What difference makes a difference?
We often encourage patients to make small behavioral changes, in the hope that even one step in the right direction is at least small progress. However, when it comes to medical care, and testing in particular, I think we forget that some changes are not really changes at all.
As we continue to think collectively about overdiagnosis, we also need to look at the impact of “minimal change disease.” With apologies to my nephrology colleagues, I am not here referring to the renal disorder that leads to nephrotic syndrome. Rather, I am thinking of the tendency to focus on numbers and trends without due attention to the question: “What is a real change?”
I recall, 20 years ago, discussing with an older patient a letter he received from the cardiologist recommending efforts to combat a rising LDL cholesterol level—horror of horrors, it had increased by five points. More recently, I’ve seen colleagues fret over BNP (brain natriuretic peptide) levels fluctuating between 200 and 300 in patients with chronic heart failure, despite no worsening in dyspnoea. Likewise, I recall a discussion over whether or not we needed to “trend” Troponin I levels in a patient with chest pain—all were below the threshold for diagnosis of NSTEMI (non-ST elevation myocardial infarction), but they continued to fluctuate above the “normal” level, varying by about 5-10% from test to test.
In 2008, a review of data from one of the major pravastatin trials found that too frequent monitoring of cholesterol levels may lead to decisions based more on random “noise” rather than true change: “The signal of a small increase in cholesterol level is difficult to detect against the background of a short term variability of 7%.”
As for BNP levels, the benefit of serial measurement is unclear for in-hospital management of heart failure. When it comes to diagnosis of acute heart failure, levels less than 100 pg/ml or greater than 400 pg/ml may be useful for excluding or diagnosing heart failure, but levels in the middle are of completely uncertain significance.
I’ve been unable to find similar evidence on Troponin I testing, however, a lab technician at Sacred Heart Hospital recently advised me that Troponin I variations on the equipment we use that demonstrate a less than 10% change are clinically insignificant.
In our work of caring for people, relieving suffering, and saving lives, appropriate accuracy and precision are vital—but what level of precision is appropriate?
During my last year of medical school, I spent two months working at PCEA Kikuyu Hospital outside Nairobi. Having previously done all my rotations at the Milwaukee County Medical Center, I found the work in Kenya quite a change: we treated people who were often much sicker than those in Milwaukee, with far fewer resources, and often much less technology. Despite this, there were many patients who did just as well (or better), even with a far simpler hospital set-up.
One of the many lessons I learnt from my time in Kenya was that the human spirit and body are resilient. When routine labs are not always available, you learn to make do. When an ECG is a one hour drive away, you learn to get by. When x-rays are of questionable quality, you focus on the clearly significant findings.
Yes, precision in medicine can be important—I am grateful that my neurosurgery and ophthalmology colleagues have the tools to do work that is sometimes measured in millimeters. Nevertheless, there are times that tests can give us a perception of “precision” that is unwarranted.
We need an appreciation for what differences or degrees of change matter and we need to place in context numbers that may look different, but which actually convey no real world significance.
Overdiagnosis has many root causes, but one important step in rolling back overdiagnosis is learning to combat “numerical minimal change disease.”
William E Cayley Jr practices at the Augusta Family Medicine Clinic; teaches at the Eau Claire Family Medicine Residency; and is a professor at the University of Wisconsin, Department of Family Medicine.
Competing interests: “I declare that I have read and understood BMJ policy on declaration of interests and I have no relevant interests to declare.”