Measures Derived from a 2 X 2 Table for an Accuracy of a Diagnostic Test
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The Statistical Significance of Randomized Controlled Trial Results Is Frequently Fragile: a Case for a Fragility Index
The statistical significance of randomized controlled trial results is frequently fragile: A case for a Fragility Index Walsh, M., Srinathan, S. K., McAuley, D. F., Mrkobrada, M., Levine, O., Ribic, C., Molnar, A. O., Dattani, N. D., Burke, A., Guyatt, G., Thabane, L., Walter, S. D., Pogue, J., & Devereaux, P. J. (2014). The statistical significance of randomized controlled trial results is frequently fragile: A case for a Fragility Index. Journal of Clinical Epidemiology, 67(6), 622-628. https://doi.org/10.1016/j.jclinepi.2013.10.019 Published in: Journal of Clinical Epidemiology Document Version: Publisher's PDF, also known as Version of record Queen's University Belfast - Research Portal: Link to publication record in Queen's University Belfast Research Portal Publisher rights 2014 The Authors. Published by Elsevier Inc. This is an open access article published under a Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/3.0/), which permits distribution and reproduction for non-commercial purposes, provided the author and source are cited. General rights Copyright for the publications made accessible via the Queen's University Belfast Research Portal is retained by the author(s) and / or other copyright owners and it is a condition of accessing these publications that users recognise and abide by the legal requirements associated with these rights. Take down policy The Research Portal is Queen's institutional repository that provides access to Queen's research output. Every effort has been made to ensure that content in the Research Portal does not infringe any person's rights, or applicable UK laws. -
Why Do You Need a Biostatistician? Antonia Zapf1* , Geraldine Rauch2 and Meinhard Kieser3
Zapf et al. BMC Medical Research Methodology (2020) 20:23 https://doi.org/10.1186/s12874-020-0916-4 DEBATE Open Access Why do you need a biostatistician? Antonia Zapf1* , Geraldine Rauch2 and Meinhard Kieser3 Abstract The quality of medical research importantly depends, among other aspects, on a valid statistical planning of the study, analysis of the data, and reporting of the results, which is usually guaranteed by a biostatistician. However, there are several related professions next to the biostatistician, for example epidemiologists, medical informaticians and bioinformaticians. For medical experts, it is often not clear what the differences between these professions are and how the specific role of a biostatistician can be described. For physicians involved in medical research, this is problematic because false expectations often lead to frustration on both sides. Therefore, the aim of this article is to outline the tasks and responsibilities of biostatisticians in clinical trials as well as in other fields of application in medical research. Keywords: Medical research, Biostatistician, Tasks, Responsibilities Background Biometric Society (IBS) provides a definition of biomet- What is a biostatistician, what does he or she actually do rics as a ‘field of development of statistical and mathem- and what distinguishes him or her from, for example, an atical methods applicable in the biological sciences’ [2]. epidemiologist? If we would ask this our main cooper- In here, we will focus on (human) medicine as area of ation partners like physicians or biologists, they probably application, but the results can be easily transferred to could not give a satisfying answer. This is problematic the other biological sciences like, for example, agricul- because false expectations often lead to frustration on ture or ecology. -
Outcome Reporting Bias in COVID-19 Mrna Vaccine Clinical Trials
medicina Perspective Outcome Reporting Bias in COVID-19 mRNA Vaccine Clinical Trials Ronald B. Brown School of Public Health and Health Systems, University of Waterloo, Waterloo, ON N2L3G1, Canada; [email protected] Abstract: Relative risk reduction and absolute risk reduction measures in the evaluation of clinical trial data are poorly understood by health professionals and the public. The absence of reported absolute risk reduction in COVID-19 vaccine clinical trials can lead to outcome reporting bias that affects the interpretation of vaccine efficacy. The present article uses clinical epidemiologic tools to critically appraise reports of efficacy in Pfzier/BioNTech and Moderna COVID-19 mRNA vaccine clinical trials. Based on data reported by the manufacturer for Pfzier/BioNTech vaccine BNT162b2, this critical appraisal shows: relative risk reduction, 95.1%; 95% CI, 90.0% to 97.6%; p = 0.016; absolute risk reduction, 0.7%; 95% CI, 0.59% to 0.83%; p < 0.000. For the Moderna vaccine mRNA-1273, the appraisal shows: relative risk reduction, 94.1%; 95% CI, 89.1% to 96.8%; p = 0.004; absolute risk reduction, 1.1%; 95% CI, 0.97% to 1.32%; p < 0.000. Unreported absolute risk reduction measures of 0.7% and 1.1% for the Pfzier/BioNTech and Moderna vaccines, respectively, are very much lower than the reported relative risk reduction measures. Reporting absolute risk reduction measures is essential to prevent outcome reporting bias in evaluation of COVID-19 vaccine efficacy. Keywords: mRNA vaccine; COVID-19 vaccine; vaccine efficacy; relative risk reduction; absolute risk reduction; number needed to vaccinate; outcome reporting bias; clinical epidemiology; critical appraisal; evidence-based medicine Citation: Brown, R.B. -
Statistical Evaluation of Diagnostic Tests – Part 2 [Pre-Test and Post-Test Probability and Odds, Likelihood Ratios, Receiver
86 Journal of The Association of Physicians of India ■ Vol. 65 ■ July 2017 STATISTICS FOR RESEARCHERS Statistical Evaluation of Diagnostic Tests – Part 2 [Pre-test and post-test probability and odds, Likelihood ratios, Receiver Operating Characteristic Curve, Youden’s Index and Diagnostic test biases] NJ Gogtay, UM Thatte Introduction Understanding Probability From the example, it follows that and Odds and the Odds = p/1-p, where p is the n the previous article on probability of the event occurring. the statistical evaluation Relationship between the I Probability, on the other hand, of diagnostic tests –Part 1, we Two is given by the formula understood the measures of sensitivity, specificity, positive Let us understand probability p = Odds/1+Odds and negative predictive values. and odds with the example of The use of these metrices stems a drug producing bleeding in Bayesian Statistics, Pre- from the fact that no diagnostic 10/100 patients treated with it. Test Probability and Pre- test is ever perfect and every time The probability of bleeding will Test Odds we carry out a test, it will yield be 10/100 [10%], while the odds of one of four possible outcomes– bleeding will be 10/90 [11%]. This A clinician often suspects that true positive, false positive, true is because odds is defined as the a patient has the disease even negative or false negative. The 2 x probability of the event occurring before he orders a test [screening 2 table [Table 1] gives each of these divided by the probability of or diagnostic] on the patient. For four possibilities along with their the event not occurring.2 Thus, example, when a patient who is mathematical calculations when a every odds can be expressed as a chronic smoker and presents new test is compared with a gold probability and every probability with cough and weight loss of a standard test.1 as odds as these are two ways of six-month duration, the suspicion In this article, the second in explaining the same concept. -
Clinical Epidemiologic Definations
CLINICAL EPIDEMIOLOGIC DEFINATIONS 1. STUDY DESIGN Case-series: Report of a number of cases of disease. Cross-sectional study: Study design, concurrently measure outcome (disease) and risk factor. Compare proportion of diseased group with risk factor, with proportion of non-diseased group with risk factor. Case-control study: Retrospective comparison of exposures of persons with disease (cases) with those of persons without the disease (controls) (see Retrospective study). Retrospective study: Study design in which cases where individuals who had an outcome event in question are collected and analyzed after the outcomes have occurred (see also Case-control study). Cohort study: Follow-up of exposed and non-exposed defined groups, with a comparison of disease rates during the time covered. Prospective study: Study design where one or more groups (cohorts) of individuals who have not yet had the outcome event in question are monitored for the number of such events, which occur over time. Randomized controlled trial: Study design where treatments, interventions, or enrollment into different study groups are assigned by random allocation rather than by conscious decisions of clinicians or patients. If the sample size is large enough, this study design avoids problems of bias and confounding variables by assuring that both known and unknown determinants of outcome are evenly distributed between treatment and control groups. Bias (Syn: systematic error): Deviation of results or inferences from the truth, or processes leading to such deviation. See also Referral Bias, Selection Bias. Recall bias: Systematic error due to the differences in accuracy or completeness of recall to memory of past events or experiences. -
Enrichment Strategies for Clinical Trials to Support Determination of Effectiveness of Human Drugs and Biological Products Guidance for Industry
Enrichment Strategies for Clinical Trials to Support Determination of Effectiveness of Human Drugs and Biological Products Guidance for Industry U.S. Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research (CDER) Center for Biologics Evaluation and Research (CBER) March 2019 Clinical/Medical Enrichment Strategies for Clinical Trials to Support Determination of Effectiveness of Human Drugs and Biological Products Guidance for Industry Additional copies are available from: Office of Communications, Division of Drug Information Center for Drug Evaluation and Research Food and Drug Administration 10001 New Hampshire Ave., Hillandale Bldg., 4th Floor Silver Spring, MD 20993-0002 Phone: 855-543-3784 or 301-796-3400; Fax: 301-431-6353; Email: [email protected] https://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm and/or Office of Communication, Outreach, and Development Center for Biologics Evaluation and Research Food and Drug Administration 10903 New Hampshire Ave., Bldg. 71, rm. 3128 Silver Spring, MD 20993-0002 Phone: 800-835-4709 or 240-402-8010; Email: [email protected] https://www.fda.gov/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Guidances/default.htm U.S. Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research (CDER) Center for Biologics Evaluation and Research (CBER) March 2019 Clinical/Medical TABLE OF CONTENTS I. INTRODUCTION............................................................................................................ -
The Diagnostic Odds Ratio: a Single Indicator of Test Performance Afina S
Journal of Clinical Epidemiology 56 (2003) 1129–1135 The diagnostic odds ratio: a single indicator of test performance Afina S. Glasa,*, Jeroen G. Lijmerb, Martin H. Prinsc, Gouke J. Bonseld, Patrick M.M. Bossuyta aDepartment of Clinical Epidemiology & Biostatistics, University of Amsterdam, Academic Medical Center, Post Office Box 22700, 100 DE Amsterdam, The Netherlands bDepartment of Psychiatry, University Medical Center, Post Office Box 85500, 3508 GA, Utrecht, The Netherlands cDepartment of Epidemiology, University of Maastricht, Post Office Box 6166200 MD, Maastricht, The Netherlands dDepartment of Public Health, Academic Medical Center, Post Office Box 22700, 1100 DE, Amsterdam, The Netherlands Accepted 17 April 2003 Abstract Diagnostic testing can be used to discriminate subjects with a target disorder from subjects without it. Several indicators of diagnostic performance have been proposed, such as sensitivity and specificity. Using paired indicators can be a disadvantage in comparing the performance of competing tests, especially if one test does not outperform the other on both indicators. Here we propose the use of the odds ratio as a single indicator of diagnostic performance. The diagnostic odds ratio is closely linked to existing indicators, it facilitates formal meta-analysis of studies on diagnostic test performance, and it is derived from logistic models, which allow for the inclusion of additional variables to correct for heterogeneity. A disadvantage is the impossibility of weighing the true positive and false positive rate separately. In this article the application of the diagnostic odds ratio in test evaluation is illustrated. Ć 2003 Elsevier Inc. All rights reserved. Keywords: Diagnostic odds ratio; Tutorial; Diagnostic test; Sensitivity and specificity; Logistic regression; Meta-analysis 1. -
Evidence-Based Clinical Question Does Dantrolene Sodium Prevent Recurrent Exertional Rhabdomyolysis in Horses? M
EQUINE VETERINARY EDUCATION / AE / March 2007 97 Evidence-based Clinical Question Does dantrolene sodium prevent recurrent exertional rhabdomyolysis in horses? M. A. HOLMES University of Cambridge, Department of Veterinary Medicine, Madingley Road, Cambridge CB3 0ES, UK. Three part question of any other clinical manifestation of disease. An arbitrary level of >900 iu/l was selected as a case definition to provide In Thoroughbred horses (population) does treatment with a means of counting the number of animals that might be dantrolene sodium (intervention) reduce the recurrence of described as constituting a case of exertional rhabdomyolysis exertional rhabdomyolysis (outcome)? (ER). Clinical cases of ER may exhibit considerably greater levels of CK and it should not be implied that lower CK levels Clinical scenario may not be associated with clinical signs of ER. The key results are presented as absolute risk reductions A client requests advice on the prevention of recurrent (ARR) and relative risk reductions (RRR). The ARR indicates the exertional rhabdomyloysis (RER) for a Thoroughbred horse proportion of all horses in the treatment group that have an with a history of this condition. The veterinarian is aware that improved clinical outcome as a result of the treatment (i.e. the dantrolene sodium has been suggested as a suitable proportion of horses that benefit from dantrolene treatment). preventive treatment. Both the trials described here are unusual in that a number of horses are being treated that might not be considered Search strategy appropriate candidates for prophylactic treatment. There were 74 horses in the Edwards trial and 3 horses in the McKenzie Pubmed/Medline (1966–Jan 2007) (http://pubmed.org/): trial that failed to develop high CK levels either with or dantrolene AND equine. -
Understanding Measures of Treatment Effect in Clinical Trials a K Akobeng
54 Arch Dis Child: first published as 10.1136/adc.2004.061747 on 21 December 2004. Downloaded from CURRENT TOPIC Understanding measures of treatment effect in clinical trials A K Akobeng ............................................................................................................................... Arch Dis Child 2005;90:54–56. doi: 10.1136/adc.2004.052233 Evidence based medicine implies that healthcare admitted with RSV infection was10.6% for those receiving placebo and 4.8% for those receiving professionals are expected to base their practice on the prophylactic palivizumab. It should be noted that best available evidence. This means that we should acquire AR and all the other measures of treatment effect the necessary skills for appraising the medical literature, discussed below are statistical estimates and the uncertainty in the estimates should be accom- including the ability to understand and interpret the results panied by confidence intervals. of published articles. This article discusses in a simple, practical, ‘non-statistician’ fashion some of the important Absolute risk reduction outcome measures used to report clinical trials comparing In a study comparing a group of patients who different treatments or interventions. Absolute and relative were exposed to a particular intervention with another group who did not receive the interven- risk measures are explained, and their merits and demerits tion, the absolute risk reduction (ARR) is discussed. The article aims to encourage healthcare calculated as the arithmetic difference in the professionals to appreciate the use and misuse of these AR of an outcome in individuals who were outcome measures and to empower them to calculate these exposed to the intervention and the AR of the outcome in those unexposed to the intervention. -
Medical Statistics PDF File 9
M249 Practical modern statistics Medical statistics About this module M249 Practical modern statistics uses the software packages IBM SPSS Statistics (SPSS Inc.) and WinBUGS, and other software. This software is provided as part of the module, and its use is covered in the Introduction to statistical modelling and in the four computer books associated with Books 1 to 4. This publication forms part of an Open University module. Details of this and other Open University modules can be obtained from the Student Registration and Enquiry Service, The Open University, PO Box 197, Milton Keynes MK7 6BJ, United Kingdom (tel. +44 (0)845 300 60 90; email [email protected]). Alternatively, you may visit the Open University website at www.open.ac.uk where you can learn more about the wide range of modules and packs offered at all levels by The Open University. To purchase a selection of Open University materials visit www.ouw.co.uk, or contact Open University Worldwide, Walton Hall, Milton Keynes MK7 6AA, United Kingdom for a brochure (tel. +44 (0)1908 858779; fax +44 (0)1908 858787; email [email protected]). Note to reader Mathematical/statistical content at the Open University is usually provided to students in printed books, with PDFs of the same online. This format ensures that mathematical notation is presented accurately and clearly. The PDF of this extract thus shows the content exactly as it would be seen by an Open University student. Please note that the PDF may contain references to other parts of the module and/or to software or audio-visual components of the module. -
SUPPLEMENTARY APPENDIX Powering Bias and Clinically
SUPPLEMENTARY APPENDIX Powering bias and clinically important treatment effects in randomized trials of critical illness Darryl Abrams, MD, Sydney B. Montesi, MD, Sarah K. L. Moore, MD, Daniel K. Manson, MD, Kaitlin M. Klipper, MD, Meredith A. Case, MD, MBE, Daniel Brodie, MD, Jeremy R. Beitler, MD, MPH Supplementary Appendix 1 Table of Contents Content Page 1. Additional Methods 3 2. Additional Results 4 3. Supplemental Tables a. Table S1. Sample size by trial type 6 b. Table S2. Accuracy of control group mortality by trial type 6 c. Table S3. Predicted absolute risk reduction in mortality by trial type 6 d. Table S4. Difference in predicted verses observed treatment effect, absolute risk difference 6 e. Table S5. Characteristics of trials by government funding 6 f. Table S6. Proportion of trials for which effect estimate includes specified treatment effect size, 7 all trials g. Table S7. Inconclusiveness of important effect size for reduction in mortality among trials 7 without a statistically significant treatment benefit h. Table S8. Inconclusiveness of important effect size for increase in mortality among trials 7 without a statistically significant treatment harm 4. Supplemental Figures a. Figure S1. Screening and inclusion of potentially eligible studies 8 b. Figure S2. Butterfly plot of predicted and observed mortality risk difference, grouped by 9 journal c. Figure S3. Butterfly plot of predicted and observed mortality risk difference, grouped by 10 disease area d. Figure S4. Trial results according to clinically important difference in mortality on absolute 11 and relative scales, grouped by journal e. Figure S5. Trial results according to clinically important difference in mortality on absolute 12 and relative scales, grouped by disease area f. -
The Use of Stata in Medical Statistics and Epidemiology: a Long Journey
A retrospective view Stata Progress Epidemiology and Biostatistics with Stata My Journey with Stata The use of Stata in Medical Statistics and Epidemiology: a long journey Rino Bellocco, Sc.D. Department of Statistics and Quantitative Methods University of Milano-Bicocca & Department of Medical Epidemiology and Biostatistics Karolinska Institutet Nordic and Baltic Stata Users Group meeting, Stockholm, September 1, 2017 1 / 44 A retrospective view Stata Progress Epidemiology and Biostatistics with Stata My Journey with Stata Outline A retrospective view Stata Progress Epidemiology and Biostatistics with Stata My Journey with Stata 2 / 44 A retrospective view Stata Progress Epidemiology and Biostatistics with Stata My Journey with Stata Outline A retrospective view Stata Progress Epidemiology and Biostatistics with Stata My Journey with Stata 3 / 44 A retrospective view Stata Progress Epidemiology and Biostatistics with Stata My Journey with Stata Some History 1985-1995 • Version 1.0 - 1.5, January 1985 - February 1987 (around 48 commands, regress logit ) 4 / 44 N. J. Cox 15 Table 2: Releases of Stata 1.0 January 1985 3.1 August 1993 1.1 February 1985 4.0 January 1995 1.2 March 1985 5.0 October 1996 1.4 August 1986 6.0 January 1999 1.5 February 1987 7.0 December 2000 2.0 June 1988 8.0 January 2003 A retrospective view Stata2.05 Progress June 1989Epidemiology and Biostatistics8.1 July with 2003 Stata My Journey with Stata 2.1 September 1990 8.2 October 2003 3.0 MarchBasic 1992 Commands Table 3: Stata 1.0 and Stata 1.1 append dir infile plot spool beep do input query summarize by drop label regress tabulate capture erase list rename test confirm exit macro replace type convert expand merge run use correlate format modify save count generate more set describe help outfile sort Stata 1.0 had int, long, float,anddouble variables; it did not have byte or str#.