In Clinical Trials, Does One Size Fit All?
Practicing evidence-based medicine can be difficult in nephrology, where randomized controlled trials are few and far between.
In general, the more that trials use hard outcomes such as morbidity and mortality, the greater our confidence that the therapies will have an impact on patients' lives.
Using end points such as these, however, often require large sample sizes. The need to identify and recruit adequate numbers of patients makes these studies expensive and difficult to perform.
Many studies in nephrology have ended with results that were neutral or counterintuitive to the hypotheses on which they were based in the intention-to-treat analyses. The natural next step in trials such as these should be to look at subgroups in which efficacy or safety might be different from the overall cohort.
It is widely recognized and always repeated, however, that such secondary analyses are limited and generally considered “hypothesis generating.” When we see these results where a subgroup may have a particular benefit it could be a difference entirely related to chance or it could really indicate that in terms of therapeutic strategies for persons with kidney disease “one size may not fit all.”
Different subgroups based on age, comorbidity, or other less tangible clinical characteristics may truly derive a benefit from a therapy not seen in “all comers.”
These secondary analyses have definite clinical implications and prompt a larger question. If these secondary analyses are hypothesis generating, why are we stopping before we test these new hypotheses? The clinical question is just as valid as it was prior to the initial trial, and we now have a real sense for the group in whom the therapy will really benefit.
Examining treatment efficacy within a subgroup does not obviate the existence of efficacy in other subgroups. It does, however, demonstrate a commitment to improving the quantity and quality of lives of patients with kidney disease.
We as a research community (academic centers, practicing physicians, and the pharmaceutical industry) should proactively identify and study subgroups that are part of larger cohorts in all-comer trials and design trials testing those subgroups.
One size likely doesn't fit all in nephrology. Our patients are complex. These complexities affect their response to treatment. Let's finish what we start in our attempt to improve and prolong the lives of our patients.