When One Trial Leads To Rethinking Them All

By Dan Schell, Chief Editor, Clinical Leader

Usually, when someone sees my name badge at a conference, they say, “Oh, you’re that guy who sends me all those emails.” (For the record, those are not coming from me personally.) Thankfully, that wasn’t what Dan Nicolau, Ph.D., said to me when we met at the Clinical Trials Technology Congress (CTTC) in London earlier this year. Instead, Nicolau, who was familiar with Clinical Leader, told me a story that quickly got my attention.

It began on a COVID ward in Oxford during the earliest days of the pandemic. It led to a clinical trial that influenced treatment around the world. But perhaps more importantly, it forced him to ask a question that has stayed with him ever since: If a clinical trial is already telling us the answer, why do we insist on waiting until the end to acknowledge it?

That question ultimately led Nicolau and fellow physician and entrepreneur Tom Coates to found Presentient Technologies. But as we talked, it became clear the company wasn’t really the story. The story was how one unexpected experience as a PI fundamentally changed the way Nicolau thinks clinical trials should work.

A Fresh Set Of Eyes

Nicolau never set out to become a clinical trial entrepreneur. A Romanian-Australian physician-scientist whose academic work spans medicine and AI, he found himself unexpectedly called back to the UK during the COVID-19 pandemic. Although AI had been a major focus of his career, he was attached to the John Radcliffe Hospital and associated centers simply because he was a physician available to help.

What he saw immediately didn’t make sense.

Patients with COPD and severe asthma, individuals widely expected to fare especially poorly against a respiratory virus, were largely absent. “Sometimes, if you come to something with a beginner’s mind,” Nicolau told me, “you can often see something that the rest of us don’t see.”

So, rather than dismissing the observation he made at the hospital, he began making phone calls.

Friends and colleagues in Australia reported seeing the same pattern. Physicians in China and Romania observed it as well. Contacts in the United States echoed the same experience. Across very different healthcare systems, one surprising trend appeared remarkably consistent.

Many of those patients routinely used inhaled corticosteroids, particularly budesonide.

That observation became the foundation for the STOIC trial.

The study enrolled patients with early COVID and compared standard care against treatment with inhaled budesonide. Because patients were inhaling an active medication, the study necessarily became an open-label trial. Investigators knew who received budesonide and who did not.

Watching The Answer Emerge

As patients enrolled, Nicolau and his colleagues began seeing a pattern develop. The treatment arm appeared to be outperforming standard care by a wide margin. Eventually, the investigators believed the evidence had become compelling enough that continuing enrollment was difficult to justify. After discussions with the independent review committee, the study was stopped after enrolling 73 patients in each arm rather than reaching its original target. The findings were later published in The Lancet Respiratory Medicine and contributed to treatment recommendations in multiple countries during the pandemic.

But while much of the world focused on budesonide, Nicolau found himself thinking about something else entirely. “The world forgot about it because vaccines came along,” he said. “But what this experience taught my friend and I was to ask the question: Why couldn’t you do that for other trials?”

The experience exposed something Nicolau hadn’t fully appreciated before running a clinical trial. Clinical research has always balanced two competing priorities: scientific rigor and speed. Blinded studies remain the gold standard because preventing investigators from knowing who receives treatment minimizes bias and strengthens confidence in the results. Yet sponsors invest years and enormous resources into studies while patients volunteer hoping to advance medicine.

If there were a reliable way to determine that a study had already become overwhelmingly likely to succeed — or fail — would continuing exactly as planned always be the right decision?

Today’s trials already include interim analyses in certain situations, but most pivotal studies still follow a predetermined roadmap established long before the first patient enrolls.

Nicolau eventually shared those ideas with Coates. “We essentially spent six months locked in a basement trying to work out how to solve blinding,” Coates joked. In 2022, they founded Presentient, which has technology designed to analyze trial data within a secure environment and estimate whether continuing enrollment is likely to change the outcome of the study. The decision to continue or stop would remain with sponsors and regulators.

Challenge Old Assumptions

The FDA’s Real-Time Clinical Trials (RTCT) initiative has already sparked debate over whether emerging technologies can safely modernize clinical development without compromising scientific standards. Nicolau believes we’re approaching one of those moments when long-standing assumptions begin to shift. “I expect we’ll look back on this period and say, ‘Really? They did trials like that in 2026? They had AI, but they were running trials like they were done right after World War II’”

Perhaps he’s right. I hope not.

Either way, his story is a reminder that meaningful innovation doesn’t always begin with a startup idea. Sometimes it begins with a physician noticing something everyone else overlooked. And sometimes, running a single clinical trial changes not only how you think about a disease, but how you think clinical trials themselves should work.