The Half-Life of the Truth

My fellow was laughing at me.

By itself, I don’t think this was an unusual occurrence. I am quite certain that my fellows laugh at me all the time. That said, when such laughter is called for, I am accustomed to a certain protocol being observed. In general, I expect the laughter to be contained, discreet. To be blunt, I expect my trainees to laugh at me behind my back. Having a trainee laugh at my front was a novel experience.

I was working with said fellow on the inpatient consult service. We had been asked to evaluate an older patient with a long-standing diagnosis of scleroderma who had developed digital gangrene. If this were a question on a multiple choice test, the answer would be epoprostenol.

In patients with digital ischemia, prostacyclins may improve circulation at both the microvascular and macrovascular levels, by inducing vasodilation, increasing intra­cellular cyclic adenosine monophosphate (cAMP) and inhibiting smooth muscle proliferation. Clinically, these benefits can be profound; I remember life before epoprostenol, and I can tell you that it was worse. It seems to be particularly good for helping patients with the pain associated with digital ischemia, which is even more heartbreaking than the loss of tissue.

This particular patient was admitted to our main hospital, where, for reasons that defy both good medicine and good logic, epoprostenol is unavailable to patients with scleroderma. Because the drug is formally indicated only for the treatment of pulmonary hypertension, in my hospital, its use has been restricted only to patients with that diagnosis. Ironically, some patients with ischemic digits are too healthy to merit the drugs they need.

In those cases, we tweak. We use calcium channel blockers and nitrates, increase the ambient temperature and work on pain control, in hopes that some combination of all of these nudges will push the patient in the right direction.

This particular patient also had a long-standing diagnosis of anemia from gastric antral vascular ectasia (GAVE), which is sometimes referred to as watermelon stomach. On endoscopy, it is described as “rough parallel folds and dilated blood vessels departing from the pylorus and converging in the gastric antrum”; in a moment of whimsy, you could see why this might make a hungry gastroenterologist think of a watermelon. Although GAVE can be found in a number of medical conditions, including cirrhosis, renal failure, chronic pulmonary disease and diabetes, a rheuma­tologist would most often associate it with a diagnosis of scleroderma. GAVE is more than a piece of rheumatic trivia, because the ectatic blood vessels tend to bleed, leading to a chronic iron-deficiency anemia.

The pipe organ in Wanamaker’s department store, Philadelphia.
Dmitry Br / shutterstock.com

When I was in training, blood trans­fusions for anemia were common. We referred to it as “tanking the patient up,” as if it were a service, such as checking the oil or cleaning the windows. Any patient who was admitted with cardiac ischemia would be discharged with a hemoglobin of 10 g/dL, automatically. It was just good medicine.

Until it wasn’t. The Transfusion Requirements in Clinical Care (TRICC) investigators decided to challenge this practice by conducting a study in which critically ill patients were randomized to different transfusion goals. Half the patients were transfused to a goal of 10 g/dL, and half the patients were transfused to a goal of 7 g/dL.¹

What followed was a game-changer. Contrary to the popular wisdom, critically ill patients who were transfused to the higher goal hemoglobin did not have a reduction in mortality. In fact, patients who were younger or less ill fared better if we just left them alone. Subsequent studies tried and failed to find subgroups who routinely benefited from an aggressive trans­fusion strategy until it became clear: The common wisdom was wrong.

Hence, we come to the cause of the laughter.

When talking to patients, I always describe ischemic digits as akin to having a heart attack of the hand—part of their body is screaming for oxygen. Given this, I was wondering if this patient, with her history of anemia, might benefit from a blood transfusion, to increase her perfusion pressure.

I knew that no such studies existed in scleroderma patients, but I knew someone must have studied this in patients with myocardial ischemia. It has been years since I have practiced internal medicine regularly, so I asked my fellow: Had the findings of the TRICC study been replicated in patients with acute coronary syndromes?

And she laughed at me.

She later explained that she had never heard of the TRICC study referred to by name. The original study was published in the New England Journal of Medicine when she was still in grade school. It was as if she had knocked a glass off a table, and I had referred her to a passage in Principia. No one referred to the study anymore. It was just fact.

If she only knew.

The Truth & Other Myths

I have been alive long enough that I have lived through many versions of the truth. I feel most betrayed by the estrogen story: When I was in medical school, estrogens were thought to be the fountain of youth, the reason why women had fewer heart attacks and strokes than men. Post-menopausal women could continue to experience these benefits if they started to take estrogen supplements, which became an integral part of primary cardiac prophylaxis, as integral as taking an aspirin.

When I was in residency, the story changed. The Women’s Health Initiative demonstrated that estrogens actually increased the rates of heart attacks and strokes among post-menopausal women.² Because this occurred during my training, I vividly remember the denial that took place around the time the Women’s Health Initiative published its findings. The cohort was skewed. The intervention was wrong.

It was only years later, after much wailing and gnashing of teeth, that we finally became comfortable with the truth: The common wisdom was wrong. My personal takeaway? Thank God my mother never listens to me. When I was in medical school, egged on by my august professors, I harangued her about taking supplemental estrogen. In retrospect, if she had actually started taking Premarin on my say-so, I’m not sure I would have ever forgiven myself.

She also never started taking a baby aspirin, even though everyone knew that it would prevent myocardial infarctions. At least we knew it until a few years ago, when we learned that women with no history of heart disease, like my mother, actually didn’t benefit from taking an aspirin, after all.³

As an aside, I have little patience for the practitioners of revisionist history. I have sat through many lectures that have described why we should have known that estrogens or aspirin or whatever was just snake oil, and if we had looked at the older data in just the right light, the truth would have shown through clearly.

Hogwash. I am old enough that I have borne witness as, again and again, heresy has become scripture and scripture has been dismissed as myth. I can testify that many of the experts who speak with such confidence were saying very different things a decade or two ago, with an equal amount of confidence.

Scientometrics & the Study of Being Wrong

“Half of what you will learn is wrong. You just don’t know which half.”

I assume someone recited this to me during medical school. If I’m being honest, however, I’m really not sure. For me, it is probably part of the revisionist narrative we all create for ourselves, replete with half-truths and stories of dubious provenance.

It turns out this phrase may be just such an example of revisionist history. Not knowing which half of your efforts were wasted, I thought, was specific to medical training. Apparently, this observation originally belonged to the field of advertising.

John Wanamaker was an American entrepreneur who founded the first department store in Philadelphia—if his name sounds vaguely familiar to you, it may be because of the fingerprints he left on that great city, in the form of the Wanamaker building and the Wanamaker Grand Court Organ. Among other contributions, he pioneered the use of advertising in marketing. Before Wanamaker, department stores merely offered goods and services; afterward, department stores used advertising to tell you what you wanted to buy.

Wanamaker knew better than most that you couldn’t predict the effect of advertising dollars. In fact, he said, “Half of the money I spend on advertising is wasted; the trouble is I don’t know which half.”⁴

Sound familiar?

This has given birth to an entire field of study. Scientometrics, or the measurement of science, is based on the philosophy that the truth has a half-life. As time marches on, certain truths become obsolete. Although this seems counterintuitive, medicine pioneered this concept: The entire idea of continuing medical education acknowledges that facts are neither static nor absolute.

In 1962, the economist Fritz Machlup coined the phrase the half-life of knowledge to denote the time it takes for half of knowledge in a given field to be superseded by a new set of truths.⁵ In the 1920s, the half-life of an engineering degree was 35 years. In the 1960s, the half-life of the same degree was about 10 years. Now, it’s about five years.⁶

The entire idea of continuing medical education acknowledges that facts are neither static nor absolute.

Surgery is not immune to this phenomenon. In 1997, John C. Hall and Cameron Platell selected abstracts from the journal Surgical Gynecology and Obstetrics, from 1935 to 1994. Based on their review, they estimated that the rate of the loss of truth is 0.75% per year; based on this, they estimated the half-life for the truth of statements in the surgical literature is 45 years.⁷

It seems that medicine is doomed to the same fate. In 2002, Poynard et al. examined articles on cirrhosis or hepatitis published between 1945 and 1999. As of 2000, 60% of the conclusions were still presumed to be true, 19% were obsolete, and 21% were demonstrably wrong. Interestingly, this analysis led to the same estimate for the half-life of the truth: 45 years.⁸

Part of the problem is the rate at which knowledge is expanding. R. Buckminster Fuller estimated that until 1900, human knowledge doubled approximately once every century. By 1925, he asserted that knowledge doubled every 25 years, and by 1982, it doubled once every year. How this acceleration may affect the half-life of medical truth is anyone’s guess.⁹

Also, we are bad at predicting which truths will survive the test of time. The Poynard et al. study indicated that high-quality studies were no more likely to yield long-lived truths than low-quality studies. One interesting finding was that the 50-year survival of negative studies was significantly higher than that of positive studies. In other words, we are better at knowing when we are wrong than when we are right.

It is a sign of progress that this problem is now affecting rheumatology, as well. The world of vasculitis is going through conniptions trying to come to terms with the results of the PEXIVAS study, which demonstrated that plasma exchange did not benefit patients with severe forms of ANCA-associated vasculitis.¹⁰ Some of us are going through the predictable stages of denial: Perhaps the patients enrolled in the study weren’t sick enough. Perhaps we didn’t get them on plasma exchange fast enough. Perhaps it only makes a difference if we didn’t pulse patients with steroids. Perhaps it only works for patients who were dialysis dependent or oxygen dependent or had a strong craving for Italian food.

It’s hard to know whether there may be a kernel of truth to any of these misgivings. For many of us, plasma exchange for patients with severe vasculitis has been an article of faith, and it is difficult for faith to give way to mere fact. Given the half-life of the truth, it is possible that 45 years from now, our understanding of plasma exchange will be replaced by another truth. It seems equally possible, however, that my fellow will be citing PEXIVAS to her trainee only to be greeted by peals of laughter, echoing down the hospital halls. 

Philip Seo, MD, MHS, is an associate professor of medicine at the Johns Hopkins University School of Medicine, Baltimore. He is director of both the Johns Hopkins Vasculitis Center and the Johns Hopkins Rheumatology Fellowship Program.

References

1. Hébert PC, Wells G, Blajchman MA, et al. A multicenter, randomized, controlled clinical trial of transfusion requirements in critical care. New Engl J Med. 1999 Feb 11;340(6):409–417.
2. Manson JE, Chlebowski RT, Stefanick ML, et al. Menopausal hormone therapy and health outcomes during the intervention and extended poststopping phases of the Women’s Health Initiative randomized trials. JAMA. 2013 Oct 2;310(13):1353–1368.
3. Ferrario MM, Veronesi G. Aspirin use in women for primary prevention. Heart. 2015 Mar;101(5):333–336.
4. Bradt G. Wanamaker was wrong—the vast majority of advertising is wasted. Forbes. 2016 Sep 14.
5. Machlup F. (1962) The Production and Distribution of Knowledge in the United States. Princeton, NJ: Princeton University Press.
6. Kruchten P. The biological half-life of software engineering ideas. IEEE Software. 2008 Sep;25:10–11.
7. Hall JC, Platell C. Half-life of truth in surgical literature. Lancet. 1997 Dec 13;350(9093):1752.
8. Poynard T, Munteanu M, Ratziu V, et al. Truth survival in clinical research: An evidence-based requiem? Ann Intern Med. 2002 Jun 18;136(12):888–895.
9. Fuller RB, Kuromiya K. (1981) Critical Path. Macmillian: p. 347.
10. Walsh M, Merkel PA, Peh, C-A, et al. Plasma exchange and glucocorticoids in severe ANCA-associated vasculitis. N Engl J Med. 2020 Feb;382(7):622–631.