Blood Products Advisory Committee Meeting Transcript

December 14, 2010

January 2011

Harvey J. Alter, MD, MACP, is chief of the infectious disease section and associate director for research of the Department of Transfusion Medicine, Warren Grant Magnuson Clinical Center at the National Institutes of Health in Bethesda, Maryland.  He is also clinical professor of medicine at Georgetown University in Washington, DC.   

He has devoted most of his research career to the study of blood-transmitted infections, particularly viral hepatitis.  He was the principal investigator in the first study to biophysically characterize the ďAustralia antigenĒ, which was later shown to be the envelope protein of the hepatitis B virus.  He led the prospective studies that identified the clinical entity known as non-A, non-B hepatitis and the first to confirm that it was a transmissible agent.  He was the principal investigator in sequential prospective studies of transfusion-associated hepatitis that influenced national blood policy mandating donor screening assays.  Dr. Alterís unique, long-term prospective studies identified transfusion risks as well as donor-screening measures to alleviate those risks, and then measured the outcome of these interventions.  After the cloning of the hepatitis C virus (HCV), he conducted the key study that established HCV as the major cause of transfusion-associated hepatitis and demonstrated the clinical efficacy of anti-HCV screening assays. For his contributions to the discovery of the non-A, non-B/hepatitis C virus and for his vital role in reducing hepatitis risk and improving the safety of the blood supply, Dr. Alter has received many awards and other recognition.

Source: http://www.aacc.org/about/awards/hall_of_fame/Pages/HarveyAlter2005L.aspx

Dr Harvey Alterís Closing Remark at the Conference

DR. ALTER: Since Dr. Lo had to leave early, I felt I had to come up and do some defense of him and Judy as well. I think, when a group finds a new agent, they become biased that this agent is real. When another group doesn't find an agent, they become, I think, even more biased that the agent is not real. That leads to this kind of contentiousness.

I think our goal should be not to bring the other side down, but to find the truth. I think the truth will out over the next year, with studies that are already planned.

At this point I concur that we have no evidence for causality. That's going to be very difficult to come by, especially when we are detecting at the limits of detectability and when assay performance is very critical to get equal results.

But I still want to counter by saying I think the current evidence for disease association is very strong, even though not universally confirmed. But it has been confirmed now in at least four studies, two of which were presented today, that either XMRV or a polytropic MLV is associated strongly with chronic fatigue syndrome. A point that I think was misrepresented today: In those labs who do find the agent, it is very reproducible. Judy has found the same patients to be positive by culture year after year. We have found a patient to come back after 15 years and still be positive. So this is not a single, isolated finding. It's confirmed by sequencing. It's reproducible over time.

Dr. Hanson has shown today how critical the assays are. When she tweaked her assay, she went from no findings to findings almost identical to the Lo lab. The diversity is now being confirmed also in the original WPI group. XMRV isn't the only agent even in the WPI lab.

Despite the very legitimate concern for contamination -- I think this is a serious issue -- there have been hundreds of negative controls in the same laboratory that are always consistently negative. An extremely sensitive mouse mitochondrial DNA has always been negative in the Lo laboratory. Lo has done the IPA assay that Dr. Coffin recommended. That is also negative. There just has been no evidence for contamination. Although you could say maybe the negatives could be negative somehow and the positives positive for contamination reasons, it really is not logical that that would be so.

I'm not a molecular biologist. I defer to Dr. Stoye, who is world-renowned in that area. But just as a simple doctor, it seems to me that you have used single-case anecdotal evidence to knock down the various possibilities. I just want to make a case to the committee that you can't -- your conclusion is that anything can happen in assays, and therefore it probably has happened this time. I think using that kind of anecdotal probability is not valid to negate reproducible data from four different laboratories. So at least keep that in mind.

Lastly, I'm not a chronic fatigue doctor, but I have learned a lot about chronic fatigue in the last six months and have spoken to a lot of patients. I'm absolutely convinced that when you define this disease by proper criteria, this is a very serious and significant medical disease, and not a psychological disease. It has the characteristics of a viral disease. It usually starts with a viral-like illness. If XMRV is not the causative agent -- and it may well not be -- there is still need by other groups to look for the next agent which may be the case.

Sorry to take so much time.

 

http://www.fda.gov/AdvisoryCommittees/CommitteesMeetingMaterials/BloodVaccinesandOtherBiologics/BloodProductsAdvisoryCommittee/ucm239304.htm

Presentations on MLV related matters start on page 165

The UK study assisted by Invest in ME is presented on page 210.