Usefulness of interim analyses in portending study results in antipsychotic and antidepressant trials

J. Rabinowitz, N. Werbeloff, F. Mandel, F. De Ridder, A. Schacht, F. Menard, I. Caears, V. Stauffer, S. Kapur

Research output: Contribution to journalArticlepeer-review


It is unknown whether interim analyses portend final study results. Fatigue, pressure to complete trials and recruitment differences may mitigate against this. We examined the similarity of efficacy results of the first and second half of recruited patients to complete trials and explore possible intervening variables. Using data from the NewMeds repository of patient level data from placebo-controlled randomized trials of antipsychotics (AP) (22 studies, n=7056) and antidepressants (AD) (39 studies, n=12,217) we compared treatment effect size (placebo vs. active treatment) of the first and second half of patients recruited in completed trials. We found that in AP studies median difference in treatment effect between cohorts was -0.03, indicating that overall first and second cohorts yielded similar results. In AD studies, median difference between cohorts was 0.04, indicating that overall the second cohort had slightly larger active-placebo-difference. Overall, on average there were minimal differences in effect size between the first and the second cohorts, and in 30 of 39 trials interim results were a good estimate of the results on the 2nd cohort. In AD trials first and second cohort results were more similar when the proportion of patients per study centre and recruitment time of the two cohorts was similar. Results suggest that interim analyses in AD and AP studies may reliably serve to estimate ultimate effects and, at least in AD trials, are more accurate when the same sites are used to a similar extent and recruitment time of the two consequent cohorts is similar.

Original languageEnglish
Pages (from-to)1999-2007
Number of pages9
JournalEuropean Neuropsychopharmacology
Issue number11
StatePublished - Nov 2015

Bibliographical note

Funding Information:
Funding for this research was provided by the Innovative Medicine Initiative Joint Undertaking under grant agreement no. 115008 of which resources are composed of EFPIA in-kind contribution and financial contribution from the European Union׳s Seventh Framework Programme (FP7/2007–2013). Funder had no further role in study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication.

Publisher Copyright:
© 2015 Elsevier B.V. and ECNP.


  • Clinical trials
  • Interim analysis


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