Author Contributions: Dr Fowler had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
Study concept and design: Fowler, Allen, Hartzel, Chan, Kartsonis, Onorato, DiNubile.
Acquisition of data: Fowler, Allen, Moreira, Moustafa, Isgro, Boucher, Corey, Carmeli, Betts, McNeely.
Analysis and interpretation of data: Fowler, Allen, Moreira, Boucher, Corey, Carmeli, Betts, Hartzel, McNeely, Kartsonis, Guris, Smugar, Onorato, DiNubile, Sobanjo-ter Meulen.
Drafting of the manuscript: Fowler, Allen, Hartzel, Onorato, DiNubile, Sobanjo-ter Meulen.
Critical revision of the manuscript for important intellectual content: Fowler, Allen, Moreira, Moustafa, Isgro, Boucher, Corey, Carmeli, Betts, Hartzel, Chan, McNeely, Kartsonis, Guris, Smugar, Onorato, DiNubile, Sobanjo-ter Meulen.
Statistical analysis: Hartzel, Chan.
Administrative, technical, or material support: Boucher, McNeely, Guris, Onorato, Smugar, DiNubile, Fowler.
Study supervision: Kartsonis, Guris, Onorato, Sobanjo-ter Meulen.
Conflict of Interest Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Employees of Merck (Drs Hartzel, Chan, McNeely, Kartsonis, Guris, Smugar, DiNubile, and Sobanjo-ter Meulen and Mr Onorato) may own stock or stock options in the company. All academic authors have been investigators for Merck. Dr Fowler reports that he was compensated by Merck for serving as chair of the V710 Scientific Advisory Committee; has received grant support from Merck, Cerexa, Pfizer, Novartis, Advanced Liquid Logics, MedImmune, and the National Institutes of Health; has been a paid consultant for Merck, Astellas, Cubist, Cerexa, Durata, Pfizer, NovaDigm, Novartis, the Medicines Company, Biosynexus, MedImmune, Galderma, and Inimex; and has received honoraria from Merck, Astellas, Cubist, Pfizer, Theravance, and Novartis. Dr Moreira reports that he has received research grants from Merck through his institution and honoraria from Merck for speaking engagements and board membership. Dr Moustafa reports consulting fees/honoraria and support for travel from Merck. Dr Boucher reports that she was compensated by Merck for serving on the adjudication committee for this study, is the recipient of a National Institutes of Health grant to study catheter-related bloodstream infections, and has been a paid consultant for Merck, Basilea, Cubist, Durata, Johnson & Johnson, RibX, Targanta/TMC, Wyeth/Pfizer, and Paratek. Dr Corey reports that he has received grant support from Theravance, the Medicines Company, and Innoccol and has served as a consultant and/or advisor for Merck, AstraZeneca, Astellas, Cempra, Cubist Pharmaceuticals, Cerexa/Forest Pharmaceuticals Furiex, PRA International, Inimex, Pfizer, GlaxoSmithKline, Polymedix, Achaogen, Trius, RibX, Nabriva, Seachaid, BioCryst, Durata, and Gilead. Dr Carmeli reports that he has been a paid consultant for Merck, Achaogen, AstraZeneca, Basilea, Intercell, Johnson & Johnson, RibX, and Proteologics. No other disclosures were reported.
V710 Protocol 003 Principal Investigators:Austria: Martin Grabenwoeger; Belgium: Paul Herijgers, Philippe Kolh; Brazil: Cely Saad Abboud, Luiz Carlos Bodanese, Renato Kalil, Maria Patelli Lima, Edson Duarte Moreira Jr, Eliana Lima Bicudo dos Santos, Tania Mara Strabelli, Flavio Queiroz Telles; Chile: Francisco Arancibia, Michael Howard, Luis Sepulveda; Colombia: Alvaro Ignacio Arango, Victor Raul Castillo, Alejandro Escobar; Denmark: Peter Skov Olssen; Finland: Kalervo Werkkala; France: Bernard Albat, Christian Auboyer, Laurent Barandon, Laurent Beydon, Lionel Camilleri, Hervé Dupont, Roland Henaine, Marc Laskar, Jean-Luc Mainardi, Pascal Menestret, Fabrice Vanhuyse; Germany: Manju Guha, Gerhard F. Hauf, Christian Hengstenberg, Frank Isgro, Arndt H. Kiessling, Alexandros Paraforos, Ali Peivandi, Gerhard Walterbusch; Guatemala: Luis Velasquez; Ireland: Mark DaCosta; Italy: Elvio Covino, Ruggero DePaulis, Francesco Musumeci, Gian Federico Possati; Japan: Shuhei Azuma, Joji Hoshino, Hiroshi Iida, Toshiaki Ito, Hiromi Kurosawa, Hidenori Sako, Kazuyoshi Tajima, Toshifumi Takeuchi, Imun Tei, Fumio Yamazaki, Kenji Yamazaki, Hideo Yoshida; Korea: Hyuk Ahn, Byung-Chul Chang, Kun Jik Kim, Kyong Ran Peck; Malaysia: Venugopal Balchand, Kui Hian Sim; Mexico: Luis Humberto Gomez, Reynaldo Jimenez, Jesus Octavio Martinez-Reding; New Zealand: Shay McGuinness; Norway: Rune Haaverstad, Asbjørn Karevold; Peru: Hector Bedoya, Carlos Cerron, Jaime Ulloa; Russia: Olga Barbarash, Vladimir V. Lomivorotov, Natalia G. Mezentseva, Viktor F. Mordovin, Iliya Staroverov, Alexander V. Troitskiy; Singapore: Chong Hee Lim; Spain: Benito Almirante; Emilio Bouza Santiago, Angel Fernandez Gonzalez, Juan José Goiti-Unibaso, Jose Maria Gonzalez Santos, Jesus Herreros Gonzalez, Eduardo Otero, Jose Luis Pomar, Guillermo Reyes-Copa, Jesus Rodriguez-Bano, Jacobo Silva-Guisasola; Sweden: Gunnar Engstrom, Ulf Kjellman, Dan Lindblom, Jan Thorelius; Taiwan: Jiun-Yi Li, Chien-Sung Tsai, Shoei-Shen Wang; United Kingdom: Christopher Blauth, Frank Y. Lie, Tom J. Spyt, Catherine Sundarshan; United States: David Affleck, Lishon Aklog, Edmund Alexander, Keith B. Allen, Michael Argenziano, Joseph S. Auteri, Robert F. Betts, Steven W. Boyce, Emmanouil Brilakis, Martha I. Buitrago, David Caparrelli, Paul Carson, Thomas L. Carter Jr, Alfred Casale, Thomas D. Christopher, Michael Climo, Clarence B. Creech, Harry D’Agostino, Ralph Damiano Jr, Bruce Darrow, R. Duane Davis, Ramzi K. Deeik, Barry Charles Esrig, Michael Firstenberg, Tim Alexander Fischell, James S. Gammie, Mauricio J. Garrido; Ralf E. Gebhard, Eliot W. Godofsky, Kamal M. F. Itani, Paul Kanaly, James Keegan, Junaid Khan, Michael Lazar, Kwan S. Lee, John Lucke, Steven Kent Macheers, Jeffery C. Milliken, Sang (Alex) H. Na, Richard A. Nathan, Rathel L. Nolan, Steven D. Owens, Timothy L. Pansegrau, Brenda Peart, Eric Peck, Chand Ramaiah, John F. Reinhardt, Anthony J. Rongione, Todd Rosengart, Thomas G. Sharp, Patrick J. Simpson, David Spielvogel, Stephen A. Tahta, Antone Tatooles, Richard Thompson, James C. Todd, Jeffery Veluz, Michael Wait, Peter Walts, Daniel R. Watson, John B. Weiss, J. Alan Wolfe, Duane G. Wombolt, James K. Wu, James L. Zellner. Data Monitoring Committee: Adolf W. Karchmer, MD (Harvard Medical School), Kyung Mann Kim, PhD (University of Wisconsin–Madison), William Schaffner, MD (Vanderbilt University School of Medicine), Sara E. Cosgrove, MD, MS (Johns Hopkins Medical School). Efficacy Endpoint Adjudication Committee: Helen W. Boucher, Ralph Corey, Yehuda Carmeli.
Funding/Support: The study was sponsored and funded by Merck Sharp & Dohme Corp, a subsidiary of Merck & Co Inc, Whitehouse Station, New Jersey.
Role of the Sponsor: In collaboration with the academic coauthors, Merck as the study sponsor was directly involved in design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, and approval of the manuscript. Specifically, the trial was designed, managed, and analyzed by employees of the sponsor in conjunction with external academic investigators under the oversight of an independent data review advisory board. Each author was provided with a summary of every performed analysis and had access to the detailed results on request. A penultimate draft of the manuscript was reviewed by the sponsor. All coauthors approved a substantively final version of the manuscript.
Independent Statistical Analysis: An independent statistical review of our analyses was performed by Bruce Turnbull, PhD, Cornell University. He reviewed the protocol, statistical analysis plan, interim data reports, clinical study report, and manuscript. He traveled to the Merck facility in Upper Gwynedd, Pennsylvania, where he was given full access to the electronic data files. Dr Turnbull chose and reran a number of the key analyses included in this article. In all cases, he obtained identical findings to the results presented here. He provided several suggestions to clarify the presentation of results, which were incorporated into the final version of the manuscript. Dr Turnbull was compensated by Merck for his travel expenses and for his independent statistical review.
Disclaimer: The opinions expressed in this report represent the consensus of the authors and do not necessarily reflect the formal position of Merck or the other institutions listed as author affiliations.
Previous Presentations: These data were presented in part at the 22nd European Congress of Clinical Microbiology and Infectious Diseases, March 31–April 3, 2012; London, England (http://onlinelibrary.wiley.com/doi/10.1111/j.1469-0691.2012.03801.x /pdf) and at IDWeek 2012, October 16-21, 2012, San Diego, California (http://idsa.confex.com/idsa/2012/webprogram/Paper38533.html).
Additional Contributions: We thank all of the patients, health care practitioners, and investigators involved with this study. We also appreciate the invaluable administrative and technical assistance of Pia Graham, MSc, and Karyn Davis, BA, Merck & Co Inc, during the preparation of the manuscript.