For many years the healthcare industry has relied on classical randomized clinical trials (RCTs) for evaluating drug safety and efficacy. But times have changed. We see regulators questioning their limits and constructs. Seeking richer, more diverse information. Accepting a greater role for real-world evidence (RWE).
We can think about innovating RCTs in a pragmatic fashion, where treatment arms are balanced through randomization and outcomes are events that would be observed by typical care providers. It is a faster and lower-cost approach that could be game-changing for certain types of drug development. Consider $110M for a classical Phase 3b RCT of cardiovascular outcomes vs. $40M for a pragmatic RCT (pRCT) to study the same outcomes. The question is, when is real-world reliable?
Framing the evidence
We offer a framework for evaluating RWE. A means to qualifying the reliability of real-world data (RWD) sources in the context of specific medical products and conditions. A means that allows us to determine if and when real-world studies can be used for meaningful inference.
We have identified four key elements of such a framework:
- Patient numbers. Are sufficient patients of interest likely to be available for study after applying inclusion/exclusion criteria?
- Availability of must-have data. How well does the data characterize the exposures and outcomes of interest?
- Accessibility of systematic follow-up data. What is the likelihood that patients have been followed-up in the data for the desired length of time?
- Systematic error. What is the potential for and likely magnitude of bias in data collection?
Time to rethink
Just because RWD exists does not mean it will be appropriate for every purpose. We believe that a structured approach will help regulators evaluate meaningful applications of RWE in addition to safety, resulting in use of a broader evidence base that includes both RCTs and RWE to approve safe and effective products faster and more affordably.
There is a lot of talk about the need to be more agile in drug development. Those who are willing to rethink the traditional paradigms will want to understand the issues and opportunities for using pRCTs and other types of RWD for regulatory purposes. Download the full publication showing how the US and European regulatory frameworks are changing, complete with examples.