insulin, as this is a group where intensive other things, examine effectiveness amongst lifestyle intervention may avoid the need for predefined subgroups, look for interactions with insulin133 – it may be that motivation would be behavioural variables, assess the effect of co- stronger at that stage; short, targeted bursts of intervention with psychosocial and educational SMBG may be more effective interventions, and provide more detail on the

• assess the size and duration of the HbA1c effect interventions used in the trials. in those in whom it does work • assess the impact of structured education on A three-armed RCT of SMBG versus urine testing how to read and interpret results of SMBG versus standard care is planned by Malanda et al.135 • compare education containing empowerment from Amsterdam, the Netherlands: 600 patients techniques for patients with/without the aid of will be recruited. The primary outcomes will be SMBG in patients treated with diet and/or oral changes in diabetes-specific emotional distress and glucose-lowering medication to determine the efficacy. Secondary outcomes include glycaemic effective component, for example education, control, patient satisfaction, physical activity, health empowerment or SMBG status, depressive status, hypoglycaemia and cost– • assess the effect of feedback in response to utility. SMBG with respect to treatment changes (by HCP or patient) and behavioural/lifestyle A trial funded by Diabetes UK is comparing SMBG changes and examine the interaction/ with SMUG.136 It is an extension of the DESMOND communication between HCP and patient (Diabetes Education and Self-Management for regarding SMBG readings and resulting action; On-going and Newly Diagnosed) study, and is this would include assessing the impact on measuring effects on glycaemic control (both

intensification of treatment, such as whether HbA1c level and hypoglycaemia) and QoL, with SMBG can prolong the time on diet alone or an 18-month follow-up. If differences between the on oral agents prior to insulin arms are seen then there will be a full economic • assess the effects of SMBG on QoL and assessment using the Sheffield Diabetes Model. It patient satisfaction, especially with respect started early in 2007. to depression and anxiety and try to elicit the causes of depression/anxiety and the A German study is comparing once-weekly glucose

interaction between self-efficacy, depression/ profile self-monitoring with 3-monthly HbA1c to anxiety and clinical outcomes; if patients feel see which is better after 1 year. There are four

that SMBG can help them to improve their arms: SMBG, HbA1c, both and neither, with all control, would that remove the depression and arms having urine glucose monitoring. The study anxiety? duration is 5 years and it was expected to end by • determine situations in which urinary glucose December 2008.137 monitoring may be of value and whether it causes less anxiety (a trial is under way – see An Italian study called PRISMA (Prospective below) Randomised trial on Intensive Self-Monitoring • assess the role pharmacists play in SMBG. If Blood Glucose Management Added Value in they are selling meters, are they providing Non-insulin treated type 2 diabetes), funded education? What role could pharmacists play in by Hoffman-La Roche, has two arms, both with delivering education? People usually have to go SMBG: one arm has standard care and the other to the pharmacy to pick up their test strips arm provides patients with specific glycaemic • check as to whether newer devices with quicker targets and suggestions on how to achieve them by results and memory for storing results are more changes in diet or physical activity.138 effective.

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Another Dutch study in people with T2DM, not on result of SMBG – there is no point in collecting insulin, is comparing SMBG (four times per day, data on blood glucose levels if nothing is done with 2 days per week) with standard care (not defined) the data. with glycaemic control, QoL, treatment satisfaction, weight and need to start insulin as outcomes. It The current evidence on cost-effectiveness is was due to end in 2008. It is funded by the Medical mixed, but the best economics paper is from the Research Foundation.139 DiGEM trial in the UK, which concluded that SMBG in patients with T2DM not on insulin was In the USA, Bergenstal et al.140 are examining the not cost-effective. effects of different frequencies and timing (SMBG three times per day versus only once-daily fasting) It may be that the key should be to identify those but with a control arm with no SMBG. The trial is patients who will most benefit and divert some due to end in 2009. It is supported by LifeScan. of the money currently allocated to SMBG to improved education for both HCPs and patients. SMBG might be more effective if associated with Conclusions appropriate self-care plans developed between HCPs and patients to best meet patient needs and Self-monitoring of blood glucose seems to provide fit into their own lifestyle. only slight benefit in terms of glycaemic control, and it can have psychological disbenefits. There The prevalence and costs of T2DM are rising was a lack of evidence regarding the subgroups of steadily at a time when NHS development funds patients who may benefit most from SMBG, and are going to be very scarce. If we fund an increase optimal frequency and timing. But SMBG clearly in SMBG, funding will have to be taken from other can yield benefits if used appropriately. One issue aspects of care. The case for investing in SMBG for is that a number of studies showed that no changes patients with T2DM not treated with insulin has to in self-management or treatment were made as a be regarded at present as ‘not proven’.

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Acknowledgements

We thank the following for commenting on a near About the Aberdeen HTA final draft of this report, but absolve them from any group errors in the final report, responsibility for which rests with the review team: The Aberdeen Health Technology Assessment Group is part of the Institute of Applied Health • Professor Simon Heller, Sheffield, UK Sciences (IAHS), which is part of the College of • Dr Mark Houliston, general practitioner and Medicine and Life Sciences of the University of lead clinician, Grampian Diabetes Managed Aberdeen, Aberdeen, UK. The IAHS is made up Clinical Network of discrete but methodologically related research • Dr Maurice O’Kane, Londonderry, Northern groups. The HTA Group is drawn mainly from the Ireland, UK. Health Services Research Unit, Public Health, and the Health Economics Research Unit. We also thank the members of the Department of Health Working Group on self-monitoring of blood The HTA Group produces independent health glucose, whose discussions and comments on both TARs for the UK HTA programme, which this research review and the drafts of the Working commissions TARs for NICE and other bodies, Group Report were very useful. The members of such as the National Screening Committee. It also the working group included: carries out evidence reviews to support the NICE Single Technology Appraisal Programme. • Simon Heller (Chair) • Eleanor Kennedy Particular interests include evaluation of non- • Andrew Farmer pharmacological technologies, screening and • Adrian Griffin diabetes. Previous TARs from Aberdeen include: • Martin Gulliford • Julia Lawton • The clinical effectiveness and cost-effectiveness • Maurice O’Kane of inhaled insulin in diabetes mellitus: a • Mark Samuels systematic review and economic evaluation. • Grace Sweeney Health Technol Assess 2007;11(33). • Bridget Turner. • Clinical effectiveness and cost-effectiveness of continuous subcutaneous insulin infusion for diabetes: systematic review and economic Contributions of authors evaluation. Health Technol Assess 2009; in press. • Screening for type 2 diabetes: literature review • Christine Clar led the review of clinical and economic modelling. Health Technol Assess effectiveness, commented on other sections, 2007;11(17). and edited the report after peer review and • Non-pharmacological prevention of diabetes editorial comments. in those with impaired glucose tolerance. In • Katharine Barnard led the review of qualitative preparation. studies and commented on other sections. • Newer agents for blood glucose control in type • Ewen Cummins led the review of economic 2 diabetes. Health Technol Assess 2010; in press. studies. • Pamela Royle did searches, quality assurance We also do Cochrane reviews on diabetic topics. and editing, and commented on all sections. • Norman Waugh wrote Chapters 1 and 4, and undertook final editing.

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References

1. National Institute for Health and Clinical 12. Simon J, Gray A, Clarke P, Wade A, Neil A, Farmer Excellence. Type 2 diabetes: the management A, et al. Cost-effectiveness of self monitoring of of type 2 diabetes (update). 2008. URL: http:// blood glucose in patients with non-insulin treated guidance.nice.org.uk/CG66 type 2 diabetes: economic evaluation of data from the DiGEM trial. BMJ 2008;336:1177–80. 2. British Medical Association and the Royal Pharmaceutical Society of Great Britain. British 13. O’Kane MJ, Bunting B, Copeland M, Coates VE, National Formulary 57. URL: www.bnf.org/bnf/bnf/ ESMON study group. Efficacy of self monitoring of current/104945.htm 2009 (accessed 21 July 2009). blood glucose in patients with newly diagnosed type 2 diabetes (ESMON study): randomised controlled 3. McAndrew L, Schneider SH, Burns E, Leventhal trial. BMJ 2008;336:1174–7. H. Does patient blood glucose monitoring improve diabetes control? A systematic review of the 14. Karter AJ, Parker MM, Moffet HH, Spence MM, literature. Diabetes Educ 2007;33:991–1011. Chan J, Ettner SL, et al. Longitudinal study of new and prevalent use of self-monitoring of blood 4. Yorkshire and Humber Public Health Observatory. glucose. Diabetes Care 2006;29:1757–63. URL: www.yhpho.org.uk/ (accessed August 2009). 15. Martin S, Schneider B, Heinemann L, Lodwig V, 5. The Health and Social Care Information Centre Kurth HJ, Kolb H, et al. Self-monitoring of blood PSUatYaHPHO. Prescribing for diabetes in England. An glucose in type 2 diabetes and long-term outcome: analysis of volume, expenditure and trends. URL: www. an epidemiological cohort study. Diabetologia yhpho.org.uk/resource/item.aspx?RID=9711 2009 2006;49:271–8. (accessed 21 July 2009). 16. Wen L, Parchman ML, Linn WD, Lee S. Association 6. Chapman RH, Benner JS, Petrilla AA, Tierce between self-monitoring of blood glucose and JC, Collins SR, Battleman DS, et al. Predictors of glycemic control in patients with type 2 diabetes adherence with antihypertensive and lipid-lowering mellitus. Am J Health Syst Pharm 2004;61:2401–5. therapy. Arch Intern Med 2005;165:1147–52. 17. Davis TME, Van-Minnen K, Bruce DG, Davis WA. 7. Lawton J, Peel E, Douglas M, Parry O. ‘Urine The relationship between self-monitoring of blood testing is a waste of time’: newly diagnosed Type 2 glucose results and glycosylated haemoglobin in diabetes patients’ perceptions of self-monitoring. type 2 diabetes: The Fremantle Diabetes Study. Diabet Med 2004;21:1045–8. Diabetologia 2007;50:1003.

8. Lawton J. Patients’ perceptions and experiences of 18. Davis WA, Bruce DG, Davis TM. Is self-monitoring taking oral glucose-lowering agents: a longitudinal of blood glucose appropriate for all type 2 diabetic qualitative study. Diabet Med 2008;25:491–5. patients? The Fremantle Diabetes Study. Diabetes Care 2006;29:1764–70. 9. Song M, Lipman TH. Concept analysis: self- monitoring in type 2 diabetes mellitus. Int J Nurs 19. Davis WA, Bruce DG, Davis TM. Does self- Stud 2008;45:1700–10. monitoring of blood glucose improve outcome in type 2 diabetes? The Fremantle Diabetes Study. 10. Farmer A, Wade A, Goyder E, Yudkin P, French Diabetologia 2007;50:510–5. D, Craven A, et al. Impact of self monitoring of blood glucose in the management of patients with 20. Moreland EC, Volkening LK, Lawlor MT, Chalmers non-insulin treated diabetes: open parallel group KA, Anderson BJ, Laffel LM. Use of a blood randomised trial. BMJ 2007;335:132. glucose monitoring manual to enhance monitoring adherence in adults with diabetes: a randomized 11. Farmer AJ, Wade AN, French DP, Simon J, Yudkin P, controlled trial. Arch Intern Med 2006;166:689–95. Gray A, et al. Blood glucose self-monitoring in type 2 diabetes: a randomised controlled trial. Health Technology Assessment 2009;13(15).

21. Siebolds M, Gaedeke O, Schwedes U, SMBG 33. Poolsup N, Suksomboon N, Jiamsathit W. Systematic Study Group. Self-monitoring of blood glucose-- review of the benefits of self-monitoring of blood psychological aspects relevant to changes in HbA1c glucose on glycemic control in type 2 diabetes in type 2 diabetic patients treated with diet or diet patients. Diabetes Technol Ther 2008;10(Suppl. 1): plus oral antidiabetic medication. Patient Educ Couns S51–66. 2006;62:104–10. 34. Sarol JN, Nicodemus NA, Jr, Tan KM, Grava MB. 22. Palmer AJ, Dinneen S, Gavin JR, III, Gray A, Self-monitoring of blood glucose as part of a multi- Herman WH, Karter AJ. Cost-utility analysis in a component therapy among non-insulin requiring UK setting of self-monitoring of blood glucose in type 2 diabetes patients: a meta-analysis (1966– patients with type 2 diabetes. Curr Med Res Opin 2004). Curr Med Res Opin 2005;21:173–84. 2006;22:861–72. 35. Towfigh A, Romanova M, Weinreb JE, Munjas B, 23. Moher D, Cook DJ, Eastwood S, Olkin I, Rennie Suttorp MJ, Zhou A, et al. Self-monitoring of blood D, Stroup DF. Improving the quality of reports glucose levels in patients with type 2 diabetes of meta-analyses of randomised controlled trials: mellitus not taking insulin: a meta-analysis. Am J the QUOROM statement. Quality of Reporting of Manag Care 2008;14:468–75. Meta-analyses. Lancet 1999;354:1896–900. 36. Welschen LM, Bloemendal E, Nijpels G, Dekker 24. Coster S, Gulliford MC, Seed PT, Powrie JK, JM, Heine RJ, Stalman WA, et al. Self-monitoring of Swaminathan R. Monitoring blood glucose control blood glucose in patients with type 2 diabetes who in diabetes mellitus: a systematic review. Health are not using insulin: a systematic review. Diabetes Technol Assess 2000;4(12). Care 2005;28:1510–7.

25. Brunner GA, Ellmerer M, Sendlhofer G, Wutte A, 37. Welschen LM, Bloemendal E, Nijpels G, Dekker Trajanoski Z, Schaupp L, et al. Validation of home JM, Heine RJ, Stalman WA, et al. Self-monitoring blood glucose meters with respect to clinical and of blood glucose in patients with type 2 diabetes analytical approaches. Diabetes Care 1998;21:585–90. who are not using insulin. Cochrane Database Syst Rev 2005;CD005060. 26. Williams CD, Scobie IN, Till S, Crane R, Lowy C, Sonksen PH. Use of memory meters to measure 38. St John A, Davis WA, Price CP, Davis TM. The value reliability of self blood glucose monitoring. Diabet of self-monitoring of blood glucose: a review of Med 1988;5:459–62. recent evidence. J Diabetes Complications 2009; in press. 27. Arabadjief D, Nichols JH. Assessing glucose meter accuracy. Curr Med Res Opin 2006;22:2167–74. 39. Sarol JN, Nicodemus NA, Tan KM, Flores JVPG. Self-monitoring of blood glucose as part of a 28. AHRQ. Applicability of the evidence regarding intensive multi-component treatment strategy in non- glycemic control and self-monitored blood glucose to insulin requiring type 2 diabetes mellitus. Diabetes Medicare patients with type 2 diabetes. Rockvill, MD: 2004;53:A73. AHRQ; 2007. 40. Allen BT, DeLong ER, Feussner JR. Impact of 29. Coster S, Gulliford MC, Seed PT, Powrie JK, glucose self-monitoring on non-insulin-treated Swaminathan R. Self-monitoring in type 2 diabetes patients with type II diabetes mellitus. Randomized mellitus: a meta-analysis. Diabet Med 2000;17: controlled trial comparing blood and urine testing. 755–61. Diabetes Care 1990;13:1044–50.

30. Faas A, Schellevis FG, Van Eijk JT. The efficacy 41. Barnett AH, Krentz AJ, Strojek K, Sieradzki J, of self-monitoring of blood glucose in NIDDM Azizi F, Embong M, et al. The efficacy of self- subjects. A criteria-based literature review. Diabetes monitoring of blood glucose in the management Care 1997;20:1482–6. of patients with type 2 diabetes treated with a gliclazide modified release-based regimen. A 31. Jansen JP. Self-monitoring of glucose in type 2 multicentre, randomized, parallel-group, 6-month diabetes mellitus: a Bayesian meta-analysis of evaluation (DINAMIC 1 study). Diabetes Obes Metab direct and indirect comparisons. Curr Med Res Opin 2008;10:1239–47. 2006;22:671–81. 42. Bonomo K, De Salve A, Pignatelli S, Fiora E, 32. McGeoch G, Derry S, Moore RA. Self-monitoring Mularoni E, Cavalot F, et al. Self-monitoring of of blood glucose in type-2 diabetes: what is the blood glucose in type 2 diabetic patients not on evidence? Diabetes Metab Res Rev 2007;23:423–40. insulin treatment: waist of money or tool to reach the glyeaemic targets? Diabetologia 2006;49:0815. 50 DOI: 10.3310/hta14120 Health Technology Assessment 2010; Vol. 14: No. 12

43. Brown SA, Garcia AA, Kouzekanani K, Hanis CL. using preprandial versus postprandial self blood Culturally competent diabetes self-management glucose monitoring in a primary care setting. education for Mexican Americans: the Starr County Diabetes 2003;52:A96–7. border health initiative. Diabetes Care 2002;25: 259–68. 54. Kibriya MG, Ali L, Banik NG, Khan AK. Home monitoring of blood glucose (HMBG) in Type-2 44. Cho JH, Chang SA, Kwon HS, Choi YH, Ko SH, diabetes mellitus in a developing country. Diabetes Moon SD, et al. Long-term effect of the Internet- Res Clin Pract 1999;46:253–7. based glucose monitoring system on HbA1c reduction and glucose stability: a 30-month follow- 55. Kwon HS, Cho JH, Kim HS, Song BR, Ko SH, up study for diabetes management with a ubiquitous Lee JM, et al. Establishment of blood glucose medical care system. Diabetes Care 2006;29:2625–31. monitoring system using the internet. Diabetes Care 2004;27:478–83. 45. Davidson MB, Castellanos M, Kain D, Duran P. The effect of self monitoring of blood glucose 56. Miles P, Everett J, Murphy J, Kerr D. Comparison concentrations on glycated hemoglobin levels in of blood or urine testing by patients with newly diabetic patients not taking insulin: a blinded, diagnosed non-insulin dependent diabetes: patient randomized trial. Am J Med 2005;118:422–5. survey after randomised crossover trial. BMJ 1997;315:348–9. 46. Estey AL, Tan MH, Mann K. Follow-up intervention: its effect on compliance behavior to a diabetes 57. Muchmore DB, Springer J, Miller M. Self- regimen. Diabetes Educ 1990;16:291–5. monitoring of blood glucose in overweight type 2 diabetic patients. Acta Diabetol 1994;31:215–19. 47. Fontbonne A, Billault B, Acosta M, Percheron C, Varenne P, Besse A, et al. Is glucose self-monitoring 58. Rutten G, van EJ, de NE, Beek M, van der Helden beneficial in non-insulin-treated diabetic patients? H. Feasibility and effects of a diabetes type II Results of a randomized comparative trial. Diabete protocol with blood glucose self-monitoring in Metab 1989;15:255–60. general practice. Fam Pract 1990;7:273–8.

48. Gallichan MJ. Self-monitoring by patients 59. Scherbaum WA, Ohmann C, Abholz HH, Lankisch receiving oral hypoglycemic agents: a survey and a M. Evaluating the optimal frequency of self- comparative trial. Pract Diabetes 1994;11:28–30. monitoring blood glucose in type 2 diabetes at glycaemic target: a multi-centre, randomized 49. Guerci B, Drouin P, Grange V, Bougneres P, controlled trial. Diabetes 2007;56:A24. Fontaine P, Kerlan V, et al. Self-monitoring of blood glucose significantly improves metabolic control 60. Scherbaum WA, Ohmann C, Abholz HH, Dragano in patients with type 2 diabetes mellitus: the Auto- N, Lankisch M. Effect of the frequency of self- Surveillance Intervention Active (ASIA) study. monitoring blood glucose in patients with type Diabetes Metab 2003;29:587–94. 2 diabetes treated with oral antidiabetic drugs-a multi-centre, randomized controlled trial. PLoS 50. Jaber LA, Halapy H, Fernet M, Tummalapalli S, ONE 2008;3:e3087. Diwakaran H. Evaluation of a pharmaceutical care model on diabetes management. Ann Pharmacother 61. Schwedes U, Siebolds M, Mertes G. Meal-related 1996;30:238–43. structured self-monitoring of blood glucose: effect on diabetes control in non-insulin-treated type 2 51. Johnson JA, Majumdar SR, Bowker SL, Toth EL, diabetic patients. Diabetes Care 2002;25:1928–32. Edwards A. Self-monitoring in Type 2 diabetes: a randomized trial of reimbursement policy. Diabet 62. Seaton TL. Benefit of self-monitoring of blood Med 2006;23:1247–51. glucose in patients with NIDDM receiving oral sulfonylureas [abstract]. Pharmacotherapy 52. Jones H, Edwards L, Vallis TM, Ruggiero L, Rossi 1996;16:498. SR, Rossi JS, et al. Changes in diabetes self-care behaviors make a difference in glycemic control: 63. Wing RR, Epstein LH, Nowalk MP, Scott N, Koeske the Diabetes Stages of Change (DiSC) study. Diabetes R, Hagg S. Does self-monitoring of blood glucose Care 2003;26:732–7. levels improve dietary compliance for obese patients with type II diabetes? Am J Med 1986;81:830–6. 53. Joy S, Rodgers P, Elmore L, Calvert S. Assessment of therapeutic interventions and degree of glycemic 64. Bajkowska-Fiedziukiewicz A, Cypryk K, Kozdraj T, control for patients with type 2 diabetes mellitus Mikolajczyk-Swatko A, Kosinski M, Jozefowska M.

Self-monitoring of blood glucose and treatment 75. Karter AJ, Ackerson LM, Darbinian JA, D’Agostino outcomes in type 2 diabetic patients. Polskie RB, Jr, Ferrara A, Liu J, et al. Self-monitoring of Archiwum Medycyny Wewnetrznej 2008;118:267–72. blood glucose levels and glycemic control: the Northern California Kaiser Permanente Diabetes 65. Banister NA, Jastrow ST, Hodges V, Loop R, registry. Am J Med 2001;111:1–9. Gillham MB. Diabetes self-management training program in a community clinic improves 76. Karter AJ, Moffet HH, Liu J, Parker MM, Ahmed patient outcomes at modest cost. J Am Diet Assoc AT, Ferrara A, et al. Achieving good glycemic 2004;104:807–10. control: initiation of new antihyperglycemic therapies in patients with type 2 diabetes from the 66. Blonde L, Ginsberg BH, Horn S. Frequency of Kaiser Permanente Northern California Diabetes blood glucose monitoring in relation to glycemic Registry. Am J Manag Care 2005;11:262–70. control in patients with type 2 diabetes. Diabetes Care 2002;25:245–55. 77. Klein CE, Oboler SK, Prochazka A, Oboler S, Frank M, Glugla M, et al. Home blood glucose monitoring: 67. Capelson R, Principe A, Trey G, Hayes M, Suhl E, effectiveness in a general population of patients Ayres D, et al. Does increased home monitoring of who have non-insulin-dependent diabetes mellitus. blood glucose (HMBG) improve glycemic control in J Gen Intern Med 1993;8:597–601. patients over 75? Diabetes 2006;55:A453. 78. Martin S, Kolb H, Schneider B, Heinemann L, 68. Chan WB, Chan JC, Chow CC, Yeung VT, So WY, Weber C, Kocher S, et al. Myocardial infarction Li JK, et al. Glycaemic control in type 2 diabetes: and stroke in early years after diagnosis of type 2 the impact of body weight, beta-cell function and diabetes: risk factors and relation to self-monitoring patient education. QJM 2000;93:183–90. of blood glucose. Diabetes Technol Ther 2009;11: 234–41. 69. Evans JM, Newton RW, Ruta DA, MacDonald TM, Stevenson RJ, Morris AD. Frequency of blood 79. Meier JL, Swislocki AL, Lopez JR, Noth RH, glucose monitoring in relation to glycaemic control: Bartlebaugh P, Siegel D. Reduction in self- observational study with diabetes database. BMJ monitoring of blood glucose in persons with type 1999;319:83–6. 2 diabetes results in cost savings and no change in glycemic control. Am J Manag Care 2002;8:557–65. 70. Franciosi M, Pellegrini F, De Berardis G, Belfiglio M, Cavaliere D, Di Nardo B, et al. The impact of 80. Mitchell CG, Bowker SL, Majumdar SR, Toth EL, blood glucose self-monitoring on metabolic control Johnson JA. Lack of correlation between patient- and quality of life in type 2 diabetic patients: an reported outcomes and glycemic control in type urgent need for better educational strategies. 2 diabetes not managed by insulin. Can J Diabetes Diabetes Care 2001;24:1870–7. 2004;28:362–8.

71. Franciosi M, Pellegrini F, De Berardis G, Belfiglio 81. Murata GH, Shah JH, Hoffman RM, Wendel CS, M, Di Nardo B, Greenfield S, et al. Self-monitoring Adam KD, Solvas PA, et al. Intensified blood glucose of blood glucose in non-insulin-treated diabetic monitoring improves glycemic control in stable, patients: a longitudinal evaluation of its impact on insulin-treated veterans with type 2 diabetes: the metabolic control. Diabet Med 2005;22:900–6. Diabetes Outcomes in Veterans Study (DOVES). Diabetes Care 2003;26:1759–63. 72. Hanninen J, Takala J, Keinanen-Kiukaanniemi S. Good continuity of care may improve quality 82. Murata GH, Duckworth WC, Shah JH, Wendel of life in Type 2 diabetes. Diabetes Res Clin Pract CS, Mohler MJ, Hoffman RM. Blood glucose 2001;51:21–7. monitoring is associated with better glycemic control in type 2 diabetes: a database study. J Gen 73. Harris MI, National Health and Nutrition Int Med 2009;24:48–52. Examination Survey (NHANES III). Frequency of blood glucose monitoring in relation to glycemic 83. Newman WP, Laqua D, Engelbrecht D. Impact control in patients with type 2 diabetes. Diabetes Care of glucose self-monitoring on glycohemoglobin 2001;24:979–82. values in a veteran population. Arch Intern Med 1990;150:107–10. 74. Jaworska J, Dziemidok P, Kulik TB, Rudnicka- Drozak E. Frequency of self-monitoring and its 84. Oki JC, Flora DL, Isley WL. Frequency and impact effect on metabolic control in patients with type of SMBG on glycemic control in patients with 2 diabetes. Ann Univ Mariae Curie Sklodowska Med NIDDM in an urban teaching hospital clinic. 2004;59:310–16. Diabetes Educ 1997;23:419–24.

52 DOI: 10.3310/hta14120 Health Technology Assessment 2010; Vol. 14: No. 12

85. Ozmen B, Boyvada S. The relationship between glucose and glycaemic control in type 2 diabetes. self-monitoring of blood glucose control and Scand J Prim Health Care 2007;25:140–6. glycosylated haemoglobin in patients with type 2 diabetes with and without diabetic retinopathy. 96. Wieland LD, Vigil JM, Hoffman RM, Janis LW. J Diabetes Complications 2003;17:128–34. Relationship between home glucose testing and hemoglobin Alc in type II diabetes patients. Am J 86. Patrick AW, Gill GV, MacFarlane IA, Cullen A, Power Health Syst Pharm 1997;54:1062–5. E, Wallymahmed M. Home glucose monitoring in type 2 diabetes: is it a waste of time? Diabet Med 97. Worth R, Home PD, Johnston DG, Anderson J, 1994;11:62–5. Ashworth L, Burrin JM, et al. Intensive attention improves glycaemic control in insulin-dependent 87. Rindone JP, Austin M, Luchesi J. Effect of home diabetes without further advantage from home blood glucose monitoring on the management blood glucose monitoring: results of a controlled of patients with non-insulin dependent diabetes trial. Br Med J (Clin Res Ed) 1982;285:1233–40. mellitus in the primary care setting. American J Manag Care 1997;3:1335–8. 98. International Diabetes Federation. IDF Guideline on self-monitoring of blood glucose in non-insulin 88. Roblin DW, Barizlay JI. Self-monitoring of blood treated type 2 diabetes. October 2008. URL: www. glucose: Variation in frequency of monitoring idf.org/idf-guideline-self-monitoring-blood-glucose- and its association with glycemic control. Diabetes non-insulin-treated-type-2-diabetes (accessed 5 2001;50:A2. December 2009).

89. Rost KM, Flavin KS, Schmidt LE, McGill JB. Self- 99. Schneider B, Martin S, Heinemann L, Lodwig V, care predictors of metabolic control in NIDDM Kolb H. Interrelations between diabetes therapy, patients. Diabetes Care 1990;13:1111–3. self-monitoring of blood glucose, blood glucose and non-fatal or fatal endpoints in patients with type 90. Schiel R, Muller UA, Rauchfub J, Sprott H, Muller 2 diabetes/results of a longitudinal cohort study R. Blood-glucose self-monitoring in insulin treated (ROSSO 5). Arzneimittelforschung 2007;57:762–9. type 2 diabetes mellitus a cross-sectional study with an intervention group. Diabetes Metab 1999;25: 100. Belsey JD, Pittard JB, Rao S, Urdahl H, Jameson 334–40. K, Dixon T. Self blood glucose monitoring in type 2 diabetes. A financial impact analysis based on UK 91. Schütt M, Kern W, Krause U, Busch P, Dapp A, primary care. Int J Clin Pract 2009;63:439–48. Grziwotz R, et al. Is the frequency of self-monitoring of blood glucose related to long-term metabolic 101. Peel E, Parry O, Douglas M, Lawton J. Blood control? Multicenter analysis including 24,500 glucose self-monitoring in non-insulin-treated patients from 191 centers in Germany and Austria. type 2 diabetes: a qualitative study of patients’ Exp Clin Endocrinol Diabetes 2006;114:384–8. perspectives. Br J Gen Pract 2004;54:183–8.

92. Secnik K, Yurgin N, Lage MJ, Donald-Everett C. 102. Peel E, Douglas M, Lawton J. Self monitoring of Patterns of blood glucose monitoring in relation blood glucose in type 2 diabetes: longitudinal to glycemic control among patients with type qualitative study of patients’ perspectives. BMJ 2 diabetes in the UK. J Diabetes Complications 2007;335:493. 2007;21:181–6. 103. Zgibor JC, Simmons DS. Barriers to self glucose 93. Soumerai SB, Mah C, Zhang F, Adams A, Barton monitoring in a multi-ethnic community. Diabetes M, Fajtova V, et al. Effects of health maintenance 2001;50:A500–1. organization coverage of self-monitoring devices on diabetes self-care and glycemic control. Arch Intern 104. Stewart D, McCaig D, Davie A, Juroszek L, Med 2004;164:645–52. Blackwood L, Findlay N, et al. Glucose self- monitoring in primary care: a survey of current 94. Stiptzarov N, Zhang Q, Pogach L. Increased practice. J Clin Pharm Ther 2004;29:273–7. utilization of self monitoring of blood glucose (SMBG) is associated with decreased A1c levels. 105. National Prescribing Centre. When and how should Diabetes 2003;52:A270. patients with diabetes mellitus test blood glucose? URL: www.npc.co.uk/ebt/merec/cardio/diabetes1/resources/ 95. Tengblad A, Grodzinsky E, Lindstrom K, Molstad S, merec_bulletin_vol13_no1.pdf 2002 (accessed 21 Borgquist L, Ostgren CJ. Self-monitoring of blood July 2009).

106. O’Kane MJ, Pickup J. Self-monitoring of blood 118. Aspinall SL, Glassman PA. Cost-effectiveness of glucose in diabetes: is it worth it? Ann Clin Biochem blood glucose monitoring is controversial. Am J 2009;46:273–82. Manag Care 2008;14:398–9.

107. Funnell M, Anderson RM. Empowerment and self- 119. Tunis SL. Cost-effectiveness of changing self- management of diabetes. Clin Diabetes 2004;22:123. monitoring of blood glucose frequency. Diabetes 2009;58:A505. 108. Curtis L, Netten A. Unit costs of health and social care 2006. Personal Social Services Research Unit 2006. 120. Mataveli F, Turatti L, Pimazoni Netto A. Short-term URL: www.pssru.ac.uk/pdf/uc/uc2006/uc2006.pdf economic benefits of self monitoring blood glucose (accessed August 2009). (SMBG) in type 2 diabetes for health maintenance organisations (HMOs). Diabetologia 2008;51:1096. 109. Weber C, Schneider B, Lodwig V, Holm MV, Neeser K. Cost impact of blood glucose self-monitoring 121. Erny-Albrecht KM, Tunis SL, Minshall ME, on complications of type 2 diabetes: a Swiss Valentine W, Foos V, Palmer AJ. Frequency of self- perspective (ROSSO study No.11). Swiss Med Wkly monitoring of blood glucose in type 2 diabetes: a 2007;137:545–50. cost-effectiveness modeling study in the US setting. Diabetes 2007;56:A308–9. 110. Tiley S. Home blood glucose monitoring – What cost? Pract Diabetes Int 2002;19:S1–4. 122. Weber C, Neeser K, Schneider B, Heinemann L, Lodwig V, Scherbaum WA. Cost-effectiveness of self 111. Neeser K, Weber C, Wenzel H, Schneider B. Costs measurement of blood glucose (SMBG) in function of self-measurement of blood glucose (SMBG) of the testing frequency in patients with type 2 regarding morbidity and mortality in type 2 diabetes. Diabetes 2007;56:A317. diabetes in a reality of care setting (The ROSSO study No. 6). Diabetologia 2006;49:0225. 123. Weber C, Erny-Albrecht K, Neeser K. Cost effectiveness of SMBG for the treatment of non 112. Clarke PM, Gray AM, Briggs A, Farmer AJ, Fenn P, insulin dependent diabetes mellitus. Diabetologia Stevens RJ, et al. A model to estimate the lifetime 2006;49:0895. health outcomes of patients with type 2 diabetes: the United Kingdom Prospective Diabetes Study 124. Neeser K, Erny-Albrecht K, Weber C. Cost- (UKPDS) Outcomes Model (UKPDS no. 68). effectiveness of self-monitoring of blood glucose Diabetologia 2004;47:1747–59. in type 2 diabetic patients not receiving insulin [comment]. [Erratum appears in Diabetes Care 113. Department of Health. NHS reference costs 2005–06. 2006;29:959.] Diabetes Care 2006;29:480–1. URL: www.dh.gov.uk/en/Publicationsandstatistics/ Publications/PublicationsPolicyAndGuidance/ 125. Davidson MB. Cost-effectiveness of self-monitoring DH_062884 (accessed August 2009). of blood glucose in type 2 diabetic patients not receiving insulin: Response to Neeser et al. Diabetes 114. National Health Service. Annual financial returns Care 2006;29:480–1. of NHS trusts 2003–2004. Leeds: NHS Executive; 2005. 126. Kempf K, Neukirchen W, Martin S, Kolb H. Self- monitoring of blood glucose in type 2 diabetes: 115. Netten A, Curtis L. Unit costs of health and social care a new look at published trials. Diabetologia 2002. URL: www.pssru.ac.uk/UC2002.htm (accessed 2008;51:686–8. August 2009). 127. Davidson MB. Counterpoint: Self-monitoring 116. Tunis SL, Minshall ME. Self-monitoring of blood of blood glucose in type 2 diabetic patients not glucose in type 2 diabetes: cost-effectiveness in the receiving insulin: a waste of money. Diabetes Care united states. Am Journal Manag Care 2008;14: 2005;28:1531–3. 131–40. 128. Joslin Diabetes Center. Blood sugar monitoring 117. Palmer AJ, Roze S, Valentine WJ, Minshall ME, Foos owner’s manual. URL: www.joslin.org/ (accessed V, Lurati FM, et al. The CORE Diabetes Model: August 2009). projecting long-term clinical outcomes, costs and cost-effectiveness of interventions in diabetes 129. Daly JM, Hartz AJ, Xu Y, Levy BT, James PA, mellitus (types 1 and 2) to support clinical and Merchant ML, et al. An assessment of attitudes, reimbursement decision-making. Curr Med Res Opin behaviors, and outcomes of patients with type 2 2004;20:5–26. diabetes. J Am Board Fam Med 2009;22:280–90.

54 DOI: 10.3310/hta14120 Health Technology Assessment 2010; Vol. 14: No. 12

130. Wagner J, Malchoff C, Abbott G. Invasiveness as education? URL: http://public.ukcrn.org.uk/Search/ a barrier to self-monitoring of blood glucose in StudyDetail.aspx?StudyID=3773 (accessed 13 diabetes. Diabetes Technol Ther 2005;7:612–9. August 2009).

131. Weijman I, Ros WJ, Rutten GE, Schaufeli WB, 137. Deutsche Diabetes Gesellschaft. Blood Glucose Self Schabracq MJ, Winnubst JA. The role of work- Monitoring and HbA1c Effects on Glucose Control. May related and personal factors in diabetes self- 2008. URL: http://clinicaltrials.gov/ct2/show/NCT0 management. Patient Educ Couns 2005;59:87–96. 0688363?term=NCT00688363&rank=1 (accessed 13 August 2009) 132. IQWiG (Institute for Quality and Efficiency in Health Care). Urine and blood glucose self-measurement 138. Hoffmann-La Roche. Intensive Self-Monitoring Blood in diabetes mellitus type 2. December 2009. URL: www. Glucose Management Added Value in Non-Insulin iqwig.de/index.559.en.html (accessed 21 October Treated Type 2 Diabetes Mellitus Patients. January 2009. 2009). URL: www.clinicaltrials.gov/ct2/show/NCT00643 474?term=NCT00643474&rank=1 (accessed 13 133. Aas AM, Bergstad I, Thorsby PM, Johannesen O, August 2009). Solberg M, Birkeland KI. An intensified lifestyle intervention programme may be superior to insulin 139. Medical Research Foundation, Langerhans treatment in poorly controlled Type 2 diabetic Foundation. Effect of Self-Monitoring of Blood Glucose patients on oral hypoglycaemic agents: results of a in Patients With Type 2 Diabetes Mellitus Not Using feasibility study. Diabet Med 2005;22:316–22. Insulin. April 2008. URL: http://clinicaltrials.gov/ show/NCT00287807 (accessed 13 August 2009). 134. Farmer AJ, Heneghan C, Barnett AH, Davidson MB, Guerci B, O’Kane M, et al. Individual patient 140. International Diabetes Center, Park Nicollet data meta-analysis of trials of self-monitoring of Institute, LifeScan. Impact of self-monitoring blood blood glucose in non-insulin treated type 2 diabetes: glucose frequency on glycemic control in patients with Protocol for a systematic review. Prim Care Diabetes type 2 diabetes. 2009. URL: www.parknicollet.com/ 2009;3:117–21. diabetes/ (accessed 13 August 2009).

135. Malanda UL, Bot SDM, Kostense PJ, Snoek FJ, 141. Downs SH, Black N. The feasibility of creating a Dekker JM, Nijpels G. Effects of self-monitoring of checklist for the assessment of the methodological glucose in non-insulin treated patients with type 2 quality both of randomised trials and non- diabetes: design of the IN CONTROL-trial. BMC randomised studies of health care interventions. Fam Pract 2009;10. J Epid Community Health 1998;52:377–84.

136. Heller S. Does self monitoring of blood glucose as opposed 142. Franciosi M, De Berardis G, Cavaliere I, Valentini to urinalysis provide additional benefit to newly diagnosed M, Nicolucci A. The impact of blood glucose self- individuals with Type 2 diabetes receiving structured monitoring on quality of life in type 2 diabetic patients. Diabetes 2001;50:A391.

DOI: 10.3310/hta14120 Health Technology Assessment 2010; Vol. 14: No. 12

Appendix 1 Search strategy and flow of studies

Search strategy for clinical Search strategy for a cost- effectiveness studies effectiveness studies The following MEDLINE search strategy was The MEDLINE strategy below was used and adapted as appropriate for other databases: adapted as appropriate for other databases:

1. (self monitor* adj3 blood glucose).tw. 1. (self monitor* adj3 blood glucose).tw. 2. (home monitor* adj3 blood glucose).tw. 2. (home monitor* adj3 blood glucose).tw. 3. (HMBG or HBGM or SMBG or BGSM).tw. 3. (HMBG or HBGM or SMBG or BGSM).tw. 4. exp Blood Glucose Self-Monitoring/ 4. exp Blood Glucose Self-Monitoring/ 5. (glucose adj2 monitor* adj3 (self or 5. (glucose adj2 monitor* adj3 (self or home)).tw. home)).tw. 6. 4 or 1 or 3 or 2 or 5 6. 4 or 1 or 3 or 2 or 5 7. exp Diabetes Mellitus, Type 2/ 7. exp Diabetes Mellitus, Type 2/ 8. type 2 diabetes.tw. 8. type 2 diabetes.tw. 9. 8 or 7 9. 8 or 7 10. 6 and 9 10. 6 and 9 11. ((self or home) and monitor* and glucose).m_ 11. ((self or home) and monitor* and titl. glucose).m_titl. 12. 11 or 10 12. 11 or 10 13. limit 12 to english language 13. limit 12 to english language 14. (cost* or economic or financial).mp. [mp=title, original title, abstract, name of substance word, subject heading word] 15. 13 and 14

Flow of studies for SMBG general search

2051 studies identified from all searches 989 duplicate studies removed

1062 unique studies remaining 736 studies excluded as not relevant to SMBG

326 studies remaining

255 studies retained for background reading and general references

71 studies selected for data extraction

16 references to 11 18 RCTs + 8 from 32 observational 5 qualitative systematic reviews reference lists studies studies

Flow of studies for SMBG cost-effectiveness search

507 studies in searches 458 studies excluded on basis of abstracts

Full text of remaining 49 studies obtained

17 studies included in cost-effectiveness section

Title: 09-19-01 Proof Stage: 1 Figure Number: 00.04.ai

Cactus Design and Illustration Ltd

Title: 09-19-01 Proof Stage: 3 Figure Number: 00.05.ai

Cactus Design and Illustration Ltd DOI: 10.3310/hta14120 Health Technology Assessment 2010; Vol. 14: No. 12

Appendix 2 Characteristics of systematic reviews

© 2010 Queen’s Printer and Controller of HMSO. All rights reserved. Appendix 2 DOI: 10.3310/hta14120 Health Technology Assessment 2010; Vol. 14: No. 12 : yes : yes : : yes Inclusion criteria described: (limited) yes search given : Details of literature no Study selection described : no described : Data extraction yes Study quality assessment described : narratively yes, : shown Study flow Study characteristics of individual studies (limited) yes described : Quality of individual studies given yes Inclusion criteria described : yes search given : Details of literature no Study selection described : no described : Data extraction yes Study quality assessment described : yes : shown Study flow Study characteristics of individual studies yes described : Quality of individual studies given : yes : Results of individual studies shown yes Statistical analysis appropriate : yes : Results of individual studies shown yes Statistical analysis appropriate : Quality • • • • • • • • • • • • • • • • • • moderate – limited QUALITY: OVERALL description of methods and study characteristics use of therapy investigated COMMENT: the investigator, decision scheme by key of SMBG device; nature comparisons, points of patient instruction and education, assessment of self- self-monitoring regimen, from received feedback monitoring frequency, provider care • • high – but some QUALITY: OVERALL HTA methodology not described (but probably standard) programme , weight, fasting weight, , fasting blood , 1c 1c : 8 Number of included trials : 734 Number of participants : TRIALS: RCTs Design : 3–12 months : Duration 15 of 27 mean quality score Quality : see trial PARTICIPANTS: descriptions some INTERVENTIONS: interventions including education – see descriptions HbA OUTCOMES: : 11; 6 RCTs, 6 RCTs, 11; Number of included trials : 5 non-RCTs not further evaluated 592 Number of participants : TRIALS: RCTs further only evaluated Design : 12–62 weeks n: Duratio 3/7 rest 4 RCTs 7/7 points, Quality : and 4/7 see trial PARTICIPANTS: descriptions SMBG, 4 only INTERVENTIONS: 3 vs urine testing; 4 vs no SMBG, some interventions including education HbA OUTCOMES: Included studies glucose, lifestyle adherence, SMBG adherence, lifestyle glucose, fructosamine adherence, body weight, fructosamine, glucose, QoL : none : , weight, any other outcomes reported any weight, , ; other outcomes as reported ; 1c 1c : no : Inclusion criteria RCTs but only non-RCTs included initially, unclear; Study design : detail in more investigated with patients using insulin studies exclusively T2DM; Participants : excluded comparison any SMBG; Intervention s: HbA Outcomes : Methodology of Index and Bibliography EMBASE; MEDLINE, strategy: Search database of Diabetes Health Economic Social Science (IBSS), 1980–98 dates 1976–99 (MEDLINE); search Study Group; Diabetic Medicine hand-searching given; keywords (EMBASE); to British requests (1990–9); (1990–9) and Diabetes Care of testing equipment Association and manufacturers Diabetic to restriction lists; reference and Roche Diagnostics); (Bayer English language Methodology given; keywords MEDLINE (1976–1996); Search: strategy searched bibliographies method not reported Study selection : and ter Riet Deyo criteria by Quality assessment : method not reported : Data extraction Meta-analysis text and tables Data analysis : analyses Subgroups/sensitivity Inclusion criteria and methodology Inclusion criteria RCTs Study design : type independent of treatment T2DM; Participants : SMBG vs SMUG or no monitoring Interventions : HbA Outcomes : 29 30 : not reported : NHS R&D HTA : Review Netherlands efficacy of self- : Focus monitoring of blood glucose in patients with non insulin-dependent diabetes mellitus Funding UK – NHS HTA of effectiveness : Focus blood or urine glucose T2DM self-monitoring in Funding programme Faas (1997) Faas 60 Coster (2000) 61

© 2010 Queen’s Printer and Controller of HMSO. All rights reserved. Appendix 2 DOI: 10.3310/hta14120 Health Technology Assessment 2010; Vol. 14: No. 12 : yes : : yes Inclusion criteria described : yes search given : Details of literature yes Study selection described : yes described : Data extraction yes Study quality assessment described : narratively yes, : shown Study flow Study characteristics of individual studies yes described : Quality of individual studies given : yes : Results of individual studies shown yes Statistical analysis appropriate : • • • • • • • • • • high QUALITY: OVERALL Quality 1c : 8 Number of included trials : 1307 Number of participants : TRIALS: RCTs Design : 12–44 weeks : Duration 5 studies and C quality B for Quality : 3 studies for see trial PARTICIPANTS: descriptions some INTERVENTIONS: interventions including education – see descriptions HbA OUTCOMES: Included studies : sensitivity analyses used that did sensitivity analyses : 1c : yes : : yes : applied by two reviewers independently reviewers two by applied 141 Methodology CRD EMBASE, Cochrane Library, MEDLINE, Search: strategy personal collections (up Index Journals, ADA Online databases, English or lists searched; reference listed; keywords to 2004); English translation two assessed by titles and abstracts independently Study selection : reviewers Cochrane Collaboration criteria Quality assessment : items extracted listed : Data extraction Meta-analysis assessed heterogeneity and random effects; fixed Data analysis : : method not reported : Data extraction Meta-analysis assessed heterogeneity model; random effects Data analysis : analyses Subgroups/sensitivity (based on study design and results not change the overall comparisons) Inclusion criteria RCTs Study design : T2DM without insulin treatment Participants : diabetes management strategy with SMBG Interventions : component vs strategy without SMBG component HbA Outcomes : Inclusion criteria and methodology method not reported Study selection : and Black by Downs modified quality checklist Quality assessment : (1998);

1c 34,39 : Johnson & Johnson : Sarol (2005) Sarol in non-insulin-requiring in non-insulin-requiring T2DM patients with Funding Johnson 60 Review Philippines self-monitoring of : Focus blood glucose on HbA 61

© 2010 Queen’s Printer and Controller of HMSO. All rights reserved. Appendix 2 DOI: 10.3310/hta14120 Health Technology Assessment 2010; Vol. 14: No. 12 : yes : : yes : 1c : yes Inclusion criteria described : yes search given : Details of literature yes Study selection described : yes described : Data extraction yes Study quality assessment described : narratively yes, : shown Study flow Study characteristics of individual studies yes described : Quality of individual studies given : yes : Results of individual studies shown yes Statistical analysis appropriate : : yes Inclusion criteria described: yes search given : Details of literature yes Study selection described : yes described : Data extraction yes Study quality assessment described : narratively yes, : shown Study flow Study characteristics of individual studies yes described : Quality of individual studies given : yes : Results of individual studies shown yes Statistical analysis appropriate : • • • • • • • • • • high QUALITY: OVERALL SMBG with feedback compares COMMENT: outcomes only with SMBG without feedback; HbA Quality • • • • • • • • • • high QUALITY: OVERALL 1c and/or fasting glucose, and/or fasting glucose, 1c : 13 Number of included trials : 2092 Number of participants : TRIALS: all RCTs Design : 3 months to 62 weeks : Duration 8.5 of 13 mean quality score Quality : no demographic PARTICIPANTS: on participantsinformation insulin 2 studies – mixed provided; 11 studies and non-insulin patients; – patients did not use insulin or on insulin was no information there use but some, INTERVENTIONS: studies used education not all, component HbA OUTCOMES: : 6 Number of included trials : 1285 Number of participants : TRIALS: RCTs Design : 6 months to 44 weeks : Duration 4 1 trial 6/11, 1 trial 7/11, Quality : trials 5/11 see trial PARTICIPANTS: descriptions education on INTERVENTIONS: one reported by diet and lifestyle study control glycaemic OUTCOMES: – HbA Included studies QoL – SF-36, well-being, patient well-being, QoL – SF-36, hypoglycaemic satisfaction – DTSQ, effects, adverse morbidity, episodes, weight costs,

141 : planned but not carried out planned but not carried : , FPG, QoL, patient satisfaction, hypoglycaemia, hypoglycaemia, patient satisfaction, QoL, FPG, , 1c 1c : no for Cochrane review/yes for published paper for Cochrane review/yes no for : Inclusion criteria RCTs Study design: non-insulin treated T2DM; Participants: SMBG vs SMUG or no monitoring Interventions: HbA Outcomes: assessed independently by two reviewers two by assessed independently two data extracted by data extraction sheet; : Data extraction independently reviewers morbidity, adverse effects, costs effects, adverse morbidity, Methodology NHS Economic Cochrane Library, MEDLINE, Search: strategy lists; reference trials, ongoing EMBASE, Evaluation database, strategy search electronic dates up to September 2004; search no language restriction given; two assessed by titles and abstracts independently Study selection : reviewers assessed score; Maastricht–Amsterdam Quality assessment : reviewers two by independently data extracted data extraction form; : Data extraction reviewers two by independently Meta-analysis assessed heterogeneity model, random effects Data analysis : analyses Subgroups/sensitivity Inclusion criteria published reports) RCTs (full, Study design : type independent of treatment T2DM; Participants : self-monitoring of blood (SMBG) or urine glucose Interventions : SMBG with SMBG vs SMUG, SMBG vs no SMBG; (SMUG); vs SMBG without feedback feedback HbA Outcomes : Methodology Cochrane Library (1966– EMBASE, MEDLINE, Search: strategy searched; systematic reviews previous given; keywords 2005); Dutch French, German, English, identified checked independently reviewers two Study selection : studies against inclusion criteria and Black (1998); Downs checklist by Quality assessment : Inclusion criteria and methodology 37 31 reductions in reductions 1c : Roche : : non-commercial : T2DM Funding Diagnostics Review Netherlands of SMBG in effects : Focus T2DM who patients with not using insulin are Funding Netherlands relative : Focus of effectiveness interventions with SMBG and SMUG vs interventions without self-monitoring in terms of HbA Welschen (2005) Welschen 62 Jansen (2006) 63

© 2010 Queen’s Printer and Controller of HMSO. All rights reserved. Appendix 2 DOI: 10.3310/hta14120 Health Technology Assessment 2010; Vol. 14: No. 12 : no : : yes Inclusion criteria described : yes search given : Details of literature no Study selection described : partly described : Data extraction no Study quality assessment described : no : shown Study flow Study characteristics of individual studies very limited described : Quality of individual studies given : yes : Results of individual studies shown yes Statistical analysis appropriate : • • • • • • • • • • poor – no description of QUALITY: OVERALL English only study quality, Quality 1c : 5 RCTs, 8 5 RCTs, Number of included trials : non-RCTs 2092 Number of participants : TRIALS: RCTs and cohort studies Design : rather chart (but some probably etc.) reviews RCTs 6–18 months, : Duration cohort up to 3 years not reported Quality : see trial details PARTICIPANTS: 1 out of 5 RCTs INTERVENTIONS: on training how did not report to readings to respond HbA OUTCOMES: Included studies : none : : all T2DM and non-insulin-treated T2DM and non-insulin-treated all : 1c : no : : yes : Inclusion criteria studies with at least 50 patients and 6 prospective Study design : FU weeks independent of treatment duration; T2DM of any Participants : T1DM excluded than 50% studies with more type; SMBG vs no monitoring Interventions : HbA Outcomes : Methodology given; keywords April 2006); MEDLINE (up to Search: strategy English only and guidelines searched; lists of reviews reference reviewers two by abstracts screened Study selection : quality not assessed Quality assessment : single tables by data extraction into evidence : Data extraction reviewer Meta-analysis text and tables Data analysis : analyses Subgroups/sensitivity Inclusion criteria and methodology Meta-analysis model (simultaneous random effects Bayesian Data analysis : comparisons) and indirect direct analyses Subgroups/sensitivity T2DM only 28 : AHRQ : in patients with 1c Review USA of frequency effect : Focus of glucose monitoring on clinical outcomes and HbA AHRQ (2007) 62 T2DM Funding 63

© 2010 Queen’s Printer and Controller of HMSO. All rights reserved. Appendix 2 DOI: 10.3310/hta14120 Health Technology Assessment 2010; Vol. 14: No. 12 : no : : yes : : yes Inclusion criteria described: yes search given : Details of literature unclear Study selection described : yes described : Data extraction yes Study quality assessment described : yes : shown Study flow Study characteristics of individual studies (but limited) yes described : Quality of individual studies given : yes : Results of individual studies shown yes Statistical analysis appropriate : : yes Inclusion criteria described : yes search given : Details of literature no Study selection described : yes described : Data extraction yes Study quality assessment described : no : shown Study flow Study characteristics of individual studies yes described : Quality of individual studies given : yes : Results of individual studies shown yes Statistical analysis appropriate : • • • • • • • • • • moderate QUALITY: OVERALL Quality • • • • • • • • • • moderate/high QUALITY: OVERALL , , 1c , frequency of frequency , 1c 60,000 in observational : 29 (30, 29 (30, Number of included trials : in addendum) DiGEM added 1759 RCTs, Number of participants : 36,091 non-RCTs TRIALS: 9 9 cross-sectional, Design : 11 RCTs longitudinal, non-RCTs RCTs unclear, : Duration up to 3 years 8.5 of 13 mean quality score Quality : see trial PARTICIPANTS: descriptions some included INTERVENTIONS: education – see trial details HbA depression, OUTCOMES: QoL : 16 Number of included trials : 1000 in Number of participants : > RCTs, TRIALS: 13 observational 3 RCTs, Design : RCTs 6–12 months, : Duration observational up to 6.5 years RCTs 1 or 2 of 5 points Quality : see trial info PARTICIPANTS: interventions INTERVENTIONS: in the amount significantly differed and in advised of education given groups control monitoring practice; amounts of differing also received training in diabetes management HbA OUTCOMES: Included studies SMBG, weight, BMI, medication use, medication use, BMI, weight, SMBG, (including diabetic effects adverse complications) : none : : none : and diabetes-related morbidity and diabetes-related 1c 1c : no : : no : Inclusion criteria and longitudinal studies cross-sectional RCT, Study design : non-insulin treated T2DM; Participants : comparator unclear SMBG, Interventions : HbA Outcomes : Inclusion criteria at least 50 patients, RCTs and observational studies; Study design : FU at least 6 months non-insulin treated T2DM; Participants : comparator unclear SMBG, Interventions : HbA Outcomes : Methodology CINAHL Cochrane Library, PsycInfo, MEDLINE, Search: strategy given keywords (up to first quarter 2006); only? one reviewer unclear – by Study selection : one rated by grading criteria, evidence ADA Quality assessment : studies of only to other reviewers; if in doubt referring reviewer, B or C included A, grade evidence ADA a by checked one reviewer, data extracted by : Data extraction second one Meta-analysis text and tables Data analysis : analyses Subgroups/sensitivity Methodology MEDLINE; Cochrane Library, EMBASE, PubMed, Search: strategy Google and Scholar; 2006; Jan 1990–Nov dates: search no language restrictions given; keywords no details of methods Study selection : quality scale 1–5 score Quality assessment : extracted independently reviewers two : Data extraction items listed information; Meta-analysis text and tables Data analysis : analyses Subgroups/sensitivity Inclusion criteria and methodology 2 32 levels in levels 1c : NIH : : non-commercial : 1c patients with T2DM and patients with mediators and to explore moderators Funding Review USA a to perform : Focus review comprehensive studies of of relevant SMBG on HbA UK of SMBG on effect : Focus HbA Funding McGeoch (2007) 64 (2007) McAndrew 65

© 2010 Queen’s Printer and Controller of HMSO. All rights reserved. Appendix 2 DOI: 10.3310/hta14120 Health Technology Assessment 2010; Vol. 14: No. 12 : yes : yes : : yes Inclusion criteria described: yes search given : Details of literature yes Study selection described : yes described: Data extraction yes Study quality assessment described : narratively yes, : shown Study flow Study characteristics of individual studies yes described : Quality of individual studies given yes Inclusion criteria described : yes search given : Details of literature yes Study selection described : yes described : Data extraction yes Study quality assessment described : yes : shown Study flow Study characteristics of individual studies yes described : Quality of individual studies given : yes : Results of individual studies shown yes Statistical analysis appropriate : yes : Results of individual studies shown yes Statistical analysis appropriate : Quality • • • • • • • • • • • • • • • • • • high QUALITY: OVERALL • • high/moderate – criteria QUALITY: OVERALL somewhat but some information fulfilled, limited , body , hypoglycaemia, , 1c 1c : 9 Number of included trials : 1862 Number of participants : TRIALS: all RCTs Design : 6 months to 62 weeks : Duration most trials quality variable, Quality : on less than half of positively scored the criteria of Delphi list see trial details PARTICIPANTS: all patients INTERVENTIONS: without insulin T2DM treated with except one study HbA OUTCOMES: : 7 RCTs Number of included trials : 1625 Number of participants : TRIALS: all RCTs Design : 4–12 months : Duration 2/7 low 5/7 high quality, Quality : quality see trial details PARTICIPANTS: some including INTERVENTIONS: education/counselling – see trial details HbA OUTCOMES: Included studies weight, BMI, QoL score, FPG, FPG, QoL score, BMI, weight, serum creatinine, blood pressure, microalbumin– clearance, creatinine total cholesterol, ratio, creatinine well- LDL, HDL, triglycerides, satisfaction, treatment being, episodes hypoglycaemic loss, BMI/weight fasting glucose, QoL health-related ; heterogeneity heterogeneity ; 1c : meta-regression on treatment on treatment meta-regression : : use of SMBG to modify treatment vs use of SMBG to modify treatment : reported as outcome measure 1c 1c : yes : : yes : Inclusion criteria RCTs Study design : non-insulin treated T2DM; Participants : SMBG vs no Intervention s: HbA Outcomes : Inclusion criteria FU at least 12 weeks RCTs and CCTs; Study design : T2DM Participants : SMBG alone or as part of multicomponent Interventions : intervention vs no SMBG HbA Outcomes: assessed analyses Subgroups/sensitivity quality score frequency, Methodology strategy updated to search Welschen PubMed; Search: strategy reviews bibliographies/systematic given; keywords 2007; July searched reviewers two assessed by titles independently Study selection : Delphi list Quality assessment : data extracted data extraction form; : Data extraction reviewers two by independently Meta-analysis baseline HbA mode; effects random Data analysis : Methodology search Cochrane Library; EMBASE, MEDLINE, Search: strategy reference given; keywords inception to September 2007; dates: no language restriction and trials searched; lists of reviews differences reviewers, two studies selected by Study selection : consensus settled by quality assessed using Maastricht–Amsterdam Quality assessment : reviewers two by done independently and the Delphi list; score two by extracted independently items listed, : Data extraction reviewers Meta-analysis heterogeneity model; random and fixed-effects Data analysis : funnel plot assessed, analyses Subgroups/sensitivity no use of SMBG to modify treatment Inclusion criteria and methodology 33 35 : not reported : non-commercial : Review Thailand of SMBG on effects : Focus in non- control glycaemic patients insulin-treated T2DM with Funding USA of SMBG in effect : Focus patients withT2DM Funding Poolsup (2008) Poolsup Towfigh (2008) Towfigh 64 65

© 2010 Queen’s Printer and Controller of HMSO. All rights reserved. Appendix 2 DOI: 10.3310/hta14120 Health Technology Assessment 2010; Vol. 14: No. 12 : no : : yes Inclusion criteria described : yes search given : Details of literature no Study selection described : no described : Data extraction no Study quality assessment described : narratively yes, : shown Study flow Study characteristics of individual studies yes described : Quality of individual studies given : yes : Results of individual studies shown yes Statistical analysis appropriate : Quality • • • • • • • • • • poor/moderate – limited QUALITY: OVERALL no description of description of methodology, study quality 75,000 in , SMBG , 1c : in T2DM: T2DM: in Number of included trials : 23 > Number of participants : 3941 pseudo- observational studies, 2573 in RCTs experimental, TRIALS: 4 pseudo- 13 observational, Design : 6 RCTs experimental, experimental and pseudo- : Duration experimental 6 months to 4 years not reported Quality : see trial details PARTICIPANTS: some including INTERVENTIONS: education – see details trial description HbA OUTCOMES: Included studies frequency, blood pressure, weight, weight, blood pressure, frequency, hypoglycaemia, cholesterol, depression 1 year ≥ : in/excluding studies of doubtful : 1 year or 1 year Agency for Healthcare Research and Quality; BMI, body mass index; CCT, controlled clinical trial; DTSQ, Diabetes Treatment Treatment Diabetes DTSQ, clinical trial; controlled CCT, body mass index; BMI, and Quality; Research Healthcare Agency for as primary outcome measure

, SMBG use , 1c 1c : yes : AHRQ,

Inclusion criteria experimental (RCTs or pseudo-experimental) and Study design : observational or cohort studies) (cross-sectional T2DM (excluding with type 1 or adults and children Participants : women) pregnant including SMBG alone or education programmes Interventions : SMBG and HbA Methodology 1996–June dates: search MEDLINE; EMBASE, Search: strategy lists checking of reference reported, keywords 2008; not reported Study selection : not reported Quality assessment : not reported : Data extraction Meta-analysis heterogeneity models; and random effects fixed Data analysis : assessed analyses Subgroups/sensitivity vs random to fixed robustness excluding largest trial, eligibility, duration < effects, : HbA Outcomes : Inclusion criteria and methodology 38 : not reported : American Diabetes Association; American Diabetes

Review Australia/UK literature reviewing : Focus to SMBG and relating in control glycaemic T2DM T1DM and Funding St John (2009) St John ADA, 66 Short SF-36, National Institutes of Health; NIH, lipoprotein; low-density LDL, high-density lipoprotein; HDL, follow-up; FU, fasting plasma glucose; FPG, Satisfaction Questionnaire; Form-36. 67

Appendix 3 Characteristics of RCTS

66 67

© 2010 Queen’s Printer and Controller of HMSO. All rights reserved. Appendix 3 DOI: 10.3310/hta14120 Health Technology Assessment 2010; Vol. 14: No. 12 in the 1c with SMBG and SMUG 1c 0.0097). , weight, FPG, use of oral medications, use of oral medications, FPG, weight, , = 1c duration of diabetes, ethnicity did not predict ethnicity did not predict duration of diabetes, glucose control improved intervention group than in the control group (–1.15% group than in the control intervention group 0.25% (95% CI difference treatment –0.91%, versus p 0.06 to 1.03; – 27 (8.7%) of patients SMBG group Hypoglycaemia: 11 (27 symptomatic, events had 51 hypoglycaemic 2 non-graded); 11 SMBG-confirmed, asymptomatic, – 21 (7.0%) of patients had 66 group control symptomatic of which 64 were events hypoglycaemic none of the patients had non-graded; were and two but (no statistics reported hypoglycaemia severe non-significant). presumably difference but no significant difference between groups in FPG, in FPG, groups between but no significant difference GHb or body weight and better educated patients younger towards Trend more improving Baseline HbA Significant reductions in HbA Significant Significantly greater reduction in HbA greater Significantly • • • Results • After 6 months: • : patients not allowed patients not allowed : 311): patients instructed in self-monitoring 311): = 87% of visits in both groups Intervention : every other day SMBG before each meal SMBG before other day every : SMBG regimen SMBG other : (Eli Tes-Tape Accu-Chek 1; Chemstrips bG, SMBG method : urine for Lilly) yes decision scheme : Use of therapy instructed in use of patients were yes; SMBG instruction : practised for which they testing technique, prescribed 7–10 days to show required were yes; SMBG accuracy checks : during study, in technique at initial visit; proficiency associate and diabetes teaching physician’s physician, use of the monitoring proper reinforced nurse techniques instruction diary; instruction and exercise yes; Education : a dietitian, diet instruction by diary; intake and food ADA’s booklet with and activity level; based on weight items with estimate of fibre food exchange lists for content (both groups) yes Assessment of monitoring frequency : yes Feedback on SMBG : adjustment/advice SMBG treatment but encouraged to alter therapy, to alter their own urine to readings; or diet according regimen behavioural used to guide physician- and FPG were and BG results alterations initiated treatment urine glucose testing : Control complete submitted were records assessment : Adherence on > lipids fasting glucose, weight, GHb, Outcomes : SMBG ( n instruction listed); devices their blood-glucose (approved on what to do in case of asymptomatic hypoglycaemia; at each use of glucose meter was checked appropriate patients assessed BG on 2 study investigator; visit by day) and one non-working (one working per week days each meals and 2 hours after the main meal before was increased once-a-month frequency bedtime; before no to measuring postprandial values after each meal; respect to to patients with given specific information based on SMBG results changing behaviour 8.8 3.3%, C: C: 3.3%, ± 2 : 54 (27/27) : : 610 patients with : mmol, no history of mmol, kg/m 3.0% 22 : I: 12.4 I: : : 8.12% : ± 1c 1c Participants number Total FPG > Inclusion criteria : and < with diet treatment ketoacidosis, agent, and/or oral hypoglycaemic or serious infection no active no physical illness, concurrent no prior or mental handicap, poorly of monitoring; knowledge diet or oral agents controlled; only 100% male 58 years; : Age BMI : HbA 11.7 6.8 SMBG: : Diabetes duration 9.0 years SMUG: years; oral diet, : Treatment agents (details of hypoglycaemic unclear) oral treatment : 2.8 years : Diabetes duration HbA Total number Total T2DM not T2DM, Inclusion criteria : insulin treated men and women 56 years, : Age 30 BMI : : : : no : 41 40 : ? : : 6 months : 27 weeks : unclear not probably : adequate power to FU described : withdrawals/losses (11%) yes no ITT analysis : yes statistical analysis appropriate : ? baseline characteristics similar : funding trial design and participants yes described : yes describedrandomisation : allocation concealment outcome assessment blinded trial design and participants yes described : yes describedrandomisation : Allen (1990) • • • • • • poor QUALITY: OVERALL Trial – design Trial USA Follow-up • • • international DINAMIC 1 study, Follow-up • Quality : • Quality : • 68 Barnett (2008) 69

0.001) 1c = kg). 4.01 ± in group A (baseline 7.97% vs in group 1c kg, non-SMBG –0.50 kg, 5.70 ± group B (baseline 8.1% vs 7.6% at 6 months; p B (baseline 8.1% vs 7.6% at 6 months; group more changes at 3-month visit were Therapeutic A (32.8%) B (44.9%) than group in group frequent Both groups had small decrease in weight (SMBG in weight had small decrease Both groups –0.68 No change in HbA 7.78% at 6 months) but significant decrease in HbA 7.78% at 6 months) but significant decrease No significant difference in number of all-cause in No significant difference events. adverse • was observed demonstrates that the use of meal-based of enable patients to observe the effects SMBG may problem choices and motivate them to avoid their food activity to manage hyperglycaemic physical increase foods, and adjusted doses of antidiabetic excursions or evaluate not reported) were these behaviours agents (however, • • Results • of that treatment study tried to ensure COMMENT: SMBG was identical (i.e. apart from groups the two no therapy identical medication, identical counselling, either requested adjustment based on SMBG results, while provider); the care the patient or initiated by by it argues the usefulness of this in practice is debatable, in HbA a reduction nevertheless, that the fact that, mg : , hypoglycaemia, FPG, adverse events, events, adverse FPG, hypoglycaemia, , , BG, therapeutic changes therapeutic BG, , 1c 1c 299): no SMBG 299): : all patients received diet and lifestyle diet and lifestyle all patients received : = Both groups oral at each visit; which was reinforced advice, all patients for was standardised antidiabetic therapy were on insulin secretagogue – those previously dosage approved to gliclazide MR following transferred gliclazide was other patients, for recommendations; at an initial dose of 30 to their treatment added all patients had then up-titrated as necessary; once daily symptoms of hypoglycaemia diary recording for patient’s intervention and SMBG (for group) HbA Outcomes : weight ( n Control Intervention : group A – one BG profile (fasting, 2 hours (fasting, A – one BG profile group : SMBG regimen 2 hours after dinner) 2 hours after lunch, after breakfast, 2 hours (fasting, one BG profile B1: per month vs group before 2 hours after lunch, lunch, before after breakfast, B2: vs group 2 weeks 2 hours after dinner) every dinner, to call diabetes clinic as B1 but with recommendation not met when BG targets were the same stated that patients followed SMBG other : protocol education and treatment no other details given SMBG method : – not specified yes Education : adjustment/advice SMBG treatment modes of SMBG compared – three see above : Control out as SMBG carried assessment : Adherence B1 A and 44% of groups 73% of group by recommended B2 called the clinic, patients of group very few and B2; lumped together – only B1 and B2 were so groups compliant patients assessed HbA Outcomes : 2 kg/m : 273 : within last 6 months, within last 6 months, : 8.0–8.1% : 1c 1c : 70–74% previously 70–74% previously : Treatment with oral glucose treated agent (43% biguanide, lowering 46–50% insulin secretagogue) diet only) (the rest Participants number Total stable T2DM, Inclusion criteria : HbA : 10.6 years : Diabetes duration not reported : Treatment HbA already on SMBG, not on insulin on SMBG, already mean 63–66 years : Age mean 28–29 BMI : : : : : : yes : : unclear : 42 : industry : : non-industry. : allocation concealment outcome assessment blinded unclear yes : adequate power to FU described : withdrawals/losses (14%) yes yes ITT analysis : yes statistical analysis appropriate : yes baseline characteristics similar : funding outcome assessment blinded trial design and participants yes described : no describedrandomisation : allocation concealment unclear unclear : adequate power to FU described: withdrawals/losses no no ITT analysis : statistical analysis appropriate : unclear yes baseline characteristics similar : funding Bonomo (2006) • • • • • • • • high QUALITY: OVERALL • 68 – design Trial (abstract) Italy 6 months Follow-up: Quality: • • • • • • • • • poor QUALITY: OVERALL 69

© 2010 Queen’s Printer and Controller of HMSO. All rights reserved. Appendix 3 DOI: 10.3310/hta14120 Health Technology Assessment 2010; Vol. 14: No. 12 mmol/l 28 vs 0.03) ± = 1.3%, 1.3%, ± 11.64%, SD 2.85), SD 2.85), 11.64%, > 80% of SMBG 0.9% vs 7.4 ≥ ± 10.89%, SD 2.56) than in 10.89%, > mmol/l (SD 0.73) vs 1.28 0.024) – but no significant difference 0.024) – but no significant difference = reduced significantly more in the intervention more significantly reduced in intervention group lower significantly level in the lower fluctuation was also significantly 1c 1c 1c 19; p 19; 0.016 0.009) ± = = group (11.81%, SD 3.0 (11.81%, group SD 3.0 (11.8%, group the control p (6.7 group than in control p ( p group intervention than in the control Frequency of SMBG was significantly higher in the of SMBG was significantly Frequency (34 group intervention than in the control 22 complied with) and poor compliance measurements groups in total or HDL cholesterol; No significant difference in intervention group lower significantly triglycerides after 30 months [1.16 (SD 0.75)] to SMBG measurements better adherence Significantly group than in the control in the intervention group between good compliance ( good between HbA HbA No significant difference in cholesterol levels, levels, in cholesterol No significant difference or BMI triglycerides HbA • • • • After 30 months : • Results • this was a complex multicomponent COMMENT: intervention as one element including SMBG only • fluctuation index 1c , HbA , 1c 1c : patients were given glucometers; diabetes glucometers; given patients were : Intervention : unclear : SMBG regimen competent diabetes self- culturally SMBG other : management intervention with SMBG education and designed to on success, focused support sessions; feedback frequent rapid provide no further details on SMBG given SMBG method : (intervention only) yes Education : waiting list with usual care : Control not reported assessment : Adherence HbA Outcomes : : internet-based glucose monitoring system; internet-based glucose monitoring system; Intervention : and at their convenience patients logged onto a website also information additional uploaded their SMBG results; weight, blood pressure, medication, uploaded (current discuss); to wanted patients questions lifestyle, in changes participated a dietitian and nurse 3 endocrinologists, and sent and logged on daily in the online system, (based in the patients’ recommendations appropriate 2 weeks SMBG data) every 3 outpatient visits every SMBG; standard : Control usual system; record note-keeping conventional months; dosage and lifestyle about medications, recommendation modification Both groups of SMBG method and frequency education programme; monitoring HbA Outcomes: mg/ 140 (Asian 2 : 252 : 80 patients with : kg/m 1 year; poorly poorly 1 year; : I: 11.8 (SD 3.0), C: 11.8 C: 11.8 (SD 3.0), I: : : 7.5–7.7% : 1c 1c Participants number Total FBG Inclusion criteria : glucose lowering taken have dl; agents > oral agents controlled; 54 years : Age NR BMI : HbA number Total T2DM 51–55 years : Age 23–24 BMI : (SD 3.0) 7.9 years : Diabetes duration 67% oral 7% diet only, : Treatment 6% oral 20% insulin only, only, plus insulin (no details on oral treatment) : 6.7–6.9 years : Diabetes duration 18 patients were : Treatment (7 in intervention, insulin treated (no details on oral 11 in control) treatment) population!) HbA : no : : : unclear : : unclear 43 44 : non-industry : : non-industry : 12 months : 30 months : : unclear : adequate power to FU described : withdrawals/losses no unclear ITT analysis : yes statistical analysis appropriate : yes baseline characteristics similar : funding unclear : unclea r adequate power to FU described : withdrawals/losses (11%) yes ITT analysis : yes statistical analysis appropriate : yes baseline characteristics similar : yes funding trial design and participants yes described : no describedrandomisation : allocation concealment outcome assessment blinded trial design and participants described : yes describedrandomisation : unclear allocation concealment outcome assessment blinded Brown (2002) Brown • • • • • • poor QUALITY: OVERALL • • • • • • moderate/poor QUALITY: OVERALL Trial – design Trial Follow-up • • • Korea Follow-up • • • Quality : • Quality : • 70 Cho (2006) 71

© 2010 Queen’s Printer and Controller of HMSO. All rights reserved. Appendix 3 DOI: 10.3310/hta14120 Health Technology Assessment 2010; Vol. 14: No. 12 in both groups significant but no in both groups 1c significant difference between groups between significant difference weight or BMI in No significant difference in medication at study end No significant difference Fall in HbA • • • Results : did not report training did not report : determination every 2 determination every 1c 43): SMBG 6 days per week before before per week SMBG 6 days 43): = , BMI/weight loss BMI/weight , 7.5%) 1c 45): regular HbA regular 45): = goal of < goal 1c months by a physician; 5 dietitian visits a physician; months by of an average patients performed assessment : Adherence tests 45% of required HbA Outcomes : Intervention ( n SMBG regimen and after each meal (6 times per day) dietitian visits five SMBG other : NR SMBG method : yes decision scheme : Use of therapy NR SMBG instruction : NR SMBG accuracy checks: dietitian used glucose values and dietitian visits; Education : counselling to educate meal descriptions in nutritional of meal components and the patient on effects portion sizes on the rise of postprandial glucose values (both groups) Assessment of monitoring frequency : Feedback on SMBG : adjustment/advice SMBG treatment detailed followed nurse to readings; to respond on how decisions (to achieve therapeutic to make algorithm HbA Control ( n Control 2 : 88 (43/45) : kg/m : I: 8.4 (SD 2.1), C: 8.5 C: 8.4 (SD 2.1), I: : 1c Participants number Total patients with Inclusion criteria: T2DM on oral antidiabetic treatment 50 years : Age 32.2 BMI : (SD 2.2) 5.6 years : Diabetes duration MET (27–28% : Treatment 51–53% in combination alone, SU (0–9% alone, with SU), 51–53% in combination with and/or thiazolidinedione MET), with MET and SU, (triple therapy 7–21%) HbA : yes : : unclear : 45 : industry : : 6 months : trial design and participants yes described : no describedrandomisation : allocation concealment outcome assessment blinded : unclear : adequate power to FU described : withdrawals/losses (none) yes yes ITT analysis : yes statistical analysis appropriate : yes baseline characteristics similar : funding Davidson (2005) Davidson • • • Quality : • 70 – design Trial USA Follow-up • • • • • • high/moderate QUALITY: OVERALL 71

© 2010 Queen’s Printer and Controller of HMSO. All rights reserved. Appendix 3 DOI: 10.3310/hta14120 Health Technology Assessment 2010; Vol. 14: No. 12 0.001) < for all groups for 1c 1c 0.0001) < was already quite low at the beginning quite low was already 1c one or more grade 2 hypoglycaemic episodes grade 2 hypoglycaemic one or more 33 in less group, 14 patients in control experienced by ( p group intensive 43 in more group, intensive No significant difference in HbA No significant difference in HbA no significant difference No significant difference in body weight, but of patients weight, in body No significant difference more significantly instructed to lose weight, who were in the intervention than in the control lost weight group frequently SMBG more performed Intervention group ( p group than control significantly fewer patients in more intensive group group intensive patients in more fewer significantly but persisted with meter use (52.3% vs 66%), monitored group intensive meter users in the more often more significantly in systolic or diastolic blood no significant difference BMI weight, pressure, reduced in the more significantly total cholesterol than control group intensive more intensive for more QoL (EQ-5D) lower significantly anxiety/ due to increased mainly vs control, group self- in mobility, (no significant difference depression or pain) usual activities, care, neither SMBG intervention was judged to be cost- effective • • After 12 months : • • • Results • • • • • HbA COMMENT: : no details on changes : , weight, SMBG adherence weight, , blood BMI, lipids, hypoglycaemia, , 1c 1c mmol/l after fasting and before meals and levels of meals and levels mmol/l after fasting and before to nurse advised by mmol/l 2 hours after meals; pressure Intervention : continued to use goal setting and to use goal continued SMBG less intensive : were at assessment visit; techniques introduced review 3 values daily to record a glucose meter and asked given meals (one after fasting and 2 before per week on 2 days of glucose levels or 2 ours after meals) and to aim for 4–6 6–8 high or low consistently were contact doctor if readings BG to interpret on how no information given (defined); readings training and given and were as before, SMBG intensive : of and using the results interpreting support in timing, SMBG to enhance motivation and maintain adherence activity and drug regimens physical to diet, including the use of goal usual care, standardised : Control not to use a glucose meter asked setting and review; their it essential for unless their doctor considered clinical management HbA Outcomes : : no details of protocols for SMBG for no details of protocols : SMBG regimen intense FU and education plus SMBG; 3-day SMBG other : series by on SMBG testing practices was given feedback a registered of telephone calls and one home visit from nurse diary no description of device, SMBG method : decision scheme : Use of therapy yes SMBG instruction : no SMBG accuracy checks : education (both groups) 3-day yes; Education : yes Assessment of monitoring frequency : yes Feedback on SMBG : adjustment/advice SMBG treatment or lifestyle made to therapy education plus SMBG 3-day standard : Control patient data sheets or memory assessment : Adherence of tests number of meters consulted to compare of tests requested conducted with number HbA Outcomes : 1.4% ± kg; 36–46% kg; 2 1.1%, C: 6.1 C: 1.1%, : 60 (controls 25 60 (controls : 453 patients with : ± kg/m : I: 6.3 I: : 7.4–7.5% : 1c 1c 115% ideal body weight Participants number Total 28) after dropouts/intervention T2DM; Inclusion criteria : with diet and/or treatment agents; oral hypoglycaemic completion of the 3-day provided education programme at the Diabetes Centre; telephone accessibility by 54 years C: 56 years, I: : Age 85.6 weight BMI : > HbA number Total T2DM not T2DM, Inclusion criteria : insulin treated 65.7 years : Age 31–32 BMI : : diet only 26–29%, 26–29%, diet only : Treatment 37.5–39%; oral monotherapy 34–35% combined oral therapy (no details on oral treatment) : median 3 years : Diabetes duration HbA : NR : Diabetes duration oral diet, : Treatment agents (no details hypoglycaemic on oral treatment) : : yes : : unclear : yes : 10,11 46 : unclear : non-industry : : 4 months : unclear unclear (probably : adequate power not) to FU described : withdrawals/losses (12%) yes yes ITT analysis : yes statistical analysis appropriate : yes baseline characteristics similar : funding yes : adequate power to FU described : withdrawals/losses (12.6%) yes yes ITT analysis : yes statistical analysis appropriate : yes baseline characteristics similar : funding trial design and participants yes described : no describedrandomisation : allocation concealment outcome assessment blinded trial design and participants yes described : yes describedrandomisation : allocation concealment outcome assessment blinded Estey (1990) Estey • • • • • • moderate/poor QUALITY: OVERALL • • • • • • high QUALITY: OVERALL Trial – design Trial Canada Follow-up • • • DiGEM trial 12 months p: Follow-u Quality : • • • • Quality : • 72 (2007) UK Farmer 73

© 2010 Queen’s Printer and Controller of HMSO. All rights reserved. Appendix 3 DOI: 10.3310/hta14120 Health Technology Assessment 2010; Vol. 14: No. 12 or body weight 1c No significant difference in HbA No significant difference • Results was 1c : no instructions on : , weight, number of reactive strips of reactive number weight, , 1c determined every 2 months at the outpatient clinic visit; 2 months at the outpatient clinic visit; determined every sent to the patient with physician’s were the results comment on their metabolic control strips of reactive number assessment : Adherence had used been used – urine group that should have compliance than SMBG or poorer less; significantly group control HbA Outcomes : reported Intervention : SMBG twice every other day, fasting and 2 other day, SMBG twice every : SMBG regimen with an extra test 2 hours meal, hours after the evening after lunch on Sunday not reported SMBG other : diary; Glucometer (Ames), Dextrostix, SMBG method : urine for Ketodiastix not reported decision scheme : Use of therapy yes SMBG instruction : no SMBG accuracy checks : individualised dietary patients received no; Education : or but no specific algorithms recommendations, changes strategy behavioural for predetermined yes Assessment of monitoring frequency : yes Feedback on SMBG : adjustment/advice SMBG treatment (all to SMBG readings according to alter therapy how physician) changes made by other urine glucose monitoring twice every 1 : Control voided in the morning and first on the first urine day, with an extra test meal, after the evening urine voided voided after lunch on Sundays on the first urine HbA no self-testing of urine or BG; 2 : Control mmol/l 11 mmol/l or 2 8.8 : 208 (68/72/68) : kg/m 3 years : I: 8.2 (SE 0.3), C1: 8.6 (SE C1: 8.2 (SE 0.3), I: : 1c Participants Total number Total with treatment Inclusion criteria: diet and/or oral hypoglycaemic FBG > agents, postprandial BG > year; 3 times within preceding at least occasional glucosuria; progressing no rapidly illness, no severe complications, DM > 56 C: SMUG 55; SMBG 55; : Age 27.1 BMI : 0.3), C2: 8.2 (SE 0.3) C2: 0.3), 12.5 years : Diabetes duration oral diet, : Treatment agents (details of hypoglycaemic unclear) oral treatment HbA : : : unclear : 47 : ? : : 6 months : trial design and participants yes described : no describedrandomisation : allocation concealment outcome assessment blinded unclear unclear : adequate power to FU described : withdrawals/losses (21%) yes no ITT analysis : yes statistical analysis appropriate : yes baseline characteristics similar : funding Fontbonne (1989) Fontbonne Trial – design Trial France Follow-up Quality : • • • • 72 • • • • • • poor QUALITY: OVERALL 73

© 2010 Queen’s Printer and Controller of HMSO. All rights reserved. Appendix 3 DOI: 10.3310/hta14120 Health Technology Assessment 2010; Vol. 14: No. 12 0.007) = at baseline at 3 months 1c 1c predicted by HbA by predicted 1c , shorter duration of diabetes, lower lower shorter duration of diabetes, , 1c 0.001) and SMBG group (OR 0.665, (OR 0.665, 0.001) and SMBG group < 0.015) = (OR 1.749, p (OR 1.749, p 57.1% patients had improvement in HbA 57.1% patients had improvement BMI weight, in blood pressure, No significant difference medication patients in the SMBG group more Significantly dietary following continued instructions than in the in exercise no significant difference group; control behaviour compared to 46.8% in the control group ( p group to 46.8% in the control compared improvement in HbA improvement No significant difference in fructosamine concentration No significant difference Patients doing SMBG were more likely reporting that likely more Patients doing SMBG were dietary advice followed they included SMBG group, of improvement Predictors higher initial HbA • • • • Results • • • 6 : no details on changes : 345): patients received a conventional a conventional patients received 345): = every 12 weeks and underwent SMBG ( ≥ and underwent 12 weeks every 1c times per week) unclear SMBG other : unclear SMBG method : unclear decision scheme : Use of therapy GP by initial training given yes; SMBG instruction : yes SMBG accuracy checks: of informed patients were at GP visits, no; Education : diabetes control, the necessity of good their BG values, loss in combination with and importance of weight activity physical ( n SMBG regimen: laboratory based on laboratory work-up measurement of HbA Intervention : no details of protocols for blood or urine for no details of protocols : SMBG regimen monitoring per week FBG and after meals 2 days SMBG other : no description SMBG method : not reported decision scheme : Use of therapy yes SMBG instruction : no SMBG accuracy checks : no Education : no Assessment of monitoring frequency : no Feedback on SMBG : adjustment/advice SMBG treatment or lifestyle made to therapy SMUG : Control not reported assessment : Adherence fructosamine Outcomes : 1 year, 1 year, 7.5 and > 1c 2 : 27 (15/12) : : 689 (345/344) : kg/m : NR : 1c 11%), age 40–75 years and not age 40–75 years 11%), Participants : NR : Diabetes duration oral diet, : Treatment agents (details of hypoglycaemic unclear) oral treatment Total number Total on oral Inclusion criteria : agents hypoglycaemic (47–80) 64 years : Age NR BMI : HbA < with insulin treated previously than 7 consecutive more (for insulin at and not requiring days) patients who did not inclusion, SMBG but receive previously able to carry out SMBG 62 (40–75) years : Age 30 BMI : patients insufficiently controlled controlled patients insufficiently with oral glucose lowering (HbA treatment Total number Total T2DM < Inclusion criteria :

30 : ? : : : ? : unclear : 48 4/11 reporting, 4/11 reporting, 29 49 : 24 weeks : 24 weeks : : ? : adequate power to FU described : withdrawals/losses ? (26%) ITT analysis :? yes statistical analysis appropriate : ? baseline characteristics similar : ? funding: unclear yes : adequate power to FU described : withdrawals/losses (31%) yes trial design and participants unclear described : ? describedrandomisation : allocation concealment outcome assessment blinded trial design and participants yes described : no describedrandomisation : allocation concealment outcome assessment blinded 3/7; Coster 2000 3/7; Gallichan (1994) • • • • • • study not QUALITY: OVERALL rated as assessment; for available Faas 1997: other reviews: by follows • • Trial – design Trial UK Follow-up • • • France Follow-up • • • Quality : • Quality : • 3/3 external validity, 3/7 bias, 3/6 3/7 bias, 3/3 external validity, 13/27 total (poor) confounding, 74 (2003) Guerci 75

© 2010 Queen’s Printer and Controller of HMSO. All rights reserved. Appendix 3 DOI: 10.3310/hta14120 Health Technology Assessment 2010; Vol. 14: No. 12 0.05) This 0.05) < education vs nothing + significantly lower in the SMBG group after in the SMBG group lower significantly 1c HbA treatment (SMBG 7.6% vs control 9.65%, p 9.65%, (SMBG 7.6% vs control treatment but size, study seems to be a bit of an outlier in effect it was SMBG • Results : yes : : did not report training did not report : 1c , hypoglycaemia, weight, blood pressure weight, hypoglycaemia, , HRQoL hypoglycaemia, , 1c 1c 344): conventional laboratory only work-up conventional 344): = : not reported assessment : Adherence HbA Outcomes : ( n Control Intervention : 4 times per day for 2 days per week 2 days for 4 times per day : SMBG regimen instruction on diabetes and SMBG other : SMBG exercise, medical counselling, regulation, unclear SMBG method : unclear decision scheme : Use of therapy yes SMBG instruction : SMBG accuracy checks: (intervention only) yes Education : unclear Assessment of monitoring frequency : unclear Feedback on SMBG : adjustment/advice SMBG treatment usual care : Control unclear assessment : Adherence HbA Outcomes : : unclear Assessment of monitoring frequency : unclear Feedback on SMBG : adjustment/advice SMBG treatment GP could change to readings; to respond on how based on HbA treatment 1.3% ± ACE I or ACE

1.3%, C: 9.0 C: 1.3%, 2 : 39 (17/22) : ± kg/m : I: 9.0 I: : 9.7 (SD C: 9.2 (SD 2.0), I: : 1c 1c HbA Participants number Total African- urban Inclusion criteria : T2DM American patients with attending currently who were internal a university-affiliated, medicine outpatient clinic 65 years C: 59 years, I: : Age 33 BMI : 2.5) 6.8 years : Diabetes duration details of treatment : Treatment unclear HbA HMG-CoA reductase inhibitors HMG-CoA reductase : 8.0 years : Diabetes duration 99.5% on oral : Treatment antidiabetic agents (80.8% on 30% 61.1% on biguanides, SUs, on alpha-glucosidase inhibitors), ~80% on fibrates, : : unclear 50 : unclear : : ? : 4 months : : yes ITT analysis : yes statistical analysis appropriate : yes baseline characteristics similar : funding trial design and participants yes described : describedrandomisation : no allocation concealment outcome assessment blinded unclear not : probably adequate power to FU described : withdrawals/losses (13%) yes ITT analysis : yes statistical analysis appropriate : yes baseline characteristics similar : yes funding • • • • moderate/poor QUALITY: OVERALL • • • Quality : • Trial – design Trial Follow-up • • • • • • moderate/poor QUALITY: OVERALL 74 Jaber (1996) 75

© 2010 Queen’s Printer and Controller of HMSO. All rights reserved. Appendix 3 DOI: 10.3310/hta14120 Health Technology Assessment 2010; Vol. 14: No. 12 kg 0.001) 2.5 vs < ± 1.2%, adjusted 1.2%, ± 0.001) levels at 6 months levels 1c < 1.5% vs control 7.1 1.5% vs control than TAU, but not statistically but not statistically TAU, than ± 1c 0.01) < was significantly reduced ( p was significantly 1c kg; p kg; 2.5, adjusted difference 0.64 (95% CI 0.18 to 1.10; 0.64 (95% CI 0.18 to 1.10; adjusted difference 2.5, 1c ± 0.007), i.e. patients receiving free strips monitored strips monitored free patients receiving i.e. 0.007), = (intervention 7.3 No significant difference in HbA No significant difference For SMBG intervention, 43.4% of those receiving PTC 43.4% of those receiving SMBG intervention, For to an action stage vs 30.5% receiving plus strips moved plus strips and TAU PTC alone vs 27.0% receiving alone ( p TAU 18.4% receiving For SMBG intervention, PTC resulted in greater in greater PTC resulted SMBG intervention, For of HbA decrease significant; however, for those who moved to an action for those who moved however, significant; HbA stage, difference 0.02% (95% CI –0.16 to 0.22) difference Activities significantly Summary of Diabetes Self-Care (4.1 in intervention group better results 3.5 p on average 0.64 days more than patients who did more 0.64 days on average of monitoring was not associated with frequency not; HbA vs –0.26 Weight loss for those enrolled in both SMBG and those enrolled loss for Weight SMBG eating interventions and who increased healthy for than greater was significantly as recommended stage (–1.78 in the pre-action those who remained • • • COMMENT: no information on SMBG messages and no information COMMENT: readings or how diabetes education patients received was or what feedback used to adjust treatment, were controlled well relatively patients were to patients; given study aimed to at the beginning of study already; to testing financial barriers reducing that merely show improve strips) will not necessarily free providing (by and education, to appropriate outcomes if it is not linked this seemed to be the case Results • • , weight, behaviour behaviour weight, , 1c SMBG: treatment as usual treatment SMBG: + : , diabetes self-care activities [Summary diabetes self-care , 1c SMBG: Pathways to Change (based on Pathways SMBG: + of Diabetes Self-Care Activities (SDSCA)] of Diabetes Self-Care (SMBG monitoring – and healthy eating, smoking for smoking for eating, (SMBG monitoring – and healthy other parts of the study) Intervention : free BG meter, free 6-month supply of 6-month supply free BG meter, free Intervention : testing strips BG meter free : Control meter (Glucometer free all participants received Both : study training at the pharmacy; all received Elite XL); testing of 7 times average pharmacists recommended those on and for patients on oral agents, for per week FU visits at 3 3 or 4 times per week; once daily diet only, of testing procedures reinforcement and 6 months for to changes in response on therapy No information SMBG HbA Outcomes : comparisonFour groups PTC PTC: strips; Model of Change) plus free Transtheoretical mail monthly intervention multicomponent programme; on SMBG, focus 12 months; or telephone contact for or smoking eating, and/or healthy strips no free to Change, Pathways PTC: as usual) (treatment TAU strips plus free strips no free as usual, treatment TAU: HbA stage of change, Outcomes: 1 year); 1 year); 2 2 : 262 : : 860 : kg/m kg/m : 7.3–7.5% : 8.4–8.6% : 1c 1c Participants : 7.7–8.6 years : Diabetes duration 96–97% on oral agents : Treatment (no details) Total number Total T2DM (> Inclusion criteria : not insulin treated men and women 68.4 years, : Age 29–32 BMI : HbA HbA Total number Total patients with Inclusion criteria : SMBG T2DM for T1DM or intervention (all in pre-action using less SMBG (i.e. stage for (of a total than recommended) 58.2% were of 1029 patients, 89% 2 behaviours, for enrolled SMBG and healthy of those for eating) men and women 55 years, : Age 32 BMI : : yes yes : ) 2 : unclear : : unclear : kg/m 51 52 ) 1c : non-industry : : 6 months : 12 months : : yes : Adequate power to FU described : Withdrawals/losses (45% withdrawals/losses yes 36% in group, to FU in control intervention group) yes ITT analysis : yes Statistical analysis appropriate : Baseline characteristics similar : (67 younger slightly group control higher and slightly vs 70 years) BMI 31.7 vs 29.1 Trial design and participants Trial yes described : no Randomisation described : Allocation concealment Outcome assessment blinded HbA (for trial design and participants yes described : no describedrandomisation : allocation concealment Funding Jones (2003) Jones • • • • • Johnson (2006) Johnson Trial – design Trial Canada Follow-up • • • Diabetes Stages of Change Study Canada (DiSC), by diabetes treatment RCT stratified but no detailed separate reporting T2DM and insulin vs T1DM and for non-insulin Follow-up • • Quality : • Quality : • 76 • moderate QUALITY: OVERALL 77

© 2010 Queen’s Printer and Controller of HMSO. All rights reserved. Appendix 3 DOI: 10.3310/hta14120 Health Technology Assessment 2010; Vol. 14: No. 12 decreased by 0.8% in preprandial SMBG 0.8% in preprandial by decreased 1c group and by 0.9% in postprandial SMBG group – no 0.9% in postprandial SMBG group and by group significant difference HbA COMMENT: does not meet our inclusion criteria (cannot COMMENT: but interesting insulin/non-insulin), T1DM/T2DM, separate SMBG as it demonstrates the interaction between education/counselling and and appropriate behaviour other outcomes • Results : physician could give could give physician : 1c Intervention : twice-daily, preprandial SMBG preprandial twice-daily, : SMBG regimen SMBG method not reported SMBG other : NR SMBG method : NR decision scheme : Use of therapy NR SMBG instruction : NR SMBG accuracy checks: NR Education : NR Assessment of monitoring frequency : NR Feedback on SMBG : adjustment/advice SMBG treatment advice treatment postprandial SMBG twice-daily, : Control NR assessment : Adherence HbA Outcomes : : 57 : : 8.3–8.4% : 1c : 10–11 years : Diabetes duration about half of the : Treatment insulin-treated patients were (no details of oral treatment); not were patients on diet only included Participants number Total using T2DM, Inclusion criteria : medication NR : Age NR BMI : HbA : NR : Diabetes duration NR : Treatment : : : : : unclear : 53 : industry : : unclear : : 4 months : outcome assessment blinded unclear unclear : adequate power to FU described : withdrawals/losses (22.3%) yes yes ITT analysis : yes statistical analysis appropriate : yes baseline characteristics similar : funding Quality : trial design and participants yes described : no describedrandomisation : allocation concealment outcome assessment blinded unclear unclear (probably : adequate power not) to FU described : withdrawals/losses (33%) yes unclear ITT analysis : statistical analysis appropriate : unclear baseline characteristics similar : unclear funding Joy (2003) Joy • • • • • • • poor QUALITY: OVERALL • • • • • 76 – design Trial USA (abstract) Follow-up • • • • • • poor QUALITY: OVERALL 77

© 2010 Queen’s Printer and Controller of HMSO. All rights reserved. Appendix 3 DOI: 10.3310/hta14120 Health Technology Assessment 2010; Vol. 14: No. 12 0.03) = 0.022) in SMBG group 0.022) in SMBG group 7% = ≥ p 1c 0.05) < decreased 1.37% ( decreased in the internet intervention lower significantly 1c 1c No significant difference between groups in lipid groups between No significant difference parameters not meet our inclusion criteria because no no- Would as it seems to but is of interest group, SMBG control that extra support SMBG to work show is needed for HbA group after treatment than in the control group group than in the control after treatment group p (–0.54% vs +0.33%; in pronounced more groups between Differences patients with initial HbA and 0.38% in control group (NS) – not reported if (NS) – not reported group and 0.38% in control groups between significant difference with hypoglycaemia episodes of fewer Significantly p SMBG (0.172 vs 0.354 per patient-year; Intervention judged to be cost-effective HbA • • • • • • Results • : patients were advised patients were : 3 days per week 1–3 per week 3 days ≥ 40): SMBG pre and post meals; and post meals; SMBG pre 40): = , costs, hypoglycaemia costs, , 1c Intervention : 2–3 times/day every 2 weeks (FPG and 2 2 weeks every 2–3 times/day : SMBG regimen and/or lunch) hours after breakfast not reported SMBG other : Glucostix SMBG method : unclear decision scheme : Use of therapy class on SMBG 2-day SMBG instruction : yes SMBG accuracy checks : both groups yes, Education : unclear Assessment of monitoring frequency : unclear Feedback on SMBG : adjustment/advice SMBG treatment medications to act based on SMBG measurements; how as necessary patients based on SMBG, adjusted by doctor made visits, monthly no SMBG, : Control medication changes unclear assessment : Adherence HbA Outcomes : ( n SMBG regimen to use SMBG recommended including after meals times per day SMBG with internet-assisted patient SMBG other : consultations without outpatient management visits; asking questions, SMBG values online, included recording exercise, diet, re (recommendations feedback receiving medication) not reported SMBG method : no decision scheme : Use of therapy NR SMBG instruction : 30 years, no 30 years, (Asian 2 (Asian population!) 2 : 64 : : 101 (50/51) : kg/m kg/m : 7.55–8.2% : C: 7.59% (SD 1.42), I: : 1 year; age > 1 year; 1c 1c Total number Total oral T2DM, Inclusion criteria : medication or insulin 50 (35–65) years : Age 23.9 BMI : Participants medication limits reported 54 years : Age 24 BMI : : NR : Diabetes duration oral hypoglycaemic : Treatment agents or insulin (not reported no using insulin, were many how details of oral medication) 7.19% (SD 1.17) 6.8 years : Diabetes duration NR : Treatment population!) HbA HbA Total number Total men and Inclusion criteria : T2DM diagnosed with women > for : no : : : unclear : unclear : ) 2 54 55 kg/m : industry : : 18 months : 12 weeks : funding : unclear (probably unclear (probably : adequate power not) to FU described : withdrawals/losses (11 patients in the control yes excluded due to were group by visits and replaced irregular another 11!) no ITT analysis : statistical analysis appropriate : unclear baseline characteristics similar : BMI lower slightly group control (23 vs 25 unclear trial design and participants yes described : no describedrandomisation : allocation concealment outcome assessment blinded trial design and participants yes described : unclear describedrandomisation : randomisation) (adaptive allocation concealment outcome assessment blinded • OVERALL QUALITY: poor QUALITY: OVERALL Kibriya (1999) Kibriya • • • • • Trial – design Trial Bangladesh Follow-up • • • Korea Follow-up • • • Quality : • Quality : • 78 (2004) Kwon 79

© 2010 Queen’s Printer and Controller of HMSO. All rights reserved. Appendix 3 DOI: 10.3310/hta14120 Health Technology Assessment 2010; Vol. 14: No. 12 No significant difference between groups in GHb or groups between No significant difference well-being 70% patients based on ease of use: by Preferences 44% SMUG vs 31% acceptability: SMUG vs 15% SMBG; 11% SMUG vs 76% SMBG; accuracy: perceived SMBG; 21% SMUG vs 49% SMBG) usefulness: Results • • crossover does not mention randomisation; COMMENT: : no details on : mmol/l) 8 : internet : 1c 3 days per week 1–3 times per day including 1–3 times per day per week 3 days 41): SMBG and usual care involved monthly monthly involved SMBG and usual care 41): ≥ = aglucosuria) = visits with two or three visits with senior staff during or three visits with two to also recommended group control period; 12-week use SMBG after meals yes assessment : Adherence HbA Outcomes : : NR SMBG accuracy checks : to use taught how intervention patients were Education : the internet system yes Assessment of monitoring frequency : via the received recommendations Feedback on SMBG : internet adjustment/advice SMBG treatment included medication changes recommendations ( n Control Intervention : SMBG once daily before a different meal a different before SMBG once daily : SMBG regimen (target < each day or at bedtime, no details given SMBG method : yes SMBG accuracy checks: 4 education sessions (both groups) Education : adjustment/advice NR SMBG treatment or lifestyle changes made to therapy alternating glucosuria, for test once daily : Control or at bedtime meals, or 2 hours after different before (target : NR assessment : Adherence weight QoL, GHb, Outcomes : 2 : 150 : kg/m : I: 10.3 (SD 2.6), C: 10.3 C: 10.3 (SD 2.6), I: : 1c Participants number Total diagnosed newly Inclusion criteria : oral agents or insulin T2DM; 65 (31–91) years : Age 27.3 BMI : (SD 2.3) 0 (newly : Diabetes duration diagnosed) treatment of details no : Treatment HbA : : : no : 56 : non-industry : : unclear : : 24 weeks : : yes : adequate power to FU described : withdrawals/losses (8%) yes no ITT analysis : yes statistical analysis appropriate : yes baseline characteristics similar : funding outcome assessment blinded trial design and participants unclear described : no (not describedrandomisation : allocation randomised, really to week) week from altered allocation concealment unclear unclear : adequate power to FU described : withdrawals/losses (24%) yes unclear ITT analysis : statistical analysis appropriate : unclear baseline characteristics similar : unclear funding • • • • • • poor QUALITY: OVERALL • Trial – design Trial Miles (1997) UK Follow-up Quality : • • • • • • • • • poor QUALITY: OVERALL 78 79

© 2010 Queen’s Printer and Controller of HMSO. All rights reserved. Appendix 3 DOI: 10.3310/hta14120 Health Technology Assessment 2010; Vol. 14: No. 12 0.01) 0.05), 0.05), = < and , duration of , 1c 1c 1.3 ( p ± and SMBG , body weight or QoL body weight , , SMBG frequency , 1c 1c 1c 1c 0.4)] = levels not significantly different different not significantly levels 1c 1c 1.5 times per day vs 2.0 1.5 times per day ± 0.05); in a multivariate model controlling model controlling in a multivariate 0.05); levels compared with 44% in the other compared levels 1c = 1.7 ( p ± reduced by 1.54% in SMBG group ( p 1.54% in SMBG group by reduced 1c 0.03) = Only 38% of patients in the BGM+ group reported 38% of patients in the BGM+ group Only BG monitoring results regarding affect negative and 57% in SC group with 65% in MT group compared ( p duration of diabetes, initial HbA duration of diabetes, between groups at study end (BGM+: –0.13%, MT: MT: –0.13%, at study end (BGM+: groups between improved but 61% in BGM+ group +0.4%); SC: –0.04%, their HbA frequency not related to HbA not related frequency groups ( p groups for age, sex, diabetes type, baseline HbA diabetes type, sex, age, for 0.84% in control group (NS) group 0.84% in control initial HbA Duration of diabetes, diabetes, education level and SES, assignment to BGM+ and SES, education level diabetes, of improvement was a significant predictor group at study end (no significant control in glycaemic T2DM) T1DM and between difference No significant correlations between HbA between No significant correlations between groups between HbA Patients in BGM+ group were checking BG levels checking BG levels were Patients in BGM+ group often than patients in MT and SC more significantly [2.8 groups and 2.1 absolute HbA No significant difference in HbA No significant difference • • COMMENT: not an inclusion (no clear separation of COMMENT: T1DM on but some limited information T2DM, T1DM and emotions that negative as it stresses interesting, T2DM); vs to SMBG can be changed and that this in response a positive – have change and – possibly in behaviour result influence on HbA • • After 6 months: • • Results • , affect , 1c 12): initially 6 times per day before before 6 times per day initially 12): = 50): BG meter and received blood sugar BG meter and received 50): : BG meter received and 30-minute diabetes and 30-minute BG meter received : = 50): BG meter 50): 99): standard care [individual or group standard standard [individual or group care standard 99): = = Intervention Three comparison groups: Three BGM+ (n monitoring owner’s manual – includes practical manual monitoring owner’s to help people but also information information, emphasis on to monitoring (e.g. barriers overcome etc.) not self-blame, emotions, positive MT (n Both groups on BG monitoring and education session focusing patients certifiedsupport diabetes educator; from received meters but no test strips; new received health by monitoring supplies (covered for prescriptions insurance) SC ( n accredited)] diabetes education (ADA no SMBG regimen, on recommended No information to adjustments in response on therapy information on accuracy checks no information SMBG; HbA SMBG monitoring, Outcomes : ( n SMBG regimen and and after meals then just one set of tests before after meals per day control weight proprietary behavioural SMBG other : a diabetes one-on-one counselling by programme, and dietitian during a run-in period of 8 weeks; nurse using the blood counting training, carbohydrate SMBG, monitoring meters reflectance One touch (LifeScan) SMBG method : NR decision scheme : Use of therapy yes SMBG instruction : yes SMBG accuracy checks: counselling (both groups) Education : Assessment of monitoring frequency : NR Feedback on SMBG : 9.5–13%, 9.5–13%, 1c 1 year, no SMBG 1 year, 2 2 : 199 patients with : : 29 : kg/m kg/m : 8.9–9.3% : : I: 10.3 (SD 1.1), C: 10.5 C: 10.3 (SD 1.1), I: : 1c 1c Participants number Total T2DM (26–39% in T1DM or T1DM) had each group T2DM T1DM or Inclusion criteria : 46–50 years : Age 30 BMI : : 16–18% were not 16–18% were : Treatment (no details of oral insulin-treated therapy) (SD 1.5) C: 5.7 years, I: : Diabetes duration 5.2 years : 9.5–11 years : Diabetes duration HbA HbA no serious underlying medical or no serious underlying drug abuse or psychiatric illness, alcoholism 60 years C: 57 years, I: : Age 34 BMI : Total number Total overweight Inclusion criteria : age 40–75 T2DM, patients with T2DM > years, within the previous 3 months, 3 months, within the previous not instructed to count dietary HbA carbohydrate, : : : : unclear : no : 57 20 : industry and non-industry : : 6 months : 44 weeks : unclear unclear : adequate power to FU described : withdrawals/losses no (none?) unclear ITT analysis : yes statistical analysis appropriate : baseline characteristics similar : unclear funding unclear unclear (probably : adequate power not) to FU described : withdrawals/losses no (21%) trial design and participants yes described : no describedrandomisation : allocation concealment outcome assessment blinded trial design and participants yes described : unclear describedrandomisation : groups) (blocked allocation concealment outcome assessment blinded Moreland (2006) Moreland • • • • • • poor QUALITY: OVERALL • • Trial – design Trial USA Follow-up • • • (1994) Muchmore USA Follow-up • • • 80 Quality : • Quality : • 81

© 2010 Queen’s Printer and Controller of HMSO. All rights reserved. Appendix 3 DOI: 10.3310/hta14120 Health Technology Assessment 2010; Vol. 14: No. 12 vs 2 0.8% ± kg/m 6.4 ± : 6.9 at 12 months : 1c control) 2 1.2% control ± kg/m 6.0 ± 31.8 No significant difference in hypoglycaemia but the hypoglycaemia in No significant difference to detect a difference power study lacked No significant difference in BMI (33.1 No significant difference No significant difference in HbA No significant difference • Results SMBG vs 6.9 in anxiety, no significant difference Psychological variables : SMBG but patients receiving energy, well-being, positive (scoring 6% higher on depressed more significantly were questionnaire) subscale of the well-being the depression • : SMBG used to supportto used SMBG : 1c , QoL, weight QoL, , use of oral BMI, hypoglycaemia, , 1c 1c 11): proprietary behavioural weight control control weight proprietary behavioural 11): : identical structured core education core identical structured : = programme, one-on-one counselling by a diabetes nurse a diabetes nurse one-on-one counselling by programme, and dietitian during a run-in period of 8 weeks 4.67 SMBG frequency average assessment : Adherence times/week HbA Outcomes : hypoglycaemic drugs, well-being, treatment satisfaction, satisfaction, treatment well-being, drugs, hypoglycaemic attitude : HbA Outcomes : SMBG treatment adjustment/advice treatment SMBG patients dietary intervention based on caloric counting; (but could be therapy to alter their own not allowed but encouraged to alter behavioural GP), by altered to readings or diet according regimen ( n Control Intervention : provided with glucose monitor (LifeScan with glucose monitor (LifeScan provided SMBG : instruction on monitoring; Ultra) and given OneTouch to monitor 4 fasting and asked patients were per week; postprandial capillary BG measurements to high or low responses advised on appropriate were or suggestion dietary (including need for review readings at each to high readings); in response of exercise with self-monitoring regimen concordance clinic visit, ongoing readings; meter by downloading was verified of and interpretation advice and support in appropriate to their BG results response no monitoring : Control Both groups practitioners, diabetes nurse involving programme all patients reviewed medical staff; podiatrists, dietitians, practitioner and dietitian at diabetes nurse doctor, by at each visit all aspects of diabetes intervals; 3-monthly dietary for identical algorithm and reviewed; were care both for pharmacological management of glycaemia based on HbA groups 2 : 184 (96/88) : kg/m : 8.6–8.8% : 1c : 74% on oral agents : Treatment on diet rest (no details given), Participants Total number Total patients with Inclusion criteria : not T2DM; diagnosed newly insulin treated men and 58–61 years, : Age women 32–34 BMI: : 0 : Diabetes duration not reported : Treatment HbA : yes : : yes : 13 : industry and non-industry : : non-industry, meters non-industry, : : 1 year : : unclear ITT analysis : yes statistical analysis appropriate : yes baseline characteristics similar : funding trial design and participants yes described : yes describedrandomisation : allocation concealment outcome assessment blinded Johnson of charge by supplied free & Johnson : yes : adequate power to FU described : withdrawals/losses (2.2%) yes yes ITT analysis : yes statistical analysis appropriate : yes baseline characteristics similar : funding • • • • poor QUALITY: OVERALL Trial – design Trial UK ESMON study Follow-up Quality : • • • • high QUALITY: OVERALL • • • • • • 80 O’Kane (2008) 81

1c in the low in the low 1c 1.0% in low group vs group 1.0% in low ± 1c 10% were more likely to likely more 10% were > in the intervention group in the intervention group 1c 1c 0.05), increase by 0.5% in control group group 0.5% in control by increase 0.05), < 0.0022); no significant difference in HbA no significant difference 0.0022); = : 1 SMBG per week is as sufficient and safe as 4 is as sufficient and safe 1 SMBG per week : 1.0% in high group at 12 months) 1.0% in high group 0.001); difference between groups not reported groups between difference 0.001); ± < values at 3, 6 or 12 months (6.9 values at 3, 7.1 improve Small reduction in HbA Small reduction group ( p group by 0.5% ( p by ( p Non-inferiority demonstrated for HbA demonstrated for Non-inferiority No significant difference in healthcare utilisation in healthcare No significant difference groups between (including hospital stays) in changes diabetes No significant difference treatment (QoL and satisfaction data to be published separately.) Patients with initial HbA • Results • • • • Conclusion to maintain HbA SMBG per week • no instructions on how : no instructions on how , weight, FPG weight, , 102): SMBG with four measurements measurements SMBG with four 102): 1c 100): SMBG with one measurement SMBG with one measurement 100): = = : case-management approach, all patients case-management approach, : Intervention Low SMBG ( n Low per week and additional measurement in the event of in the event measurement and additional per week hyperglycaemia or severe suspected hypoglycaemia High SMBG ( n per week on Tuesdays, Thursdays and one day of the and one day Thursdays Tuesdays, on per week measurement dinner and one additional before weekend in the event measurement lunch – also additional before hyperglycaemia or severe of suspected hypoglycaemia Both groups of back to their doctor in the event to report asked based on the targets set diabetes control, inappropriate the patient and their doctor between : no fixed regimen; patients were told to were patients regimen; no fixed : SMBG regimen had or if they well did not feel monitor BG when they activity partstrenuous in unusually taken patients accepting opportunity of SMBG SMBG other : patients contacted practice instructions; given were patients under of FBG; to state level monthly nurse (not practising SMBG) consulted their GP care during which patients doctors at least 4 times per year, all patients in for BG level; of current was informed scheme was used a therapeutic experimental group regulation and with weight and for targets with fixed emphasis on loss of body weight 20–800 strips Haemo-Glukotest SMBG method : yes decision scheme : Use of therapy (2–5 sessions) yes SMBG instruction : yes SMBG accuracy checks: 2–3 training visits Education : no Assessment of monitoring frequency : no Feedback on SMBG : adjustment/advice SMBG treatment (all changes to SMBG readings according to alter therapy with GP when made appointment physician); made by BG high no instruction in SMBG appointments; no fixed : Control noting low by inferred adherence assessment : Adherence of trial dropouts number HbA Outcomes : 6 2 , 21% 27– , 2 kg/m 30 kg/m : 149 (66/83) : : 202 : 27 , 27% > , 2 : 7.2% : : I: 9.7 (SD 2.1), C: 8.9 (SD C: 9.7 (SD 2.1), I: : 1c 1c kg/m Total number Total T2DM > Inclusion criteria : no age 40–75 years, months, internist by no treatment insulin, diseases other than diabetes, for obesity or hypertension 63 (40–75) years : Age 51% < BMI : Participants : 7.8–8.2 years : Diabetes duration ~50% 71–75% MET, : Treatment and various others SUs, 1.9) 8.8 years : Diabetes duration oral diet, : Treatment agents (not details hypoglycaemic given) HbA 30 Total number Total patients with Inclusion criteria : not insulin-treated T2DM; men and 61–62 years, : Age women not reported BMI : HbA : : : : unclear : yes : 59,60 58 (8.9% vs 9.7%) 1c : unclear : : 12 months : 12 months : funding unclear unclear : adequate power to FU described : withdrawals/losses (13%) yes no ITT analysis : yes statistical analysis appropriate : baseline characteristics similar : shorter duration group control and of diabetes (6.6 vs 10 years) HbA lower unclear trial design and participants yes described : no describedrandomisation : allocation concealment outcome assessment blinded trial design and participants yes described : yes describedrandomisation : allocation concealment outcome assessment blinded • OVERALL QUALITY: poor; poor; QUALITY: OVERALL with furtherSMBG confounded interventions Rutten (1990) • • • • • Trial – design Trial Netherlands Follow-up • • • Germany Follow-up • • • Quality : • Quality : • 82 Scherbaum (2008) 83

1c 1c in the low in the low 1c 3.9 per week/ ± 0.0086) 1.0% in low group vs group 1.0% in low = ± 1c 10% were more likely to likely more 10% were reduction in SMBG group in SMBG group reduction > 1c in the intervention group in the intervention group 1c 1.41%; p 1.41%; 1c ± led to failure 1c 0.05), increase by 0.5% in control group group 0.5% in control by increase 0.05), < 0.0022); no significant difference in HbA no significant difference 0.0022); = 1.08% vs –0.54 : 1 SMBG per week is as sufficient and safe as 4 is as sufficient and safe 1 SMBG per week : ± 1.0% in high group at 12 months) 1.0% in high group 0.001); difference between groups not reported groups between difference 0.001); ± < values at 3, 6 or 12 months (6.9 values at 3, 7.1 improve Small reduction in HbA Small reduction group ( p group by 0.5% ( p by ( p Non-inferiority demonstrated for HbA demonstrated for Non-inferiority No significant difference in healthcare utilisation in healthcare No significant difference groups between (including hospital stays) in changes diabetes No significant difference treatment (QoL and satisfaction data to be published separately.) Patients with initial HbA patient reduction weight in body No significant difference in the intervention group less depression Significantly (SMBG) after 6 months changes in not making behavioural In the SMBG group, to HbA response (–1.0 of SMBG tests 24.8 number Average predicted a delay in response a delay predicted Significantly greater HbA greater Significantly Longer diabetes duration and higher baseline HbA • Results • • • • Conclusion to maintain HbA SMBG per week • • • • • • • Results no instructions on how : no instructions on how : did not report training did not report : 113): patients requested to measure to measure patients requested 113): = , weight, FPG weight, , , adherence, change in diabetes adherence, , BMI QoL, , 102): SMBG with four measurements measurements SMBG with four 102): 1c 1c 1c 100): SMBG with one measurement SMBG with one measurement 100): = = 110): non-standardised counselling with focus counselling with focus non-standardised 110): : case-management approach, all patients case-management approach, : = Intervention Low SMBG ( n Low per week and additional measurement in the event of in the event measurement and additional per week hyperglycaemia or severe suspected hypoglycaemia High SMBG ( n per week on Tuesdays, Thursdays and one day of the and one day Thursdays Tuesdays, on per week measurement dinner and one additional before weekend in the event measurement lunch – also additional before hyperglycaemia or severe of suspected hypoglycaemia Both groups of back to their doctor in the event to report asked based on the targets set diabetes control, inappropriate the patient and their doctor between : no fixed regimen; patients were told to were patients regimen; no fixed : SMBG regimen had or if they well did not feel monitor BG when they activity partstrenuous in unusually taken patients accepting opportunity of SMBG SMBG other : patients contacted practice instructions; given were patients under of FBG; to state level monthly nurse (not practising SMBG) consulted their GP care during which patients doctors at least 4 times per year, all patients in for BG level; of current was informed scheme was used a therapeutic experimental group regulation and with weight and for targets with fixed emphasis on loss of body weight 20–800 strips Haemo-Glukotest SMBG method : yes decision scheme : Use of therapy (2–5 sessions) yes SMBG instruction : yes SMBG accuracy checks: 2–3 training visits Education : no Assessment of monitoring frequency : no Feedback on SMBG : adjustment/advice SMBG treatment (all changes to SMBG readings according to alter therapy with GP when made appointment physician); made by BG high no instruction in SMBG appointments; no fixed : Control noting low by inferred adherence assessment : Adherence of trial dropouts number HbA Outcomes : on diet and lifestyle 87% after 6 months’ intervention, assessment : Adherence their BG of patients still monitored HbA Outcomes : treatment, hypoglycaemia, QoL, satisfaction, adverse adverse satisfaction, QoL, hypoglycaemia, treatment, events : HbA Outcomes : Intervention ( n SMBG regimen BG 6 times on 2 days per week (before and 1 hour after (before per week BG 6 times on 2 days and Sunday) weekday 3 meals; given SMBG were patients undergoing SMBG other : to patients requested instructions in use of BG device; values obtained in a diary documentation where record was also recorded; of eating and state well-being related counselling designed to discuss problems/issues to SMBG SMBG counselling yes, decision scheme : Use of therapy nurse used by algorithm yes SMBG instruction : use of the assessed correct nurses SMBG accuracy checks: in the intervention group monitoring device counselling SMBG instruction and standardised Education : counselling vs non standardised at nurses checks by Assessment of monitoring frequency : visits regular not applicable Feedback on SMBG : adjustment/advice SMBG treatment to readings to respond on how ( n Control

1c 6 2 2 , 21% 27– , 2 kg/m 30 ; with HbA ; kg/m 2 : 149 (66/83) : : 202 : 25) kg/m : 223 : 27 kg/m , 27% > , 2 25 : 7.2% : : I: 9.7 (SD 2.1), C: 8.9 (SD C: 9.7 (SD 2.1), I: : : I: 8.5 (SD 0.9), C: 8.4 (SD C: 8.5 (SD 0.9), I: : 1c 1c 1c kg/m Total number Total T2DM > Inclusion criteria : no age 40–75 years, months, internist by no treatment insulin, diseases other than diabetes, for obesity or hypertension 63 (40–75) years : Age 51% < BMI : Participants : 7.8–8.2 years : Diabetes duration ~50% 71–75% MET, : Treatment and various others SUs, 1.9) 8.8 years : Diabetes duration oral diet, : Treatment agents (not details hypoglycaemic given) HbA 30 Total number Total patients with Inclusion criteria: not insulin-treated T2DM; men and 61–62 years, : Age women not reported BMI : HbA values between 7.5% and 10%; 7.5% and 10%; values between either with diet alone or treated diet in combination with SUs or at least 3 diabetes known MET; participants in a diabetes months; within educational programme 2 years the previous 60 (45–70) years : Age 31.4 (> BMI : Participants number Total age 45–70 years, Inclusion criteria: BMI > 0.8) 5.3 years : Diabetes duration with or diet alone, : Treatment without SU or MET (no details given) HbA : : : : : : unclear : yes : : unclear : 59,60 / 61 21 58 (8.9% vs 9.7%) 1c : unclear : : non-industry, meters non-industry, : : industry : : 12 months : 12 months : : 12 months : funding unclear unclear : adequate power to FU described : withdrawals/losses (13%) yes no ITT analysis : yes statistical analysis appropriate : baseline characteristics similar : shorter duration group control and of diabetes (6.6 vs 10 years) HbA lower unclear trial design and participants yes described : no describedrandomisation : allocation concealment outcome assessment blinded trial design and participants yes described : yes describedrandomisation : allocation concealment outcome assessment blinded provided by Roche Diagnostics by provided : yes : adequate power to FU described : withdrawals/losses (17%) yes yes ITT analysis : yes statistical analysis appropriate : yes baseline characteristics similar : funding trial design and participants yes described : no describedrandomisation : allocation concealment outcome assessment blinded unclear yes : adequate power to FU described : withdrawals/losses (11%) yes no ITT analysis : yes statistical analysis appropriate : yes baseline characteristics similar : funding • OVERALL QUALITY: poor; poor; QUALITY: OVERALL with furtherSMBG confounded interventions Rutten (1990) • • • • • Trial – design Trial Netherlands Follow-up • • • Germany Follow-up • • • Quality : • Quality : • Scherbaum (2008) Schwedes (2002) Schwedes Siebolds (2006) OVERALL QUALITY: high QUALITY: OVERALL • • • • • • Trial – design Trial Germany Follow-up • • • Quality : • 82 • • • • • • poor QUALITY: OVERALL 83

© 2010 Queen’s Printer and Controller of HMSO. All rights reserved. Appendix 3 DOI: 10.3310/hta14120 Health Technology Assessment 2010; Vol. 14: No. 12 of 0.8% in the SMBG 1c group, no change in the control group; not reported if not reported group; no change in the control group, groups between significant difference Significant reduction in HbA Significant No significant difference in GHb, FPG or body weight FPG or body in GHb, No significant difference • Results • : participants required participants required : 1c Intervention : NR : SMBG regimen NR SMBG other : no details reported SMBG method : standardised yes, decision scheme : Use of therapy algorithm treatment no SMBG : Control NR assessment : Adherence HbA Outcomes : and 2 per week fasting BG on 5 days : SMBG regimen after 12 per week; postprandial glucose measurements per week FBG on 5 days only weeks treatment control weight behavioural SMBG other : on weight–BG SMBG and focusing programme, relationship diary Chemstrips bG, SMBG method : yes decision scheme : Use of therapy yes SMBG instruction : yes SMBG accuracy checks: (both); programme control weight behavioural Education : per year FU sessions over 3 months, yes Assessment of monitoring frequency : yes Feedback on SMBG : adjustment/advice SMBG treatment to SMBG habits according to modify diet and exercise to change therapy patients not allowed results; programme treatment control weight behavioural : Control patient data sheets or memory assessment : Adherence of tests number of meters consulted to compare item marked of tests requested; conducted with number technique lifestyle fasting glucose, weight, GHb, Outcomes : serum lipids medication changes, adherence, kg : 50 (25/25) : : 10 : : NR : 10.86 C: 10.19 (SD 2.51), I: : 1c 1c 20% above ideal weight for for ideal weight 20% above Participants number Total age 35–65 years; Inclusion criteria: > use of oral hypoglycaemic height; BG medication or insulin for of diabetes development control; after the age of 30 (35–65) 54 years : Age 98 weight BMI : HbA : NR : Diabetes duration NR : Treatment (SD 2.00) NR : Diabetes duration oral diet, : Treatment about half agents; hypoglycaemic of the patients used insulin Total number Total T2DM on oral Inclusion criteria : medication NR : Age NR BMI : HbA 62 63 : NR : 62 weeks : unclear (not available for for unclear (not available investigation) trial design and participants yes described : no randomisation described: unclear allocation concealment: outcome assessment blinded: unclear (probably) unclear adequate power: not) (probably to FU withdrawals/losses no (10%) described: unclear ITT analysis: yes appropriate: statistical analysis baseline characteristics similar: unclear non-industry funding: Seaton (1996) Trial – design Trial USA (abstract) Follow-up USA Follow-up • • • • • • • • • poor QUALITY: OVERALL Quality : • Quality : • Wing (1986) 84 fasting FBG, diabetes mellitus; DM, confidence interval; CI, control; C, body mass index; BMI, blood glucose; BG, Association; American Diabetes ADA, treatment health- HRQol, enzyme; angiotensin converting TAU, reductase; 1, ACE hydroxy-methyl-glutaryl-CoA HMG-CoA, sulphonylurea(s); high-density lipoprotein; SU(s), HDL, error; standard haemoglobin; glycosylated SE, GHb, deviation; standard follow-up; FU, SD, ratio; fasting plasma glucose; odds FPG, OR, blood glucose; not reported; NR, metformin; MET, intention to treat; ITT, intervention; I, quality of life; related as usual. 85

Appendix 4 Results of RCTs (included in reviews and additional)

84 85

© 2010 Queen’s Printer and Controller of HMSO. All rights reserved. Appendix 4 DOI: 10.3310/hta14120 Health Technology Assessment 2010; Vol. 14: No. 12 0.029 0.016 = = p -value NS NS NS 0.012 NS Difference between between Difference not reported groups p p NS 0.007 in 1c FB: –0.7% (SD 0.9) FB: + Difference SMBG: –2.0% (SD 3.4) SMBG: –2.0% (SD 2.4) SMUG: in HbA Significant decrease –0.8% (SD 1.6) SMBG: –0.6% (SD 2.1) C: –0.36% (SD 3.14) SMBG: –0.13% (SD 2.20) SMUG: –0.5% (SD 1.54) C: –0.88% (SD 1.54) SMBG: –0.6% (SD 1.54) C: SMBG –0.3% (SD 0.7) SMBG: twice monthly no SMBG monitoring group, in once monthly decrease SMBG intensive: –0.17% (SD 0.73) SMBG intensive: –0.14% (SD 0.82) SMBG simple: –0% (SD 1.02) C: µmol/l FB: 5.6% (SD 0.7) FB: 322 µmol/l

+ End of study SMBG: 10.4% (SD 2.9) SMBG: 9.7% (SD 2.6) SMUG: 6.95% (SD 0.97) SMBG: 7.2% (SD 1.22) C: 7.6% (SD SMBG: frequent More 0.73) 7.78% (SD SMBG: Less frequent 1.05) 6.7% (SD 0.9) SMBG internet: 7.4% (SD 1.3) SMBG: 10.89% (SD 2.56) SMBG: 11.64% (SD 2.85) C: 7.53% (SE 0.236) SMBG: 7.88% (SE 0.221) C: 7.84% SMBG: 8.47% SMUG: 7.7% C: 8.1% (SD 1.6) SMBG: 8.4% (SD 1.4) C: SMBG SMBG: 5.8% (SD 1.5) SMBG: SMBG: 333 SMBG: SMUG: SMBG: 57.1% SMBG: 46.8% C: µmol/l µmol/l FB: 6.3% (SD 1.1) FB: + Baseline SMBG: 12.4% (SD 3.3) SMBG: 11.7% (SD 3.0) SMUG: 8.12% (SD 0.89) SMBG: 8.12% (SD 0.84) C: 8.08% (SD SMBG: frequent More 0.84) 7.97% (SD SMBG: Less frequent 0.72) 7.7% (SD 1.5) SMBG internet: 7.5% (SD 1.3) SMBG: 11.8% (SD 3.0) SMBG: 11.8% (SD 3.0) C: 8.4% (SD 2.1) SMBG: 8.5% (SD 2.2) C: SMBG 7.53% (SD 1.12) SMBG intensive: 7.41% (SD 1.02) SMBG simple: 7.49% (SD 1.09) C: 8.2% (SD 2.5) SMBG: 8.6% (SD 2.5) SMUG: 8.2% (SD 2.5) C: 9.0% (SD 1.3) SMBG: 9.0% (SD 1.3) C: SMBG: 6.1% (SD 1.4) SMBG: SMUG: 343 SMUG: SMBG: 324 SMBG: improvement 1c 1c 1c 1c 1c 1c 1c 1c 1c 1c 1c HbA Outcome HbA HbA HbA HbA HbA HbA HbA HbA HbA Fructosamine HbA 47 45 48 42 41 10 49 43 46 40 44 /glucose control 1c HbA Bonomo (2006) Barnett (2008) (1990) Estey Gallichan (1994) Farmer (2007) Study Allen (1990) Cho (2006) Brown (2002) Brown (2005) Davidson (1989) Fontbonne 86 (2003) Guerci 87

© 2010 Queen’s Printer and Controller of HMSO. All rights reserved. Appendix 4 DOI: 10.3310/hta14120 Health Technology Assessment 2010; Vol. 14: No. 12 0.001 0.05 0.001 < p -value NS NS no significant NS; between difference T2DM T1DM and NS < p NS NS NS 0.046 < FB: –0.54% FB: + SC: +0.04% (SD 1.1) SC: MT: –0.04% (SD 1.31) MT: Difference SMBG: –1.62% (SD 1.83) SMBG: –0.07% (SD 2.12) C: –0.99% SMBG: –0.38% C: –1.5% (SD 2.1) SMBG: –1.6% (SD 1.9) SMUG: –0.13% (SD 1.28) BGM+: –1.54% (SD 1.46) SMBG: –0.85% (SD 1.87 C: –0.4%) SMBG: +0.5% C: SMBG +0.33% SMBG: Preprandial SMBG: –0.8% SMBG: Preprandial –0.9% SMBG: Postprandial FB: 6.94% (SD 0.92) FB: FB: 6.38% (SE 0.22) FB: 7.38% (SE 0.16) FB: + + + SC: 9.0% (SD 1.5) SC: MT: 9.1% (SD 1.3) MT: End of study SMBG: 7.6% (SD 1.48) SMBG: 9.65% (SD 2.61) C: 7.3% (SD 1.5) strips: Free 7.3% (SD 1.2) strips: No free 7.11% (SD 1.0.8) SMBG: 7.12% (SD 1.85) C: 8.8% (SD 1.9) SMBG: 8.7% (SD 1.7) SMUG: 9.3% (SD 1.7) BGM+: 8.75% (SD 1.66) SMBG: 9.6% (SD 2.1) C: 6.9% (SD 0.8) SMBG: 6.9% (SD 1.2) C: 9.2% (SD 1.49) SMBG: 9.4% (SD 1.14) C: SMBG SMBG: 7.62% (SD 0.93) SMBG: SMBG SMBG SMBG: 6.99% (SE 0.18) SMBG: 8.12% (SE 0.19) SMBG: FB: 7.59% (SD 1.42) FB: + SC: 8.9% (SD 0.9) SC: MT: 9.1% (SD 1.2) MT: Baseline SMBG: 9.2% (SD 2.0) SMBG: 9.7% (SD 2.5) C: 7.5% (SD 1.6) strips: Free 7.3% (SD 1.2) strips: No free 8.3% SMBG: Preprandial 8.4% SMBG: Postprandial 8.19% (SD 1.37) SMBG: 7.55% (SD 1.62) C: SMBG 10.3% (SD 2.6) SMBG: 10.3% (SD 2.3 SMUG: 9.3% (SD 1.2) BGM+: 10.29% (SD 1.1) SMBG: 10.45% (SD 1.5 C: 8.8% (SD 2.1) SMBG: 8.6% (SD 2.3) C: 9.7% (SD 2.1) SMBG: 8.9% (SD 1.9) C: SMBG: 7.19% (SD 1.17) SMBG: 7% at 7% at < ≥ 1c 1c 1c 1c 1c 1c 1c 1c 1c 1c 1c 1c HbA Outcome HbA HbA HbA HbA HbA HbA HbA HbA HbA HbA baseline baseline HbA 57 20 51 13 54 58 55 56 50 53 Muchmore (1994) Muchmore Jaber (1996) Johnson (2006) Johnson Kwon (2004) Kwon (2006) Moreland O’Kane (2008) Study Joy (2003) Joy Rutten (1990) Kibriya (1999) 86 Miles (1997) 87

© 2010 Queen’s Printer and Controller of HMSO. All rights reserved. Appendix 4 DOI: 10.3310/hta14120 Health Technology Assessment 2010; Vol. 14: No. 12 p -value 0.009 NS 0.03 0.003 p -value not reported Difference SMBG: –1.0% (SD 1.08) SMBG: –0.54% (SD 1.41) C: 0.0% (SD 2.16) SMBG: –0.24% (SD 1.87) C: SMBG: 5 patients with 7 episodes; 5 patients with 7 episodes; SMBG: 0.172/patient-year 10 patients with 17 episodes; C: 0.354/patient-year Significant difference in Significant difference asymptomatic hypoglycaemia (10.4% of patients in SMBG and group), 5.2% of patients in control but based on capillary blood, which could not be determined – probably group control by no serious comparison; invalid hypoglycaemia 27 (8.7%) with 51 3 patients = = 21 (7%) with 66 7 patients = = End of study Low SMBG: 6.9% (SD 1.0) SMBG: Low 7.1% (SD 1.0) High SMBG: 7.47% (SD 1.27) SMBG: 7.81% (SD 1.52) C: 10.2% (SD 2.29) SMBG: 10.4% (SD 2.16) C: SMBG: n SMBG: (27, events hypoglycaemic 11 asymptomatic, symptomatic, 2 non- 11 SMBG confirmed, graded) n C: 43 intensive: SMBG more 33 SMBG less intensive: 14 C: hypoglycaemic events (64, (64, events hypoglycaemic 2 non-graded) symptomatic, n SMBG: n C: Baseline Low SMBG: 7.2% (SD 1.4) SMBG: Low 7.2% (SD 1.0) High SMBG: 8.5% (SD 0.9) SMBG: 8.4% (SD 0.8) C: 10.2% (SD 2.5) SMBG: 10.7% (SD 2.0) C: 1c 1c 1c mmol/l) 3 Outcome HbA HbA HbA events Hypoglycaemic Hypoglycaemic episodes Hypoglycaemic episodes (capillary BG < Hypoglycaemic episodes Nocturnal hypoglycaemia 60 61 41 10 54 49 63 Scherbaum (2008) Schwedes (2002) Schwedes Wing (1986) Hypoglycaemia Barnett (2008) Guerci (2003) Guerci Kibriya (1999) Study 88 Farmer (2007) 89

2 kg/m kg kg/m kg (SD (SD 2.3) 2 kg (SD 5.70) (SD 1.6) (SD 1.0) 2 2 kg (SD 6.3) kg/m kg kg kg (SD 4.01) kg (SD 2.9) kg/m kg/m kg (SD 2.7) kg (95% CI –2.95 to 0.75) Difference Significantly more with 1 event in event with 1 more Significantly group than low high group –2 SMBG: +0 SMUG: –0.68 SMBG: –0.50 C: SMBG vs control Difference –1.10 –0.7 SMBG: –0.1 C: –0.3 SMBG: C: –0.1 C: (SD 0.9) –0.1 C: (SD 1.2) –0.2 SMBG less intensive: SMBG more intensive: –0.3 intensive: SMBG more SMBG more intensive: –0.8 intensive: SMBG more (SD 3.3) –0.5 SMBG less intensive: 2.6) –0.3 C:

2 kg/m kg (SD kg/m kg (SD (SD 6.45) 2 kg (SD 22.2) (SD 6.52) 2 kg/m (SD 6.3) 2 kg (SD 17.3) kg/m FB: 82.4 FB: kg/m kg (SD 19.4) + End of study C: 32.28 C: SMBG: 31 episodes SMBG: 36 episodes C: 5 patients (1 with 1 SMBG: Low events) 4 with several event, 18 patients (9 with 1 High SMBG: 9 with several) event, SMBG SMBG: 86.1 SMBG: (SD 6.3) 30.8 C: (SD 5.0) 31.8 SMBG less intensive: SMBG: 32.17 SMBG: 30.7 intensive: SMBG more SMBG more intensive: 86.1 intensive: SMBG more 15.7) 89.9 SMBG less intensive: 19.0) 86.4 C:

2 kg kg/m kg kg/m (SD 5.97) 2 kg (SD 15.8) (SD 6.35) 2 kg/m (SD 6.1) 2 kg (SD 17.3) kg/m FB: 84.2 FB: kg/m kg (SD 18.9) + Baseline C: 32.12 C: (SD 6.2) 30.9 C: (SD 18.9) 86.7 C: SMBG: 32.33 SMBG: SMBG 86.9 intensive: SMBG more (SD 16.4) 90.4 SMBG less intensive: SMBG: 86.1 SMBG: (SD 5.3) 31.9 SMBG less intensive: SMBG more intensive: 31.0 intensive: SMBG more Outcome Hypoglycaemic Hypoglycaemic episodes Relevant hypoglycaemia Weight Weight BMI Weight Weight Weight BMI BMI 60 45 13 41 10 43 46 40 O’Kane (2008) Weight Allen (1990) Barnett (2008) Study Estey (1990) Estey Scherbaum (2008) (2002) Brown (2005) Davidson 88 Farmer (2007) 89

© 2010 Queen’s Printer and Controller of HMSO. All rights reserved. Appendix 4 DOI: 10.3310/hta14120 Health Technology Assessment 2010; Vol. 14: No. 12 0.013 p -value NS 0.01 NS NS NS p -value not reported NS NS kg kg kg kg 4.35 2.99 kg (95% CI –1.36 ± ± kg 4.87 3.54 ± ± kg kg (95% CI –12.28 to 12.08) kg (95% CI –1.07 to 9.27) Significantly more reduction in more Significantly vs control intensive more Difference Difference SMBG/SMUG vs Difference –0.22 control to 0.93) –0.93 SMBG: –0.83 C: SMBG vs control Difference –0.10 –0.4 SMBG: +0.1 C: –1.96 SMBG: –1.62 C: No significant difference No significant difference in the lower Significantly intervention group No significant difference No significant difference reduction in more Significantly vs control intensive more Difference SMBG vs control SMBG vs control Difference 4.10 (SD 6.4) 2 kg (SD 16.50) (SD 6.0) 2 kg/m kg (SD 17.79) kg/m End of study C: 31.8 C: SMBG: 33.1 SMBG: SMBG: 94.92 SMBG: 88.11 C: 0.04) = (SD 7.0) 2 kg (SD 16.13) (SD 6.2; p (SD 6.2; 2 kg/m kg (SD 23.57) kg/m Baseline C: 32.0 C: SMBG: 34.0 SMBG: 99.02 SMBG: 96.35 C: Total–HDL Total–HDL ratio cholesterol Outcome Triglycerides HDL cholesterol Triglycerides Weight Weight Weight BMI Weight Weight Weight Cholesterol cholesterol Total cholesterol Total 57 47 61 13 10 58 49 43 63 44 Fontbonne (1989) Fontbonne Cho (2006) Farmer (2007) Guerci (2003) Guerci Study Rutten (1990) Muchmore (1994) Muchmore (2002) Schwedes Wing (1986) O’Kane (2008) 90 Lipid parameters (2002) Brown 91

© 2010 Queen’s Printer and Controller of HMSO. All rights reserved. Appendix 4 DOI: 10.3310/hta14120 Health Technology Assessment 2010; Vol. 14: No. 12 0.0001 p -value < 0.022 0.024 0.012 FB group (no data FB group + Difference No significant differences No significant differences reported baseline from Significant increase but not group, in control between significant differences reported groups No significant differences reported No significant differences reported No significant difference No significant difference No significant difference in greater SMBG adherence SMGB shown) in the more more Significantly group intensive 28 times ± 19 times per month ± internet: 34 internet: + End of study SMBG 52.3% intensive: SMBG more to use meter at least continued 12 months for twice weekly 66% SMBG less intensive: to use meter at least continued 12 months for twice weekly per month 22 SMBG: Baseline Outcome Total cholesterol Total cholesterol Total Lipid parameters (cholesterol, triglycerides) SMBG frequency SMBG adherence SMBG adherence HDL cholesterol LDL cholesterol Triglycerides Triglycerides Number of readings Number of readings in meter users 61 10 55 63 46 44 Kwon (2004) Kwon Schwedes (2002) Schwedes Wing (1986) Adherence Cho (2006) Farmer (2007) Study 90 (1990) Estey 91

© 2010 Queen’s Printer and Controller of HMSO. All rights reserved. Appendix 4 DOI: 10.3310/hta14120 Health Technology Assessment 2010; Vol. 14: No. 12 0.05 BGM+ vs the p -value 0.007 < groups other two NS NS p -value not reported NS Difference Patients receiving free strips free Patients receiving of 0.64 days tested and average often than more per week strips free patients not receiving No significant difference SU, SU, + SU, SU, + 36.2 ± 24.8 ± oral, 2% insulin alone oral, oral, 0 insulin alone oral, + + End of study (at 6 months) 85–88% SMBG: Low 84–88% High SMBG: SMBG internet: 71.5 SMBG internet: 2.8 (SD 1.5) BGM+: 2.0 (SD 1.3) MT: 2.1 (SD 1.7) SC: (at 6 months) 73% SMBG: Low 83% High SMBG: 89.1% of strips used SMBG: 70.2% during initial treatment, 83% of patients during FU; within 20% of results interpreted actual level 35% MET 19% MET, SMBG: 7% 37% triple oral therapy, insulin increased intensive: SMBG more in 31.8% of patients in increased SMBG less intensive: 28.7% of patients in 29.6% of patients increased C: SMBG: 38.1 SMBG: 38% MET 22% MET, C: 27% triple oral therapy, 13% 27% triple oral therapy, insulin Baseline Outcome Adherence assessed Adherence patient by Days of testing Days of SMBG Frequency during study (3 months) of SMBG Frequency assessed Adherence investigator by with self- Adherence monitoring Medication at end of study Medication increase Medication change 60 20 45 51 10 49 55 63 Johnson (2006) Johnson Wing (1986) Changes in treatment (2005) Davidson Kwon (2004) Kwon Study Scherbaum (2008) (2003) Guerci Moreland (2006) Moreland 92 Farmer (2007) 93

© 2010 Queen’s Printer and Controller of HMSO. All rights reserved. Appendix 4 DOI: 10.3310/hta14120 Health Technology Assessment 2010; Vol. 14: No. 12 p -value NS NS 0.03 NS Difference No significant difference 40, 2 40, = n 34, 1 drug 34, = 11 n = 29, 1 drug 29, n = n 6 = n 44, 2 drugs 44, = End of study SMBG: 64% unchanged SMBG: 78% unchanged C: in oral agents decrease SMBG: in insulin 83% decrease 73%, in oral agents 64%, decrease C: in insulin 64% decrease values on EQ- lower Significantly vs group intensive more 5D for due to increased mainly control, anxiety/depression urine testing to 71% preferred blood testing 15% urine testing, 70% preferred blood testing preferred No significant difference 57% 65% SC: 38% MT: BGM+: No significant difference No significant difference SMBG: no drugs SMBG: n no drugs C: drugs 7, 2 7, = n 86, 1 drug 86, = 0 n 78, 1 drug 78, = = n n 2 = n 8, 2 drugs 8, = Baseline SMBG: no drugs SMBG: n no drugs C: drugs Outcome Medication use Medication change oral Change from agents to insulin Change in medication QoL (EQ-5D) Preference Preference with affect Negative to SMBG respect Quality-of-life (satisfaction, inventory worry – impact, social/vocational, worry –diabetes related) Well-being Well-being questionnaire Satisfaction 60 57 20 48 13 10 58 63 56 O’Kane (2008) Wing (1986) Gallichan (1994) Miles (1997) (2006) Moreland Muchmore (1994) Muchmore Study Scherbaum (2008) QoL/preference Farmer (2007) 92 Rutten (1990) 93

© 2010 Queen’s Printer and Controller of HMSO. All rights reserved. Appendix 4 DOI: 10.3310/hta14120 Health Technology Assessment 2010; Vol. 14: No. 12 0.07 NS NS p -value 0.011 0.032 Marginally worse in the SMBG worse Marginally group Difference Significantly worse in the SMBG Significantly group in both Similar improvement groups less in the SMBG Significantly group in both improved Significantly no significant difference groups, patients in the more Significantly following continued SMBG group dietary instructions than in the no significant group; control behaviour in exercise difference No significant difference End of study SMBG 12 times more in first year, year, in first SMBG 12 times more in later years 8 times more Baseline Positive well-being Positive Energy Anxiety Outcome Depression treatment Well-being, satisfaction Mood Diet and exercise behaviour Diet and exercise habits Cost Depression 61 13 49 63 63 40 Schwedes (2002) Schwedes O’Kane (2008) Changes in behaviour (2003) Guerci Wing (1986) Cost Allen (1990) Wing (1986) 94 Study 95

© 2010 Queen’s Printer and Controller of HMSO. All rights reserved. Appendix 4 DOI: 10.3310/hta14120 Health Technology Assessment 2010; Vol. 14: No. 12 p -value Difference No significant difference No significant difference No significant difference No significant difference No significant difference No significant difference No significant difference No significant difference No significant difference End of study SMBG: 13.2% SMBG: 15.1% C: Baseline Outcome Systolic blood pressure Systolic blood pressure visits Physician Blood pressure All-cause adverse events (with events Adverse details) Diastolic blood pressure Diastolic blood pressure Inpatient stay to work Incapacity 60 60 41 10 49 63 Other Farmer (2007) Scherbaum (2008) Guerci (2003) Guerci Scherbaum (2008) Wing (1986) Adverse events Barnett (2008) SC, not significant; NS, treatment; mixed MT, lipoprotein; low-density LDL, intervention; I, high-density lipoprotein; HDL, feedback; FB, control; C, blood glucose monitoring; BGM, error. standard SE, deviation; standard SD, care; standard 94 Study 95

DOI: 10.3310/hta14120 Health Technology Assessment 2010; Vol. 14: No. 12

Appendix 5 Observational and non-randomised studies (included in reviews and new)

© 2010 Queen’s Printer and Controller of HMSO. All rights reserved. Appendix 5 DOI: 10.3310/hta14120 Health Technology Assessment 2010; Vol. 14: No. 12 1c 0.001 < and SMBG 1c 1.08% ± 7.45 1c 8%: 70% regular users, 18% irregular users, users, 18% irregular users, 70% regular 8%: irrespective of diabetes treatment irrespective p to 8.2%); –1.5% (9.7% reduced ≤ 1c 1c 1c frequency 22% non-SMBG users Frequency of SMBG: 44.3% monitored 1–2 per 44.3% monitored of SMBG: Frequency 31.8% 1–2 per week day, Mean HbA in HbA each point reduction Cost US$185 for No association between SMBG frequency and SMBG frequency No association between HbA SMBG users irregular 21%; Regular SMBG users: non-SMBG users 37% 42%; HbA HbA HbA No association between • • • Results • • • • • 4 : did not : , frequency of SMBG frequency , of SMBG frequency , 1c 1c 1c 1c 1c 1c 1c Interventions report on how to respond to readings to respond report on how HbA Outcomes : : association between SMBG use association between Comparison : and HbA SMBG once per day : SMBG regimen glucometer SMBG method : diabetes self-management Education : training programme adjustment/advice SMBG treatment SMBG use association between Comparison : and HbA SMBG use association between Comparison : and HbA : maximum and minimum and minimum maximum : SMBG regimen plus 8-point during last week glucose levels selected day on freely profile glucometer SMBG method : diabetes education standard Education : HbA Outcomes : no details of SMBG use/ : SMBG regimen protocols HbA Outcomes : (1) no divided into groups: : SMBG regimen (3) (2) SMBG 1–2 times per day; SMBG; (4) SMBG > SMBG 3–4 times per day; times per day HbA Outcomes : 75 years, 75 years, 14.9 years ± 25) T2DM

(90% > 2 : 600 : 70 : 228 : 808 : 4.5 years ± : most Hispanic or African-American most Hispanic or : kg/m : diabetes clinic, Lódź diabetes clinic, : clinic community : chart review USA health clinics, : Clinic 2001–2005 Joslin chart review : : 7.45% : 9.7% (range 5.2–16.2%) : NR : 7.5–7.7% : 1c 1c 1c 1c : NR BMI : HbA insulin use 80.4 : Age Participants number Total Setting insulin and/or oral treatment T2DM, Inclusion criteria : 63.4 years : Age NR BMI : HbA number Total Setting Inclusion criteria: 49 years : Age Ethnicity 34 BMI : number Total Setting no medication limits T2DM, Inclusion criteria : range 35–65 years : Age NR BMI : HbA number Total Setting > diabetes (type not specified), Inclusion criteria : : 11.4 years : Diabetes duration medication oral glucose-lowering insulin, : Treatment NR : Diabetes duration NR : Diabetes duration no details : Treatment 21.3 : Diabetes duration insulin : Treatment HbA 67 65 66 : NA : 2–12 months : NA : NA : 64 Banister (2004) Capelson (2006) Capelson Study Poland cross-sectional Design : Follow-up USA before cohort, Design : and after Follow-up Blonde (2002) USA cross-sectional Design : Follow-up USA cross-sectional Design : Follow-up 98 Bajkowska- Fiedziukiewicz (2008) 99

© 2010 Queen’s Printer and Controller of HMSO. All rights reserved. Appendix 5 DOI: 10.3310/hta14120 Health Technology Assessment 2010; Vol. 14: No. 12 than no 1c 1c SMBG (7.9% vs 8.6%; p -value not reported) SMBG (7.9% vs 8.6%; No association between SMBG frequency and SMBG frequency No association between HbA SMBG associated with lower HbA SMBG associated with lower by age was influenced Reagent strip uptake was a direct There deprivation category. and by control and glycaemic uptake between correlation for but no such relation T1DM, patients with for T2DM who used insulin. patients with 162 (21%) obtained no strips; T2DM, In those with 50 and 10,100 628 participants obtained between with 0.05 and 9.2 strips per day between i.e. strips, than 1095 131 participants (17%) obtaining more strips age with increasing uptake A pattern of decreasing of a trend T2DM; among patients with was evident deprivation was with increasing uptake increasing T2DM particularly among patients with evident, strips reagent for The 6381 prescriptions T2DM who used insulin dispensed to patients with cost £134,907 (£56.92 per patient year). strip association between was a direct There 6 months and glycaemic in the previous uptake but not in those T1DM, in patients with control T2DM with Results • • • • • • • , frequency of SMBG (no. of SMBG (no. frequency , 1c 1c 1c 1c Interventions : association between SMBG use association between Comparison : and HbA SMBG use association between Comparison : and HbA of strips dispensed) : no details of SMBG use/ : SMBG regimen protocols HbA Outcomes : no details of SMBG use/ : SMBG regimen protocols HbA Outcomes : : 562 : T1DM 807 with T2DM; 790 with : : teaching hospital : UK diabetes database : : 8.4% (SD 2.3%) : NR : 1c 1c Participants T2DM Inclusion criteria: 53 years : Age mean 2.4 BMI : HbA insulin treated diabetes mellitus, Inclusion criteria : unclear : Age NR BMI : HbA Total number Total Setting number Total Setting : 5 (SD 6) years : Diabetes duration no rest 9% insulin, 21% diet alone, 63% OHA, : Treatment treatment mean NR : Diabetes duration some with OHAs in addition all on insulin, : Treatment 69 68 : NA : NA : Evans (1999) Study China cross-sectional Design : Follow-up UK cross-sectional Design : Follow-up 98 Chan (2000) 99

© 2010 Queen’s Printer and Controller of HMSO. All rights reserved. Appendix 5 DOI: 10.3310/hta14120 Health Technology Assessment 2010; Vol. 14: No. 12 65 years, 65 years, during 3-year FU; increasing increasing FU; during 3-year over time only present in present time only over 1c once per day significantly significantly once per day 1c 1c , were more often treated with often treated more were , higher in those testing more often higher in those testing more 2 1c 1c kg/m 25 only in patients who could adjust insulin; no in patients who could adjust insulin; only 1c a combination of SUs and MET, had a higher a combination of SUs and MET, episodes and were of hypoglycaemic frequency in the charge of a diabetes clinic frequently more SMBG monitoring no association between Overall, and HbA frequency SMBG frequency was associated with a slight SMBG frequency in HbA decrease relationship in non-insulin-treated patients in non-insulin-treated relationship > SMBG frequency and worries of distress, to higher levels related symptoms among non-insulin-treated depressive patients psychological with poorer The correlation of to the feeling could be related well-being unsatisfactory caused by results powerlessness not able to improve that patients are female, Higher use of SMBG associated with: use of insulin symptoms, hypoglycaemic > use of SMBG associated with: Lower GP by treated educated, less well but not those who changed their treatment, in those who just changed SMBG monitoring frequency no family SMBG: performing for likelihood Lowest highest likelihood support and on diet alone; support family of SMBG, SMBG: of performing a diabetologist (rather than GP), by followed BMI < Overall, HbA Overall, Frequency of SMBG: 10.3% at least once per day, 10.3% at least once per day, of SMBG: Frequency 59.2% less than 30.5% at least once per week, once per week/never were Patients practising SMBG regularly of school had higher levels younger, significantly higher longer diabetes duration, education, of HbA levels SMBG frequency In 40% of patients who increased changes this was associated with major treatment in HbA – decrease Higher frequency of SMBG associated with lower of SMBG associated with lower Higher frequency HbA • • • • • • Results • • • • • , frequency of SMBG, QoL of SMBG, frequency , 1c 1c 1c 1c Interventions : association between SMBG use association between Comparison : and HbA : no details of SMBG use/ : SMBG regimen protocols HbA Outcomes : no details of SMBG use/ : SMBG regimen protocols SMBG other : 99% of glucometer used by SMBG method : patients using SMBG at least once per day; 95.8% of patients using SMBG at least by 20.8% of the rest by once per week; HbA Outcomes : : association between SMBG use association between Comparison : and HbA once once per week), 7.2% (testing ≥ once per week), MET (35.3–55.4%) + 1.7% : 2855 : T2DM 1896 people with : ± : Italian diabetes clinics and GP practices : outpatient diabetes clinics : : ~7.3 : 7.0% (testing < : 1c 1c Participants number Total Setting T2DM Inclusion criteria : 63 years : Age NR BMI : HbA number Total Setting no users and non-users of SMBG; T2DM, Inclusion criteria : insulin use 62.4 years : Age 28 females males 27, BMI : HbA per week), 7.3% (testing ≥ once per day) per week), 9.1 years : Diabetes duration MET SUs (23.6–27.9%), (14.4–28.7%), diet only : Treatment SU (6.6–9.3%), : NR : Diabetes duration insulin agents, oral antihyperglycaemic diet only, : Treatment

70,142 71 : 3 years : 3 years : Franciosi (2005) Franciosi Study Part of QuED Study Italy cross-sectional Design : Follow-up Part of QuED Study Italy longitudinal Design : Follow-up 100 (2001) Franciosi 101

© 2010 Queen’s Printer and Controller of HMSO. All rights reserved. Appendix 5 DOI: 10.3310/hta14120 Health Technology Assessment 2010; Vol. 14: No. 12 3.5 ± and 1c 0.005) = SMBG frequency within treatment groups (oral or groups within treatment SMBG frequency no medications) 79% had diabetes education; Of those using SMBG, 41% had diabetes of those not using SMBG, education of FU (mean 9.8 During 12,491 patient-years T2DM 486 (38.0%) participants with years), SMBG causes; cardiac died – 196 (15.3%) from in those who died less prevalent was significantly at the still alive during FU than in those who were p 2006 (65.4 vs 73.0%; end of June and explanatory confounding After adjustment for associated SMBG was not independently variables, but was associated with a with all-cause mortality, mortality in risk of cardiovascular 79% increased with insulin patients not treated time-dependent SMBG was cohort, the 5-year For risk associated with a 48% reduced independently of retinopathy of self-care, the burden as increasing As well to diabetes SMBG contributes significantly costs health-care attributable and total direct no not monitoring: for Participant reasons no to do SMBG (45%); education on how motivation to start SMBG (31%); or to continue or mental and physical of finger pricks (9%); fear its use (5%) disability preventing less Patients with longer diabetes duration were to self-monitor likely in those self- General health status was worse not were although DQoL measures monitoring, associated with SMBG At baseline, 70.2% (898 out of 1280) patients At baseline, T2DM used SMBG with HbA No significant association between Results • • • • • • • • • • , morbidity , 1c 1c Interventions : association between SMBG use association between Comparison : and HbA : no details of SMBG use/ : SMBG regimen protocols no use of SMBG : Control HbA Outcomes : 2 kg/m : 1286 patients with T2DM at entry, 531 T2DM at entry, 1286 patients with : 5.5 ± 11 years ± : community-based : : 7.4% (6.4–8.9) : 1c : T2DM Inclusion criteria: 64 : Age 29.6 BMI : Total number Total (longitudinal cohort significantly 5 years up over followed control) better glycaemic healthier, younger, Setting Participants : NR : Diabetes duration NR : Treatment HbA ] : 5 years : 17,19 Australia cross-sectional Design : and longitudinal Follow-up Study 100 Diabetes Fremantle Study [Davis (2007) 101

© 2010 Queen’s Printer and Controller of HMSO. All rights reserved. Appendix 5 DOI: 10.3310/hta14120 Health Technology Assessment 2010; Vol. 14: No. 12 1c once 1 times (9% vs 8.5% 1c in patients who 1c once per day 39.1%; 39.1%; once per day : never or < never : 1 time per day 6.5% 1 time per day once per month 65.2%, 1–3 once per month 65.2%, 1c once per week; 10.7% of patients never 10.7% of patients never once per week; ≤ : never or < never diet only : 4.6%; once per day 21.4% of them tested their BG once per day, 8.7% of patients tested whereas once per week, without SMBG) (possibly because those with without SMBG) (possibly to do SMBG) asked were control poorer could change insulin dose based on SMBG practised SMBG SMBG and HbA No association between SMBG associated with higher HbA insulin of SMBG: Frequency 1–3 times per month 11.1%, per month 28.7%, ≥ 21.1%, 1–6 times per week or < never : agents oral 21.0%, 1–6 times per week times per month 9.2%, ≥ 1–6 1–3 times per month 4.6%, per month 79.7%, ≥ 9.2%, times per week at home 59.2% of patients tested their BG levels ≥ ≥ glucose to HbA SMBG also not related No association between SMBG monitoring No association between and HbA frequency Results • • • • • • 1c 1c 1c 1c 1c 1c Interventions SMBG use association between Comparison : and HbA : association between SMBG use association between Comparison : and HbA SMBG use association between Comparison : and HbA : no details of SMBG use/ : SMBG regimen protocols HbA Outcomes : no details of SMBG use/ : SMBG regimen protocols HbA Outcomes : no details of SMBG use/ : SMBG regimen protocols HbA Outcomes : : 260 : T2DM 1480 people with : T2DM 218 people with : : NHANES III database : outpatient : : 8.5% (SEM 0.2) : 8.04% (oral agents), 6.37% (diet only), mean 7.64%, : 1c 1c Participants number Total Setting no medication limits T2DM, Inclusion criteria: 63 years : Age 30 (SEM 0.5) BMI : HbA number Total Setting users and non-users of SMBG T2DM, Inclusion criteria : 62.5 years : Age NR BMI : HbA number Total Setting no medication limits reported T2DM, Inclusion criteria : 62 years : Age : some newly diagnosed some newly : Diabetes duration OHA or insulin : Treatment 8.29% (insulin) NR : Diabetes duration agents oral hypoglycaemic (27.2%), diet only : Treatment insulin (27.3%) (45.5%), 72 74 73 : NA : NA : NA : Harris (2001) Harris Study Finland cross-sectional Design : Follow-up USA cross-sectional Design : Follow-up (2001) Jaworska Poland cross-sectional Design : Follow-up 102 Hanninen (2001) 103

© 2010 Queen’s Printer and Controller of HMSO. All rights reserved. Appendix 5 DOI: 10.3310/hta14120 Health Technology Assessment 2010; Vol. 14: No. 12 once daily once daily in adherent in adherent ≥ 1c in adherent vs in adherent in patients 1c 1c occasionally (diet only) occasionally 7.0%): (case-mix 7.0%): 0.0001] 0.0001] ≥ 1.0 per day < < ≤ ± 1c 0.0001) < p in new users regardless of diabetes therapy of diabetes therapy users regardless in new 1c 0.0001) and in pharmacologically treated treated 0.0001) and in pharmacologically < non-adherent [8.2% (95% CI 8.2 to 8.3) vs 8.8% non-adherent p (95% CI 8.8 to 8.9); HbA lower significantly Oral agents: adjustments with a wide range of covariates used) adjustments with a wide range of covariates 13.4% (95% CI 11.3 to 15.8) No SMBG: 15.5% (95% CI 14.0 Some SMBG but < once daily: to 17.2) 18.8% (95% CI 16.9 to 20.9) SMBG: Daily performing SMBG than in those who did not performing white, to be female, patients likely Adherent healthier lifestyle higher income, better educated, in analysis) (adjusted for (hospital or ER visit) 41% non- events Adverse patients vs 36% non-insulin non- insulin adherent patients adherent ( p users ( prevalent Adherent patients (following ADA ADA patients (following Adherent monitoring were recommendations) (insulin/oral agents) or 0.9 SMBG frequency associated with of SMBG inversely Frequency HbA Insulin: significantly lower HbA lower significantly Insulin: (HbA Good control vs non-adherent [8.1% (95% CI 8.0 to 8.2) vs 8.7% vs non-adherent p (95% CI 8.7 to 8.7); of HbA levels lower Diet only: • • • • • • Results • • • • • • , frequency of SMBG frequency , of SMBG frequency , of SMBG frequency , 1c 1c 1c 1c 1c 1c Interventions : ADA recommendations ADA : SMBG regimen no use of SMBG : Control HbA Outcomes : not reported : SMBG regimen HbA Outcomes : no details of SMBG use/ : SMBG regimen protocols HbA Outcomes : : association between SMBG use association between Comparison : and HbA : association between SMBG use association between Comparison : and HbA : association between SMBG use association between Comparison : and HbA 7409 = 5867 = 10 years ≥ 1622 no medication, n 1622 no medication, >8%, initiating new therapies initiating new >8%, 1c = 9264 no medication, n 9264 no medication, : n : 19 years, pharmacy benefits, pharmacy benefits, 19 years, 2.0% (new user cohort2.0% (new higher = ± : n : 1 year 2.2% : 23,153 people with T2DM 23,153 people with : T2DM 4775 people with : users with 15347 prevalent users, 16091 new : measured during FU; on insulin, oral agents or on insulin, during FU; measured 1.5% 0.8% to 8.6 ± 1c 10 years ± ± ± : Kaiser Permanente database Kaiser Permanente : database Kaiser Permanente : database Kaiser Permanente : ) : ~8.4 : 9.9 : 6.4 : 1c 1c 1c 1c Participants > T2DM, Inclusion criteria : single HbA HbA T2DM, Inclusion criteria : or diet oral therapy insulin, T2DM, Inclusion criteria : ~60 : Age NR BMI : HbA Total number Total Setting number Total Setting number Total T2DM Setting HbA : 60 years : Age NR BMI : HbA : NR : Diabetes duration users new Treatment: diet only 60 years : Age NR BMI : HbA : 75% 0–9 years; 25% 75% 0–9 years; : Diabetes duration ≥ : Diabetes duration 74.2% not using insulin (pre-initiation) : Treatment : diet only (21%), oral hypoglycaemic agents oral hypoglycaemic (21%), diet only : Treatment insulin (24%) (55%), oral only; prevalent users prevalent oral only; oral only 75 76 14 : NA : 1 year : 3.5 years : Karter (2006) Karter (2005) Study (Kaiser Permanente) USA cross-sectional Design : Follow-up (Kaiser Permanente) USA retrospective Design : database Follow-up (Kaiser Permanente) USA longitudinal Design : Follow-up 102 Karter (2001) 103

© 2010 Queen’s Printer and Controller of HMSO. All rights reserved. Appendix 5 DOI: 10.3310/hta14120 Health Technology Assessment 2010; Vol. 14: No. 12 1c and 1c 0.92 0.001) ± < 1.04 to ± before (oral before 1c and SMBG 1c 210), decrease by by decrease 210), 0.862, p 0.862, = = 159) = 1.21%) 1.67% ( n 0.001; diet: 1.17 diet: 0.001; ± ± < 0.001 1.22%) and after strip reduction 1.22%) and after strip reduction < 8.1 ± 1c 1c 0.44; p 0.44; ± 0.44; p 0.44; 1.17 at 1 year ( n 1.17 at 1 year did not differ based on length of time did not differ 1c ± ± (oral agents: 7.83 (oral agents: agents: 7.82 agents: oral agents 1.35 Strip use reduction: to 0.67 0.61 monitored or number of strips dispensed or number monitored making insulin changes in patients reported Seven this was not associated to monitoring; response with HbA No significant differences between SMBG and between No significant differences urine monitoring HbA HbA SMBG associated with lower Chart review: No significant difference in HbA No significant difference HbA No association between compliance with SMBG ( r 0.32 Decrease predicted by entry level HbA entry by level predicted Decrease Entry HbA • • Results • • • • • • • 1c , frequency of SMBG frequency , strip use , 1c 1c 1c 1c 1c Interventions SMBG/ association between Comparison : SMUG use and HbA : association between SMBG use association between Comparison : and HbA intensified SMBG Intervention : SMBG using an electronic : SMBG regimen all meals and at bedtime BG meter before then usual monitoring 8 weeks for resumed HbA Outcomes : : reduced access to test strips reduced Intervention : HbA Outcomes : : no details of SMBG use/ : SMBG regimen protocols HbA Outcomes : HbA Outcomes : at 1 year 27.1% dropouts Quality : : 471 patients with T2DM; chart review of chart review T2DM; 471 patients with : T2DM 434 patients with : 218 : : chart review at Veterans Affairs medical centre Veterans at chart review : and after and before Affairs chart review Veterans : pharmacies community : administration veterans’ : : NR : : 7.3% (SD 1.3%) : 8.1% (SD 1.7%) : 1c 1c 1c Participants 229 number: Total Setting patients who no medication limits; T2DM, Inclusion criteria : blood or urine monitoring supplies received 97% male 62 years; : Age number Total 1467 patients Setting study no insulin T2DM, Inclusion criteria: 98% male 64 years; : Age NR BMI: HbA number Total Setting no insulin T2DM, Inclusion criteria : 64 years : Age 30.7 (SD 6) BMI : HbA number Total Setting stable T2DM, Inclusion criteria : mean 65 years : Age mean 31 (SD 5.7) BMI : HbA : 7.8 (SD 6.5) years : Diabetes duration diet and OHA only : Treatment NR : Diabetes duration 35% on OHAs as well insulin, Treatment: : NR : Diabetes duration most on agents (89%, oral antihyperglycaemic : Treatment diet (11%) SU), 80 81 79 77 : 6 months : NA : 12 months : Murata (2003) Study USA chart review Design : Follow-up Meier (2002) USA before/after Design : Follow-up Canada cross-sectional Design : Follow-up USA before/after Design : Follow-up Klein (1993) 104 Mitchell (2004) 105

© 2010 Queen’s Printer and Controller of HMSO. All rights reserved. Appendix 5 DOI: 10.3310/hta14120 Health Technology Assessment 2010; Vol. 14: No. 12 in groups 1, 1, in groups 1c and SMBG and SMBG 1c 1c between patients with between 1c overall; more frequent frequent more overall; 1c 7 times per week and patients with 7 times per week 7 times per week not associated with SMBG when analysed not associated with SMBG when analysed 1c SMBG < SMBG > HbA No difference in HbA No difference testing associated with lower HbA testing associated with lower based on treatment group (insulin vs diet/oral) group based on treatment 4 and 5, effect ranged from –0.22% to –0.94% for –0.22% to –0.94% for ranged from effect 4 and 5, 10 glucose test strips/week every SMBG use, subdivided by treatment alterations: treatment subdivided by SMBG use, 36.3% used OHA dose(s) unchanged: 1 : Group monitoring a median of 2.5 times SMBG and were range 1.2–4.0) (interquartile weekly 38.0% used OHA dose(s) increased: 2 : Group monitoring a median of 2.6 times SMBG and were range 1.2–4.1) (interquartile weekly 39.7% used SMBG and OHA added: new 3 : Group monitoring a median of 2.8 times weekly were range 0.9–4.1) (interquartile OHA and new OHA dose(s) increased 4 : Group monitoring a 41.8% used SMBG and were added: range (interquartile median of 2.7 times weekly 1.1–3.9) 77.6% used SMBG and Insulin added: 5 : Group monitoring a median of 3.7 times weekly were range 1.7–7.2) (interquartile SMBG monitoring No association between and HbA frequency HbA No association between HbA No association between • • Results • • • • • • • • • 1c 1c 1c and medication change 1c 1c 1c Interventions : association between SMBG use association between Comparison : and HbA SMBG use association between Comparison : and HbA SMBG use association between Comparison : and HbA : no details of SMBG use/ : SMBG regimen protocols HbA Outcomes : : HbA Outcomes : HbA Outcomes : : 38 patients with T1DM or T2DM T1DM or 38 patients with : T2DM 98 patients with : : Veteran Affairs chart review Veteran : care routine : : NR : graph) 8.2% (from : NR : 1c 1c 1c Participants no medication limits T2DM, T1DM or Inclusion criteria : 60 years : Age NR BMI : HbA no medication limits T2DM, Inclusion criteria : 56 years : Age NR BMI : HbA Total number: 5862 patients with T2DM 5862 patients with number: Total veterans Network Healthcare Southwest Setting: taking oral antihyperglycaemic T2DM, Inclusion criteria : agents NR : Age NR BMI : HbA number Total Setting number Total Setting : NR : Diabetes duration no details : Treatment 14 years : Diabetes duration OHA or insulin diet, : Treatment NR : Diabetes duration insulin OHAs, diet, : Treatment 83 82 84 : 24 months : 3 years : NA : Oki (1997) Study USA database study Design : Follow-up USA cross-sectional Design : Follow-up USA cross-sectional Design : Follow-up Murata (2008) Newman (1990) Newman 104 105

© 2010 Queen’s Printer and Controller of HMSO. All rights reserved. Appendix 5 DOI: 10.3310/hta14120 Health Technology Assessment 2010; Vol. 14: No. 12 4); 103 4); = n between people between 1c and SMBG 12) than group 2 12) than group 1c = 19) or both ( = n 0.05 74), blood ( 74), < = reduced by 1.9% after 12 months by reduced 1c 0.001) 4); p 4); < = No difference between patients who reported patients who reported between No difference and those act on monitoring results would they not act on monitoring would who reported they results of diabetic complications was Prevalence peripheral comparable and only also closely being the groups, between differed neuropathy 1 ( n common in group more ( n with and without access to strips changes made to SU medication in either Few not used to probably (so SMBG results group change treatment) ( p HbA monitored 1) regularly 97 (48%) patients (group urine ( n in HbA No significant difference (52%) patients (group 2) performed no home 2) performed (52%) patients (group monitoring HbA No association between • • • Results • • • • : clinicians : 1c 1c 1c 1c 1c Interventions : association between SMBG use association between Comparison : and HbA SMBG/ association between Comparison : SMUG use and HbA evaluated SMBG readings to adjust SMBG readings evaluated treatment none : Control HbA Outcomes : : month 1: 2–3 per week, 2–3 per week, month 1: : SMBG regimen as 11 months: during the following necessary to maintain normoglycaemia adjustment/advice SMBG treatment no details of SMBG use/ : SMBG regimen protocols HbA Outcomes : : access to strips vs no Comparison : no details of SMBG use/ : SMBG regimen protocols Chemstrips SMBG method : HbA Outcomes : SUs, SUs, ± 2 years; no insulin 2 years; kg 20 ± 2 : 267 patients with T2DM 267 patients with : 200 : 115 : 1.5% ± kg/m : hospital diabetes clinic : outpatient clinics : : 9.1% : NR : 8.1 : 1c 1c 1c Participants number Total 58 years : Age 29.1 BMI : number Total Setting no insulin T2DM, Inclusion criteria : 65 years : Age NR BM I: HbA number Total Setting > for SU therapy T2DM, Inclusion criteria : or MET 68 years : Age 91 weight BMI : HbA : 8.6 years : Diabetes duration insulin diet alone, 34% using insulin; : Treatment acarbose or MET 6.4 years : Diabetes duration agents diet oral hypoglycaemic : Treatment HbA : NR : Diabetes duration agents (SU) oral hypoglycaemic : Treatment 87 85 86 : 1 year : NA : 2 years : Study Turkey cohort Design : Follow-up UK cross-sectional Design : Follow-up USA retrospective Design : chart review Follow-up Ozmen (2003) Rindone (1997) 106 (1994) Patrick 107

© 2010 Queen’s Printer and Controller of HMSO. All rights reserved. Appendix 5 DOI: 10.3310/hta14120 Health Technology Assessment 2010; Vol. 14: No. 12 8.1% vs 1c 0.05) < (independent 1c was independent 1c significantly lower in insulin-treated in insulin-treated lower significantly 1c than non-SMBG group (HbA than non-SMBG group 0.002) 1c = 0.004) = patients using at least daily SMBG than those using patients using at least daily p SMBG (8.8% vs 9.7%; less than daily in patients not using insulin No difference 7.2%) (suggestion insufficient control may have have may 7.2%) (suggestion insufficient control initiating SMBG) for been reason in SMBG lower rate of non-fatal events Total (7.2% vs than non-SMBG after 6.5 years group p 10.4%; (2.7% vs 4.6%; in SMBG group lower Fatal events p of treatment) Relationship of SMBG to HbA of other self-care behaviours of other self-care Mean HbA 45.3% began SMBG prior to an end SMBG use : 64 patients started an additional SMBG after point, 32% used SMBG while being a non-fatal end point; with diet or oral agents treated had higher mean FPG SMBG group At baseline, and HbA SMBG associated with lower HbA SMBG associated with lower Effects remained when analysing only patients not only when analysing remained Effects using insulin at baseline in classic No significant difference risk factors cardiovascular SMBG initiation often associated with treatment a problem) change/intensification (so confounding • • • • Results • • • • • • • , SMBG frequency , diabetes-related , 1c 1c 1c in insulin users and non-insulin 1c 1c Interventions SMBG use association between Comparison : and HbA : association between SMBG use association between Comparison : and HbA morbidity (non-fatal myocardial infarction, infarction, morbidity (non-fatal myocardial blindness, amputation, foot stroke, all-cause mortality haemodialysis), users HbA Outcomes : : HbA Outcomes : : association between SMBG use association between Comparison : and morbidity/mortality no details of SMBG use/ : SMBG regimen protocols HbA Outcomes : 2 2515 not using insulin : 955 : T2DM 84 patients with : : 3268 patients with T2DM 3268 patients with : = kg/m : 3 sites of an HMO : inpatient : : 192 doctors’ practices : : NR : 7.7% : 1c 1c Participants treated pharmacologically T2DM (95%), Inclusion criteria: 53 years : Age NR BMI : HbA no medication limitation T2DM, Inclusion criteria : 56 years : Age diagnosis from followed : Diabetes duration oral medication insulin, Treatment: Total number Total Setting number Total Setting : 12 years : Diabetes duration 52% oral agents 43% insulin, : Treatment diagnosis from followed : Diabetes duration n : Treatment : T2DM, followed from diagnosis from followed T2DM, Inclusion criteria: 62.4 years : Age 29.8 BMI : Total number Total Setting HbA / 99 / ) 15 78 88 89 : NA : NA : : mean 6.5 years : ROSSO Study ROSSO (Martin (2006) Martin (2009) Study (abstract) USA cross-sectional Design : Follow-up USA cross-sectional Design : Follow-up Roblin (2001) Roblin Germany longitudinal Design : study Follow-up Schneider (2007) 106 Rost (1990) 107

1c , with , 0.0001) 1c < included 1c concentration of 0.65% for concentration of 0.65% for 1c 0.001) (presumably because those with (presumably (–0.16%/one additional SMBG per (–0.16%/one additional < 1c 1c 0.0001) < –0.17, p –0.17, = day; p day; every extra 180 test strips dispensed (equivalent every to 1 per day) the cohort for on oral found No such relation agents a decrease of HbA a decrease Frequency of SMBG inversely related to HbA related of SMBG inversely Frequency poorer control were asked to test more often) to test more asked were control poorer p SMBG per day; (+0.14%/one additional : average SMBG frequency 2.7 times SMBG frequency average : Insulin treated associated with frequency increased per day; HbA lower ( r frequency of SMBG frequency In the insulin cohort, the total number of test the total number In the insulin cohort, of HbA was a predictor strips prescribed : average SMBG frequency 2.0 SMBG frequency average : Non-insulin treated associated with frequency increased times per day; higher HbA Most important determinants of HbA • Results • • • • • , SMBG use , 1c , frequency of SMBG frequency , 1c 1c 1c 1c Interventions SMBG use association between Comparison : and HbA Intervention: access to free BG monitors access to free Intervention: HbA Outcomes: : no details of SMBG use/ : SMBG regimen protocols HbA Outcomes : no details of SMBG use/ : SMBG regimen protocols of SMBG, frequency most recent Outcomes : HbA most recent : association between SMBG use association between Comparison : and HbA 65 years ≥ 1 year 2436 oral agents = 347 insulin, n 347 insulin, : 842 : T2DM 5009 people with : 2783 : = 80% overweight or obese 80% overweight : hospital outpatient clinic : 191 centres database, German/Austrian DPV-Wiss : Database UK General Practice Research : : mean 7.64%, 6.37% (diet only), 8.04% (oral agents), 8.04% (oral agents), 6.37% (diet only), mean 7.64%, : NR : 1c 1c 2988 not using insulin) = : > BMI : Participants number Total Setting > insulin treatment T2DM, Inclusion criteria: 60 (SD 1.1) years : Age 12.6 (SD 7) years : Diabetes duration insulin : Treatment number Total Setting T2DM Inclusion criteria : NR : Age NR BMI : HbA number Total Setting 12-month insulin or oral agent, T2DM, Inclusion criteria : postinitiation data 47% 45% 45–64 years, 8% 20–44 years, : Age HbA 8.29% (insulin) 10 years : Diabetes duration diet agents, oral antihyperglycaemic insulin, : Treatment ( n NR : Diabetes duration n : Treatment 91 92 90 : NA : NA : 12 months : Study Germany cross-sectional Design : Follow-up Germany/Austria cross-sectional Design : Follow-up UK database study Design : Follow-up Schiel (1999) Secnik (2007) 108 Schütt (2006) 109

© 2010 Queen’s Printer and Controller of HMSO. All rights reserved. Appendix 5 DOI: 10.3310/hta14120 Health Technology Assessment 2010; Vol. 14: No. 12 of 1c in 1c 1791) = in those with n levels between between levels 1c 1c 0.03 = 1c 0.75 strips per day 0.75 strips per day ≥ levels might preclude might preclude levels 1c 10%, decrease in HbA decrease 10%, significantly higher [but not significantly 8.13%, those who received those who received 8.13%, 1c 1c > 0.0001) with a reduction 0.0001) with a reduction 1c < p in patients on SUs ( for people not receiving people not receiving for 1c 1c 8.0% 1.7%; in 90 initiators of SMBG vs 43 control in 90 initiators of SMBG vs 43 control 1.7%; 1c ± 0.63% (95% CI 1.14 to 0.12); p 0.63% (95% CI 1.14 to 0.12); No association of SMBG and HbA antihyperglycaemic medication, 0.07% for oral 0.07% for medication, antihyperglycaemic and treatment, insulin only 0.13% for treatment, oral plus insulin treatment 0.32% for relevant??] in SMBG group (5.5% vs 5.3%) in SMBG group relevant??] HbA low COMMENT: less than 0.75 strips per day (mean 0.17) had less than 0.75 strips per day HbA meaningful difference in HbA meaningful difference SMBG was associated with reduced HbA SMBG was associated with reduced good (7.1%) or adequate (8.0%) control good initiation rate of baseline trend) Adjusted (for 14 (95% CI 10 to by SMBG in SU users increased 17) patients/1000 patients per month significant sudden Initiators of SMBG showed 6 of medication use by in regularity improvements months post initiation Baseline HbA 8.4 subjects with HbA (mean per day 0.75 strips or more 36% received 1.7) with mean HbA 54% in group, of SMBG 36% in diet only Frequency 79% in patients on insulin patients on oral agents, in HbA No significant differences SMBG users and non-users on insulin (6.9% vs in or on oral agents (6.3% in both groups), 6.8%), HbA group diet only was associated ( subsequent quarter: using subsequent quarter: of 0.1% HbA • • • • • Results • • • • , SMBG use, medication SMBG use, , 1c 1c 1c 1c 1c : association between SMBG use association between Comparison : and HbA Interventions : association between SMBG use association between Comparison : and HbA use : no details of SMBG use/ : SMBG regimen protocols HbA Outcomes : no details of SMBG use/ : SMBG regimen protocols SMBG other : SMBG method : HbA Outcomes : : access to free BG monitors access to free Intervention : no details of SMBG use/ : SMBG regimen protocols HbA Outcomes : 4 44.5% 2 kg/m 30 24.6%, ≥ 24.6%, 2 kg/m 2 years, 4–33%; 2–4 years, 9–35%; > 9–35%; 2–4 years, 4–33%; 2 years, 11.8%, 25–30 11.8%, 2 : 3219 people with T1DM or T2DM T1DM or 3219 people with : 14329 : further exploration T2DM, 6495 people with : 1.7% ± kg/m 12.3 years ± : database : Affairs facilities Veterans : in Östergötland and 18 primary health centres care : : 8.4 : NR : 5.4% to 6.9% : 1c 1c 1c years, 32–87% years, agents oral hypoglycaemic (32%), diet only : Treatment insulin (31%) (37%), HbA Participants treatment any T2DM, Inclusion criteria: 56 : Age <25 BMI : 98% male 65 years; : Age NR BMI : HbA Sweden Jönköping, users and non-users of SMBG T2DM, Inclusion criteria : 69 years : Age NR BMI : HbA Total number Total Setting number Total Setting number Total telephone interviews with 533 of 896, of medical records patients using SMBG on their opinions and habits Setting : NR : Diabetes duration no details given insulin; OHAs, : Treatment < : Diabetes duration : NR : Diabetes duration agents (57% on SUs) oral hypoglycaemic insulin, : Treatment 94 93 95 : 4 years : NA : NA : Tengblad (2007) Tengblad Stiptzarov (2003) Stiptzarov Study USA time interrupted Design : series Follow-up USA cross-sectional, Design : survey Follow-up Sweden cross-sectional Design : Follow-up 108 Soumerai (2004) 109

© 2010 Queen’s Printer and Controller of HMSO. All rights reserved. Appendix 5 DOI: 10.3310/hta14120 Health Technology Assessment 2010; Vol. 14: No. 12 1c (but 1c 1c already quite low) already 1c HbA Median usage of strips 4 per week SMBG frequency not associated with HbA SMBG frequency of SMBG not associated with HbA Frequency significantly Age and glibenclamide dose were associated with HbA • Results • • • twice per day 1c 1c ≥ Interventions : no SMBG vs SMBG year 3 or no SMBG vs year Comparison : 1–3 2–3 or SMBG years SMBG years HbA Outcomes : : no SMBG vs once per Comparison : vs SMBG day HbA Outcomes : T2DM, prescribed oral medication prescribed T2DM, 2

: 976 people with T2DM 976 people with : : 216 people with T2DM 216 people with : 1.4% kg/m ± 6 ± Veteran Affairs Veteran

: : Veteran Affairs Veteran : : 7–7.3% : : 7.9 : 1c 1c Participants Total number Total Setting Inclusion criteria: 97% male 63 years; : Age 31 BMI : Total number Total Setting glyburide prescribed T2DM, Inclusion criteria : all male range 39–89 years; : Age NR BMI : HbA : NR : Diabetes duration OHAs only : Treatment HbA : NR : Diabetes duration OHAs only : Treatment 96 16 : 3 years : : NA : Wieland (1997) Study USA chart review Design : Follow-up Wen (2004) Wen 110 USA retrospective Design : chart review Follow-up follow- FU, emergency room; ER, Measure; Diabetes Quality-of-Life DQoL, oral quality management and documentation of diabetes in Germany; database for OHA, not reported; DPV-DISS, NR, blood glucose; National Health and Nutrition Examination Survey; Third BG, NHANES III, not available; NA, metformin; MET, health maintenance organisation; HMO, up; sulphonylurea(s). SU(s), of the mean; error standard SEM, and outcomes in type 2 diabetes; quality of care QuED, agent; hypoglycaemic 111

Appendix 6 Characteristics and results of qualitative studies

110 111

© 2010 Queen’s Printer and Controller of HMSO. All rights reserved. Appendix 6 DOI: 10.3310/hta14120 Health Technology Assessment 2010; Vol. 14: No. 12 ering between groups there was no there groups ering between 1c 1c SMBG value is less clear-cut for patients unlikely to alter their treatment dose/behaviour, or if they are using treatments using treatments are or if they dose/behaviour, to alter their treatment patients unlikely for SMBG value is less clear-cut that lack the potential to cause hypoglycaemia British people tend not to act on their SMBG results with that of patients who do not self- and anxiety compared of depression levels SMBG is associated with increased monitor with those taking test strip cost per patient was £62.06, mean annual in the UK 2006–7 was £164,648,000; Expenditure a mean of £21.56 having oral antidiabetic treatment This MET/glitazones (2.6–3.3 mean per week). alone (mean 2.5 strips per week), on diet and exercise Patients who are is high in these groups thus the absolute expenditure 22% of all patients testing, represents group to be due in and this appears patients use SMBG to guide and maintain changes their behaviour/lifestyle few In the UK, could be considerable wastage due to inappropriate and acting upon result; part to a lack of education about interpreting prescriptions repeat corresponding change in self-reported health behaviours change in self-reported corresponding Results participants to control relative in both self-monitoring groups, Concerns about the consequences of diabetes increased to usual care relative in both self-monitoring groups Beliefs about the importance of self-testing increased in general and specific increases greater patients reported but control did not differ, Changes in psychological well-being dietary than patients in either self-monitoring groups adherence Authors concluded that despite changes in some beliefs about diabetes diff SMBG thought to be more accurate than SMUG, but participants expressed reservations but participants about its accuracy when expressed accurate than SMUG, SMBG thought to be more with HbA compared Several patients mentioned an increased awareness of having diabetes as a consequence of SMBG of having awareness patients mentioned an increased Several one participant threatened felt of abnormality, as tangible evidence respondents by viewed BG level of elevated Presence of illness constant reminder by symptoms and their blood their physical between Some participants noted SMBG helped them establish the relationship hyperglycaemia rather than hypoglycaemia this used SMBG to confirm suspected sugar – most who reported when associated with normal readings; respondents several for reassurance provided of blood sugar levels Awareness of failure associated with feelings outside parameters were readings however, of effect example timing of monitoring, for of behaviour, could use SMBG to assess effects Some participants they felt certain foods feedback on general diabetes Respondents used to self-management emerged as benefit of SMBG. of adherence Promotion in both monitoring groups and on specific behaviours control long- change in patients who did not recognise might be needed to encourage maintenance of behaviour Other incentives change term benefits of behaviour satisfactory got only readings they participants timed their SMBG to ensure said they Two evaluation and ability to contribute physician’s their health care over control more to take Participants empowered felt of their status was a benefit of SMBG participants said convenience Several expressed 2 respondents only of their diabetes, in control enabled some participants more to feel have While SMBG may periodic clinic visits and HbA SMBG over for an absolute preference 9.0) 40,651 records examined 40,651 records 40 participants interviews to Semistructured discuss experiences of having diabetes and taking part in the trial ( ± 68.5 years Age: questionnaire Standard Illness Perceptions (revised Questionnaire) 399 patients returned completed questionnaires Topics of specific inquiry: of specific inquiry: Topics understanding of the RCT; usefulness of taking part in the comparison of SMBG and RCT; usefulness of clinical monitoring; control; of glycaemic knowledge prompts, use of SMBG – ease, to behaviour relationship timing, • Participants/issues • • • • • • 10 UK 100 DiGEM RCT, UK DiGEM RCT, Belsey (2009), Belsey Prevalence data assessed Prevalence using Quality and Outcomes Framework 112 design Study, component Qualitative UK DiGEM RCT, study Questionnaire measuring patients’ beliefs about diabetes and self-monitoring 113

© 2010 Queen’s Printer and Controller of HMSO. All rights reserved. Appendix 6 DOI: 10.3310/hta14120 Health Technology Assessment 2010; Vol. 14: No. 12 w readings should be interpreted w readings : Analysis highlights the importance of understanding the meanings that newly diagnosed patients attach to highlights the importanceAnalysis of understanding the meanings that newly : 16 patients performed urine testing post diagnoses: of these, 6 had changed to SMBG by round 2, and 2 further had 2, round 6 had changed to SMBG by of these, urine testing post diagnoses: 16 patients performed point (SMBG mainly 3 patients did not monitor at any 3 had stopped monitoring altogether; 3; round changed to SMBG by advised urine testing or nothing) GPs generally initiated after visiting hospital clinic, to subsequent use of SMBG – when compared especially about urine testing, views negative Patients expressed and accurate hygienic convenient, to be more perceived this could of diabetes; advanced or serious forms to those with more given Most patients assumed that BG meters were disease thought about their own they implications on how have diabetes could not have as indicating that they urine results negative Patients often interpreted Results In round 1 interviews, 37.5% of patients used glucose meters, 7 did not self-monitor; by round 2, 52.5% used glucose 2, round by 7 did not self-monitor; 37.5% of patients used glucose meters, 1 interviews, In round group-based hospital clinics and had attended structured with meters by been provided having meters – most reported education sessions including instructions on meter use readings low modifications; and regimen can encourage self-regulation and cons in self-monitoring; Patients see both pros example dietary for of the impact lifestyle, glucose monitoring can heighten patients’ awareness reassurance; can offer resulting in often about self-management, ‘failure’ ‘success’ or glucose monitoring amplifies a sense of on BG levels; choices, patients’ self- effect monitoring can negatively Moreover, high. consistently remain anxiety and self-blame if glucose readings counterintuitive are management when readings Conclusions that patients should ensure health professionals of self-monitoring, effects maximise the positive To glucose self-monitoring. understand the purpose of monitoring and should clarify with patients ho 40 patients diagnosed as having 40 patients diagnosed as having 6 T2DM within previous months Mean age 53.5 (range 21–77), range of 22 men; 18 women, social classes white All but one patient were diet alone or by Treatment and MET and/or gliclazide asked: Patients were self-monitored whether they what means and by had changed their whether they of self- method and frequency monitoring thought about they how to (different) and responded readings 40 patients diagnosed as having 40 patients diagnosed as having 6 T2DM within previous months Mean age 53.5 (range 21–77), range of 21 men; 19 women, social classes white All but one patients were diet alone or by Treatment and MET and/or gliclazide same sample as (Presumably above?) asked: Patients were me about monitoring your Tell blood sugar been changes in the there Have do? amount of monitoring you think and do What do you get high and low when you readings? • • • • • • • • Participants/issues • • • • • • • • • UK 6 UK 16) in 16) in 101 = = 3) and general 3) and general = = Peel (2004), Peel Lawton (2004), Lawton Qualitative study using Qualitative in-depth interviews, by study informed theorygrounded Patients were at interviewed intervals6-monthly over (3 interviews) 1 year recruited Patients were hospital clinics from ( n practices ( n Lothian, Scotland Lothian, Study, design Study, Qualitative study using Qualitative interviews; repeat based thematic analysis theoryin grounded 6 interviews over Two months recruited Patients were hospital clinics from ( n practices ( n 112 Scotland Lothian, 113

© 2010 Queen’s Printer and Controller of HMSO. All rights reserved. Appendix 6 8%, higher diabetes 8%, > 1c , and lack of perceived interest in meter readings, in meter readings, interest and lack of perceived , 1c : Clinical uncertainty about the efficacy and role of BG self-monitoring in patients with T2DM is mirrored in T2DM is mirrored role of BG self-monitoring in patients with Clinical uncertainty about the efficacy and : Results Analysis revealed three main themes – the role of health professionals, interpreting readings and managing high values, and and managing high values, readings interpreting of health professionals, main themes – the role three revealed Analysis seemed behaviour and health professionals’ time, over Self-monitoring decreased of BG self-monitoring. role the ongoing of HbA on levels participantsdoctors’ focus interpreted crucial in this: knowledge scores, insulin use; multivariate analyses demonstrated that those reporting external physical barriers barriers external physical demonstrated that those reporting analyses multivariate insulin use; scores, knowledge SMBG to perform less likely were internal psychological barriers external psychological barriers, (particularly financial), control and glycaemic diabetes knowledge sex, age, insulin use, independent of ethnicity, participation in self-care to encourage increased need to be addressed Carriers socioeconomic status and patients with lower lower SMBG in ethnic minorities, lower shown studies have Previous diabetes knowledge and family community to finance and access, – particularly relating to diabetes care Individuals reporting personal barriers SMBG prescribed to perform less likely were motivation and health beliefs – support and self-efficacy, Patient-reported barriers to diabetes care associated with SMBG include financial, psychosocial and self-efficacy issues associated with SMBG include financial, to diabetes care Patient-reported barriers HbA sex, female were than or twice weekly Characteristics associated with SMBG greater as indicating that self-monitoring was not worth continuing. Some participants saw readings as a proxy measure of good of good measure as a proxy readings Some participants saw continuing. as indicating that self-monitoring was not worth Some participants continued high. were when readings chastising themselves especially, – with women, and bad behaviour were Reassurance and habit readings. respond to high with uncertaintyhow to about readings difficult to interpret, to find and maintain using self-monitoring to effect was little indication that participants were There continuing. for reasons key change behaviour Conclusions in part because of a lack education Patients tended not to act on their self-monitoring results, accounts. patients’ own should be explicit about whether and when such patients Health professionals to readings. response about the appropriate high readings especially and act upon the results, should interpret they should self-monitor and how 18 patients with T2DM 18 patients with 4 over interviewed repeatedly years 323 participants from the South 323 participants from Auckland Diabetes project 9.2–12.7% T1DM, (2.2–5.5% T2DM the rest insulin treated; non-insulin treated) men and 52–63 years, Age: women to to determine barriers Survey and to SMBG diabetes care, Participants/issues • • • • New New 103 UK 102 Peel (2007), Peel BG, blood glucose; MET, metformin. MET, blood glucose; BG, Zgibor (2002), Study, design Study, Qualitative study as Qualitative interviews repeat above, after 4 years over diagnosis 114 Zealand survey Qualitative DOI: 10.3310/hta14120 Health Technology Assessment 2010; Vol. 14: No. 12

Health Technology Assessment reports published to date Volume 1, 1997 No. 11 No. 6 Newborn screening for inborn errors of Effectiveness of hip prostheses in No. 1 metabolism: a systematic review. primary total hip replacement: a critical Home parenteral nutrition: a systematic By Seymour CA, Thomason MJ, review of evidence and an economic review. Chalmers RA, Addison GM, Bain MD, model. By Richards DM, Deeks JJ, Sheldon Cockburn F, et al. By Faulkner A, Kennedy LG, Baxter TA, Shaffer JL. K, Donovan J, Wilkinson M, Bevan G. No. 12 No. 2 Routine preoperative testing: a No. 7 Diagnosis, management and screening systematic review of the evidence. Antimicrobial prophylaxis in colorectal of early localised prostate cancer. By Munro J, Booth A, Nicholl J. surgery: a systematic review of A review by Selley S, Donovan J, randomised controlled trials. Faulkner A, Coast J, Gillatt D. No. 13 By Song F, Glenny AM. Systematic review of the effectiveness of No. 3 No. 8 laxatives in the elderly. The diagnosis, management, treatment Bone marrow and peripheral By Petticrew M, Watt I, Sheldon T. and costs of prostate cancer in England blood stem cell transplantation for and Wales. malignancy. No. 14 A review by Chamberlain J, Melia J, A review by Johnson PWM, When and how to assess fast-changing Moss S, Brown J. Simnett SJ, Sweetenham JW, Morgan GJ, technologies: a comparative study of Stewart LA. No. 4 medical applications of four generic Screening for fragile X syndrome. technologies. No. 9 A review by Murray J, Cuckle H, A review by Mowatt G, Bower DJ, Screening for speech and language Taylor G, Hewison J. Brebner JA, Cairns JA, Grant AM, delay: a systematic review of the McKee L. literature. No. 5 By Law J, Boyle J, Harris F, A review of near patient testing in Harkness A, Nye C. primary care. Volume 2, 1998 By Hobbs FDR, Delaney BC, No. 10 Fitzmaurice DA, Wilson S, Hyde CJ, No. 1 Resource allocation for chronic Thorpe GH, et al. Antenatal screening for Down’s stable angina: a systematic review of effectiveness, costs and No. 6 syndrome. cost-effectiveness of alternative Systematic review of outpatient services A review by Wald NJ, Kennard A, for chronic pain control. Hackshaw A, McGuire A. interventions. By McQuay HJ, Moore RA, Eccleston By Sculpher MJ, Petticrew M, C, Morley S, de C Williams AC. No. 2 Kelland JL, Elliott RA, Holdright DR, Screening for ovarian cancer: a Buxton MJ. No. 7 systematic review. Neonatal screening for inborn errors of By Bell R, Petticrew M, Luengo S, No. 11 metabolism: cost, yield and outcome. Sheldon TA. Detection, adherence and control of A review by Pollitt RJ, Green A, hypertension for the prevention of McCabe CJ, Booth A, Cooper NJ, No. 3 stroke: a systematic review. Leonard JV, et al. Consensus development methods, By Ebrahim S. and their use in clinical guideline No. 12 No. 8 development. Postoperative analgesia and vomiting, Preschool vision screening. A review by Murphy MK, Black NA, with special reference to day-case A review by Snowdon SK, Lamping DL, McKee CM, Sanderson Stewart-Brown SL. surgery: a systematic review. CFB, Askham J, et al. By McQuay HJ, Moore RA. No. 9 No. 4 Implications of socio-cultural contexts No. 13 A cost–utility analysis of interferon beta for the ethics of clinical trials. Choosing between randomised and for multiple sclerosis. A review by Ashcroft RE, Chadwick nonrandomised studies: a systematic DW, Clark SRL, Edwards RHT, Frith L, By Parkin D, McNamee P, Jacoby A, review. Hutton JL. Miller P, Thomas S, Bates D. By Britton A, McKee M, Black N, McPherson K, Sanderson C, Bain C. No. 10 No. 5 A critical review of the role of neonatal Effectiveness and efficiency of methods No. 14 hearing screening in the detection of of dialysis therapy for end-stage renal Evaluating patient-based outcome congenital hearing impairment. disease: systematic reviews. measures for use in clinical trials. By Davis A, Bamford J, Wilson I, By MacLeod A, Grant A, Donaldson A review by Fitzpatrick R, Davey C, Ramkalawan T, Forshaw M, Wright S. C, Khan I, Campbell M, Daly C, et al. Buxton MJ, Jones DR. 115

No. 15 No. 4 No. 15 Ethical issues in the design and conduct A randomised controlled trial of Near patient testing in diabetes clinics: of randomised controlled trials. different approaches to universal appraising the costs and outcomes. antenatal HIV testing: uptake and A review by Edwards SJL, Lilford RJ, By Grieve R, Beech R, Vincent J, acceptability. Annex: Antenatal HIV Mazurkiewicz J. Braunholtz DA, Jackson JC, Hewison J, testing – assessment of a routine Thornton J. voluntary approach. By Simpson WM, Johnstone FD, No. 16 No. 16 Boyd FM, Goldberg DJ, Hart GJ, Positron emission tomography: Qualitative research methods in health Gormley SM, et al. establishing priorities for health technology assessment: a review of the technology assessment. literature. No. 5 A review by Robert G, Milne R. Methods for evaluating area-wide and By Murphy E, Dingwall R, organisation-based interventions in No. 17 (Pt 1) Greatbatch D, Parker S, Watson P. health and health care: a systematic The debridement of chronic wounds: a review. systematic review. No. 17 By Ukoumunne OC, Gulliford MC, By Bradley M, Cullum N, Sheldon T. The costs and benefits of paramedic Chinn S, Sterne JAC, Burney PGJ. skills in pre-hospital trauma care. No. 17 (Pt 2) By Nicholl J, Hughes S, Dixon S, No. 6 Assessing the costs of healthcare Systematic reviews of wound care Turner J, Yates D. technologies in clinical trials. management: (2) Dressings and topical A review by Johnston K, Buxton MJ, agents used in the healing of chronic No. 18 Jones DR, Fitzpatrick R. wounds. Systematic review of endoscopic By Bradley M, Cullum N, Nelson EA, ultrasound in gastro-oesophageal No. 7 Petticrew M, Sheldon T, Torgerson D. cancer. Cooperatives and their primary care emergency centres: organisation and By Harris KM, Kelly S, Berry E, No. 18 impact. Hutton J, Roderick P, Cullingworth J, By Hallam L, Henthorne K. A systematic literature review of et al. spiral and electron beam computed No. 8 tomography: with particular reference No. 19 Screening for cystic fibrosis. to clinical applications in hepatic Systematic reviews of trials and other A review by Murray J, Cuckle H, lesions, pulmonary embolus and studies. Taylor G, Littlewood J, Hewison J. coronary artery disease. By Sutton AJ, Abrams KR, Jones DR, By Berry E, Kelly S, Hutton J, No. 9 Sheldon TA, Song F. Harris KM, Roderick P, Boyce JC, et al. A review of the use of health status measures in economic evaluation. No. 20 By Brazier J, Deverill M, Green C, No. 19 Primary total hip replacement surgery: Harper R, Booth A. What role for statins? A review and a systematic review of outcomes economic model. and modelling of cost-effectiveness No. 10 By Ebrahim S, Davey Smith associated with different prostheses. Methods for the analysis of quality- G, McCabe C, Payne N, Pickin M, A review by Fitzpatrick R, Shortall of-life and survival data in health Sheldon TA, et al. technology assessment. E, Sculpher M, Murray D, Morris R, A review by Billingham LJ, No. 20 Lodge M, et al. Abrams KR, Jones DR. Factors that limit the quality, number No. 11 and progress of randomised controlled Volume 3, 1999 Antenatal and neonatal trials. haemoglobinopathy screening in the A review by Prescott RJ, Counsell CE, No. 1 UK: review and economic analysis. Gillespie WJ, Grant AM, Russell IT, By Zeuner D, Ades AE, Karnon J, Informed decision making: an Kiauka S, et al. Brown J, Dezateux C, Anionwu EN. annotated bibliography and systematic No. 21 review. No. 12 Antimicrobial prophylaxis in total hip By Bekker H, Thornton JG, Assessing the quality of reports of replacement: a systematic review. Airey CM, Connelly JB, Hewison J, randomised trials: implications for the By Glenny AM, Song F. Robinson MB, et al. conduct of meta-analyses. A review by Moher D, Cook DJ, No. 22 No. 2 Jadad AR, Tugwell P, Moher M, Jones A, et al. Health promoting schools and health Handling uncertainty when performing promotion in schools: two systematic economic evaluation of healthcare No. 13 reviews. interventions. ‘Early warning systems’ for identifying By Lister-Sharp D, Chapman S, A review by Briggs AH, Gray AM. new healthcare technologies. Stewart-Brown S, Sowden A. By Robert G, Stevens A, Gabbay J. No. 3 No. 23 No. 14 The role of expectancies in the placebo Economic evaluation of a primary A systematic review of the role of effect and their use in the delivery of human papillomavirus testing within a care-based education programme for health care: a systematic review. cervical screening programme. patients with osteoarthritis of the knee. By Crow R, Gage H, Hampson S, By Cuzick J, Sasieni P, Davies P, A review by Lord J, Victor C, 116 Hart J, Kimber A, Thomas H. Adams J, Normand C, Frater A, et al. Littlejohns P, Ross FM, Axford JS. DOI: 10.3310/hta14120 Health Technology Assessment 2010; Vol. 14: No. 12

Volume 4, 2000 No. 11 No. 21 Cost and outcome implications of the Systematic reviews of wound care No. 1 organisation of vascular services. management: (3) antimicrobial agents The estimation of marginal time By Michaels J, Brazier J, for chronic wounds; (4) diabetic foot preference in a UK-wide sample Palfreyman S, Shackley P, Slack R. ulceration. (TEMPUS) project. By O’Meara S, Cullum N, Majid M, A review by Cairns JA, No. 12 Sheldon T. van der Pol MM. Monitoring blood glucose control in diabetes mellitus: a systematic review. No. 22 No. 2 By Coster S, Gulliford MC, Seed PT, Using routine data to complement Geriatric rehabilitation following Powrie JK, Swaminathan R. and enhance the results of randomised fractures in older people: a systematic controlled trials. By Lewsey JD, Leyland AH, Murray review. No. 13 GD, Boddy FA. By Cameron I, Crotty M, Currie C, The effectiveness of domiciliary Finnegan T, Gillespie L, Gillespie W, health visiting: a systematic review of international studies and a selective No. 23 et al. review of the British literature. Coronary artery stents in the treatment of ischaemic heart disease: a rapid and No. 3 By Elkan R, Kendrick D, Hewitt M, Robinson JJA, Tolley K, Blair M, et al. systematic review. Screening for sickle cell disease and By Meads C, Cummins C, Jolly K, thalassaemia: a systematic review with No. 14 Stevens A, Burls A, Hyde C. supplementary research. The determinants of screening uptake By Davies SC, Cronin E, Gill M, and interventions for increasing No. 24 Greengross P, Hickman M, Normand C. uptake: a systematic review. Outcome measures for adult critical By Jepson R, Clegg A, Forbes C, care: a systematic review. No. 4 Lewis R, Sowden A, Kleijnen J. By Hayes JA, Black NA, Jenkinson C, Community provision of hearing aids Young JD, Rowan KM, Daly K, et al. and related audiology services. No. 15 A review by Reeves DJ, Alborz A, The effectiveness and cost-effectiveness No. 25 Hickson FS, Bamford JM. of prophylactic removal of wisdom A systematic review to evaluate the teeth. effectiveness of interventions to No. 5 A rapid review by Song F, O’Meara S, promote the initiation of breastfeeding. By Fairbank L, O’Meara S, False-negative results in screening Wilson P, Golder S, Kleijnen J. programmes: systematic review of Renfrew MJ, Woolridge M, Sowden AJ, impact and implications. No. 16 Lister-Sharp D. By Petticrew MP, Sowden AJ, Ultrasound screening in pregnancy: No. 26 Lister-Sharp D, Wright K. a systematic review of the clinical Implantable cardioverter defibrillators: effectiveness, cost-effectiveness and arrhythmias. A rapid and systematic No. 6 women’s views. review. By Bricker L, Garcia J, Henderson J, Costs and benefits of community By Parkes J, Bryant J, Milne R. postnatal support workers: a Mugford M, Neilson J, Roberts T, et al. randomised controlled trial. No. 27 No. 17 By Morrell CJ, Spiby H, Stewart P, Treatments for fatigue in multiple Walters S, Morgan A. A rapid and systematic review of the sclerosis: a rapid and systematic review. effectiveness and cost-effectiveness of By Brañas P, Jordan R, Fry-Smith A, No. 7 the taxanes used in the treatment of Burls A, Hyde C. Implantable contraceptives (subdermal advanced breast and ovarian cancer. implants and hormonally impregnated By Lister-Sharp D, McDonagh MS, No. 28 intrauterine systems) versus other Khan KS, Kleijnen J. Early asthma prophylaxis, natural forms of reversible contraceptives: two history, skeletal development and No. 18 systematic reviews to assess relative economy (EASE): a pilot randomised Liquid-based cytology in cervical effectiveness, acceptability, tolerability controlled trial. screening: a rapid and systematic and cost-effectiveness. By Baxter-Jones ADG, Helms PJ, review. By French RS, Cowan FM, Russell G, Grant A, Ross S, Cairns JA, By Payne N, Chilcott J, McGoogan E. Mansour DJA, Morris S, Procter T, et al. Hughes D, et al. No. 19 No. 29 Randomised controlled trial of non- No. 8 Screening for hypercholesterolaemia directive counselling, cognitive– versus case finding for familial An introduction to statistical methods behaviour therapy and usual general hypercholesterolaemia: a systematic for health technology assessment. practitioner care in the management of review and cost-effectiveness analysis. A review by White SJ, Ashby D, depression as well as mixed anxiety and By Marks D, Wonderling Brown PJ. depression in primary care. D, Thorogood M, Lambert H, By King M, Sibbald B, Ward E, Humphries SE, Neil HAW. No. 9 Bower P, Lloyd M, Gabbay M, et al. Disease-modifying drugs for multiple No. 30 sclerosis: a rapid and systematic review. No. 20 A rapid and systematic review of By Clegg A, Bryant J, Milne R. Routine referral for radiography of the clinical effectiveness and cost- patients presenting with low back pain: effectiveness of glycoprotein IIb/IIIa No. 10 is patients’ outcome influenced by GPs’ antagonists in the medical management Publication and related biases. referral for plain radiography? of unstable angina. A review by Song F, Eastwood AJ, By Kerry S, Hilton S, Patel S, By McDonagh MS, Bachmann LM, Gilbody S, Duley L, Sutton AJ. Dundas D, Rink E, Lord J. Golder S, Kleijnen J, ter Riet G. 117

No. 31 Volume 5, 2001 No. 11 A randomised controlled trial Effectiveness of autologous chondrocyte of prehospital intravenous fluid No. 1 transplantation for hyaline cartilage replacement therapy in serious trauma. Clinical and cost-effectiveness defects in knees: a rapid and systematic By Turner J, Nicholl J, Webber L, of donepezil, rivastigmine and review. Cox H, Dixon S, Yates D. galantamine for Alzheimer’s disease: a By Jobanputra P, Parry D, Fry-Smith rapid and systematic review. A, Burls A. No. 32 By Clegg A, Bryant J, Nicholson T, No. 12 Intrathecal pumps for giving opioids in McIntyre L, De Broe S, Gerard K, et al. Statistical assessment of the learning chronic pain: a systematic review. curves of health technologies. By Williams JE, Louw G, No. 2 The clinical effectiveness and cost- By Ramsay CR, Grant AM, Wallace Towlerton G. SA, Garthwaite PH, Monk AF, Russell IT. effectiveness of riluzole for motor neurone disease: a rapid and systematic No. 33 No. 13 Combination therapy (interferon review. The effectiveness and cost-effectiveness alfa and ribavirin) in the treatment By Stewart A, Sandercock J, Bryan S, of temozolomide for the treatment of of chronic hepatitis C: a rapid and Hyde C, Barton PM, Fry-Smith A, et al. recurrent malignant glioma: a rapid systematic review. and systematic review. By Shepherd J, Waugh N, No. 3 By Dinnes J, Cave C, Huang S, Hewitson P. Equity and the economic evaluation of Major K, Milne R. healthcare. No. 34 By Sassi F, Archard L, Le Grand J. No. 14 A systematic review of comparisons of A rapid and systematic review of effect sizes derived from randomised No. 4 the clinical effectiveness and cost- and non-randomised studies. Quality-of-life measures in chronic effectiveness of debriding agents in treating surgical wounds healing by By MacLehose RR, Reeves BC, diseases of childhood. By Eiser C, Morse R. secondary intention. Harvey IM, Sheldon TA, Russell IT, By Lewis R, Whiting P, ter Riet G, Black AMS. No. 5 O’Meara S, Glanville J. Eliciting public preferences for No. 35 healthcare: a systematic review of No. 15 Intravascular ultrasound-guided techniques. Home treatment for mental health interventions in coronary artery By Ryan M, Scott DA, Reeves C, Bate problems: a systematic review. disease: a systematic literature review, A, van Teijlingen ER, Russell EM, et al. By Burns T, Knapp M, Catty J, with decision-analytic modelling, of Healey A, Henderson J, Watt H, et al. outcomes and cost-effectiveness. No. 6 No. 16 By Berry E, Kelly S, Hutton J, General health status measures for How to develop cost-conscious Lindsay HSJ, Blaxill JM, Evans JA, et al. people with cognitive impairment: guidelines. learning disability and acquired brain No. 36 By Eccles M, Mason J. injury. A randomised controlled trial to By Riemsma RP, Forbes CA, No. 17 evaluate the effectiveness and cost- Glanville JM, Eastwood AJ, Kleijnen J. effectiveness of counselling patients The role of specialist nurses in multiple sclerosis: a rapid and systematic review. with chronic depression. No. 7 By De Broe S, Christopher F, By Simpson S, Corney R, An assessment of screening strategies Waugh N. Fitzgerald P, Beecham J. for fragile X syndrome in the UK. By Pembrey ME, Barnicoat AJ, No. 18 No. 37 Carmichael B, Bobrow M, Turner G. A rapid and systematic review Systematic review of treatments for of the clinical effectiveness and atopic eczema. No. 8 cost-effectiveness of orlistat in the By Hoare C, Li Wan Po A, Issues in methodological research: management of obesity. Williams H. perspectives from researchers and By O’Meara S, Riemsma R, commissioners. Shirran L, Mather L, ter Riet G. No. 38 By Lilford RJ, Richardson A, Stevens Bayesian methods in health technology A, Fitzpatrick R, Edwards S, Rock F, et al. No. 19 assessment: a review. The clinical effectiveness and cost- By Spiegelhalter DJ, Myles JP, No. 9 effectiveness of pioglitazone for Jones DR, Abrams KR. Systematic reviews of wound type 2 diabetes mellitus: a rapid and care management: (5) beds; systematic review. By Chilcott J, Wight J, Lloyd Jones No. 39 (6) compression; (7) laser therapy, M, Tappenden P. The management of dyspepsia: a therapeutic ultrasound, electrotherapy systematic review. and electromagnetic therapy. No. 20 By Delaney B, Moayyedi P, Deeks J, By Cullum N, Nelson EA, Extended scope of nursing practice: Innes M, Soo S, Barton P, et al. Flemming K, Sheldon T. a multicentre randomised controlled trial of appropriately trained nurses No. 40 No. 10 and preregistration house officers in A systematic review of treatments for Effects of educational and psychosocial preoperative assessment in elective severe psoriasis. interventions for adolescents with general surgery. By Griffiths CEM, Clark CM, diabetes mellitus: a systematic review. By Kinley H, Czoski-Murray C, Chalmers RJG, Li Wan Po A, By Hampson SE, Skinner TC, Hart J, George S, McCabe C, Primrose J, 118 Williams HC. Storey L, Gage H, Foxcroft D, et al. Reilly C, et al. DOI: 10.3310/hta14120 Health Technology Assessment 2010; Vol. 14: No. 12

No. 21 No. 31 No. 5 Systematic reviews of the effectiveness Design and use of questionnaires: a The clinical effectiveness and cost- of day care for people with severe review of best practice applicable to effectiveness of inhaler devices used mental disorders: (1) Acute day hospital surveys of health service staff and in the routine management of chronic versus admission; (2) Vocational patients. asthma in older children: a systematic rehabilitation; (3) Day hospital versus By McColl E, Jacoby A, Thomas L, review and economic evaluation. outpatient care. Soutter J, Bamford C, Steen N, et al. By Peters J, Stevenson M, Beverley C, By Marshall M, Crowther R, Lim J, Smith S. Almaraz- Serrano A, Creed F, Sledge W, No. 32 Kluiter H, et al. A rapid and systematic review of No. 6 the clinical effectiveness and cost- The clinical effectiveness and cost- No. 22 effectiveness of paclitaxel, docetaxel, effectiveness of sibutramine in the The measurement and monitoring of gemcitabine and vinorelbine in non- management of obesity: a technology surgical adverse events. small-cell lung cancer. assessment. By Bruce J, Russell EM, Mollison J, By Clegg A, Scott DA, Sidhu M, By O’Meara S, Riemsma R, Shirran Krukowski ZH. Hewitson P, Waugh N. L, Mather L, ter Riet G.

No. 23 No. 33 No. 7 Action research: a systematic review and Subgroup analyses in randomised The cost-effectiveness of magnetic guidance for assessment. controlled trials: quantifying the risks resonance angiography for carotid By Waterman H, Tillen D, Dickson R, of false-positives and false-negatives. artery stenosis and peripheral vascular de Koning K. By Brookes ST, Whitley E, Peters TJ, disease: a systematic review. Mulheran PA, Egger M, Davey Smith G. By Berry E, Kelly S, Westwood ME, No. 24 Davies LM, Gough MJ, Bamford JM, A rapid and systematic review of No. 34 et al. the clinical effectiveness and cost- Depot antipsychotic medication effectiveness of gemcitabine for the in the treatment of patients with No. 8 treatment of pancreatic cancer. schizophrenia: (1) Meta-review; (2) Promoting physical activity in South By Ward S, Morris E, Bansback N, Patient and nurse attitudes. Asian Muslim women through ‘exercise Calvert N, Crellin A, Forman D, et al. By David AS, Adams C. on prescription’. By Carroll B, Ali N, Azam N. No. 25 No. 35 No. 9 A rapid and systematic review of the A systematic review of controlled Zanamivir for the treatment of evidence for the clinical effectiveness trials of the effectiveness and cost- influenza in adults: a systematic review and cost-effectiveness of irinotecan, effectiveness of brief psychological and economic evaluation. oxaliplatin and raltitrexed for the treatments for depression. By Burls A, Clark W, Stewart T, treatment of advanced colorectal By Churchill R, Hunot V, Corney R, Preston C, Bryan S, Jefferson T, et al. cancer. Knapp M, McGuire H, Tylee A, et al. By Lloyd Jones M, Hummel S, No. 10 Bansback N, Orr B, Seymour M. No. 36 Cost analysis of child health A review of the natural history and surveillance. epidemiology of multiple sclerosis: No. 26 implications for resource allocation and Comparison of the effectiveness of By Sanderson D, Wright D, Acton C, Duree D. health economic models. inhaler devices in asthma and chronic By Richards RG, Sampson FC, obstructive airways disease: a systematic Beard SM, Tappenden P. review of the literature. By Brocklebank D, Ram F, Wright J, Volume 6, 2002 No. 11 Barry P, Cates C, Davies L, et al. Screening for gestational diabetes: No. 1 a systematic review and economic No. 27 A study of the methods used to select evaluation. The cost-effectiveness of magnetic review criteria for clinical audit. By Scott DA, Loveman E, McIntyre resonance imaging for investigation of By Hearnshaw H, Harker R, L, Waugh N. the knee joint. Cheater F, Baker R, Grimshaw G. By Bryan S, Weatherburn G, Bungay No. 12 H, Hatrick C, Salas C, Parry D, et al. No. 2 The clinical effectiveness and cost- Fludarabine as second-line therapy for effectiveness of surgery for people with No. 28 B cell chronic lymphocytic leukaemia: a morbid obesity: a systematic review and A rapid and systematic review of technology assessment. economic evaluation. the clinical effectiveness and cost- By Hyde C, Wake B, Bryan S, Barton By Clegg AJ, Colquitt J, Sidhu MK, effectiveness of topotecan for ovarian P, Fry-Smith A, Davenport C, et al. Royle P, Loveman E, Walker A. cancer. By Forbes C, Shirran L, Bagnall A-M, No. 3 No. 13 Duffy S, ter Riet G. Rituximab as third-line treatment for The clinical effectiveness of refractory or recurrent Stage III or IV trastuzumab for breast cancer: a No. 29 follicular non-Hodgkin’s lymphoma: systematic review. Superseded by a report published in a a systematic review and economic By Lewis R, Bagnall A-M, Forbes C, later volume. evaluation. Shirran E, Duffy S, Kleijnen J, et al. By Wake B, Hyde C, Bryan S, Barton No. 30 P, Song F, Fry-Smith A, et al. No. 14 The role of radiography in primary The clinical effectiveness and cost- care patients with low back pain of at No. 4 effectiveness of vinorelbine for breast least 6 weeks duration: a randomised A systematic review of discharge cancer: a systematic review and (unblinded) controlled trial. arrangements for older people. economic evaluation. By Kendrick D, Fielding K, Bentley By Parker SG, Peet SM, McPherson By Lewis R, Bagnall A-M, King S, E, Miller P, Kerslake R, Pringle M. A, Cannaby AM, Baker R, Wilson A, et al. Woolacott N, Forbes C, Shirran L, et al. 119

No. 15 No. 24 No. 33 A systematic review of the effectiveness A systematic review of the effectiveness The effectiveness and cost-effectiveness and cost-effectiveness of metal-on- of interventions based on a stages-of- of imatinib in chronic myeloid metal hip resurfacing arthroplasty for change approach to promote individual leukaemia: a systematic review. treatment of hip disease. behaviour change. By Garside R, Round A, Dalziel K, By Vale L, Wyness L, McCormack K, By Riemsma RP, Pattenden J, Bridle Stein K, Royle R. McKenzie L, Brazzelli M, Stearns SC. C, Sowden AJ, Mather L, Watt IS, et al. No. 34 No. 16 No. 25 A comparative study of hypertonic The clinical effectiveness and cost- A systematic review update of the saline, daily and alternate-day rhDNase effectiveness of bupropion and nicotine clinical effectiveness and cost- in children with cystic fibrosis. replacement therapy for smoking effectiveness of glycoprotein IIb/IIIa By Suri R, Wallis C, Bush A, cessation: a systematic review and antagonists. Thompson S, Normand C, Flather M, economic evaluation. By Robinson M, Ginnelly L, Sculpher et al. By Woolacott NF, Jones L, Forbes CA, M, Jones L, Riemsma R, Palmer S, et al. Mather LC, Sowden AJ, Song FJ, et al. No. 35 No. 26 A systematic review of the costs and No. 17 A systematic review of the effectiveness, effectiveness of different models of A systematic review of effectiveness cost-effectiveness and barriers to paediatric home care. and economic evaluation of new drug implementation of thrombolytic and By Parker G, Bhakta P, Lovett CA, treatments for juvenile idiopathic neuroprotective therapy for acute Paisley S, Olsen R, Turner D, et al. arthritis: etanercept. ischaemic stroke in the NHS. By Cummins C, Connock M, By Sandercock P, Berge E, Dennis M, Fry-Smith A, Burls A. Forbes J, Hand P, Kwan J, et al. Volume 7, 2003

No. 18 No. 27 No. 1 Clinical effectiveness and cost- A randomised controlled crossover trial How important are comprehensive effectiveness of growth hormone in of nurse practitioner versus doctor- literature searches and the assessment children: a systematic review and led outpatient care in a bronchiectasis of trial quality in systematic reviews? economic evaluation. clinic. Empirical study. By Bryant J, Cave C, Mihaylova B, By Caine N, Sharples LD, By Egger M, Juni P, Bartlett C, Hollingworth W, French J, Keogan M, Chase D, McIntyre L, Gerard K, et al. Holenstein F, Sterne J. Exley A, et al. No. 19 No. 2 No. 28 Clinical effectiveness and cost- Systematic review of the effectiveness Clinical effectiveness and cost – effectiveness of growth hormone and cost-effectiveness, and economic consequences of selective serotonin in adults in relation to impact on evaluation, of home versus hospital or reuptake inhibitors in the treatment of quality of life: a systematic review and satellite unit haemodialysis for people sex offenders. economic evaluation. with end-stage renal failure. By Adi Y, Ashcroft D, Browne K, By Bryant J, Loveman E, Chase D, By Mowatt G, Vale L, Perez J, Wyness Beech A, Fry-Smith A, Hyde C. Mihaylova B, Cave C, Gerard K, et al. L, Fraser C, MacLeod A, et al. No. 29 No. 3 No. 20 Treatment of established osteoporosis: Systematic review and economic Clinical medication review by a a systematic review and cost–utility evaluation of the effectiveness of pharmacist of patients on repeat analysis. infliximab for the treatment of Crohn’s prescriptions in general practice: a By Kanis JA, Brazier JE, Stevenson disease. randomised controlled trial. M, Calvert NW, Lloyd Jones M. By Clark W, Raftery J, Barton P, By Zermansky AG, Petty DR, Raynor Song F, Fry-Smith A, Burls A. DK, Lowe CJ, Freementle N, Vail A. No. 30 Which anaesthetic agents are cost- No. 4 No. 21 effective in day surgery? Literature A review of the clinical effectiveness The effectiveness of infliximab and review, national survey of practice and and cost-effectiveness of routine anti-D etanercept for the treatment of randomised controlled trial. prophylaxis for pregnant women who rheumatoid arthritis: a systematic By Elliott RA Payne K, Moore JK, are rhesus negative. review and economic evaluation. Davies LM, Harper NJN, St Leger AS, By Chilcott J, Lloyd Jones M, Wight By Jobanputra P, Barton P, Bryan S, et al. J, Forman K, Wray J, Beverley C, et al. Burls A. No. 31 No. 5 No. 22 Screening for hepatitis C among Systematic review and evaluation of the A systematic review and economic injecting drug users and in use of tumour markers in paediatric evaluation of computerised cognitive genitourinary medicine clinics: oncology: Ewing’s sarcoma and behaviour therapy for depression and systematic reviews of effectiveness, neuroblastoma. anxiety. modelling study and national survey of By Riley RD, Burchill SA, By Kaltenthaler E, Shackley P, current practice. Abrams KR, Heney D, Lambert PC, Stevens K, Beverley C, Parry G, By Stein K, Dalziel K, Walker A, Jones DR, et al. Chilcott J. McIntyre L, Jenkins B, Horne J, et al. No. 6 No. 23 No. 32 The cost-effectiveness of screening for A systematic review and economic The measurement of satisfaction with Helicobacter pylori to reduce mortality evaluation of pegylated liposomal healthcare: implications for practice and morbidity from gastric cancer and doxorubicin hydrochloride for ovarian from a systematic review of the peptic ulcer disease: a discrete-event cancer. literature. simulation model. By Forbes C, Wilby J, Richardson G, By Crow R, Gage H, Hampson S, By Roderick P, Davies R, Raftery J, 120 Sculpher M, Mather L, Reimsma R. Hart J, Kimber A, Storey L, et al. Crabbe D, Pearce R, Bhandari P, et al. DOI: 10.3310/hta14120 Health Technology Assessment 2010; Vol. 14: No. 12

No. 7 No. 16 No. 26 The clinical effectiveness and cost- Screening for fragile X syndrome: a Can randomised trials rely on existing effectiveness of routine dental checks: literature review and modelling. electronic data? A feasibility study to a systematic review and economic By Song FJ, Barton P, Sleightholme explore the value of routine data in evaluation. V, Yao GL, Fry-Smith A. health technology assessment. By Davenport C, Elley K, Salas By Williams JG, Cheung WY, C, Taylor-Weetman CL, Fry-Smith A, No. 17 Cohen DR, Hutchings HA, Longo MF, Bryan S, et al. Systematic review of endoscopic sinus Russell IT. surgery for nasal polyps. No. 8 No. 27 By Dalziel K, Stein K, Round A, A multicentre randomised controlled Evaluating non-randomised Garside R, Royle P. trial assessing the costs and benefits intervention studies. of using structured information and By Deeks JJ, Dinnes J, D’Amico R, No. 18 analysis of women’s preferences in the Sowden AJ, Sakarovitch C, Song F, et al. management of menorrhagia. Towards efficient guidelines: how to By Kennedy ADM, Sculpher MJ, monitor guideline use in primary care. No. 28 Coulter A, Dwyer N, Rees M, Horsley S, By Hutchinson A, McIntosh A, A randomised controlled trial to assess et al. Cox S, Gilbert C. the impact of a package comprising a patient-orientated, evidence-based self- No. 9 No. 19 help guidebook and patient-centred Clinical effectiveness and cost–utility Effectiveness and cost-effectiveness consultations on disease management of photodynamic therapy for wet of acute hospital-based spinal cord and satisfaction in inflammatory bowel age-related macular degeneration: injuries services: systematic review. disease. a systematic review and economic By Bagnall A-M, Jones L, Richardson By Kennedy A, Nelson E, Reeves D, evaluation. G, Duffy S, Riemsma R. Richardson G, Roberts C, Robinson A, By Meads C, Salas C, Roberts T, et al. Moore D, Fry-Smith A, Hyde C. No. 20 Prioritisation of health technology No. 29 No. 10 assessment. The PATHS model: The effectiveness of diagnostic tests for Evaluation of molecular tests for the assessment of shoulder pain due prenatal diagnosis of chromosome methods and case studies. to soft tissue disorders: a systematic abnormalities. By Townsend J, Buxton M, review. By Grimshaw GM, Szczepura A, Harper G. By Dinnes J, Loveman E, McIntyre L, Hultén M, MacDonald F, Nevin NC, Waugh N. Sutton F, et al. No. 21 Systematic review of the clinical No. 30 No. 11 effectiveness and cost-effectiveness of The value of digital imaging in diabetic First and second trimester antenatal tension-free vaginal tape for treatment retinopathy. screening for Down’s syndrome: of urinary stress incontinence. By Sharp PF, Olson J, Strachan F, the results of the Serum, Urine and By Cody J, Wyness L, Wallace S, Hipwell J, Ludbrook A, O’Donnell M, Ultrasound Screening Study (SURUSS). Glazener C, Kilonzo M, Stearns S, et al. By Wald NJ, Rodeck C, Hackshaw et al. AK, Walters J, Chitty L, Mackinson AM. No. 22 No. 31 The clinical and cost-effectiveness of No. 12 Lowering blood pressure to prevent patient education models for diabetes: The effectiveness and cost-effectiveness myocardial infarction and stroke: a new a systematic review and economic of ultrasound locating devices for preventive strategy. central venous access: a systematic evaluation. By Law M, Wald N, Morris J. review and economic evaluation. By Loveman E, Cave C, Green C, By Calvert N, Hind D, McWilliams Royle P, Dunn N, Waugh N. No. 32 RG, Thomas SM, Beverley C, Clinical and cost-effectiveness of Davidson A. No. 23 capecitabine and tegafur with uracil for The role of modelling in prioritising the treatment of metastatic colorectal No. 13 and planning clinical trials. cancer: systematic review and economic A systematic review of atypical By Chilcott J, Brennan A, Booth A, evaluation. antipsychotics in schizophrenia. Karnon J, Tappenden P. By Ward S, Kaltenthaler E, Cowan J, By Bagnall A-M, Jones L, Lewis R, Brewer N. Ginnelly L, Glanville J, Torgerson D, No. 24 et al. Cost–benefit evaluation of routine No. 33 Clinical and cost-effectiveness of new influenza immunisation in people and emerging technologies for early No. 14 65–74 years of age. localised prostate cancer: a systematic Prostate Testing for Cancer and By Allsup S, Gosney M, Haycox A, Treatment (ProtecT) feasibility study. review. Regan M. By Donovan J, Hamdy F, Neal D, By Hummel S, Paisley S, Morgan A, Peters T, Oliver S, Brindle L, et al. Currie E, Brewer N. No. 25 The clinical and cost-effectiveness of No. 15 No. 34 Early thrombolysis for the treatment pulsatile machine perfusion versus cold Literature searching for clinical and of acute myocardial infarction: a storage of kidneys for transplantation cost-effectiveness studies used in health systematic review and economic retrieved from heart-beating and non- technology assessment reports carried evaluation. heart-beating donors. out for the National Institute for By Boland A, Dundar Y, Bagust A, By Wight J, Chilcott J, Holmes M, Clinical Excellence appraisal system. Haycox A, Hill R, Mujica Mota R, et al. Brewer N. By Royle P, Waugh N. 121

No. 35 No. 2 No. 11 Systematic review and economic Systematic review and modelling of the The use of modelling to evaluate decision modelling for the prevention investigation of acute and chronic chest new drugs for patients with a chronic and treatment of influenza A and B. pain presenting in primary care. condition: the case of antibodies By Turner D, Wailoo A, Nicholson K, By Mant J, McManus RJ, Oakes RAL, against tumour necrosis factor in Cooper N, Sutton A, Abrams K. Delaney BC, Barton PM, Deeks JJ, et al. rheumatoid arthritis. By Barton P, Jobanputra P, Wilson J, No. 36 No. 3 Bryan S, Burls A. A randomised controlled trial The effectiveness and cost-effectiveness No. 12 to evaluate the clinical and cost- of microwave and thermal balloon Clinical effectiveness and cost- effectiveness of Hickman line insertions endometrial ablation for heavy effectiveness of neonatal screening in adult cancer patients by nurses. menstrual bleeding: a systematic review for inborn errors of metabolism using By Boland A, Haycox A, Bagust A, and economic modelling. tandem mass spectrometry: a systematic Fitzsimmons L. By Garside R, Stein K, Wyatt K, review. Round A, Price A. By Pandor A, Eastham J, Beverley C, No. 37 Chilcott J, Paisley S. Redesigning postnatal care: a No. 4 randomised controlled trial of protocol- A systematic review of the role of No. 13 based midwifery-led care focused bisphosphonates in metastatic disease. Clinical effectiveness and cost- on individual women’s physical and By Ross JR, Saunders Y, effectiveness of pioglitazone and psychological health needs. Edmonds PM, Patel S, Wonderling D, rosiglitazone in the treatment of type By MacArthur C, Winter HR, Normand C, et al. 2 diabetes: a systematic review and Bick DE, Lilford RJ, Lancashire RJ, economic evaluation. Knowles H, et al. No. 5 By Czoski-Murray C, Warren E, Systematic review of the clinical Chilcott J, Beverley C, Psyllaki MA, No. 38 effectiveness and cost-effectiveness Cowan J. Estimating implied rates of discount in of capecitabine (Xeloda®) for locally No. 14 healthcare decision-making. advanced and/or metastatic breast Routine examination of the newborn: By West RR, McNabb R, Thompson cancer. the EMREN study. Evaluation of an AGH, Sheldon TA, Grimley Evans J. By Jones L, Hawkins N, Westwood M, extension of the midwife role including Wright K, Richardson G, Riemsma R. a randomised controlled trial of No. 39 appropriately trained midwives and Systematic review of isolation policies No. 6 paediatric senior house officers. in the hospital management of Effectiveness and efficiency of guideline By Townsend J, Wolke D, Hayes J, methicillin-resistant Staphylococcus dissemination and implementation Davé S, Rogers C, Bloomfield L, et al. aureus: a review of the literature strategies. with epidemiological and economic By Grimshaw JM, Thomas RE, No. 15 modelling. MacLennan G, Fraser C, Ramsay CR, Involving consumers in research and By Cooper BS, Stone SP, Kibbler CC, Vale L, et al. development agenda setting for the Cookson BD, Roberts JA, Medley GF, NHS: developing an evidence-based et al. No. 7 approach. Clinical effectiveness and costs of the By Oliver S, Clarke-Jones L, Rees R, No. 40 Sugarbaker procedure for the treatment Milne R, Buchanan P, Gabbay J, et al. Treatments for spasticity and pain in of pseudomyxoma peritonei. No. 16 multiple sclerosis: a systematic review. By Bryant J, Clegg AJ, Sidhu MK, A multi-centre randomised controlled By Beard S, Hunn A, Wight J. Brodin H, Royle P, Davidson P. trial of minimally invasive direct coronary bypass grafting versus No. 41 No. 8 percutaneous transluminal coronary The inclusion of reports of randomised Psychological treatment for insomnia angioplasty with stenting for proximal trials published in languages other than in the regulation of long-term hypnotic stenosis of the left anterior descending English in systematic reviews. drug use. coronary artery. By Moher D, Pham B, Lawson ML, By Morgan K, Dixon S, Mathers N, By Reeves BC, Angelini GD, Bryan Klassen TP. Thompson J, Tomeny M. AJ, Taylor FC, Cripps T, Spyt TJ, et al.

No. 42 No. 9 No. 17 The impact of screening on future Improving the evaluation of Does early magnetic resonance imaging health-promoting behaviours and therapeutic interventions in multiple influence management or improve health beliefs: a systematic review. sclerosis: development of a patient- outcome in patients referred to By Bankhead CR, Brett J, Bukach C, based measure of outcome. secondary care with low back pain? A Webster P, Stewart-Brown S, Munafo M, By Hobart JC, Riazi A, Lamping DL, pragmatic randomised controlled trial. et al. Fitzpatrick R, Thompson AJ. By Gilbert FJ, Grant AM, Gillan MGC, Vale L, Scott NW, Campbell MK, et al. No. 10 A systematic review and economic Volume 8, 2004 No. 18 evaluation of magnetic resonance The clinical and cost-effectiveness No. 1 cholangiopancreatography compared of anakinra for the treatment of What is the best imaging strategy for with diagnostic endoscopic retrograde rheumatoid arthritis in adults: a acute stroke? cholangiopancreatography. systematic review and economic By Wardlaw JM, Keir SL, Seymour J, By Kaltenthaler E, Bravo Vergel Y, analysis. Lewis S, Sandercock PAG, Dennis MS, Chilcott J, Thomas S, Blakeborough T, By Clark W, Jobanputra P, Barton P, 122 et al. Walters SJ, et al. Burls A. DOI: 10.3310/hta14120 Health Technology Assessment 2010; Vol. 14: No. 12

No. 19 No. 28 No. 37 A rapid and systematic review and Effectiveness and cost-effectiveness Rituximab (MabThera®) for aggressive economic evaluation of the clinical of imatinib for first-line treatment non-Hodgkin’s lymphoma: systematic and cost-effectiveness of newer drugs of chronic myeloid leukaemia in review and economic evaluation. for treatment of mania associated with chronic phase: a systematic review and By Knight C, Hind D, Brewer N, bipolar affective disorder. economic analysis. Abbott V. By Bridle C, Palmer S, Bagnall A-M, By Dalziel K, Round A, Stein K, Darba J, Duffy S, Sculpher M, et al. Garside R, Price A. No. 38 Clinical effectiveness and cost- No. 29 No. 20 effectiveness of clopidogrel and Liquid-based cytology in cervical VenUS I: a randomised controlled trial modified-release dipyridamole in the screening: an updated rapid and of two types of bandage for treating secondary prevention of occlusive systematic review and economic venous leg ulcers. vascular events: a systematic review and analysis. By Iglesias C, Nelson EA, Cullum By Karnon J, Peters J, Platt J, NA, Torgerson DJ, on behalf of the economic evaluation. Chilcott J, McGoogan E, Brewer N. VenUS Team. By Jones L, Griffin S, Palmer S, Main C, Orton V, Sculpher M, et al. No. 21 No. 30 Systematic review of the long-term Systematic review of the effectiveness No. 39 effects and economic consequences of and cost-effectiveness, and economic Pegylated interferon α-2a and -2b treatments for obesity and implications evaluation, of myocardial perfusion in combination with ribavirin in the for health improvement. scintigraphy for the diagnosis and treatment of chronic hepatitis C: By Avenell A, Broom J, Brown TJ, management of angina and myocardial a systematic review and economic Poobalan A, Aucott L, Stearns SC, et al. infarction. evaluation. By Mowatt G, Vale L, Brazzelli M, By Shepherd J, Brodin H, Cave C, Hernandez R, Murray A, Scott N, et al. No. 22 Waugh N, Price A, Gabbay J. Autoantibody testing in children No. 31 with newly diagnosed type 1 diabetes No. 40 A pilot study on the use of decision mellitus. Clopidogrel used in combination with By Dretzke J, Cummins C, theory and value of information analysis as part of the NHS Health aspirin compared with aspirin alone Sandercock J, Fry-Smith A, Barrett T, Technology Assessment programme. in the treatment of non-ST-segment- Burls A. By Claxton K, Ginnelly L, Sculpher elevation acute coronary syndromes: a systematic review and economic No. 23 M, Philips Z, Palmer S. evaluation. Clinical effectiveness and cost- No. 32 By Main C, Palmer S, Griffin S, Jones effectiveness of prehospital intravenous The Social Support and Family Health fluids in trauma patients. L, Orton V, Sculpher M, et al. Study: a randomised controlled trial By Dretzke J, Sandercock J, Bayliss and economic evaluation of two S, Burls A. No. 41 alternative forms of postnatal support Provision, uptake and cost of cardiac for mothers living in disadvantaged No. 24 rehabilitation programmes: improving inner-city areas. Newer hypnotic drugs for the short- services to under-represented groups. By Wiggins M, Oakley A, Roberts I, term management of insomnia: a By Beswick AD, Rees K, Griebsch I, Turner H, Rajan L, Austerberry H, et al. systematic review and economic Taylor FC, Burke M, West RR, et al. evaluation. No. 33 No. 42 By Dündar Y, Boland A, Strobl J, Psychosocial aspects of genetic Dodd S, Haycox A, Bagust A, et al. screening of pregnant women and Involving South Asian patients in newborns: a systematic review. clinical trials. No. 25 By Green JM, Hewison J, Bekker HL, By Hussain-Gambles M, Leese B, Development and validation of Bryant, Cuckle HS. Atkin K, Brown J, Mason S, Tovey P. methods for assessing the quality of diagnostic accuracy studies. No. 34 No. 43 By Whiting P, Rutjes AWS, Dinnes J, Evaluation of abnormal uterine Clinical and cost-effectiveness of Reitsma JB, Bossuyt PMM, Kleijnen J. bleeding: comparison of three continuous subcutaneous insulin outpatient procedures within cohorts infusion for diabetes. No. 26 defined by age and menopausal status. By Colquitt JL, Green C, Sidhu MK, EVALUATE hysterectomy trial: By Critchley HOD, Warner P, Lee AJ, Hartwell D, Waugh N. a multicentre randomised trial Brechin S, Guise J, Graham B. comparing abdominal, vaginal and No. 44 laparoscopic methods of hysterectomy. No. 35 Identification and assessment of By Garry R, Fountain J, Brown J, Coronary artery stents: a rapid ongoing trials in health technology Manca A, Mason S, Sculpher M, et al. systematic review and economic assessment reviews. evaluation. By Song FJ, Fry-Smith A, Davenport No. 27 By Hill R, Bagust A, Bakhai A, Methods for expected value of Dickson R, Dundar Y, Haycox A, et al. C, Bayliss S, Adi Y, Wilson JS, et al. information analysis in complex health economic models: developments on No. 36 No. 45 the health economics of interferon-β Review of guidelines for good practice Systematic review and economic and glatiramer acetate for multiple in decision-analytic modelling in health evaluation of a long-acting insulin sclerosis. technology assessment. analogue, insulin glargine By Tappenden P, Chilcott JB, By Philips Z, Ginnelly L, Sculpher M, By Warren E, Weatherley-Jones E, Eggington S, Oakley J, McCabe C. Claxton K, Golder S, Riemsma R, et al. Chilcott J, Beverley C. 123

No. 46 No. 4 No. 13 Supplementation of a home-based Randomised evaluation of alternative Cervical screening programmes: can exercise programme with a class- electrosurgical modalities to treat automation help? Evidence from based programme for people bladder outflow obstruction in men systematic reviews, an economic with osteoarthritis of the knees: a with benign prostatic hyperplasia. analysis and a simulation modelling randomised controlled trial and health By Fowler C, McAllister W, Plail R, exercise applied to the UK. By Willis BH, Barton P, Pearmain P, economic analysis. Karim O, Yang Q. Bryan S, Hyde C. By McCarthy CJ, Mills PM, Pullen R, No. 5 Richardson G, Hawkins N, Roberts CR, No. 14 A pragmatic randomised controlled et al. Laparoscopic surgery for inguinal trial of the cost-effectiveness of hernia repair: systematic review of No. 47 palliative therapies for patients with effectiveness and economic evaluation. Clinical and cost-effectiveness of once- inoperable oesophageal cancer. By McCormack K, Wake B, Perez J, daily versus more frequent use of same By Shenfine J, McNamee P, Steen N, Fraser C, Cook J, McIntosh E, et al. potency topical corticosteroids for Bond J, Griffin SM. atopic eczema: a systematic review and No. 15 economic evaluation. No. 6 Clinical effectiveness, tolerability and By Green C, Colquitt JL, Kirby J, Impact of computer-aided detection cost-effectiveness of newer drugs for Davidson P, Payne E. prompts on the sensitivity and epilepsy in adults: a systematic review specificity of screening mammography. and economic evaluation. No. 48 By Taylor P, Champness J, Given- By Wilby J, Kainth A, Hawkins N, Epstein D, McIntosh H, McDaid C, et al. Acupuncture of chronic headache Wilson R, Johnston K, Potts H. disorders in primary care: randomised No. 7 No. 16 controlled trial and economic analysis. A randomised controlled trial to By Vickers AJ, Rees RW, Zollman CE, Issues in data monitoring and interim analysis of trials. compare the cost-effectiveness of McCarney R, Smith CM, Ellis N, et al. tricyclic antidepressants, selective By Grant AM, Altman DG, Babiker serotonin reuptake inhibitors and AB, Campbell MK, Clemens FJ, No. 49 lofepramine. Generalisability in economic evaluation Darbyshire JH, et al. By Peveler R, Kendrick T, Buxton M, studies in healthcare: a review and case Longworth L, Baldwin D, Moore M, et al. studies. No. 8 By Sculpher MJ, Pang FS, Manca A, Lay public’s understanding of equipoise No. 17 and randomisation in randomised Drummond MF, Golder S, Urdahl H, Clinical effectiveness and cost- controlled trials. et al. effectiveness of immediate angioplasty By Robinson EJ, Kerr CEP, for acute myocardial infarction: No. 50 Stevens AJ, Lilford RJ, Braunholtz DA, systematic review and economic evaluation. Virtual outreach: a randomised Edwards SJ, et al. By Hartwell D, Colquitt J, Loveman controlled trial and economic No. 9 E, Clegg AJ, Brodin H, Waugh N, et al. evaluation of joint teleconferenced Clinical and cost-effectiveness of medical consultations. electroconvulsive therapy for depressive No. 18 By Wallace P, Barber J, Clayton W, illness, schizophrenia, catatonia A randomised controlled comparison of Currell R, Fleming K, Garner P, et al. and mania: systematic reviews and alternative strategies in stroke care. economic modelling studies. By Kalra L, Evans A, Perez I, Knapp M, Swift C, Donaldson N. By Greenhalgh J, Knight C, Hind D, Volume 9, 2005 Beverley C, Walters S. No. 19 The investigation and analysis of No. 1 No. 10 Randomised controlled multiple critical incidents and adverse events in Measurement of health-related quality healthcare. treatment comparison to provide a cost- of life for people with dementia: By Woloshynowych M, Rogers S, effectiveness rationale for the selection development of a new instrument Taylor-Adams S, Vincent C. of antimicrobial therapy in acne. (DEMQOL) and an evaluation of By Ozolins M, Eady EA, Avery A, current methodology. No. 20 Cunliffe WJ, O’Neill C, Simpson NB, By Smith SC, Lamping DL, Banerjee Potential use of routine databases in et al. S, Harwood R, Foley B, Smith P, et al. health technology assessment. By Raftery J, Roderick P, Stevens A. No. 2 No. 11 Do the findings of case series studies Clinical effectiveness and cost- No. 21 vary significantly according to effectiveness of drotrecogin alfa Clinical and cost-effectiveness of newer methodological characteristics? (activated) (Xigris®) for the treatment immunosuppressive regimens in renal By Dalziel K, Round A, Stein K, of severe sepsis in adults: a systematic transplantation: a systematic review and modelling study. Garside R, Castelnuovo E, Payne L. review and economic evaluation. By Woodroffe R, Yao GL, Meads C, By Green C, Dinnes J, Takeda A, Bayliss S, Ready A, Raftery J, et al. No. 3 Shepherd J, Hartwell D, Cave C, et al. Improving the referral process No. 22 for familial breast cancer genetic No. 12 A systematic review and economic counselling: findings of three A methodological review of how evaluation of alendronate, etidronate, randomised controlled trials of two heterogeneity has been examined in risedronate, raloxifene and teriparatide interventions. systematic reviews of diagnostic test for the prevention and treatment of By Wilson BJ, Torrance N, accuracy. postmenopausal osteoporosis. Mollison J, Wordsworth S, Gray JR, By Dinnes J, Deeks J, Kirby J, By Stevenson M, Lloyd Jones M, De 124 Haites NE, et al. Roderick P. Nigris E, Brewer N, Davis S, Oakley J. DOI: 10.3310/hta14120 Health Technology Assessment 2010; Vol. 14: No. 12

No. 23 No. 32 No. 40 A systematic review to examine Longer term clinical and economic A randomised controlled trial and the impact of psycho-educational benefits of offering acupuncture care to cost-effectiveness study of systematic interventions on health outcomes patients with chronic low back pain. screening (targeted and total and costs in adults and children with By Thomas KJ, MacPherson population screening) versus routine difficult asthma. H, Ratcliffe J, Thorpe L, Brazier J, practice for the detection of atrial By Smith JR, Mugford M, Holland Campbell M, et al. fibrillation in people aged 65 and over. R, Candy B, Noble MJ, Harrison BDW, The SAFE study. et al. No. 33 By Hobbs FDR, Fitzmaurice DA, Cost-effectiveness and safety of Mant J, Murray E, Jowett S, Bryan S, No. 24 epidural steroids in the management et al. An evaluation of the costs, effectiveness of sciatica. and quality of renal replacement No. 41 By Price C, Arden N, Coglan L, therapy provision in renal satellite units Displaced intracapsular hip fractures Rogers P. in England and Wales. in fit, older people: a randomised By Roderick P, Nicholson T, Armitage comparison of reduction and fixation, No. 34 A, Mehta R, Mullee M, Gerard K, et al. bipolar hemiarthroplasty and total hip The British Rheumatoid Outcome arthroplasty. No. 25 Study Group (BROSG) randomised By Keating JF, Grant A, Masson M, Imatinib for the treatment of patients controlled trial to compare the Scott NW, Forbes JF. with unresectable and/or metastatic effectiveness and cost-effectiveness of gastrointestinal stromal tumours: aggressive versus symptomatic therapy No. 42 systematic review and economic in established rheumatoid arthritis. Long-term outcome of cognitive evaluation. By Symmons D, Tricker K, Roberts behaviour therapy clinical trials in By Wilson J, Connock M, Song F, C, Davies L, Dawes P, Scott DL. central Scotland. Yao G, Fry-Smith A, Raftery J, et al. By Durham RC, Chambers JA, No. 35 Power KG, Sharp DM, Macdonald RR, No. 26 Conceptual framework and systematic Major KA, et al. Indirect comparisons of competing review of the effects of participants’ interventions. and professionals’ preferences in No. 43 By Glenny AM, Altman DG, Song F, randomised controlled trials. The effectiveness and cost-effectiveness Sakarovitch C, Deeks JJ, D’Amico R, By King M, Nazareth I, Lampe F, of dual-chamber pacemakers compared et al. Bower P, Chandler M, Morou M, et al. with single-chamber pacemakers for bradycardia due to atrioventricular No. 27 No. 36 block or sick sinus syndrome: systematic Cost-effectiveness of alternative review and economic evaluation. The clinical and cost-effectiveness of strategies for the initial medical By Castelnuovo E, Stein K, Pitt M, implantable cardioverter defibrillators: management of non-ST elevation acute Garside R, Payne E. a systematic review. coronary syndrome: systematic review and decision-analytical modelling. By Bryant J, Brodin H, Loveman E, No. 44 By Robinson M, Palmer S, Sculpher Payne E, Clegg A. Newborn screening for congenital heart M, Philips Z, Ginnelly L, Bowens A, et al. defects: a systematic review and cost- No. 37 effectiveness analysis. No. 28 A trial of problem-solving by By Knowles R, Griebsch I, Outcomes of electrically stimulated community mental health nurses for Dezateux C, Brown J, Bull C, Wren C. gracilis neosphincter surgery. anxiety, depression and life difficulties By Tillin T, Chambers M, Feldman R. among general practice patients. The No. 45 CPN-GP study. The clinical and cost-effectiveness of No. 29 By Kendrick T, Simons L, left ventricular assist devices for end- The effectiveness and cost-effectiveness Mynors-Wallis L, Gray A, Lathlean J, stage heart failure: a systematic review of pimecrolimus and tacrolimus for Pickering R, et al. and economic evaluation. atopic eczema: a systematic review and By Clegg AJ, Scott DA, Loveman E, economic evaluation. No. 38 Colquitt J, Hutchinson J, Royle P, et al. By Garside R, Stein K, Castelnuovo The causes and effects of socio- E, Pitt M, Ashcroft D, Dimmock P, et al. demographic exclusions from clinical No. 46 trials. The effectiveness of the Heidelberg No. 30 Retina Tomograph and laser diagnostic By Bartlett C, Doyal L, Ebrahim S, Systematic review on urine albumin glaucoma scanning system (GDx) in Davey P, Bachmann M, Egger M, et al. testing for early detection of diabetic detecting and monitoring glaucoma. complications. By Kwartz AJ, Henson DB, Harper No. 39 By Newman DJ, Mattock MB, RA, Spencer AF, McLeod D. Is hydrotherapy cost-effective? Dawnay ABS, Kerry S, McGuire A, A randomised controlled trial of Yaqoob M, et al. No. 47 combined hydrotherapy programmes Clinical and cost-effectiveness of No. 31 compared with physiotherapy land autologous chondrocyte implantation Randomised controlled trial of the cost- techniques in children with juvenile for cartilage defects in knee joints: effectiveness of water-based therapy for idiopathic arthritis. systematic review and economic lower limb osteoarthritis. By Epps H, Ginnelly L, Utley M, evaluation. By Cochrane T, Davey RC, Southwood T, Gallivan S, Sculpher M, By Clar C, Cummins E, McIntyre L, Matthes Edwards SM. et al. Thomas S, Lamb J, Bain L, et al. 125

No. 48 No. 6 No. 15 Systematic review of effectiveness of Systematic review and evaluation Measurement of the clinical and cost- different treatments for childhood of methods of assessing urinary effectiveness of non-invasive diagnostic retinoblastoma. incontinence. testing strategies for deep vein By McDaid C, Hartley S, Bagnall By Martin JL, Williams KS, Abrams thrombosis. A-M, Ritchie G, Light K, Riemsma R. KR, Turner DA, Sutton AJ, Chapple C, By Goodacre S, Sampson F, et al. Stevenson M, Wailoo A, Sutton A, No. 49 Thomas S, et al. Towards evidence-based guidelines No. 7 The clinical effectiveness and cost- for the prevention of venous No. 16 thromboembolism: systematic effectiveness of newer drugs for Systematic review of the effectiveness reviews of mechanical methods, oral children with epilepsy. A systematic and cost-effectiveness of HealOzone® anticoagulation, dextran and regional review. for the treatment of occlusal pit/fissure anaesthesia as thromboprophylaxis. By Connock M, Frew E, Evans B-W, By Roderick P, Ferris G, Wilson K, Bryan S, Cummins C, Fry-Smith A, et al. caries and root caries. Halls H, Jackson D, Collins R, et al. By Brazzelli M, McKenzie L, Fielding No. 8 S, Fraser C, Clarkson J, Kilonzo M, et al. No. 50 Surveillance of Barrett’s oesophagus: exploring the uncertainty through The effectiveness and cost-effectiveness No. 17 systematic review, expert workshop and of parent training/education Randomised controlled trials of economic modelling. programmes for the treatment conventional antipsychotic versus By Garside R, Pitt M, Somerville M, of conduct disorder, including new atypical drugs, and new atypical Stein K, Price A, Gilbert N. oppositional defiant disorder, in drugs versus clozapine, in people with children. No. 9 schizophrenia responding poorly to, or By Dretzke J, Frew E, Davenport C, Topotecan, pegylated liposomal intolerant of, current drug treatment. Barlow J, Stewart-Brown S, Sandercock J, doxorubicin hydrochloride and By Lewis SW, Davies L, Jones PB, et al. paclitaxel for second-line or subsequent Barnes TRE, Murray RM, Kerwin R, treatment of advanced ovarian cancer: et al. a systematic review and economic Volume 10, 2006 evaluation. No. 18 By Main C, Bojke L, Griffin S, Diagnostic tests and algorithms used No. 1 Norman G, Barbieri M, Mather L, et al. in the investigation of haematuria: The clinical and cost-effectiveness of systematic reviews and economic donepezil, rivastigmine, galantamine No. 10 evaluation. Evaluation of molecular techniques and memantine for Alzheimer’s By Rodgers M, Nixon J, Hempel S, disease. in prediction and diagnosis Aho T, Kelly J, Neal D, et al. By Loveman E, Green C, Kirby J, of cytomegalovirus disease in Takeda A, Picot J, Payne E, et al. immunocompromised patients. By Szczepura A, Westmoreland D, No. 19 Cognitive behavioural therapy in No. 2 Vinogradova Y, Fox J, Clark M. FOOD: a multicentre randomised trial addition to antispasmodic therapy for evaluating feeding policies in patients No. 11 irritable bowel syndrome in primary admitted to hospital with a recent Screening for thrombophilia in high- care: randomised controlled trial. stroke. risk situations: systematic review By Kennedy TM, Chalder T, By Dennis M, Lewis S, Cranswick G, and cost-effectiveness analysis. The McCrone P, Darnley S, Knapp M, Forbes J. Thrombosis: Risk and Economic Jones RH, et al. Assessment of Thrombophilia No. 3 Screening (TREATS) study. No. 20 The clinical effectiveness and cost- By Wu O, Robertson L, Twaddle S, A systematic review of the Lowe GDO, Clark P, Greaves M, et al. effectiveness of computed tomography clinical effectiveness and cost- screening for lung cancer: systematic effectiveness of enzyme replacement No. 12 reviews. A series of systematic reviews to inform therapies for Fabry’s disease and By Black C, Bagust A, Boland A, a decision analysis for sampling and mucopolysaccharidosis type 1. Walker S, McLeod C, De Verteuil R, et al. treating infected diabetic foot ulcers. By Connock M, Juarez-Garcia A, By Nelson EA, O’Meara S, Craig D, Frew E, Mans A, Dretzke J, Fry-Smith A, No. 4 Iglesias C, Golder S, Dalton J, et al. et al. A systematic review of the effectiveness and cost-effectiveness of neuroimaging No. 13 No. 21 assessments used to visualise the seizure Randomised clinical trial, observational Health benefits of antiviral therapy for focus in people with refractory epilepsy study and assessment of cost- mild chronic hepatitis C: randomised being considered for surgery. effectiveness of the treatment of controlled trial and economic By Whiting P, Gupta R, Burch J, varicose veins (REACTIV trial). evaluation. Mujica Mota RE, Wright K, Marson A, By Michaels JA, Campbell WB, By Wright M, Grieve R, Roberts J, et al. Brazier JE, MacIntyre JB, Palfreyman SJ, Main J, Thomas HC, on behalf of the Ratcliffe J, et al. No. 5 UK Mild Hepatitis C Trial Investigators. Comparison of conference abstracts No. 14 and presentations with full-text articles The cost-effectiveness of screening for No. 22 in the health technology assessments of oral cancer in primary care. Pressure relieving support surfaces: a rapidly evolving technologies. By Speight PM, Palmer S, Moles DR, randomised evaluation. By Dundar Y, Dodd S, Dickson R, Downer MC, Smith DH, Henriksson M, By Nixon J, Nelson EA, Cranny G, 126 Walley T, Haycox A, Williamson PR. et al. Iglesias CP, Hawkins K, Cullum NA, et al. DOI: 10.3310/hta14120 Health Technology Assessment 2010; Vol. 14: No. 12

No. 23 No. 31 No. 40 A systematic review and economic Etanercept and infliximab for the What are the clinical outcome and cost- model of the effectiveness and cost- treatment of psoriatic arthritis: a effectiveness of endoscopy undertaken effectiveness of methylphenidate, systematic review and economic by nurses when compared with doctors? dexamfetamine and atomoxetine evaluation. A Multi-Institution Nurse Endoscopy for the treatment of attention deficit By Woolacott N, Bravo Vergel Y, Trial (MINuET). Hawkins N, Kainth A, Khadjesari Z, hyperactivity disorder in children and By Williams J, Russell I, Durai D, Misso K, et al. adolescents. Cheung W-Y, Farrin A, Bloor K, et al. By King S, Griffin S, Hodges Z, No. 32 Weatherly H, Asseburg C, Richardson G, No. 41 et al. The cost-effectiveness of testing for hepatitis C in former injecting drug The clinical and cost-effectiveness of oxaliplatin and capecitabine for the No. 24 users. adjuvant treatment of colon cancer: The clinical effectiveness and cost- By Castelnuovo E, Thompson-Coon systematic review and economic effectiveness of enzyme replacement J, Pitt M, Cramp M, Siebert U, Price A, et al. therapy for Gaucher’s disease: a evaluation. systematic review. By Pandor A, Eggington S, Paisley S, No. 33 By Connock M, Burls A, Frew E, Tappenden P, Sutcliffe P. Computerised cognitive behaviour Fry-Smith A, Juarez-Garcia A, McCabe C, therapy for depression and anxiety et al. No. 42 update: a systematic review and A systematic review of the effectiveness economic evaluation. of adalimumab, etanercept and No. 25 By Kaltenthaler E, Brazier J, infliximab for the treatment of Effectiveness and cost-effectiveness De Nigris E, Tumur I, Ferriter M, of salicylic acid and cryotherapy for Beverley C, et al. rheumatoid arthritis in adults and cutaneous warts. An economic decision an economic evaluation of their cost- model. No. 34 effectiveness. By Thomas KS, Keogh-Brown MR, Cost-effectiveness of using prognostic By Chen Y-F, Jobanputra P, Barton P, Chalmers JR, Fordham RJ, Holland RC, information to select women with breast Jowett S, Bryan S, Clark W, et al. Armstrong SJ, et al. cancer for adjuvant systemic therapy. By Williams C, Brunskill S, Altman D, No. 43 No. 26 Briggs A, Campbell H, Clarke M, et al. Telemedicine in dermatology: a A systematic literature review of the randomised controlled trial. effectiveness of non-pharmacological No. 35 By Bowns IR, Collins K, Walters SJ, interventions to prevent wandering in Psychological therapies including McDonagh AJG. dementia and evaluation of the ethical dialectical behaviour therapy for implications and acceptability of their borderline personality disorder: a No. 44 use. systematic review and preliminary Cost-effectiveness of cell salvage and By Robinson L, Hutchings D, Corner economic evaluation. alternative methods of minimising L, Beyer F, Dickinson H, Vanoli A, et al. By Brazier J, Tumur I, Holmes M, Ferriter M, Parry G, Dent-Brown K, et al. perioperative allogeneic blood No. 27 transfusion: a systematic review and A review of the evidence on the effects No. 36 economic model. and costs of implantable cardioverter Clinical effectiveness and cost- By Davies L, Brown TJ, Haynes S, defibrillator therapy in different effectiveness of tests for the diagnosis Payne K, Elliott RA, McCollum C. patient groups, and modelling of cost- and investigation of urinary tract effectiveness and cost–utility for these infection in children: a systematic No. 45 groups in a UK context. review and economic model. Clinical effectiveness and cost- By Buxton M, Caine N, Chase D, By Whiting P, Westwood M, Bojke L, effectiveness of laparoscopic surgery Connelly D, Grace A, Jackson C, et al. Palmer S, Richardson G, Cooper J, et al. for colorectal cancer: systematic reviews and economic evaluation. No. 37 No. 28 By Murray A, Lourenco T, de Verteuil Cognitive behavioural therapy Adefovir dipivoxil and pegylated R, Hernandez R, Fraser C, McKinley A, in chronic fatigue syndrome: a interferon alfa-2a for the treatment of randomised controlled trial of an et al. chronic hepatitis B: a systematic review outpatient group programme. and economic evaluation. By O’Dowd H, Gladwell P, Rogers No. 46 By Shepherd J, Jones J, Takeda A, CA, Hollinghurst S, Gregory A. Etanercept and efalizumab for the Davidson P, Price A. treatment of psoriasis: a systematic No. 38 review. No. 29 A comparison of the cost-effectiveness By Woolacott N, Hawkins N, An evaluation of the clinical and cost- of five strategies for the prevention Mason A, Kainth A, Khadjesari Z, Bravo effectiveness of pulmonary artery of nonsteroidal anti-inflammatory Vergel Y, et al. catheters in patient management in drug-induced gastrointestinal toxicity: intensive care: a systematic review and a a systematic review with economic No. 47 randomised controlled trial. modelling. By Harvey S, Stevens K, Harrison D, Systematic reviews of clinical decision By Brown TJ, Hooper L, Elliott RA, tools for acute abdominal pain. Young D, Brampton W, McCabe C, et al. Payne K, Webb R, Roberts C, et al. By Liu JLY, Wyatt JC, Deeks JJ, No. 30 No. 39 Clamp S, Keen J, Verde P, et al. Accurate, practical and cost-effective The effectiveness and cost-effectiveness assessment of carotid stenosis in the of computed tomography screening No. 48 UK. for coronary artery disease: systematic Evaluation of the ventricular assist By Wardlaw JM, Chappell FM, review. device programme in the UK. Stevenson M, De Nigris E, Thomas S, By Waugh N, Black C, Walker S, By Sharples L, Buxton M, Caine N, Gillard J, et al. McIntyre L, Cummins E, Hillis G. Cafferty F, Demiris N, Dyer M, et al. 127

No. 49 No. 7 No. 16 A systematic review and economic Glucocorticoid-induced osteoporosis: Additional therapy for young model of the clinical and cost- a systematic review and cost–utility children with spastic cerebral palsy: a analysis. effectiveness of immunosuppressive randomised controlled trial. By Kanis JA, Stevenson M, therapy for renal transplantation in McCloskey EV, Davis S, Lloyd-Jones M. By Weindling AM, Cunningham CC, children. Glenn SM, Edwards RT, Reeves DJ. By Yao G, Albon E, Adi Y, Milford D, No. 8 Bayliss S, Ready A, et al. Epidemiological, social, diagnostic and No. 17 economic evaluation of population Screening for type 2 diabetes: literature No. 50 screening for genital chlamydial review and economic modelling. Amniocentesis results: investigation of infection. By Waugh N, Scotland G, McNamee By Low N, McCarthy A, Macleod J, anxiety. The ARIA trial. P, Gillett M, Brennan A, Goyder E, et al. By Hewison J, Nixon J, Fountain J, Salisbury C, Campbell R, Roberts TE, et al. Cocks K, Jones C, Mason G, et al. No. 18 No. 9 The effectiveness and cost-effectiveness Methadone and buprenorphine for the of cinacalcet for secondary Volume 11, 2007 management of opioid dependence: hyperparathyroidism in end-stage renal a systematic review and economic disease patients on dialysis: a systematic No. 1 evaluation. review and economic evaluation. Pemetrexed disodium for the treatment By Connock M, Juarez-Garcia A, By Garside R, Pitt M, Anderson R, of malignant pleural mesothelioma: Jowett S, Frew E, Liu Z, Taylor RJ, et al. Mealing S, Roome C, Snaith A, et al. a systematic review and economic evaluation. No. 10 Exercise Evaluation Randomised No. 19 By Dundar Y, Bagust A, Dickson R, Trial (EXERT): a randomised trial The clinical effectiveness and cost- Dodd S, Green J, Haycox A, et al. comparing GP referral for leisure effectiveness of gemcitabine for centre-based exercise, community-based metastatic breast cancer: a systematic No. 2 walking and advice only. review and economic evaluation. A systematic review and economic By Isaacs AJ, Critchley JA, See Tai model of the clinical effectiveness S, Buckingham K, Westley D, Harridge By Takeda AL, Jones J, Loveman E, and cost-effectiveness of docetaxel SDR, et al. Tan SC, Clegg AJ. in combination with prednisone or prednisolone for the treatment of No. 11 No. 20 hormone-refractory metastatic prostate Interferon alfa (pegylated and non- A systematic review of duplex pegylated) and ribavirin for the cancer. ultrasound, magnetic resonance treatment of mild chronic hepatitis angiography and computed By Collins R, Fenwick E, Trowman R, C: a systematic review and economic Perard R, Norman G, Light K, et al. evaluation. tomography angiography for By Shepherd J, Jones J, Hartwell D, the diagnosis and assessment of No. 3 Davidson P, Price A, Waugh N. symptomatic, lower limb peripheral A systematic review of rapid diagnostic arterial disease. tests for the detection of tuberculosis No. 12 By Collins R, Cranny G, Burch J, infection. Systematic review and economic Aguiar-Ibáñez R, Craig D, Wright K, evaluation of bevacizumab and By Dinnes J, Deeks J, Kunst H, et al. Gibson A, Cummins E, Waugh N, et al. cetuximab for the treatment of metastatic colorectal cancer. By Tappenden P, Jones R, Paisley S, No. 21 No. 4 Carroll C. The clinical effectiveness and cost- The clinical effectiveness and cost- effectiveness of treatments for children effectiveness of strontium ranelate for No. 13 with idiopathic steroid-resistant the prevention of osteoporotic fragility A systematic review and economic nephrotic syndrome: a systematic fractures in postmenopausal women. evaluation of epoetin alfa, epoetin review. By Stevenson M, Davis S, Lloyd-Jones beta and darbepoetin alfa in anaemia By Colquitt JL, Kirby J, Green C, M, Beverley C. associated with cancer, especially that attributable to cancer treatment. Cooper K, Trompeter RS. No. 5 By Wilson J, Yao GL, Raftery J, No. 22 A systematic review of quantitative and Bohlius J, Brunskill S, Sandercock J, et al. A systematic review of the routine qualitative research on the role and monitoring of growth in children of effectiveness of written information No. 14 primary school age to identify growth- available to patients about individual A systematic review and economic related conditions. medicines. evaluation of statins for the prevention By Raynor DK, Blenkinsopp of coronary events. By Fayter D, Nixon J, Hartley S, A, Knapp P, Grime J, Nicolson DJ, By Ward S, Lloyd Jones M, Pandor A, Rithalia A, Butler G, Rudolf M, et al. Pollock K, et al. Holmes M, Ara R, Ryan A, et al. No. 23 No. 6 No. 15 Systematic review of the effectiveness of A systematic review of the effectiveness Oral naltrexone as a treatment for preventing and treating Staphylococcus and cost-effectiveness of different aureus carriage in reducing peritoneal relapse prevention in formerly opioid- models of community-based respite dependent drug users: a systematic care for frail older people and their catheter-related infections. review and economic evaluation. carers. By McCormack K, Rabindranath K, By Adi Y, Juarez-Garcia A, Wang D, By Mason A, Weatherly H, Spilsbury Kilonzo M, Vale L, Fraser C, McIntyre L, 128 Jowett S, Frew E, Day E, et al. K, Arksey H, Golder S, Adamson J, et al. et al. DOI: 10.3310/hta14120 Health Technology Assessment 2010; Vol. 14: No. 12

No. 24 No. 32 No. 40 The clinical effectiveness and cost Current practice, accuracy, effectiveness Taxanes for the adjuvant treatment of of repetitive transcranial magnetic and cost-effectiveness of the school early breast cancer: systematic review stimulation versus electroconvulsive entry hearing screen. and economic evaluation. therapy in severe depression: a By Bamford J, Fortnum H, Bristow By Ward S, Simpson E, Davis S, Hind multicentre pragmatic randomised K, Smith J, Vamvakas G, Davies L, et al. D, Rees A, Wilkinson A. controlled trial and economic analysis. By McLoughlin DM, Mogg A, Eranti No. 33 No. 41 S, Pluck G, Purvis R, Edwards D, et al. The clinical effectiveness and cost- The clinical effectiveness and cost- effectiveness of inhaled insulin in effectiveness of screening for open No. 25 diabetes mellitus: a systematic review angle glaucoma: a systematic review A randomised controlled trial and and economic evaluation. and economic evaluation. economic evaluation of direct versus By Black C, Cummins E, Royle P, By Burr JM, Mowatt G, Hernández indirect and individual versus group Philip S, Waugh N. R, Siddiqui MAR, Cook J, Lourenco T, modes of speech and language therapy et al. for children with primary language No. 34 impairment. Surveillance of cirrhosis for No. 42 By Boyle J, McCartney E, Forbes J, hepatocellular carcinoma: systematic Acceptability, benefit and costs of early O’Hare A. review and economic analysis. screening for hearing disability: a study By Thompson Coon J, Rogers G, of potential screening tests and models. No. 26 Hewson P, Wright D, Anderson R, By Davis A, Smith P, Ferguson M, Hormonal therapies for early breast Cramp M, et al. Stephens D, Gianopoulos I. cancer: systematic review and economic evaluation. No. 35 No. 43 By Hind D, Ward S, De Nigris E, The Birmingham Rehabilitation Contamination in trials of educational Uptake Maximisation Study (BRUM). Simpson E, Carroll C, Wyld L. interventions. Homebased compared with hospital- By Keogh-Brown MR, Bachmann No. 27 based cardiac rehabilitation in a multi- MO, Shepstone L, Hewitt C, Howe A, Cardioprotection against the toxic ethnic population: cost-effectiveness Ramsay CR, et al. effects of anthracyclines given to and patient adherence. children with cancer: a systematic By Jolly K, Taylor R, Lip GYH, No. 44 review. Greenfield S, Raftery J, Mant J, et al. Overview of the clinical effectiveness of By Bryant J, Picot J, Levitt G, positron emission tomography imaging Sullivan I, Baxter L, Clegg A. No. 36 in selected cancers. A systematic review of the clinical, By Facey K, Bradbury I, Laking G, No. 28 public health and cost-effectiveness of Payne E. Adalimumab, etanercept and infliximab rapid diagnostic tests for the detection for the treatment of ankylosing and identification of bacterial intestinal No. 45 spondylitis: a systematic review and pathogens in faeces and food. The effectiveness and cost-effectiveness economic evaluation. By Abubakar I, Irvine L, Aldus CF, of carmustine implants and By McLeod C, Bagust A, Boland A, Wyatt GM, Fordham R, Schelenz S, et al. temozolomide for the treatment of Dagenais P, Dickson R, Dundar Y, et al. No. 37 newly diagnosed high-grade glioma: No. 29 A randomised controlled trial a systematic review and economic Prenatal screening and treatment examining the longer-term outcomes evaluation. strategies to prevent group B of standard versus new antiepileptic By Garside R, Pitt M, Anderson R, streptococcal and other bacterial drugs. The SANAD trial. Rogers G, Dyer M, Mealing S, et al. infections in early infancy: cost- By Marson AG, Appleton R, Baker effectiveness and expected value of GA, Chadwick DW, Doughty J, Eaton B, No. 46 information analyses. et al. Drug-eluting stents: a systematic review By Colbourn T, Asseburg C, Bojke L, and economic evaluation. Philips Z, Claxton K, Ades AE, et al. No. 38 By Hill RA, Boland A, Dickson R, Clinical effectiveness and cost- Dundar Y, Haycox A, McLeod C, et al. No. 30 effectiveness of different models Clinical effectiveness and cost- of managing long-term oral anti- No. 47 effectiveness of bone morphogenetic coagulation therapy: a systematic The clinical effectiveness and proteins in the non-healing of fractures review and economic modelling. cost-effectiveness of cardiac and spinal fusion: a systematic review. By Connock M, Stevens C, Fry-Smith resynchronisation (biventricular pacing) By Garrison KR, Donell S, Ryder J, A, Jowett S, Fitzmaurice D, Moore D, for heart failure: systematic review and Shemilt I, Mugford M, Harvey I, et al. et al. economic model. By Fox M, Mealing S, Anderson R, No. 31 No. 39 Dean J, Stein K, Price A, et al. A randomised controlled trial of A systematic review and economic postoperative radiotherapy following model of the clinical effectiveness No. 48 breast-conserving surgery in a and cost-effectiveness of interventions Recruitment to randomised trials: minimum-risk older population. The for preventing relapse in people with strategies for trial enrolment and PRIME trial. bipolar disorder. participation study. The STEPS study. By Prescott RJ, Kunkler IH, Williams By Soares-Weiser K, Bravo Vergel Y, By Campbell MK, Snowdon C, LJ, King CC, Jack W, van der Pol M, Beynon S, Dunn G, Barbieri M, Duffy S, Francis D, Elbourne D, McDonald AM, et al. et al. Knight R, et al. 129

No. 49 No. 4 No. 12 Cost-effectiveness of functional Does befriending by trained lay workers The clinical effectiveness and cost- cardiac testing in the diagnosis and improve psychological well-being and effectiveness of central venous catheters management of coronary artery quality of life for carers of people treated with anti-infective agents in disease: a randomised controlled trial. with dementia, and at what cost? A preventing bloodstream infections: The CECaT trial. randomised controlled trial. a systematic review and economic By Sharples L, Hughes V, Crean A, By Charlesworth G, Shepstone L, evaluation. Dyer M, Buxton M, Goldsmith K, et al. Wilson E, Thalanany M, Mugford M, By Hockenhull JC, Dwan K, Boland Poland F. A, Smith G, Bagust A, Dundar Y, et al. No. 50 No. 13 Evaluation of diagnostic tests when No. 5 Stepped treatment of older adults on there is no gold standard. A review of A multi-centre retrospective cohort laxatives. The STOOL trial. methods. study comparing the efficacy, safety By Mihaylov S, Stark C, McColl E, By Rutjes AWS, Reitsma and cost-effectiveness of hysterectomy Steen N, Vanoli A, Rubin G, et al. JB, Coomarasamy A, Khan KS, and uterine artery embolisation for Bossuyt PMM. the treatment of symptomatic uterine No. 14 fibroids. The HOPEFUL study. A randomised controlled trial of No. 51 By Hirst A, Dutton S, Wu O, Briggs cognitive behaviour therapy in Systematic reviews of the clinical A, Edwards C, Waldenmaier L, et al. adolescents with major depression effectiveness and cost-effectiveness of treated by selective serotonin reuptake proton pump inhibitors in acute upper No. 6 inhibitors. The ADAPT trial. gastrointestinal bleeding. Methods of prediction and prevention By Goodyer IM, Dubicka B, By Leontiadis GI, Sreedharan of pre-eclampsia: systematic reviews of Wilkinson P, Kelvin R, Roberts C, A, Dorward S, Barton P, Delaney B, accuracy and effectiveness literature Byford S, et al. Howden CW, et al. with economic modelling. By Meads CA, Cnossen JS, Meher S, No. 15 No. 52 Juarez-Garcia A, ter Riet G, Duley L, The use of irinotecan, oxaliplatin A review and critique of modelling in et al. and raltitrexed for the treatment of prioritising and designing screening advanced colorectal cancer: systematic programmes. No. 7 review and economic evaluation. By Karnon J, Goyder E, Tappenden The use of economic evaluations in By Hind D, Tappenden P, Tumur I, P, McPhie S, Towers I, Brazier J, et al. NHS decision-making: a review and Eggington E, Sutcliffe P, Ryan A. empirical investigation. No. 16 No. 53 By Williams I, McIver S, Moore D, Ranibizumab and pegaptanib for An assessment of the impact of the Bryan S. the treatment of age-related macular NHS Health Technology Assessment degeneration: a systematic review and Programme. No. 8 economic evaluation. By Hanney S, Buxton M, Green C, Stapled haemorrhoidectomy By Colquitt JL, Jones J, Tan SC, Coulson D, Raftery J. (haemorrhoidopexy) for the treatment Takeda A, Clegg AJ, Price A. of haemorrhoids: a systematic review and economic evaluation. No. 17 Volume 12, 2008 By Burch J, Epstein D, Baba-Akbari Systematic review of the clinical A, Weatherly H, Fox D, Golder S, et al. effectiveness and cost-effectiveness No. 1 of 64-slice or higher computed A systematic review and economic No. 9 tomography angiography as an model of switching from The clinical effectiveness of diabetes alternative to invasive coronary nonglycopeptide to glycopeptide education models for Type 2 diabetes: a angiography in the investigation of antibiotic prophylaxis for surgery. systematic review. coronary artery disease. By Cranny G, Elliott R, Weatherly H, By Loveman E, Frampton GK, By Mowatt G, Cummins E, Waugh N, Chambers D, Hawkins N, Myers L, et al. Clegg AJ. Walker S, Cook J, Jia X, et al.

No. 2 No. 10 No. 18 ‘Cut down to quit’ with nicotine Payment to healthcare professionals for Structural neuroimaging in psychosis: replacement therapies in smoking patient recruitment to trials: systematic a systematic review and economic cessation: a systematic review of review and qualitative study. evaluation. By Albon E, Tsourapas A, Frew E, effectiveness and economic analysis. By Raftery J, Bryant J, Powell J, Davenport C, Oyebode F, Bayliss S, et al. By Wang D, Connock M, Barton P, Kerr C, Hawker S. Fry-Smith A, Aveyard P, Moore D. No. 19 No. 11 Systematic review and economic No. 3 Cyclooxygenase-2 selective non- analysis of the comparative A systematic review of the effectiveness steroidal anti-inflammatory drugs effectiveness of different inhaled of strategies for reducing fracture risk (etodolac, meloxicam, celecoxib, corticosteroids and their usage with in children with juvenile idiopathic rofecoxib, etoricoxib, valdecoxib and long-acting beta2 agonists for the arthritis with additional data on long- lumiracoxib) for osteoarthritis and treatment of chronic asthma in adults term risk of fracture and cost of disease rheumatoid arthritis: a systematic and children aged 12 years and over. management. review and economic evaluation. By Shepherd J, Rogers G, Anderson By Thornton J, Ashcroft D, O’Neill T, By Chen Y-F, Jobanputra P, Barton P, R, Main C, Thompson-Coon J, 130 Elliott R, Adams J, Roberts C, et al. Bryan S, Fry-Smith A, Harris G, et al. Hartwell D, et al. DOI: 10.3310/hta14120 Health Technology Assessment 2010; Vol. 14: No. 12

No. 20 No. 28 Volume 13, 2009 Systematic review and economic Intravenous magnesium sulphate analysis of the comparative and sotalol for prevention of atrial No. 1 effectiveness of different inhaled fibrillation after coronary artery Deferasirox for the treatment of iron corticosteroids and their usage with bypass surgery: a systematic review and overload associated with regular blood transfusions (transfusional long-acting beta agonists for the economic evaluation. 2 haemosiderosis) in patients suffering treatment of chronic asthma in children By Shepherd J, Jones J, Frampton GK, Tanajewski L, Turner D, Price A. with chronic anaemia: a systematic under the age of 12 years. review and economic evaluation. By Main C, Shepherd J, Anderson R, No. 29 By McLeod C, Fleeman N, Kirkham Rogers G, Thompson-Coon J, Liu Z, J, Bagust A, Boland A, Chu P, et al. Absorbent products for urinary/faecal et al. incontinence: a comparative evaluation No. 2 of key product categories. No. 21 Thrombophilia testing in people with By Fader M, Cottenden A, Getliffe K, Ezetimibe for the treatment of venous thromboembolism: systematic Gage H, Clarke-O’Neill S, Jamieson K, hypercholesterolaemia: a systematic review and cost-effectiveness analysis. et al. By Simpson EL, Stevenson MD, review and economic evaluation. Rawdin A, Papaioannou D. By Ara R, Tumur I, Pandor A, No. 30 Duenas A, Williams R, Wilkinson A, et al. A systematic review of repetitive No. 3 functional task practice with modelling Surgical procedures and non-surgical No. 22 of resource use, costs and effectiveness. devices for the management of non- Topical or oral ibuprofen for chronic By French B, Leathley M, Sutton C, apnoeic snoring: a systematic review of knee pain in older people. The TOIB McAdam J, Thomas L, Forster A, et al. clinical effects and associated treatment study. costs. By Underwood M, Ashby D, Carnes No. 31 By Main C, Liu Z, Welch K, Weiner D, Castelnuovo E, Cross P, Harding G, The effectiveness and cost-effectivness G, Quentin Jones S, Stein K. et al. of minimal access surgery amongst people with gastro-oesophageal reflux No. 4 Continuous positive airway pressure No. 23 disease – a UK collaborative study. The devices for the treatment of obstructive reflux trial. A prospective randomised comparison sleep apnoea–hypopnoea syndrome: a By Grant A, Wileman S, Ramsay C, of minor surgery in primary and systematic review and economic analysis. Bojke L, Epstein D, Sculpher M, et al. secondary care. The MiSTIC trial. By McDaid C, Griffin S, Weatherly H, By George S, Pockney P, Primrose J, Durée K, van der Burgt M, van Hout S, No. 32 Smith H, Little P, Kinley H, et al. Akers J, et al. Time to full publication of studies of anti-cancer medicines for breast cancer No. 24 No. 5 and the potential for publication bias: a A review and critical appraisal Use of classical and novel biomarkers short systematic review. of measures of therapist–patient as prognostic risk factors for localised By Takeda A, Loveman E, Harris P, prostate cancer: a systematic review. interactions in mental health settings. Hartwell D, Welch K. By Sutcliffe P, Hummel S, Simpson E, By Cahill J, Barkham M, Hardy G, Young T, Rees A, Wilkinson A, et al. Gilbody S, Richards D, Bower P, et al. No. 33 Performance of screening tests for No. 6 No. 25 child physical abuse in accident and The harmful health effects of The clinical effectiveness and cost- emergency departments. recreational ecstasy: a systematic review effectiveness of screening programmes By Woodman J, Pitt M, Wentz R, of observational evidence. for amblyopia and strabismus in Taylor B, Hodes D, Gilbert RE. By Rogers G, Elston J, Garside R, children up to the age of 4–5 years: Roome C, Taylor R, Younger P, et al. a systematic review and economic No. 34 No. 7 evaluation. Curative catheter ablation in atrial Systematic review of the clinical fibrillation and typical atrial flutter: By Carlton J, Karnon J, Czoski- effectiveness and cost-effectiveness systematic review and economic Murray C, Smith KJ, Marr J. of oesophageal Doppler monitoring evaluation. in critically ill and high-risk surgical No. 26 By Rodgers M, McKenna C, Palmer patients. A systematic review of the clinical S, Chambers D, Van Hout S, Golder S, By Mowatt G, Houston G, Hernández effectiveness and cost-effectiveness et al. R, de Verteuil R, Fraser C, Cuthbertson and economic modelling of minimal B, et al. No. 35 incision total hip replacement Systematic review and economic approaches in the management of No. 8 modelling of effectiveness and cost The use of surrogate outcomes in arthritic disease of the hip. utility of surgical treatments for men model-based cost-effectiveness analyses: By de Verteuil R, Imamura M, Zhu S, with benign prostatic enlargement. a survey of UK Health Technology Glazener C, Fraser C, Munro N, et al. By Lourenco T, Armstrong N, N’Dow Assessment reports. J, Nabi G, Deverill M, Pickard R, et al. By Taylor RS, Elston J. No. 27 A preliminary model-based assessment No. 36 No. 9 of the cost–utility of a screening Immunoprophylaxis against respiratory Controlling Hypertension and programme for early age-related syncytial virus (RSV) with palivizumab Hypotension Immediately Post Stroke macular degeneration. in children: a systematic review and (CHHIPS) – a randomised controlled By Karnon J, Czoski-Murray C, economic evaluation. trial. By Potter J, Mistri A, Brodie F, Smith K, Brand C, Chakravarthy U, By Wang D, Cummins C, Bayliss S, Chernova J, Wilson E, Jagger C, et al. Davis S, et al. Sandercock J, Burls A. 131

No. 10 No. 19 No. 27 Routine antenatal anti-D prophylaxis Dipsticks and diagnostic algorithms in Paracetamol and ibuprofen for the for RhD-negative women: a systematic urinary tract infection: development treatment of fever in children: the review and economic evaluation. and validation, randomised trial, PITCH randomised controlled trial. By Pilgrim H, Lloyd-Jones M, Rees A. economic analysis, observational cohort By Hay AD, Redmond NM, Costelloe and qualitative study. C, Montgomery AA, Fletcher M, No. 11 By Little P, Turner S, Rumsby K, Hollinghurst S, et al. Amantadine, oseltamivir and zanamivir Warner G, Moore M, Lowes JA, et al. for the prophylaxis of influenza No. 28 (including a review of existing guidance No. 20 A randomised controlled trial to no. 67): a systematic review and Systematic review of respite care in the compare minimally invasive glucose economic evaluation. frail elderly. monitoring devices with conventional By Tappenden P, Jackson R, Cooper By Shaw C, McNamara R, Abrams monitoring in the management of K, Rees A, Simpson E, Read R, et al. K, Cannings-John R, Hood K, Longo insulin-treated diabetes mellitus M, et al. (MITRE). No. 12 By Newman SP, Cooke D, Casbard A, Improving the evaluation of No. 21 Walker S, Meredith S, Nunn A, et al. therapeutic interventions in multiple Neuroleptics in the treatment of sclerosis: the role of new psychometric aggressive challenging behaviour for No. 29 methods. people with intellectual disabilities: Sensitivity analysis in economic By Hobart J, Cano S. a randomised controlled trial evaluation: an audit of NICE current (NACHBID). practice and a review of its use and No. 13 By Tyrer P, Oliver-Africano P, Romeo value in decision-making. By Andronis L, Barton P, Bryan S. Treatment of severe ankle sprain: a R, Knapp M, Dickens S, Bouras N, et al. pragmatic randomised controlled trial Suppl. 1 comparing the clinical effectiveness No. 22 Trastuzumab for the treatment of and cost-effectiveness of three types of Randomised controlled trial to primary breast cancer in HER2-positive mechanical ankle support with tubular determine the clinical effectiveness women: a single technology appraisal. bandage. The CAST trial. and cost-effectiveness of selective By Ward S, Pilgrim H, Hind D. By Cooke MW, Marsh JL, Clark M, serotonin reuptake inhibitors plus Nakash R, Jarvis RM, Hutton JL, et al., supportive care, versus supportive care Docetaxel for the adjuvant treatment on behalf of the CAST trial group. alone, for mild to moderate depression of early node-positive breast cancer: a with somatic symptoms in primary single technology appraisal. No. 14 care: the THREAD (THREshold for By Chilcott J, Lloyd Jones M, Non-occupational postexposure AntiDepressant response) study. Wilkinson A. prophylaxis for HIV: a systematic By Kendrick T, Chatwin J, Dowrick C, review. Tylee A, Morriss R, Peveler R, et al. The use of paclitaxel in the By Bryant J, Baxter L, Hird S. management of early stage breast No. 23 cancer. No. 15 Diagnostic strategies using DNA testing By Griffin S, Dunn G, Palmer S, Blood glucose self-monitoring in type 2 for hereditary haemochromatosis in Macfarlane K, Brent S, Dyker A, et al. diabetes: a randomised controlled trial. at-risk populations: a systematic review Rituximab for the first-line treatment By Farmer AJ, Wade AN, French DP, and economic evaluation. of stage III/IV follicular non-Hodgkin’s Simon J, Yudkin P, Gray A, et al. By Bryant J, Cooper K, Picot J, Clegg lymphoma. A, Roderick P, Rosenberg W, et al. By Dundar Y, Bagust A, Hounsome J, No. 16 McLeod C, Boland A, Davis H, et al. How far does screening women for No. 24 domestic (partner) violence in different Enhanced external counterpulsation Bortezomib for the treatment of health-care settings meet criteria for for the treatment of stable angina and multiple myeloma patients. a screening programme? Systematic heart failure: a systematic review and By Green C, Bryant J, Takeda A, reviews of nine UK National Screening economic analysis. Cooper K, Clegg A, Smith A, et al. Committee criteria. By McKenna C, McDaid C, Fludarabine phosphate for the first- By Feder G, Ramsay J, Dunne D, Suekarran S, Hawkins N, Claxton K, line treatment of chronic lymphocytic Rose M, Arsene C, Norman R, et al. Light K, et al. leukaemia. By Walker S, Palmer S, Erhorn S, No. 17 No. 25 Brent S, Dyker A, Ferrie L, et al. Spinal cord stimulation for chronic Development of a decision support pain of neuropathic or ischaemic tool for primary care management of Erlotinib for the treatment of relapsed origin: systematic review and economic patients with abnormal liver function non-small cell lung cancer. evaluation. tests without clinically apparent liver By McLeod C, Bagust A, Boland A, By Simpson, EL, Duenas A, Holmes disease: a record-linkage population Hockenhull J, Dundar Y, Proudlove C, MW, Papaioannou D, Chilcott J. cohort study and decision analysis et al. (ALFIE). Cetuximab plus radiotherapy for the No. 18 By Donnan PT, McLernon D, Dillon treatment of locally advanced squamous The role of magnetic resonance JF, Ryder S, Roderick P, Sullivan F, et al. cell carcinoma of the head and neck. imaging in the identification of By Griffin S, Walker S, Sculpher M, suspected acoustic neuroma: a No. 26 White S, Erhorn S, Brent S, et al. systematic review of clinical and cost- A systematic review of presumed effectiveness and natural history. consent systems for deceased organ Infliximab for the treatment of adults By Fortnum H, O’Neill C, Taylor R, donation. with psoriasis. Lenthall R, Nikolopoulos T, Lightfoot By Rithalia A, McDaid C, Suekarran By Loveman E, Turner D, Hartwell 132 G, et al. S, Norman G, Myers L, Sowden A. D, Cooper K, Clegg A. DOI: 10.3310/hta14120 Health Technology Assessment 2010; Vol. 14: No. 12

No. 30 No. 38 Rituximab for the treatment of Psychological interventions for The effectiveness and cost-effectiveness rheumatoid arthritis. postnatal depression: cluster of methods of storing donated kidneys By Bagust A, Boland A, Hockenhull randomised trial and economic from deceased donors: a systematic J, Fleeman N, Greenhalgh J, Dundar Y, evaluation. The PoNDER trial. review and economic model. et al. By Morrell CJ, Warner R, Slade P, By Bond M, Pitt M, Akoh J, Moxham Omalizumab for the treatment of Dixon S, Walters S, Paley G, et al. T, Hoyle M, Anderson R. severe persistent allergic asthma. By Jones J, Shepherd J, Hartwell D, No. 31 No. 39 Harris P, Cooper K, Takeda A, et al. The effect of different treatment Rehabilitation of older patients: day durations of clopidogrel in patients hospital compared with rehabilitation Rituximab for the treatment of relapsed with non-ST-segment elevation acute at home. A randomised controlled trial. or refractory stage III or IV follicular coronary syndromes: a systematic By Parker SG, Oliver P, Pennington non-Hodgkin’s lymphoma. review and value of information M, Bond J, Jagger C, Enderby PM, et al. analysis. By Boland A, Bagust A, Hockenhull By Rogowski R, Burch J, Palmer S, J, Davis H, Chu P, Dickson R. No. 40 Craigs C, Golder S, Woolacott N. Breastfeeding promotion for infants in Adalimumab for the treatment of psoriasis. No. 32 neonatal units: a systematic review and economic analysis By Turner D, Picot J, Cooper K, Systematic review and individual Loveman E. patient data meta-analysis of diagnosis By Renfrew MJ, Craig D, Dyson L, of heart failure, with modelling of McCormick F, Rice S, King SE, et al. Dabigatran etexilate for the prevention implications of different diagnostic of venous thromboembolism in patients strategies in primary care. No. 41 undergoing elective hip and knee By Mant J, Doust J, Roalfe A, Barton The clinical effectiveness and cost- surgery: a single technology appraisal. P, Cowie MR, Glasziou P, et al. effectiveness of bariatric (weight loss) By Holmes M, C Carroll C, surgery for obesity: a systematic review and Papaioannou D. No. 33 economic evaluation. A multicentre randomised controlled By Picot J, Jones J, Colquitt JL, Romiplostim for the treatment trial of the use of continuous positive Gospodarevskaya E, Loveman E, Baxter of chronic immune or idiopathic airway pressure and non-invasive L, et al. thrombocytopenic purpura: a single positive pressure ventilation in the early technology appraisal. treatment of patients presenting to the No. 42 By Mowatt G, Boachie C, Crowther emergency department with severe Rapid testing for group B streptococcus M, Fraser C, Hernández R, Jia X, et al. acute cardiogenic pulmonary oedema: during labour: a test accuracy study Sunitinib for the treatment of the 3CPO trial. with evaluation of acceptability and gastrointestinal stromal tumours: a By Gray AJ, Goodacre S, Newby cost-effectiveness. DE, Masson MA, Sampson F, Dixon critique of the submission from Pfizer. By Daniels J, Gray J, Pattison H, By Bond M, Hoyle M, Moxham T, S, et al., on behalf of the 3CPO study Roberts T, Edwards E, Milner P, et al. investigators. Napier M, Anderson R. No. 43 No. 45 No. 34 Screening to prevent spontaneous Early high-dose lipid-lowering therapy Vitamin K to prevent fractures in preterm birth: systematic reviews of to avoid cardiac events: a systematic older women: systematic review and accuracy and effectiveness literature review and economic evaluation. economic evaluation. with economic modelling. By Ara R, Pandor A, Stevens J, Rees By Stevenson M, Lloyd-Jones M, A, Rafia R. By Honest H, Forbes CA, Durée KH, Papaioannou D. Norman G, Duffy SB, Tsourapas A, et al. No. 35 No. 46 Adefovir dipivoxil and pegylated No. 44 The effects of biofeedback for the interferon alpha for the treatment The effectiveness and cost-effectiveness treatment of essential hypertension: a of chronic hepatitis B: an updated of cochlear implants for severe to systematic review. systematic review and economic profound deafness in children and By Greenhalgh J, Dickson R, evaluation. adults: a systematic review and Dundar Y. By Jones J, Shepherd J, Baxter L, economic model. Gospodarevskaya E, Hartwell D, Harris By Bond M, Mealing S, Anderson R, No. 47 P, et al. Elston J, Weiner G, Taylor RS, et al. A randomised controlled trial of the use of aciclovir and/or prednisolone for No. 36 Suppl. 2 the early treatment of Bell’s palsy: the Methods to identify postnatal Gemcitabine for the treatment of BELLS study. depression in primary care: an metastatic breast cancer. By Sullivan FM, Swan IRC, Donnan integrated evidence synthesis and value By Jones J, Takeda A, Tan SC, PT, Morrison JM, Smith BH, McKinstry of information analysis. Cooper K, Loveman E, Clegg A. B, et al. By Hewitt CE, Gilbody SM, Brealey S, Paulden M, Palmer S, Mann R, et al. Varenicline in the management of Suppl. 3 smoking cessation: a single technology Lapatinib for the treatment of HER2- No. 37 appraisal. overexpressing breast cancer. A double-blind randomised placebo- By Hind D, Tappenden P, Peters J, By Jones J, Takeda A, Picot J, von controlled trial of topical intranasal Kenjegalieva K. Keyserlingk C, Clegg A. corticosteroids in 4- to 11-year-old children with persistent bilateral otitis Alteplase for the treatment of acute Infliximab for the treatment of media with effusion in primary care. ischaemic stroke: a single technology ulcerative colitis. By Williamson I, Benge S, Barton S, appraisal. By Hyde C, Bryan S, Juarez-Garcia A, Petrou S, Letley L, Fasey N, et al. By Lloyd Jones M, Holmes M. Andronis L, Fry-Smith A. 133

Rimonabant for the treatment of No. 52 No. 60 overweight and obese people. The clinical effectiveness of Colour vision testing for diabetic By Burch J, McKenna C, Palmer S, glucosamine and chondroitin retinopathy: a systematic review of Norman G, Glanville J, Sculpher M, et supplements in slowing or arresting diagnostic accuracy and economic al. progression of osteoarthritis of the evaluation. Telbivudine for the treatment of knee: a systematic review and economic evaluation. By Rodgers M, Hodges R, Hawkins chronic hepatitis B infection. J, Hollingworth W, Duffy S, McKibbin By Hartwell D, Jones J, Harris P, By Black C, Clar C, Henderson R, M, et al. Cooper K. MacEachern C, McNamee P, Quayyum Z, et al. Entecavir for the treatment of chronic No. 61 hepatitis B infection. By Shepherd J, Gospodarevskaya E, No. 53 Systematic review of the effectiveness Frampton G, Cooper, K. Randomised preference trial of and cost-effectiveness of weight medical versus surgical termination of management schemes for the under Febuxostat for the treatment of pregnancy less than 14 weeks’ gestation fives: a short report. hyperuricaemia in people with gout: a (TOPS). By Bond M, Wyatt K, Lloyd J, Welch single technology appraisal. K, Taylor R. By Stevenson M, Pandor A. By Robson SC, Kelly T, Howel D, Deverill M, Hewison J, Lie MLS, et al. Rivaroxaban for the prevention of No. 62 venous thromboembolism: a single No. 54 technology appraisal. Are adverse effects incorporated in By Stevenson M, Scope A, Holmes M, Randomised controlled trial of the use economic models? An initial review of Rees A, Kaltenthaler E. of three dressing preparations in the current practice. management of chronic ulceration of Cetuximab for the treatment of the foot in diabetes. By Craig D, McDaid C, Fonseca T, Stock C, Duffy S, Woolacott N. recurrent and/or metastatic squamous By Jeffcoate WJ, Price PE, Phillips cell carcinoma of the head and neck. CJ, Game FL, Mudge E, Davies S, et al. By Greenhalgh J, Bagust A, Boland A, Fleeman N, McLeod C, Dundar Y, Volume 14, 2010 et al. No. 55 VenUS II: a randomised controlled trial Mifamurtide for the treatment of of larval therapy in the management of No. 1 osteosarcoma: a single technology leg ulcers. appraisal. Multicentre randomised controlled By Pandor A, Fitzgerald P, Stevenson By Dumville JC, Worthy G, Soares trial examining the cost-effectiveness of M, Papaioannou D. MO, Bland JM, Cullum N, Dowson C, contrast-enhanced high field magnetic et al. resonance imaging in women with Ustekinumab for the treatment of primary breast cancer scheduled for moderate to severe psoriasis. No. 56 wide local excision (COMICE). By Gospodarevskaya E, Picot J, Cooper K, Loveman E, Takeda A. A prospective randomised controlled By Turnbull LW, Brown SR, Olivier trial and economic modelling of C, Harvey I, Brown J, Drew P, et al. No. 48 antimicrobial silver dressings versus Endovascular stents for abdominal non-adherent control dressings for No. 2 aortic aneurysms: a systematic review venous leg ulcers: the VULCAN trial and economic model. By Michaels JA, Campbell WB, Bevacizumab, sorafenib tosylate, sunitinib and temsirolimus for renal By Chambers D, Epstein D, Walker S, King BM, MacIntyre J, Palfreyman SJ, cell carcinoma: a systematic review and Fayter D, Paton F, Wright K, et al. Shackley P, et al. economic evaluation. No. 49 No. 57 By Thompson Coon J, Hoyle M, Clinical and cost-effectiveness of Green C, Liu Z, Welch K, Moxham T, epoprostenol, iloprost, bosentan, Communication of carrier status et al. sitaxentan and sildenafil for pulmonary information following universal arterial hypertension within their newborn screening for sickle cell No. 3 licensed indications: a systematic review disorders and cystic fibrosis: qualitative and economic evaluation. study of experience and practice. The clinical effectiveness and cost- By Chen Y-F, Jowett S, Barton P, By Kai J, Ulph F, Cullinan T, effectiveness of testing for cytochrome Malottki K, Hyde C, Gibbs JSR, et al. Qureshi N. P450 polymorphisms in patients with schizophrenia treated with No. 50 No. 58 antipsychotics: a systematic review and Cessation of attention deficit economic evaluation. hyperactivity disorder drugs Antiviral drugs for the treatment of By Fleeman N, McLeod C, Bagust A, in the young (CADDY) – a influenza: a systematic review and Beale S, Boland A, Dundar Y, et al. pharmacoepidemiological and economic evaluation. qualitative study. By Burch J, Paulden M, Conti S, By Wong ICK, Asherson P, Bilbow A, Stock C, Corbett M, Welton NJ, et al. No. 4 Clifford S, Coghill D, R DeSoysa R, et al. Systematic review of the clinical No. 59 effectiveness and cost-effectiveness of No. 51 photodynamic diagnosis and urine ARTISTIC: a randomised trial of Development of a toolkit and glossary biomarkers (FISH, ImmunoCyt, human papillomavirus (HPV) testing in to aid in the adaptation of health NMP22) and cytology for the detection primary cervical screening. technology assessment (HTA) reports and follow-up of bladder cancer. By Kitchener HC, Almonte M, for use in different contexts. Gilham C, Dowie R, Stoykova B, Sargent By Chase D, Rosten C, Turner S, By Mowatt G, Zhu S, Kilonzo M, 134 A, et al. Hicks N, Milne R. Boachie C, Fraser C, Griffiths TRL, et al. DOI: 10.3310/hta14120 Health Technology Assessment 2010; Vol. 14: No. 12

No. 5 No. 8 No. 10 Effectiveness and cost-effectiveness of Dissemination and publication of Comparison of case note review arthroscopic lavage in the treatment research findings: an updated review of methods for evaluating quality and of osteoarthritis of the knee: a mixed related biases. safety in health care. methods study of the feasibility By Song F, Parekh S, Hooper L, Loke By Hutchinson A, Coster JE, Cooper of conducting a surgical placebo- YK, Ryder J, Sutton AJ, et al. KL, McIntosh A, Walters SJ, Bath PA, controlled trial (the KORAL study). et al. By Campbell MK, Skea ZC, No. 9 Sutherland AG, Cuthbertson BH, The effectiveness and cost-effectiveness No. 11 Entwistle VA, McDonald AM, et al. of biomarkers for the prioritisation Clinical effectiveness and cost- of patients awaiting coronary effectiveness of continuous No. 6 revascularisation: a systematic review subcutaneous insulin infusion for A randomised 2 × 2 trial of and decision model. diabetes: systematic review and community versus hospital pulmonary By Hemingway H, Henriksson economic evaluation. rehabilitation for chronic obstructive M, Chen R, Damant J, Fitzpatrick N, By Cummins E, Royle P, Snaith A, pulmonary disease followed by Abrams K, et al. Greene A, Robertson L, McIntyre L, et al. telephone or conventional follow-up. By Waterhouse JC, Walters SJ, Oluboyede Y, Lawson RA.

No. 7 The effectiveness and cost-effectiveness of behavioural interventions for the prevention of sexually transmitted infections in young people aged 13–19: a systematic review and economic evaluation. By Shepherd J, Kavanagh J, Picot J, Cooper K, Harden A, Barnett-Page E, et al.

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DOI: 10.3310/hta14120 Health Technology Assessment 2010; Vol. 14: No. 12

Health Technology Assessment programme

Director, Deputy Director, Professor Tom Walley, Professor Jon Nicholl, Director, NIHR HTA Director, Medical Care Research programme, Professor of Unit, University of Sheffield Clinical Pharmacology, University of Liverpool

Prioritisation Strategy Group Members

Chair, Dr Andrew Cook, Professor Paul Glasziou, Ms Lynn Kerridge, Professor Tom Walley, Consultant Advisor, NETSCC, Professor of Evidence-Based Chief Executive Officer, Director, NIHR HTA HTA Medicine, University of Oxford NETSCC and NETSCC, HTA programme, Professor of Clinical Pharmacology, Dr Peter Davidson, Dr Nick Hicks, Dr Ruairidh Milne, University of Liverpool Director of Science Support, Director of NHS Support, Director of Strategy and NETSCC, HTA NETSCC, HTA Development, NETSCC Deputy Chair, Professor Jon Nicholl, Professor Robin E Ferner, Dr Edmund Jessop, Ms Kay Pattison, Director, Medical Care Research Consultant Physician and Medical Adviser, National Section Head, NHS R&D Unit, University of Sheffield Director, West Midlands Centre Specialist, National Programme, Department of for Adverse Drug Reactions, Commissioning Group (NCG), Health Dr Bob Coates, City Hospital NHS Trust, Department of Health, London Consultant Advisor, NETSCC, Birmingham Ms Pamela Young, HTA Specialist Programme Manager, NETSCC, HTA

HTA Commissioning Board Members

Programme Director, Professor Deborah Ashby, Professor Freddie Hamdy, Professor Ian Roberts, Professor Tom Walley, Professor of Medical Statistics, Professor of Urology, Professor of Epidemiology & Director, NIHR HTA Queen Mary, University of University of Sheffield Public Health, London School programme, Professor of London of Hygiene and Tropical Clinical Pharmacology, Professor Allan House, Medicine University of Liverpool Professor John Cairns, Professor of Liaison Psychiatry, Professor of Health Economics, University of Leeds Professor Mark Sculpher, Chair, London School of Hygiene and Professor of Health Economics, Professor Jon Nicholl, Tropical Medicine Dr Martin J Landray, University of York Director, Medical Care Research Reader in Epidemiology, Unit, University of Sheffield Professor Peter Croft, Honorary Consultant Physician, Professor Helen Smith, Director of Primary Care Clinical Trial Service Unit, Professor of Primary Care, Deputy Chair, Sciences Research Centre, Keele University of Oxford University of Brighton Dr Andrew Farmer, University Senior Lecturer in General Professor Stuart Logan, Professor Kate Thomas, Practice, Department of Professor Nicky Cullum, Director of Health & Social Professor of Complementary & Primary Health Care, Director of Centre for Evidence- Care Research, The Peninsula Alternative Medicine Research, University of Oxford Based Nursing, University of Medical School, Universities of University of Leeds York Exeter and Plymouth Professor Ann Ashburn, Professor David John Professor of Rehabilitation Professor Jenny Donovan, Dr Rafael Perera, Torgerson, and Head of Research, Professor of Social Medicine, Lecturer in Medical Statisitics, Director of York Trials Unit, Southampton General Hospital University of Bristol Department of Primary Health University of York Care, Univeristy of Oxford Professor Steve Halligan, Professor Hywel Williams, Professor of Gastrointestinal Professor of Dermato- Radiology, University College Epidemiology, University of Hospital, London Nottingham

Observers

Ms Kay Pattison, Dr Morven Roberts, Section Head, NHS R&D Clinical Trials Manager, Programme, Department of Medical Research Council Health 137

Diagnostic Technologies & Screening Panel Members

Chair, Dr Stephanie Dancer, Dr Anne Mackie, Dr W Stuart A Smellie, Professor Paul Glasziou, Consultant Microbiologist, Director of Programmes, UK Consultant in Chemical Professor of Evidence-Based Hairmyres Hospital, East National Screening Committee Pathology, Bishop Auckland Medicine, University of Oxford Kilbride General Hospital Dr Michael Millar, Deputy Chair, Professor Glyn Elwyn, Consultant Senior Lecturer in Dr Nicholas Summerton, Dr David Elliman, Primary Medical Care Research Microbiology, Barts and The Consultant Clinical and Public Consultant Paediatrician and Group, Swansea Clinical School, London NHS Trust, Royal Health Advisor, NICE Honorary Senior Lecturer, University of Wales London Hospital Great Ormond Street Hospital, Ms Dawn Talbot, London Dr Ron Gray, Mr Stephen Pilling, Service User Representative Consultant Clinical Director, Centre for Outcomes, Professor Judith E Adams, Epidemiologist, Department Research & Effectiveness, Dr Graham Taylor, Consultant Radiologist, of Public Health, University of Joint Director, National Scientific Advisor, Regional Manchester Royal Infirmary, Oxford Collaborating Centre for DNA Laboratory, St James’s Central Manchester & Mental Health, University University Hospital, Leeds Manchester Children’s Professor Paul D Griffiths, College London Professor of Radiology, Professor Lindsay Wilson University Hospitals NHS Trust, Turnbull, and Professor of Diagnostic University of Sheffield Mrs Una Rennard, Service User Representative Scientific Director of the Radiology, Imaging Science Dr Jennifer J Kurinczuk, Centre for Magnetic Resonance and Biomedical Engineering, Consultant Clinical Dr Phil Shackley, Investigations and YCR Cancer & Imaging Sciences, Epidemiologist, National Senior Lecturer in Health Professor of Radiology, Hull University of Manchester Perinatal Epidemiology Unit, Economics, School of Royal Infirmary Ms Jane Bates, Oxford Population and Health Consultant Ultrasound Sciences, University of Dr Susanne M Ludgate, Newcastle upon Tyne Practitioner, Ultrasound Medical Director, Medicines & Department, Leeds Teaching Healthcare Products Regulatory Hospital NHS Trust Agency, London

Observers

Dr Tim Elliott, Dr Catherine Moody, Dr Ursula Wells, Team Leader, Cancer Programme Manager, Principal Research Officer, Screening, Department of Neuroscience and Mental Department of Health Health Health Board

Pharmaceuticals Panel Members

Chair, Dr Peter Elton, Professor Jonathan Ledermann, Dr Martin Shelly, Professor Robin Ferner, Director of Public Health, Professor of Medical Oncology General Practitioner, Leeds, Consultant Physician and Bury Primary Care Trust and Director of the Cancer and Associate Director, NHS Director, West Midlands Centre Research UK and University Clinical Governance Support for Adverse Drug Reactions, Dr Ben Goldacre, College London Cancer Trials Team, Leicester City Hospital NHS Trust, Research Fellow, Division of Centre Birmingham Psychological Medicine and Dr Gillian Shepherd, Psychiatry, King’s College Dr Yoon K Loke, Director, Health and Clinical Deputy Chair, London Senior Lecturer in Clinical Excellence, Merck Serono Ltd Professor Imti Choonara, Pharmacology, University of Professor in Child Health, Mrs Barbara Greggains, East Anglia Mrs Katrina Simister, University of Nottingham Service User Representative Assistant Director New Professor Femi Oyebode, Medicines, National Prescribing Mrs Nicola Carey, Dr Bill Gutteridge, Consultant Psychiatrist Centre, Liverpool Senior Research Fellow, Medical Adviser, London and Head of Department, School of Health and Social Strategic Health Authority University of Birmingham Mr David Symes, Service User Representative Care, The University of Dr Dyfrig Hughes, Reading Dr Andrew Prentice, Reader in Pharmacoeconomics Senior Lecturer and Consultant Dr Lesley Wise, Mr John Chapman, and Deputy Director, Centre Obstetrician and Gynaecologist, Unit Manager, Service User Representative for Economics and Policy in The Rosie Hospital, University Pharmacoepidemiology Health, IMSCaR, Bangor of Cambridge Research Unit, VRMM, University Medicines & Healthcare Products Regulatory Agency Observers Mr Simon Reeve, Dr Heike Weber, Dr Ursula Wells, Ms Kay Pattison, Head of Clinical and Cost- Programme Manager, Principal Research Officer, Section Head, NHS R&D Effectiveness, Medicines, Medical Research Council Department of Health Programme, Department of Pharmacy and Industry Group, Health 138 Department of Health

Current and past membership details of all HTA programme ‘committees’ are available from the HTA website (www.hta.ac.uk) DOI: 10.3310/hta14120 Health Technology Assessment 2010; Vol. 14: No. 12

Therapeutic Procedures Panel Members

Chair, Mrs Val Carlill, Mr Paul Hilton, Dr Kate Radford, Dr John C Pounsford, Service User Representative Consultant Gynaecologist Senior Lecturer (Research), Consultant Physician, North and Urogynaecologist, Royal Clinical Practice Research Bristol NHS Trust Mrs Anthea De Barton-Watson, Victoria Infirmary, Newcastle Unit, University of Central Service User Representative upon Tyne Lancashire, Preston Deputy Chair, Professor Scott Weich, Mr Mark Emberton, Professor Nicholas James, Mr Jim Reece Professor of Psychiatry, Division Senior Lecturer in Oncological Professor of Clinical Oncology, Service User Representative of Health in the Community, Urology, Institute of Urology, University of Birmingham, University of Warwick, University College Hospital, and Consultant in Clinical Dr Karen Roberts, Coventry London Oncology, Queen Elizabeth Nurse Consultant, Dunston Hill Hospital Hospital Cottages Professor Jane Barlow, Professor Steve Goodacre, Professor of Public Health in Professor of Emergency Dr Peter Martin, the Early Years, Health Sciences Medicine, University of Consultant Neurologist, Research Institute, Warwick Sheffield Addenbrooke’s Hospital, Medical School, Coventry Professor Christopher Griffiths, Cambridge Ms Maree Barnett, Professor of Primary Care, Barts Acting Branch Head of Vascular and The London School of Programme, Department of Medicine and Dentistry Health

Observers

Dr Phillip Leech, Dr Morven Roberts, Professor Tom Walley, Dr Ursula Wells, Principal Medical Officer for Clinical Trials Manager, Director, NIHR HTA Principal Research Officer, Primary Care, Department of Medical Research Council programme, Professor of Department of Health Health Clinical Pharmacology, University of Liverpool Ms Kay Pattison, Section Head, NHS R&D Programme, Department of Health Disease Prevention Panel Members Chair, Dr John Jackson, Dr Julie Mytton, Dr Kieran Sweeney, Dr Edmund Jessop, General Practitioner, Parkway Locum Consultant in Public Honorary Clinical Senior Medical Adviser, National Medical Centre, Newcastle Health Medicine, Bristol Lecturer, Peninsula College Specialist, National upon Tyne Primary Care Trust of Medicine and Dentistry, Commissioning Group (NCG), Universities of Exeter and London Professor Mike Kelly, Miss Nicky Mullany, Plymouth Director, Centre for Public Service User Representative Deputy Chair, Health Excellence, NICE, Professor Carol Tannahill, Dr David Pencheon, London Professor Ian Roberts, Glasgow Centre for Population Director, NHS Sustainable Professor of Epidemiology and Health Development Unit, Cambridge Dr Chris McCall, Public Health, London School General Practitioner, The of Hygiene & Tropical Medicine Professor Margaret Thorogood, Dr Elizabeth Fellow-Smith, Hadleigh Practice, Corfe Professor of Epidemiology, Medical Director, West London Mullen, Dorset Professor Ken Stein, University of Warwick Medical Mental Health Trust, Middlesex Senior Clinical Lecturer in School, Coventry Ms Jeanett Martin, Public Health, University of Director of Nursing, BarnDoc Exeter Limited, Lewisham Primary Care Trust

Observers

Ms Christine McGuire, Dr Caroline Stone, Research & Development, Programme Manager, Medical Department of Health Research Council

139

Expert Advisory Network Members

Professor Douglas Altman, Mr Jonothan Earnshaw, Professor Alan Horwich, Professor Miranda Mugford, Professor of Statistics in Consultant Vascular Surgeon, Dean and Section Chairman, Professor of Health Economics Medicine, Centre for Statistics Gloucestershire Royal Hospital, The Institute of Cancer and Group Co-ordinator, in Medicine, University of Gloucester Research, London University of East Anglia Oxford Professor Martin Eccles, Professor Allen Hutchinson, Professor Jim Neilson, Professor John Bond, Professor of Clinical Director of Public Health and Head of School of Reproductive Professor of Social Gerontology Effectiveness, Centre for Health Deputy Dean of ScHARR, & Developmental Medicine & Health Services Research, Services Research, University of University of Sheffield and Professor of Obstetrics University of Newcastle upon Newcastle upon Tyne and Gynaecology, University of Tyne Professor Peter Jones, Liverpool Professor Pam Enderby, Professor of Psychiatry, Professor Andrew Bradbury, Dean of Faculty of Medicine, University of Cambridge, Mrs Julietta Patnick, Professor of Vascular Surgery, Institute of General Practice Cambridge National Co-ordinator, NHS Solihull Hospital, Birmingham and Primary Care, University of Cancer Screening Programmes, Sheffield Professor Stan Kaye, Sheffield Mr Shaun Brogan, Cancer Research UK Professor Chief Executive, Ridgeway Professor Gene Feder, of Medical Oncology, Royal Professor Robert Peveler, Primary Care Group, Aylesbury Professor of Primary Care Marsden Hospital and Institute Professor of Liaison Psychiatry, Research & Development, of Cancer Research, Surrey Royal South Hants Hospital, Mrs Stella Burnside OBE, Centre for Health Sciences, Southampton Chief Executive, Regulation Barts and The London School Dr Duncan Keeley, and Improvement Authority, of Medicine and Dentistry General Practitioner (Dr Burch Professor Chris Price, Belfast & Ptnrs), The Health Centre, Director of Clinical Research, Mr Leonard R Fenwick, Thame Bayer Diagnostics Europe, Ms Tracy Bury, Chief Executive, Freeman Stoke Poges Project Manager, World Hospital, Newcastle upon Tyne Dr Donna Lamping, Confederation for Physical Research Degrees Programme Professor William Rosenberg, Therapy, London Mrs Gillian Fletcher, Director and Reader in Professor of Hepatology Antenatal Teacher and Tutor Psychology, Health Services and Consultant Physician, Professor Iain T Cameron, and President, National Research Unit, London School University of Southampton Professor of Obstetrics and Childbirth Trust, Henfield of Hygiene and Tropical Gynaecology and Head of the Medicine, London Professor Peter Sandercock, School of Medicine, University Professor Jayne Franklyn, Professor of Medical Neurology, of Southampton Professor of Medicine, Mr George Levvy, Department of Clinical University of Birmingham Chief Executive, Motor Neurosciences, University of Dr Christine Clark, Neurone Disease Association, Edinburgh Medical Writer and Consultant Mr Tam Fry, Northampton Pharmacist, Rossendale Honorary Chairman, Child Dr Susan Schonfield, Growth Foundation, London Professor James Lindesay, Consultant in Public Health, Professor Collette Clifford, Professor of Psychiatry for the Hillingdon Primary Care Trust, Professor of Nursing and Professor Fiona Gilbert, Elderly, University of Leicester Middlesex Head of Research, The Consultant Radiologist and Medical School, University of NCRN Member, University of Professor Julian Little, Dr Eamonn Sheridan, Birmingham Aberdeen Professor of Human Genome Consultant in Clinical Genetics, Epidemiology, University of St James’s University Hospital, Professor Barry Cookson, Professor Paul Gregg, Ottawa Leeds Director, Laboratory of Hospital Professor of Orthopaedic Infection, Public Health Surgical Science, South Tees Professor Alistaire McGuire, Dr Margaret Somerville, Laboratory Service, London Hospital NHS Trust Professor of Health Economics, Director of Public Health London School of Economics Learning, Peninsula Medical Dr Carl Counsell, Bec Hanley, School, University of Plymouth Clinical Senior Lecturer in Co-director, TwoCan Associates, Professor Rajan Madhok, Neurology, University of West Sussex Medical Director and Director Professor Sarah Stewart-Brown, Aberdeen of Public Health, Directorate Professor of Public Health, Dr Maryann L Hardy, of Clinical Strategy & Public Division of Health in the Professor Howard Cuckle, Senior Lecturer, University of Health, North & East Yorkshire Community, University of Professor of Reproductive Bradford & Northern Lincolnshire Warwick, Coventry Epidemiology, Department Health Authority, York of Paediatrics, Obstetrics & Mrs Sharon Hart, Professor Ala Szczepura, Gynaecology, University of Healthcare Management Professor Alexander Markham, Professor of Health Service Leeds Consultant, Reading Director, Molecular Medicine Research, Centre for Health Services Studies, University of Professor Robert E Hawkins, Unit, St James’s University Dr Katherine Darton, Hospital, Leeds Warwick, Coventry Information Unit, MIND – The CRC Professor and Director Mental Health Charity, London of Medical Oncology, Christie Dr Peter Moore, Mrs Joan Webster, CRC Research Centre, Freelance Science Writer, Consumer Member, Southern Professor Carol Dezateux, Christie Hospital NHS Trust, Ashtead Derbyshire Community Health Professor of Paediatric Manchester Council Epidemiology, Institute of Child Dr Andrew Mortimore, Health, London Professor Richard Hobbs, Public Health Director, Professor Martin Whittle, Head of Department of Primary Southampton City Primary Clinical Co-director, National Mr John Dunning, Care & General Practice, Care Trust Co-ordinating Centre for Consultant Cardiothoracic University of Birmingham Women’s and Children’s Surgeon, Papworth Hospital Dr Sue Moss, Health, Lymington NHS Trust, Cambridge Associate Director, Cancer Screening Evaluation Unit, Institute of Cancer Research, Sutton 140

Current and past membership details of all HTA programme ‘committees’ are available from the HTA website (www.hta.ac.uk)

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