The Food and Drug Administration on February 16-18, 2005 held an advisory committee meeting to discuss the cardiovascular risk posed by painkillers known as Cox-2 inhibitors, which include Celebrex, Bextra and Vioxx. The former two drugs are manufactured by Pfizer. The latter is manufactured by Merck. Novartis also has a Cox-2 inhibitor in its pipeline. At the end of the hearing, the FDA advisory panel voted to keep all three on the market, though with heightened warnings about the dangers posed by this class of drugs.
At the request of the New York Times, the Center for Science in the Public Interest evaluated the 32 scientific experts chosen by the FDA to evaluate these drugs. The CSPI research uncovered affiliations between 10 of the scientists that served on the committee and the three manufacturers of Cox-2 inhibitors. This would appear to be a direct violation of the Federal Advisory Committee Act, which prohibits scientists with direct conflicts of interest from serving on panels offering advise to federal regulatory agencies. Another 17 scientists had other ties to drug manufacturers, though not the three with products under consideration at the meeting.
According to a New York Times analysis of the votes, the advisory committee would have voted against Bextra and Vioxx staying on the market had scientists with conflicts of interest been excluded from the vote.
Here is the CSPI analysis of the FDA Advisory Panel:
CSPI found ten (10) physician/researchers with direct ties to Pfizer, Merck or Novartis (including G.D. Searle and Pharmacia, which are now part of Pfizer). They were:
Steven Abramson, M.D., Professor and Chairman, Division of Rheumatology, NYU School of Medicine, New York. Has an interest in Merck. (“Food and Drug Administration Center for Drug Evaluation and Research,” Congressional Hearing Transcripts, 7/20/99) Received speaker's honoraria or consulting fees from Pfizer, Amgen, Novartis, and Pharmacia. Consultant for Searle, and a member of the Speakers Bureau for Pfizer. Received an unrestricted educational grant from Pharmacia.
Joan M. Bathon, M.D., Professor of Medicine, Division of Rheumatology, Department of Medicine, Johns Hopkins University. Received consultancies and/or honoraria from Centocor, Inc., a subsidiary of Johnson & Johnson, totaling less than $10,000 per year. (Arthritis Rheum. 2004;50:3432-43.) Received ad hoc consultant fees and support for this research from Immunex. (Arthritis Rheum. 2002 Jun;46(6):1443-50.) Received support for research on etanercept and methotrexate in patients with early rheumatoid arthritis from Immunex, Inc. (N Engl J Med. 2000 Nov 30;343(22):1586-93.) Consultant for: National Advisory Board CTLA4-IG Project, Bristol Myers Squibb, 2000; International Advisory Board, Anti-TNF Project, Centocor, 2000; National Advisory Board, Anti-TNF Project, Knoll Pharmaceuticals, 2000; National Advisory Board, Anti-TNF Project, Immunex and Wyeth, 1998-99; National Advisory Board, Cox-2 Project, Searle, 1998-2000; Consultant, Bradykinin receptor antagonist project, Fournier Pharmaceuticals, 1996; Consultant, Anti-inflammatory initiative, Procter & Gamble.
John J. Cush, M.D., Chief of Rheumatology and Clinical Immunology, Presbyterian Hospital, Dallas, TX. Article on concomitant leflunomide therapy in patients with active rheumatoid arthritis despite stable doses of methotrexate listed potential conflicts of interest due to consultancies, honoraria and grants received. (Ann Intern Med. 2002 Nov 5;137(9):726-33.) Consultant: Abbott, Amgen, Wyeth, Centocor, Pfizer, Regeneron; Disclosure: Current Investigator: Abbott, Amgen, Biogen Idec, Pfizer. (J Rheumatol. 2005 Feb;32(2):203-7.) ) Received grants from Abbott, Amgen/Weiss, Aventis, Centocor, IDEC/Genentech, Isis Pharmaceuticals. Dr. Cush is a member of The Cadeuceus Group, LLC.
Robert H. Dworkin, Ph.D., Professor of Anesthesiology, Neurology, Oncology and Psychiatry, School of Medicine and Dentistry, University of Rochester, NY. Member of the Steering Committee of the Pfizer Medical and Academic Partnerships in Pain Medicine. Received research support, consulting fees, or speakers bureau honoraria in the past year from Abbott Laboratories, Allergan, AstraZeneca, Bristol-Myers Squibb, Elan Pharmaceuticals, Eli Lilly and Co, Endo Pharmaceuticals, King Pharmaceuticals, Johnson and Johnson, NeurogesX, Novartis Pharmaceuticals, Ortho-McNeil Pharmaceutical, Pfizer, Purdue Pharma, Quigley Pharma, Reliant Pharmaceuticals, and UCB Pharma.
John T. Farrar, M.D., Senior Scholar, University of Pennsylvania, Center for Clinical Epidemiology and Biostatistics, Philadelphia. Received research or grant support from Pfizer, Cephalon, Smithkline Beecham, Knoll, and Searle; served as a consultant for Abbott Laboratories, Alza, Endo Pharmaceuticals, UCB Pharma, and Faulding; and served on the speakers bureau of Purdue Frederick.
J. Michael Finley, D.O., Associate Professor and Chair of Medicine, Western University College of Osteopathic Medicine. Received funding for the Zometa Trial from Novartis Pharmaceuticals in 2000.
Allan Gibofsky, M.D., J.D., Professor of Medicine and Public Health, Weill Medical College, Cornell University, New York, NY. Independent advisor to Amgen and Wyeth trial to evaluate the impact of a tumor necrosis factor (TNF) inhibitor in patients with rheumatoid arthritis (RA) in the United States (RADIUS study). (2002 Drug Week via NewsRx.com and NewsRx.net , Drug Week, November 29) Clinical trial comparing the efficacy of cyclooxygenase 2-specific inhibitors in treating osteoarthritis supported by Pharmacia (Arthritis Rheum. 2003 Nov;48(11):3102-11.) On the Speaker’s Bureau for Abbott, Amgen/Wyeth, Pfizer and TAP Pharmaceuticals. Consultant to Abbott, Amgen/Wyeth and Pfizer. Stockholder: Abbott, Amgen, Bristol Myers-Squibb and Pfizer. Dr. Gibofsky is a member of The Cadeuceus Group, LLC.
Charles H. Hennekens, M.D., Visiting Professor of Medicine and Epidemiology and Public Health, School of Medicine, University of Miami, Boca Raton, FL. Coinventor on a patent application filed by Brigham and Women’s Hospital on the use of markers of inflammation in coronary artery disease. (N Engl J Med. 2000; 342:836-43) Consultant for AstraZeneca, Bristol-Myers Squibb/Sanofi, Novartis, Pfizer, and Reliant. Co-author of Pfizer funded study, “Absence of Interaction Between Atorvastatin or Other Statins and Clopidogrel.” (Arch Int Med. 2004; 164: 2051-7) Serves as a consultant, including Chair or membership on Data and Safety Monitoring Boards, to AstraZeneca, Bayer, Bristol-Myers Squibb, Chattem, Delaco, Glaxo-Smith Kline, McNeil, Novartis, Pfizer, and Reliant. (Circulation. 2003;108(10):1191-5)
Steven E. Nissen, M.D., Vice-chairman of Cardiology, and Head of Clinical Cardiology, Department of Cardiovascular Medicine, Cleveland Clinic Foundation, Cleveland, OH. Research on lipid-lowering therapy on progression of coronary atherosclerosis through the use of statins Pravachol (pravastatin) and Lipitor (atorvastatin) funded by Pfizer. Research support from AstraZeneca, Merck-Schering Plough, Esperion Therapeutics, Takeda, Pfizer, and Sankyo. (JAMA. 2004;291:1071-80)
Richard Platt, M.D., M.Sc., Professor and Chair, Department of Ambulatory Care and Prevention, Harvard Medical School, Boston, MA. Primary investigator in 9/1/04-8/31/05 project funded by Pfizer on enhanced identification of adverse drug events. Primary investigator in 9/1/04-8/31/05 project funded by TAP Pharmaceuticals on Gout Pharmacoepidemiology. Co-investigator of 01/01/03-12/31/05 study funded by GlaxoSmithKline on Safety and Utilization of Lotronex in the United States.
In addition, CSPI found seventeen (17) physician/researchers who received research support or had other financial ties to pharmaceutical firms (but not direct ties to manufacturers of Cox-2 inhibitors). In three cases, the ties were to Merck or Pfizer but were deemed too old to be relevant. They were:
Ralph B. D’Agostino, Ph.D., Professor of Mathematics/Statistics and Public Health, Boston University, MA. On the scientific advisory board of Gentium S.p.A. On scientific advisory board of Penwest. (“Penwest Appoints Pharmaceutical Industry Leaders Dr. William M. Wardell And Dr. Ralph B. D'Agostino to Scientific Advisory Board,” PR NewsWire, 6/8/01) Has interests in pharmaceutical companies which necessitate his being granted a full waiver in order to participate in a Food and Drug Administration Nonprescription Drugs Advisory Committee meeting regarding OTC Vaginal Antifungal Class Labeling. (“Nonprescription Drugs Advisory Subcommittee with Industry Representation from the Reproductive Health Drugs and Anti-Infective Drugs Advisory Committee,” Congressional Hearing Transcripts, 9/11/98)
Michael R. Cohen, R.Ph., M.S., D. Sc., President, Institute for Safe Medication Practices, Huntington Valley, PA. Consultant and advisory board member for Merck(1988-1992).
Stephanie Y. Crawford, Ph.D., M.P.H., Associate Professor, College of Pharmacy, University of Illinois, Chicago. Research on cost effectiveness of HMG-CoA reductase inihibitors in the treatment of hypercholesterolemia sponsored by Sandoz Pharmaceuticals (1995-1997).
Ruth S. Day, Ph.D., Professor, Department of Psychology, Duke University, Durham, NC. Research on optimizing patient comprehension through medicine information leaflets sponsored by U.S. Pharmacopeia, Inc., (1998). Consultant on gastric distress syndrome and migraine management for Glaxo, and on auto injectors for drug delivery to Dey, Inc.
Janet Elashoff, Ph.D., Director, Division of Biostatistics, Cedars-Sinai Medical Center, Los Angeles, CA. Has interests in pharmaceutical companies which necessitate her being granted a general matters waiver in order to participate in a Food and Drug Administration Anti-Infective Drugs Advisory Committee meeting regarding the ranking of antimicrobial drugs according to their importance in human medicine.
Thomas Fleming, Ph.D., Professor and Chairman, Department of Biostatistics, University of Washington, Seattle. 17 Receives between $10,000 and $50,001 in consulting fees from GlaxoSmithKline and receives less than $10,001 per year from each of four of its competitors. Fleming received a consulting fee for a limited consultation with Boehringer-Ingelheim. (Circulation. 2004;109:e9004-5) Served on oncology Clinical Advisory Board for Sunesis. (“Sunesis Begins Phase I Clinical Study of SNS-595 for Cancer; Prestigious Oncology Clinical Advisory Board Established,” PR Newswire, 6/28/04) Speaker on IntraBiotics’ live web cast featuring a panel of experts to discuss iseganan for the treatment of oral mucositis. (“IntraBiotics to Host a Conference Call and Web Cast with a Panel of Experts,” PR NewsWire, 3/18/02)
Curt D. Furberg, M.D., Ph.D., In 2002 to 2003, his services were retained by plaintiffs’ attorneys as expert in cases related to cerivastatin and rhabdomyolysis or myopathy. In that capacity, he was compensated for reviewing this issue and providing expert opinions for use in litigation. Plaintiffs’ attorneys reviewed and commented on written expert reports resulting from this work. These expert reports were disclosed to the defendants in the cases, including Bayer Corporation, and the author has been questioned in deposition regarding the reports. (JAMA. 2004 Dec 1;292(21):2622-31. Epub 2004 Nov 22) Wake Forest University. A “member of a paid panel asked by Wyeth-Ayerst to ensure the validity of the firm’s research” re diet drug Redux (USA Today, 4/1/98, p. 1A) Co-author of a study of a Sandias calcium channel blocker, DynaCirc. (Lingua Franca, June/July, 1997; p. 56) Chair (1992-present), Investigators Committee of the Heart, Estrogen-Progestin Replacement Study, Wyeth; Co-chair (1992-1999), Steering Committee of Prospective Randomized Evaluation of the Vascular Effects of Norvasc Trials, Pfizer; Chair (1992-present), Prospective Pravastatin Pooling Project, Bristol Myers Squibb.
Jacqueline S. Gardner, Ph.D., M.P.H., Associate Professor, Department of Pharmacy, University of Washington, Seattle, WA. Received support from Glaxo for a comparative study of prescription and medical service utilization patterns among pediatric asthmatics in Medicaid and HMO’s (1993-1994); research supported by Solvay Pharmaceuticals and The Upjohn Company.
Peter A. Gross, M.D., Chairman, Department of Internal Medicine, Hackensack, NJ. Received grants from Wyeth (1994-1995, 2000), Abbott (1995).
Gary Stuart Hoffman, M.D., Chairman, Rheumatic and Immunologic Diseases, The Cleveland Clinic Foundation, OH. Studies evaluating anti-tumor necrosis factor (anti-TNF) therapies in Wegener's granulomatosis and giant cell arteritis, were partially funded by Centocor, Immunex, and Amgen. (Arthritis Rheum. 2004 Jul;50(7):2296-304.)
Norman T. Ilowite, M.D., Director, Division of Rheumatology, Schneider Children’s Hospital, New Hyde Park, NY. Industry sponsored on-going research: A 12 week randomized double blind trial with a 12 week open label extension to investigate the efficacy and safety of novel agent administered once daily and naproxen oral suspension administered twice daily in children with juvenile rheumatoid arthritis (2001-2003); Safety population pharmacokinetics of a novel agent in the treatment of JRA (1997-2003); Randomized multi center, blinded, placebo-controlled study with an open label run in period to evaluate the efficacy, safety and pharmacokinetics of a novel agent in particular course JRA (2000-02); Companion study to evaluate the long term safety of a novel agent in polyarticular course JRA (200-02); Phase IV registry of a novel agent in JRA(2000-05); Phase III, double-blind, randomized study comparing methotrexate plus novel agent vs. methotrexate alone in polyarticular course JRA (2000-02). Completed industry sponsored research: Pharmokinetics, safety and efficacy of TNFR:Fc in the treatment of methotrexate resistant polyarticular JRA (1996-1999); Open, oral dose study to evaluate the steady state plasma concentration profile of a novel agent, followed by a 12 week, double-blind, active comparator-controlled extension in late and post-pubertal adolescents with JRA (1999-2001); Open label study of a NSAID in patients with JRA (1999-2000).
Susan M. Manzi, M.D., M.P.H., Associate Professor of Medicine, University of Pittsburgh. An open label, multi-center study (1997-2001) to evaluate the long term safety and reliability of GL701 in patients with systemic Lupus erythomatosus sponsored by Genelabs Technologies, Inc. Received grants from LaJolla Pharmaceuticals (2000-2001). Biogen, Inc. (1998-2000), Dupont (1998), Merck (1998) .
Louis A. Morris, Ph.D., President, Louis A. Morris & Associates, Dix Hills, NY. He has Served as an expert consultant to numerous pharmaceutical and communication companies.
Emil Paganini, M.D., F.A.C.P., F.R.C.P., Section Head, Dialysis, Cleveland, OH. Co-inventor of 05/13/03 US Patent 6,561,997 “Extracorporeal fluid circuit and related methods” assigned to The Regents of the University of Michigan and Nephros Therapeutics.
Steven L. Shafer, M.D., Professor of Anesthesia, Stanford University, Palo Alto, CA. Vice President of Product Development at the Pharsight Corporation. Owns 1.3 percent of the company’s stocks. Study partially funded by AstraZeneca on “Propofol Dosing Regimens for ICU Sedation based upon an Integrated Pharmacokinetic-Pharmacodynamic Model.” (Anesthesiology. 2001;95:324-33)
Robyn S. Shapiro, J.D., Ursula Von der Ruhr Professor of Bioethics, Medical College of Wisconsin, Milwaukee. Speaker at a Medical Education Symposium Sponsored by PointOne Systems. (“National Leaders Will Share Expertise in Genetics and Application of Genetic Knowledge in Clinical Practice at Daylong Event, 'Clinical Application of Genomic Discovery,'” PR NewsWires, 3/4/03) Served on Glaxo/Wellcome Data and Safety Monitoring Board. Speaker at 5/12/99 Ethics Conference sponsored by SSM Ministry Corporation, "Ethical Issues in Health Care: End-of-Life Issues."
Alastair Wood, M.D., Assistant Vice Chancellor, Professor of Medicine and Pharmacology, Vanderbilt University School of Medicine, Nashville, TN. Co-inventor of 12/11/01 U.S. patent 6,329,153 “Method for evaluating immunosuppressive” assigned to Vanderbilt University. Served on Board of Directors of Antigenics. (“Antigenics Reports Third Quarter 2004 Financial Results and Recent Highlights.” Business Wire. 10/19/04)For more information, contact: Center for Science in the Public Interest