How EHR-Based Clinical Trials Can Accelerate Research Strategies

EHR-based clinical trials can accelerate the pace of research discoveries and generate sufficient evidence to inform treatment strategies, according to a recent article from the Clinical Journal of the American Society of Nephrology.

For years, there has been a substantial problem with access to novel therapies for kidney disease, and clinical trial design is a major challenge.

Randomized, controlled trials have faced major roadblocks over the years due to lack of adequate research funding, shortage of nephrology investigators at each stage of the research spectrum, and feasibility barriers, researchers from Vanderbilt University Medical Center and University of Pittsburgh highlighted in the article.

These barriers include difficulty with patient recruitment, crossover between treatment arms, and limited adherence to interventions.

But EHRs have many characteristics that would help better conduct randomized, controlled trials, including functions that fall beyond their familiar role as sources of secondary information.

EHRs also address the specific challenges of clinical trial design, such as enrollment and high costs.

“EHRs can provide a powerful platform to enroll and randomize patients and deliver interventions, thus lowering the cost and enhancing the feasibility of conducting a clinical trial,” researchers said.

For example, a 2018 single-center, randomized, comparative effectiveness EHR trial uncovered the effectiveness of balanced crystalloids versus saline to prevent adverse kidney events in patients with critical illness.

The Isotonic Solutions and Major Adverse Renal Events Trial enrolled 16,000 patients in under two years. And it was also deemed minimal risk because of the lack of data regarding a superior crystalloid and safeguards present in the EHR decision-support process, researchers said.

Therefore, the institutional review board granted a waiver of informed consent.

Overall, researchers found that the use of balanced crystalloids for intravenous fluid administration resulted in a lower rate of the composite outcome endpoint from any cause, new renal-replacement therapy, or persistent renal dysfunction than the use of saline.

“Most notably, the study succeeded in reaching its enrollment targets (using fewer dialysis facilities than anticipated), implementing the opt-out approach (with only 17 patients choosing to opt out), obtaining data with a high level of completeness, harmonizing data across EHR platforms, and monitoring safety using aggregate data from the EHRs,” researchers stated.

Additionally, maintenance dialysis is appropriate for clinical trials, researchers stated, because EHRs are widely used to document and store various clinical measurements, including patient reported outcomes.

End-stage kidney disease care is also provided by a small number of large dialysis organizations. Therefore, large-scale studies can be organized and rolled out using a small number of EHR platforms as the main source for clinical measurements of interest, researchers noted.

Although the infrastructure created as part of the study may be useful in future studies, the study outcomes raised several questions, researchers noted.

For example, researchers questioned if comparable future trials can be conducted while incorporating participant informed consent. If this isn’t the case, then similar trials would be limited to interventions that are minimal risk.

Another question raised regarded how researchers should view the smallest clinically important difference in outcomes if EHR-based trials become more common.

“Investigators must consider their research design carefully to ensure that EHR-based intervention trials are relatively convenient for patients and providers (align with provider workflow, provide ongoing engagement and education to patients and providers, and obtain patient and provider feedback to improve acceptability),” researchers said.

“Despite these potential barriers, EHR-based clinical trials will continue to grow, answering many research questions that were impractical to address before, and providing opportunities to enrich the quality of evidence that informs nephrology care and health policy decisions.”