Study concept and design: Bezerra, Magee, Shneider, Rosenthal, Haber, Karpen, Schwarz, Shepherd, Suchy, Whitington, Robuck, Sokol.
Acquisition, analysis, or interpretation of data: All authors.
Drafting of the manuscript: Bezerra, Spino, Magee, Shneider, Rosenthal, Wang, Erlichman, Moore, Sherker, Sokol.
Critical revision of the manuscript for important intellectual content: All authors.
Statistical analysis: Spino, Magee, Moore.
Obtained funding: Bezerra, Magee, Shneider, Rosenthal, Wang, Karpen, Kerkar, Loomes, Molleston, Murray, Romero, Schwarz, Turmelle, Whitington, Sokol.
Administrative, technical, or material support: Spino, Magee, Sherker, Robuck.
Study supervision: Bezerra, Spino, Magee, Shneider, Sherker, Robuck, Sokol.
Conflict of Interest Disclosures: The authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Bezerra reported receiving grants from Molecular Genetics Laboratory of Cincinnati Children’s Hospital Medical Center outside the submitted work. Dr Shneider reported serving on data monitoring committes for Bristol-Myers Squibb and Vertex on hepatitis B and C, respectively; serving as associate editor for the American Association for the Study of Liver Diseases; and receiving royalites from PMPH-USA for a pediatric gastrointestinal textbook. Dr Rosenthal reported receiving grants from Roche, Bristol-Myers Squibb, Vertex, and Gilead; and receiving consulting fees from General Electric and Hyperion. Dr Haber reported receiving grants from the National Institutes of Health during the conduct of the study while with Children’s Hospital of Philadelphia, University of Pennsylvania. In January 2012, Dr Haber changed employment and now works at Merck in the area of viral hepatitis; however, her current work does not overlap or effect any aspect of the article. Dr Loomes reported receiving book royalties from Lippincott Williams & Wilkins and payment for an article on biliary atresia from Up-to-Date. Dr Molleston reported receiving grants from Schering, Roche, and Vertex outside the submitted work. Dr Schwarz reported serving as a consultant to Roche/Genentech; providing expert testimony for the State of Pennsylvania; and receiving institutional grants from the National Institute of Diabetes, Digestive and Kidney Diseases, Bristol-Myers Squibb, Roche/Genentech, and Vertex. Dr Sokol reported receiving grants from National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health; receiving nonfinancial support from Mead Johnson Nutrition during the conduct of the study; receiving consulting fees from Yasoo Health Inc, Ikaria Pharmaceuticals, Roche Products, and Cardax Pharmaceuticals; and having a patent for use of antioxidants for treatment of cholestasis licensed to Yasoo Health Inc. No other disclosures were reported.
Funding/Support: The following National Institute of Diabetes, Digestive and Kidney Diseases (NIDDK) grants supported the START study: DK62503 and TR000424 (awarded to Johns Hopkins University School of Medicine), DK62436 and TR000150 (Lurie Children’s Hospital of Chicago), DK62497 and TR000077 (Cincinnati Children’s Hospital Medical Center), DK62453 and TR000154 (University of Colorado School of Medicine and Children’s Hospital Colorado, Aurora), DK62445 (Mount Sinai School of Medicine), DK62481 and TR000003 (Children’s Hospital of Philadelphia), DK62466 and TR000005 (Children’s Hospital of Pittsburgh of UPMC), DK62500 and TR000004 (UCSF Benioff Children’s Hospital), DK62452 and TR000448 (Washington University School of Medicine and St Louis Children’s Hospital), DK62470 (Baylor College of Medicine and Texas Children’s Hospital, Houston), DK84575 and TR000423 (Seattle Children’s Hospital), DK84538 and TR000130 (Children’s Hospital Los Angeles and University of Southern California), DK84585, DK62470, and TR000454 (Emory University School of Medicine and Children’s Healthcare of Atlanta), DK84536 and TR000007 (Indiana University School of Medicine and Riley Hospital for Children), and DK62456 (University of Michigan data coordinating center). The following companies provided support for the START study, each of which provided formula or medications as part of a cooperative agreement with the NIDDK: GlaxoSmithKline supplied ranitidine; Axcan Pharma US Inc, fat-soluble vitamins and tocopherol polyethylene glycol succinate; Axcan Pharma US Inc, ursodiol until 2009; and Mead Johnson Nutrition, Pregestimil.
Role of the Sponsors: The companies listed at the end of the Funding/Support section were provided copies of the START protocol prior to the start of the trial. They did not participate in the design and conduct of the study; collection, management, analysis or interpretation of the data; or preparation, review, or approval of the manuscript; or decision to submit the manuscript for publication. These industries were given a copy of the manuscript before submission for publication as per policy of the ChiLDREN Network.
Group Information: The Childhood Liver Disease Research and Education Network (ChiLDREN) additional investigators are NIDDK: Edward Doo, MD, Rebecca Torrance, RN, Rebekah van Raaphorst, MPH, Jay H. Hoofnagle, MD. Johns Hopkins University School of Medicine: Paul Colombani, MD, Henry Lau, MD, Kim Kafka, RN, Anitha Devadason. Lurie Children’s Hospital of Chicago: Riccardo Superina, MD, Sue Kelly, RN. Cincinnati Children’s Hospital Medical Center: Greg Tiao, MD, Frederick Ryckman, MD, Maria Alonso, MD, Jaimie Nathan, MD, John Bucuvalas, MD, Alexander Miethke, MD, James Heubi, MD, William F. Balistreri, MD, Kathleen Campbell, MD, Rohit Kohli, MD, Mike Leonis, MD, Julie Denlinger, RN, Andrea Ferris. University of Colorado School of Medicine and Children’s Hospital Colorado, Aurora: Frederick Karrer, MD, Cara Mack, MD, Michael R. Narkewicz, MD, Shikha S. Sundaram, MD, Mark Lovell, MD, Joan Hines, MPH, Sheryl Faut, RN, Michelle Hite, MA. Mount Sinai School of Medicine, New York: Kishore Iyer, MBBS, Ronen Arnon, MD. Children’s Hospital of Philadelphia: Alan Flake, MD, Elizabeth Rand, MD. Children’s Hospital of Pittsburgh of UPMC: Beverly Bernard, RN, Cartland Burns, MD, Kathryn Bukauskas, RN, Robert Squires, MD, Veena Venkat, MD. UCSF Benioff Children’s Hospital: Camille Langlois, MS, Shannon Fleck. Washington University School of Medicine and St Louis Children’s Hospital: Patrick Dillon, MD, Frances White, MD, Alexander Weymann, MD, David Rudnick, MD, Kathy Harris, Stacy Postma. Baylor College of Medicine and Texas Children’s Hospital, Houston: Kimberly Pieplow, MPH, Mary Brandt, MD, Milton Finegold, MD, Beth Carter, MD, Doug Fishman, MD, Val McLin, MD, David Wesson, MD, Zoe Apted, BA, Alejander DeLaTorre, BBS, Darrell Cass, MD. Seattle Children’s Hospital: Simon Horslen MB, ChB, FRCPCH, Evelyn Hsu, MD, Patrick Healey, MD, Melissa Young, Laura Finn, MD. Children’s Hospital Los Angeles and University of Southern California: Cat Goodhue, NP, Daniel Thomas, MD, Sonia Michael, MD. Emory University School of Medicine and Children’s Healthcare of Atlanta: Carlos Abramowsky, MD, Matthew Clifton, MD, Liezl De La Cruz, BA, Nitika Gupta, MD, DCH, DNM, MRCPCH, Richard Ricketts, MD, Sundari Sekar, MBBS, DGO, Bahig Shehata, MD, Miriam Vos, MD, MSPH. Indiana University School of Medicine and Riley Hospital for Children: Girish Subbarao, MD, Karen West, MD, Beth Byam, RN. University of Michigan Data Coordinating Center: Trivellore Raghunathan, PhD, James Lopez, MD, Emily Fredericks, PhD, Beverley Marchant, BSN, Karen Jones, BS, Kristina Slusser, Yang Casher, MA. Investigators with different institutional affiliations at the beginning of START: Benjamin L. Shneider and Frederick J. Suchy (Mount Sinai School of Medicine, New York, New York), Saul J. Karpen (Texas Children’s Hospital, Houston), Ross Shepherd (Washington University School of Medicine, St Louis, Missouri).
Study Safety Monitor: M. James Lopez, MD, University of Michigan School of Medicine.
Members of the Data and Safety Monitoring Board of START: Keith Oldham, MD (Medical College of Wisconsin, Milwaukee), P. Joan Chesney, MD (St Jude Children’s Research Hospital, Memphis, Tennessee), Richard Ehrenkranz, MD (Yale University School of Medicine, New Haven, Connecticut), Peter Imrey, PhD (Cleveland Clinic Foundation, Cleveland, Ohio), Esther J. Israel, MD (Massachusetts General Hospital for Children, Boston, Massachusetts).
Additional Contributions: We acknowledge the current and former members of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) START and ChiLDREN listed above who played important roles in the development of START and enrollment of participants in the trial. We thank all the ChiLDREN investigators, the research coordinators, the participants, and the families who agreed to participate in this study. We also thank Denise Lagory, RPh, who was the central research pharmacist for the trial. No compensation was received by the individuals for contributions to the trial outside the NIDDK grant funding.