Ethical Challenges During Clinical Trials of New Drugs

Monday, September 20, 2010

We often hear about successful medical drug clinical trials, and assume that such trials frequently test "magic bullet" cures. Nearly every trial, however, requires a control group: people who are not given the new drugs and, thus, don't benefit from them if they are later proven to work.  Many doctors, researchers and patients are asking questions about the fairness of maintaining these control groups, once a given drug being tested has positive results.

Amy Harmon, a national correspondent for The New York Times, wrote an article about two cousins from California: Brandon Ryan and Thomas McLaughlin. Both were diagnosed with melanoma in 2009. Ryan and McLaughlin were admitted to a clinical trial for a new drug, PLX4032, that had shown it could safely slow the cancer's progress in some patients.  McLaughlin was given the new drug, while Ryan was assigned by a computer lottery to the control group, meaning he would receive chemotherapy.  Ultimately, Ryan died from the disease, while McLaughlin's tumors stopped growing after just two months on the drug.

So, is it unethical to prevent someone from receiving medication that has shown it can improve one's condition, simply because it will skew the results of a clinical trial?

Dr. Bartosz Chmielowski is an assistant clinical professor of medicine the University of California, Los Angeles' oncology department.  He treated both McLaughlin and Ryan and says, "I'm kind of torn apart a little bit...we recognize that more clinical trials trials should be designed in a different way."  Chmielowski says, "On one side, [there's] society as a whole.  On the other side, there's the patient in a doctor's office."


Dr. Bartosz Chmielowski and Amy Harmon

Produced by:

Amanda Moore

Comments [2]

Chris P from Utah

PLX4032 is not a cure and even if someone sees response from the drug it is not permanent. Long term data from the early studies of the drug showed that 4/5 of the people responded, but the response only lasted from 2-18 months. Let's not jump on the bandwagon and call this a cure until we know what the full consequences are.

A single patient responding to a drug is not in and of itself evidence that the drug is safe and effective to be used in a broad population. There are many drugs that looked like they worked in some populations in early stages, but in broader populations this was not the case. Alzheimer's disease is littered with Phase 3 trials that did not show evidence of effect, for example.

Sep. 20 2010 06:16 PM
Steven Walker

The design, and indeed even the existence of this trial obliterates even the weak ethical basis for these types of trials, called "equipoise." We know beyond any reasonable doubt that PLX4032 is a much better drug for advanced melanoma patients with the molecular target (a specific genetic mutation that can be accurately detected) than the comparison drug, darcarbazine, an old, toxic chemo drug approved in 1975 that in dozens of trials over decades has never shown a response rate higher than 10 to 20 percent, a response duration higher than a couple of months or a survival advantage. PLX4032 has fewer, more tolerable side effects, a response rate of more than 80 percent, and a median duration of response of 7 to 8 months. Some patients do far better than that. We already know the answer. PLX4032 is far better than dacarbazine, and there is virtually no chance at all that the randomized trial will change that understanding. All it will do is cause the patients in the control arm to suffer, and to die prematurely. in the meantime, the thousands who will not be able to get PLX4032 by any means, will die waiting for it to be approved by the FDA, while the FDA in turn waits for its statistics from the trial. That statistic will be nothing more than a simplistic statistical comparison of the death rates between the two trial arms - body count statistics - and we already know what it will tell us. This trial is just using people up in a control arm to satisfy Dr. Richard Pazdur, the incompetent and reactionary regulator that heads the FDA's Office of Oncology Drug Products. He has been doing this to cancer patients for years. Many were troubled by what he has been doing, but with this drug now highlighting the problem at FDA in starkly clear terms, the problem can no longer be ignored.

Sep. 20 2010 07:22 AM

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