The Fine Line Between Alarmism and Oversight

Responding to yesterday's post on the death of Jolee Mohr during a gene therapy trial for rheumatoid arthritis, reader JD responded with this comment:

I'm struck by the alarmist tone of your words, and your willingness to play armchair doctor when all you've done is read newspaper articles and talk to a lawyer--the latter probably due in no small part to your previous coverage, which another poster aptly called a "hatchet job".

There's no need to wonder if the medical establishment has run amuck trying to "do gene therapy for mild rheumatoid arthritis"--that's why we have the FDA to oversee something called "Good Clinical Practice".
If Jolee's trial is anything like the other 22,000 regulated human clinical trials currently active, it's 1) likely that she sought it out herself, 2) probable that she had to fight to get in, and even if 1 and
2 are wrong 3) DEFINITE that she gave her INFORMED CONSENT after reviewing the risks with her physician. Was it wrong to administer the experimental treatment to a patient with a "mild fever"? I'd bet the
FDA-approved study protocol is more reliable than your appeal to common sense on that matter, Brandon. Did you read it?

Jolee's family describes her as being healthy and active, then in the same breath say that she was being offered a "cure". For what? Make no mistake, Jolee was SICK--if she didn't look it, that's likely thanks to whatever DMARDs she was taking to manage her RA. My brother has rheumatoid arthritis. Contrary to Milstein's assurances to the contrary, there's nothing "mild" about it. Anyone familiar with the condition and the currently available treatments will tell you that when it comes to RA, an "active, healthy life", as he puts it, is definitely not the norm, and I find it hard to imagine Jolee would have accepted the risks of the trial and given her informed consent if in fact she was leading such an active, healthy life.

Unmedicated RA leads to (among other things) debilitating chronic pain;
permanent nerve, bone, and joint damage; and sometimes death. With medication, symptoms can slow or sometimes remit entirely, in exchange for a life-long battle with infections, liver and bone marrow damage, and lots of other wonderful side effects of the anti-inflammatory meds
(read: immune system suppressors) you have to take for the rest of your life.

Please get out of your cubicle and go talk to people who suffer from inflammatory disorders before you write your next article casting suspicion on new therapies. And then read up on clinical trials before writing further rubbish about how to properly carry them on, for goodness’ sake.

There's a lot to address here, so I'll start from the top. I don't worry about a "medical establishment run amok" -- that's JD's interpretation. What I and others worry about are mistakes that the medical establishment can make and how those mistakes can be reduced.

The FDA isn't a villain in this story, and the US regulatory process for clinical trials is one of the best in the world. But that doesn't mean it's perfect, or that people -- including journalists -- ought to assume that every trial is flawlessly designed and run.

JD says Mohr probably sought out the trial herself -- as far as we know, she didn't. He says she probably had to fight to get in -- that we don't know, and it's irrelevant. Even if she didn't, he writes, she still gave informed consent -- but the consent process in this case appears to have broken down, as Mohr's arthritis doctor was also an investigator in the trial, and allegedly presented the trial as providing a cure when it was only testing safety.

As for whether administering an immunosuppressant therapy when a patient already on immunosuppressant drugs shows signs of infection was a "mistake," as I called it, that's open to debate. Jeff Chamberlain wrote to me today, "The situation you describe is something likely written into many protocols, but again it would be a case by case basis." Whether or not the doctor who made the injection was told not to do this is unknown; I haven't yet seen the exact protocol, and there is no public record detailing the training sessions held by Targeted
Genetics. But it does strike me as a bad idea, and there's nothing wrong about suggesting that trial protocols be written to prevent people from having their immune systems compromised right when they're getting sick.

Could all this have been avoided by having the trial conducted by doctors who were experts at gene therapy, rather than non-experts hired and given training sessions by the company? That's a question that at least deserves to be asked.

JD goes on to insist that there's no such thing as "mild" rheumatoid arthritis, and that if Mohr didn't seem sick it was probably because of the drugs she was taking. Then he says that Mohr wouldn't have accepted the risks of the trial if she was in fact living an active, healthy life.

As for the latter point, Mohr's decision to accept those risks wasn't just influenced by the severity of her condition, but by the apparently overstatement of the trial's benefits by her doctor. As for the potentially debilitating nature of the disease, that's not at issue here. But rather than speaking in generalities, we ought to deal in specifics -- namely, that the trial was aimed at people with non-severe cases of rheumatoid arthritis.

At this point, gene therapy is imperfectly understood. A lot remains to be learned about making it work. The vast majority of gene therapy trials are aimed at people suffering from cancer and other immediately deadly diseases.These people have fewer treatment options and are at greater risk of death than people with moderate rheumatoid arthritis. The gene therapists I've spoken with recommend that trials like Targeted Genetics' be avoided until an understanding of the therapies is developed in people whose predicaments are so severe that the experimental risks are justified. Once scientists have a better grasp on gene therapy, they can set about treating diseases like arthritis.

If this is "alarmist," so be it.
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Image: Rupert Ganzer*