20 A TALE OF TWO TRIAL DESIGNS: EVALUATION OF EFFICACY VS EFFECTIVENESS IN SCHIZOPHRENIA

Friday, October 19, 2012
The Atrium (Hyatt Regency)
Poster Board # 20
Health Services, and Policy Research (HSP)

Reuven Ferziger, MD1, Lian Mao, PhD2, Joseph Hulihan, MD1, Cynthia A. Bossie, PhD1 and Larry Alphs, MD, PhD1, (1)Janssen Scientific Affairs, LLC, Titusville, NJ, (2)Johnson & Johnson Pharmaceutical Research & Development, LLC, Titusville, NJ

Purpose: Public health decision making is informed by data on how interventions work under actual conditions (“real-world” or effectiveness data), which are captured in pragmatic studies. These studies differ from explanatory studies, which examine whether an intervention can work in controlled circumstances (efficacy data). In any given trial, different design elements may be independently more pragmatic or explanatory—an important consideration for interpretation and generalizability of results. This analysis compares two studies that evaluate the same medication, using an instrument that categorizes various design domains along a pragmatic–explanatory continuum.

Method: Two studies that differed appreciably in terms of their objectives and overall approach were compared: an ongoing study of antipsychotic treatment for people with schizophrenia who have been incarcerated (study 1; PRIDE) and a placebo-controlled trial used for regulatory approval (study 2; Pandina et al, 2010). Studies were scored on a modification of the Pragmatic–Explanatory Continuum Indicator Summary (PRECIS) tool (Thorpe et al, 2009). Modified PRECIS rates 10 key design domains, each on a 7-point rating scale from 0=extremely explanatory to 6=extremely pragmatic (total study score range, 0-60). Five individual raters (the authors) independently scored the studies.

Result: Average (SD) modified PRECIS total scores were 34.0 (6.36) for study 1 (rater scores: 26, 29, 35, 40, 40) and 5.8 (2.17) for study 2 (rater scores: 3, 5, 6, 6, 9). In study 1, 3 of 10 domains had mean scores suggesting that they were predominantly pragmatic (~5), 4 had features of both approaches (~3), and 3 were predominantly explanatory (~2). All 10 mean domain scores for study 2 were predominantly explanatory (0-1) and were more explanatory than those for study 1.

Conclusion: This analysis demonstrates how study 1 (PRIDE; antipsychotic treatment for people with schizophrenia who have been incarcerated) captured more pragmatic (effectiveness) information than study 2 (controlled study supporting regulatory approval). Some of the variability in the ratings was likely due to imprecise definitions of certain domains and inadequate anchoring for the ratings. Evaluation of studies using a modified PRECIS instrument can inform the use of clinical trial results for better public health decision making. Modification of the tool to provide anchoring of the domains is currently under way.  Support: Janssen Scientific Affairs, LLC