Last week, Vinay Prasad and Martin Makary published a landmark piece in the New England Journal of Medicine announcing that the FDA’s new default standard for marketing authorization will be one adequate and well-controlled clinical trial, supported by confirmatory evidence. The two-trial dogma is officially over.
Truveta CEO Terry Myerson articulated what this means for Truveta’s evidence infrastructure. I want to offer a complementary perspective—shaped by two decades in oncology drug development and by the patients I’ve treated whose diseases outpaced our regulatory timelines.
This is more than a regulatory modernization. We are moving from an era where certainty was manufactured before approval to one where credibility must be continuously earned after it. This will be remembered as the moment when drug development shifted from episodic validation to continuous accountability.
The clinical case for change is clear … and overdue
As a gynecologic oncologist, I spent years watching patients with advanced ovarian cancer wait for therapies that had already demonstrated transformative efficacy in a single trial, only to be told the regulatory process required a second study to confirm what the biology had already made obvious.
The statistical rationale for two trials was designed for an era when we tested substances with limited preclinical understanding. Today, we select targets with molecular specificity, validate in preclinical models, and measure pharmacodynamic proof of concept before a patient ever enters a Phase III trial. A second large trial doesn’t just add cost. It adds time. For patients with serious illness, time is the one currency that cannot be refunded.
The economics are transformative, if we follow through
A single pivotal trial can cost $30–150 million and take years to complete. Eliminating the second trial reduces capital requirements, particularly for smaller biotechs and rare disease programs where financing a second pivotal study can be existential.
But let me be direct. The industry has long cited R&D costs as justification for high drug prices. If development costs fall but drug prices do not, public trust in this entire framework will erode. Real-world evidence becomes the transparency mechanism, connecting what a therapy costs to what it actually delivers. Evidence transparency is the foundation of value-based pricing—and of the accountability patients deserve.
The greater opportunity: Closing the representativeness gap
This policy change does something else that deserves equal attention. By elevating the role of confirmatory evidence, it creates both the mandate and the mechanism to finally address a problem that has persisted for decades: the representativeness gap.
Today, the evidence that guides most of medicine comes from patients who look nothing like most of the patients actually receiving the care. Clinical trials enroll patients who are younger, fitter, and less diverse than those who will ultimately receive the therapy. Patients with organ dysfunction, multiple comorbidities, or who live far from an academic medical center are routinely excluded. That gap existed long before this policy change. But by making post-market evidence a structural requirement rather than an afterthought, the one-trial default gives us the strongest mandate we have ever had to close it.
No patient should be left behind by the evidence that guides their care.
The solution: Real patient data at regulatory-grade and national scale
If we compress pre-approval evidence requirements, we must expand post-approval evidence obligations. That is the trade.
I intentionally use the term “real patient data” rather than “real-world data.” The distinction matters. “Real-world data” describes where the data comes from. “Real patient data” describes who it must represent. The obligation is not simply to collect data from outside the trial—it is to ensure that every patient who receives a therapy is reflected in the evidence that evaluates it.
Real patient data that anchors this framework must be:
Representative, capturing outcomes in patients excluded from the pivotal trial
Timely, operating at the pace of clinical adoption, not years after widespread use
Rigorous, transparent, reproducible, and robust in handling confounding
And continuous, an ongoing commitment for the life of the product
The post-market evidence system is the load-bearing wall of this new framework.
The standard is higher now, not lower
Critics will say the FDA is lowering the bar. I believe the opposite. The question is no longer, “Did the sponsor run two trials?” It is, “Does the totality of evidence—from bench to bedside to real-world practice—give us confidence that this therapy helps the patients who need it?” That is a harder question, and answering it will require the best science, the best data, and the deepest commitment to patients our industry can muster.
At Truveta, we see this not as an opportunity, but as an obligation.
The FDA has changed the default. Now the responsibility shifts to us to ensure that acceleration never comes at the expense of accountability.
The future of drug development will not be defined by the number of trials. It will be defined by the quality, transparency, and inclusiveness of the evidence that follows.
