Author Contributions: Dr Wilber 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: Wilber, Pappone, Natale, Calkins, Vinekar, Liu, S. Berry, D. Berry.
Acquisition of data: Wilber, Pappone, Neuzil, De Paola, Marchlinski, Macle, Daoud, Hall, Reddy, Augello, Reynolds.
Analysis and interpretation of data: Wilber, Pappone, Marchlinski, Calkins, Augello, Reynolds, Vinekar, Liu, S. Berry, D. Berry.
Drafting of the manuscript: Wilber, Natale, Hall, Vinekar, Liu.
Critical revision of the manuscript for important intellectual content: Wilber, Pappone, Neuzil, De Paola, Marchlinski, Natale, Macle, Daoud, Calkins, Reddy, Augello, Reynolds, Liu, S. Berry, D. Berry.
Statistical analysis: Marchlinski, Calkins, Reynolds, Liu, S. Berry, D. Berry.
Administrative, technical, or material support: Wilber, Pappone, Neuzil, Marchlinski, Reddy, Augello, Vinekar.
Study supervision: Wilber, Pappone, Marchlinski, Natale, Daoud.
Financial Disclosures: Dr Wilber reported receiving grants from Biosense Webster, Boston Scientific, Medtronic, and St Jude Medical; consulting fees from Biosense Webster, Medtronic, and Sanofi-Aventis; honoraria from Biosense Webster, Boston Scientific, Medtronic, and St Jude Medical; and royalties from Blackwell/Futura. Dr Pappone reported receiving grants and consulting fees from St Jude Medical and Johnson & Johnson, and honorarium from Biosense Webster. Dr Neuzil reported receiving grants from Biosense Webster, Cardiofocus, Cyrocath Technologies, Hansen Medical, NIH BARI 2D, and St Jude Medical; consulting fees from Stereotaxis; and honorarium from Biosense Webster. Dr De Paola reported receiving a grant from Bristol-Myers Squibb. Dr Marchlinski reported receiving grants and honoraria from Biosense Webster, Boston Scientific, and St Jude Medical; consulting fees from Biosense Webster, Boston Scientific, GE Healthcare, Medtronic, and St Jude Medical; and speakers' bureau fees from Biosense Webster. Dr Natale reported receiving grants from Biosense Webster and St Jude Medical, and speakers' bureau fees from Biosense Webster, Boston Scientific, Medtronic, and St Jude Medical. Dr Macle reported receiving consulting fees and honorarium from Biosense Webster. Dr Daoud reported receiving consulting fees from BARD and Biosense Webster, and honorarium from Biosense Webster. Dr Calkins reported receiving consulting fees from Ablation Frontiers, Atricure, BARD, Biosense Webster, Boston Scientific, CryoCor, CyberHeart, Medtronic, ProRhythm, Sanofi-Aventis, and TASER International; a grant and honorarium from Biosense Webster; speakers' bureau fees from Atricure, BARD, Biosense Webster, Boston Scientific, Medtronic, and Reliant; and fellowship fees from BARD, Boston Scientific, and Medtronic. Dr Hall reported receiving consulting fees from Biosense Webster. Dr Reddy reported receiving grants from Atritech, Boston Scientific, Biosense Webster, Cardiofocus, CryoCath Technologies, Endosense Hansen Medical, St Jude Medical, and Stereotaxis; consulting fees from Biosense Webster and St Jude Medical; and honoraria from Boston Scientific, Biosense Webster, Medtronic, and St Jude Medical. Dr Augello reported receiving honoraria from BARD, Biosense Webster, and St Jude Medical. Dr Reynolds reported receiving consulting fees from Biosense Webster, Cardiome Pharma Corp, and Sanofi-Aventis. Mr Vinekar and Ms Liu are employees of Biosense Webster. Drs S. Berry and D. Berry reported receiving consulting fees from Biosense Webster, Veridex LLC, Boston Scientific, Endologix, R.R. Bard, W.L. Gore, Medtronic, Bristol-Myers Squibb, Pfizer, and Teva Pharmaceuticals.
Funding/Support: This study was funded by Biosense Webster, who provided the catheters used.
Role of the Sponsor: The sponsor designed the study protocol in collaboration with the Food and Drug Administration (FDA) and participating investigators. The study was intended to support market approval of the NaviStar ThermoCool RF ablation catheter, which was manufactured by the sponsor. The sponsor had the overall responsibility for the conduct of the study, including assurance that the study met the regulatory requirements of the FDA. The sponsor's general duties consisted of submitting the Investigational Device Exemption application to the FDA, obtaining FDA and institutional review board approvals before shipping the devices, approval of the investigators, ensuring proper clinical site monitoring, and ensuring patient informed consent was obtained. The sponsor was responsible for providing quality data that satisfied federal regulations and informing proper authorities of serious unanticipated adverse events and deviations from the protocol, and for training all participating investigators on the study device and protocol and monitoring the study for data integrity throughout the duration of the investigation. In addition, the sponsor was responsible for data collection and basic data analysis. The sponsor participated in additional data analysis, data interpretation, and the drafting of the manuscript in conjunction with the principal and other investigators, as well as the decision to submit the manuscript for publication.
Independent Statistical Analysis: All efficacy and primary safety results and conclusions presented in this manuscript have been confirmed by an independent statistical review and analysis performed by Joe Massaro, PhD (Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts, and Senior Biostatistical Consultant, Harvard Clinical Research Institute [HCRI], Boston, Massachusetts). Dr Massaro was provided the raw SAS data sets, analysis SAS data sets, the study protocol containing a statistical analytical plan, a blank copy of the study case report forms, and the original version of the manuscript by the authors/sponsor of the trial. Overall, Dr Massaro was in agreement with the statistical methods used in the manuscript and independently verified the primary and secondary efficacy results and conclusions presented in the final manuscript. Based on Dr Massaro's analysis, the final manuscript also included more details on the multiple imputation approach and a “worst case” approach to the frequentist analysis. Dr Massaro was compensated by the authors/sponsor for his independent statistical review through the HCRI, a nonprofit academic research organization.
The ThermoCool AF Trial Investigators:Principal Investigator: David Wilber (Loyola University Medical Center, Maywood, Illinois); co-investigators: Joseph Akar, Peter Santucci, M. Schneck; study-coordinator: Cynthia Finn. Clinical Centers:Hospital San Raffaele, Milan, Italy: Carlo Pappone (principal investigator), Giuseppe Augello, Simone Sala; Na Homolce Hospital, Prague, Czech Republic: Petr Neuzil (principal investigator), Vivek Reddy, Liz Coling, Mirka Kanova, Stepan Kralovec, Andreas Kruger, Jindrich Kupec, Jan Petru, Lucie Sediva, Milena Sidova, Jan Skoda, Milos Taborsky; Hospital São Paulo, São Paulo, Brazil: Angelo de Paola (principal investigator), Raquel de Jesus Pires Brito, Paulo Alexandre da Costa, Charles Dalegrave, Cristiano Dietrich, Carlos Romerio Costa Ferro, Veruska Hernandes, Stevie Jorge Horbach; Hospital of the University of Pennsylvania, Philadelphia: Francis Marchlinski (principal investigator), Rupa Bala, Joshua Cooper, Sanjay Dixit, Fermin Garcia, Edward Gerstenfeld, Mary Gnap, Henry Hsia, Tony Killian, David Lin, Andrea Russo, Gerilyn Schott, Ralph Verdino, Erica Zado; Cleveland Clinic Foundation, Cleveland, Ohio: Andrea Natale (principal investigator), Oussama Wazni, Mandeep Bhargava, Mauricio Arruda, J. David Burkhardt, Mina Chung, Jean Cross, Thomas Dressing, Kathy Elliott, Christina Fariello, Lon W. Castle, Jennifer E. Cummings, Donald Holmes, Frederick J. Jaeger Jr, Mark Jarosz, Mohamed Kanj, Sidney Koepp, David O. Martin, Nassir Marrouche, John Mays, Juliet Pryce, Raquel Rozich, Walid Saliba, Robert Schweikert, J. Michael Sullivan, Denise K. Sweeney, Terence Semenec, Stephanie Spencer, Patrick J. Tchou, Bruce Wilkoff; Montreal Heart Institute, Montreal, Quebec, Canada: Laurent Macle (principal investigator), Mariano Badra, Miguel Barrero, Ghislaine Bertrand, Ramon Brugada, Helene Creo, Diane David, Fabrice Demoniere, Marc Dubuc, Frederic Dumont, Pierre Gagne, Peter Guerra, Grigorios Katsouras, Paul Khairy, Kristina Lemola, Raoi Mansour, Anna Proietti, Lena Rivard, Jean-Francois Roux, Denis Roy, Lanthier Sylvain, Mario Talajic, Bernard Thibault; Midwest Cardiology, Columbus, Ohio: Emile Daoud (principal investigator), Ralph Augostini, Rose Chumita, Georgia Dawson, John Hummel, Steven Kalbfleisch; Ohio State University, Columbus: Emile Daoud (principal investigator), Ralph Augostini, Jennifer Bremer, Rose Chumita, Georgia Dawson, Kathryn Crow, John Hummel, Steven Kalbfleisch, Julie Ryan, Raul Weiss; Johns Hopkins University, Baltimore, Maryland: Hugh Calkins (principal investigator), Kathleen Avara, Ronald Berger, Cynthia Hawes, Charles Henrickson, Joseph Marine, Elizabeth Robinson, Gina Robinson, Janice Stack; University of Rochester Medical Center, Rochester, New York: Burr Hall (principal investigator), James Daubert, David Huang, Coleen Patterson, Kathryn Pyykkonen, Spencer Rosero, Janice Schrack, Carol Yeager; Arrhythmia Management, Plano, Texas: Brian Deville, Tara Weaver, Dustin Williams, Tina Worley; Marin General Hospital, Greenbae, California: Steven Hao, Linda Bartek, Salwa Beheiry, Eric Bernier, Jeremy Carnam, Richard Hongo, Gina Im, Jan Voskyul, Darla Watanabe, Raul Weiss; Arizona Arrhythmia Consultants, Scottsdale: Vijendra Swarup, Nicholas Arroyo, Marwan Bahu, Gayle Bodner, Renzo Cataldo, Nicole Ellingson, Peeyush Khanna, Angela Krebsbach, Thomas Mattioni, Ami Ning, David Riggio, Sara Scrivano, Drory Tendler, Claudia Williams, Bianca Vandermate, Lori Fausett; St Luke's Roosevelt Hospital, New York, New York: Jonathan Steinberg, Aysha Arshad, Delia Cotiga, Frederick Ehlert, Robin Knox, Walter Pierce; Inova Fairfax Hospital, Fairfax, Virginia: Ted Friehling, Margaret H. (Schenck) Bell, Marie Blake, Andrea Doctor, Sarfraz A. K. Durrani, Albert A. Del Negro, David A. Strouse, Marc H. Wish; Florida Hospital, Orlando: Scott Pollack, Leann Goodwin, Shannon Harrison, George Monir, Carol Stastny; Lahey Clinic, Burlington, Massachusetts: Roy M. John, Jean M. Byrne, Bruce G. Hook, David T. Martin, Gregory F. Michaud, Florence M. Parrella; Medical University of South Carolina, Charleston: Marcus Wharton, Elizabeth Clarke, Mariann Schultz.
Additional Contributions: We thank Albert Waldo, MD (the Walter H. Pritchard Professor of Cardiology, University Hospitals Case Medical Center, Cleveland, Ohio), for chairing the Clinical Events Committee; and Byron Allen, MD (Department of Cardiology, University of California, Irvine), for adjudicating all electrocardiographic data from the TTM transmissions. Dr Allen was compensated for his efforts by Biosense Webster. We also express our appreciation to the following affiliates from Biosense Webster, who were compensated for their efforts, in the design and execution of this study: Marcia Yaross, PhD, Brenda Aker, Robert Stagg, PhD, Kendra Lan Franco, Don Nguyen, Cheyi Lin, MS, and Brian Ramos, MS.