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Representation and Outcomes of Individuals With Schizophrenia Seen in Everyday Practice Who Are Ineligible for Randomized Clinical Trials
IMPORTANCE: Most evidence about efficacy and safety of antipsychotics in schizophrenia spectrum disorders relies on randomized clinical trials (RCTs). However, owing to their strict eligibility criteria, RCTs represent only a part of the real-world population (ie, unselected patients seen in everyda...
Autores principales: | , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Medical Association
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8792792/ https://www.ncbi.nlm.nih.gov/pubmed/35080618 http://dx.doi.org/10.1001/jamapsychiatry.2021.3990 |
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author | Taipale, Heidi Schneider-Thoma, Johannes Pinzón-Espinosa, Justo Radua, Joaquim Efthimiou, Orestis Vinkers, Christiaan H. Mittendorfer-Rutz, Ellenor Cardoner, Narcís Pintor, Luis Tanskanen, Antti Tomlinson, Anneka Fusar-Poli, Paolo Cipriani, Andrea Vieta, Eduard Leucht, Stefan Tiihonen, Jari Luykx, Jurjen J. |
author_facet | Taipale, Heidi Schneider-Thoma, Johannes Pinzón-Espinosa, Justo Radua, Joaquim Efthimiou, Orestis Vinkers, Christiaan H. Mittendorfer-Rutz, Ellenor Cardoner, Narcís Pintor, Luis Tanskanen, Antti Tomlinson, Anneka Fusar-Poli, Paolo Cipriani, Andrea Vieta, Eduard Leucht, Stefan Tiihonen, Jari Luykx, Jurjen J. |
author_sort | Taipale, Heidi |
collection | PubMed |
description | IMPORTANCE: Most evidence about efficacy and safety of antipsychotics in schizophrenia spectrum disorders relies on randomized clinical trials (RCTs). However, owing to their strict eligibility criteria, RCTs represent only a part of the real-world population (ie, unselected patients seen in everyday clinical practice), which may result in an efficacy-effectiveness gap. OBJECTIVE: To quantify the proportion of real-world individuals with schizophrenia spectrum disorders who would be ineligible for participation in RCTs, and to explore whether clinical outcomes differ between eligible and ineligible individuals. DESIGN, SETTING, AND PARTICIPANTS: This study applied eligibility criteria typically used in RCTs for relapse prevention in schizophrenia spectrum disorders to real-world populations. Individuals with diagnoses of schizophrenia spectrum disorders recorded in national patient registries in Finland and Sweden were identified. Individuals who had used antipsychotics continuously for 12 weeks in outpatient care were selected. Individuals were followed up for up to 1 year while they were receiving maintenance treatment with any second-generation antipsychotic (excluding clozapine). Follow-up was censored at treatment discontinuation, initiation of add-on antipsychotics, death, and end of database linkage. MAIN OUTCOMES AND MEASURES: Proportions of RCT-ineligible individuals with schizophrenia spectrum disorders owing to any and specific RCT exclusion criteria. The risk of hospitalization due to psychosis within 1-year follow-up in ineligible vs eligible persons were compared using hazard ratios (HR) and corresponding 95% CIs. RESULTS: The mean (SD) age in the Finnish cohort (n = 17 801) was 47.5 (13.8) years and 8972 (50.4%) were women; the mean (SD) age in the Swedish cohort (n = 7458) was 44.8 (12.5) years and 3344 (44.8%) were women. A total of 20 060 individuals (79%) with schizophrenia spectrum disorders would be ineligible for RCTs (Finnish cohort: 14 221 of 17 801 [79.9%]; Swedish cohort: 5839 of 7458 [78.3%]). Most frequent reasons for ineligibility were serious somatic comorbidities and concomitant antidepressant/mood stabilizer use. Risks of hospitalization due to psychosis was higher among ineligible than eligible individuals (Finnish cohort: 18.4% vs 17.2%; HR, 1.14 [95% CI, 1.04-1.24]; Swedish cohort: 20.1% vs 14.8%; HR, 1.47 [95% CI, 1.28-1.92]). The largest risks of hospitalization due to psychosis were observed in individuals ineligible owing to treatment resistance, tardive dyskinesia, and history of suicide attempts. Finally, with more ineligibility criteria met, larger risks of hospitalization due to psychosis were observed in both countries. CONCLUSIONS AND RELEVANCE: RCTs may represent only about a fifth of real-world individuals with schizophrenia spectrum disorders. Underrepresented (ineligible) patients with schizophrenia spectrum disorders have moderately higher risks of admission due to psychosis while receiving maintenance treatment than RCT-eligible patients. These findings set the stage for future studies targeting real-world populations currently not represented by RCTs. |
format | Online Article Text |
id | pubmed-8792792 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | American Medical Association |
record_format | MEDLINE/PubMed |
spelling | pubmed-87927922022-02-07 Representation and Outcomes of Individuals With Schizophrenia Seen in Everyday Practice Who Are Ineligible for Randomized Clinical Trials Taipale, Heidi Schneider-Thoma, Johannes Pinzón-Espinosa, Justo Radua, Joaquim Efthimiou, Orestis Vinkers, Christiaan H. Mittendorfer-Rutz, Ellenor Cardoner, Narcís Pintor, Luis Tanskanen, Antti Tomlinson, Anneka Fusar-Poli, Paolo Cipriani, Andrea Vieta, Eduard Leucht, Stefan Tiihonen, Jari Luykx, Jurjen J. JAMA Psychiatry Original Investigation IMPORTANCE: Most evidence about efficacy and safety of antipsychotics in schizophrenia spectrum disorders relies on randomized clinical trials (RCTs). However, owing to their strict eligibility criteria, RCTs represent only a part of the real-world population (ie, unselected patients seen in everyday clinical practice), which may result in an efficacy-effectiveness gap. OBJECTIVE: To quantify the proportion of real-world individuals with schizophrenia spectrum disorders who would be ineligible for participation in RCTs, and to explore whether clinical outcomes differ between eligible and ineligible individuals. DESIGN, SETTING, AND PARTICIPANTS: This study applied eligibility criteria typically used in RCTs for relapse prevention in schizophrenia spectrum disorders to real-world populations. Individuals with diagnoses of schizophrenia spectrum disorders recorded in national patient registries in Finland and Sweden were identified. Individuals who had used antipsychotics continuously for 12 weeks in outpatient care were selected. Individuals were followed up for up to 1 year while they were receiving maintenance treatment with any second-generation antipsychotic (excluding clozapine). Follow-up was censored at treatment discontinuation, initiation of add-on antipsychotics, death, and end of database linkage. MAIN OUTCOMES AND MEASURES: Proportions of RCT-ineligible individuals with schizophrenia spectrum disorders owing to any and specific RCT exclusion criteria. The risk of hospitalization due to psychosis within 1-year follow-up in ineligible vs eligible persons were compared using hazard ratios (HR) and corresponding 95% CIs. RESULTS: The mean (SD) age in the Finnish cohort (n = 17 801) was 47.5 (13.8) years and 8972 (50.4%) were women; the mean (SD) age in the Swedish cohort (n = 7458) was 44.8 (12.5) years and 3344 (44.8%) were women. A total of 20 060 individuals (79%) with schizophrenia spectrum disorders would be ineligible for RCTs (Finnish cohort: 14 221 of 17 801 [79.9%]; Swedish cohort: 5839 of 7458 [78.3%]). Most frequent reasons for ineligibility were serious somatic comorbidities and concomitant antidepressant/mood stabilizer use. Risks of hospitalization due to psychosis was higher among ineligible than eligible individuals (Finnish cohort: 18.4% vs 17.2%; HR, 1.14 [95% CI, 1.04-1.24]; Swedish cohort: 20.1% vs 14.8%; HR, 1.47 [95% CI, 1.28-1.92]). The largest risks of hospitalization due to psychosis were observed in individuals ineligible owing to treatment resistance, tardive dyskinesia, and history of suicide attempts. Finally, with more ineligibility criteria met, larger risks of hospitalization due to psychosis were observed in both countries. CONCLUSIONS AND RELEVANCE: RCTs may represent only about a fifth of real-world individuals with schizophrenia spectrum disorders. Underrepresented (ineligible) patients with schizophrenia spectrum disorders have moderately higher risks of admission due to psychosis while receiving maintenance treatment than RCT-eligible patients. These findings set the stage for future studies targeting real-world populations currently not represented by RCTs. American Medical Association 2022-01-26 2022-03 /pmc/articles/PMC8792792/ /pubmed/35080618 http://dx.doi.org/10.1001/jamapsychiatry.2021.3990 Text en Copyright 2022 Taipale H et al. JAMA Psychiatry. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the CC-BY License. |
spellingShingle | Original Investigation Taipale, Heidi Schneider-Thoma, Johannes Pinzón-Espinosa, Justo Radua, Joaquim Efthimiou, Orestis Vinkers, Christiaan H. Mittendorfer-Rutz, Ellenor Cardoner, Narcís Pintor, Luis Tanskanen, Antti Tomlinson, Anneka Fusar-Poli, Paolo Cipriani, Andrea Vieta, Eduard Leucht, Stefan Tiihonen, Jari Luykx, Jurjen J. Representation and Outcomes of Individuals With Schizophrenia Seen in Everyday Practice Who Are Ineligible for Randomized Clinical Trials |
title | Representation and Outcomes of Individuals With Schizophrenia Seen in Everyday Practice Who Are Ineligible for Randomized Clinical Trials |
title_full | Representation and Outcomes of Individuals With Schizophrenia Seen in Everyday Practice Who Are Ineligible for Randomized Clinical Trials |
title_fullStr | Representation and Outcomes of Individuals With Schizophrenia Seen in Everyday Practice Who Are Ineligible for Randomized Clinical Trials |
title_full_unstemmed | Representation and Outcomes of Individuals With Schizophrenia Seen in Everyday Practice Who Are Ineligible for Randomized Clinical Trials |
title_short | Representation and Outcomes of Individuals With Schizophrenia Seen in Everyday Practice Who Are Ineligible for Randomized Clinical Trials |
title_sort | representation and outcomes of individuals with schizophrenia seen in everyday practice who are ineligible for randomized clinical trials |
topic | Original Investigation |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8792792/ https://www.ncbi.nlm.nih.gov/pubmed/35080618 http://dx.doi.org/10.1001/jamapsychiatry.2021.3990 |
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