Eleanor is energized after her second cup of ristretto. It’s a few minutes before her eight o’clock clinical program-planning meeting — the one that could shape her company’s future and the prospects for patients with Alzheimer’s disease.
As program lead at AlphaBeta Inc., a mid-sized biotech advancing a novel cell therapy for neurological disorders, her team is responsible for both clinical studies and regulatory approval. She’s a drug-development scientist with deep field experience and has seen firsthand the devastating effects of Alzheimer’s and dementia on patients and their families.
A global network of collaborators — medical, clinical operations, finance, legal, hospitals, service providers, patient groups, and more — each holds a stake and a say in the discovery voyage. It’s a daunting challenge — like steering a kayak crew through turbulent waters.
Eleanor’s task seems deceptively simple: design a plan robust enough to meet the board’s ambitious target — three clinical studies in four years.
“It’s a feasible undertaking,” the Chief Medical Officer had said when she asked how the numbers were set.
She nodded, though her stomach tightened. She had seen aspirational targets like this before; they often place crushing pressure on teams and invite mistakes. The ristretto steadied her nerves as she walked to the meeting room.
Study Pre-mortem
Instead of rehearsing hopeful projections, Eleanor’s team turns to a pre-mortem — an exercise in imagining failure before it happens. The idea, developed by cognitive psychologist Gary Klein in 2007, is simple: assume the trial has already failed, then work backward to uncover why.
The method punctures comforting myths. It reveals that what most often delays trial start-ups isn’t contracts or budgets but the overlooked fundamentals — weak protocol design, poor feasibility, hasty site selection, and relationships that were never cultivated.
A Back-to-the-Future View
As Eleanor entered the meeting room, she noticed the Chief Medic and leaders from finance, legal, and HR clustered on one side of the U-shaped table. Opposite them sat the heads of clinical and functional groups — fault lines already visible. Quality and medical experts took up the flanks, ready to tend to any “casualties.”
The mood lightened when Eleanor invited everyone to share a witty line about why the program might fail.
“Every study team has a neat timeline until the redlined CTA punches it in the face,” the Contracts Manager quipped.
“Ouch — I didn’t see that coming,” she said, smiling as the room laughed.
The exercise produced over 130 one-liners, later distilled into a few central themes.
It all begins with the target product profile — the document defining the desired characteristics and therapeutic purpose of the investigational drug. When that profile is incomplete or unrealistic, it ripples through to poor protocol design and limited feasibility, making it hard to recruit eligible patients or sites.
That, in turn, leads to a strenuous path through country-specific regulatory hurdles. Misalignment of goals, priorities, and capabilities among all parties quickly follows. Add in multiple systems and administrative layers, and the mix breeds delays, stress, and preventable mistakes.
Hindsight and Reality Checks
The head of Quality, quiet until now, stood and wrote two words on the flip chart: complex system. He explained that clinical trials, like startups, behave as complex adaptive systems — dynamic, nonlinear, and full of surprises. The room fell silent. Good sign, thought Eleanor.
He launched into a crisp, ten-minute TED-style talk. Silence lingered afterward. Eleanor sensed the CMO wasn’t fully persuaded but had no alternative hypothesis to offer.
“Imagine a loose flotilla of kayakers from different tribes trying to navigate rapids without a skipper,” the Quality head said. “A small shift can upend the entire group — or the entire trial.”
“No wonder more than 90% of studies fail,” someone murmured.
The group moved on to discuss how to avoid those failures.
“We need clear goals with partners — and commitment tied to the right incentives,” said the Chief Medic.
“We must stay adaptable and open in how we work,” added the ClinOps head, smiling wryly.
“Contracts should be tools for trust — where minds, intent, and understanding meet,” said another. “Friction in contracts is often an early warning sign of deeper issues.”
The HR lead added, “We should be as competent in collaboration as we are in negotiation.”
Eleanor concluded: “We learn fast, surface risks early, and dedicate resources to fix them.”
Around the room, heads nodded.
Contracts: Trust Handrails not straitjackets
Contracts are the final step before a trial can begin. Yet long before formal negotiation starts, deal-making is already underway — budget discussions, staffing debates, early talks with investigators, and informal understandings with regulators, sites, and CROs.
Even when nothing is yet signed, expectations may have been set. So the later back-and-forth between legal teams and the drawn-out budget haggling should surprise no one; they often reveal gaps in trust and understanding. When sponsors, sites, and CROs can’t find common ground, the discord tends to echo through every subsequent stage of the study.
Precise language on standard provisions is necessary, but collaboration thrives in the spaces between the words and numbers — in shared intent, transparency, and goodwill.
And even when trust flows freely and contracts function smoothly, studies can still fail: too few patients enroll; endpoints fall short; safety concerns outweigh benefits; or biology simply refuses to cooperate. Eleanor knew all this.
But as the team sat around the U-shaped table, sketching out what might go wrong, she felt a cautious hope. They were, at last, beginning to name the real risks.
In the next part, we’ll follow their journey to design a system built to survive that uncertainty — the Zero-Redline approach.
Copyright. 2025. RHIEOS Ventures Production in collaboration with Engage CCS
