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Qualitative methods in early-phase drug trials : data and methods from a trial of N-acetylcysteine in schizophrenia

journal contribution
posted on 2011-07-01, 00:00 authored by Michael BerkMichael Berk, A Munib, Olivia DeanOlivia Dean, G Malhi, K Kohlmann, I Schapkaitz, S Jeavons, F Katz, Murray Anderson-Hunt, P Conus, Barbara Hanna, Renee OtmarRenee Otmar, F Ng, D Copolov, A Bush
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.



Journal of clinical psychiatry






909 - 913


Physicians Postgraduate Press


[Memphis, Tenn.]







Publication classification

C1.1 Refereed article in a scholarly journal

Copyright notice

2010, Physicians Postgraduate Press