FDA needs to think of itself as an information curator, rather than an arbiter of information, FDA Commissioner Scott Gottlieb of the National Academy of Sciences’ workshop on the impact of real-world evidence (RWE) on Tuesday, September 19th. Further stating, “where a single truth standard is secured to a fixed orthodoxy”.
If only it were that easy.
A single truth standard sounds great in a world where patients are homogeneous, human biology is fully understood, and motivated trial sponsors don’t design studies to hit specific goals.
However, the world of drug research is far from perfect. Patients react in different ways, often for unknown reasons, and p-values may be the result of a well powered treatment arm, not necessarily the power of the treatment itself.
Looking for a single truth standard is appealing in today’s lax regulatory environment. It sets a defined minimally acceptable bar. Give us this, show us that, and then round go and collect $2 billion.
This type of binary thinking worked for Dr. Gottlieb when he was creating an investment thesis at his hedge fund. But in the real world its not just capital, but patient lives at stake.
We agree that FDA should be an information curator, but health information is not binary. There can be many variations of the truth when it comes to drug safety - and those variations can even be used in combination to validate one another.
Before a clinical study even begins, safety teams try to understand what adverse events to watch for. They use data seen in competitor trials, in literature reviews, and in post-marketing as a benchmark. When a potential signal is spotted, data are gathered from numerous sources and evidence is generated to characterize the signal. When multiple datasets (different versions of the truth) align, there is more confidence the signal is real.
The same process follows into post-marketing. While there is no requirement in the U.S., the EMA instructs marketing authorization holders to monitor multiple channels of information including their own safety database, curated national and regional databases such as EudraVigilance, and social media. All different versions of the truth that, when used in combination by trained reviewers, can reveal a holistic risk profile.
As Dr. Gottlieb’s FDA evolves, these processes of validation and the role of pharmacovigilance will be more important than ever to ensure patient safety. Our vision at Advera Health is to be able to support drug safety decision making and risk mitigation through data, analytics, and software that enables these modern pharmacovigilance teams.