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Comparison of Clinical Trial Changes in Primary Outcome and Reported Intervention Effect Size Between Trial Registration and Publication

Chen, Tao ORCID:, Li, Chao, Qin, Rui, Wang, Yang, Yu, Dahai, Dodd, James, Wang, Duolao ORCID: and Cornelius, victoria (2019) 'Comparison of Clinical Trial Changes in Primary Outcome and Reported Intervention Effect Size Between Trial Registration and Publication'. JAMA Network Open, Vol 2, Issue 7, e197242.

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IMPORTANCE Primary outcome change could threaten the validity of a clinical trial; however, evidence about the consequences on the reported intervention effect size is unclear.

OBJECTIVES To examine the status of randomized clinical trials whose primary outcome changed between trial registration and publication and to quantify the association of this change with the
reported intervention effect size.

DESIGN, SETTING, AND PARTICIPANTS In this cross-sectional study on the primary report of randomized clinical trials with clear prospectively registered primary outcomes, PubMed and Embase
were searched for articles published between January 1, 2011, and December 31, 2015. The search was conducted in January 2016, identifying randomized clinical trials and the combination of
keywords and text words related to registry.
MAIN OUTCOMES AND MEASURES Based on the developed approach, trials were classified as having primary outcome change when there was a major discrepancy between the registered and
published primary outcomes. Intervention effect was estimated or recalculated using the odds ratio (OR) for each comparison. Each component OR is structured so that an OR is less than 1 if the
intervention group has a more favorable result than the control group. The ratio of ORs (ROR), which is the summary OR for trials with primary outcome change divided by those without, and its 95%CI were calculated, with a value less than 1 indicating a larger reported intervention effect size in trials with primary outcome change than those without.

RESULTS Among 29 749 searched articles (28 810 MEDLINE and 939 Embase), 1488 articles were randomly selected for review. Of 389 trials with clear primary outcomes prospectively described in
the registry (416 outcomes reported), 33.4%(130 of 389) of trials had at least 1 primary outcome change. Most (66 of 130) of the changes were either not reporting or omitting the primary outcome.
In total, 338 trials (365 outcomes and 487 comparisons) were available for quantitative analysis on the reported intervention effect size bias assessment. Compared with those without primary
outcome change, trials with primary outcome change showed a 16%(pooled ROR, 0.84; 95%CI,0.73-0.96) larger reported intervention effect size. The result persisted after adjustment for potential confounders (ROR, 0.81; 95%CI, 0.71-0.93) and other sensitivity and subgroup analyses.

CONCLUSIONS AND RELEVANCE Results of this study suggest that inconsistencies between registered and published primary outcomes of clinical trials are common, and trials with primary outcome change are likely to have a larger intervention effect than those without.

Item Type: Article
Subjects: QV Pharmacology > Drug Standardization. Pharmacognosy. Medicinal Plants > QV 771 Standardization and evaluation of drugs
WA Public Health > Statistics. Surveys > WA 900 Public health statistics
WA Public Health > Statistics. Surveys > WA 950 Theory or methods of medical statistics. Epidemiologic methods
Faculty: Department: Clinical Sciences & International Health > Clinical Sciences Department
Digital Object Identifer (DOI):
Depositing User: Christine Bradbury
Date Deposited: 01 Aug 2019 08:02
Last Modified: 06 Sep 2019 15:27


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