Qualitative methods in early-phase drug trials: broadening the scope of data and
methods from an RCT of N-acetylcysteine in schizophrenia.
Author(s): Berk M, Munib A, Dean O, Malhi GS, Kohlmann K, Schapkaitz I, Jeavons S, Katz F,
Anderson-Hunt M, Conus P, Hanna B, Otmar R, Ng F, Copolov DL, Bush AI.
Affiliation(s): Department of Clinical and Biomedical Sciences: Barwon Health, University of
Melbourne, PO Box 281, Geelong 3220, Victoria, Australia.
mikebe@barwonhealth.org.au
Publication date & source: 2011, J Clin Psychiatry. , 72(7):909-13
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.
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