Comparison of Academic and Nonacademic Sites in Multi-Center Clinical Trials Christina M. Dording, MD,* Elizabeth D. Dalton, BA,* Michael J. Pencina, PhD,Þ Maurizio Fava, MD,* and David Mischoulon, MD* Abstract: The selection of appropriate subjects is a critical element of successful clinical trials. Failure to properly identify, select, and retain subjects in clinical trials of antidepressant medications may affect the ability to show separation from placebo. Little is known about which type of site, academic or nonacademic, is superior in selecting and retaining appropriate subjects. In the present investigation, the authors conducted a retrospective analysis comparing the performance of academic and nonacademic sites in selecting and retaining appropriate subjects in a recently completed multi-site clinical study of aripiprazole augmenta- tion. The authors used a set of operationalized criteria called the SAFER to identify appropriate study subjects. No significant differences were found in rates of SAFER interview passing, study completion, and clini- cal outcomes between academic and nonacademic sites. Our findings suggest that academic and nonacademic sites are equally effective in their ability to identify and retain appropriate study participants. Key Words: academic, nonacademic, depression, clinical trial, subject selection (J Clin Psychopharmacol 2012;32: 65Y68) S ome proportion of drugs being investigated as treatments for depression is never brought to market because of failure to demonstrate superior efficacy to placebo in clinical trials. Among the many proposed reasons for the inability to show separation from placebo, inappropriate selection and recruit- ment, trial design 1 as well as inadequate retention of subjects at clinical sites may be a significant factor. It is critical that sites participating in clinical trials be able to accurately identify, se- lect, and retain those patients who are appropriate for inclusion in a clinical study on the effectiveness of an antidepressant. Many clinical trials nowadays use a combination of aca- demic and nonacademic recruitment sites, yet it is not clear whether either of these is superior in selecting and retaining appropriate subjects. A literature review through PubMed found only one study that compared the performance of academic and nonacademic research sites, specifically in a population with Alzheimer disease, 2 with the findings favoring the academic centers. However, no such published studies of treatment of mood disorders were identified. A similar comparison of aca- demic and nonacademic centers in the context of psychophar- macologic clinical trials would therefore be of interest. In 2008, Targum et al 3 proposed a set of operationalized criteria known as the SAFER interview to identify patients with the acute primary symptoms that the novel drug is supposed to influence. Criteria for the SAFER inventory include an assess- ment of the following: State versus trait, Assessability, Face validity, Ecological validity, and Rule of the three P’s (pervasive, persistent, and pathological). As part of the Clinical Trials Network and Institute (CTNI) at Massachusetts General Hospital, our experienced physicians are trained in the administration of the SAFER and use this instrument for selecting appropriate research patients after they have been provisionally admitted into a study per usual admissions criteria. We recently completed a multi-site clinical study of aripi- prazole augmentation that included academic and nonacademic study sites and used the SAFER as a screening instrument. 4,5 In a retrospective analysis, we used the SAFER interview outcomes to compare the performance of academic sites versus nonaca- demic sites in selecting and retaining appropriate subjects for the length of this research trial. Given that nonacademic sites are often under greater financial pressure to recruit subjects for clinical trials, we hypothesized that academic sites would have a more rigorous recruiting standard (as confirmed by a lower rate of SAFER interview failures) than nonacademic sites and that the more rigorous selection would result in greater retention rates as well. MATERIALS AND METHODS The parent trial was a 60-day multi-center, double-blind, placebo-controlled study on the efficacy and tolerability of low- dose aripiprazole (2 mg/d) augmentation in patients with Major Depressive Disorder with inadequate antidepressant treatment (ADT) response. 4,5 The study was conducted in accordance with rules and guidelines established by the Partners Human Re- search Committee, and was conducted with approval of the Partners Human Research Committee Internal Review Board. Written informed consent was obtained from all participants by a licensed physician before all study-related procedures. The primary outcome was the difference in response (decrease in Montgomery-Asberg Depression Rating Scale [MADRS] 6 total score of at least 50%) rate using the sequential parallel com- parison design. 7 In accordance with the sequential parallel de- sign, the 60-day double-blind treatment was divided into two 30-day phases, with assessments performed every 10 days. After the 14- to 28-day screening period, eligible patients were ran- domized to either aripiprazole, 2 mg/d (n = 56), or placebo From the *Depression Clinical and Research Program, Massachusetts General Hospital, Harvard Medical School; and †Harvard Clinical Research Institute, Boston, MA. Received November 15, 2010; accepted after revision August 12, 2011. Reprints: Christina M. Dording, MD, Depression Clinical and Research Program, Massachusetts General Hospital, 6th Floor, 1 Bowdoin Square, Boston, MA 02114 (e-mail: cdording@partners.org). The study from which data for the present paper was taken (‘‘A double-blind, placebo-controlled study of aripiprazole adjunctive to antidepressant therapy [ADT] among depressed outpatients with inadequate response to prior ADT [ADAPT-A Study]’’) was an investigator-initiated study supported by Bristol-Myers Squibb, which provided blinded study medication. Bristol-Myers Squibb did not have a role in the study design and in the collection, analysis, or interpretation of data in the ADAPT-A Study. Bristol-Myers Squibb had no role in the writing of the present paper or the decision to submit the paper for publication. The present paper was submitted for review by Bristol-Myers Squibb before submission to the Journal of Clinical Psychopharmacology . Copyright * 2012 by Lippincott Williams & Wilkins ISSN: 0271-0749 DOI: 10.1097/JCP.0b013e31823f3b47 ORIGINAL CONTRIBUTION Journal of Clinical Psychopharmacology & Volume 32, Number 1, February 2012 www.psychopharmacology.com 65 Copyright © 2011 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.