Do Reference Standards Hold Back the Progress of Medicine?

IN RESPONSE:

Although we agree with Drs. Smulders and Thijs that researchers and clinicians should pay more attention to the changes in spectrum that may occur with new tests, we think that the ideas of reference standards and diagnosis will remain useful. Some new tests do clearly alter the spectrum of illness, which is why we emphasized the need to consider the clinical consequences of such additional cases. Indeed, we have been particularly concerned about the detection of “inconsequential” disease (that is, test-detected diseases that will have no impact on the patient during his or her lifetime) (1).

However, not all new tests purport to be more accurate or detect different spectrums of disease. Many are simply safer, less invasive, quicker, or cheaper than the current best test. Therefore, we will always need to have a reference standard against which to evaluate these tests. Discarding the idea of the “reference standard” would hinder our ability to evaluate these new tests. Discarding the idea of “disease” is also problematic. Although disease may be a (multidimensional) spectrum, there is rarely a “continuous spectrum” of therapeutic options, but rather a limited set of discrete options. Decisions require 2 elements: the dichotomous diagnostic category and the subdivision into distinct groups. These are shortcuts to allow the best treatment allocations that maximize benefit and minimize harm. Of note, all the examples listed by Drs. Smulders and Thijs involve this initial disease dichotomy plus a spectrum as a subsidiary element.

The middle ground here is to retain diagnostic categories but be more aware that disease is not homogeneous and requires subdivision or quantification of degree to guide decision making.