When evidence contradicts entrenched medical practices

‘Medical reversal’ harms patients and undermines faith in the medical system. Hematologist-oncologist Vinay Prasad is pushing to change how medicine adopts new technologies.


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Medical reversal is the phenomenon when a medical practice falls out of favor not by being surpassed, but when researchers discover that it didn’t really work all along.

“I think the lesson of reversal is we need robust, large-scale, pragmatic, randomized control trials,” said OHSU assistant professor Vinay Prasad, M.D., M.P.H. “That should be the rule of biomedicine and not the exception.”

Prasad, a hematologist-oncologist with the Knight Cancer Institute and a senior scholar in the Center for Health Care Ethics at OHSU, asserted the case for ending medical reversal in a video interview with MedPage Today.

Reversal is not the same as replacement, in that it harms patients who undergo the contradicted therapy before a change in medical practice. And it creates a loss of faith in the medical system by physicians and patients, Prasad says.

Examples abound: The drug Atenolol lowers blood pressure but ultimately proved no better than placebo in increasingly survival. The once commonly performed back surgery vertebroplasty worked no better than sham-vertebroplasty in diminishing pain or promoting spine stability. Mounting evidence suggests that mammographic screening does not benefit women in their 40s.

During his time as a resident, Prasad recalled, “we really chased tight glycemic control in the medical ICU. But of course, just a few years later, a randomized control trial, NICE-SUGAR, came out showing that that actually led to net harm without benefit.”

Interviewer Perry Wilson, M.D., pointed to a particularly instructive example, the attempt to lower early mortality after myocardial infarction with the antiarrhythmic drug flecainide:

Wilson: All the biological plausibility in the world is there suggesting that this drug should reduce the rate of death after MI, and yet when the definitive trial was done, a trial that you point out many questioned even the ethics of doing in the first place. But when the definitive trial was done, quite the opposite was shown. Is it the standard that these large, randomized trials are redefining what we think or is it smaller ancillary studies that sort of build up to a new understanding?

Prasad: Yeah, so I think that’s a fantastic question. The history of the CAS trial really revealed sort of the highlights of reversal. It came into prominence for good reason. It made perfect biological sense. PVCs, the R-on-T phenomenon, those were implicated at sudden cardiac death. This is a drug that suppresses those aberrant beats. This is a drug that should lower early mortality after myocardial infarction. As you point out, cardiologists, in many cases, were reluctant to enroll patients on the CAS study saying that there was no equipoise. It is unethical not to give these patients access to medication, and of course, that turned out to be a study where the drug actually caused harm.

So, I will say there are some takeaway lessons. There are many things in modern medicine that there are practitioners who say, “It would be unethical to study this rigorously.” I believe we have to really take those claims with a grain of salt. The history of medicine is littered with the smartest, most compassionate, thoughtful investigators being reluctant to test things they thought they knew were true and only to find that when they were tested by courageous investigators, they were contradicted.

I think the lesson of reversal is we need robust, large-scale, pragmatic, randomized control trials. That should be the rule of biomedicine and not the exception. And that anecdotal, case-based, retrospective, uncontrolled studies, while those things have a role, they’re hypothesis generating. They shouldn’t be used for definitive understanding of the efficacy of particularly novel treatments.

You can watch the full interview online at MedPageToday.com.

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About the Author

Joe worked as a cell biology researcher at the Rockefeller University in New York City until he figured out he could make a living writing about science for newspapers and magazines. He's been a science writer with the OHSU Knight Cancer Institute since September 2015.

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