Harms reported by patients in rheumatology drug trials: a systematic review of randomized trials in the cochrane library from an OMERACT working group.


Journal

Seminars in arthritis and rheumatism
ISSN: 1532-866X
Titre abrégé: Semin Arthritis Rheum
Pays: United States
ID NLM: 1306053

Informations de publication

Date de publication:
06 2021
Historique:
received: 22 08 2020
accepted: 30 09 2020
pubmed: 24 1 2021
medline: 30 9 2021
entrez: 23 1 2021
Statut: ppublish

Résumé

Underreporting of harms in randomized controlled trials (RCTs) may lead to incomplete or erroneous assessments of the perceived benefit-to-harm profile of an intervention. To compare benefit with harm in clinical practice and future clinical studies, adverse event (AE) profiles including severity need to be understood. Even though patients report harm symptoms earlier and more frequently than clinicians, rheumatology RCTs currently do not provide a reporting framework from the patient's perspective regarding harms. Our objective for this meta-research project was to identify AEs in order to determine harm clusters and whether these could be self-reported by patients. Our other objective was to examine reported severity grading of the reported harms. We considered primary publications of RCTs eligible if they were published between 2008 and 2018 evaluating pharmacological interventions in patients with a rheumatic or musculoskeletal condition and if they were included in Cochrane reviews. We extracted data on harms such as reported AE terms together with severity (if described), and categorized AE- and severity-terms into overall groups. We deemed all AEs with felt components appropriate for patient self-reporting. The literature search identified 187 possible Cochrane reviews, of which 94 were eligible for evaluation, comprising 1,297 articles on individual RCTs. Of these RCTs, 93 pharmacological trials met our inclusion criteria (including 31,023 patients; representing 20,844 accumulated patient years), which reported a total of 21,498 AEs, corresponding to 693 unique reported terms for AEs. We further sub-categorized these terms into 280 harm clusters (i.e., themes). AEs appropriate for patient self-reporting accounted for 58% of the AEs reported. Among the reported AEs, we identified medical terms for all of the 117 harm clusters appropriate for patient reporting and lay language terms for 86%. We intended to include severity grades of the reported AEs, but there was no evidence for systematic reporting of clinician- or patient-reported severity in the primary articles of the 93 trials. However, we identified 33 terms suggesting severity, but severity grading was discernible in only 9%, precluding a breakdown by severity in this systematic review. Our results support the need for a standardized framework for patients' reporting of harms in rheumatology trials. Reporting of AEs with severity should be included in future reporting of harms, both from the patients' and investigators' perspectives. PROSPERO: CRD42018108393.

Sections du résumé

BACKGROUND
Underreporting of harms in randomized controlled trials (RCTs) may lead to incomplete or erroneous assessments of the perceived benefit-to-harm profile of an intervention. To compare benefit with harm in clinical practice and future clinical studies, adverse event (AE) profiles including severity need to be understood. Even though patients report harm symptoms earlier and more frequently than clinicians, rheumatology RCTs currently do not provide a reporting framework from the patient's perspective regarding harms. Our objective for this meta-research project was to identify AEs in order to determine harm clusters and whether these could be self-reported by patients. Our other objective was to examine reported severity grading of the reported harms.
METHODS
We considered primary publications of RCTs eligible if they were published between 2008 and 2018 evaluating pharmacological interventions in patients with a rheumatic or musculoskeletal condition and if they were included in Cochrane reviews. We extracted data on harms such as reported AE terms together with severity (if described), and categorized AE- and severity-terms into overall groups. We deemed all AEs with felt components appropriate for patient self-reporting.
RESULTS
The literature search identified 187 possible Cochrane reviews, of which 94 were eligible for evaluation, comprising 1,297 articles on individual RCTs. Of these RCTs, 93 pharmacological trials met our inclusion criteria (including 31,023 patients; representing 20,844 accumulated patient years), which reported a total of 21,498 AEs, corresponding to 693 unique reported terms for AEs. We further sub-categorized these terms into 280 harm clusters (i.e., themes). AEs appropriate for patient self-reporting accounted for 58% of the AEs reported. Among the reported AEs, we identified medical terms for all of the 117 harm clusters appropriate for patient reporting and lay language terms for 86%. We intended to include severity grades of the reported AEs, but there was no evidence for systematic reporting of clinician- or patient-reported severity in the primary articles of the 93 trials. However, we identified 33 terms suggesting severity, but severity grading was discernible in only 9%, precluding a breakdown by severity in this systematic review.
CONCLUSIONS
Our results support the need for a standardized framework for patients' reporting of harms in rheumatology trials. Reporting of AEs with severity should be included in future reporting of harms, both from the patients' and investigators' perspectives.
REGISTRATION
PROSPERO: CRD42018108393.

Identifiants

pubmed: 33483129
pii: S0049-0172(21)00006-8
doi: 10.1016/j.semarthrit.2020.09.023
pii:
doi:

Substances chimiques

Pharmaceutical Preparations 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't Review Systematic Review

Langues

eng

Sous-ensembles de citation

IM

Pagination

607-617

Informations de copyright

Copyright © 2021 Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of Competing Interest Berthelsen: none Woodworth: none Ioannidis: none Tugwell: none relevant Devoe: none relevant Williamson: none Terwee: none Suarez-Almazor: none Strand: none relevant Leong: none Goel: none relevant Conaghan: none relevant Boers: none relevant Shea: none relevant Brooks: none relevant Simon: none relevant Furst: none relevant Christensen: none relevant

Auteurs

Dorthe B Berthelsen (DB)

Musculoskeletal Statistics Unit, The Parker Institute, Bispebjerg and Frederiksberg Hospital, Copenhagen, Denmark; Department of Rehabilitation, Municipality of Guldborgsund, Nykoebing F, Denmark.

Thasia G Woodworth (TG)

David Geffen School of Med. Division Rheumatology. UCLA, USA.

Niti Goel (N)

Duke University School of Medicine, Durham, NC, USA.

John P A Ioannidis (JPA)

Departments of Medicine, Epidemiology and Population Health, Biomedical Data Science and Statistics, and Meta-Research Innovation Center at Stanford (METRICS), Stanford University, California, USA.

Peter Tugwell (P)

Department of Medicine, School of Epidemiology, Public Health and Community Medicine, University of Ottawa, Canada.

Dan Devoe (D)

Department of Medicine, University of Calgary, Cumming School of Medicine, Calgary, Canada.

Paula Williamson (P)

MRC North West Hub for Trials Methodology Research, Institute of Translational Medicine, University of Liverpool, Liverpool, UK.

Caroline B Terwee (CB)

Amsterdam UMC, Vrije Universiteit Amsterdam, Department of Epidemiology and Biostatistics and the Amsterdam Public Health Research Institute, Amsterdam, NL.

Maria E Suarez-Almazor (ME)

Department of Health Services Research and Section of Rheumatology and Clinical Immunology, University of Texas MD Anderson Cancer Centre, Houston, TX, USA.

Vibeke Strand (V)

Division of Immunology/Rheumatology, Stanford University, Palo Alto CA, USA.

Amye L Leong (AL)

Healthy Motivation; Global Alliance for Musculoskeletal Health, Bone and Joint Decade, Santa Barbara, California USA.

Philip G Conaghan (PG)

Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, UK; NIHR Leeds Biomedical Research Centre, Leeds, UK.

Maarten Boers (M)

Department of Epidemiology and Biostatistics and the Amsterdam Rheumatology and immunology Centre, Amsterdam University Medical Centers, Vrije Universiteit, Amsterdam, NL.

Beverley J Shea (BJ)

Ottawa Hospital Research Institute, Clinical Epidemiology Program and School of Epidemiology and Public Health, University of Ottawa, Canada.

Peter M Brooks (PM)

Centre for Health Policy Melbourne School of Population and Global Health University of Melbourne and Northern Health, Australia.

Lee S Simon (LS)

SDG LLC Cambridge, MA 02138, USA.

Daniel E Furst (DE)

David Geffen School of Med. Division Rheumatology. UCLA, USA.

Robin Christensen (R)

Musculoskeletal Statistics Unit, The Parker Institute, Bispebjerg and Frederiksberg Hospital, Copenhagen, Denmark; Research Unit of Rheumatology, Department of Clinical Research, University of Southern Denmark, Odense University Hospital, Denmark. Electronic address: Robin.Christensen@regionh.dk.

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Classifications MeSH