Monday, August 06, 2007

Irregularities in Recruitment in Potential Gene Therapy Research Death

Last week I linked to an emerging story about a woman who has died while being involved in gene therapy for arthritis: Not a good day for research. While it is not yet confirmed whether the woman's death was due to the gene therapy it does appear that there were some irregularities in process of recruitment that lead her to be involved. The Washington Post has a very comprehensive article: Death Points to Risks in Research

Key points are:

"It was presented to her like this is going to make her knee better," said Robb Mohr, an agronomist who lived with his wife of nine years in a modest vinyl-sided ranch home near Springfield, Ill. "It was supposed to be just a simple thing."

A two-sentence paragraph halfway through a 15-page consent document that Jolee Mohr signed warns of the possibility of "unknown side effects," including, "in rare circumstances, death."

Further in, after long descriptions of how the product may help, a single sentence states: "We do not expect you to receive any direct medical benefits from participation in this study."

Mohr was in an early-phase study, the prime goal of which was to see whether the treatment was safe, not to provide a therapeutic benefit. If the drug passed muster, other studies would determine whether it was an effective treatment.

So first things first, a 15 page consent document is worse than useless, few people will read this much material in detail. Especially if, as later emerges in the article, they are not given the document to take away and study. And while the disclaimers are there by the sounds of things, they are hidden by the context, it isn't appropriate to talk about the potential benefits of a treatment, at great length, in what is effectively a safety study.

It then gets worse, since her rheumatologist gets payments from the company involved for each person they recruit onto the study. So we have direct therapeutic recruitment, which is bound to cause therapeutic confusion coupled with a conflict of interest.

The sad thing is that it is unlikely that this is an isolated case of poor practice, instead this is likely to be only the tip of the iceberg, revealed by a tragic death.


Greg Pawelski said...

There may be a good reason to be cautious in considering a clinical trial offered by a doctor. Being involved in many trials may make them give a subtle pull towards getting patients in those trials. The possibility that the doctor has a conscious or subconscious stake in increasing the number of patients in a trial that may bias their advice or subtly influence the doctor to downgrade the potential of a standard or different therapy. The doctor may have a readiness to believe that the trial would be reasonable for the patient coupled with a readiness to believe other options do not offer an advantage. While some bias occurs simply because researchers are human beings who have a special interest in advancing knowledge for the good of humanity, on the other hand, many of these researchers are often paid up to several thousand dollars for enrolling patients in clinical trials, making financial gain the key motivation.

David Hunter said...

Hi Greg
I agree with you it is something to be cautious of. The difficulty is I guess who is the appropriate person for enrolling people into clinical trials? Research Ethics Committees, at least in the UK often frown on direct recruitment by the researcher. And doctors have access both to likely research subjects and have (in principle) the knowledge to explain the study appropriately.

But I agree I think at best the doctor should ask people if they are happy to be contacted by the research team who should handle it from there.

I'm quite wary of the practice of paying or giving other benefits for referrals, I think it introduces too strong a conflict of interest. I have seen one study myself where it said any doctor who recruited more than 5 participants would be put on the resulting research paper as an author!