Site growth

How to review a protocol for enrollment risk before you sign

By TrialNotice · Updated
Hands annotating a printed clinical trial protocol with colored tabs and a highlighter
Short answerBefore you sign, identify the criteria that decide most cases, count how many of your patients meet them, estimate screen failure against industry benchmarks, check the visit and procedure burden, and map which referring physicians can supply patients your records cannot. Most enrollment problems are visible in the protocol before anyone is screened.

Why do protocols carry more enrollment risk than they used to?

They are more restrictive. Eligibility criteria in a typical Phase III protocol rose from 31 to 50 between 2002 and 2012 (Tufts CSDD, Getz), and the average screen failure rate reached 36.3% across therapeutic areas, 57% in CNS trials (Tufts CSDD), and 70 to 80% in MASH trials (JHEP Reports).

What are the six review steps?

  1. Find the deciding criteria. Of the full list, three to five usually decide most cases: diagnosis confirmation, severity, prior treatments, key labs, and disallowed medications.
  2. Count your patients. Query your records against those criteria only.
  3. Estimate the funnel. Apply expected consent and a screen failure rate. Use your own history, or the Tufts benchmark for the therapeutic area.
  4. Check patient burden. Visit frequency, study length, and procedures. In one physician survey, concern about exposing patients to uncomfortable procedures was among the strongest barriers to referral (PubMed).
  5. Map referral sources. For each deciding criterion, identify which local specialists see those patients. See referral sources by therapeutic area.
  6. Check the budget. 42% of sites say screen failure terms never or rarely cover actual screen fails (SCRS). High expected screen failure needs matching payment terms.

What are the red flags?

  • A confirmation step, such as a biopsy or imaging, that most patients fail.
  • A washout period that requires stopping a treatment patients depend on.
  • A population your site has never enrolled and no referral source for it.
  • Screen failure payments capped far below your expected failure rate.

What should the review produce?

A one page go or no go note: expected randomizations from records, expected randomizations from referrals, the top three risks, and the budget terms you need. It turns a feasibility guess into a decision, and it becomes the backbone of your recruitment plan. See how to write a recruitment plan.

Get your study in front of the right local physicians

TrialNotice builds a physician referral pipeline around one active study. We identify relevant local physicians within driving distance of your site, send study aligned direct mail, follow up by email and LinkedIn, track engagement with recipient level QR codes, and route warm responses into your site team's workflow.

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Sources

  1. Ken Getz, Tufts CSDD, "The Cost of Clinical Trial Delays" (CTTI presentation)
  2. Applied Clinical Trials, "Can Recruitment and Retention Get Any Worse?" (Tufts CSDD screen failure study)
  3. "Non invasive tests for fibrotic MASH for reducing screen failure in therapeutic trials," JHEP Reports, PubMed
  4. "Predictors of physician referral for patient recruitment to Alzheimer disease clinical trials," Alzheimer Disease and Associated Disorders, PubMed
  5. SCRS 2024 Global Site Landscape results, Site Solutions Summit

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