Ethics of placebo in cancer treatment clinical trials

The New York Times recently ran an article tackling a complex ethical dilemma in cancer care: the withholding of treatment in clinical trials. Because I was treated in 3 clinical trials in the 1990s, the topic is close to my heart.

Scientists have advanced the treatment of disease using the scientific method. By that, I mean they have tested a theory using rigorous methods that give a reliable and reproducible answer. This answer is not at all likely to be due to chance.

The gold standard of testing new treatments is the double-blind placebo-controlled randomized clinical trial.

In many medical situations for which effective therapies exist, researchers try to improve on the standard therapies by testing treatments in randomized clinical trial (RCT). Here, patients are randomly sorted into groups to compare different types of treatment for the same condition. In most cases, patients receive either the therapy being studied or state-of-the-art standard therapy (and not placebo — “sugar pill” or, more accurately, an inactive intervention).

For decades now, the RCT has been the way scientists have reined in emotions that might bias the results. The RCT has saved millions of patients from being treated with therapies that, in truth, don’t work. The RCT has preventing researchers from pursuing blind alleys (lines of investigation that will not yield effective therapies) and prompted them to pursue promising new lines of investigation.

So what is the problem? The problem is that many well-respected scientific researchers, and droves of desperate patients, believe we can do better. They believe that given modern technology, the old gold standard is now slowing progress and, most contentiously, keeping optimal therapies from patients who might benefit.

According the article, one particular trial of a therapy (called PLX4032) for malignant melanoma ”ignited an anguished debate among oncologists about whether a controlled trial that measures a drug’s impact on extending life is still the best method for evaluating hundreds of genetically targeted cancer drugs being developed.”

Some clinicians maintain their belief that the control arm is indispensable to assessing whether new therapies are better. Why the stubbornness? Because innumerable past trials that included a control arm proved promising therapies to be, disappointingly, no better than the standard therapies.

Other clinicians believe ”the new science behind the drugs has eclipsed the old rules — and ethics — of testing them.” These oncologists believe it is unethical to put patients on a control arm when the following conditions are present:

  • the standard therapy has been proven to be rarely or minimally effective
  • the investigational therapy has
    • mechanisms of action that are understood
    • shown effectiveness in pre-clinical and early clinical testing
    • minimal toxicity

Today’s clinicians struggle with the tension between fulfilling their obligations (1) to their individual patients and (2) to gathering scientific knowledge that will lead to better therapies for tomorrow’s patients.

Wendy S. Harpham is an internal medicine physician who blogs at Dr. Wendy Harpham on Health Survivorship and is the author of Only 10 Seconds to Care: Help and Hope for Busy Clinicians.

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  • justin

    the control arm is always necessary, whether it includes placebo or another proven treatment. without the control there is nothing to compare to.

  • Brian

    I suppose you could make the case that the accepted therapy could be tested as a historical control, but even then, I think it would be a mistake to do so.

  • Diora

    When my (late) mother was in clinical trial for PF-02341066, it didn’t appear to have a control arm, at least not in this trial: it was a dose escalation trial to determine safe dose, but by the time my mother went into this trial they have already established the dose, so everyone just got the drug. The stage 3 that they started after that was just comparing this drug to the standard chemo with the opportunity for people in chemo arm to switch if the chemo doesn’t work or if the side effects are intolerable. So yes, phase 3 has a control, but it’s not a placebo.

    I was always curious if there has ever been a trial comparing PF02341066 and placebo or if the response rate was so striking early on that it just was considered unethical.

  • Joseph Putnoki

    Another serious ethical issue is missed: not all placebos are really neutral and some drug companies request the placebo contents to include substances and quantities of their choice. This scandal errupted put a cloud over the integrity of some placebo manufacturers who sell their soul to the Devil and assist doctoring some trials and corrupt the results for th benefit of corrupt drug manufacturers!

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