NCDEU Poster Session 2012

Analysis of the Impact of Family History Subgroups on Drug Placebo Separation and Placebo Response on Tandem Rater and Computer Outcomes in RCTS

Daniel DeBonis, BS; Jean Dries, RN, MSN; Michelle Arkow; Rachel Cummings; and Gary Sachs, MD
From Bracket Global, Wayne, Pennsylvania (Dr Sachs, Ms Arkow, Ms Cummings, Ms DeBonis, and Ms Dries), and Massachusetts General Hospital, Boston (Dr Sachs).

This poster presentation was supported by Bracket Global.

Introduction: High placebo response is associated with clinical trial failure. Family history is considered a validator of psychiatric diagnosis, and is one factor to examine when researching placebo response in clinical trials.

Methods: We have examined patterns of placebo response in multiple depression (MDD and bipolar) studies to explore hypotheses regarding the failure of double-blind, RCT trials. Each trial also included tandem assessments of the primary outcome measure (MADRS or HAMD) administered by site-based raters (MADRSSBR or HAMDSBR) and independently assessed by computer (MADRSCOMP or HAMDCOMP). Placebo response was compared for subgroups reporting no reported family history of mood disorder (FHx(-)) and subjects reporting at least one first or secondary family member with a mood disorder (FHx(+)).

Results: In each trial, no significant differences were found between the placebo group and active treatment groups for both the rater and computer tandem assessments on any of the efficacy measures. Among FHx(-) subjects the active vs placebo difference favored placebo in all 4 trials. This difference reached statistical significance based on MADRSCOMP or HAMDCOMP, but not MADRSSBR or HAMDSBR, in three of the four trials examined. Placebo response was numerically higher in the FHx(-) groups than in the FHx(+) groups across each study that was reviewed.

Conclusions: Our review of recent RCTs suggests high rates of placebo response in subjects reporting no family history of mood disorder may be a causal factor in failure of these efficacy studies. Further studies are needed to clarify which correlates of the FHx(-) subject status may be associated with high placebo response (e.g. diagnostic validity or enrollment rate).

Learning Objectives:
Utility of family history as diagnostic validity

Clinical trial methodologies

References
Nierenberg AA, Trivedi MH, Fava M, et al. Family history of mood disorder and characteristics of major depressive disorder: a STAR*D (Sequenced Treatment Alternatives to Relieve Depression) study. J Psychiatr Res. 2007;41(3–4):214–221. PubMed

Feighner JP, Robins E, Guze SB, et al. Diagnostic criteria for use in psychiatric research. Arch Gen Psychiatry. 1972;26(1):57–63. PubMed

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