Author + information
- Jalal K. Ghali, MD∗ ()
- ↵∗Department of Internal Medicine, Mercer University, 707 Pine Street, Macon, Georgia 31201
I read with great interest the thoughtful editorial by Greene and Gheorghiade (1) proposing rigorous testing in a small homogenous cohort of patients hospitalized with heart failure in early phase trials in order to elucidate the mechanisms of action and benefit for maximal pairing of the new therapy with subsequent phase III trial population. Considering that the last heart failure drug approved by the Food and Drug Administration was the combination of hydralazine and isosorbide dinitrate in 2005, this concept could be equally applied to outpatient heart failure population.
In assessing the merit of this innovative approach, however, 2 issues need to be taken into consideration:
1. Even if the new therapy is of proven benefit in the highly selected cohort, it will need to be tested in a wider less selected cohort and having more insight into the mechanism of action may not necessarily help in selecting a wider patient population.
2. Differences between trials and community patients have long been recognized (2) and adoption of the proposed new approach will likely undermine the generalizability of the new therapy to a greater extent.
In our zeal to maximize the likelihood that the study is successful, we should not lose sight of the possibility that the more selective the study population, the narrower the scope of the application of the newer intervention.
It may be that it is still appropriate to continue to search for newer therapies that have wider application (3) with more emphasis on effective utilization of various biomarkers to maximally identify best responders.
- American College of Cardiology Foundation