Inside The Rush To Accelerated Approval: A Consultant's View
By John Oncea, Chief Editor, Clinical Tech Leader
Consultants get a particular vantage point on an industry: they see the same failure mode across companies that otherwise have nothing in common. For Natasa Rajicic, ScD, who has spent the last several years consulting on study design and clinical program strategy after more than two decades at Pfizer and Cytel, one pattern has become impossible to ignore. “One thing that I noticed in maybe the last couple of years,” she told me, “is people or companies trying to skip the steps: go from Phase 1 to Phase 3, do these conditional approvals, accelerated approvals, adaptive designs.”
She was careful to frame this as a consultant’s-eye view rather than an industry-wide census. “That could be because they turn to consultants like me if they’re going down that road,” she noted. “Maybe there’s a lot of other companies that are doing a more traditional path, but as a consultant, that’s what I see.” Selection bias acknowledged, the pattern she’s describing is specific enough, and consequential enough, to be worth understanding on its own terms.
What “Skipping Steps” Actually Looks Like
The regulatory pathways Rajicic is describing exist for legitimate reasons. Conditional and accelerated approvals let promising therapies, especially for serious or rare conditions, reach patients faster based on early evidence, with confirmatory data required afterward. Adaptive designs let a trial’s parameters shift in response to accumulating data. None of these tools are inherently reckless.
What concerns Rajicic isn’t the existence of these pathways. It’s sponsors using the appeal of speed to justify skipping the underlying scientific homework that’s supposed to make an accelerated pathway defensible in the first place, particularly the dose-response work that normally happens in a well-run Phase 2. “I would say that probably there is this tender point,” she said, “during Phase 2, when you’re doing your dose-ranging studies, or going from Phase 1 to Phase 2, like recommended Phase 2 dose.”
The Overlooked Discipline: Clinical Pharmacology
Asked what organizations are consistently overlooking, Rajicic didn’t point to a data infrastructure gap or a talent shortage in general terms. She named a specific function that she believes doesn’t get pulled in enough at exactly the moment it matters most. “Clinical pharmacology can step in and do... I think people are overlooking possibilities of clinical pharmacology that can step in and answer some questions of how well we chose this dose. Is it reliable? What is the dose-response relationship? What are the expected responses for certain populations?”
Her read on recent engagements reinforces the point: “That part I’ve seen in recent interactions is that just going to Phase 3 without a clear understanding of the dose-response relationship.” In a traditional development timeline, that understanding is what a properly resourced Phase 2 program is supposed to produce. When sponsors compress or skip that phase in pursuit of an accelerated pathway, the dose-response question doesn’t go away. It just goes unanswered until it resurfaces, more expensively, in Phase 3 or in a post-approval confirmatory requirement.
Why The Incentives Point This Direction
It’s worth being honest about why this pattern is increasing rather than shrinking. Accelerated and conditional approval pathways exist because there’s real value, for patients and for sponsors, in getting effective therapies to market faster. Investors and boards reward speed. The regulatory pathways that reward speed are real and, when used properly, valuable. The problem Rajicic is flagging isn’t that sponsors are using these pathways; it’s that some are treating the pathway itself as a substitute for the dose-response and population-definition work the pathway was never meant to replace.
That distinction matters for how a clinical technology leader should read a program’s accelerated-approval strategy. A defensible, accelerated approval plan still answers the core dose-response questions early, just on a compressed and well-designed timeline, often with clinical pharmacology deeply involved in that compression. An indefensible one treats the accelerated designation as a reason those questions can be deferred.
What To Ask Before Signing Off On A Compressed Timeline
For readers evaluating a program that’s pursuing an accelerated or conditional pathway, Rajicic’s experience points to a short, specific set of questions worth asking before the program moves forward. Has clinical pharmacology been formally engaged at the Phase 1-to-Phase 2 transition, not just consulted after the fact? Is there a documented, defensible answer to what the expected response is for the specific dose and population going into the pivotal study? And is the accelerated pathway being used to compress a genuinely completed body of dose-response evidence, or to skip generating that evidence in the first place?
Rajicic’s broader advice to anyone leading a clinical development strategy, accelerated pathway or otherwise, is less about any single technical fix and more about humility at scale: bring in the best people you can find, use an advisory board or steering committee if you don’t have an in-house team, and take seriously what other sponsors have gotten wrong before you.
“You don’t know what you don’t know,” she said. “And also, to learn from other people’s mistakes. Everybody in this business has failed once or twice. There’s so much that can be learned from past experiences.” In a rush toward accelerated approval, that’s often the discipline that gets sacrificed first, and it’s the one Rajicic sees, consistently, missing when a program later runs into trouble.