Faculty of Pharmacy, Université de Montréal, Montreal, Quebec, Canada.
YolaRX Consultants, Montreal, Quebec, Canada.
Pharmacol Res Perspect. 2022 Feb;10(1):e00915. doi: 10.1002/prp2.915.
Although relapse is an important outcome to measure the effectiveness of schizophrenia treatment, no standard definition exists. This review aimed at identifying definitions and measurements of schizophrenia relapse in observational studies of long-acting injectables (LAIs) versus oral antipsychotics (OAPs) and at determining their impact on heterogeneity of comparative effectiveness estimates. A systematic review was conducted using MEDLINE and Embase (01 January 2010-11 November 2019 [date last searched]). Pragmatic searches of gray literature and snowballing were also conducted. Search outputs were screened independently by two assessors at first stage, and full-text of potentially eligible sources at second stage. For each retained source, definition and measurement of relapse, study methods, and comparative effectiveness estimates were extracted. Heterogeneity of estimates was assessed using I statistic with a threshold of 50% for substantial heterogeneity. Literature search yielded 543 sources and pragmatic searches, 21, of which 35 were eligible. Twelve definitions of relapse were found based on hospitalization/emergency department (ED) data (28 studies) or clinical assessment (5 studies). No definition was provided in five studies. According to quantitative analyses, in studies defining relapse as schizophrenia-related hospitalization and/or ED visits over 1-year follow-up, LAIs were significantly more effective than OAPs. For studies measuring relapse based on all-cause hospitalization, heterogeneity was too high for pooling; yet this definition is the most frequently found in pooled estimates published in the literature. Schizophrenia relapse definitions led to substantial heterogeneity of comparative effectiveness estimates of LAIs versus OAPs. Creating study subgroups based on relapse definition effectively reduces statistical heterogeneity.
尽管复发是衡量精神分裂症治疗效果的重要指标，但目前尚没有统一的定义。本研究旨在确定长效注射剂（LAIs）与口服抗精神病药（OAPs）的观察性研究中精神分裂症复发的定义和测量方法，并确定它们对比较有效性估计值异质性的影响。本研究采用 MEDLINE 和 Embase 进行了系统评价（2010 年 1 月 1 日至 2019 年 11 月 11 日[最后检索日期]）。还进行了实用搜索的灰色文献和滚雪球搜索。搜索结果首先由两名评估人员进行独立筛选，然后对可能符合条件的来源进行全文筛选。对于每个保留的来源，都提取了复发的定义和测量、研究方法和比较有效性估计值。使用 I 统计量评估估计值的异质性，当 I 统计量超过 50%时认为存在显著异质性。文献搜索产生了 543 个来源和实用搜索，其中 21 个来源，其中 35 个来源符合条件。根据住院/急诊（ED）数据（28 项研究）或临床评估（5 项研究），发现了 12 种复发的定义。有 5 项研究没有提供定义。根据定量分析，在将复发定义为 1 年随访期间与精神分裂症相关的住院和/或 ED 就诊的研究中，LAIs 明显比 OAPs 更有效。对于基于全因住院治疗测量复发的研究，由于异质性过高而无法进行合并；然而，该定义是文献中发表的合并估计中最常发现的定义。精神分裂症复发的定义导致了 LAIs 与 OAPs 比较有效性估计值的显著异质性。根据复发定义创建研究亚组可以有效降低统计异质性。
