Over the years, I have written dozens of articles and thousands of posts related to clinical research. Of all the advice I can offer sponsors looking to accelerate enrollment, reduce unnecessary cost, and protect valuable patent time, one recommendation stands above the rest:
Before the protocol is drafted, identify the top-enrolling sites from the most recent similar study your CRO supported, and invite the Site Manager and Principal Investigator from those sites to help shape protocol development and study design.
That sounds simple because it is simple. But it is also one of the most overlooked opportunities in clinical research.
Sponsors routinely seek input from key opinion leaders (KOLs), and they should. KOLs often bring deep scientific credibility, therapeutic-area expertise, and valuable strategic perspective. But if the goal is to build a protocol that sites can execute and patients can realistically complete, sponsors also need the practical insight that only proven high-enrolling sites can provide.
Those sites understand far more than the underlying science. They understand the patient population in the real world. They know what visit schedules patients can actually manage, what travel burdens become dropout triggers, where home health support creates friction, what inclusion and exclusion criteria reduce feasibility, and which operational details quietly undermine recruitment and retention. In short, they know why patients say yes, why they say no, and why they stay or leave once enrolled.
Of course, protocol development must still account for the fundamentals: dosing, enrollment targets, statistical assumptions, dropout contingencies, missing data, safety monitoring, and the collection of submission-ready data. Those are givens. The problem is that the patient-facing and site-facing realities are too often missing from the design process until it is too late.
I have spent more than twenty years on the site side of this industry, leading sites, working with independent sites across our network, and collaborating with major pharmaceutical companies, CROs, and others across more than a thousand studies. In nearly every case, sites first see the protocol after it has already been finalized. And in nearly every case, sites quickly identify obvious operational issues that could have been addressed earlier.
Too often, those issues lead to protocol amendments. Once that happens, timelines stretch, costs rise, teams retrain, documents are revised, and momentum is lost. Patients feel the impact. Sites feel the burden. Sponsors and investors feel the delay. Most importantly, the path to a potential FDA approval becomes longer than it needed to be.
This is not an indictment of KOLs. Many are outstanding partners, and I have deep respect for the role they play. They are often highly committed to advancing better therapies and, where possible, cures. But in my experience, they are rarely the highest enrollers. Because of their scientific and advisory responsibilities, they are often removed from the day-to-day operational realities of site execution. High-enrolling sites live in those realities every day.
That distinction matters. A protocol can be scientifically elegant and still be operationally inefficient. It can satisfy every internal review and still be unnecessarily difficult for patients to navigate. It can look strong on paper and fail in practice.
The sponsor who wants a faster, more executable study should not wait until site activation or first-patient-in to learn what the best sites already know. Ask the CRO a simple question early: Which three sites were the top enrollers in the most recent similar study? Then bring those sites into the room before the protocol is finalized.
Keep the KOL. Add the high-enrolling sites. Let scientific excellence and executional reality shape the protocol together.
If sponsors consistently do that, they will reduce avoidable amendments, improve patient experience, strengthen enrollment performance, shorten timelines, and increase the likelihood that promising therapies reach patients sooner.
Sometimes the most important advice is also the simplest: involve the people who know how studies actually enroll.
“Back to the Sites” is inspired by Back to the Future (1985), the American science-fiction film directed by Robert Zemeckis, written by Zemeckis and Bob Gale, produced by Amblin Entertainment, and distributed by Universal Pictures. The reference works because the article argues that clinical research does not need another small adjustment at the margins; it needs a genuine paradigm shift. Like the film’s time-travel premise, the title suggests that we sometimes need an imagined look ahead to a better future state before we can see how to change course in the present. In this case, that future becomes clearer when sponsors “go back to the sites” and involve proven high-enrolling investigators and site leaders early in protocol development, so studies are designed for real-world execution, patient participation, and faster completion.
