# Comparative effectiveness of pharmacologic strategies to treat first episode psychosis

> **NIH NIH P50** · MCLEAN HOSPITAL · 2024 · $191,882

## Abstract

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.

## Key facts

- **NIH application ID:** 10918301
- **Project number:** 5P50MH115846-06
- **Recipient organization:** MCLEAN HOSPITAL
- **Principal Investigator:** MIGUEL HERNAN
- **Activity code:** P50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $191,882
- **Award type:** 5
- **Project period:** 2019-05-15 → 2028-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10918301

## Citation

> US National Institutes of Health, RePORTER application 10918301, Comparative effectiveness of pharmacologic strategies to treat first episode psychosis (5P50MH115846-06). Retrieved via AI Analytics 2026-06-11 from https://api.ai-analytics.org/grant/nih/10918301. Licensed CC0.

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