Statistical choices can affect inferences about treatment efficacy: A case study from obsessive-compulsive disorder research

Helen Blair Simpson*, Eva Petkova, Jianfeng Cheng, Jonathan Huppert, Edna Foa, Michael R. Liebowitz

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

15 Scopus citations


Longitudinal clinical trials in psychiatry have used various statistical methods to examine treatment effects. The validity of the inferences depends upon the different method's assumptions and whether a given study violates those assumptions. The objective of this paper was to elucidate these complex issues by comparing various methods for handling missing data (e.g., last observation carried forward [LOCF], completer analysis, propensity-adjusted multiple imputation) and for analyzing outcome (e.g., end-point analysis, repeated-measures analysis of variance [RM-ANOVA], mixed-effects models [MEMs]) using data from a multi-site randomized controlled trial in obsessive-compulsive disorder (OCD). The trial compared the effects of 12 weeks of exposure and ritual prevention (EX/RP), clomipramine (CMI), their combination (EX/RP&CMI) or pill placebo in 122 adults with OCD. The primary outcome measure was the Yale-Brown Obsessive Compulsive Scale. For most comparisons, inferences about the relative efficacy of the different treatments were impervious to different methods for handling missing data and analyzing outcome. However, when EX/RP was compared to CMI and when CMI was compared to placebo, traditional methods (e.g., LOCF, RM-ANOVA) led to different inferences than currently recommended alternatives (e.g., multiple imputation based on estimation-maximization algorithm, MEMs). Thus, inferences about treatment efficacy can be affected by statistical choices. This is most likely when there are small but potentially clinically meaningful treatment differences and when sample sizes are modest. The use of appropriate statistical methods in psychiatric trials can advance public health by ensuring that valid inferences are made about treatment efficacy.

Original languageAmerican English
Pages (from-to)631-638
Number of pages8
JournalJournal of Psychiatric Research
Issue number8
StatePublished - Jul 2008
Externally publishedYes

Bibliographical note

Funding Information:
This study was supported by NIMH (R01 MH45436 to Dr. Liebowitz, R01 MH45404 to Dr. Foa, and K23 MH01907 to Dr. Simpson). We would like to thank the staff who helped conduct the clinical trial, Mr. Andrew B. Schmidt and Dr. Ning Zhao for expert data management, and Drs. Donald Klein and Franklin Schneier for helpful comments on earlier versions of this manuscript. The first author had full access to the data in the study and takes responsibility for its integrity and the accuracy of the data analysis.


  • Clinical trials
  • Clomipramine
  • Cognitive-behavioral therapy
  • Mixed-effects models
  • Obsessive-compulsive disorder
  • Statistical methods


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