A clinical trial may have a scientifically compelling protocol, experienced investigators and sufficient funding-and still struggle after launch.
Sites activate slowly.
Recruitment falls behind.
Screen-failure rates are unexpectedly high.
Competing trials absorb the available patient population.
Investigators discover that protocol procedures do not fit routine clinical practice.
More sites are opened.
Additional countries are added.
Budgets increase.
Timelines move.
Often, these problems appear to be execution failures.
But some actually began much earlier:
during feasibility.
Clinical trial feasibility is therefore not a box to tick before site selection.
It is one of the earliest opportunities sponsors have to test whether a clinical development strategy can survive contact with the real world.
What Is Clinical Trial Feasibility?
At its simplest, feasibility asks:
Can this study actually be delivered as planned?
That question needs to be answered at several levels.
Protocol feasibility
Can the study procedures realistically be performed?
Country feasibility
Which countries have the appropriate patients, investigators, regulatory environment and operational capability?
Site feasibility
Which institutions can actually execute the protocol and recruit the required participants?
Patient feasibility
Does the target population exist, and can eligible patients realistically access and participate in the study?
Operational feasibility
Can regulatory, contracting, supply, laboratory, technology and monitoring requirements be delivered within the development timeline?
These questions are connected.
A country with a large disease population may still be unsuitable if regulatory or operational timelines mean sites activate too late.
A prestigious hospital may still be a poor site if the eligible patients are referred elsewhere.
And an investigator's estimate of 20 participants may mean little if the protocol excludes 90% of the patients they treat.
Feasibility Should Start With the Protocol
Before asking:
“Which sites can recruit this study?”
the sponsor should ask:
“Is this protocol realistically recruitable?”
Eligibility criteria are an obvious place to start.
Consider a protocol requiring patients to have:
- A narrowly defined disease subtype
- A particular biomarker
- A specific prior treatment history
- Adequate organ function
- No prohibited concomitant medicines
- No relevant comorbidities
- No competing treatment options
- Ability to attend frequent study visits
Each criterion may be scientifically justified.
Together, however, they may reduce the recruitable population dramatically.
The Clinical Trials Transformation Initiative recommends that recruitment planning begin upstream during protocol development and explicitly identifies trial design and protocol development, feasibility/site selection and communication as core components of strategic recruitment planning.
Disease Prevalence Is Not the Same as Recruitable Population
Suppose a hospital manages 1,000 patients per year with the target disease.
It is tempting to conclude:
Excellent site.
But apply the protocol:
1,000 patients with the condition
↓
450 at the required disease stage
↓
250 meet treatment-history requirements
↓
140 meet laboratory criteria
↓
90 have no exclusion criteria
↓
60 are not receiving competing treatment
↓
40 are potentially available during the recruitment window
↓
25 agree to screening
↓
18 ultimately qualify
The site's apparent population of 1,000 has become perhaps 18 realistically enrollable participants.
This is why feasibility should work through a patient funnel, rather than relying on top-line disease numbers.
Investigator Estimates Need Evidence
Investigators know their patients and clinical environment better than most central study teams.
Their input is essential.
But investigator estimates are still estimates.
When a site reports:
“We can recruit five patients per month,”
the next questions should be:
- How many patients with the indication were seen last year?
- How many would meet the major eligibility criteria?
- How many competing trials are currently recruiting?
- How many eligible patients are expected during the recruitment window?
- Does the investigator personally manage these patients?
- Are they referred from elsewhere?
- What proportion historically consent to research?
- What was the site's enrolment performance in comparable trials?
Good feasibility does not challenge investigators because they are untrusted.
It tests assumptions because development decisions depend on them.
Historical Performance Matters-but Context Matters More
Past site performance can be highly informative.
Sponsors may consider:
- Historical enrolment
- Time to first participant
- Screen-failure rates
- Participant retention
- Data quality
- Protocol deviations
- Monitoring findings
- Start-up timelines
- Responsiveness
But a site that performed exceptionally in one study will not automatically perform equally well in another.
A different protocol may have:
- More restrictive eligibility
- A different line of therapy
- A less attractive comparator
- More demanding procedures
- Greater participant burden
- Different competition
Historical performance is evidence.
It is not a guarantee.
Competing Trials Can Completely Change Feasibility
Competition is one of the most important variables in modern site feasibility.
A hospital may have 100 potentially eligible patients.
But if four studies are targeting the same population, those patients are not exclusively available to your trial.
Sponsors should therefore ask:
What competing studies are open now?
What studies are expected to open during our recruitment period?
Do they have broader eligibility?
Do they offer a more attractive treatment option?
Which study will investigators prioritize?
Feasibility should evaluate the future recruitment environment, not only today's environment.
Patient Pathways Matter
Knowing how many patients exist is insufficient.
Sponsors need to understand where those patients receive care.
In oncology, for example, a patient may move through:
Primary/Community Care
↓
Diagnostic Centre
↓
Surgery
↓
Medical Oncology
↓
Specialist/Tertiary Centre
If eligibility requires enrolment immediately after diagnosis but the research site only sees patients later in the pathway, prevalence data may dramatically overestimate recruitment potential.
The same issue can arise in rare disease, respiratory medicine, dermatology and other therapeutic areas.
Feasibility therefore requires patient-pathway mapping, not merely epidemiology.
Protocol Burden Is a Feasibility Variable
Consider two trials for the same disease.
Trial A: one visit every four weeks.
Trial B: weekly visits for eight weeks, multiple blood draws, imaging, electronic diaries and long pharmacokinetic sampling days.
The theoretical eligible population may be identical.
The participating population may not be.
Feasibility needs to consider whether patients can realistically manage:
- Travel
- Visit frequency
- Visit duration
- Procedures
- Caregiver requirements
- Time away from work
- Technology
- Long-term follow-up
Patient burden is not a secondary consideration.
It can determine recruitment and retention.
FDA's final December 2025 guidance on enhancing clinical-trial participation also encourages sponsors to consider enrolment practices, eligibility and trial designs that facilitate participation of populations representative of those likely to use the medicine.
Site Capability Goes Beyond the Principal Investigator
A recognized investigator can make a site attractive.
But the investigator does not deliver the trial alone.
Sponsors should assess whether the site has:
Experienced CRCs
Research nurses
Pharmacy capability
Laboratory capability
Appropriate equipment
Regulatory support
Data-entry capacity
Adequate space
Backup personnel
Time
A PI managing ten trials with one overloaded CRC may be less operationally suitable than a less prominent investigator supported by a highly experienced research team.
Site feasibility should evaluate the research ecosystem, not only the investigator's CV.
Start-Up Feasibility Is Recruitment Feasibility
Suppose Site A can recruit:
2 patients/month
but requires six months to activate.
Site B can recruit:
1.5 patients/month
but activates in two months.
If recruitment is open for only eight months, Site B may contribute more participants.
This is why feasibility should incorporate:
- Regulatory timelines
- Ethics timelines
- Contracting
- Budget negotiations
- Essential documentation
- Site initiation
- IMP availability
The meaningful question is not simply:
“How quickly can this site recruit?”
It is:
“How many participants can this site realistically enrol during the period in which it will actually be active?”
Feasibility Should Challenge Country Strategy Too
The same thinking applies at country level.
Country selection should evaluate:
- Patient population
- Standard of care
- Investigator/site capability
- Competition
- Regulatory timeline
- Start-up timeline
- Recruitment potential
- Cost
A large theoretical population does not automatically make a country attractive.
Likewise, a smaller country with efficient activation and concentrated specialist centres may sometimes make a meaningful contribution.
Poor Recruitment Has Real Consequences
Recruitment failure is not merely inconvenient.
A retrospective cohort published in JAMA examined 1,017 randomized trials and found that approximately 25% were discontinued, with poor recruitment the most frequently reported reason for discontinuation.
A discontinued or severely under-recruited trial can mean:
- Participants exposed to research that cannot answer its intended question
- Lost time
- Increased costs
- Delayed development
- Wasted site resources
- Potentially inconclusive evidence
Feasibility therefore has an ethical dimension as well as an operational one.
What Should a Strong Feasibility Process Produce?
A feasibility exercise should not finish with:
Site interested: YES / NO
It should provide decision-quality information.
For each site, sponsors should ideally understand:
Eligible population
Realistic recruitment rate
Evidence supporting the estimate
Competing trials
Patient pathway
Site resources
Protocol challenges
Start-up timeline
Operational risks
Overall confidence in the projection
This allows sponsors to compare sites based on realistic contribution rather than enthusiasm alone.
Feasibility Does Not End When the Site Is Selected
One of the most important principles is that feasibility assumptions should be tested against reality.
After activation, compare:
Forecast vs actual screening
Forecast vs actual enrolment
Expected vs actual screen failures
Expected vs actual start-up
Expected vs actual retention
If assumptions prove wrong, the study team should understand why.
This creates a feedback loop:
Feasibility → Execution → Evidence → Better future feasibility
Organizations that never compare forecasts with actual performance repeatedly make the same planning errors.
The Sponsor's Practical Feasibility Checklist
Before approving a country or site, the sponsor should be able to answer:
Patients: Do the eligible patients genuinely exist?
Access: Does the investigator actually see them?
Protocol: Can the study procedures be delivered?
Competition: What other studies are competing for them?
Site: Does the full research team have sufficient capacity?
Start-up: Can the site activate early enough to matter?
Recruitment: Is the enrollment forecast evidence-based?
Retention: Can participants realistically remain in the study?
Quality: Can the site generate reliable data and protect participants?
Risk: What could prevent the forecast from being achieved?
If these questions cannot be answered, feasibility is not complete.
The Agile Clinical Trendz Perspective
At Agile Clinical Trendz, we believe feasibility should function as an early go/no-go decision tool, not simply as a questionnaire distributed to sites.
Strong feasibility connects:
- Protocol understanding
- Disease epidemiology
- Patient pathways
- Local clinical practice
- Site intelligence
- Regulatory/start-up realities
- Evidence-based recruitment assumptions
For sponsors, the objective is not to find the greatest number of interested sites.
It is to identify the smallest appropriate network of sites capable of delivering the study reliably.
Because every poorly selected site creates cost and oversight burden.
And every unrealistic recruitment assumption eventually becomes somebody's operational problem.
The best time to solve a recruitment problem is before recruitment begins.
References
- Huang GD, Bull J, Johnston McKee K, et al. Clinical trials recruitment planning: A proposed framework from the Clinical Trials Transformation Initiative. Contemp Clin Trials. 2018;66:74–79. doi:10.1016/j.cct.2018.01.003.
- Kasenda B, von Elm E, You J, et al. Prevalence, characteristics, and publication of discontinued randomized trials. JAMA. 2014;311(10):1045–1051. doi:10.1001/jama.2014.1361.
- International Council for Harmonisation. ICH E6(R3): Guideline for Good Clinical Practice. 2025.
- International Council for Harmonisation. ICH E8(R1): General Considerations for Clinical Studies. 2021.
- U.S. Food and Drug Administration. Enhancing Participation in Clinical Trials—Eligibility Criteria, Enrollment Practices, and Trial Designs. Final Guidance. December 2025.