A group of community advocates have written the FDA with concerns about a study of a new hepatitis C drug that initially excluded African Americans. The study, sponsored by Schering-Plough, investigates different doses of SCH 503034 (a new hepatitis C protease inhibitor) in combination with Peg-Intron (pegylated interferon), with or without ribavirin. The initial study design called for the enrollment of 300 people with hepatitis C genotype 1 who did not respond to prior hepatitis C treatment. The study was recently amended to add an additional group who would receive a higher dose of SCH 503034 (800 mg, compared to initial doses of 100, 200, or 400 mg) in combination with Peg-Intron; this higher-dose arm allows enrollment of African Americans.
There's been some debate within the community about Schering's initial exclusion of African Americans from this study, with different perspectives on the scientific justification (which hinges on the well-established fact that for unknown reasons, African Americans have lower overall response rates to interferon-based treatment for hepatitis C) and ethical issues. For some perspectives, see the following articles and posts:
No Blacks Allowed? A Drug Trial Comes Under Fire - article from Poz Magazine, April 5, 2006
Advocates Slam 'Racist' Drug Trial - article from Newark Star Ledger, March 29, 2006
Download the letter to the FDA here, or read the text by clicking on the link below.
April 20th, 2006
Dr. Debra B Birnkrant
Director, FDA Division of Antiviral Products
White Oak CDER Office Building 22
10903 New Hampshire Avenue
Silver Spring MD 20993
Dear Dr. Birnkrant,
We are writing to express outrage about the exclusion of African Americans from
Schering-Plough's phase II trials of SCH 503034, an investigational hepatitis C
protease inhibitor. Study NCT00160521 is evaluating multiple doses of SCH
503034 in combination with Peg-Intron, with and without ribavirin, in people with
hepatitis C who did not respond to prior treatment. The exclusion began at the
time of study initiation in September 2005 and continued until March 2006, when
the protocol was amended to create an additional dosing arm that permitted
African Americans to enroll. However, the amendment does not remedy the
fundamental problems with Schering's study design.
Schering-Plough's initial exclusion of African Americans-the highest-prevalence
population in the United States-was scientifically unjustified and ethically
unacceptable. A hallmark of clinical research is the principle that each prospective
research participant should have the opportunity to make an informed decision
about the relative risks and benefits of participating in a clinical trial.
We cannot overemphasize the importance of obtaining a complete picture of the
relative safety and efficacy of SCH 503034 and other experimental therapies in
African Americans, including during early stages of research when safety, dosing,
and pharmacokinetics/ pharmacodynamics are explored. Higher prevalence of
hepatitis C and suboptimal response rates to current treatment among African
Americans make it incumbent upon pharmaceutical sponsors of novel therapies to
design trials that provide sufficient data at the time of licensure about how drugs
perform in the people most likely to use them. Registration trials of pegylated
interferon failed to produce this data due to low enrollment of African Americans.
As a result, African Americans with hepatitis C and their clinicians were forced to
make decisions about the relative risks and benefits of treatment based on
inadequate information. This scenario must not be allowed to recur with promising
new agents currently in, or soon to enter, clinical trials.
Relevant and timely data on Schering's 503034 can only be generated by enrolling
adequate numbers of African Americans in phase III trials to power statistically
meaningful subgroup analyses of response to treatment by race. We ask that FDA
strongly encourage Schering to address this issue in its communications with the
company, request and review detailed plans for statistical analysis and
recruitment, and, if necessary, recommend changes in the phase III program as
appropriate. Relegating research on African Americans and SCH 503034 to a later
post-marketing commitment would represent a gross failure and injustice on the
part of both Schering-Plough and the FDA.
Finally, Schering's exclusion of African Americans from study NCT00160251 must
not set a precedent for future trials of other investigational agents. We request that
the FDA work with companies pursuing new hepatitis C therapies on designing
robust development programs capable of generating clear profiles on the relative
safety and efficacy of these agents in African Americans. We urge the FDA to
advise sponsors that any neglect of their responsibilities to African Americans with
hepatitis C will be reflected in the drug's labeling at the time of approval.
We will convey these concerns to Schering-Plough and other companies involved
in hepatitis C drug development, and look forward to a productive dialogue with
FDA on this crucial issue.
Community HIV/AIDS Mobilization Project (CHAMP)
New York, NY 10012
Harm Reduction Coalition
22 West 27th Street, 5th Floor
New York, NY 10001
Hepatitis C Action and Advocacy Coalition (HAAC)
53 Divisadero Street
San Francisco, CA 94117-3210
Hepatitis C Multicultural Outreach
10603 Blue Ridge Blvd
Kansas City, MO 64134
Treatment Action Group
611 Broadway Suite 608
New York, NY 10012