Sunday, April 09, 2006

Respecting research subjects

The recent debacle in drug testing, which nearly killed the 6 participants, has been attributed in large part to the greed of the drug company. They were so intent on developing a profitable new product that they ignored the possible devastating impact on the study participants. Such unconcern is not limited to researchers motivated by profit. There is always a tremendous danger that research subjects will not be treated properly and respectfully by any scientist undertaking human studies research.

I saw this up close and personally when a dear friend entered a phase two trial for an ovarian cancer vaccine. My friend had had surgical debulking for a presumed borderline tumor and completed 6 months of platinum based therapy. She wanted to do everything possible to prevent recurrence and when she learned of a study of a potential vaccine, she enrolled.

I read the consent for the study and did a little background research. The vaccine sounded promising and the study appeared to have the appropriate safeguards in place. One of the most interesting details was that the vaccine preparation elicited antibodies that interfered with tumor markers assays. Therefore, the test for CA 125, the primary test used to follow disease recurrence and progression, was rendered inaccurate in study subjects. They would be monitored with a special assay for CA 125 that was not subject to the same cross-reactivity. The cost for this assay would be born by the study.

My friend had an allergic reaction to the vaccine, and, of course, was not allowed to receive further doses. Shortly thereafter, a regular CA 125 assay was elevated, indicating possible recurrence. Her oncologist was aware that the vaccine might be responsible and asked the principal investigator of the vaccine study for access to the special CA 125 test. The investigator refused.

In my naivete, I could not believe that the investigator refused, so I called him myself. We had a very unpleasant argument. The principal investigator, an MD, claimed that he was not responsible for anything that happened to women who dropped out of the study. Yes, he understood that the elevated CA 125 assay might be erroneous, but that was not his problem. He would not spend study money for the special assay and he would not help me obtain the assay even if the patient paid. I cannot even begin to imagine how this doctor could manage to justify to himself that complications from HIS study were not his responsiblity.

The matter might have ended there, except that I know how human research studies work, and I reported him to his IRB (institutional review board). Within 2 hours of talking with the head of the IRB, I received a call from the vice president of the company that manufactured the vaccine. He was so sorry for any difficulty; they had already arranged for my friend to have the assay performed and would pay for all costs associated with it. Shortly thereafter, the head of the IRB called back to assure me that he had spoken with the principal investigator and had made it clear to him that this would never happen again to any patient in the study.

Unfortunately, there was no happy ending. The special assay for CA 125 was also elevated. My friend had a true recurrence and has stage IV disease; she has been undergoing a succession of treatments ever since.

I have tried to understand why the principal investigator refused to help. The most cynical explanation is that he was planning to delete my friend from the study altogether, so he would not have to report any adverse results. Yet I suspect that the reasoning was not so malign. It was simply that the investigator felt that so much good would come from testing and gaining approval for the vaccine, that nothing else mattered. That is why IRBs are so important. An IRB that is functioning properly protects that patients' safety, but also assures that the welfare of individual patients will not be sacrificed for the success of the enterprise.

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