This page is a repository of useful books and articles on all things EBM.
Books and user manuals
- Users' Guides to the Medical Literature: A Manual for Evidence-Based Clinical Practice.
- User manual for trial sequential analysis (TSA). Copenhagen Trial Unit, Centre for Clinical Intervention Research, Copenhagen, Denmark. 2011. p. 1-115.
- Pocock SJ, et al. Statistical controvesies in reporting of clinical trials. J Am Coll Cardiol 2015;66:2648-62 (review of various aspects of clinical trial reporting, including secondary outcomes, intention-to-treat vs per-protocol, subgroup analyses, and interpreting unexpected/surprising findings)
- Pocock SJ, et al. Design of major randomized trials. J Am Coll Cardiol 2015;66:2757-66 (review of key design considerations for clinical trials)
- Pocock SJ, et al. Challenging issues in clinical trial design. J Am Coll Cardiol 2015;66:2886-98 (review of alternate clinical trial designs, including non-inferiority trials, factorial trials, and adaptive designs)
Generalizability (external validity)
- Rothwell PM. Factors that can affect the external validity of randomized controlled trials. PLoS Clin Trials 2006;1:e9.
Risk of bias (internal validity)
- Higgins JP, et al. The Cochrane Collaboration's tool for assessing risk of bias in randomised trials. BMJ 2011;343:d5928.
- Juni P, et al. The hazards of scoring the quality of clinical trials for meta-analysis. JAMA 1999;282:1054-60.
- Savovic J, et al. Influence of reported study design characteristics on intervention effect estimates from randomized, controlled trials. Ann Intern Med 2012;157:429-38.
- Hrobjartsson A, et al. Observer bias in randomized clinical trials with measurement scale outcomes: A systematic review of trials with both blinded and nonblinded assessors. CMAJ 2013;185:E201-11.
- Lane P. Handling drop-out in longitudinal clinical trials: A comparison of the LOCF and MMRM approaches. Pharm Stat 2008;7:93-106.
- Molnar FJ, et al. Have last-observation-carried-forward analyses caused us to favour more toxic dementia therapies over less toxic alternatives? A systematic review. Open Med 2009;3:e31-50.
- Kjaergard LL, et al. Reported methodologic quality and discrepancies between large and small randomized trials in meta-analyses. Ann Intern Med 2001;135:982-9.
Results and statistics
- Pocock SJ, et al. Making sense of statistics in clinical trial reports. J Am Coll Cardiol 2015;66:2536-49 (fantastic review of fundamental statistical concepts used in clinical trials)
- Pereira TV, et al. Empirical evaluation of very large treatment effects of medical interventions. JAMA 2012;308:1676-84.
- Furukawa TA, et al. Can we individualize the 'number needed to treat'? An empirical study of summary effect measures in meta-analyses. Int J Epidemiol 2002;31:72-6.
- Freemantle N. Interpreting the results of secondary end points and subgroup analyses in clinical trials: Should we lock the crazy aunt in the attic? BMJ 2001;322:989-91.
- Hackshaw A, et al. Interpreting and reporting clinical trials with results of borderline significance. BMJ 2011;343:d3340.
- Schulz KF, et al. Multiplicity in randomised trials II: Subgroup and interim analyses. Lancet 2005;365:1657-61.
- Bassler D, et al. Stopping randomized trials early for benefit and estimation of treatment effects: Systematic review and meta-regression analysis. JAMA 2010;303:1180-7.
- Sun X, et al. Is a subgroup effect believable? Updating criteria to evaluate the credibility of subgroup analyses. BMJ 2010;340:c117.
- Rothwell PM. Treating individuals 2. Subgroup analysis in randomised controlled trials: Importance, indications, and interpretation. Lancet 2005;365:176-86.
- Turgeon RD. Critically appraising randomized controlled trials: Is there substance in subgroups? UBC PSSJ 2013;1:19-21.
- Wallach JD, et al. Evaluation of evidence of statistical support and corroboration of subgroup claims in randomized clinical trials. JAMA Intern Med 2017;epub.
- Mulla SM, et al. How to use a noninferiority trial: Users' guides to the medical literature. JAMA 2012;308:2605-11
- Kaji AH, et al. Noninferiority trials: Is a new treatment almost as effective as another? JAMA 2015;313:2371-2
- Thornby KA, et al. Simplifying and interpreting the FACTS of noninferiority trials: A stepwise approach. Am J Health Syst Pharm 2014;71:1926
- Kaul S, et al. Good enough: A primer on the analysis and interpretation of noninferiority trials. Ann Intern Med 2006;145:62-9.
- Head SJ, et al. Non-inferiority study design: Lessons to be learned from cardiovascular trials. Eur Heart J 2012;33:1318-24.
Trials used as examples in NERDCAT-RCT
- HYVET Beckett NS, et al. Treatment of hypertension in patients 80 years of age or older. NEJM 2008;358:1887-98.
- HPS MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: A randomised placebo-controlled trial. Lancet 2002;360:7-22.
- ROCKET-AF Patel MR, et al. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. NEJM 2011;365:883-91.
- El-Khalili N, et al. Extended-release quetiapine fumarate (quetiapine XR) as adjunctive therapy in major depressive disorder (MDD) in patients with an inadequate response to ongoing antidepressant treatment: A multicentre, randomized, double-blind, placebo-controlled study. Int J Neuropsychopharmacol 2010;13:917-32.
- Wilt TJ, et al. Effectiveness of statin therapy in adults with coronary heart disease. Arch Intern Med 2004;164:1427-36.
- Tonelli M, et al. Efficacy of statins for primary prevention in people at low cardiovascular risk: A meta-analysis. CMAJ 2011;183:E1189-202.
- CAPRIE A randomised, blinded, trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE). Lancet 1996;348:1329-39.
- HOPE Yusuf S, et al. Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. NEJM 2000;342:145-53.
- FIELD Keech A, et al. Effects of long-term fenofibrate therapy on cardiovascular events 9795 people with type 2 diabetes mellitus (the FIELD study): Randomised controlled trial. Lancet 2005;366:1849-61.
- ELITE Pitt B. Randomised trial of losartan versus captopril in patients over 65 with heart failure (Evaluation of Losartan in the Elderly Study, ELITE). Lancet 1997;349:747-52.
- ELITE II Pitt B. Effect of losartan compared with captopril on mortality in patients with symptomatic heart failure: Randomised trial - the Losartan Heart Failure Survival Study ELITE II. Lancet 2000;355:1582-7.
- Nguyen-Khac E, et al. Glucocorticoids plus N-acetylcysteine in severe alcoholic hepatitis. NEJM 2011;365:1781-9.
- CONDOR Chan FK, et al. Celecoxib versus omeprazole and diclofenac in patients with osteoarthritis and rheumatoid arthritis (CONDOR): A randomised trial. Lancet 2010;376:173-9.
- UKPDS 38 UK Prospective Diabetes Study Group. Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 38. BMJ 1998;317:703-13.
- JUPITER Ridker PM, et al. Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. NEJM 2008;359:2195-207.
- Ridker PM, et al. Rosuvastatin in the primary prevention of cardiovascular disease among patients with low levels of low-density lipoprotein cholesterol and elevated high-sensitivity C-reactive protein: Rationale and design of the JUPITER trial. Circulation 2003;108:2292-7.
- PHS Steering Committee of the Physicians' Health Study Research Group. Final report of the aspirin component of the ongoing Physicians' Health Study. NEJM 1989;321:129-35.
- WHS Ridker PM, et al. A randomized trial of low-dose aspirin in the primary prevention of cardiovascular disease in women. NEJM 2005;352:1293-304.
- RE-LY Connolly SJ, et al. Dabigatran versus warfarin in patients with atrial fibrillation. NEJM 2009;361:1139-51.
- RESET Kim BK, et al. A new strategy for discontinuation of dual antiplatelet therapy: The RESET Trial (REal Safety and Efficacy of 3-month dual antiplatelet Therapy following Endeavor zotarolimus-eluting stent implantation). J Am Coll Cardiol 2012;60:1340-8.
- CREDO Steinhubl SR, et al. Early and sustained dual oral antiplatelet therapy following percutaneous coronary intervention: A randomized controlled trial. JAMA 2002;288:2411-20.
- EINSTEIN-PE Buller HR, et al. Oral rivaroxaban for the treatment of symptomatic pulmonary embolism. NEJM 2012;366:1287-97.
- Hart RG, et al. Antithrombotic therapy to prevent stroke in patients with atrial fibrillation: A meta-analysis. Ann Intern Med 1999;131:492-501.
Systematic review +/- meta-analysis
- Royle P, et al. Literature searching for randomized controlled trials used in Cochrane reviews: Rapid versus exhaustive searches. Int J Technol Assess Health Care 2003;19:591-603.
- Scott I, et al. Cautionary tales in the interpretation of systematic reviews of therapy trials. Intern Med J 2006;36:587-99.
- Pogue J, et al. Overcoming the limitations of current meta-analysis of randomised controlled trials. Lancet 1998;351:47-52.
- Tierney JF, et al. Individual participant data (IPD) meta-analyses of randomized controlled trials: Guidance on their use. PLoS Med 2015;12:e1001855.
Risk of bias assessment
Publication bias and grey literature
- Ioannidis JP. Effect of the statistical significance of results on the time to completion and publication of randomized efficacy trials. JAMA 1998;279:281-6.
- Hopewell S, et al. Publication bias in clinical trials due to statistical significance or direction of trial results. Cochrane Database Syst Rev 2009;(1):MR000006.
- McAuley L, et al. Does the inclusion of grey literature influence estimates of intervention effectiveness reported in meta-analyses? Lancet 2000;356:1228-31.
- Jones CW, et al. Non-publication of large randomized clinical trials: Cross sectional analysis. BMJ 2013;347:f6104.
Selective outcome reporting bias
- Hart B, et al. Effect of reporting bias on meta-analyses of drug trials: Reanalysis of meta-analyses. BMJ 2012;344:d7202.
- Chan AW, et al. Empirical evidence for selective reporting of outcomes in randomized trials: Comparison of protocols to published articles. JAMA 2004;291:2457-65.
- Chan AW, et al. Outcome reporting bias in randomized trials funded by the Canadian Institute of Health Research. CMAJ 2004;171:735-40.
Results: Heterogeneity and fixed- versus random-effects models
- Higgins JP, et al. Measuring inconsistency in meta-analyses. BMJ 2003;327:557-60.
- Guyatt GH, et al. GRADE guidelines: 7. Rating the quality of evidence - Inconsistency. J Clin Epidemiol 2011;64:1294-302.
- Fleiss JL. The statistical basis of meta-analysis. Stat Methods Med Res 1993;2:121-45.
- Poole C, et al. Random-effects meta-analyses are not always conservative. Am J Epidemiol 1999;150:469-75.
- Engels EA, et al. Heterogeneity and statistical significance in meta-analysis: An Empirical study of 125 meta-analyses. Stat Med 2000;19:1707-28.
- Hill AB. The environment and disease: Association or causation. Proc R Soc Med 1965;58:295-300 (Sir Bradford-Hill's 9 proposed criteria for determining causation)
Clinical prediction rules
- McGinn TG, et al. Users' guides to the medical literature: XXII: How to use articles about clinical decision rules. JAMA 2000;284:79-84.
- Braitman LE, et al. Predicting clinical states in individual patients. Ann Intern Med 1996;125:406-12.
- Laupacis A, et al. Clinical prediction rules. A review and suggested modifications of methodological standards. JAMA 1997;277:488-94.
- Stiell IG, et al. Methodologic standards for the development of clinical decision rules in emergency medicine. Ann Emerg Med 1999;33:437-47.
- Altman DG, et al. What do we mean by validating a prognostic model? Stat Med 2000;19:453-73.
- Moons KG, et al. Prognosis and prognostic research: What, why, and how? BMJ 2009;338:b375.
- Moons KG, et al. Risk prediction models: I. Development, internal validation, and assessing the incremental value of a new (bio)marker. Heart 2012;98:683-90.
Generalizability of clinical prediction rules
- Justice AC, et al. Assessing the generalizability of prognostic information. Ann Intern Med 1999;130:515-24.
- Altman DG, et al. Prognosis and prognostic research: Validating a prognostic model. BMJ 2009;338:b605.
- Moons KG, et al. Prognosis and prognostic research: Application and impact of prognostic models in clinical practice. BMJ 2009;338:b606.
- Moons KG, et al. Risk prediction models: II. External validation, model updating, and impact assessment. Heart 2012;98:691-8.
Risk of bias in studies of clinical prediction rules
Statistics used in studies of diagnostic tests and clinical prediction rules
- Cook NR. Statistical evaluation of prognostic versus diagnostic models: Beyond the ROC curve. Clin Chem 2008;54:17-23.
- Concato J, et al. The risk of determining risk with multivariable models. Ann Intern Med 1993;118:201-10.
- Cook EF, et al. Empiric comparison of multivariable analytic techniques: Advantages and disadvantages of recursive partitioning analysis. J Chronic Dis 1984;37:721-31.
- Moons KG, et al. Using the outcome for imputation of missing predictor values was preferred. J Clin Epidemiol 2006;59:1092-101.
- Janssen KJ, et al. Missing covariate data in medical research: To impute is better than to ignore. J Clin Epidemiol 2010;63:721-7.
- Peduzzi P, et al. Importance of events per independent variable in proportional hazards regression analysis. II. Accuracy and precision of regression estimates. J Clin Epidemiol 1995;48:1503-10.
Clinical prediction rules used as examples in NERDCAT-CPR
- CHADS2 derivation study Gage BF, et al. Validation of clinical classification schemes for predicting stroke: Results from the National Registry of Atrial Fibrillation. JAMA 2001;285:2864-70.
- Rothberg MB, et al. Risk factor model to predict venous thromboembolism in hospitalized medical patients. J Hosp Med 2011;6:202-9.