Issue 36 / 19 September 2016

THE randomised, placebo-controlled trial may be considered the gold standard in medical research, but that doesn’t mean it’s always the best approach.

A 2003 systematic review, Parachute use to prevent death and major trauma related to gravitational challenge, lamented the lack of placebo-controlled trials examining that particular health strategy.

“The perception that parachutes are a successful intervention is based largely on anecdotal evidence,” the authors wrote.

The only studies they could find were observational, leading the authors to warn of possible bias from a “healthy cohort effect”. Those using parachutes might be generally healthier than those not using them, in other words, making them more likely to survive jumping out of an airplane.

Good luck recruiting people for the placebo arm of a parachute trial.

The risks of placebo are not always that obvious, but the use of non-treatment arms in clinical trials does raise ethical questions.

In an article published in The BMJ last week, the authors examined the practice in relation to two trials of the rheumatoid arthritis drug, ocrelizumab. (They also examined the ethics of a homeopathy trial for the condition, but that’s another story …)

Both trials randomised patients with active arthritis, who had not previously responded adequately to methotrexate, to one of two groups: treatment with ocrelizumab plus methotrexate, or with placebo plus methotrexate.

Given that participants had already been found not to respond to methotrexate and that other effective treatments would have been available, this “potentially deprived participants of effective treatment for as much as a year”, the British and Australian researchers wrote.

“Inadequate treatment can lead to irreversible structural damage, additional pain, and functional impairment.”

The drug’s manufacturer was not exactly forthcoming when the researchers asked for copies of information provided to participants and submissions to ethics committees. It took a UK freedom of information request to obtain all the documents needed.

In an application to a UK ethics committee, the manufacturer had acknowledged that “the main ethical concern with this study is the need for the control arm to receive placebo ocrelizumab infusions”.

This concern was not, however, shared with participants in the two trials and consent forms “did not explicitly state the additional risk to members of the placebo control group such as increased pain, impairment, and permanent structural damage”, the researchers wrote.

There are good reasons, of course, to test treatments against placebo. You wouldn’t want to test different homeopathic potions against each other without a placebo arm.

But what are the ethics of including a placebo group in a trial when an effective treatment is already available for the condition being studied?

In the case of those rheumatoid arthritis trials, for example, there are other biologic drugs similar to the one being studied on the market.

When trials fail to put rival treatments up against each other, it’s not just participants who suffer.

If the “whizz-bang” new drug is not tested against the current preferred treatment, clinicians have no way of knowing whether the new treatment is any better than the old.

Have placebo-controlled trials had their day? Hardly.

But they do need to be subjected to scrutiny, and that means transparency about trial design and potential ethical concerns for participants and the broader public.

After all, we wouldn’t want anybody to be left without a parachute.

Jane McCredie is a Sydney-based science and health writer.

 

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