Five members of the Harvard Partners’ group were on the panel of the Eight American College of Chest Physicians Consensus Conference on Antithrombotic Therapy (2008). This anticoagulant guideline producing conference was funded entirely by drug companies that produce anticoagulants: AstraZeneca LP, Eisai Inc., Sanofi-aventis, Bayer Healthcare AG and Scios Inc., GlaxoSmithKline.

The Harvard research scientists, their hospital affiliations, and their financial disclosures from the proceedings of the conference were the following:

· Christopher P. Cannon, MD, Brigham and Women’s Hospital, “Dr. Cannon discloses that he has received grant monies from Accumetrics, AstraZeneca, Bristol-Myers Squibb, GlaxoSmithKline, Merck, Sanofi-Aventis, and Schering Plough.”

· Daniel Singer, MD, Massachusetts General Hospital. He has served as a consultant to Medtronic, Boehringer Ingelheim, Bayer HealthCare, Johnson & Johnson, Sanofi-Aventis, and Daiichi Sankyo Inc.

· Samuel Goldhaber, MD, Brigham and Women’s Hospital. Dr. Goldhaber did not disclose any financial conflicts for the anticoagulation guidelines article. However, in another article, he disclosed the following: “Samuel Z. Goldhaber, MD, has disclosed that he has received grants for clinical research from Sanofi-Aventis, GlaxoSmithKline, Eisai, and Boehringer Ingelheim, and has served as an advisor or consultant for Sanofi-Aventis, Eisai, Boehringer Ingelheim, Bristol-Myers Squibb, and Scios.” (http://cme.medscape.com/viewprogram/8483)

· Jeffrey J. Popma, MD, Brigham and Women’s Hospital. “Dr. Popma discloses that he has received monies from Cordis, Boston Scientific, Medtronic, and Abbott. He is involved with the speakers bureaus of Pfizer, BMS, Lilly, and Sanofi, and has served on advisory committees of Medtronix, BSC, Abbott, and Cordis.”

· Patrick T. O’Gara, MD, Brigham and Women’s Hospital. Nothing to disclose.

In January 2009, Medscape Journal of Medicine published my “Systematic Review of Cochrane Anticoagulation Reviews (http://www.medscape.com/viewarticle/584084). This review challenged the evidence basis for efficacy of anticoagulants for 30 medical indications. Anticoagulants used for these 30 indications cause at least 50,000 people per year to bleed to death. No one rebutted the findings of the review.

To bring this article to the attention of the FDA, I emailed FDA Director Janet Woodcock, MD (see below) and copied these five Harvard anticoagulation researchers and about 140 other academic anticoagulation experts, Cochrane collaboration scientists, medical editors, and government anticoagulation experts from the NIH and FDA.

Consider taking this story about Harvard scientists capping their drug company reimbursement to the next level by exploring this incidence of patient harm coming from anticoagulant guidelines purchased by drug companies from academic researchers.

Thank you.

David K. Cundiff, MD

Apr 30, 2009 09:31:17 PM, dkcundiff3@verizon.net wrote:

Janet Woodcock, MD, Director of CDER
Food and Drug Administration

Dear Dr. Woodcock,

I am requesting that you consider conducting a transparent investigation of the evidence I presented in the article “A Systematic Review of Cochrane Anticoagulation Reviews,” challenging the evidence-basis for anticoagulant use for 30 FDA approved and off-label indications (http://www.medscape.com/viewarticle/584084).

1. This review was based on my letters to authors of 57 Cochrane anticoagulation reviews pointing out methodological errors, biases, and undisclosed financial conflicts and my own Cochrane review of anticoagulants for venous thromboembolism.

2. Authors replied to only 13 of those 57 letters. At least 50,000 people worldwide bleed to death yearly from anticoagulants used for those 30 indications.

3. Medscape Journal of Medicine also recently published my meta-analysis titled, “Clinical Evidence For Rebound Hypercoagulability After Discontinuing Oral Anticoagulants For Venous Thromboembolism.” (http://www.medscape.com/viewarticle/582408) By demonstrating the extent of VTE recurrences in the 2 months after stopping oral anticoagulants, this study calls into question all trials of antithrombotics for prophylaxis or treatment that did not report rebound hypercoagulability related adverse events. The limited available evidence suggests that tens of thousands of patients die of rebound hypercoagulability related events each year.

So that you can receive a wide spectrum of comments/opinions/rebuttals from experts in antithrombotic medicine, copies of this letter will also go to the following:

1. FDA and NIH experts in antithrombotic and thrombolytic therapy and drug safety

2. Authors and editors of Cochrane reviews of anticoagulation prophylaxis and treatment interventions

3. Authors of antithrombotic and thrombolytic therapy guidelines published in 8supplements of the journal CHEST 4-11 under the auspices of the American College of Chest Physicians (ACCP)

4. Editors of other medical journals that have published articles supporting the use of anticoagulants for the 30 indications that my review challenges

5. Other antithrombotic and thrombolytic therapy researchers

In the USA, the process of medical guideline development for antithrombotic drugs has been ceded to the pharmaceutical industry. DuPont Pharmaceuticals funded development of the first 6 ACCP antithrombotic and thrombolytic therapy guidelines publications. DuPont produced Coumadin until 2001 when it was sold to Bristol-Myers Squibb. Subsequently, a coalition of antithrombotic drug producing companies has funded the development of the 2004 and 2008 ACCP guidelines.

The pharmaceutical companies directly financially supported the anticoagulant and thrombolytic drug guideline authors in the following ways:

1. Travel to and from the conferences

2. Hotel accommodations

3. Meals

4. Payments for guideline authorships

Indirect forms of compensation to the authors for the drafting of the guidelines include the following:

1. Speakers’ bureau participation fees

2. Consultantships

3. Research grants

4. Financial support of faculty positions (e.g., research scholars program of the Heart and Stroke Foundation of Canada funded in part by Pfizer Canada Inc., Sanofi-Aventis, AstraZeneca Canada, Bayer, Hoffmann-LaRoche, Boehringer Ingelheim Ltd./Ltée)12

The process of selecting individuals to draft the ACCP anti coagulation guidelines has not been transparent. The selection process has not been detailed in any of the eight ACCP anticoagulation guideline supplements published in CHEST. Although the guidelines are published under the auspices of the ACCP, the journal CHEST does not announce the conferences or invite interested ACCP members to participate in the guidelines producing conferences. ACCP antithrombotic drug guideline authors do not disclose their financial conflicts with pharmaceutical companies funding the guideline supplements in CHEST when authoring antithrombotic drug promoting articles in other medical journals. Among those not represented on the committees to draft guidelines are the following:

1. Patients receiving anticoagulants

2. Consumer groups

3. Government experts from the FDA, NIH or other agencies

4. Physicians, pharmacists, or nurses who have not received funding in one form or another from pharmaceutical companies that make anticoagulants.

For the sake of the many people who die of bleeding and rebound clotting from anticoagulants, thank you for addressing the material I am presenting.

Best wishes,

David K. Cundiff, MD

1. Cundiff DK. A Systematic Review of Cochrane Anticoagulation Reviews. Medscape Journal of Medicine. January 6, 2009; http://www.medscape.com/viewarticle/584084.

2. Cundiff DK,Manyemba J, Pezzullo JC. Anticoagulants versus non-steroidalanti-inflammatories or placebo for treatment of venous thromboembolism. The Cochrane Database of Systematic Reviews.2006;Issue 1. Art. No.: CD003746. DOI: 10.1002/14651858.CD003746.pub2.Abstract available at: http://www.mrw.interscience.wiley.com/cochrane/clsysrev/articles/CD003746/frame.html,Commentary: http://medgenmed.medscape.com/viewarticle/557263.

3. Cundiff DK.Clinical Evidence For Rebound Hypercoagulability After Discontinuing OralAnticoagulants For Venous Thromboembolism. MedscapeJournal of Medicine. 2008;10(11):258, http://www.medscape.com/viewarticle/582408.

4. Hyers TM, Hull RD, Weg JG. Antithrombotic therapy for venous thromboembolic disease. Chest. 1986;89(2 Suppl):26S-35S.

5. 2nd ACCP Conference on Antithrombotic Therapy. American College of Chest Physicians.June 21, 1988. Proceedings. Chest. 1989;95(SUPPLEMENT):1- 169.

6. Third ACCP Consensus Conference on Antithrombotic Therapy. Chest. October 1992;102(4_Supplement.):305S - 549.

7. Fourth ACCP Consensus Conference on Antithrombotic Therapy. Chest. October 1995;108(4_Supplement):225S-522S.

8. Fifth ACCP Consensus Conference on Antithrombotic Therapy. Chest. November 1998; 114(5):439S-769S.

9. Sixth ACCP Consensus Conference on Antithrombotic Therapy. Chest. 2001 Jan;119(1 Suppl):1S - 370S.

10. The Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy: Financial Disclosures. CHEST. September 2004;126(no. 3suppl):167S-171S doi: 110.1378/chest.1126.1373_suppl.1167S.

11. Antithrombotic and Thrombolytic Therapy, 8th Ed: ACCP Guidelines. Chest. 2008 Jun;133(6 Suppl):67S - 968S.

12. Our National Corporate Partners. The Heart and Stroke Foundation of Canada. Available at: http://www.heartandstroke.com/site/c.ikIQLcMWJtE/b.4389517/k.3AF2/Our_National_Corporate_Partners.htm.Accessed April 24, 2009.