Mario Gaudino1, Marc Ruel2, Jean-Francois Obadia3, Michele De Bonis4, John Puskas5, Giuseppe Biondi-Zoccai6, Dominick J Angiolillo7, Mary Charlson8, Filippo Crea9, David P Taggart10. 1. Department of Cardiothoracic Surgery, Weill Cornell Medicine, New York, NY, USA. Electronic address: mfg9004@med.cornell.edu. 2. Division of Cardiac Surgery, University of Ottawa Heart Institute, University of Ottawa, Ottawa, ON, Canada. 3. Department of Cardiovascular Surgery, Hôpital Cardiologique Louis Pradel, Lyon, France. 4. Department of Cardiac Surgery, IRCCS San Raffaele University Hospital, Milan, Italy. 5. Department of Cardiovascular Surgery, Mount Sinai Saint Luke's, New York, NY, USA. 6. Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Latina, Italy; Mediterranea Cardiocentro, Napoli, Italy. 7. Division of Cardiology, University of Florida College of Medicine, Jacksonville, Florida, USA. 8. Department of Healthcare Policy and Research, Weill Cornell Medical College, New York, NY, USA. 9. Department of Cardiovascular and Thoracic Sciences, Fondazione Policlinico Gemelli, IRCCS, Università Cattolica del Sacro Cuore, Roma, Italy. 10. John Radcliffe Hospital, University of Oxford, Oxford, UK.
Abstract
BACKGROUND: Contradictory findings from randomized trials addressing similar research questions are not uncommon in medicine. While differing results may reflect true differences in the treatment effects or in the deliverability of the intervention, more commonly it is as a consequence of small but important discrepancies in study design. METHODS: The writing group selected four recent trials with apparently contradictory results (two on revascularization for left main coronary stenosis and two on treatment of secondary mitral regurgitation). Detailed methodological analysis was performed to elucidate the difference in findings. RESULTS: Differences in the definition of the primary outcome are the most likely explanation for the contradictory findings of NOBLE vs EXCEL. Differences in study design (leading to substantially different patient populations) as well as differences in outcome definition might explain the discrepant findings of MITRA-FR vs COAPT. CONCLUSIONS: As shown by the comparative analysis of NOBLE and EXCEL and MITRA-FR and COAPT, changes in study design, outcome definitions and patient population can markedly affect the outcome of randomized clinical trials.
BACKGROUND: Contradictory findings from randomized trials addressing similar research questions are not uncommon in medicine. While differing results may reflect true differences in the treatment effects or in the deliverability of the intervention, more commonly it is as a consequence of small but important discrepancies in study design. METHODS: The writing group selected four recent trials with apparently contradictory results (two on revascularization for left main coronary stenosis and two on treatment of secondary mitral regurgitation). Detailed methodological analysis was performed to elucidate the difference in findings. RESULTS: Differences in the definition of the primary outcome are the most likely explanation for the contradictory findings of NOBLE vs EXCEL. Differences in study design (leading to substantially different patient populations) as well as differences in outcome definition might explain the discrepant findings of MITRA-FR vs COAPT. CONCLUSIONS: As shown by the comparative analysis of NOBLE and EXCEL and MITRA-FR and COAPT, changes in study design, outcome definitions and patient population can markedly affect the outcome of randomized clinical trials.