Maria Elena Flacco1, Lamberto Manzoli2, Stefania Boccia3, Lorenzo Capasso4, Katina Aleksovska3, Annalisa Rosso5, Giacomo Scaioli6, Corrado De Vito5, Roberta Siliquini6, Paolo Villari5, John P A Ioannidis7. 1. Department of Medicine and Aging Sciences, University of Chieti, Via dei Vestini 5, 66013 Chieti, Italy; Regional Healthcare Agency of the Abruzzo Region, Via Attilio Monti 9, 65127 Pescara, Italy. 2. Department of Medicine and Aging Sciences, University of Chieti, Via dei Vestini 5, 66013 Chieti, Italy; Regional Healthcare Agency of the Abruzzo Region, Via Attilio Monti 9, 65127 Pescara, Italy; CEsI Biotech, Foundation "Università G. d'Annunzio" of Chieti, Via dei Vestini 31, 66013 Chieti, Italy. Electronic address: lmanzoli@post.harvard.edu. 3. Institute of Public Health, Catholic University of the Sacred Heart, Largo Francesco Vito 1, 00168 Rome, Italy. 4. Department of Medicine and Aging Sciences, University of Chieti, Via dei Vestini 5, 66013 Chieti, Italy; CEsI Biotech, Foundation "Università G. d'Annunzio" of Chieti, Via dei Vestini 31, 66013 Chieti, Italy. 5. Department of Public Health and Infectious Diseases, Sapienza University of Rome, Piazzale Aldo Moro 5, 00185 Rome, Italy. 6. Department of Public Health Sciences, University of Turin, Via Verdi 8, 10124 Turin, Italy. 7. Departments of Medicine and Health Research and Policy, Stanford Prevention Research Center, Stanford University School of Medicine, 291 Campus Drive, Stanford, CA 94305, USA.
Abstract
OBJECTIVES: To map the current status of head-to-head comparative randomized evidence and to assess whether funding may impact on trial design and results. STUDY DESIGN AND SETTING: From a 50% random sample of the randomized controlled trials (RCTs) published in journals indexed in PubMed during 2011, we selected the trials with ≥ 100 participants, evaluating the efficacy and safety of drugs, biologics, and medical devices through a head-to-head comparison. RESULTS: We analyzed 319 trials. Overall, 238,386 of the 289,718 randomized subjects (82.3%) were included in the 182 trials funded by companies. Of the 182 industry-sponsored trials, only 23 had two industry sponsors and only three involved truly antagonistic comparisons. Industry-sponsored trials were larger, more commonly registered, used more frequently noninferiority/equivalence designs, had higher citation impact, and were more likely to have "favorable" results (superiority or noninferiority/equivalence for the experimental treatment) than nonindustry-sponsored trials. Industry funding [odds ratio (OR) 2.8; 95% confidence interval (CI): 1.6, 4.7] and noninferiority/equivalence designs (OR 3.2; 95% CI: 1.5, 6.6), but not sample size, were strongly associated with "favorable" findings. Fifty-five of the 57 (96.5%) industry-funded noninferiority/equivalence trials got desirable "favorable" results. CONCLUSION: The literature of head-to-head RCTs is dominated by the industry. Industry-sponsored comparative assessments systematically yield favorable results for the sponsors, even more so when noninferiority designs are involved.
OBJECTIVES: To map the current status of head-to-head comparative randomized evidence and to assess whether funding may impact on trial design and results. STUDY DESIGN AND SETTING: From a 50% random sample of the randomized controlled trials (RCTs) published in journals indexed in PubMed during 2011, we selected the trials with ≥ 100 participants, evaluating the efficacy and safety of drugs, biologics, and medical devices through a head-to-head comparison. RESULTS: We analyzed 319 trials. Overall, 238,386 of the 289,718 randomized subjects (82.3%) were included in the 182 trials funded by companies. Of the 182 industry-sponsored trials, only 23 had two industry sponsors and only three involved truly antagonistic comparisons. Industry-sponsored trials were larger, more commonly registered, used more frequently noninferiority/equivalence designs, had higher citation impact, and were more likely to have "favorable" results (superiority or noninferiority/equivalence for the experimental treatment) than nonindustry-sponsored trials. Industry funding [odds ratio (OR) 2.8; 95% confidence interval (CI): 1.6, 4.7] and noninferiority/equivalence designs (OR 3.2; 95% CI: 1.5, 6.6), but not sample size, were strongly associated with "favorable" findings. Fifty-five of the 57 (96.5%) industry-funded noninferiority/equivalence trials got desirable "favorable" results. CONCLUSION: The literature of head-to-head RCTs is dominated by the industry. Industry-sponsored comparative assessments systematically yield favorable results for the sponsors, even more so when noninferiority designs are involved.
Authors: Mario Gaudino; Irbaz Hameed; Mohamed Rahouma; Faiza M Khan; Derrick Y Tam; Giuseppe Biondi-Zoccai; Michelle Demetres; Mary E Charlson; Marc Ruel; Filippo Crea; Volkmar Falk; Leonard N Girardi; Stephen Fremes; Joanna Chikwe Journal: JAMA Intern Med Date: 2020-07-01 Impact factor: 21.873
Authors: Deepa V Cherla; Cristina P Viso; Julie L Holihan; Karla Bernardi; Maya L Moses; Krislynn M Mueck; Oscar A Olavarria; Juan R Flores-Gonzalez; Courtney J Balentine; Tien C Ko; Sasha D Adams; Claudia Pedroza; Lillian S Kao; Mike K Liang Journal: J Gen Intern Med Date: 2019-01-02 Impact factor: 5.128