TY - JOUR
T1 - Harms reported by patients in rheumatology drug trials
T2 - a systematic review of randomized trials in the cochrane library from an OMERACT working group
AU - OMERACT Safety Working Group
AU - Berthelsen, Dorthe B.
AU - Woodworth, Thasia G.
AU - Goel, Niti
AU - Ioannidis, John P.A.
AU - Tugwell, Peter
AU - Devoe, Dan
AU - Williamson, Paula
AU - Terwee, Caroline B.
AU - Suarez-Almazor, Maria E.
AU - Strand, Vibeke
AU - Leong, Amye L.
AU - Conaghan, Philip G.
AU - Boers, Maarten
AU - Shea, Beverley J.
AU - Brooks, Peter M.
AU - Simon, Lee S.
AU - Furst, Daniel E.
AU - Christensen, Robin
N1 - Funding Information: The Parker Institute is supported by grants from the Oak Foundation. The Oak Foundation is a group of philanthropic organizations and, since its establishment in 1983; it has given grants to not-for-profit organizations around the world. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. The Parker Institute, Bispebjerg and Frederiksberg Hospital is supported by a core grant from the Oak Foundation (OCAY-18-774-OFIL); the Oak Foundation had no role in the study design, data collection and analyses, interpretation or reporting of this work, or the decision to submit the work for publication. P.G. Conaghan is supported in part by the UK National Institute for Health Research (NIHR) Leeds Biomedical Research Centre. The views expressed are those of the authors and not necessarily those of the UK National Health Service, the NIHR, or the Department of Health. Publisher Copyright: © 2021 Elsevier Inc.
PY - 2021/6
Y1 - 2021/6
N2 - 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
AB - 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
KW - Adverse events
KW - Core Outcome Set
KW - Harms
KW - OMERACT
KW - Rheumatology
UR - http://www.scopus.com/inward/record.url?scp=85099634122&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/j.semarthrit.2020.09.023
DO - https://doi.org/10.1016/j.semarthrit.2020.09.023
M3 - Review article
C2 - 33483129
SN - 0049-0172
VL - 51
SP - 607
EP - 617
JO - Seminars in Arthritis and Rheumatism
JF - Seminars in Arthritis and Rheumatism
IS - 3
ER -