Department of Clinical and Biomedical Sciences: Barwon Health, University of Melbourne, PO Box 281, Geelong 3220, Victoria, Australia.
J Clin Psychiatry. 2011 Jul;72(7):909-13. doi: 10.4088/JCP.09m05741yel. Epub 2010 Sep 21.
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.
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.
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.
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.
www.anzctr.org.au Identifier: ACTRN12605000363684.
药物的药代动力学特征通常不能说明其潜在的治疗应用，许多药物的治疗用途是在研究不同适应症时偶然发现的。由于假设驱动的定量研究方法仅在早期试验中使用，因此可能会遗漏意外但重要的现象。在这种情况下，本研究旨在检查将定性研究方法与早期药物试验中的定量方法相结合的可能性。据我们所知，这种混合方法以前尚未应用于盲法精神药理学试验。
我们对 N-乙酰半胱氨酸 (NAC) 治疗 DSM-IV-TR 诊断的精神分裂症患者（N = 140）的随机、双盲、安慰剂对照试验数据集的临床观察进行了定性数据分析。为了这个目的，我们对所有参与者的文本数据进行了编码，使用 NVivo 2，并以盲法在 NAC 和安慰剂组中分析了新出现的主题。该试验于 2002 年 11 月至 2005 年 7 月进行。
使用定性方法可以复制已发表试验的主要发现。此外，NAC 和安慰剂治疗的参与者在阳性和情感症状方面出现了显著差异，这些差异未被定量试验中使用的评分量表捕捉到。本研究的定性数据随后导致了 NAC 在双相情感障碍中的阳性试验。
定性方法的使用可以产生更广泛的数据，并有可能补充传统的定量方法，检测意外的疗效和安全性信号，从而最大限度地提高早期临床试验研究的发现。
www.anzctr.org.au 标识符：ACTRN12605000363684。
