What is the Role of the EHR in Pragmatic Clinical Trials?

While using EHR data to fuel clinical research may help cut costs and human effort, additional analysis is needed to understand how pragmatic clinical trials can be optimized while maintaining scientific integrity of results, according to commentary published in JAMA Network Open.

The healthcare industry has long acknowledged randomized clinical trials (RCTs) as the reference standard for testing the efficacy of an intervention for evidence-based medicine.

RCTs are performed in a rigorous controlled setting to reduce the effect of biases and maximize the effect of a treatment. The commentary authors noted that while RCTs have strong internal validity, that validity may be hindered in real-world applications, as clinical care dynamics are much different compared to the controlled setting of an RCT.

Pragmatic trials, which are conducted in everyday clinical settings, aim to enhance the external validity of clinical research and cut costs associated with conducting traditional RCTs. The National Institutes of Health (NIH) has promoted pragmatic trials as a viable path forward given the availability of EHRs that permit the adoption of such trials.

After all, routinely collected EHR data can be beneficial because that data does not require participant contact or adjudication, which are costly and labor intensive.

Present analyses have revealed that outcomes obtained using EHR data can be comprehensive and yield effect estimates in RCTs similar to directly adjudicated outcomes, the authors pointed out.

“Assessment of study outcomes via linkage with EMRs decreases burden on the participants and the research team,” the authors explained. “This is especially important in the current COVID-19 pandemic.”

“Cutting costs also allows pragmatic trials to be performed on a large scale, which increases statistical power, improves external validity of findings, and may allow a wider breadth of therapies to be evaluated for the same amount of human and financial resources,” they added.

However, the external validity of pragmatic trials may come at the expense of reduced internal validity, the authors noted. Therefore, they said that it is important to evaluate the agreement between results of both trial designs to identify potential obstacles and places for improvement.  

For instance, researchers conducting pragmatic trials may require a larger sample size or longer duration of follow-up if there are fewer events identified through routine data compared with adjudicated events.

Additionally, forgoing in-person visits in trials would prevent researchers from collecting laboratory measurements. Therefore, evaluating certain outcomes using EHR data may be difficult if those outcomes are not metrics documented routinely in clinical care.

Future clinical trials should perform direct comparisons between routinely collected and adjudicated data and look into the reasons for discrepancies between the two.

Take the Aspirin Dosing–A Patient-Centric Trial Assessing Benefits and Long-term Effectiveness (ADAPTABLE) trial, the authors offered as an example. The pragmatic trial compared the long-term effectiveness of 81 mg vs 325 mg of aspirin among patients with cardiovascular disease.

The ADAPTABLE Trial’s innovative study design randomized and allocated participants via a web platform. Researchers assessed outcomes by linkage queries of the National Patient-Centered Clinical Research Network.

“Similar studies are needed before widespread implementation of pragmatic trials to understand how this study design can be optimized while maintaining scientific integrity of results,” the authors wrote.

“Widespread adoption of strategies like these represent the pillars of a learning health system,” they concluded. “This strategy could facilitate adoption of pragmatic trials in any healthcare system not only to track health outcomes in real time but also to provide the evidence base that is necessary for accurate decision-making.”