I first heard from Dr. Alain Braillon back in 2010 when he contacted me through social media. He was the first civil servant in France ever to be fired for whistleblowing. A number of European sources publicized his case. healthwatch_oct10.pdf
The brave doctor is not well know in the U.S., but he should be because his work involved U.S. tax payer money from a Department of Health and Human Services (HHS), National Institutes of Health (NIH) grant to foreign hospitals conducting experiments on human patients with alcoholic hepatitis.
In 2009, Dr. Braillon attempted to notify HHS Office of the Inspector General (OIG) about the violations of international law (Helsinki Declaration) and misuse of grant funding. The OIG referred him to the Office of Research Inegrity (ORI). In an email below Dr. Braillon contacted ORI, expressing serious concern that human subjects were dying. Essentially the treatment being used was actually known to cause death. Thus, patients were being experimented on without full knowledge and consent to the risks.
It is not yet known whether HHS played a role in notifying Dr. Braillon’s employers who fired him for whistleblowing. For 2 years, the renown doctor fought to get his job back. On May 10, 2012, the Paris Administrative Court cancelled the decision of the Ministery of Health which fired Dr. Braillon from his tenured position at the university hospital of Amiens.
De : Dahlberg, John E (HHS/OPHS) [mailto:John.Dahlberg@hhs.gov]
Envoyé : lundi 2 février 2009 16:59
À : Braillon Alain
Cc : Morgan, Tracy S (HHS/OPHS); Dahlberg, John E (HHS/OPHS)
Objet : RE: Very serious breach of the Helsinki Declaration
Dear Dr. Baillon,
Thank you for sharing your concerns about the propriety of this study with this office. However, ORI lacks the jurisdiction to deal with matters of this sort, as we are constrained to address allegations of possible research misconduct that conform to the Public Health Service definition at 42 C.F.R. part 93.103, and where the allegedly falsified or fabricated research has been supported by funds from the Public Health Service (such as NIH). You note that although the legal requirements of obtaining IRB approval were met, and the journal accepted the logic of the study protocol, there were reasons why, in your view, the study should not have been carried out in the way that it was. ORI is not able to opine on this view, but I suggest you share your views with the Journal, as this represents the appropriate venue for airing alternative opinions for the medical community to consider.
John Dahlberg, Ph.D.
Director, Division of Investigative Oversight
Office of Research Integrity
From: Braillon Alain [mailto:Braillon.Alain@chu-
Sent: Monday, February 02, 2009 7:34 AM
To: OS OPHS askORI (HHS/OPHS)
Subject: Very serious breach of the Helsinki Declaration
Very serious breach of the Helsinki Declaration in a published trial (see abstract below)
Point 32 of the Helsinki Declaration states that “new intervention must be tested against those of the best current proven intervention, except in the following circumstances: The use of placebo, or no treatment, is acceptable in studies where no current proven intervention exists; or Where for compelling and scientifically sound methodological reasons the use of placebo is necessary to determine the efficacy or safety of an intervention and the patients who receive placebo or no treatment will not be subject to any risk of serious or irreversible harm. Extreme care must be taken to avoid abuse of this option”.
Investigators, several IRB, Gastroenterology’s reviewers and the editor validated the placebo arm in the trial of Etanercet for the treatment of alcoholic hepatitis.
However, the American Society of Gastroenterology stated that “corticosteroids should be used in patients with severe alcoholic hepatitis in whom the diagnosis is certain” (McCullough AJ, O’Connor JF. Alcoholic liver disease: proposed recommendations for the American College of Gastroenterology. Am. J. Gastroenterol. 1998; 93: 2022-36).
Indeed, pooling data from all published studies shows a relative risk reduction of 0.32 (number needed to treat 9.2) and the most recent of these studies, of higher quality, showed a survival benefit( Morgan MY. The treatment of alcoholic hepatitis. Alcohol Alcohol. 1996; 31: 117-34).
-The Etanercet dosage was the one used for rheumatoid arthritis. This bypassed the necessary drug-development process (pre-clinical studies, phase I and II) because patients with alcoholic hepatitis are more prone to serious infectious adverse effects.
Lastly, the authors choose an effect size of 35%, which has no scientific basis but hope.
Surrogate end points (bilirubin à day 7) were not reported to detect treatment failure.
And so on.
The editor of Gastroenterology denied to discuss this issue and refused the correspondence that I submitted.
Looking forward hearing from you
Dr Alain Braillon
Service du Professeur Gérard Dubois
80054 Amiens CEDEX 1
Tél. : 33 (0) 3 2266 79 37 et 06 87 99 58 12
A Randomized, Double-Blinded, Placebo-Controlled Multicenter Trial of Etanercept in the Treatment of Alcoholic Hepatitis
Received 28 April 2008; accepted 28 August 2008. published online 16 September 2008.
Background & Aims
Alcoholic hepatitis is a cause of major morbidity and mortality that lacks effective therapies. Both experimental and clinical evidence indicate that the multifunctional cytokine tumor necrosis factor-α (TNF-α) contributes to pathogenesis and clinical sequelae of alcoholic hepatitis. A pilot study demonstrated that the TNF-α-neutralizing molecule etanercept could be an effective treatment for patients with alcoholic hepatitis.
Forty-eight patients with moderate to severe alcoholic hepatitis (Model for End-Stage Liver Disease score ≥15) were enrolled and randomized to groups that were given up to 6 subcutaneous injections of either etanercept or placebo for 3 weeks. Primary study end points included mortality at 1- and 6-month time points.
There were no significant baseline differences between the placebo and etanercept groups in demographics or disease severity parameters including age, gender, and Model for End-Stage Liver Disease score. The 1-month mortality rates of patients receiving placebo and etanercept were similar on an intention-to-treat basis (22.7% vs 36.4%, respectively; OR, 1.8; 95% CI, 0.5–6.5). The 6-month mortality rate was significantly higher in the etanercept group compared with the placebo group (57.7% vs 22.7%, respectively; OR, 4.6; 95% CI, 1.3–16.4; P = .017). Rates of infectious serious adverse events were significantly higher in the etanercept group compared with the placebo group (34.6% vs 9.1%, respectively, P = .04).
In patients with moderate to severe alcoholic hepatitis, etanercept was associated with a significantly higher mortality rate after 6 months, indicating that etanercept is not effective for the treatment of patients with alcoholic hepatitis.
Miles and Shirley Fiterman Center for Digestive Diseases, Mayo Clinic, Rochester, Minnesota
‡ Division of Gastroenterology/Department of Medicine, Hennepin County Medical Center, Minneapolis, Minnesota
§ Department of Medicine, Indiana University, Indianapolis, Indiana
∥ Alabama Liver & Digestive Specialists, Montgomery, Alabama
¶ Department of Medicine, Scott & White Clinic, Temple, Texas
# Division of Gastroenterology/Department of Medicine, Mayo Clinic, Scottsdale, Arizona
Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota
‡‡ Departments of Medicine and Pharmacology & Toxicology, University of Louisville and Louisville VAMC, Louisville, Kentucky
Address requests for reprints to: Vijay Shah, MD, Miles and Shirley Fiterman Center for Digestive Diseases, Mayo Clinic, 200 First Street SW, Rochester, Minnesota 55905. fax: (507) 255-6318
Supported by the NIH (R01 AA013933 to V.S.), the NIH funded Mayo Clinical Research Unit (CTSA), and Amgen (to V.S.), which provided study drug and partially defrayed costs for cytokine analyses that exceeded the NIH budget.