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.

Avastin®, Plan B®, and Magical Thinking

“Magical thinking” is believing something is true because you want it to be true even when there is strong evidence that it is not. It is normal in young children. They believe in Santa Claus and the Easter Bunny and conjurer’s tricks. This is in part because adults encourage them to, and because they do not know the evidence and they haven’t enough brain maturity to make the connections. Beyond a certain age, however, it is not normal. Yet we do it all the time.

It is common enough in politics, for sure. A wise expert (OK, me) once said “Data is only useful if it confirms your preconceived notions”. Otherwise, hearing the data that should demonstrate that you are wrong only confirms your pre-existing beliefs because it reminds you of why you believe it. The evidence is the evidence, and sometimes it is inconclusive and subject to different interpretations depending upon one’s perspective. That’s what makes horse races. Sometimes it is conclusive, but leads to a different conclusion than the one that you want to hear.

Religion is different; it is, by definition, based on faith. It becomes confusing, for me, when this is complicated by searching for evidence (e.g., the Catholic Church searching for evidence of a miracle in order to sanctify someone), but at bottom it is about faith. Some people have lost their faith in the religion in which they were brought up because of seeing contradictory evidence in the world, others have reconciled that evidence with their beliefs, others manage to separate the evidence from their faith, and still others reject all the evidence of their senses if it contradicts their faith. We have classic examples of this last, with lecturers in the early European medical schools reading from Aristotle on anatomy, ignoring the visual evidence provided by the cadavers being dissected in front of them that demonstrated that what Aristotle described was wrong. Luckily for anatomy and medicine, the schools were able to move on from this, in part because Aristotle, while revered, was not a Christian expert. It was rougher for Galileo when he demonstrated that the earth rotates around the sun.

I understand people’s interest in believing to be true things that the evidence demonstrates is not. It is comforting, it offers hope, and it can offer consistency. I wish, sometimes, I had more of it. My son died 9 years ago from completing suicide. If I believed that there was an afterlife, and that he was somewhere happily being cared for by my mother, who died over 30 years ago, it would make me feel better. After all, she was a wonderful, nurturing person, a kindergarten teacher who loved children, and she died just after he turned 2, so never got to see him grow up. It would be great to believe that they were getting to know and enjoy each other now. But I don’t.

Nonetheless, I am sure there are things that I believe that are contrary to the evidence. Certainly, things I believe that have conflicting evidence. Like that people are good, that the world can be a better place, that the ‘better angels’ of our nature may overcome selfishness and greed and hypocrisy and meanness. Sometimes that belief is sorely tried. It has been a particularly hard couple of years as the perpetrators of the greatest worldwide financial crisis have gotten off and maintained and increased their wealth while hundreds of millions of their victims have had their lives ruined, with no end in sight. And with whole cohorts of politicians and pundits advocating that these perpetrators be spared any penalty while slashing any programs that benefit their victims.

For most of us, and in most societies, there are limits to what we tolerate because of people’s beliefs. We do not, as a rule, accept that a false belief, a delusion, about another is an excuse for murder. Of course, if that false belief is on the part of the government that sends young people to war and to kill, it is accepted. And for many zealots, of many beliefs and causes, whether Islamic terrorists or anti-abortion murderers, there is a portion of the population who will accept it.

One group that has good reason to want to believe in things for which there is no evidence is those who are threatened with death from a disease for which there is no effective, “approved”, treatment. Cancer, for instance, or AIDS. In the 1980s and 1990s, AIDS advocacy groups pushed for quick FDA approval for drugs to fight a disease that was killing lots of people. To some degree it happened, and luckily those drugs were effective, and better drugs were developed, and today AIDS is most often a chronic disease. When a study showed that bevacizumab (Avastatin®), an anti-cancer drug created through recombinant DNA that had positive effect for some other cancers such as colorectal cancer, was also effective in prolonging the lives of women with metastatic breast cancer for a few months (not curing them), the large breast-cancer advocacy community pushed the FDA for early approval. It was approved. But then more studies appeared that showed it was not effective. Several of them. And the FDA, appropriately based upon the evidence, withdrew their approval. Blue Cross/Blue Shield of California then decided it wouldn’t pay for it. Yes, much of the motivation was financial – it costs $90,000 per year to treat a patient (except less, really, because few last a year), but it was based on the evidence. Would you pay $90,000 for a drug that didn’t work? How about spending that on treating someone else with a drug that doesn’t work? But having someone else pay for it for you (your insurance company and those other people who are paying premiums)is less painful. There was a big uproar. BC/BS (and Medicare) are now again paying $90,000 a year for treatment of breast cancer with a drug that doesn’t work.

On the other hand, kowtowing to true believers can have the opposite effect. It can lead to restricting access to a drug that does work. This has occurred recently with Plan B One-Step®, “the morning-after pill” which effectively provides emergency contraception if taken within 72 hours (maybe more) of unprotected intercourse. Approved for women 17 and over without a prescription, this form of the hormone levonorgestrel is kept “behind the counter” so those under 17 cannot get it. It doesn’t make sense, since girls under 17 can and do have unprotected sex and get pregnant. It is also safe. So, recently the FDA, examining all the evidence, recommended that it be made available without a prescription and sold “over the counter”. Then Secretary of HHS Kathleen Sebelius overruled, in an almost unprecedented action, the FDA’s recommendation. There was no science or evidence behind the Secretary’s action. Her stated reason, that younger women cannot understand the instructions, would, if one wanted to believe it, be an unreasonable standard. Can they understand the instructions to prevent adverse effects from ibuprofen or acetaminophen? Is the risk of pregnancy in these girls less than the risk from taking Plan B incorrectly? Nonsense. It is a political judgment, pandering to the belief of those who magically believe that because they don’t want young girls to have sex they won’t as long as contraception is not available to them to “encourage” it.

People read and support things that agree with what they think. I do not delude myself into thinking that what I write in this blog “converts” people; I recognize that people who read and like it probably already agree with me. But I do try to present evidence. And sometimes readers challenge me on my interpretation of the evidence (see, for example, the comments on Fluoridation: Dental health for all, October 26, 2011). One of the hardest things for physicians to do is to “un-learn”, to change the beliefs that they have had for years or decades when new information shows that what they believed is wrong. It is hard for them, and harder for the lay public, to understand that doing something was the right thing in the past because of the best evidence at the time, but is the wrong thing now. And what we think is the right thing now, based on the best evidence available, not be true in the future. That is how science evolves.

But magical thinking should have nothing to do with it.

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Oh, yes. And in support of a tradition which Dilbert correctly points out is only a random point in time (and despite his use of "oxytocin" when he may have meant "oxycodone"):

HAPPY NEW YEAR!