Speaker
Jonathan D. Casey, MD, MSc
Assistant Professor, Pulmonary & Critical Care, Vanderbilt University
Co-PI, Vanderbilt Trial Innovation Center
Director, Coordinating Center, Pragmatic Critical Care Research Group
Keywords
Randomization; Randomized Clinical Trial; REDCap; Innovation
Key Points
- In a traditional randomized trial, trial procedures—including eligibility criteria, group allocation, intervention, and sample size—are specified before the trial and proceed unchanged throughout trial conduct. There are challenges associated with this method. Trials are expensive and take a long time; they’re designed to answer only 1 question; they commonly provide results that are underpowered and are therefore uninformative; they aren’t generalizable; and more.
- For each of these issues, there are proposed solutions. Platform trials attempt to answer multiple questions within a single trial. Adaptive trials either increase allocation for better-performing groups (response-adaptive) or minimize imbalances (covariate-adjusted). Pragmatic or decentralized trials attempt to address generalizability.
- To support these advanced trial designs, researchers may need a platform with the capacity to add or drop groups; randomize multiple times within the same record; generate randomization sequences that change allocation probabilities; and more.
- REDCap is a secure web platform for building and managing online databases, available at no cost to nonprofit, academic, and government organizations. It’s one of the most commonly used platforms for clinical trials, and has included an embedded tool for randomization since 2012.
- The original REDCap randomization tool embedded randomization into the data collection instrument and allowed one randomization for each study record. Users were able to stratify by sites or other key variables. However, there were gaps: users couldn’t add or drop a group; change the allocation ratio; randomize into multiple domains or at multiple points in time; and more.
- This was identified as an area for improvement by Dr. Casey’s team in 2023, and the REDCap Advanced Randomization Module was developed. The new tool supports multiple randomizations, blinding, more meta-data, integration with non-REDCap systems, and more.
- The next steps for this project include a methods and dissemination manuscript, which is currently under review; the incorporation of the randomization functionality into REDCap’s 21CFR Part 11 Validation framework; and the exploration of methods to support randomization within the EHR for pragmatic, EHR-embedded trials.
- Clinical trials need to be efficient because resources – from personnel to funding—are limited. Innovators in the clinical trials space can target logistical efficiency, regulatory efficiency, or statistical efficiency. The REDCap Advanced Randomization module focuses on statistical efficiency.
- Dr. Casey posited that the toughest question for clinical trial efficiency is when to use which design tool. Investigators facing these decision points can reach out to the Trial Innovation Center for guidance.
Discussion Themes
The Advanced Randomization Module has received a positive reception from the REDCap user base since its release in October. The group has also helped the REDCap team think through ways to refine the new features. Importantly, there have been no documented disruptions to ongoing projects.
In terms of clinical acceptability, the research team can track how many people are using the modules. How clinicians interpret and accept advanced the randomization features is harder to track, but the team is open to ideas.
There are some risks associated with introducing these complex tools into clinical settings; they increase the complexity of interpretation and can lead to unanticipated errors. Some people have raised concerns that a clinician audience might have a limited understanding of the biases that adaptive randomization can introduce.
The REDCap team is working on some exciting features for the next version of REDCap, including identity verification; data sharing and real-time data availability; and participant-mediated data sharing.