Individualizing endpoints in randomized clinical trials to better inform individual patient care: the TARGET proposal.

Theodore J Iwashyna,Adam M Deane

doi:10.1186/s13054-016-1388-0

Abstract

In practice, critical care practitioners individualize treatments and goals of care for each patient in light of that patient’s acute and chronic pathophysiology, as well as their beliefs and values. Yet critical care researchers routinely measure one endpoint for all patients during randomized clinical trials (RCTs), eschewing any such individualization. More recent methodology work has explored the possibility that enrollment criteria in RCTs can be individualized, as can data analysis plans. Here we propose that the specific endpoints of a RCT can be individualized—that is, different patients within a single RCT might have different secondary endpoints measured. If done rigorously and objectively, based on pre-randomization data, such individualization of endpoints may improve the bedside usefulness of information obtained during a RCT, while perhaps also improving the power and efficiency of any RCT. We discuss the theoretical underpinnings of this proposal in light of related innovations in RCT design such as sliding dichotomies. We discuss what a full elaboration of such individualization would require, and outline a pragmatic initial step towards the use of “individualized secondary endpoints” in a large RCT evaluating optimal enteral nutrition targets in the critically ill.

Highlights

Selecting endpoints that are both measurable and important to patients for randomized clinical trials (RCTs) during critical illness is challenging but inadequately studied
We suggest that the conventional RCT practice of measuring exactly the same endpoint for all study participants can be improved upon. (For an overview, see Fig. 1) We suggest that our trial designs can and should better reflect our clinical approach, which is to
Given that individualizing endpoints may better illuminate the truth of an intervention administered to participants with a single organ problem, we propose that the advantages could be even greater when implementing this methodology in critical care RCTs enrolling a more heterogeneous cohort of patients

Summary

Introduction

Background Selecting endpoints that are both measurable and important to patients for randomized clinical trials (RCTs) during critical illness is challenging but inadequately studied. (There are limitations, as discussed below.) In particular, this approach allows a single RCT to enroll patients across a spectrum of disease or injury, since the sliding dichotomy individualizes the endpoint to the severity of the presenting problem.

Results

Conclusion