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，因为它们可以降低复发的风险 和住院治疗。因此，迫切需要加强抗精神病药物依从性的策略， 精神科实践。理想情况下，抗精神病药物将在随机试验中进行研究。然而，在这方面， FEP治疗的进展不能完全依赖于随机试验，随机试验不能回答所有问题。 临床相关问题。因为随机试验不能真实地回答所有关于 早期FEP干预在所有临床人群中的有效性和及时的所有结局， 随机试验的结果需要得到观察性研究结果的补充。因果 从观察数据中推断可以被看作是试图模仿一种假设的语用学 随机试验-目标试验。我们将使用来自FEP-CAUSAL协作的数据来模拟靶向试验 开始口服和长效注射抗精神病药物。为了克服对 由于不同治疗组中个体的不可比性，我们将进行我们的 观察分析分两步进行。首先，我们将确定复制发现所需的观测数据 来自该领域的两项旗舰随机临床试验：EUFEST和PRELAPSE试验。这一基准 现有随机试验估计值的观察效应估计值允许校准， 对观察分析的信心。其次，我们将模拟目标试验， 以前的试验用于FEP患者的管理。具体而言，我们将研究 在青少年和成人中， FEP诊断后的不同治疗策略。这些分析的结果将有助于指导选择 抗精神病药物，以提高依从性和临床结果。本项目2还补充了调查结果 来自项目1的随机试验，使用FEP-CAUSAL协作，一个国际联盟， 由LEAP的方法核心协调的FEP个体的前瞻性队列。我们的目标试验 仿真将率先实施因果推理方法，以观察前景 在FEP中的队列。这种方法的优越性已在以下几个领域得到证明： 医学，但还没有在精神病学。我们期望我们的工作将导致方法上的进步， 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.