Letters - A Cancer Drug Trial, and a Wrenching Choice

Re “When Testing a Drug Means Withholding It” (“Target: Cancer” series, front page, Sept. 19):

Drug trials are important, but let’s revisit how to conduct them: in the case of melanoma, data already exist for chemotherapy results. Why not give everyone in the trial the new drugs (or if more than one new treatment is ready for testing, give some participants one, and some another)?

Their progress can be compared with a “control group” of previous recipients of chemotherapy, a treatment long proved ineffective and painful.

This not only gives more cancer patients the possibility of help, but it also lifts the burden of guilt from doctors and researchers who must justify the unjustifiable to patients and their loved ones.

Nancy B. Weil
Denver, Sept. 19, 2010

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To the Editor:

It is truly tragic that Brandon Ryan died during the trial of a very promising drug for melanoma after being randomized into a control group of a standard therapy that is known to be ineffective.

But it isn’t clear why the Phase III trial wasn’t stopped earlier, if the experimental treatment was shown to be effective. Clinical trials like the one discussed are overseen by data safety monitoring boards, which watch the unblinded data from all study participants.

These boards are charged with monitoring if the study falls out of “equipoise,” a state of uncertainty in which one drug or treatment is not believed to be better, or worse, than a competing drug or treatment. If it turns out that the risks of one therapy strongly outweigh the benefits of the other, or the benefits of one therapy strongly outweigh the risks of the other, the study is said to fall out of equipoise.

Studies in the past have been stopped early for exactly this reason. You imply that the study had fallen out of equipoise — there is no longer any uncertainty as to which treatment is better. And yet, there was no mention of the data safety monitoring board, and its role in potentially stopping the study early.

It isn’t necessarily the case that randomized controlled trials are inherently unethical. Two other options present themselves: it may be the case that the study had not truly fallen out of equipoise, or the D.S.M.B. isn’t doing its job.

Deborah Barnbaum
Kent, Ohio, Sept. 19, 2010

The writer is a professor of philosophy at Kent State University and a member of the Data Safety Monitoring Board for the Diabetic Retinopathy Clinical Research Network.

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To the Editor:

You delved into one of the most controversial issues in cancer research — whether it’s ethical to put patients on a therapy that is known to be nearly ineffective for the sake of “clean” control data.

While these are difficult issues to navigate, this issue arises only because of the tremendous explosion of progress we’ve seen in melanoma research in the last few years. As the research field changes in melanoma, aspects of traditional trial design urgently need to be re-evaluated.

With quick action among stakeholders — pharmaceutical companies, academia, the Food and Drug Administration, foundations and patients — protocols can be designed that meet the needs of patients, scientific standards and the regulatory environment.

A related problem not addressed in your article is that too many patients are never even told about their clinical trial options. If patients do not enter clinical trials, their chance of receiving promising investigational drugs is 0 percent, rather than 50 percent. A 2001 study reported that about 85 percent of cancer patients didn’t know that participation in clinical trials was an option, and 75 percent said they would have been willing to enroll in one if only they had known.

Stakeholders must address the sticky ethical issues that you discuss. Until that happens, the virtual ineffectiveness of standard therapies means that clinical trials — “warts and all” — hold the best promise for melanoma patients. All patients have the right to know what their clinical trial options are, and all physicians have the responsibility to tell them.

Timothy J. Turnham
Executive Director
Melanoma Research Foundation
Washington, Sept. 21, 2010

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To the Editor:

Your Sept. 19 article about testing PLX4032 for advanced melanoma was sympathetic and engaging. I wonder, however, why the lessons learned early in the AIDS epidemic through the actions of activists have not been applied to this case.

Steven Epstein’s book “Impure Science: AIDS, Activism and the Politics of Knowledge” documents how AIDS activists successfully fought to avoid assignment to randomized trials.

Because the early AIDS drugs were so much better than the control treatment available at the time, randomized clinical trials were not needed to get statistically significant results. Perhaps we need a more appropriate protocol for testing promising new drugs, one that addresses both epistemic and ethical challenges.

Miriam Solomon
Philadelphia, Sept. 19, 2010

The writer is a professor of philosophy and director of graduate studies at Temple University.

via nytimes.com

Posted via email from Peace Jaway