Clinical trials on the efficacy of treatments for schizophrenia have a number of exclusion criteria for patients, such as the existence of a severe somatic comorbidity or concomitant use of antidepressants. A new international study by the Parc Taulí Institute of Research and Innovation (I3PT) and CIBERSAM, in which Hospital Clínic-IDIBAPS researchers took part, shows that people with schizophrenia who are not eligible for clinical trials have a higher risk of being hospitalized. This means that people with schizophrenia who take part in clinical trials may not be representative of the population with this disorder.
The Clínic-IDIBAPS and CIBERSAM researchers Joaquim Raduà, leader of the Imaging of mood- and anxiety-related disorders (IMARD) group, Luis Pintor and Eduard Vieta, leader of the Bipolar and Depressive Disorders group, and Justo Pinzón Espinosa, joint principal investigator on the study, together with Narcís Cardoner, researchers from I3PT and CIBERSAM (from the group led by Diego José Palao), took part in the study, which was published in JAMA Psychiatry.
The study quantified the proportion of people in the real world with schizophrenia spectrum disorders who would not be eligible to take part in a clinical trial and aimed to identify differences in the risk of hospitalization between eligible and ineligible subjects. The result was a major difference between the clinical course in clinical trials (linked to efficacy) and in routine clinical practice (linked to effectiveness), which has been called the efficacy-effectiveness gap.
To understand how inclusion and exclusion criteria in clinical trials affect results, the authors applied these criteria to real-world populations. Specifically, they identified all people with schizophrenia from the national records of Finland and Sweden and selected 25,259 who had been taking antipsychotic drugs continuously for 12 weeks in outpatient care and followed them (in the records) for a year, emulating the treatment and monitoring performed in a clinical trial.
The researchers found that the fact that almost 80% of people with schizophrenia had not been eligible for a clinical trial was due especially to a severe somatic comorbidity and concomitant use of antidepressants or mood stabilizers. This majority of patients showed an increased risk of being hospitalized due to psychosis (hazard ratio, 1.14-1,47). The increased risk was observed in people who presented a higher number of ineligibility criteria, notably resistance to treatment, tardive dyskinesia, and a history of attempted suicide.
“Clinical trials may represent approximately just one-fifth of real-world people with schizophrenia spectrum disorders”, according to the authors. They also emphasize the fact that “ineligible people have a moderately higher risk of being admitted to hospital due to psychosis”. These results indicate that patients who take part in clinical trials tend to be less severe than those who are visited in a purely patient-care setting and that new studies are required aimed at the real-world population, which is currently poorly represented in clinical trials.
JAMA Psychiatry. 2022 Jan 26. doi: 10.1001/jamapsychiatry.2021.3990.