Study recruitment projections are a key requirement to assess the overall feasibility and predict important value potentials of a proposed clinical trial. It is fair to say that for many research organisations, the ability to positively enrol a minimum number of participants, relative to site capacity, is a foundational rationale that informs decisions to either agree to, or decline involvement in any particular clinical trial.

Responsible feasibility assessment of clinical trial protocols for research sites ultimately serves to identify, qualify, or quantify risk associated with clinical trials, but this alone is insufficient. Thorough feasibility assessment should stimulate implementation of appropriate control and adherence to reliable, evidence-based processes, tools or methods that have been developed and revised in response to accumulation of predictable data over time, through identical or comparable experiences. Each feasibility you assess shapes subsequent assessments and guides determination of enrolment goals decisions that are either attainable, unachievable, or inappropriate.

Through repetition and revision, feasibility assessment and enrolment projection become considerably easier over time and should evolve into a systematic process, the predominant function of which is to prevent reactive or overly optimistic projections that promote unique risk (e.g. financial, reputational) to your own operations.

To aid decision making, relative to your own institution, you may employ a management tool or decision matrix/classification system that provides a framework for internal determinations and important external communications that can effectively moderate expectation, preserve reputation, and leverage study accession, timelines and budgets.

Regardless of your decision-making process, feasibility assessments are subject to most or a combination of the following pertinent criteria:

1. Referral Sources

  • How many do you have?
  • Will they be active and willing to contribute?
  • Do you have a large enough advertising or recruitment budget to make an appropriately positive impact on enrolment?

2. Length of Recruitment Period

  • Longer enrolment periods generally produce more opportunity to enrol
  • Shorter enrolment periods may lead to unreasonable expectations, internal stress, and inhibit ability to contribute enrolments.

3. Number of Sites

  • The number of sites recruiting the same study population may dilute your maximum number of potential enrolments.

4. Size of Site Database

  • How many potential participants are you able to identify, quantify and access?
  • 0-10% of this estimated database represents the actual realistic enrolment figure.

5. Methods and Efficacy of Communications Pathways

  • What methods or platforms can you deploy to systematically contact, inform, and pre-screen potential participants? (e.g. Text, Phone, Email, Print, etc).

6. Inclusion/Exclusion Criteria

  • Regardless of efforts or resources applied to recruitment for a trial, an overly restrictive inclusion/exclusion criteria will limit your capacity to enrol.

7. Competing Studies

  • If you are enrolling for multiple studies in the same population or indication, you may be reducing your own recruitable population
  • With a large enough, accessible database, conducting multiple recruiting studies in the same population can create an ideal method for targeted distribution of institutional efforts and participant opportunity.

8. Infrastructure and Resources

  • Do you have the personnel, space, equipment, and third-party support to achieve desired recruitment goals?
  • Some studies may have follow-up requirements that last years, other studies require multiple investigators and coordinators.

9. Screen Failure Rates

  • If a study has a 50% screen fail rate, then your enrolment efforts toward your projections need to be doubled.

10. Perceived Value or Exclusiveness of Intervention

  • Clinical trials that afford participants access to otherwise inaccessible or exclusive therapies can be relatively easier to enrol for as the perceived value of enrolment is substantially disproportionate to any perceived harms or inconveniences.

11. Experience with Similar or Comparable Trial Designs

  • Conduct of comparable or previous phase studies using the same intervention or product in the same or similar population affords a valuable insight that enables reliable inferences to be made about one’s ability to enrol participants into such subsequent or interrelated trials.

Based the above criteria and supported by standard feasibility assessment processes, training, delegation of personnel and documentation, we have a proposed decision-making framework based on what we feel are industry-specific intervals of confidence that outline principles of acceptance, the logic for such acceptance, and an examination of proactive measures in response to the conclusions you have reached. We have named this tool The Genesis Confidence System.


Confidence Level 1 – “Predictable”
(Yellow)
It is reasonably certain that you will meet your maximum enrolment target
Total Clinical Trial Load = 10-20%


Definition (Some or all may apply):

  • You have a profound understanding of the enrollable population and can make explicit, evidence-based estimations about rates of expected recruitment into the study.
  • You have a profound understanding of the type of intervention used in the study, which enables precise estimation of interest and appeal for the intended intervention.
  • You have an identifiable and specifically quantifiable database of appropriate size, relative to enrolment target, that:
    I. Is easily and ethically accessible
    II. Meets a desired criterion for inclusion
    III. Can be communicated confidently and promptly.
  • The protocol presents no readily apparent barriers to enrolment.
  • Your standard recruitment methods and referral sources are either not required or exceed the requirements for the study.
  • Enrolment time is not a considered a barrier.
  • The amount or quality of competing sites or studies is not expected to impact your own enrolment potential.
  • The prevalence of the indication of interest is significant (% of population).
  • Inclusion in the study presents an opportunity of well-established importance for potential participants.
  • Your staff are not only sufficient in number and availability, they are intimately familiar with this type of study and require little to no training or preparation to contribute enrolments to target.

Management Strategy:

  • Proceed with the study feasibility.
  • Consider negotiation of a higher or fixed allocation of enrolments.
  • Consider negotiation of higher per participant fees.
  • Consider negotiating for a reduction in total sites if appropriate.

Confidence Indicators:

  • Yellow Level studies should represent at least 10-20% of total clinical trial load at any one time.
  • The possible return on investment associated with these studies exceeds the cost of capital to a point where the likelihood of profit outweighs the chance of loss so disproportionately that the value of participation is reasonably assured.
  • Yellow Level studies support those of a lesser confidence level and facilitate growth, investment, and diversification of service capacity.
  • Yellow level studies may be ideal studies to onboard new investigators or justify the hiring of new staff as you can provide definitive assurances that relate to consistency of workload, potential for income, and accelerated professional development due to an assumed volume.
  • Yellow level studies enable you to accumulate important evidence about your maximal outputs, and thus potential.
  • Yellow level studies allow the production of well-known metrics that can be advertised and used as a vehicle for new study lead generation. (E.g. You may have an opportunity to be the only enroller or highest enroller).

Confidence Level 2 = “Probable”
(Green)
It is reasonably probable that you will meet maximum enrolment target
Clinical Trial Load = 30-40%


Definition (Some or all may apply):

  • You have an assured understanding of the enrollable population and can make informed estimations about rates of expected recruitment into the study.
  • You have an assured understanding of the type of intervention used in the study, which enables reasonable estimation of interest and appeal for the intended intervention.
  • You have an identifiable and reasonably quantifiable database of appropriate size, relative to enrolment target, that:
    I. Is ethically accessible
    II. Largely meets a desired criterion for inclusion
    III. Can be communicated confidently and promptly.
  • The protocol design presents mostly qualifiable and manageable barriers to enrolment.
  • Your standard recruitment methods and referral sources are required, although may be inadequate to meet maximum enrolment targets without additional support for the study.
  • Enrolment time is an influential but manageable factor.
  • The amount or quality of competing sites or studies is expected to pose a small limit to your own enrolment potential.
  • The prevalence of the indication of interest is substantial.
  • Inclusion in the study presents an opportunity of reasonably assumed importance for potential participants.
  • Your staff are sufficient in number and availability, and are reasonably familiar with this type of study, but may require new training or adoption of new competence to contribute enrolments to target.

Management Strategy:

  • Proceed with the study feasibility.
  • Consider cautious estimation of enrolment targets (e.g. Divide Yellow feasibility enrolment estimates by 2).
  • Consider reducing your high-end enrolment targets to offset risk.
  • Per participant fees should represent your baseline or standard fees.
  • These studies may be profitable, but you may underperform against your maximum enrolment targets or industry peers.
  • These studies may be difficult to realise when and where corrective action needs to be taken.
  • You may need to employ advanced strategies to prevent underperformance issues associated with the study, such as:
    I. Motivation and production from coordinators.
    II. Complacent business management.
    III. Aggressive Recruitment strategies and advanced pre-screening.
    IV. Formalise mutual processes to assure efficiency with 3rd party providers that you depend upon.
  • Encourage protocol design input. There may be 1-2 inclusion criteria that affect enrolment projections that can be altered.

Confidence Indicators:

  • Green Level studies should represent at least 30-40% of clinical trial load at any one time.
  • Green Level studies support those of a lesser confidence level and provide the most regular source of income, security, and largely ensure sustainability.
  • Through repetition, Green Level studies will become Yellow Level opportunities.
  • Competition in enrolment is often healthy in multisite Green Level studies and you can learn a great deal about superior management strategies and potential of other stakeholders.
  • Assume that your staff may need to undertake specific training that may be new or completely distinct from previous experience or study involvement.
  • Green level studies may still be ideal to onboard new investigators or staff as you can provide reasonable assurances that relate to consistency of workload, potential for income, and professional development due to an assumed volume.
  • Green level studies enable you to accumulate important evidence about your most common outputs, and thus justification of standard operating processes.
  • Green level studies allow the production of well-known industrial metrics that can be advertised and used as a vehicle for new study lead generation

Confidence Level 3 = “Possible”
(Orange)
It is reasonably possible that you meet maximum enrolment target
Clinical Trial Load = 20-30%


Definition (Some or all may apply):

  • You have a modest understanding of the enrollable population and can make plausible estimations about rates of expected recruitment into the study.
  • You have a modest understanding of the type of intervention used in the study, which enables limited estimation of interest and appeal for the intended intervention.
  • You have a limited but identifiable and reasonably quantifiable database relative to enrolment target, that:
    I. Is ethically accessible
    II. Partially meets a desired criterion for inclusion
    III. Can be communicated confidently and promptly.
  • You may reserve responsible safety concerns associated with the therapy and wish to measure your enrolment targets accordingly to offset or control the risk potential.
  • The protocol design presents a combination of mostly known and quantifiable barriers to enrolment but also some unknown and unqualifiable potential barriers for enrolment.
  • Your standard recruitment methods and referral sources are required but are inadequate to meet maximum enrolment targets without additional support for the study.
  • Enrolment time is expected to restrict capacity to enrol to maximum target.
  • The amount or quality of competing sites or studies is expected to pose a significant limit to your own enrolment potential.
  • The prevalence of the indication of interest is modest.
  • Inclusion in the study presents an opportunity of limited importance for potential participants.
  • Your staff are likely insufficient in number and/or availability, and they are reasonably unfamiliar with this type of study and require new training or adoption of new competence to contribute enrolments to target.

Management Strategy:

  • You may consider not proceeding with these feasibilities due to risk profile.
  • Be upfront, transparent, and constructively critical with your enrolment concerns with study sponsors. This will serve you well in difficult or slow recruiting studies, particularly in the long-term.
  • The presence and study load of higher confidence level feasibilities may provide responsible rationale for acceptance.
  • Consider reducing your high-end and minimum enrolment targets to offset risk.
  • Consider cautious estimation of enrolment targets (e.g. Divide Green Level feasibility enrolment estimates by 3).
  • Per participant fees should represent your baseline or standard fees.
  • You may need to employ advanced strategies to prevent underperformance issues associated with the study, such as:
    I. Motivation and production from coordinators
    II. Complacent business management
    III. Aggressive Recruitment strategies and advanced pre-screening
    IV. Formalise mutual processes to assure efficiency with 3rd party providers that you depend upon.
  • Encourage protocol design input. There are likely multiple inclusion/exclusion criteria that affect enrolment projections that can be altered.

Confidence Indicators:

  • These feasibilities should represent no more than 20-30% of clinical trial load at any one time as a counter measure to conceivable overburden of liability.
  • Orange Level studies support those of a lesser confidence level and represent a modest level of income, support growth of trial diversity, exposure to new areas of interest for investigators, and involvement in investigations for unique indications.
  • Through repetition, Orange Level studies will become Green Level opportunities.
  • Competition for enrolment may be healthy in multisite Orange Level studies and you can learn a great deal about superior management strategies and potential of other stakeholders.
  • Assume that your staff require specific training that may be new or completely distinct from previous experience or study involvement.
  • Orange level studies may be investigations that you are attempting for the first time, such as a completely new indication or unfamiliar intervention, you may be working with a new investigator for the first time, you may be employing a new trial coordinator.
  • It is reasonable to assume at least some inconsistency of workload, inhibition of income potential, and difficulty using these studies as a regular means of internal professional development.
  • Orange level studies enable you to accumulate important evidence about some of your weakest areas of competence and thus help to identify measures and improvements that may be implemented to develop and grow strength.
  • Orange level studies may or may not allow the achievement of well-known industrial metrics that can be advertised and, as a result, may not be an effective vehicle for new study lead generation.
  • These are not ideal studies to stimulate organisational growth or justify hiring more staff.

Confidence Level 4 = “Exploratory”
(Red)
It is highly unlikely that you meet minimum enrolment target
Trial Load = 10-20%


Definition (Some or all may apply):

  • You have a minimal understanding of the enrollable population and can only make very basic or vague estimations about rates of expected recruitment into the study.
  • You have a minimal understanding of the type of intervention used in the study, which prevents accurate estimation of interest and appeal for the intended intervention.
  • You have a database that is difficult to identify and appropriately quantify relative to enrolment target.
  • You are largely unable to pre-qualify potential participants against the desired criterion for inclusion.
  • You may reserve responsible safety concerns associated with the therapy and wish to measure your enrolment targets accordingly to offset or control the risk potential.
  • The protocol design presents a combination of both known and many unknown or unqualifiable potential barriers for enrolment.
  • Your standard recruitment methods and referral sources are expected to be largely inadequate to meet minimum enrolment targets without additional support for the study.
  • Enrolment time is expected to restrict capacity to enrol to minimum target.
  • The amount or quality of competing sites or studies is expected to pose a drastic restraint to your own enrolment potential.
  • The prevalence of the indication of interest is less than 5% of the population.
  • Inclusion in the study presents an opportunity of obscure importance for potential participants.
  • Your staff are likely insufficient in number and/or availability, and they are completely unfamiliar with this type of study and require considerable training or adoption of new competence to contribute enrolments to minimum target.

Management Strategy:

  • You should only consider proceeding with these feasibilities for reasons of exclusivity, exploratory or verification reasons.
    I. You may have a unique relationship with the developer or sponsor that allows acceptance of such a feasibility
    II. You may want to explore a new therapy or indication
    III. You may want to verify or test internal trial management systems.
  • Be upfront, transparent, and constructively critical with your enrolment concerns with study sponsors. This will serve you well in these difficult or slow recruiting studies, particularly in the long-term.
  • The presence and study load of higher confidence level feasibilities may provide responsible rationale for acceptance.
  • Consider reducing your high-end and minimum enrolment targets to offset risk.
  • Consider cautious estimation of enrolment targets (e.g. Divide Orange Level feasibility enrolment estimates by 4).
  • Per participant fees may need to be proportionally higher than standard fees due to the limited capacity to enrol.
  • You will need to employ advanced strategies to prevent underperformance issues associated with the study, such as:
    I. Motivation and production from coordinators
    II. Complacent business management
    III. Aggressive Recruitment strategies and advanced pre-screening
    IV. Formalise mutual processes to assure efficiency with 3rd party providers that you depend upon.
  • Encourage protocol design input. There are likely multiple inclusion/exclusion criteria, follow up schedule and other interventions that affect enrolment projections that can be altered.

Confidence Indicators:

  • These feasibilities should represent no more than 10-20% of clinical trial load at any one time as a counter measure to conceivable overburden of liability.
  • Red Level studies provide an insignificant level of income, allow unique examination of noteworthy trials, promote exposure to new areas of interest for investigators, and involvement in investigations for uncommon or rare indications.
  • Although difficult, through repetition, Red Level studies will become Orange Level opportunities.
  • Competition for enrolment may be extreme in multisite Red Level studies or comparably limited across all sites
  • Assume that your staff require comprehensive and specific training that may be new or completely distinct from previous experience or study involvement
  • Red level studies may be investigations that you are attempting for the first time, such as a completely new indication or unfamiliar intervention, you may be working with a new investigator for the first time, you may be employing a new trial coordinator.
  • These studies represent inconsistent workloads, low income potential, and difficulty developing management acumen.
  • Red Level studies enable you to accumulate important evidence about completely distinct areas of clinical trials and thus help to identify measures and improvements that may be implemented to develop and grow competence.
  • Red level studies provide a very low chance of achieving industrial metrics and, as a result, are not an effective vehicle for new study lead generation.
  • These are not ideal studies to stimulate organisational growth or justify hiring more staff.

Dom Bailey