RCTs Represent Just a Minority of Real-World Patients With Schizophrenia

Four out of 5 real-world patients with schizophrenia spectrum disorders are typically ineligible for participation in randomized clinical trials (RCTs), suggests a study published in JAMA Psychiatry.

“Furthermore, we found that RCT-ineligible real-world individuals had, on average, a moderately higher risk for rehospitalization due to psychosis while receiving maintenance treatment with antipsychotics,” researchers wrote. “This increased risk was observed in several subpopulations, ie, individuals ineligible for specific reasons such as substance use, risk of suicide, treatment resistance, or tardive dyskinesia.”

The study applied typical RCT inclusion criteria to 25,259 people with schizophrenia and schizoaffective disorder in national patient registries in Finland and Sweden. Researchers also identified outpatients who had used antipsychotics continuously for 12 weeks and followed them for up to 1 year while on maintenance treatment with a second-generation antipsychotic to gauge the risk of hospitalization for psychosis by RCT eligibility status.

Some 79% of the study population was ineligible for RCT inclusion, the study found. Serious somatic comorbidities and concomitant antidepressant or mood stabilizer use were the most common reasons for ineligibility, followed by history of substance use and risk of suicide.

Patients ineligible for RCTs had higher risks of hospitalization due to psychosis compared with patients eligible for RCT inclusion: 18.4% vs 17.2% in the Finnish cohort, and 20.1% vs 14.8% in the Swedish cohort. Among patients ineligible for RCTs, the largest risks of hospitalization due to psychosis were among those ineligible because of treatment resistance, tardive dyskinesia, and history of suicide attempts, according to the study. As a patient met more ineligibility criteria, their risk of hospitalization grew.

“Because we showed that the majority of individuals with schizophrenia are not represented by typical RCTs and that clinical outcomes can differ between eligible and ineligible individuals,” researchers wrote, “targeted RCTs, subgroup analyses of RCTs with broader inclusion criteria, and observational cohorts focusing on underrepresented subpopulations are warranted.”

Reference

Taipale H, Schneider-Thoma J, Pinzón-Espinosa J, et al. Representation and outcomes of individuals with schizophrenia seen in everyday practice who are ineligible for randomized clinical trials. JAMA Psychiatry. 2022;79(3):210-218. doi: 10.1001/jamapsychiatry.2021.3990