LECTURE 22 2011

- Subgroup Analysis An irresistible temptation Deciding on analysis after looking at the data is dangerous useful and often done(IJ Good 1983 Most

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Subgroup Analysis An irresistible temptation! Deciding on analysis after looking at the data is “dangerous, useful, and often done.” (IJ Good, 1983)
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Most trials report subgroup analyses (median=4 subgroups) Assmann SF, Lancet 2000; 355:1064-1069
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Influence of Study Characteristics on Reporting of Subgroups 44% of 469 randomized trials published in major journals reported subgroup analyses Subgroup analyses were more likely to be reported in high impact journals, non-surgical trials, and large trials. There was an interaction between source of funding and reporting of subgroups in trials without significant overall results – a subgroup finding! Sun et al, BMJ, 2011
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Conclusion: Sun et al, BMJ 2011 “Industry funded randomised controlled trials, in the absence of statistically significant primary outcomes, are more likely to report subgroup analyses than non-industry funded trials. Industry funded trials less frequently test for interaction than non-industry funded trials. Subgroup analyses from industry funded trials with negative results for the primary outcome should be viewed with caution.”
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Aims of Subgroup Analysis To show consistency of trial findings for major endpoints for important patient subsets To assess whether there are large differences in the treatment effect among different types of patients and, if so, identify hypotheses for future research. (Assess the possibility of treatment X subgroup or covariate interactions) Aim should not be to salvage a trial for which the overall results were not as hoped for!
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Subgroup Analysis by Astrological Birth Sign Gemini or Libra 9% (NS) Other signs -28% (p < 0.00001) Overall -23% (p < 0.00001) Percentage Reduction in 5 Week Vascular Mortality “Lack of evidence of benefit just in one particular subgroup is not good evidence of lack of benefit.” ISIS-2: Streptokinase and Aspirin for Acute MI
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Subgrouping Considerations Most trials are not designed to look at subgroups (power is lower for subgroups than overall comparison). For subgroup analysis, it is often not clear how to control for type 1 error (the more subgroups examined, the greater the risk of a type 1 error). Not all subgroups of interest can be pre-specified (we are not that smart). The subgroup may not be what it appears to be (it may be a marker or label for some other characteristic).
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Subgroup Definitions Proper subgroup – grouping of patients according to baseline characteristics Improper subgroup – grouping of patients according to characteristics following randomization (i.e., factors potentially affected by treatment) Interaction – evidence that treatment effects differ by subgroup (quantitative versus qualitative) Yusuf S, et al., JAMA , 266:93-98, 1991 .
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A Priori and A Posteriori Subgroups A priori : written in the protocol in advance of the study A posteriori (post hoc): - specified … later - before unblinding - after unblinding
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INSIGHT START Protocol: Early Treatment
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This note was uploaded on 11/21/2011 for the course PUBH 7420 taught by Professor Ph7420 during the Spring '07 term at Minnesota.

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- Subgroup Analysis An irresistible temptation Deciding on analysis after looking at the data is dangerous useful and often done(IJ Good 1983 Most

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