Clinical trial feasibility has traditionally focused on a familiar set of questions: Which countries have the right investigators? Which sites have experience in the therapeutic area? How many eligible patients does a site believe it can recruit? How quickly can the study be initiated?
These questions remain important, but they are no longer sufficient.
A site may have an experienced Principal Investigator, suitable infrastructure and an impressive history of clinical research, yet still struggle to recruit patients. Conversely, a less obvious site may perform very well because it responds quickly, has an organised recruitment process and is highly visible to patients and referring physicians.
For sponsors and CROs, this means that site selection needs to evolve. The question should no longer be only “Is this a good site?” It should also be “Can this site find, engage and manage the right patients in the environment in which this particular study will operate?”
Feasibility should be more than a questionnaire.
Traditional feasibility often relies heavily on information provided by investigators or sites before study activation. Estimated patient populations, previous trial experience and anticipated recruitment numbers are important indicators, but they remain estimates.
A site declaring access to 100 potentially eligible patients does not necessarily have an effective mechanism for identifying, contacting and engaging them.
This is why feasibility should increasingly incorporate operational indicators. How quickly does the site respond to study opportunities? How complete are its answers? How long does it typically take to progress through the early stages of study start-up? How many competing studies are recruiting in the same indication and geography? Does the site have dedicated coordinators? What recruitment channels can it realistically activate?
These factors provide a much richer picture of a site’s ability to perform than patient estimates alone.
The investigator’s role is becoming more complex
There is another important change taking place within clinical research.
Modern clinical trials place considerable operational and governance demands on investigators. ICH E6(R3) reinforces expectations concerning participant safety, oversight of delegated activities, data reliability, appropriate resources and proportionate quality management.
Importantly, ICH E6(R3) states that investigators should be able to demonstrate the potential to recruit the agreed number of eligible participants within the recruitment period. It also requires sufficient time, qualified staff and adequate facilities to conduct the trial properly. Investigators may delegate trial-related activities, but they retain ultimate responsibility and must maintain appropriate oversight. (European Medicines Agency (EMA))
The consequence should not be interpreted as a regulatory transfer of recruitment responsibility away from the investigator. Medical eligibility, participant safety, informed consent and key clinical decisions remain firmly within the investigator’s responsibility.
Operationally, however, it is increasingly unrealistic to expect the Principal Investigator personally to drive every aspect of patient recruitment.
Successful recruitment increasingly depends on the capabilities of the entire research site: coordinators, recruitment teams, referral networks, administrative processes, digital tools and external partners.
In other words, recruitment is becoming less investigator-centric and more site-centric.
Patient intelligence should begin before site activation.
Another weakness of traditional feasibility is that patient recruitment is often addressed relatively late in the planning process.
Sites are selected, contracts are negotiated, activation takes place, and only then does the organisation begin asking why recruitment is slower than expected.
Patient intelligence should be considered much earlier.
Before selecting sites, sponsors and CROs should examine the environment in which patients will actually search for care and information. Where are patients located? How many competing trials are recruiting? Are patients already concentrated around large academic centres, or could community-based sites provide additional access? How visible are active trials outside professional clinical research databases?
This distinction is particularly important in Europe.
Clinical research operates across multiple countries, languages, healthcare systems and patient referral pathways. A recruitment strategy that works in one country may perform very differently in another. Even within the same protocol, the path from diagnosis to a research site may vary significantly between markets.
For that reason, patient access should be analysed alongside site capability rather than after it.
From site data to an integrated intelligence model.
The next generation of feasibility should combine three perspectives.
The first is site intelligence: investigator experience, infrastructure, therapeutic expertise, previous research activity and operational capacity.
The second is response intelligence: how sites actually behave during feasibility and start-up, including responsiveness, completeness of information and turnaround times.
The third is patient intelligence: the competitive recruitment environment, patient demand signals, referral pathways, geographic accessibility and the channels through which patients can realistically discover a study.
None of these dimensions is sufficient in isolation.
A highly experienced site with limited recruitment capacity may underperform. A responsive site without the necessary infrastructure may not be appropriate. A strong site in a geography saturated with competing trials may face challenges that would not be visible from its historical performance alone.
Combining these perspectives allows sponsors and CROs to move from static site lists toward more evidence-based selection.
Site selection should not be the end of feasibility.
Perhaps the most important shift is to stop treating site selection as a single decision.
The recruitment environment changes continuously. Competing studies open and close. Sites gain or lose resources. Investigators’ availability changes. Patient demand can shift geographically. Recruitment performance during the first months of a study may differ substantially from assumptions made during feasibility.
Therefore, feasibility should increasingly become a continuous process.
Sites can be monitored for responsiveness and recruitment activity. Recruitment assumptions can be compared with actual performance. Additional patient channels can be activated where necessary. Resources can be redirected toward regions or sites demonstrating stronger potential.
This creates a feedback loop between feasibility, site performance and patient recruitment.
A different question for sponsors and CROs.
The traditional question has been:
– Which sites should we select?
A more useful question may now be:
– Which combination of investigators, site capabilities, patient access and local recruitment conditions gives this study the greatest opportunity to reach eligible participants?
That is a more complex question, but clinical trials themselves have become more complex.
The organisations that integrate site intelligence, operational responsiveness and patient intelligence earlier in study planning will have a more realistic understanding of recruitment potential before activation – and a better opportunity to respond when assumptions do not translate into actual enrolment.
Clinical trial recruitment should therefore no longer be viewed as an activity that begins after site selection.
It should be one of the factors that determines site selection in the first place.
Reference
International Council for Harmonisation (ICH). ICH E6(R3) Guideline for Good Clinical Practice, Principles and Annex 1. Sections 2.2 Resources and 2.3 Responsibilities.)