Published Online: March 30, 2014. doi:10.1001/jama.2014.3321.
Study concept and design: Lincoff, Tardif, Schwartz, Nicholls, Rydén, Neal, Malmberg, Wedel, Buse, Henry, Cannata, Svensson, Grobbee.
Acquisition, analysis, or interpretation of data: Lincoff, Tardif, Schwartz, Nicholls, Rydén, Malmberg, Wedel, Henry, Weichert, Svensson, Volz, Grobbee.
Drafting of the manuscript: Lincoff, Henry, Cannata.
Critical revision of the manuscript for important intellectual content: Lincoff, Tardif, Schwartz, Nicholls, Rydén, Neal, Malmberg, Wedel, Buse, Henry, Weichert, Svensson, Volz, Grobbee.
Statistical analysis: Tardif, Wedel, Henry, Volz.
Obtained funding: Lincoff, Neal, Malmberg, Henry, Svensson.
Administrative, technical, or material support: Lincoff, Tardif, Nicholls, Neal, Malmberg, Henry, Weichert, Cannata, Svensson.
Study supervision: Lincoff, Tardif, Schwartz, Rydén, Malmberg, Buse, Henry, Weichert, Svensson, Grobbee.
Conflict of Interest Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Lincoff reports receiving research grants from AstraZeneca, CSL Laboratories, Eli Lilly, Regado, Roche, Takeda, and Vivus through his institution. Dr Tardif reports receiving research grants from Amarin, Cerenis, Eli Lilly, Isis, Merck, Pfizer, Roche, sanofi-aventis, and Servier through his institution and has received honoraria from Cerenis and Servier. Dr Schwartz reports receiving research grants from Anthera, Resverlogix, Roche, and sanofi-aventis through his institution. Dr Nicholls reports receiving research grants from Anthera, Amgen, AstraZeneca, Cerenis, Eli Lilly, InfraReDx, LipoScience, Novartis, Resverlogix, and Roche through his institution; consulting fees from Abbott, Amgen, AstraZeneca, Atheronova, Boehringer Ingelheim, CSL Behring, Esperion, LipoScience, Merck, Novartis, Omthera, Pfizer Roche, sanofi-aventis, and Takeda. Dr Rydén reports receiving research grants from AFA Insurance Company, Bayer AG, Karolinska Institutet Funds, Roche, the Swedish Diabetes Association, and the Swedish Heart Lung Foundation through his institution; has received honoraria from expert committee or steering committee service from AstraZeneca, Bristol-Myers Squibb, Roche, and sanofi-aventis. Dr Neal reports receiving research grants from Abbvie, Dr Reddy’s Laboratories, Janssen, Merck Schering Plough, Roche, and Servier through his institution and has received honoraria for meeting presentations from Abbott, AstraZeneca, Novartis, Pfizer, Roche, and Servier. Dr Malmberg reports being an employee of Roche. Dr Wedel reports receiving honoraria for steering committee service from Roche and honoraria from AstraZeneca and Pfizer. Dr Buse reports receiving research grants from Amylin, Andromeda, Astellas, Astrazeneda, Boehringer-Ingelheim, Bristol-Myers Squibb, Eli Lilly, GI Dynamics, GlaxoSmithKline, Halozyme, Intarcia Therapeutics, Johnson & Johnson, Lexicon, MacroGenics, Medtronic Minimed, Merck, Novo Nordisk, Orexigen, Osiris, Pfizer, Roche, sanofi-aventis, Takeda, and Tolerex through his institution; consultancy fees from PhaseBio; consultancy fees from Amylin, AstraZeneca, Bayhill Therapeutics, Bristol-Myers Squibb, Catabasis, Cebix, Cure DM, Diartis, Eicylex, Eli Lilly, Exsulin, GI Dynamics, Liposcience, Merck, Metabolic Solutions Development Company, Metabolon, Metavention, Novan, Novella Clinical, Novo Nordisk, Orexigen, Rhythm, Roche, Spherix, Transpharma, Transtech Pharma, and Verva through his institution; and has stock/stock options in PhaseBio. Dr Henry reports receiving research grants from AstraZeneca, Bristol Myers Squibb, Eli Lilly, Hitachi, sanofi-aventis; and honoraria as a consultant or advisory board member from Alere, Amgen, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, ClinMet, Daiichi Sankyo, Eisea, Elcelyx, Eli Lilly, Gilead, Hitachi, Intarcia, Isis, Johnson & Johnson/Janssen, Merck, Novo Nordisk, Roche/Genetech, and Vivus. Dr Weichert reports being an employee of Roche. Ms Cannata reports receiving research grants from Roche through her institution. Dr Svensson reports being an employee of Roche. Dr Volz reports being an employee of Roche. Dr Grobbee reports receiving research grants from Roche, Novartis, and Pfizer through his institution; has received consultantancy fees from Julius Clinical; and has received consultancy fees from Roche to his institution.
Funding/Support: The trial was sponsored by F. Hoffmann-La Roche (Basel, Switzerland).
Role of the Sponsor: F. Hoffmann-La Roche participated in the design of the trial and protocol in collaboration with the academic members of the executive steering committee; was responsible for submission of the protocol for approval by national regulatory authorities; developed and maintained the trial database and was responsible for data collection; performed blinded safety reviews of adverse events and was responsible for regulatory submissions related to safety issues; and provided the study drug and placebo. Unblinded statistical analyses for the interim reviews by the data and safety monitoring committee were performed by an independent data coordinating center, Statistics Collaborative, Inc (Washington, DC); these interim reports were not made available to the sponsor, executive steering committee, or any personnel involved in the operations of the trial. Management of clinical sites, including training and academic leadership, obtaining ethics committee approvals and regulatory documents, monitoring of sites, and ensuring that informed consent was obtained was performed by the consortium of academic research organizations. The final study database was provided by the sponsor to one of the academic research organizations (Montreal Heart Institute), where all of the statistical analyses for this manuscript were independently performed under direction of Anna Nozza, MSc, Senior Biostatistician at the Montreal Heart Institute Coordinating Center. Ms Nozza receives salary from her institution, but received no specific or additional compensation for her contribution. The results reported in this article are the results of the analyses performed at Montreal Heart Institute, aside from those interim results relating to the information acted upon by the data and safety monitoring committee at the time they recommended termination of the trial. The corresponding author drafted this manuscript and made all revisions based upon input from the coauthors, including those employed by the sponsor. The sponsor had no role in the decision to submit the manuscript for publication.
Additional Contributions: Executive Steering Committee: A. Michael Lincoff, Study Chairman and Principal Investigator; Diederick Grobbee, Co-Principal Investigator; Jean-Claude Tardif, Co-Principal Investigator; John Buse; Robert Henry; Bruce Neal; Stephen Nicholls; Lars Ryden; Gregory G. Schwartz; Hans Wedel; Klas Malmberg; Arlette Weichert. Steering Committee: Elena Baranova, Russia; Vera Bittner, US; David Brieger, Australia; Jordi Cortada Bruguera, Spain; Peter Clemmensen, Denmark; Diego Conde, Argentina; Richard Grimm, US; Hu Dayi, China; Reda Ibrahim, Canada; J. Wouter Jukema, Netherlands; Matyas Keltai, Hungary; Hyo-Soo Kim, Korea; Jose Luis Leiva, Mexico; Brendan McAdams, Ireland; Darren McGuire, US; Linda G. Melbin, Sweden; Giles Montalescot, France; Thomas Münzel, Germany; Jośe Carlos Nicolau, Brazil; Piotr Ponikowski, Poland; Neil Poulter, UK; Stefano Savonitto, Italy; Bipin Sethi, India; Kui-Hian Sim, Malaysia; Miroslav Solar, Czech Republic; Steven Steinhubl, US; Damras Tresukosol, Thailand; Richard Troughton, New Zealand; Ioan Andrei Veresiu, Romania; Scott Wright, US. Data and Safety Monitoring Committee: Paul W. Armstrong, Chairman; David L. DeMets; Christopher Granger; Philip Home; John McMurray; Lynda Szczech (through May, 2012); Patrick S. Parfrey (May, 2012 to present). Academic Research Organizations: Berman Center for Outcomes & Clinical Research (Minneapolis, MN): Richard Grimm (Medical Director), Rachel Moor, Rebecca Lohser, Terese Mitteness; C5Research: Cleveland Clinic Coordinating Center for Clinical Research (Cleveland, OH): A. Michael Lincoff, (Director), Stephen Nicholls, Ruth Cannata, Lynn Bartko, Karen Buckholz, Kathy Elliott, Tamera Gamble, Susan Jasper, Gerry McConnell, Patty St Marie; George Institute for Global Health (Sydney, Australia): Bruce Neal (Scientific Director), Manthinda Hettiarachchi, Erin Wilson, Deama Amr, Sarah Knight, Amanda Kelly, Yunhua Cao, Ranjan Ranjesh; Julius Clinical (Zeist, the Netherlands), University Medical Center Utrecht (Utrecht, the Netherlands): Diederick E. Grobbee (Director), Hans Hoogeveen, Suzanne Bruins, Rob ten Pas (Global Project Director); Montreal Heart Institute Coordinating Center (Montreal, Canada): Jean-Claude Tardif (Director, MHI Research Center), Dominique Johnson, Joanne Gavalakis, Marie-Claude Guertin, Anna Nozza, Ernest Allen, Jerry Crockatt, Annick Drouin, Micheline LaForest, Ana Viquez-Porras, Caroline Lemieux, Christina Mantzioros, Kim Vandystadt, Karim Abdel-Sheheid. Clinical Events Committee: C5Research, Cleveland, Ohio; Cleveland Clinic: Vidyasagar Kalahasti, MD (CEC Chairperson); Mary DelValle RN; Diane Fabec RN; Sachin Goel MD; Barbara Heil MD; Julie Huang MD; Michael Jolly MD; Irene Katzan MD; Evan Lau MD; Michael McCulloch MD; Venu Menon MD; Peter Monteleone MD; Sahar Naderi MD; Dermot Phelan MD; Andrew Russman MD; Daniel Sedehi MD; Todd Senn MD; Mehdi Shishehbor DO PhD; Gus Theodos MD; Ken Uchino MD; Amanda Vest MD; University Hospital Cleveland: Cathy Sila MD; Sanford Health, South Dakota: Jitendra Sharma MD. Sponsor: F. Hoffmann-La Roche Ltd, Basel, Switzerland (Sponsor)-Klas Malmberg, MD (Global Clinical Leader); Arlette Weichert, MD (Clinical Science Leader); Regina Duttlinger Maddux, Regine Schrumpf, Henry Bennett, Dietmar Volz.