Clinical Trials Represent Only One-Fifth of the Diverse Schizophrenia Population

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In this investigation, researchers examined how patients with schizophrenia are represented in randomized clinical trials and questioned if the results are different for patients not represented in randomized clinical trials.

Because of comorbidities and concomitant medication use, clinical trials only represent about a fifth of the real-world schizophrenia population according to a study published in JAMA Psychiatry.

Without data on how schizophrenia medications perform in the real world, clinical trial sponsors do not get the most comprehensive efficacy data. Those data therefore differ from what’s happening in clinical practice, which is called the efficacy-effectiveness gap. This gap exists in several therapeutic areas as well as the study of antidepressants, the researchers state.

To identify the schizophrenia patient populations who are underrepresented in clinical trials, the researchers simulated clinical trial inclusion and exclusion criteria to Finland and Sweden patient registries.

The researchers focused on individuals hospitalized at least once due to schizophrenia and who used second-generation antipsychotics at the start of follow-up. These are typical interventions used in clinical trials. They’re also the segments of individuals who most often used antipsychotics, they state.

They grouped individuals into those who would meet common eligibility criteria, those ineligible for any reason, and those ineligible for specific reasons such as substance abuse, age, suicide risk, and pregnancy, among others. The mean age was 47.5 and 44.8 for the Finnish and Swedish cohorts, respectively. The cohorts were fairly evenly divided between men and women.

The researchers found almost 80% of individuals with schizophrenia were ineligible for typical clinical trials. The most common reasons include serious somatic comorbidities, use of mood stabilizers and/or antidepressants, history of substance use, and risk for

suicide. The researchers also found these real-world populations on average had a moderately higher risk for rehospitalization due to psychosis while receiving maintenance treatment with antipsychotics.

The study data doesn’t take into account patients’ willingness to participate in clinical trials or dropouts. Also, the results may not apply to clinical trials with inclusion/exclusion outside of what the researchers considered typical. However, because the researchers did not investigate relative treatment effects, and because the observed risks for clinical outcomes “were not extreme,” the researchers state “no major indications from our research [indicate] that overall RCT results on efficacy and safety of antipsychotics would not apply to ineligible individuals.”

They do state that these different subgroups could have “different courses of illness, which also means they might experience differential treatment benefits.” Future studies focusing on these underrepresented groups, in addition to pragmatic trials and/or observational studies would help close the efficacy-effectiveness gap and potentially improve outcomes for all patients with schizophrenia.

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures. 


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 trial. JAMA Psychiatry. 2022;79(3):210-218. doi:10.1001/jamapsychiatry.2021.3990