Some medical care may not help. Alternatives may not either.

‘Why Doctors Still Offer Treatments That May Not Help’, by Austin Frakt in the New York Times, August 27, 2019, is a well-done article that, despite its title, is fairly optimistic. He reports that while about 50% of current medical treatments no not have good evidence supporting them, only 3% have evidence showing them to be harmful, and another 6% unlikely to be helpful. This means about 41% (or only 41%, if you prefer) have good evidence that they are helpful.

Frakt cites some of the research on health interventions that do not work, or may even harm, quoting leading researchers Vinay Prasad and Adam Cifu (although he does not mention John Ionannidis, arguably the father of the field). He discusses the important “Choosing Wisely” campaign, initiated by the American Board of Internal Medicine Foundation, that asks each medical specialty society to identify at least 5 things often done in their specialty which usually should not be done. There is not, however, always consensus. For example, among its 20 recommendations (a high number that continues to grow, perhaps because of its discipline’s broad scope), the American Academy of Family Physicians (AAFP) recommends against imaging (including MRI and CT) for uncomplicated back pain, as does the American College of Physicians (Internal Medicine) (see ‘Medicine should not be primarily a business: choosing appropriate care for all, not excess testing for some, August 19, 2018).  Yet, neither the American Academy of Orthopaedic Surgeons, or the various groups of radiologists who perform these procedures, make this recommendation. Of course, both stand to benefit financially from doing these procedures.

It is concerning to think that, at least in some cases, financial benefit may influence the selection of some medical societies’ “Choosing Wisely” recommendations. Sadly, it is not a surprise, and financial benefit is, I believe, the reason for the use of many unproven treatments. Another important reason is an understandable reluctance for providers to abandon therapies that they have used for many years and believe to be successful. After all, if 50% of treatments do not have good evidence that they help or harm, many probably often do help, even if most of the evidence is anecdotal. Much more malicious, however, is the intensive marketing of new drugs and therapies to physicians by drug and device makers with a strong financial profit motive.

Frakt provides a litany of therapies-since-found-not-to-work-or-even-do-harm, including hormone replacement for post-menopausal women. The only drug he specifically names is Vioxx®, the “miracle” anti-inflammatory pulled from the market when it was found to cause heart disease (at least publicly found; the manufacturer actually knew it before it was released!). He also mentions “tight blood sugar control in critically ill patients” (and actually, probably most patients). This certainly relates to drug. The plethora of new, expensive, and marginally advantageous diabetes drugs is a testimony to their profitability. Ironically, it is often the same physicians who are unwilling to give up on treatments that are unproven or even proven to be of no benefit or of harm who are the first to begin using new (and, redundantly) more expensive drugs heavily promoted by the manufacturers.

Of course, it is not just diabetes drugs that are expensive. Compared to some of the newer drugs for rare diseases they seem like a bargain. In “The $6 million drug claim”, Times writers Katie Thomas and Reed Abelson discuss a woman who has $1 million in drugs to treat her condition in her refrigerator! While in her case they were paid for by her husband’s union, the cost can still be backbreaking: “At one point in 2018, for every hour that one of the union’s 16,000 members worked, 35 cents of his or her pay went to Alexion to cover the Pattersons’ prescriptions.” And what about those who have poor insurance, or no insurance? Or a union that goes bankrupt paying for them? Alexion, of course, does well, though.

A new law allows “gravely ill” patients the “right to try” drugs that the FDA has not approved. It sounds good; as a friend told me “I figure if I’m going out and they want to try something that might kill me I haven’t got much to lose. At best I’m cured. At worse, I go out but knowledge is gained.” Except for maybe dying sooner or more painfully, or possibly going bankrupt. It is not uncommon for doctors to suggest something new, unproven, or even a treatment that has already failed, one more time. Not everyone in this country has good insurance, and if your insurance company appropriately refuses to pay because there is no evidence of efficacy (yes, they are sometimes right!), you are on the hook for the bill. You may be dying, but your family may need the money you were saving for retirement. Thus, there may be a great deal to lose.

A certain percentage of people will take all this to mean that mainstream medicine is not to be trusted. This is definitely an overreaction, although a healthy skepticism is warranted, especially when the treatment is incredibly expensive and it is obvious that somebody (or some corporation) is making a killing on it. Some people will decide to pursue only what used to be called “alternative” medicine. These practices, often with hundreds or thousands of years of experience, are often called “complementary” and are now frequently offered along with mainstream medical therapies in “integrative” practices. But the same cautions must apply; because something is different, or traditional, does not make it necessarily either effective or safe.

For example, while people sometimes believe it is safer to choose only “natural” medicine, because a therapy grows in nature does not mean it is necessarily safe. Earlier in my career, medicine virtually abandoned the use of digitalis, made from the natural plant foxglove, to treat heart disease, after it had been used for decades. The key point is that if a substance works biologically and has “good” (i.e., desired) effects it can also have “bad” (i.e., undesired, or “side”, effects). This is true if it is straight from the plant, modified and standardized, or completely created in the laboratory.

Another real danger is what Frakt calls “wishful thinking”. Being optimistic and hoping that things will turn out well is good, and often useful when confronting serious illness. But when this transitions into the realm of “magical thinking”, being convinced that something good will happen to you because you want it to (or vice versa, that something bad will not happen because you don’t want it to), or believing a treatment will work because it is “natural”, or because your doctor recommended it in the absence of evidence, it is a real risk. “Magical thinking” is normal in three year olds, but dangerous in adults.

So what to do? Be open to new treatments, but do not reject the old, whether “traditional” or medical. Ask for evidence for treatment, such as when just changing a drug from an inexpensive standard (say, metformin for diabetes) to a new, costly one. Learn to understand probability, and ask for numbers. Do not reject anything out of hand, but do not believe that something will work just because you want it to.

Stay skeptical but not intransigent. Look for the evidence. And look also, when something is expensive, for the profit motive. Cui bono? It may not always be you.

"Abandoning ship": is debunking ineffective screening and therapy removing hope or just removing risk?

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Sometimes I think I sound like a real medical nihilist, since many of my blogs have been about purported treatments that are ineffective, dangerous, done too often, and cost a lot of money (Cardiac stents and profit-driven corruption: do anti-fraud rules address the problem?, December 24, 2010; Greed, corruption and medical procedures: ignoring or suppressing the evidence?, August 12, 2011; Men’s Health? Women’s Health? Valid screening opportunities or “Hallmark Holidays”?, March 15, 2011).  It is a somewhat distressing feeling. I am a doctor; I want to help people, to relieve their suffering, to help facilitate the cure of their diseases. More than that, I am a family doctor, and have a strong preference for prevention, for early detection of disease when it is still treatable rather than waiting for it to be too far gone for treatment to be effective. In addition, I have regularly criticized our health non-system for leaving out too many people, creating financial disincentives for them to seek care early. This leads to their waiting until their diseases become so uncontrolled that they present to the emergency room, then require admission and costly care, making it worse for them (most important) and more expensive for everyone. So I think prevention and early intervention is a really good thing, and it would be great to have tests that could identify disease early in its course so that we can change its trajectory.

But because I want these things to be true doesn’t make them true, as I discuss in the recent post Avastin®, Plan B®, and Magical Thinking, December 31, 2011. Because we can screen you for something doesn’t mean that we should; because a test can be done doesn’t mean that it is a good test. "A good test", in my opinion, is one that has sufficient sensitivity (rate of being positive when a condition is present) or specificity (rate of being negative when a condition is absent) to tell us whether a you have a disease, or if it matters. Because it can be done also doesn’t mean that it is cost-effective. Because a treatment exists doesn’t mean it is a good treatment, a safe treatment, an effective treatment. And, as with most things being sold, the greater the publicity and advertising around it, the more it means someone will be making money on it, which does not exclude its being of benefit, but is certainly not the same thing.

Sometimes, when evidence is discovered that a test or treatment is not of benefit, eventually we stop doing it. "Eventually", however, may be a lot longer than you might think. In a recent “Viewpoint” in JAMA, Prasad, Cifu, and Ionannidis address “Reversals of established medical practice: evidence to abandon ship”[1]. They note that while “Ideally, good medical practices are replaced by better ones, based on robust comparative trials in which new interventions outperform older ones and establish new standards of care. Often, however, established standards must be abandoned not because a better replacement has been identified but simply because what was thought to be beneficial was not.” They go on to discuss a number of treatments that have been “standard of care” but were shown by good, randomized controlled trials, to be ineffective or even dangerous (not to say expensive). These include stenting of coronary arteries for stable coronary artery disease (CAD), postmenopausal hormone therapy to prevent CAD, vertebroplasty for osteoporotic fractures, bevucizamab for breast cancer.

Scarily, but unsurprisingly, “true believers” continued to defend these interventions even after the evidence was clear (their livelihoods depend upon it), and in many cases these treatments continue to be offered and performed. “There are thousands of clinical trials, but most deal with trivialities or efforts to buttress the sales of specific products,” and it is only “Rarely [that]…some investigators find the courage to test established ‘truths’ with large, rigorous randomized trials”. Prasad and colleagues have done many of these latter trials; indeed John Ioannidis is the “guru” of debunking treatments with poor evidence (see David H. Freedman’s article in the November 2011 Atlantic “Lies, damned lies, and medical science.”) The authors have some suggestions, including limiting the role of manufacturers (of drugs, devices, tests) from conducting the trials on them, although they should pay for them: “Large trials of new innovations should be designed and conducted by investigators without conflicts of interest, under the auspices of nonconflicted scientific bodies. Instead of designing, controlling, and conducting the trials, manufacturers may offer the respective budget to a centralized public pool of funding, keeping the trial design and conduct independent.”

Prevention and screening are also subject to the lure of magical-thinking-compounded-by-the-greed-of-the sellers. Screening for prostate cancer with the use of prostate-specific antigen (PSA) testing is a good recent example about which I have written (while the lack of effectiveness of treatments for prostate cancer is would be included in the group of ineffective therapies that Prasad and colleagues have written about). Pap smears are pretty good screening tests for cervical cancer, but most other cancer screening tests (even mammograms and colon cancer screening, probably the next best) are not nearly as good. Every time there is a recommendation to decrease the frequency of screening (Pap smears, mammography) or not do them at all (PSAs or pelvic exams) there is an outcry from people who think that something has been taken from them. In a scientific sense, what has been taken is unnecessary testing that doesn’t lower their risk of bad outcomes, costs money, and can have significant morbidity when positive screens need additional, more invasive tests, to follow up. But, in a more metaphysical sense, what has been taken is hope, the idea that there is something that they can do that will prevent something bad from happening to them. Something that, while perhaps a little risky (if you understand or believe it), is relatively easy. And also, frankly, something someone else, rather than you, can do. Not like, say, dieting or giving up smoking or exercising. And this false concept is encouraged by half-truths promulgated by passionate advocates of interventions with limited proven benefit, whether traditional allopathic or “alternative”.

Even public health advocates sometimes get so passionate about the health benefits of what they are advocating that they may miss other issues. For example, consider a recent discussion on a progressive public health listserve about “portion control” (limiting the amount eaten at one sitting). This is an important and effective method of addressing obesity, which is in fact a major health problem in this country, but the discussion raised many other issues. These included concerns about “blaming the victim” -- expecting self-control (difficult enough) from people who had historically not had that control in the face of major initiatives by fast-food purveyors to push large portions. Another was the economics involved in asking poor people to pay “more for less” while corporations continue to make huge profits from them. It can, and often is, as difficult for public health advocates to recognize problems arising from their positions and passions as it is for providers or manufacturers to back off from theirs.

The difference, of course, is that the former are really invested in the health of the public, while the latter are invested mostly in, well, their investments.

[1] Prasad V, Cifu A, Ioannidis JPA, Reversals of established medical practices: evidence to abandon ship”, JAMA 4Jan2012;307(1):37-8.

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