Pascale Nevins1, Shelley Vanderhout2, Kelly Carroll3, Stuart G Nicholls3, Seana N Semchishen4, Jamie C Brehaut2, Dean A Fergusson5, Bruno Giraudeau6, Monica Taljaard7. 1. Department of Chemistry and Biomolecular Sciences, University of Ottawa, STEM Complex 150 Louis-Pasteur Pvt, Room 342, Ottawa, Ontario, K1N 6N5, Canada. 2. Ottawa Hospital Research Institute, Clinical Epidemiology Program, Centre for Practice-Changing Research, The Ottawa Hospital, Ottawa, Ontario, K1H 8L6, Canada; School of Epidemiology and Public Health, University of Ottawa, 600 Peter Morand Crescent, Room 101, Ottawa, Ontario, K1G 5Z3, Canada. 3. Ottawa Hospital Research Institute, Clinical Epidemiology Program, Centre for Practice-Changing Research, The Ottawa Hospital, Ottawa, Ontario, K1H 8L6, Canada. 4. School of Epidemiology and Public Health, University of Ottawa, 600 Peter Morand Crescent, Room 101, Ottawa, Ontario, K1G 5Z3, Canada. 5. Ottawa Hospital Research Institute, Clinical Epidemiology Program, Centre for Practice-Changing Research, The Ottawa Hospital, Ottawa, Ontario, K1H 8L6, Canada; School of Epidemiology and Public Health, University of Ottawa, 600 Peter Morand Crescent, Room 101, Ottawa, Ontario, K1G 5Z3, Canada; University of Ottawa, Roger Guindon Hall 451 Smyth Rd, Ottawa, Ontario, K1H 8M5, Canada. 6. Université de Tours, Université de Nantes, INSERM, SPHERE U1246, Tours, France; INSERM CIC1415, CHRU de Tours, Tours, France. 7. Ottawa Hospital Research Institute, Clinical Epidemiology Program, Centre for Practice-Changing Research, The Ottawa Hospital, Ottawa, Ontario, K1H 8L6, Canada; School of Epidemiology and Public Health, University of Ottawa, 600 Peter Morand Crescent, Room 101, Ottawa, Ontario, K1G 5Z3, Canada. Electronic address: mtaljaard@ohri.ca.
Abstract
OBJECTIVES: To describe prevalence of multiple primary outcomes, changes in primary outcomes and target sample sizes between protocols and final reports, and how issues of multiplicity are addressed in pragmatic trials. STUDY DESIGN AND SETTING: Individually randomized trials labeled as pragmatic, published 2014-2019 in MEDLINE and registered with ClinicalTrials.gov. RESULTS: We identified 262 final reports and located protocols for 159 (61%); primary outcomes were clearly reported in 145 (91%) protocols and 256 (98%) final reports. Thirty (19%) protocols and 38 (15%) final reports had multiple primary outcomes. Primary outcomes were present and identical in 128 (81%) matched protocol-final reports. Among 140 pairs with target sample sizes reported, 28 (20.0%) reduced their target sample size (mean 543 fewer participants per trial) and 16 (11.4%) increased it (mean 192 more participants per trial). Thirteen (29.5%) provided an explanation. Only 2 of 30 (7%) protocols and 4 of 38 (11%) final reports with co-primary outcomes explained how results would be interpreted in light of multiplicity; 21 of 30 (70%) protocols and 20 of 38 (53%) final reports accounted for co-primary outcomes in power calculations. CONCLUSION: Co-primary outcomes are common in pragmatic trials; improved transparency around design and analysis decisions involving co-primary outcomes is required.
OBJECTIVES: To describe prevalence of multiple primary outcomes, changes in primary outcomes and target sample sizes between protocols and final reports, and how issues of multiplicity are addressed in pragmatic trials. STUDY DESIGN AND SETTING: Individually randomized trials labeled as pragmatic, published 2014-2019 in MEDLINE and registered with ClinicalTrials.gov. RESULTS: We identified 262 final reports and located protocols for 159 (61%); primary outcomes were clearly reported in 145 (91%) protocols and 256 (98%) final reports. Thirty (19%) protocols and 38 (15%) final reports had multiple primary outcomes. Primary outcomes were present and identical in 128 (81%) matched protocol-final reports. Among 140 pairs with target sample sizes reported, 28 (20.0%) reduced their target sample size (mean 543 fewer participants per trial) and 16 (11.4%) increased it (mean 192 more participants per trial). Thirteen (29.5%) provided an explanation. Only 2 of 30 (7%) protocols and 4 of 38 (11%) final reports with co-primary outcomes explained how results would be interpreted in light of multiplicity; 21 of 30 (70%) protocols and 20 of 38 (53%) final reports accounted for co-primary outcomes in power calculations. CONCLUSION: Co-primary outcomes are common in pragmatic trials; improved transparency around design and analysis decisions involving co-primary outcomes is required.
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