Disconnecting Preclinical and Clinical Teams Creates Blind Spots.

Disconnecting Preclinical and Clinical Teams Creates Blind Spots.

One Idea Worth Acting On.

A pivotal Phase 3 trial hits an unexpected mechanism-based roadblock.

The clinical team scrambles for answers.

The scientist who understands the molecule's biology better than anyone — the researcher who helped design it — is no longer involved.

She was transitioned off the program two years earlier. Standard practice. The molecule had moved to clinical stage. Preclinical's job was done.

Except the biology did not get that memo.

What's Actually Happening

Oncology development still runs like a relay race. Preclinical scientists discover the molecule, characterize the mechanism, build the translational hypothesis — then hand the baton to Clinical Development and step off the track.

The assumption is that once a drug enters pivotal trials, the hard scientific questions have been answered. What remains is execution — operational, regulatory, commercial.

That assumption is wrong. And it gets more wrong as oncology moves deeper into targeted therapies, combination strategies, and biomarker-defined patient populations where mechanism is everything.

As Dr. Jay Fine, preclinical research expert and contributor to Voices of Oncology, states directly: when research personnel stop participating on product teams, critical mechanism-based issues may go unrecognized or become significantly more difficult to solve. The organization creates blind spots around the very science it is trying to bring to market.

Why This Matters

Late-stage mechanism failures are among the most expensive events in drug development. A Phase 3 program stalled by a biological question that the preclinical team could have answered costs months and hundreds of millions. Sometimes it costs the program entirely.

The risk compounds over time. Oncology development cycles run five to ten years. By the time a mechanism-based problem emerges in Phase 3, the original researchers may have moved to other programs or left the company. The institutional knowledge that built the asset has no guarantee of surviving the asset's own development timeline.

When that knowledge is gone, it is gone. Not delayed. Not archived. Gone.

Where It Breaks in the Real World

Dr. Fine describes a late-stage program that stalled when a mechanism-based challenge emerged during pivotal development. The clinical team could not identify the root cause. Progress slowed.

The original preclinical scientist had never been invited into the discussion.

When she was finally brought back into the room, the mechanism became clear within days. The mitigation path emerged. Additional preclinical work guided the clinical strategy forward. A problem that could have derailed the program was resolved — because one scientist who had been excluded was finally asked.

The question nobody asked when she was transitioned off: what happens to the program if a mechanism-based question arises that only she can answer?

What Needs to Change

Preclinical scientists should not disappear from product teams when programs reach late stage. Their participation does not need to be full-time. It needs to be defined — a named seat in program governance, a standing expectation of availability when biological questions arise, a formal knowledge transfer before any transition.

This is not about adding meetings. It is about protecting the scientific continuity that the asset depends on when the mechanism is being tested most aggressively.

The Bottom Line

You cannot afford to lose your mechanism experts just when the mechanism is under its greatest pressure.

Cancer biology does not respect organizational handoffs. The organizations that understand this will solve the problems that derail everyone else.

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