A Consumer's Guide to Subgroup Analyses
Publication: Annals of Internal Medicine
Volume 116, Number 1
Abstract
▪ The extent to which a clinician should believe and act on the results of subgroup analyses of data from randomized trials or meta-analyses is controversial. Guidelines are provided in this paper for making these decisions. The strength of inference regarding a proposed difference in treatment effect among subgroups is dependent on the magnitude of the difference, the statistical significance of the difference, whether the hypothesis preceded or followed the analysis, whether the subgroup analysis was one of a small number of hypotheses tested, whether the difference was suggested by comparisons within or between studies, the consistency of the difference, and the existence of indirect evidence that supports the difference. Application of these guidelines will assist clinicians in making decisions regarding whether to base a treatment decision on overall results or on the results of a subgroup analysis.
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Information & Authors
Information
Published In
Annals of Internal Medicine
Volume 116 • Number 1 • 1 January 1992
Pages: 78 - 84
History
Published in issue: 1 January 1992
Published online: 1 December 2008
Keywords
Copyright
© 1992 American College of Physicians.
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A Consumer's Guide to Subgroup Analyses. Ann Intern Med.1992;116:78-84. doi:10.7326/0003-4819-116-1-78
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References
References
1.
Pocock S, Hughes M, and Lee R. Statistical problems in the reporting of clinical trials. N Engl J Med. 1987;317:426-32.
2.
Effectiveness of intravenous thrombolytic treatment in acute myocardial infarction. Gruppo Italiano per lo Studio della Streptochinasi Nell'Infarcto Miocardico (GISSI). Lancet. 1986;2:397-402.
3.
Lee T, Weisberg M, Brand D, Rouan G, and Goldman L. Candidates for thrombolysis among emergency room patients with acute chest pain. Ann Intern Med. 1989;110:957-62.
4.
Tate D and Dehmer G. New challenges for thrombolytic therapy. Ann Intern Med. 1989;110:953-5.
5.
Randomised trial of intravenous streptokinase, oral aspirin, both, or neither among 17,187 cases of suspected acute myocardial infarction: ISIS-2. Lancet. 1988;2:349-60.
6.
Yusuf S, Collins R, and Peto R. Why do we need some large, simple randomized trials? Stat Med. 1984;3:409-20.
7.
. Treatment of Early Breast Cancer. v 1. Worldwide evidence 1985-1990. New York: Oxford University Press; 1990:7-9.
8.
Sackett D, Haynes R, and Tugwell P. Clinical Epidemiology: A Basic Science for Clinical Medicine. Boston: Little, Brown & Company; 1985.
9.
Chalmers T, Smith H, Blackburn B, Silverman B, Schoeder B, and Reitman D. A method for assessing the quality of a randomized control trial. Controlled Clin Trials. 1981;2:31-49.
10.
Fletcher R, Fletcher S, and Wagner E. Clinical Epidemiology. 2d ed. Baltimore: Williams & Wilkins, 1988:185-6.
11.
Feinstein A. Clinical Epidemiology. Philadelphia: W.B. Saunders; 1985:306-7, 516-7.
12.
Goldman L and Feinstein A. Anticoagulants and myocardial infarction. The problems of pooling, drowning, and floating. Ann Intern Med. 1979;90:92-4.
13.
Furberg C and Morgan T. Lessons from overviews of cardiovascular trials. Stat Med. 1987;6:295-306.
14.
Horwitz R. Complexity and contradiction in clinical trial research. Am J Med. 1987;82:498-510.
15.
Buyse M. Analysis of clinical trial outcomes: some comments on subgroup analyses. Controlled Clin Trials. 1989;10:187S-194S.
17.
Byar D. Assessing apparent treatment—covariate interactions in randomized clinical trials. Stat Med. 1985;4:255-63.
18.
Shuster J and van Eys J. Interaction between prognostic factors and treatment. Controlled Clin Trials. 1983;4:209-14.
19.
Kleinbaum D, Kupper L, and Morgenstern H eds. Interaction, effect modification, and synergism. In: Epidemiologic Research. New York: Van Nostrand Reinhold Company, 1982;403-18.
20.
Last J. A Dictionary of Epidemiology. 2d ed. New York: Oxford University Press; 1988:41, 66, 127.
21.
Yusuf S, Wittes J, and Probstfield J. Evaluating effects of treatment in subgroups of patients within a clinical trial: the case of non-Q-wave myocardial infarction and beta blockers. Am J Cardiol. 1990;66:220-2.
22.
Bailey K. Inter-study differences: how should they influence the interpretation and analysis of results? Stat Med. 1987;6:351-8.
23.
Davis C and Leffingwell D. Empirical Bayes estimates of subgroup effects in clinical trials. Controlled Clin Trials. 1990;11:37-42.
24.
Sackett D. Clinical diagnosis and the clinical laboratory. Clin Invest Med. 1978;1:37-43.
25.
Yusuf S, Peto R, Lewis J, Collins R, and Sleight T. Beta blockade during and after myocardial infarction: an overview of the randomized trials. Prog Cardiovas Dis. 1985;27:335-71.
26.
Peto R. Why do we need systematic overviews of randomized trials? Stat Med. 1987;6:233-4.
27.
Schneider B. Analysis of clinical trial outcomes: alternative approaches to subgroup analysis. Controlled Clin Trials. 1989;10:176S-186S.
28.
Breslow N and Day N. Analysis of Case-Control Studies. v 1 of Statistical Methods of Cancer Research. Lyon: IARC Scientific Publications; 1980:122-59.
29.
Donner A. A Bayesian approach to the interpretation of subgroup results in clinical trials. J Chronic Dis. 1982;34:429-35.
30.
Louis T. Estimating a population parameter values using Bayes and empirical Bayes methods. J Am Stat Assoc. 1984;79:393-8.
31.
Beach M and Meier P. Choosing covariates in the analysis of clinical trials. Controlled Clin Trials. 1989;10:161S-175S.
32.
A randomized trial of aspirin and sulfinpyrazone in threatened stroke. The Canadian Cooperative Study Group. N Engl J Med 1978;299:53-9.
33.
Secondary prevention of vascular disease by prolonged antiplatelet treatment. Antiplatelet Trialists' Collaboration. Br Med J [Clin Res]. 1988;296:320-31.
34.
Canner P, Huang Y, and Meinert C. On the detection of outlier clinics in medical trials: I. Practical considerations. Controlled Clin Trials. 1981;2:231-40.
35.
Lee D, Johnson R, Bingham J, Leahy M, Dinsmore R, and Goroll A. Heart failure in outpatients. N Engl J Med. 1982;306:699-705.
36.
A randomized trial of propranolol in patients with acute myocardial infarction. I. Mortality results. Beta-blocker Heart Attack Trial Research Group. JAMA. 1982;247:1707-14.
37.
Furberg C and Byington R. What do subgroup analyses reveal about differential response to beta-blocker therapy? Circulation. 1983;67:198-1101.
38.
Cook D, Witt L, Cook R, and Guyatt G. Stress ulcer prophylaxis in the critically ill—a meta-analysis. Am J Med. [In press.]
39.
Guyatt G, Sullivan M, Fallen E, Tihal H, Rideout E, and Halcrow S. A controlled trial of digoxin in congestive heart failure. Am J Cardiol. 1988;61:371-5.
40.
Jaeschke R, Oxman A, and Guyatt G. To what extent do congestive heart failure patients in sinus rhythm benefit from digoxin therapy? A systematic overview and meta-analysis. Am J Med. 1990;88:279-86.
41.
Stieb D, Frayha H, Oxman A, Shannon H, Hutchison B, and Crombie F. Effectiveness of Haemophilus influenzae type b vaccines. Can Med Assoc J. 1990;142:719-33.
42.
Kelton J, Hirsh J, Carter C, and Buchanan M. Sex differences in the antithrombotic effect of aspirin. Blood. 1978;52;1073-6.
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