Abstract P274: A meta-analysis of meta-analyses: Is "reverse Epi" OK or not?
Introduction: Applications of observational risk models assuming “all else equal” to estimate the effect on risk of interventions expected to change the level of one or more independent variables have been criticized as “reverse Epi” since clinical trials provide better estimates of treatment effects.
Hypothesis: The purpose of this analysis is to assess how reasonable it is to use “reverse Epi” to project the number of events avoided under different scenarios in which different markers are used for determining to whom to prescribe and how to target preventative treatment. We pursued this aim by comparing two different meta-analyses which compared HRs for apoB and non-HDL-C. One meta-analysis included 12 published observational studies. In 11 of these studies all subjects were at primary CHD risk. The other meta-analysis included 7 placebo-controlled statin trials (3 primary and 4 secondary).
Methods: We calculated the reciprocal of each observational study’s HR per 1-SD increase (36 mg/dl for non-HDL-C and 27 mg/dl of apoB) to compare with each trials’ HR per 1-SD decrease; calculated the percentage difference (95% CI) in standard HRs for each report assuming a correlation between the two markers of 0.93 (calculated from NHANES 2005-2010 to be representative of adult US residents); and compared the resulting statistics using standard subgroup meta-analysis.
Results: The overall geometric mean point estimate (95% CI) of the difference favoring apoB over non-HDL-C for all observational studies was 11.1% (7.7%, 14.4%) versus 5.4% (2.9%, 9.2%) for all 7 trials (p = 0.007). However these same point estimates are 9.5% (7.3%, 14.0%) versus 10.6% (7.3%, 14.0%) (p=0.714) when only primary studies or trials were included. The geometric mean treatment effect HR among the 4 secondary trials was 0.732 (0.689, 0.792) versus 0.599 (0.504, 0.714) among the 3 primary trials (p = 0.035).
Conclusion: Meaningful differences between primary and secondary observational and interventional studies warrant stratified analysis. Among subjects at primary CHD risk, “reverse Epi” application of primary observational results may provide projections similar to those from applying primary trial results.
Author Disclosures: K. Williams: None. A.D. Sniderman: E. Honoraria; Modest; Merck.
- © 2014 by American Heart Association, Inc.