In Clinical Research, Every Day Is Groundhog Day
By Paul Ivsin

Groundhog Day has its roots in an ancient practice once believed to predict the weather. We no longer trust in its ability to see the future, but we continue to honor the tradition.
In clinical research, we uphold this superstition through a ritual known as “sending out a site feasibility questionnaire.” We chuckle at the naivete of those who came before us, but we still diligently compile responses and maintain them in a ceremonial spreadsheet1. And in many ways, “We do it this way because this is the way it is done” is a firm principle uniting Groundhog Day and clinical trial operations.
For many of us, though, Groundhog Day is less about rodent-based forecasting and more about the sense of being trapped in a loop, destined to experience the same thing over and over again — much like Bill Murray in the classic 1993 movie.
So rather than the usual New Year's predictions, let’s pause and reflect on some of our Groundhog Day traditions of reinventing the same thing over and over again.
This is the year we’ll replace ClinicalTrials.gov!
Remember TrialReach? How about Study Hippo? CureLauncher? Not that long ago, they were all going to fix ClinicalTrials.gov.
ClinicalTrials.gov was launched in 2000 but really came into its own in 2007. In that year, pharmaceutical companies were required to register all their pivotal trials before any participants were enrolled. This requirement came into effect on the heels of mounting evidence that public preregistration was the only way to ensure the scientific rigor of our trials.
The registry represented a critically important scientific and regulatory victory. But within a few years, we all apparently forgot that and started complaining: It wasn’t patient-friendly. And a new generation of startups was born — they would fix it!
And then, they didn’t. They built friendly-looking interfaces, but no one was really excited about using them and no one could demonstrate that they actually improved trial enrollment. Most of them went out of business. The best-funded one, Antidote, was the beneficiary of technology developed by Novartis, Pfizer, and Lilly It is still around but has shrunk to about 40 employees, according to LinkedIn data.
What happened? It turned out that the Clinicaltrials.gov interface was a symptom of a deeper problem: the data you need to help match a patient to a trial just doesn’t exist in ClinicalTrials.gov. It was designed to solve a scientific and regulatory problem — and it did just that, but that’s very different from a patient-matching problem.
And that’s still true today. The underlying registry data simply isn’t clear enough, or detailed enough, to help make actual eligibility decisions.
And yet here we are, with a brand-new batch of startups unironically touting themselves as the “most patient-friendly way” to access clinical trials. And their solution is… building a new interface on top of ClinicalTrials.gov. I have tried a number of them, and they all fall short in exactly the same way that the original solutions did.
The parallels are pretty stunning — even the marketing playbooks are barely rewritten: Compare this breathless hype piece on Antidote from six years ago to this breathless self-hype piece from Power in 2024. And then go and try their platforms for the full déjà vu experience.
(One fun new twist though: Now the NIH has decided it wants to play this game, too.)
This is the year we’ll get rid of sites!
The first modern “siteless” trial — Pfizer’s REMOTE — launched 14 years ago. It closed over a year later, and not with a bang: It managed to enroll just 18 participants out of an original target of 600.
But the study team felt reason to be optimistic. It was a pilot! Lessons were learned! Many of the trial tools seemed to work well! They took the moral victory, and that seemed reasonable at the time.
Three years later, the TAPIR trial boldly ran a siteless protocol head-to-head against a conventional site design. And after two-plus years, it had pulled a whopping 10 patients into the decentralized arm (80% less than the five sites in the conventional arm). Again, lessons were learned, silver linings were found, moral victories were claimed.
Flash forward to 2024: Science 372 is thrilled to announce the first “fully decentralized Phase II trial” in major depression! According to their CMO, “This study showcases that fully remote trials are achievable, setting a new standard for patient-centric trial methodologies.” Sounds like a rousing success!
But wait… oh well.
“However, despite achieving a vast patient outreach, the trial was terminated early due to deficient enrollment. Of the 136 patients who consented for enrollment and underwent screening, 45 were randomized.”
Fourteen years later, we’re still trying to take victory laps in a car with no gas.
Clinical Trial Urban Legends
No Groundhog Day list would be complete without acknowledging the hardworking stats that we pull out every day, again and again. None of these numbers appear to be even close to reality-based, but that hasn’t stopped them from showing up every year for decades:
- Eighty percent of clinical trials are delayed due to slow enrollment (an oft-cited industry figure)
- Trial delays cost the sponsor up to $4 million a day.3
- Forty-eight percent of trial sites do not enroll to study goal.
- A new PI is 50% likely to run one trial and then drop out of research.
At least three of these stats have persisted, unchanged, since the last century – and they likely weren’t even true then. And yet they never stop reappearing.
So, what to do?
Are we destined to be stuck in these loops forever?
Maybe! Many of us do seem committed to finding a magic bullet that’s going to decisively solve the problems of clinical research. And I would argue that our excitement for that magic makes us particularly good at forgetting past futility and re-embracing the same ideas over and over again.
The secret, as Bill Murray discovered, may simply be to pay more attention and remember more. We don’t need to dwell on our past mistakes, but we do need to be aware of them if we want to do better in the future. The improvements we make might be smaller (incrementally more useable technology, incrementally better patient and site experiences), but they will be concrete and have an actual chance to accumulate over time into a better research environment. Are we ready for that?
Notes:
- It is an intriguing — and untested — hypothesis that these activities may also be more fun if executed while wearing top hats and cloaks.
- Older and/or crankier readers may remember Science 37 as 2015’s “Disruptive Innovator of the Year”
- This may be replaced by $500,000 a day — a number that is remarkable for being less wrong but somehow no less absurd. See here for details.
About The Author:
Paul Ivsin has been thinking about (and building) clinical trial enrollment programs for over 20 years, supporting both large pharma and biotech companies to run better trials. He is currently the executive vice president of trial engagement services for Continuum Clinical.