Innovative designs of point-of-care comparative effectiveness trials

Abstract

One of the provisions of the health care reform legislation in 2010 was for funding pragmatic clinical trials or large observational studies for comparing the effectiveness of different approved medical treatments, involving broadly representative patient populations. After reviewing pragmatic clinical trials and the issues and challenges that have made them just a small fraction of comparative effectiveness research (CER), we focus on a recent development that uses point-of-care (POC) clinical trials to address the issue of “knowledge-action gap” in pragmatic CER trials. We give illustrative examples of POC-CER trials and describe a trial that we are currently planning to compare the effectiveness of newly approved oral anticoagulants. We also develop novel stage-wise designs of information-rich POC-CER trials under competitive budget constraints, by using recent advances in adaptive designs and other statistical methodologies.

Health Analytics, Economics and Medicine toward a 21<sup>st</sup> Century Health Care System

“…The US Department of Veteran's Affairs is capitalizing on its superior informatics to launch an effort directed at fostering embedded clinical trials, in which the option to randomize is offered as part of the automated system of guidelines and computer-aided ordering of treatments [21]. A recent enhancement of the POC design in [21] was proposed by Shih, Turakhia and Lai [22] that uses a stage-wise design to accommodate the budget constraints of these comparative effectiveness trials at the VA. The stage-wise design functions as a group sequential design with adaptive randomization insofar as the entire trial and its overarching objectives are concerned, but also separates itself into stages with their own specific questions that can be addressed at the end of a stage.…”

“…The novel point-of-care stage-wise trial designs [9] [21] [22] for comparative effectiveness studies described in Section 2.2. have the potential to close this knowledge-implementation gap in these social science experiments on behavioral response to health policies.…”

“…Based on the patients' shared decision roles on their cardiovascular health, the American Health Association announced in 2014 a new Shared Decision Making (SDM) series on Circulation: Cardiovascular Quality and Outcomes [66]. Innovative study design and data analysis feature prominently in the development of these shared decision aids [22].…”

Opportunities and barriers for pragmatic embedded trials: Triumphs and tribulations

“…Major efforts in the United States to promote embedded PCTs include PCORI's National Patient Centered Clinical Research Network, PCORnet, and the NIH's Health Care Systems Research Collaboratory . However, a real “revolution” in clinical research has yet to occur , . Pragmatic trials—embedded or not—continue to be rare; only 344 (0.2%) of 203 788 studies in http://clinicaltrials.gov are termed “pragmatic.” The relatively slow spread of embedded PCTs may be related to current policies and a paucity of knowledge and experience in both methods and practical means to implement these strategically in health care systems.…”

“…10 However, a real "revolution" in clinical research has yet to occur. 11,12 Pragmatic trials-embedded or not-continue to be rare; only 344 (0.2%) of 203 788 studies in clinicaltrials. gov are termed "pragmatic."…”