Recommendation #3: Be strategic about outcomes
Investigators conducting deprescribing trials often wish to determine
the effect of their interventions on “big-ticket” outcomes such as
mortality, hospitalization, and quality of life. We can do ourselves a
disservice by reaching for these endpoints, as we will often fall short.
Given how many factors outside of medication use impact these outcomes,
deprescribing interventions may need to have unrealistically potent
effects to detect a difference given the limited sample sizes we
typically employ. Consider cardiology trials, which often enroll tens of
thousands of patients over multiple years to try and achieve such
outcomes. And, contrast this with drugs like ezetimibe, which was
approved by the US Food and Drug Administration on the basis of
beneficial effects on lipid levels without any data on cardiovascular
morbidity or mortality.8 If this is the evidence
required to generate widespread use of a drug with well over $1 billion
in sales, we may be setting too ambitious a standard for ourselves to
attain.
An interesting contrast is set by the OPTIMIZE trial, which used a
non-inferiority design and was published in JAMA with substantial
attention. This study showed that older adults with well-controlled
blood pressure (mean systolic, 130 mm Hg) who stopped one
antihypertensive medication had similar rates of remaining at a systolic
blood pressure <150 mm Hg than people receiving usual
care.9 This flips the perceived value of deprescribing
on its head – rather than having to show that deprescribing improves
clinical outcomes, in many settings it may be enough to say that people
can fare just as well stopping their medications than continuing them.
To be clear, we should not choose outcomes just because they are easy.
However, we should pursue opportunities where outcomes are both
clinically meaningful and have realistic potential to demonstrate
benefit – or, where appropriate, non-inferiority - in response to
interventions.