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The protocol
The final protocol qualified nearly three times the patients of the initial draft. Same scientific intent, dramatically better enrollment odds.
In rare disease, the enrollment question is not hard because the math is hard. It is hard because the patients are scarce, scattered, and invisible from any one chair. The sponsor asks how many will qualify and where they are treated, and the honest answer in most rooms is a shrug dressed as a shortlist. We answer it with a count.
World-class investigators sit at the design table, and every criterion in the draft protocol feels clinically reasonable. Then the counting question arrives: how many patients would actually qualify under these criteria, and which sites can reach them? Expert intuition cannot answer a counting question. In a disease with a few hundred qualifying patients nationwide, a partial view is not a smaller answer. It is the wrong answer.
Get the first one wrong and the second one cannot be right. Most feasibility skips straight to the second.
Every eligibility criterion has a price in patients, and in rare disease that price is steep. A documented treatment history that reads as reasonable can quietly strangle the enrollment pool. Nobody at the table can say which line is doing the damage.
A bigger eligible pool only matters if your sites can enroll it. In an ultra-rare disease, most sites, however prestigious, simply do not treat these patients. The conventional shortlist of big academic names answers the wrong question.
The big names, chosen by reputation. On a rare disease, several of them sit in empty space: few or no patients who meet the protocol.
A recent rare-disease program, from draft protocol to ranked site list, on one evidence base.
The final protocol qualified nearly three times the patients of the initial draft. Same scientific intent, dramatically better enrollment odds.
Many of the big-name centers on the conventional list had few or no patients who met the protocol’s criteria. They came off before activation.
The eligibility answer and the site list came from the same national, patient-level data, so the sponsor could defend both with one story.
Every criterion’s price in qualifying patients, measured before a single site is activated, so you know where the protocol can safely open up and where it should not move.
Each site pairs a consistently high-enrolling investigator with a counted population of protocol-qualifying patients, including strong sites the conventional lists never surface.
Prestigious centers with no qualifying patients come off the list before activation dollars are spent, not six months into a stalled ramp.
Why each site made the list and why some big names did not, down to a number. It is the answer that holds up in a bid defense.
Why is site selection harder in rare disease trials?
Because the patients are scarce and scattered. There may be only a few hundred protocol-qualifying patients in the whole country, spread across institutions no single expert can see. A conventional shortlist of prestigious centers assumes the patients are where the reputation is, and in rare disease that is often wrong.
How do you find sites for a rare disease clinical trial?
Two questions, in order. First, how many patients actually qualify under the protocol as written, counted from real, national, patient-level data. Second, which investigators have both a counted population of those patients and a measured record of enrolling. The result is a ranked site list that includes strong sites the conventional lists never surface and excludes marquee centers with no qualifying patients.
Can you help optimize a rare disease protocol before site selection?
Yes. In a recent rare-disease program we measured what each eligibility criterion cost in qualifying patients and showed the sponsor where the protocol could safely open up. The final protocol qualified nearly three times the patients of the initial draft, with the same scientific intent.
Do the big academic centers usually make the list?
Only when the patients are there. In rare disease we routinely find that marquee centers have few or no patients who meet the protocol’s criteria. Those sites come off before activation, and the list is built on sites that can actually enroll.
Send the draft protocol. We will come back with how many patients actually qualify, what each criterion costs, and the sites that can reach them. In days, not a feasibility cycle.