Follow-up to the March 29 letter on Schering-Plough study P03659 (NCT00160251)
I talked with Ken Banta, Director of Strategic Communications, Robert Consalvo, Media Contact for PEG-Intron, Cecil B. Pickett, PhD, Senior Vice President and President, Schering-Plough Research Institute, and Robert J. Spiegel, MD, Senior Vice President, Medical Affairs and Chief Medical Officer. They addressed my questions, and gave me a clearer understanding of their rational for this study design. Although I still have some concerns about the study design, I was pleased that they were willing to talk with me about the protocol. Here are some of the questions I raised and the answers I received:
* How is "African-American" defined in this trial? Those who define themselves as "African-American" are considered "African-American". A patient can designate themselves as she wishes. It is important to note that several studies have shown that a higher percentage of those who self-identify as African-American are non-responsive to the standard HepC treatment (pegylated interferons and ribavirin) as compared to European-Americans. Schering-Plough acknowledged that the lack of a biological or other measurable means of defining population groups introduces complications in interpreting and applying these data.
* Can people of African-descent participate is this trial if they do not identify as African-American? Apparently so.
* Are African-Americans banned from this trial in an effort to increase genetic homogeneity? "That would be absurd." No, that is not the rationale.
* Are African-Americans banned from this trial because some studies have shown that African-Americans have lower neutrophil counts? No, neutrophil counts are very important when ribavirin is used, but ribavirin is not used in this trial. In addition, neutrophil counts are an inclusion criteria.
I asked if there were specific scientific or safety reasons for excluding African-Americans from this trial. I was not satisfied with their answers even though they were framed in the language of safety and science. For example, since we do not yet know if African-Americans (as a group) will show similar response rates to SCH 503034 as they do to the standard treatment, it seems that they should be included in the trial unless or until safety or scientific concerns suggest otherwise. Also, thorough and ongoing informed consent procedures would ensure that African-American study participants (and all other study participants) are aware of the risk of non-responsiveness over time or at higher doses. It is important to note that I have not reviewed the full protocol for this study. There could be clarifying information in that document, but that information, if it exists, was not conveyed to me during the conversation with Schering-Plough.
My interpretation is that since some studies have shown that African-Americans (as a group) respond differently to the standard HepC treatment (as compared to European-Americans, what about other ethnic groups?), it is more expedient to exclude African-Americans from the low-dose arms of the Phase II study of this new interferon based therapy. (African-Americans will be included in Phase III as mandated by law.) It seems they think this will make the data 'cleaner', but that comes at a cost to African-Americans who could potentially benefit from the low-dose drug in the trial, and it prevents researchers from studying the mechanism and effects of this drug in this population group. (Schering-Plough is currently running a separate single-dose clinical pharmacology study in African-Americans to partially address the latter concern.) It seems they feel they will save time by excluding African-Americans now. By their rationale, all people with HepC will receive a greater benefit if they can bring the drug to market sooner. In addition, Schering-Plough will be able to make money sooner.
Others, particularly the HepC and HIV advocacy groups from whom I first heard about this trial, contend that Schering-Plough's assumptions (African Americans will be more resistant to this drug, excluding them will save time, etc.) may not be correct, and that people's lives hang in the balance now. Given the information I have, I agree with this position.
My current research focuses on ethical and scientifically-responsible uses of race in biomedical research. The information I have suggests that this is not an ethical or scientifically-responsible use of race. As I noted in the original letter, defining 'race' is a complex issue that cannot be accomplished using only biological or scientific means. That makes the concept of 'race' particularly difficult to use in biomedical research, especially since it is a very real social concept that correlates strongly with certain health indicators. It is my position that this study, like many others, misuses the concept of 'race'. Fixing this problem requires a systematic and scientifically and socially-informed change in the way we understand, define and use race. Given yesterday's conversation, I hope that Schering-Plough will be on the leading edge of this change, if for no other reason than it will allow us all to produce better quality scientific and medical data that can be more easily and appropriately applied to individuals and population groups.
Let me express my gratitude again to the Schering-Plough representatives for talking with me about this issue. We may not agree on the immediate solution, but our conversation has helped advance my thought on this complex and important issue. Thank you.