Evidence-Based Medicine and the Individualization of Care

When I was in training, I was often advised to individualize care. This admonition was troubling, because it was inevitably the last comment and there were almost never any details on exactly how to individualize care! What factors should be considered, how are they prioritized, what nuances are needed?

This is commonly referred to as The Art of medicine, an area very poorly taught, almost always presented as a proverbial black box, an impenetrable mystery. Practitioners of The Art are most readily recognized when a physician states “in my experience” for his or her rationale on a particular decision.

During the last 20-25 years, practice of The Art has been overcome by evidence-based medicine (EBM). Artfulness and rigid adherence to EBM are 2 opposing extremes, and proponents of EBM can be recognized when they insist that they “trust God, but everyone else has to bring data”.

Inasmuch as the phrase “in my experience” is abused, EBM too is abused. The abuse of EBM occurs when the application of an inadequate evidence base is forced upon practitioners, and - more sinister - when constraints are put on practitioners to do nothing that isn’t supported by blinded, randomized placebo-controlled trials (RCTs).

Such knee-jerk insistence on RCT evidence reduces the biopsychosocial model of disease into just the molecular biology component. This is because factors of health ecology cannot readily be blinded, randomized or statistically adjusted - smokers know they smoke, exercisers know they are exercising, the control groups know they are not and the investigators cannot supervise the intervention and still be blinded. Depreciating the value of health ecology research a major mistake by EBM advocates that may help clarify medical aspects, but it ignores 85% of the determinants of health outcomes.

Administrators and insurance companies also use EBM to ration access to care. Unfortunately, when you’re a doctor and Mrs Jones comes in search of your help, when the EBM isn’t sufficient to guide a clear course, you can’t just say,

“Well, I’m sorry Mrs Jones but there isn’t much data about your problem, so we’ll just have to wait and see if something comes up. Can you come back in a few months”?

Mrs Jones needs you to figure something out. While it does seem unreasonable to expose an insurance company to every cockamamie idea doctors can think of, but it just plain mean to deny her access to relief when a doctor finds something that helps.

The underlying cause of this dilemma is that vast majority of medicine does not fall within the black-and-white boundaries of EBM, but somewhere in the grey zone - most patients in most circumstances lie between the known and the unknown. There are many reasons why:

1) Most patients do not meet the inclusion and exclusion criteria of most RCT studies, casting doubt on the pertinence,
2) This pertinence barrier is often even more of a limitation when considering a meta-analysis,
3) Guidelines can be still more constrained when health ecology research is not considered,
4) Few pharmaceutical RCTs fully adjusting for the health ecology (particularly exercise), and
5) It is usually impossible to do a blinded, randomized placebo/sham-controlled trial on factors of health ecology.

Consider the three examples, below.

Two health ecology factors - smoking and exercise - have been proven by epidemiologists to be the two most dominant modifiable risk factors for cardiovascular disease. When population prevalence is considered, physical inactivity confers the highest population-attributable risk of all modifiable cardiovascular risk factors. Observational epidemiologic research thus constitutes a massive and overwhelming breadth of the strongest available evidence for tobacco and exercise, though it is not from blinded RCTs. But just a year ago, working under IOM rules that devalue the data on exercise, the American College of Cardiology / American Heart Association published a cardiovascular risk assessment formula that does not include term for exercise or physical activity. A more egregious error cannot be imagined - the most important risk factor was not included in their formula.

EBM is also used to constrain covered benefits, often deep within health insurance policies. The cholesterol-lowering drug, ezetimibe, is well-tolerated, but in the last few years use of ezetimibe has fallen to just a few percent of what it had been. It was taken off formulary by most health plans because RCTs had failed to show that it reduces cardiovascular events. That was it hadn't been proven until this week’s American Heart Association meeting, where emerging data shows that ezetimibe reduces the risk of cardiovascular events, vindicating physicians who have been prescribing ezetimibe in their practice of The Art. Imagine, for a moment, that you are someone who’s spouse died because he or she had adverse effects from cholesterol lowering medications, but didn’t try ezetimibe because it wasn’t covered on the health plan formulary.

All of this is not to contend that practice of The Art is perfect and without risk. All too often we learn of adverse events of a drug, such as COX-II anti-inflammatory medications that have an uncommon but real adverse effect of causing heart attacks and death in a small percentage of patients. Because of this, COX-II inhibitors were withdrawn from the market about 8-9 years ago. One particular patient of mine suffered terribly from juvenile rheumatoid arthritis, and she was crestfallen when the COX-II medication valedcoxib was taken off the market. This was the only anti-inflammatory she ever found that provided her relief and it was being taken away. I gave her all the samples I could find.

Biology is very messy, with millions of variables, most of which humans aren’t even close to comprehending, which puts the vast majority health care squarely in the grey zone. So being, the insightful and informed practice of medicine is now and will long continue to be islands of scientific firmament awash in oceans of uncertainty. EBM guidelines provide points of reference, like lighthouses, but these beacons rarely plot an exact course through the stormy seas of illness. Our system has a long way to go to before we find the right balance between EBM and practice of The Art.

References:

Blair SN. Physical inactivity: the biggest public health problem of the 21st century. Br J Sports Med 2009; 43:1-2.

Goff DC Jr, Lloyd-Jones DM, Bennett G, Coady S, D’Agostino RB Sr, Gibbons R, Greenland P, Lackland DT, Levy D, O’Donnell CJ, Robinson J, Schwartz JS, Smith SC Jr, Sorlie P, Shero ST, Stone NJ, Wilson PW. 2013 ACC/AHA guideline on the assessment of cardiovascular risk: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2013; 127:1730-1753.
DOI: 10.1161/CIR.0b013e31828f8a94

Committee on Standards for Developing Trustworthy Clinical Practice Guidelines, Institute of Medicine. Clinical Practice Guidelines We Can Trust: The National Academies Press, 2011.

McGinnis J, Foege WH. Actual Causes of Death in the United States. JAMA. 1993;270(18):2207-2212. doi:10.1001/jama.1993.03510180077038.

Mokdad AH, Marks JS, Stroup DF, Gerberding JL. Actual Causes of Death in the United States, 2000. JAMA. 2004; 291(10):1238-1245. doi: 10.1001/jama.291.10.1238

O’Riordan M. Following ENHANCE, New Ezetimibe Users Down, Discontinuations Up. Heartwire, August 01, 2014.
URL: http://www.medscape.com/viewarticle/829328  (accessed 2014/11/23).

O’Riordan M. IMPROVE-IT: 'Modest' Benefit When Adding Ezetimibe to Statins in Post-ACS Patients. Heartwire, November 21, 2014.
URL: http://www.medscape.com/viewarticle/835030  (accessed 2014/11/23).