Are controlled clinical studies "cruel?"

Clinician Dr. Louann Brizendine is quoted in the New York Times as saying that she doesn't do research because "I don't want to give patients a placebo. It's cruel." The interviewer pushes her on the issue, pointing out that in the long term, controlled studies are necessary in order to determine the efficacy of treatments. Her reply: "I am glad someone does it, but I'd rather help each female brain that walks into my clinic walk out in better shape."

Adam Kolber wonders if something might have been lost in the transcription of the interview, but I don't doubt that Brizendine's sentiments may have been perfectly expressed in her statement.

In a former life, I did back-end work on clinical cancer studies, and I saw a lot of data. There were "compassionate" doctors who lost patients because they didn't want to see them "suffer" through chemotherapy. There were doctors who would only agree to participate if they were assured their patients wouldn't be in the control group. Some of the medical records were in such disarray that it was impossible to decipher what treatment patients had received. All these doctors said they cared about their patients more than they cared about the study, but in the end, they were just making things more difficult for patients -- their patients -- in the future, who wouldn't benefit from good research.

A lot of medical research doesn't actually use true placebos. Instead, they compare a new treatment to an older treatment. The control group gets treated, just not with the particular regimen that's under study. There's no assurance that the experimental group will fare better than the control group -- the experimental treatment could have worse side effects, or simply not be as effective as the "tried and true" medication. Yet it always seems that people who are critical of medical studies claim they are cruel to the control group.

I can't speak for Brizendine, but I suspect the real reason that many doctors don't like to participate in clinical studies is that they don't want someone looking over their shoulder. They believe they know what's best for their patients, and they don't want someone else questioning their judgment. This attitude only makes things more difficult for researchers, and probably contributes in some ways to heavy-handed behavior that doctors don't like.

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Today, in another of her cantankerous and directionless "interviews," Deborah Solomon of the New York Times at least got something right. This time, the subject of her bullying is Louann Brizendine, a professor of neuropsychiatry at the University of California, San Francisco (UCSF). Brizendine,…
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This article is cross-posted at Science-Based Medicine. Check it out. --PalMD In a previous post, I argued that placebo is an artifact of certain clinical interactions, rather than a treatment that we can exploit. Apparently, there are a whole lot of doctors out there who don't agree with me.…
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By the time a drug gets approved for a human trial, there is probably some pretty solid evidence that it should work. However, if we knew that a drug was safe and effective, we wouldn't be doing the clinical trial in the first place. The experimental group might fare no better or worse than the placebo group. It's not necessarily cruel to give someone a placebo, nor is it necessarily cruel to give someone a new drug. There could be benefits or risks to each and by definition the scientists conducting a clinical trial don't know enough about the drug to say which condition is better. Dr. Brizendine appears to have an irrational optimism about new medications, while the other doctors mentioned in the third and fourth paragraph appear to have an irrational pessimism about new medications. Both groups should realize that they do not have enough information to make such an evaluation.

By Jason McKim (not verified) on 14 Dec 2006 #permalink

I've been a participant in a placebo-controlled double-blind clinical trial, for a condition that I had not previously been treated for. Honestly, the most frustrating part was at the end of the trial, when I wanted to continue the apparently successful treatment. There were actually four groups--a placebo group and three different dosage level groups. The records for the trial (which was operating at many locations & coordinated somewhere else) were still sealed, and we had some fun times guessing at the effective dosage. Then I went back to my regular doctor, and got, "That medication isn't approved yet for your condition." Well, yeah, I knew that--but it seemed to be effective, and it's known to be safe (it was already in widespread use for other purposes), so please?

By Scott Simmons (not verified) on 14 Dec 2006 #permalink

When a clinical trial involves patients with a potentially life-threatening or disabling condition, don't they compare the experimental drug with the best current treatment, rather than with a placebo? I always thought that trials of an experimental drug vs. placebo were done only (a.) on healthy volunteers or (b.) when the health problem in question was a minor one.

Actually, because of Placebo effect, the study would also be beneficial to those who are not given the real drug.

Also, if no such studies occur, then what is the alternative? Give a drug which might be worthless (or even damaging) to everyone? Or perhaps just give the drug to some and not give others anything? Wouldn't all other choices just be worse?

It seems to me that a bigger problem is drug companies pushing a new drug that is later found to be ineffective or has potentially serious side effects. Still, it is shocking that even such intelligent and highly-trained individuals would be so close-minded.

By David Group (not verified) on 15 Dec 2006 #permalink

a bigger problem is drug companies pushing a new drug that is later found to be ineffective or has potentially serious side effects

Might this not be due to poor clinical testing, related to the problem I discuss in the post?

Interesting post, and, given that I have to analyze the data that comes out of those studies, I can tell you that screwed up data really compromises a study, and wastes time, money, and risk of having the experimental therapy be more toxic than helpful.

However, there are more mechanisms now to answer clinician's concerns. The FDA has recently expanded access to experimental medicines in certain cases (mostly life-threatening, all other possibilities exhausted). Also, because of exposure requirements for pre-marketing studies, most companies will have an open-label (non-randomized, non-masked) extension to a study where everyone gets the therapy for an extended amount of time. I don't yet know how this affects attitudes of clinicians on the whole, but I have seen cases where this solution has worked pretty well for both clinician and patients.

Also, to address the this comment:

Might this not be due to poor clinical testing, related to the problem I discuss in the post?

That's one possibility, though it takes many forms. Take anti-infectives as an example. One of the concerns with antibiotics is that, given that in some cases of serious infection a placebo-controlled trial is truly unethical (ethics of antibiotics gets rather hairy in the presence of antibiotic resistance), studies for these have to be run as non-inferiority studies. However, there's a concern over the phenomenon of biocreep, where you can approve therapies that are just a little worse than the last one until you have something that is no more effective than placebo on the market. Each study in this "chain" of studies can be well-designed and executed, but even so it's still possible to have an ineffective product succeed in clinical testing.

Modern antibiotic trials have to address that issue, and that will become part of good antibiotic trial design, but until this phenomenon was brought out into the open it was still possible to have good clinical testing pass bad products.

I think there might be an ethical problem to studies testing the effects of new drugs. After all, the doctors deal with patients that are seriously ill. So, what the patients expect the doctors to do is to try to find the best treatments to cure their diseases. This aim might conflict with the requirement of the study to have an experimental group and a control group. The rational behind this design is that you expect that one group will do better than the other. However, the assignment to each group must be completely random and is not dependent on what the doctor thinks is the best treatment for the patient.
I still think that controlled studies are absolutely necessary, but I would not agree with the opinion that there's no ethical problem involved.

The languagelog guys demonstrate pretty clearly that Brizendine has no particular interest in or understanding of science and scientific method at all.

Reply to Dave Munger:

My understanding of the article was that doctors didn't participate in studies because of personal beliefs or bias (generally because of some sense of altruism, however misguided it may be), rather than succumbing to the greed of corporate interests.

By David Group (not verified) on 17 Dec 2006 #permalink