Knowlson, Catherine, Brealey, Stephen Derek orcid.org/0000-0001-9749-7014, Keding, Ada orcid.org/0000-0002-1182-887X et al. (2 more authors) (2023) Examination of early treatment effects and related biases during the conduct of two UK-wide pragmatic orthopaedic surgical trials:ProFHER and UK FROST. Bone & Joint Open. pp. 96-103. ISSN 2633-1462
Abstract
Aims Early large treatment effects can arise in small studies, which lessen as more data accumulate. This study aimed to retrospectively examine whether early treatment effects occurred for two multicentre orthopaedic randomized controlled trials (RCTs) and explore biases related to this. Methods Included RCTs were ProFHER (PROximal Fracture of the Humerus: Evaluation by Randomisation), a two-arm study of surgery versus non-surgical treatment for proximal humerus fractures, and UK FROST (United Kingdom Frozen Shoulder Trial), a three-arm study of two surgical and one non-surgical treatment for frozen shoulder. To determine whether early treatment effects were present, the primary outcome of Oxford Shoulder Score (OSS) was compared on forest plots for: the chief investigator’s (CI) site to the remaining sites, the first five sites opened to the other sites, and patients grouped in quintiles by randomization date. Potential for bias was assessed by comparing mean age and proportion of patients with indicators of poor outcome between included and excluded/non-consenting participants. Results No bias in treatment effect was observed overall for the CI site, or the first five sites, compared with the remaining sites in either trial. An early treatment effect on the OSS was observed for the first quintile of participants recruited to ProFHER only (clinically relevant difference of seven points). Selection bias for age was observed in the ProFHER trial only, with slightly younger patients being recruited into the study. Both trials showed some selection bias for markers of poor prognosis, although these did not appear to change over time. Conclusion No bias in treatment effects overall were found at the CI or early sites set-up. An early treatment effect was found in one of the two trials, which was likely a chance effect as this did not continue during the study. Selection bias was observed in both RCTs, however this was minimal and did not impact on outcome.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2023 Author(s) et al. |
Dates: |
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Institution: | The University of York |
Academic Units: | The University of York > Faculty of Sciences (York) > Health Sciences (York) |
Funding Information: | Funder Grant number NETSCC 13/26/01 NETSCC 16/73/03 |
Depositing User: | Pure (York) |
Date Deposited: | 01 Mar 2023 15:10 |
Last Modified: | 17 Oct 2024 08:53 |
Published Version: | https://doi.org/10.1302/2633-1462.42.BJO-2022-0139 |
Status: | Published |
Refereed: | Yes |
Identification Number: | 10.1302/2633-1462.42.BJO-2022-0139 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:196935 |
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Filename: 2633_1462.42.BJO_2022_0139.pdf
Description: Examination of early treatment effects and related biases during the conduct of two UK-wide pragmatic orthopaedic surgical trials: ProFHER and UK FROST
Licence: CC-BY-NC-ND 2.5