When evidence says no, but doctors say yes

The executive had been very smart to seek more information, and now, by coming to Brown, he was very lucky, too. Brown is part of the RightCare Alliance, a collaboration between health-care professionals and community groups that seeks to counter a trend: increasing medical costs without increasing patient benefits. As Brown put it, RightCare is “bringing medicine back into balance, where everybody gets the treatment they need, and nobody gets the treatment they don’t need.” And the stent procedure was a classic example of the latter. In 2012, Brown had coauthored a paper that examined every randomized clinical trial that compared stent implantation with more conservative forms of treatment, and he found that stents for stable patients prevent zero heart attacks and extend the lives of patients a grand total of not at all. In general, Brown says, “nobody that’s not having a heart attack needs a stent.” (Brown added that stents may improve chest pain in some patients, albeit fleetingly.) Nonetheless, hundreds of thousands of stable patients receive stents annually, and one in 50 will suffer a serious complication or die as a result of the implantation procedure…

When you visit a doctor, you probably assume the treatment you receive is backed by evidence from medical research. Surely, the drug you’re prescribed or the surgery you’ll undergo wouldn’t be so common if it didn’t work, right?

For all the truly wondrous developments of modern medicine—imaging technologies that enable precision surgery, routine organ transplants, care that transforms premature infants into perfectly healthy kids, and remarkable chemotherapy treatments, to name a few—it is distressingly ordinary for patients to get treatments that research has shown are ineffective or even dangerous. Sometimes doctors simply haven’t kept up with the science. Other times doctors know the state of play perfectly well but continue to deliver these treatments because it’s profitable—or even because they’re popular and patients demand them. Some procedures are implemented based on studies that did not prove whether they really worked in the first place. Others were initially supported by evidence but then were contradicted by better evidence, and yet these procedures have remained the standards of care for years, or decades.

Even if a drug you take was studied in thousands of people and shown truly to save lives, chances are it won’t do that for you. The good news is, it probably won’t harm you, either. Some of the most widely prescribed medications do little of anything meaningful, good or bad, for most people who take them.

In a 2013 study, a dozen doctors from around the country examined all 363 articles published in The New England Journal of Medicine over a decade—2001 through 2010—that tested a current clinical practice, from the use of antibiotics to treat people with persistent Lyme disease symptoms (didn’t help) to the use of specialized sponges for preventing infections in patients having colorectal surgery (caused more infections). Their results, published in the Mayo Clinic Proceedings, found 146 studies that proved or strongly suggested that a current standard practice either had no benefit at all or was inferior to the practice it replaced; 138 articles supported the efficacy of an existing practice, and the remaining 79 were deemed inconclusive. (There was, naturally, plenty of disagreement with the authors’ conclusions.) Some of the contradicted practices possibly affect millions of people daily: Intensive medication to keep blood pressure very low in diabetic patients caused more side effects and was no better at preventing heart attacks or death than more mild treatments that allowed for a somewhat higher blood pressure…

A brand new review of 48 separate studies—comprising more than 13,000 clinicians—looked at how doctors perceive disease-screening tests and found that they tend to underestimate the potential harms of screening and overestimate the potential benefits; an editorial inAmerican Family Physician,co-written by one of the journal’s editors, noted that a “striking feature” of recent research is how much of it contradicts traditional medical opinion…

So, while Americans can expect to see more drugs and devices sped to those who need them, they should also expect the problem of therapies based on flimsy evidence to accelerate. In a recent Stat op-ed, two Johns Hopkins University physician-researchers wrote that the new 21st Century Cures Act will turn the label “FDA approved” into “a shadow of its former self.”...

Steven Galson, a retired rear admiral and former acting surgeon general under both President George W. Bush and President Barack Obama, has called the strengthened approval process created in 1962 the FDA’s “biggest contribution to health.” Before that, he said, “many marketed drugs were ineffective for their labeled uses.”…

A 2007 Journal of the American Medical Association paper coauthored by John Ioannidis—a Stanford University medical researcher and statistician who rose to prominence exposing poor-quality medical science—found that it took 10 years for large swaths of the medical community to stop referencing popular practices after their efficacy was unequivocally vanquished by science.

According to Vinay Prasad, an oncologist and one of the authors of the Mayo Clinic Proceedings paper, medicine is quick to adopt practices based on shaky evidence but slow to drop them once they’ve been blown up by solid proof…

So he[Adam Cifu]and Prasad coauthored a 2015 book, Ending Medical Reversal, a call to raise the evidence bar for adopting new medical standards. “We have a culture where we reward discovery; we don’t reward replication,” Prasad says, referring to the process of retesting initial scientific findings to make sure they’re valid…

Thanks to such guidelines, the frequency of clearly inappropriate stent placement declined significantly between 2010 and 2014. Still, the latest assessment in more than 1,600 hospitals across the country concluded that about half of all stent placements in stable patients were either definitely or possibly inappropriate…

Nissen thinks removing financial incentives can also help change behavior. “I have a dozen or so cardiologists, and they get the exact same salary whether they put in a stent or don’t,” Nissen says, “and I think that’s made a difference and kept our rates of unnecessary procedures low.”..

Almost to a person, the cardiologists, including those whose incomes were not tied to tests and procedures, gave the same answers: They said that they were aware of the data but would still send the patient for a stent. The rationalizations in each focus group followed four themes: (1) Cardiologists recalled stories of people dying suddenly—including the highly publicized case of jogging guru Jim Fixx—and feared they would regret it if a patient did not get a stent and then dropped dead. The study authors concluded that cardiologists were being influenced by the “availability heuristic,” a term coined by Nobel laureate psychologists Amos Tversky and Daniel Kahneman for the human instinct to base an important decision on an easily recalled, dramatic example, even if that example is irrelevant or incredibly rare. (2) Cardiologists believed that a stent would relieve patient anxiety. (3) Cardiologists felt they could better defend themselves in a lawsuit if a patient did get a stent and then died, rather than if they didn’t get a stent and died. “In California,” one said, “if this person had an event within two years, the doctor who didn’t [intervene] would be successfully sued.” And there was one more powerful and ubiquitous reason: (4) Despite the data, cardiologists couldn’t believe that stents did not help: Stenting just made so much sense. A patient has chest pain, a doctor sees a blockage, how can opening the blockage not make a difference?

In the late 1980s, with evidence already mounting that forcing open blood vessels was less effective and more dangerous than noninvasive treatments, cardiologist Eric Topol coined the term, “oculostenotic reflex.” Oculo, from the Latin for “eye,” and stenotic, from the Greek for “narrow,” as in a narrowed artery. The meaning: If you see a blockage, you’ll reflexively fix a blockage. Topol described “what appears to be an irresistible temptation among some invasive cardiologists” to place a stent any time they see a narrowed artery, evidence from thousands of patients in randomized trials be damned. Stenting is what scientists call “bio-plausible”—intuition suggests it should work. It’s just that the human body is a little more Book of Job and a little less household plumbing: Humans didn’t invent it, it’s really complicated, and people often have remarkably little insight into cause and effect.

Chances are, you or someone in your family has taken medication or undergone a procedure that is bio-plausible but does not work…

A 2004 analysis of clinical trials—including eight randomized controlled trials comprising more than 24,000 patients—concluded that atenolol did not reduce heart attacks or deaths compared with using no treatment whatsoever; patients on atenolol just had better blood-pressure numbers when they died…

Replication of results in science was a cause-célèbre last year, due to the growing realization that researchers have been unable to duplicate a lot of high-profile results. A decade ago, Stanford’s Ioannidis published a paper warning the scientific community that “Most Published Research Findings Are False.” (In 2012, he coauthored a paper showing that pretty much everything in your fridge has been found to both cause and prevent cancer—except bacon, which apparently only causes cancer.) Ioannidis’s prescience led his paper to be cited in other scientific articles more than 800 times in 2016 alone. Point being, sensitivity in the scientific community to replication problems is at an all-time high. So Jacobs and his coauthors were bemused when the NEJM rejected their paper…

At the same time, patients and even doctors themselves are sometimes unsure of just how effective common treatments are, or how to appropriately measure and express such things. Graham Walker, an emergency physician in San Francisco, co-runs a website staffed by doctor volunteers called the NNT that helps doctors and patients understand how impactful drugs are—and often are not. “NNT” is an abbreviation for “number needed to treat,” as in: How many patients need to be treated with a drug or procedure for one patient to get the hoped-for benefit? In almost all popular media, the effects of a drug are reported by relative risk reduction. To use a fictional illness, for example, say you hear on the radio that a drug reduces your risk of dying from Hogwart’s disease by 20 percent, which sounds pretty good. Except, that means if 10 in 1,000 people who get Hogwart’s disease normally die from it, and every single patient goes on the drug, eight in 1,000 will die from Hogwart’s disease. So, for every 500 patients who get the drug, one will be spared death by Hogwart’s disease. Hence, the NNT is 500. That might sound fine, but if the drug’s “NNH”—“number needed to harm”—is, say, 20 and the unwanted side effect is severe, then 25 patients suffer serious harm for each one who is saved. Suddenly, the trade-off looks grim…

But consider the $6.3 billion 21st Century Cures Act, which recently passed Congress to widespread acclaim. Who can argue with a law created in part to bolster cancer research? Among others, the heads of the American Academy of Family Physicians and the American Public Health Association. They argue against the new law because it will take $3.5 billion away from public-health efforts in order to fund research on new medical technology and drugs, including former Vice President Joe Biden’s “cancer moonshot.” The new law takes money from programs—like vaccination and smoking-cessation efforts—that are known to prevent disease and moves it to work that might, eventually, treat disease. The bill will also allow the FDA to approve new uses for drugs based on observational studies or even “summary-level reviews” of data submitted by pharmaceutical companies. Prasad has been a particularly trenchant and public critic, tweeting that “the only people who don’t like the bill are people who study drug approval, safety, and who aren’t paid by Pharma.”

Perhaps that’s social-media hyperbole. Medical research is, by nature, an incremental quest for knowledge; initially exploring avenues that quickly become dead ends are a feature, not a bug, in the process. Hopefully the new law will in fact help speed into existence cures that are effective and long-lived. But one lesson of modern medicine should by now be clear: Ineffective cures can be long-lived, too.

https://www.theatlantic.com/health/archive/2017/02/when-evidence-says-no-but-doctors-say-yes/517368/
Courtesy of Doximity

See:  http://childnervoussystem.blogspot.com/2015/08/number-needed-to-treat.html
http://childnervoussystem.blogspot.com/2015/08/research-reproducibility.html