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The Forerunners of EBM

The term “evidence-based medicine” first appeared in the medical literature in 1992. It quickly became popular and developed into a systematic enterprise. A book by Ulrich Tröhler To Improve the Evidence of Medicine: The 18th century British origins of a critical approach argues that its roots go back to the 1700s in Scotland and England. An e-mail correspondent recommended it to me. Can’t remember who, but I would like to thank him.

Francis Bacon (1561-1626) differentiated between “ordinary experience” (chance observations) and more objective “ordered experience” (methodological observations). Both of these involved empirical knowledge.  It’s hard to get back into the mindset of his time, when most physicians rejected empiricism as the sphere of quacks and surgeons.  Tröhler helps us understand why they did:

…since antiquity, the mark of distinction of a learned man had been the certainty of his knowledge. A doctor knew — he did not need to test his kind of knowledge empirically because this would imply acknowledgement of uncertainty.

Ancient wisdom, tradition, and dogmatism reigned supreme, in medicine as in religion. Rationalism based on accepted theory was sufficient: doctors could reason their way with no need for testing.

Surgeons were perhaps the first to empirically compare the effects of different treatments. In 1536, Paré tried a raw onion poultice on a burn case, on the advice of an old country woman, and found that the onion-treated areas of skin were free of the blisters seen on the conventionally treated areas of skin. He also found that treatment with boiling oil left wounded soldiers in agony, while an ointment containing turpentine did not. He wasn’t finding out what worked so much as finding out which remedies did the most harm.

The British Navy was an ideal place to experiment: the same doctor controlled the treatment of everyone on a ship and he had a captive group of subjects for months on end. James Lind’s famous scurvy experiment took place in 1747, but he didn’t invent his method out of the blue. He was influenced by other thinkers of the time.  It took 42 years for his discovery to be implemented, but Tröhler explains why it was logical that it took so long. No one had any idea of vitamins. Scurvy was envisioned to be a “putrid” disease. The theories of the time implicated the fermentative qualities of vegetables. Unfermented malt (“the wort”) was thought to have the same properties as citrus fruits, and some patients improved on wort, likely because it supplied missing B-vitamins that were the cause of some of the patients’ symptoms. Wort was cheaper and easier to supply than lemons. They continued to try other things, like sauerkraut, mustard, vinegar, sugar, and molasses. An early effort to supply ships with bottled lemon juice failed because it was boiled, destroying the vitamin C. When you try to re-create the thinking processes of the time, 42 years of resistance doesn’t look so shocking.

The story of fever is enlightening. They thought in terms of bad air; microbes were yet to be discovered. They lumped all fevers together into one diagnostic category. Cinchona bark is an effective treatment for malaria, but when they used it on other kinds of fevers, they naturally got varied results.

We laugh at bloodletting today, but the 4-humor theory was well established and generally believed, and early trials of bloodletting were equivocal: some showed benefit, others didn’t. It might have seemed a simple matter to test it and discard it, but the situation was much more complicated in practice. Those who favored it could actually point to convincing empirical evidence.  Battles raged for decades before it was abandoned.

Early controlled trials were flawed. They mostly compared two treatments, with no placebo or untreated group. Unrecognized factors affected results. The placebo-controlled, randomized trial wasn’t invented until well into the 20th century. But at least they were trying.

The idea of applying “arithmetic” to medicine was a new one. They were used to writing up a detailed case report of one successful treatment so that other doctors might read all the details and notice some common feature with their own patients. Reporting failures was not the custom: they didn’t see any point in reporting about something that didn’t work. Reporting numbers of successes and failures for a group of patients was a new idea that many found objectionable, because they favored individual evaluation and treatment.  Tröhler does a good job of describing their thought processes and the oh-so-gradual groping towards better ways of “improving the evidence of medicine.”

One of my personal heroes is William Withering, for his scientific rigor and sensible humility. He wrote his Account of the Foxglove in 1787. He had observed an apparent response to the folk remedy foxglove for dropsy (congestive heart failure) and he set out to test it systematically. He described every case in detail, including dosage, method of preparation and all the failures. With the striking results he got, all too many modern doctors would have contacted the media to boast that they had discovered an effective remedy. Withering limited himself to saying that if others confirmed his observations, the plant might become a useful part of the standard treatment of heart disease. Others did confirm, and the plant did become a useful part of standard treatment. The active ingredient was isolated and improved upon, and Digoxin is still widely used today. Interestingly, it has fallen out of favor for its original use in congestive heart failure: although it reduces hospitalizations, it has been shown not to reduce mortality and we have better drugs that do. It is still commonly used for certain heart arrhythmias, although it is not the drug of first choice. Medicine evolves in response to better evidence.

I was surprised to see how large a role military medicine played in testing treatments and accumulating numerical evidence for everything from amputations to syphilis. (No need for informed consent, of course.) Outstanding work was done by thoughtful doctors outside the mainstream establishment of prestigious upper-class physicians. They worked on their own initiative, without monetary reward, to put the received wisdom of medical authority to the test. We owe those pioneers a great debt of gratitude.

One thing that struck me was the recurrent theme of “inflammation” as the alleged cause of fevers and practically everything else. It was a simplistic explanation that was wrong, and it reminded me of today’s simplistic claims for anti-inflammatory diets and antioxidant supplements.

Tröhler’s book is no literary masterpiece and its recital of details becomes frankly boring at times, but it’s full of tidbits of interesting information for history buffs and of lucid explanations for those who want to understand the evolution in thinking processes that led, slowly but surely, to modern scientific medicine. The book is not easy to find. It was published in 2000 by the Royal College of Physicians of Edinburgh. It is out of print and not available in used bookstores. The only way to obtain it is through interlibrary loan. My local public library located a copy at a university library in Ohio and shipped it all the way to Washington State for me to read. Didn’t take long, and didn’t cost me a penny. I found the book enlightening, and I feel more charitable towards our predecessors than I once did.

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