Keefe Richard S E, Davis Vicki G, Harvey Philip D, Atkins Alexandra S, Haig George M, Hagino Owen, Marder Stephen, Hilt Dana C, Umbricht Daniel
Department of Psychiatry and Behavioral Sciences, Duke University, Duke University Medical Center, Durham, North Carolina2NeuroCog Trials, Durham, North Carolina.
NeuroCog Trials, Durham, North Carolina.
JAMA Psychiatry. 2017 Aug 1;74(8):807-814. doi: 10.1001/jamapsychiatry.2017.1574.
Patients' previous experience with performance-based cognitive tests in clinical trials for cognitive impairment associated with schizophrenia can create practice-related improvements. Placebo-controlled trials for cognitive impairment associated with schizophrenia are at risk for these practice effects, which can be difficult to distinguish from placebo effects.
To conduct a systematic evaluation of the magnitude of practice effects on the Measurement and Treatment Research to Improve Cognition in Schizophrenia Consensus Cognitive Battery (MCCB) in cognitive impairment associated with schizophrenia and to examine which demographic, clinical, and cognitive characteristics were associated with improvement in placebo conditions.
DESIGN, SETTING, AND PARTICIPANTS: A blinded review was conducted of data from 813 patients with schizophrenia who were treated with placebo in 12 randomized placebo-controlled clinical trials conducted mostly in outpatient clinics in North America, Europe, Asia, and Latin America from February 22, 2007, to March 1, 2014. A total of 779 patients provided data for the primary outcome measure at baseline and at least 1 follow-up. Seven trials had prebaseline assessments wherein the patients knew that they were not receiving treatment, allowing a comparison of practice and placebo effects in the same patients.
Placebo compared with various experimental drug treatments.
Composite score on the MCCB.
Of the 813 patients in the study (260 women and 553 men; mean [SD] age, 41.2 [11.5] years), the mean MCCB composite score at baseline was 22.8 points below the normative mean, and the mean (SEM) total change in the MCCB during receipt of placebo was 1.8 (0.2) T-score points (95% CI, 1.40-2.18), equivalent to a change of 0.18 SD. Practice effects in the 7 studies in which there was a prebaseline assessment were essentially identical to the postbaseline placebo changes. Baseline factors associated with greater improvements in the MCCB during receipt of placebo included more depression/anxiety (F1,438 = 5.41; P = .02), more motivation (F1,272 = 4.63; P = .03), and less improvement from screening to baseline (F1,421 = 59.32; P < .001).
Placebo effects were minimal and associated with the number of postbaseline assessments and several patient characteristics. Given that the patients performed 2.28 SDs below normative standards on average at baseline, a mean placebo-associated improvement of less than 0.2 SD provides evidence that ceiling effects do not occur in these trials. These minimal changes in the MCCB could not be responsible for effective active treatments failing to separate from placebo.
在与精神分裂症相关的认知障碍的临床试验中，患者之前接受基于表现的认知测试的经历可能会带来与实践相关的改善。针对与精神分裂症相关的认知障碍的安慰剂对照试验存在这些实践效应的风险，而这些效应可能难以与安慰剂效应区分开来。
对与精神分裂症相关的认知障碍中实践效应在精神分裂症认知改善测量与治疗研究共识认知成套测验（MCCB）上的程度进行系统评估，并检查哪些人口统计学、临床和认知特征与安慰剂条件下的改善相关。
设计、设置和参与者：对2007年2月22日至2014年3月1日期间在北美、欧洲、亚洲和拉丁美洲的门诊诊所进行的12项随机安慰剂对照临床试验中接受安慰剂治疗的813例精神分裂症患者的数据进行了盲法审查。共有779例患者在基线和至少1次随访时提供了主要结局指标的数据。7项试验进行了基线前评估，其中患者知道自己未接受治疗，从而能够在同一患者中比较实践效应和安慰剂效应。
安慰剂与各种实验性药物治疗进行比较。
MCCB的综合评分。
在该研究的813例患者中（260例女性和553例男性；平均[标准差]年龄为41.2[11.5]岁），基线时MCCB综合评分平均比正常均值低22.8分，接受安慰剂治疗期间MCCB的平均（标准误）总变化为1.8（0.2）T分数点（95%置信区间，1.40 - 2.18），相当于0.18标准差的变化。在有基线前评估的7项研究中，实践效应与基线后安慰剂变化基本相同。与接受安慰剂治疗期间MCCB更大改善相关的基线因素包括更多的抑郁/焦虑（F1,438 = 5.41；P = 0.02）、更多的动机（F1,272 = 4.63；P = 0.03）以及从筛查到基线的改善较少（F1,421 = 59.32；P < 0.001）。
安慰剂效应极小，且与基线后评估次数及若干患者特征相关。鉴于患者在基线时平均比正常标准低2.28标准差，平均与安慰剂相关的改善小于0.2标准差，这表明在这些试验中不存在天花板效应。MCCB的这些微小变化不可能是有效活性治疗未能与安慰剂区分开来的原因。
