IMPORTANCE Most evidence about efficacy and safety of antipsychotics in schizophrenia spectrum disorders relies on randomized clinical trials (RCTs). However, owing to their strict eligibility criteria, RCTs represent only a part of the real-world population (ie, unselected patients seen in everyday clinical practice), which may result in an efficacy-effectiveness gap. OBJECTIVE To quantify the proportion of real-world individuals with schizophrenia spectrum disorders who would be ineligible for participation in RCTs, and to explore whether clinical outcomes differ between eligible and ineligible individuals. DESIGN, SETTING, AND PARTICIPANTS This study applied eligibility criteria typically used in RCTs for relapse prevention in schizophrenia spectrum disorders to real-world populations. Individuals with diagnoses of schizophrenia spectrum disorders recorded in national patient registries in Finland and Sweden were identified. Individuals who had used antipsychotics continuously for 12 weeks in outpatient care were selected. Individuals were followed up for up to 1 year while they were receiving maintenance treatment with any second-generation antipsychotic (excluding clozapine). Follow-up was censored at treatment discontinuation, initiation of add-on antipsychotics, death, and end of database linkage. MAIN OUTCOMES AND MEASURES Proportions of RCT-ineligible individuals with schizophrenia spectrum disorders owing to any and specific RCT exclusion criteria. The risk of hospitalization due to psychosis within 1-year follow-up in ineligible vs eligible persons were compared using hazard ratios (HR) and corresponding 95% CIs. RESULTS The mean (SD) age in the Finnish cohort (n = 17 801) was 47.5 (13.8) years and 8972 (50.4%) were women; the mean (SD) age in the Swedish cohort (n = 7458) was 44.8 (12.5) years and 3344 (44.8%) were women. A total of 20 060 individuals (79%) with schizophrenia spectrum disorders would be ineligible for RCTs (Finnish cohort: 14 221 of 17 801 [79.9%]; Swedish cohort: 5839 of 7458 [78.3%]). Most frequent reasons for ineligibility were serious somatic comorbidities and concomitant antidepressant/mood stabilizer use. Risks of hospitalization due to psychosis was higher among ineligible than eligible individuals (Finnish cohort: 18.4% vs 17.2%; HR, 1.14 [95% CI, 1.04-1.24]; Swedish cohort: 20.1% vs 14.8%; HR, 1.47 [95% CI, 1.28-1.92]). The largest risks of hospitalization due to psychosis were observed in individuals ineligible owing to treatment resistance, tardive dyskinesia, and history of suicide attempts. Finally, with more ineligibility criteria met, larger risks of hospitalization due to psychosis were observed in both countries. CONCLUSIONS AND RELEVANCE RCTs may represent only about a fifth of real-world individuals with schizophrenia spectrum disorders. Underrepresented (ineligible) patients with schizophrenia spectrum disorders have moderately higher risks of admission due to psychosis while receiving maintenance treatment than RCT-eligible patients. These findings set the stage for future studies targeting real-world populations currently not represented by RCTs.

中文翻译：

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日常实践中不符合随机临床试验资格的精神分裂症患者的代表性和结果。

重要性大多数关于抗精神病药在精神分裂症谱系障碍中的疗效和安全性的证据依赖于随机临床试验（RCT）。然而，由于其严格的资格标准，随机对照试验仅代表真实世界人群的一部分（即日常临床实践中未选择的患者），这可能会导致疗效-疗效差距。目的 量化现实世界中没有资格参与 RCT 的精神分裂症谱系障碍患者的比例，并探讨符合条件和不符合条件的个体之间的临床结果是否不同。设计、设置和参与者 本研究将 RCT 中通常用于预防精神分裂症谱系障碍复发的资格标准应用于现实世界的人群。确定了在芬兰和瑞典的国家患者登记处记录的精神分裂症谱系障碍诊断个体。选择在门诊连续使用抗精神病药物 12 周的个体。在接受任何第二代抗精神病药（不包括氯氮平）的维持治疗期间，对个体进行长达 1 年的随访。在停止治疗、开始添加抗精神病药物、死亡和数据库链接结束时对随访进行审查。主要结果和措施 由于任何和特定的 RCT 排除标准，患有精神分裂症谱系障碍的 RCT 不合格个体的比例。使用风险比 (HR) 和相应的 95% CI 比较了不合格与合格人员在 1 年内因精神病而住院的风险。结果 芬兰队列 (n = 17 801) 的平均 (SD) 年龄为 47.5 (13.8) 岁，其中 8972 (50.4%) 为女性；瑞典队列 (n = 7458) 的平均 (SD) 年龄为 44.8 (12.5) 岁，其中 3344 (44.8%) 为女性。共有 20060 名精神分裂症谱系障碍患者（79%）不符合 RCT 的条件（芬兰队列：17801 人中的 14221 人 [79.9%]；瑞典队列：7458 人中的 5839 人 [78.3%]）。最常见的不合格原因是严重的躯体合并症和同时使用抗抑郁药/情绪稳定剂。不符合条件的人因精神病而住院的风险高于符合条件的人（芬兰队列：18.4% vs 17.2%；HR，1.14 [95% CI，1.04-1.24]；瑞典队列：20.1% vs 14.8%；HR，1.47 [95 % CI，1.28-1.92]）。在因治疗抵抗、迟发性运动障碍和自杀未遂史而不符合条件的个体中观察到因精神病而住院的最大风险。最后，随着更多的不合格标准得到满足，两国都观察到因精神病住院的风险更大。结论和相关性 RCT 可能仅代表现实世界中精神分裂症谱系障碍患者的约五分之一。与符合 RCT 条件的患者相比，在接受维持治疗时，代表性不足（不符合条件的）精神分裂症谱系障碍患者因精神病入院的风险略高。这些发现为未来针对目前未由 RCT 代表的现实世界人群的研究奠定了基础。在满足更多不合格标准的情况下，两国都观察到因精神病住院的风险更大。结论和相关性 RCT 可能仅代表现实世界中精神分裂症谱系障碍患者的约五分之一。与符合 RCT 条件的患者相比，在接受维持治疗时，代表性不足（不符合条件的）精神分裂症谱系障碍患者因精神病入院的风险略高。这些发现为未来针对目前未由 RCT 代表的现实世界人群的研究奠定了基础。在满足更多不合格标准的情况下，两国都观察到因精神病住院的风险更大。结论和相关性 RCT 可能仅代表现实世界中精神分裂症谱系障碍患者的约五分之一。与符合 RCT 条件的患者相比，在接受维持治疗时，代表性不足（不符合条件的）精神分裂症谱系障碍患者因精神病入院的风险略高。这些发现为未来针对目前未由 RCT 代表的现实世界人群的研究奠定了基础。与符合 RCT 条件的患者相比，在接受维持治疗时，代表性不足（不符合条件的）精神分裂症谱系障碍患者因精神病入院的风险略高。这些发现为未来针对目前未由 RCT 代表的现实世界人群的研究奠定了基础。与符合 RCT 条件的患者相比，在接受维持治疗时，代表性不足（不符合条件的）精神分裂症谱系障碍患者因精神病入院的风险略高。这些发现为未来针对目前未由 RCT 代表的现实世界人群的研究奠定了基础。