Comparative effectiveness of pharmacologic strategies to treat first episode psychosis

抗精神病药物是FEP患者护理的基石，因为它们降低了复发的风险 和住院治疗。因此，提高抗精神病药物依从性的策略是#年的迫切需要。 精神科诊所。理想情况下，抗精神病药物将在随机试验中进行研究。然而， FEP管理方面的进展不能完全依赖随机试验，它不能回答所有问题 与临床相关的问题。因为随机试验不能现实地回答所有关于 早期FEP干预在所有临床人群中的有效性和及时获得所有结果， 随机试验的结果需要与观察性研究的结果相辅相成。因果关系 从观测数据进行推断可以被视为一种试图模仿假设的语用 随机试验--目标试验。我们将使用来自FEP-因果协作的数据来模拟目标试验 开始口服和长效注射抗精神病药物。克服对……的担忧 由于不同治疗组中个体的不可比较性，我们将进行 观测分析分两步进行。首先，我们将确定复制研究结果所需的观测数据 来自该领域的两个旗舰随机临床试验：EUFEST和PRELAPSE试验。这个标杆 对现有随机试验估计的观察效应估计允许校准，并增加 对观测分析的信心。其次，我们将模拟目标试验，将结果从 先前对患有FEP的个人的管理试验。具体地说，我们将研究 以下青少年和成人的长期随访中的不依从性、复发和住院 FEP诊断后不同的治疗策略。这些分析的结果将有助于指导选择 使用抗精神病药物来提高依从性和临床疗效。本项目2也是对调查结果的补充 来自项目1中使用FEP-因果合作的随机试验，一个国际财团 由LEAP的方法核心协调的FEP患者的预期队列。我们的目标试验 仿真将开创将因果推理方法论应用于观察前景的先河 FEP中的队列。这种方法论方法的优越性已经在以下几个领域得到了证明 是医学，但还不是精神病学。我们希望我们的工作将在方法上取得进展，并在 这些研究将普遍适用于心理健康研究的许多领域。

Antipsychotic medications are a cornerstone of care for FEP patients because they reduce the risk of relapse and hospitalization. Therefore, strategies to enhance adherence to antipsychotics are an urgent need in psychiatric practice. Ideally, antipsychotic medications would be studied in randomized trials. However, progress in the management of FEP cannot rely exclusively on randomized trials, which cannot answer all clinically relevant questions. Because randomized trials cannot realistically answer all questions about the effectiveness of early FEP interventions in all clinical populations and for all outcomes in a timely way, the findings from randomized trials need to be complemented with those from observational studies. Causal inference from observational data can be viewed as an attempt to emulate a hypothetical pragmatic randomized trial—the target trial. We will use data from the FEP-CAUSAL Collaboration to emulate target trials of initiation of oral and long-acting injectable antipsychotic medications. To overcome concerns about confounding due to noncomparability of individuals in different treatment groups, we will conduct our observational analyses in two steps. First, we will identify the observational data required to replicate findings from two flagship randomized clinical trials in this area: the EUFEST and PRELAPSE trials. This benchmarking of the observational effect estimates to existing randomized trial estimates allows to calibrate, and increase confidence in, the observational analyses. Second, we will emulate target trials that extend the results from previous trials for the management of individuals with FEP. Specifically, we will study the risks of nonadherence, relapse, and hospitalization over longer follow-up periods in adolescents and adults under different treatment strategies after FEP diagnosis. The findings from these analyses will help guide the choice of antipsychotics to enhance adherence and clinical outcomes. This Project 2 also complements the findings from the randomized trial in Project 1 using the FEP-CAUSAL Collaboration, an international consortium of prospective cohorts of individuals with FEP that is coordinated by LEAP’s Methods Core. Our target trial emulations will pioneer the implementation of causal inference methodology to observational prospective cohorts in FEP. The superiority of this methodological approach has been demonstrated in several areas of medicine but not yet in psychiatry. We expect that our work will result in methodological advances and in case studies that will be generally applicable across many areas of mental health research.