Qualitative Methods in Early-Phase Drug Trials: Broadening the Scope of Data and Methods From an RCT of N-Acetylcysteine in Schizophrenia

Objective: The pharmacokinetic profile of a drug often gives little indication of its potential therapeutic application, with many therapeutic uses of drugs being discovered serendipitously while being studied for different indications. As hypothesis-driven, quantitative research methodology is exclusively used in early-phase trials, unexpected but important phenomena may escape detection. In this context, this study aimed to examine the potential for integrating qualitative research methods with quantitative methods in early-phase drug trials. To our knowledge, this mixed methodology has not previously been applied to blinded psychopharmacologic trials.

Method: We undertook qualitative data analysis of clinical observations on the dataset of a randomized, double-blind, placebo-controlled trial of N-acetylcysteine (NAC) in patients with DSM-IV-TR-diagnosed schizophrenia (N = 140). Textual data on all participants, deliberately collected for this purpose, were coded using NVivo 2, and emergent themes were analyzed in a blinded manner in the NAC and placebo groups. The trial was conducted from November 2002 to July 2005.

Results: The principal findings of the published trial could be replicated using a qualitative methodology. In addition, significant differences between NAC- and placebo-treated participants emerged for positive and affective symptoms, which had not been captured by the rating scales utilized in the quantitative trial. Qualitative data in this study subsequently led to a positive trial of NAC in bipolar disorder.

Conclusions: The use of qualitative methods may yield broader data and has the potential to complement traditional quantitative methods and detect unexpected efficacy and safety signals, thereby maximizing the findings of early-phase clinical trial research.

Trial Registration: www.anzctr.org.au Identifier: ACTRN12605000363684

J Clin Psychiatry 2011;72(7):909-913

Submitted: September 21, 2009; accepted December 14, 2009.

Online ahead of print: September 21, 2010 (doi:10.4088/JCP.09m05741yel).

Corresponding author: Michael Berk, MD, PhD, Department of Clinical and Biomedical Sciences: Barwon Health, University of Melbourne, PO Box 281, Geelong 3220, Victoria, Australia ([email protected]).