For the past 50 years, Randomized Clinical Trials (RCT’s) have been a staple of pre-approval research; often referred to as the “gold standard” for their ability to minimize bias in outcomes. They are designed to maximize internal validity – or our confidence that the product being studied caused the outcomes reported under the circumstances the product was evaluated.
Unfortunately, in far too many cases, this internal validity comes at the sacrifice of our ability to generalize the results to a broader population often treated under very different circumstances to those studied. It is for this very reason that so many have begun to place an emphasis on real-world research designs meant to supplement the findings from RCT’s when informing policy and now potentially regulatory decisions.
As sources of real-world data (RWD) continue to explode, the regulatory and policy frameworks across the U.S. are continuing to move toward the incorporation of real-world evidence (RWE).
In May, FDA released Draft Guidance on Real World Data and Evidence entitled, “Submitting Documents Using Real-World Data and Real-World Evidence to FDA for Drugs and Biologics Guidance for Industry.”
In the guidance, FDA defines RWD as, “data relating to patient health status and/or the delivery of health care that are 28 routinely collected from a variety of sources.” Examples of RWD include data derived from electronic health records, medical claims and billing data, data from product and disease registries, patient-generated data, including in-home use and/or other decentralized settings, and data gathered from other sources that can inform on health status, such as mobile devices.
FDA defines RWE as, “the clinical evidence regarding the usage and potential benefits or risks of a medical product derived from analysis of RWD.” And, “RWE can be generated, for example, by collecting information about effectiveness or safety outcomes from an RWD source in randomized clinical trials or in observational studies.”
Scott Gottlieb, former FDA Commissioner summarized it well when he said, “RWE provides us with a potential source of information that can complement, augment and expand our understanding of how best to use medical products — improving what we know about our medical care.”
Under certain circumstances, opening up the design options in the pre-approval phases of drug development to include Pragmatic Clinical Trials (PCT’s) has the potential to greatly enrich and complement the findings from traditional RCT’s and, earlier in the drug approval process, broaden the generation of evidence more relevant to treated patients.
Though the creation of the infrastructure to accomplish this continues to require strong collaboration across multiple stakeholders in the healthcare system, the “raw materials” for establishing a robust, prospective, real-world evidence development environment are in place. What is needed now is for the regulatory path to be clear for those desiring to put it in place. Regulators, payers, and providers alike also must be aligned in their demand for more relevant evidence upon which to base their decisions.
Though pure gold cannot corrode or tarnish, in this case, our current gold standard is not so pure. With the increasing availability of robust real-world data and improving analytic methodologies, we have the opportunity to greatly enrich our development process by combining the relative strengths of RCT’s and RWE, bringing us to a new, much purer gold standard.