Defining recruitment feasibility
While there are some general standard operating procedures (SOPs) available to research sites for guiding a feasibility assessment,4 sponsor companies have only just begun to define their own SOPs.
"We consider strategic feasibility to be part of a global clinical development plan for a compound or protocol," Neidl said.
"It's a high-level process taking into consideration the market strategy, disease incidence and prevalence, regulatory approach,
and country selection, and maybe some preliminary idea for an investigator strategy, such as specialty selection and mix of
generalists and specialists."
Considering the infinite number of potential recruitment conundrums that varying protocols will create, it may seem an insurmountable
task to gain a full understanding of how all of these considerations will factor into a successful study. By breaking feasibility
into a few key phases, we can begin to prioritize and operationalize our efforts—a process that can be applied to any therapeutic
indication or the scope of the research in question.
"We divide feasibility into two phases, the first being protocol design, and the second operational planning," said Martin
Lee, MD, Executive Director of Site and Patient Recruitment for Pharmaceutical Product Development (PPD), a leading global
CRO. "It's in the latter process that we consider the regulatory time lines, drug supply, and other factors that ultimately
determine whether recruitment will happen in a timely fashion."
Figure 1. Example of factors assessed in a site survey.
Indeed, within the broader scope of operational feasibility for a clinical trial, recruitment feasibility is the process for
determining the time frame and parameters necessary for successful recruitment.
For the purposes of exploring new methods for improving clinical trial enrollment planning and execution, we propose the following
definition of recruitment feasibility.
Recruitment feasibility is the process by which a clinical study sponsor can forecast and manage the probable randomization
rate (number of patients per site per month) for a specific protocol and determine realistic parameters for site enrollment
months (number of sites multiplied by number of open-to-enrollment months).
With this in mind, study planners must consider each of the following factors through a recruitment lens.
Protocol design. How would each group of study community members respond to this protocol—regulators, investigators, coordinators, project
managers, monitors and patients? In what ways might the protocol design be off-putting to one or more of these groups, and
can that be changed, or must it be mitigated? Can we afford to prioritize one group over another?
Country. While there may be many business reasons to include a specific country—such as market importance, regulatory barriers affecting
speed to market, existing relationships with investigators, cost of conducting—none of these exempts a country from a recruitment
feasibility assessment. From a recruitment perspective, the goal is not merely to determine which countries should be included,
but what will it take within each country under consideration to succeed? What level of recruitment support may be required
to offset protocol design challenges?
Sites. What types of investigators are most likely to be high enrollers for this study? Will that vary by country? Do we have a
platform for contracting specific sites in each selected country? What are the likely enrollment rates for sites in each country?
Site surveys play an important role in assessing recruitment, however most current models co-mingle recruitment feasibility
with site selection—a near guarantee for collecting misleading information.
Patient. While it may seem obvious to include patient perspectives in the recruitment feasibility process, it is a rare sponsor that
consistently asks patients for their input. More often than not, investigators, key opinion leaders, or country managers are
used as surrogates for patients.
Brendan O'Neill, Manager in the Patient Recruitment Specialist Group at Merck and Co., agreed with this sequence, "We approach
recruitment feasibility in that order—country, site, and patient. It's great to consider the patient level, but if the protocol
won't be approved in a country, you're wasting everyone's time."
Indeed, from a patient recruitment perspective, these four key considerations are the root of most enrollment barriers and
certainly a thorough analysis of a given protocol will provide the necessary insight regarding ideal study countries, sites,
and ways and means to reach the patients most likely to value study participation. Assuming that we know our protocol and
our patients well, let's focus on some key considerations for country and site assessment and selection and how qualitative
data collection strategies can be applied universally for all studies, and ultimately applied to a feasibility formula to
generate quantitative insights for successful study planning.