Evolution of treatment effects over time: Empirical insight from recursive cumulative metaanalyses

被引:162
作者
Ioannidis, JPA
Lau, J
机构
[1] Tufts Univ, Sch Med, New England Med Ctr, Div Clin Care Res, Boston, MA 02111 USA
[2] Univ Ioannina, Sch Med, Dept Hyg & Epidemiol, Clin Trials & Evidence Based Med Unit, GR-45110 Ioannina, Greece
关键词
mega-trials; heterogeneity; randomized trials;
D O I
10.1073/pnas.021529998
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Evidence on how much medical interventions work may change over time. It is important to determine what fluctuations in the treatment effect reported by randomized trials and their metaanalyses may be expected and whether extreme fluctuations signal future major changes. We applied recursive cumulative metaanalysis of randomized controlled trials to evaluate the relative change in the pooled treatment effect (odds ratio) over time for 60 interventions in two medical fields (pregnancy/perinatal medicine, n = 45 interventions; myocardial infarction, n = 15 interventions). We evaluated the scatter of relative changes for different numbers of total patients in previous trials. Outlier cases were noted with changes greater than 2.5 standard deviations of the expected. With 500 accumulated patients, the pooled odds ratio may change by 0.6- to 1.7-fold in the immediate future. When 2000 patients have already been randomized, the respective figures are between 0.74- and 1.35-fold for pregnancy/ perinatal medicine and between 0.83- and 1.21-fold for myocardial infarction studies. Extreme early fluctuations in the treatment effect were observed in three interventions (magnesium in myocardial infarction, calcium and antiplatelet agents for prevention of preeclampsia), where recent mega-trials have contradicted prior metaanalyses, as well as in four other examples where early large treatment effects were dissipated when more data appeared. Past experience may help quantify the uncertainty surrounding the treatment effects reported in early clinical trials and their metaanalyses. Early wide oscillations in the evolution of the treatment effect for specific interventions may sometimes signal further major changes in the future.
引用
收藏
页码:831 / 836
页数:6
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