Head-to-head randomized trials are mostly industry sponsored and almost always favor the industry sponsor.
OBJECTIVE
To map the current status of head-to-head comparative randomized evidence and to assess whether funding may impact on trial design and results.


METHODS
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.


CONCLUSIONS
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.
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.
Maria Elena
ME
Flacco
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.
Lamberto
L
Manzoli
Institute of Public Health, Catholic University of the Sacred Heart, Largo Francesco Vito 1, 00168 Rome, Italy.
Stefania
S
Boccia
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.
Lorenzo
L
Capasso
Institute of Public Health, Catholic University of the Sacred Heart, Largo Francesco Vito 1, 00168 Rome, Italy.
Katina
K
Aleksovska
Department of Public Health and Infectious Diseases, Sapienza University of Rome, Piazzale Aldo Moro 5, 00185 Rome, Italy.
Annalisa
A
Rosso
Department of Public Health Sciences, University of Turin, Via Verdi 8, 10124 Turin, Italy.
Giacomo
G
Scaioli
Department of Public Health and Infectious Diseases, Sapienza University of Rome, Piazzale Aldo Moro 5, 00185 Rome, Italy.
Corrado
C
De Vito
Department of Public Health Sciences, University of Turin, Via Verdi 8, 10124 Turin, Italy.
Roberta
R
Siliquini
Department of Public Health and Infectious Diseases, Sapienza University of Rome, Piazzale Aldo Moro 5, 00185 Rome, Italy.
Paolo
P
Villari
Departments of Medicine and Health Research and Policy, Stanford Prevention Research Center, Stanford University School of Medicine, 291 Campus Drive, Stanford, CA 94305, USA.
John P A
JP
Ioannidis
D001208:Asia; D016265:Conflict of Interest; D004345:Drug Industry / Q000191:economics*; D036262:Empirical Research; D005060:Europe; D038622:Internationality; D018579:Patient Selection; D016032:Randomized Controlled Trials as Topic / Q000191:economics*; D012107:Research Design; D012109:Research Support as Topic / Q000379:methods / Q000458:organization & administration / Q000706:statistics & numerical data*; D014481:United States
Conflict of interest; Cross-sectional study; Head-to-head comparison; Industry sponsorship; Noninferiority trials; Randomized controlled trials