Quality of Medical Products for Diabetes Management: a Systematic Review
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Research BMJ Glob Health: first published as 10.1136/bmjgh-2019-001636 on 24 September 2019. Downloaded from Quality of medical products for diabetes management: a systematic review Kartika Saraswati, 1,2,3 Chanvilay Sichanh,1 Paul N Newton, 1,2,3 Céline Caillet 1,2,3 To cite: Saraswati K, Sichanh C, ABSTRACT Key questions Newton PN, et al. Quality of Background The global prevalence of diabetes mellitus medical products for diabetes is increasing alarmingly. However, the quality of vital What is already known? management: a systematic medicines and medical products used to treat and monitor review. BMJ Global Health Substandard and falsified medical products for man- diabetes remains uncertain but of potential great public ► 2019;4:e001636. doi:10.1136/ aging diabetes will negate the benefits of modern health significance. Here, we review the available evidence bmjgh-2019-001636 diabetes treatment and the public benefit of reduced on the quality of antidiabetic medicines and supplies for complications. self-monitoring of blood glucose (SMBG) and discuss their Handling editor Seye Abimbola Better understanding of the epidemiology of sub- potential impact for the patients and society. ► standard and falsified diabetes medications and Methods Searches were conducted in PubMed, Embase, Received 11 April 2019 self-monitoring of blood glucose (SMBG) supplies Revised 18 July 2019 Google Scholar, Google and relevant websites in English and their potential impact on patients and society Accepted 20 July 2019 and French. The Medicine Quality Assessment Reporting is needed. Guideline (MEDQUARG) was used to assess the quality of medicine quality surveys. What are the new findings? Results 52 publications on the quality of antidiabetic ► Our study demonstrated that of 674 samples anal- medicines, including 5 medicine quality prevalence ysed, about 1/10 were substandard or falsified but surveys and 20 equivalence studies, were analysed. The this prevalence is not generalisable globally. prevalence surveys and equivalence studies included 674 ► Issues with the quality of SMBG supplies were iden- samples of which 73 (10.8%) were of poor quality. The tified (including falsified products and incorrect re- median (Q1–Q3) concordance with MEDQUARG items was sults due to strip degradation or contamination). 30.8% (19.2%–42.3%). No prevalence surveys on SMBG supplies’ quality were found, but 29 publications, including What do the new findings imply? falsified products and incorrect results due to strip ► Our findings showed that, despite the scarcity of degradation or contamination, were identified. the data, there are important issues with the qual- ity of medical products for diabetes that need to be Conclusion There is little accessible evidence on the http://gh.bmj.com/ quality of antidiabetic medicines and SMBG supplies. tackled. Surveys were poorly designed and reported, making data ► Besides increasing the quality of the surveys, con- aggregation and interpretation problematic. Despite these sensus would facilitate evidence pooling and sum- caveats, these results suggest that there are important marising to better understand the global burden of © Author(s) (or their this problem. employer(s)) 2019. Re-use issues with the quality of medical products for diabetes permitted under CC BY. that need focused monitoring. There is an urgent need to Published by BMJ. achieve consensus protocols for designing, conducting and on September 25, 2021 by guest. Protected copyright. 1Lao-Oxford-Mahosot- reporting medical product quality surveys. required for type 1 diabetes treatment, and is Wellcome Trust Research PROSPERO registration number CRD42016039841. also used widely for advanced type 2 diabetes. Unit, Microbiology Laboratory, In 2015, insulin was within the top 10 best- Mahosot Hospital, Vientiane, Lao selling medications globally (in terms of People's Democratic Republic INTRODUCTION 4 5 2Centre for Tropical Medicine number of prescriptions and sales value). It and Global Health, Nuffield Diabetes mellitus (hereafter diabetes) is a is estimated that globally ~100 million people 6 Department of Medicine, growing threat to global health with significant need insulin. Type 2 diabetes treatment University of Oxford, Oxford, UK mortality and morbidity related to myriads of involves lifestyle change encouragement, but 3 Infectious Diseases Data non-communicable and communicable disease antidiabetic medicines are often required for Observatory/WorldWide consequences. In 2015, diabetes afflicted ~415 the control of hyperglycaemia and preven- Antimalarial Resistance 1 7 8 Network, Centre for Tropical million people globally and this is predicted tion of long-term complications. Oral anti- Medicine and Global Health, to reach 642 million by 2040, equivalent to 1 diabetic sale in 2016 was estimated to reach University of Oxford, Oxford, UK in 10 adults.1 The direct annual global cost of close to US$20 billion.9 There has also been diabetes is estimated at US$827 billion.2 a surge in innovative expensive oral therapies Correspondence to Dr Kartika Saraswati; In the USA, approximately four in five such as gliptins. kartika. saraswati@ndm. ox. adults with diabetes rely on antidiabetic medi- There are key public health issues with ac. uk cines to control their glucose levels.3 Insulin is cost and access to antidiabetic medicines, Saraswati K, et al. BMJ Global Health 2019;4:e001636. doi:10.1136/bmjgh-2019-001636 1 BMJ Global Health BMJ Glob Health: first published as 10.1136/bmjgh-2019-001636 on 24 September 2019. Downloaded from especially insulin,5 and to specialised diabetes care. With regulatory systems are often weak.24 26 27 30 Rising concern huge price variation between countries and increasing about the consequences of poor quality medicines over demand, insulin and new oral antidiabetic medicines the last decade has focused on anti-infectives.31 However, are likely to be attractive targets for falsification and there is growing awareness of this issue for chronic are at risk of substandard production.10 High prices of non-communicable diseases, for example, a recent some antidiabetics may prompt patients to look for more survey described that 16.3% of cardiovascular medicines affordable options, including illegitimate sources such as sampled in ten sub-Saharan African countries were poor unregistered physical and internet pharmacies.11 quality.32 These will have significant public health impact Nearly 60% of the global costs of diabetes are borne and if poor quality diabetes medical products are also by low-income and middle-income countries (LMICs), prevalent they will have an additive global toll on health. with substantial treatment costs paid out-of-pocket and The recent WHO report stated that seven member states insufficient medicines regulation. This limits access and reported 11 substandard and falsified (SF) diabetes thus risks use of poor quality medical products, exacer- medicines between 2013 and 2017 but details are not bating financial hardship and impairing peoples’ lives given.28 As there is no global understanding of the epide- and productivity.12 miology of poor quality medical products for diabetes, we Patients with diabetes often need to check their blood reviewed the available evidence and discuss the potential glucose concentration multiple times per day using impact for patients and society. strip-based hand-held glucose meters. The cost for such self-monitoring of blood glucose (SMBG) can account METHODS for approximately one-third of the total cost of consum- Search strategy ables, including insulin and needles, for type 1 diabetes Reports were identified through systematic searches management.13 This expense has prompted both falsi- in PubMed, Embase, Google Scholar in English and fication of glucose strips and reselling of secondhand French up to 30 April 2018, using the search terms unused glucose strips at reduced price.10 14 15 In 2008, the (online supplementary file 1) ‘diabetes’, ‘antidiabetics’, US Food and Drug Administration (FDA) and the Amer- the names of active pharmaceutical ingredients (eg, ican Diabetes Association warned against using resold ‘insulin’, ‘metformin’, ‘glibenclamide’), ‘glucose meter’, strips as they may give incorrect results.14 16 ‘strip’; combined with terms relevant to medicine quality Due to their vital role in diabetes management, poor (eg, ‘falsified’, ‘counterfeit’, ‘substandard’, ‘degraded’). quality antidiabetic medicines and SMBG supplies will Reports were also identified in Google from the first inevitably have adverse health impacts for patients, both 20 pages of results and other sources such as websites short and long term. Low active pharmaceutical ingre- of international organisations interested in medicine dient (API) content and, for oral preparations impaired quality and medicines regulatory authorities (online gastrointestinal dissolution, will increase the incidence of supplementary file 1). After removal of duplicates, the macrovascular and microvascular complications due to titles and abstracts were first screened, and full text of the compromised glucose control, and hence increase indi- http://gh.bmj.com/ identified articles were then assessed for eligibility. The vidual and societal economic costs.17–19 High API content reference lists of the eligible articles were also manually may also bring grim immediate consequences. Deaths screened for inclusion. have been linked to falsified antidiabetic medicines in China containing dangerously high amounts of the oral