The FDA-NIMH-MATRICS Guidelines for Clinical Trial Design of Cognitive-Enhancing Drugs: What Do We Know 5 Years Later?
The FDA-NIMH-MATRICS Guidelines for Clinical Trial Design of Cognitive-Enhancing Drugs: What Do We Know 5 Years Later?
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DOI：
10.1093/schbul/sbq038
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发表时间：
2011-11-01
影响因子：
6.6
通讯作者：
Marder, Stephen R.
中科院分区：
文献类型：
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作者：
Buchanan, Robert W.;Keefe, Richard S. E.;Marder, Stephen R.
美国食品和药物管理局 (FDA)-国家心理健康研究所 (NIMH) - 改善精神分裂症认知的测量和治疗研究 (MATRICS) 精神分裂症认知增强药物临床试验指南和 MATRICS 共识认知电池 (MCCB) 旨在促进治疗认知障碍的新型化合物开发。最近的几项研究利用了 FDA-NIMH-MATRICS 指南和 MCCB，并对指南实施的可行性和 MCCB 性能进行了评估。根据研究结果，我们建议对纳入标准进行如下修改——（1）临床状况和症状纳入标准：2期研究中幻觉和妄想的最高允许评分从中度提高到中度，并取消阴性症状标准； (2) 抗精神病药物纳入标准：应允许使用第一代抗精神病药物，但仅限于无合用抗胆碱能药物且锥体外系症状轻微的情况下，在缺乏相关药代动力学或药效学考虑的情况下，应允许抗精神病药物联合用药； (3) 使用非法物质的人不应被允许参加 1B 或 2A 阶段概念验证研究，但可以被纳入 2B 和 3 阶段研究，在这些研究中，结果的有效性和普遍性证明成为更重要的目标。建议进行这些修订，以加强招募，同时保持足够的方法学严谨性，以确保研究结果的有效性。 MCCB 已被证明具有出色的心理测量特征，包括多中心临床试验的可靠性、与现实世界功能的临床相关性以及对行为治疗可能的敏感性，并且应继续作为精神分裂症认知增强研究的标准结果测量。
The Food and Drug Administration (FDA)-National Institute of Mental Health (NIMH)-Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) clinical trial guidelines for cognitive-enhancing drugs in schizophrenia and the MATRICS Consensus Cognitive Battery (MCCB) were designed to facilitate novel compound development in the treatment of cognitive impairments. Several studies have recently utilized the FDA-NIMH-MATRICS guidelines and MCCB and allow an evaluation of the feasibility of guideline implementation and MCCB performance. In light of the study results, we would recommend the following inclusion criteria revisions-(1) clinical status and symptom inclusion criteria: maximum allowed score for hallucinations and delusions should be increased from moderate to moderately severe and the negative symptom criterion should be dropped in phase 2 studies; (2) antipsychotic medication inclusion criteria: first-generation antipsychotics should be allowed, but only in the context of no concomitant anticholinergic agents and minimal extrapyramidal symptoms, and antipsychotic polypharmacy should be allowed in the absence of pertinent pharmacokinetic or pharmacodynamic considerations; and (3) people who use illicit substances should not be allowed in phase 1B or 2A proof-of-concept studies but may be included in phase 2B and 3 studies in which proof of effectiveness and generalizability of results become more important goals. These revisions are recommended to enhance recruitment while maintaining sufficient methodological rigor to ensure the validity of study results. The MCCB has been shown to have excellent psychometric characteristics, including reliability for multisite clinical trials, clinical relevance for real-world functioning, and possible sensitivity to behavioral treatment, and should continue to serve as the standard outcome measure for cognitive enhancement studies in schizophrenia.