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Complex Systems in Medicine pp 63–74Cite as

Managing Patients: Evidence-Based Medicine Meets Human Complexity

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Abstract

“Evidence-Based Medicine” was heralded as a new approach to the practice of medicine, claiming to represent a paradigm shift by de-emphasizing intuition, unsystematic clinical experience, and pathophysiologic rationale as sufficient grounds for clinical decision making and stressing the examination of evidence from clinical research. Its major assumptions included what counted as evidence and how it was valued, the application of population data to individual patients, and the denigration of pathophysiological reasoning and clinical expertise. However, individual patients are complex systems, even if they have only one disease. EBM oversimplifies that complexity, minimizing the importance of heterogeneity of treatment effects which reflects patient diversity in risk of disease, responsiveness to treatment, vulnerability to adverse effects, and utility for different outcomes. These differences can result from intra-individual and extra-individual factors. Intra-individual factors can occur at any level of the hierarchy of biological organization, each of which consists of an extensive network of interacting elements. This issue is presented as one of the nature of the intervention by context interaction: Response = f(Intervention x CONTEXT). Every individual has a unique context even if one limits this to the level of the organism and its components. That context consists of a multitude of elements and their interactions. The response to implementing an intervention is not readily predictable in an individual. This has major implications for practice.

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Notes

  1. 1.

    It is possible to give multiple doses. The basal bolus method of insulin replacement for a patient with diabetes, i.e., the combination of an injection of a long-acting insulin with meal time injections of short-acting inulin, is designed to mimic the dynamics of normal insulin secretion as much as possible. However, only with the development of implantable insulin pumps and long-lived glucose sensors to create a closed loop system will we get close to the normal dynamics.

  2. 2.

    The names are derived from the number of iodide molecules attached to the backbone thyronine.

  3. 3.

    Paradigm shift – this term has been thrown around quite a bit ever since it was introduced by Thomas Kuhn in The Structure of Scientific Revolutions, 1970 U. Chicago Press. A search on Google Scholar for “paradigm shift” yielded 1,380,000 hits and 9,300,000 on Google. (12-27-18)

  4. 4.

    The Index Medicus was available in print form from 1879–2004 when it was felt that on-line databases, e.g., PubMed supplanted its usefulness.

  5. 5.

    Assessment in a broader and more explicit sense came about generally with the implementation of quality assurance programs, though the idea was hardly new Ernest Amory Codman kept meticulous records of his surgeries and proposed making the results public including his errors [4]. This was hardly met with enthusiastic approbation by his colleagues at Massachusetts General Hospital and he was forced to leave and establish his own hospital whose results he did publish. Even earlier he and another medical student began keeping records of the cases for whom they administered anesthesia [5, 6].

  6. 6.

    I would not be able to do this in the office while seeing the patient, but it could be done outside of clinic. Attempts to get physicians to do this real time have generally failed and there is more emphasis in the EBM movement on predigested evidence in the form of guidelines and systematic reviews.

  7. 7.

    There are relatively few randomized controlled trials addressing endocrine therapy (diabetes excepted).

  8. 8.

    Here I am more concerned about the patient’s satisfaction with how she feels than whatever satisfaction scores I get on surveys though I am sure that the two are connected. However, when what will make the patient happier is actually bad practice, the two are in conflict. The use of antibiotics for upper respiratory viral infections is a case in point. The patient may leave satisfied, though the drug itself does nothing, but may have an adverse drug event.

  9. 9.

    The frequentist approach does not depend on prior probability while the Bayesian approach does and the controversy continues unabated. https://365datascience.com/bayesian-vs-frequentist-approach/

  10. 10.

    It is quite ironic that these claims, especially that of improving care, have been made in the absence of an RCT.

  11. 11.

    Since an N-of-1 trial assesses only one patient, it is hard to draw inferences about how other patients would respond. Methods for combining the results of N-of-1 trials are somewhat limited in theory and hardly performed in practice.

  12. 12.

    I have felt compelled to include these references on philosophy of EBM because of my time in the Dept. of History and Philosophy of Science at University of Cambridge where Jacob Stegenga was a faculty member and one of the leaders of the medicine and philosophy reading group.

  13. 13.

    One of my pet peeves occurs when someone claims that a therapy is not evidence-based when what they mean is that it is not based on RCT evidence, whether it exists or not. It should be sufficient to point out that the introduction of insulin therapy for type 1 diabetes has never been subjected to RCTs. There have been studies to determine what the most appropriate level of glycemic control should be, but the idea of avoiding the use of insulin because it has not been subjected to a double blind placebo controlled trial is ludicrous. Similarly, thyroid replacement therapy for hypothyroidism was accomplished without RCTs, though there have been trials to assess different approaches to thyroid hormone replacement.

  14. 14.

    The use of Lisinopril also brings to mind the fellow who had the lab across the hall from me in the basement when I first started working at the Cleveland VA Medical Center. Leonard Skeggs was a quite unassuming and unprepossessing man but little did I know when I encountered him in the hall or borrowed something from his lab, that he was a giant. I had no idea that he had been in the navy during WWII serving on a minesweeper which was torpedoed and sunk off the coast of the Philippines. He was a biochemist who had worked at the VA for many years. He discovered angiotensin-converting enzyme and laid the groundwork for drugs such as Lisinopril, but that was only one side of his work. While waiting to report for Officers Candidate School in 1943, he: “worked at the SMA corporation on the purification of penicillin from culture medium, which consisted of corn steep liquor; a thick dark brown gooey liquid. All I remember now is that we extracted the penicillin into amyl acetate and back into water. I remember very clearly Dr. Paul Gyory storming into our laboratory one Saturday morning demanding penicillin. I gave him the dark brown solution I had just made. He took it to the hospital, gave it to his patient, and saved his life. This was a thrilling moment for me that I will never forget. The discovery of penicillin was perhaps the greatest discovery of the twentieth century” (p1425). At this time he had a master’s degree. After the war, he continued his studies in biochemistry. One day, the acting department chair came into the laboratory with a monograph written by Willem Kolff, a Dutch physician who had invented an artificial kidney. It was a very cumbersome and relatively inefficient device. Skeggs (not yet a doctor, for he was working on his PhD) thought they could do better and did. He wrote: “I remember one comatose patient that we treated who after treatment demanded steak for breakfast. Our kidney was the first flat-plate kidney and was an important step in the development of today’s artificial kidneys” (p1426). He completed his PhD and took a job as head of the

    Clinical Chemistry Laboratory at the Cleveland Veterans Administration Hospital. His boss, the chief of the clinical laboratories had worked with Harry Goldblatt, who worked at another Cleveland hospital, Mt. Sinai and had shown that hypertension could be produced in animals by reduction of the blood flow to the kidney (now known as the Goldblatt kidney model). Goldblatt also showed that the increase in blood pressure was attributable to the liberation of an unknown pressor substance into the bloodstream. It turned out that this substance was renin which is actually an enzyme that acts on a protein made in the liver – angiotensinogen – cleaving off a sequence that was angiotensin I. This substance was then converted to angiotensin II which was the highly active pressor agent. Skeggs discovered the enzyme that facilitated the conversion – angiotensin converting enzyme or ACE. ACE-inhibitors like Lisinopril play a crucial role today in the management of hypertension and heart failure.

    His tinkering knew few bounds. It is best to quote him: “While I was deep into research on hypertension, I was also being paid to run the Chemistry Laboratory for a 1000-bed hospital. I had three, sometimes four, technicians who also collected all the blood samples, washed and sterilized their glass syringes, sharpened and sterilized their own needles, and washed their own glassware… Each day, my technicians had hundreds of manual operations to perform while talking to each other about last night’s date, the baseball game, or just polishing their white shoes. I had one very good male technician, Al Nagy. He was the only one I ever knew who could smoke a pipe and pipette at the same time.

    I was worried about the quality of the results. I put unknowns into every batch of analyses and found frequent, very bad errors. There were just too many manual operations. I dreamed of a machine that would do analyses without error. One day, it suddenly occurred to me that analyses could be done in a continuously flowing stream rather than batchwise or discreetly”(p1428). The idea of the autoanalyzer was born which utterly transformed the practice of clinical chemistry. I strongly suggest you read his paper in full: Skeggs [34]. I so much wish that I had gotten to know him better.

  15. 15.

    The factors named by no means exhausts the list. Individuals vary in their preferences regarding treatment or types of treatments and how they value different outcomes. The way individuals respond to questionnaires about patient-reported outcomes also varies.

  16. 16.

    This becomes an even more important issue for social interventions which involve more levels and where large sample sizes are at best impractical and at worst impossible to obtain. See chapter on interventions to improve quality.

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  1. School of Medicine and Weatherhead School of Management, Case Western Reserve University and Cleveland Veterans Affairs Medical Center, Cleveland, OH, USA

    David C. Aron

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Aron, D.C. (2020). Managing Patients: Evidence-Based Medicine Meets Human Complexity. In: Complex Systems in Medicine. Springer, Cham. https://doi.org/10.1007/978-3-030-24593-1_6

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