Successful recruitment and retention is first and foremost a function of effective planning. Research teams need to know:
- HOW many patients they can realistically enroll within WHAT time period?
- WHERE the patients will come from (i.e., the main sources of patients)?
- HOW the patients will be identified (i.e., what study awareness and outreach tactics will be used)?
- HOW the patients will be consented, screened and retained?
- WHO will create and develop the various materials needed?
- HOW much all of the recruitment and retention efforts will cost and WHO will pay for these?
- WHEN and WHERE will the various tactics be deployed?
- HOW will we know what is and isn’t working and WHAT should be done to get enrollment back on track (or reduce the number of drop-outs) should the plan fail?
The Clinical Trials Participation Equation (CTPQ)
There are literally hundreds of ideas for enhancing patient recruitment and retention but sometimes it is difficult to know where to start. One of the frameworks for organizing the ideas is called the CTPQ or Clinical Trials Participation Equation.
The CTPQ Formula states that a subject’s willingness to sign on to, and stay in a clinical trial is a function of the following:
- The subject’s awareness of the study opportunity and the extent to which they feel their participation is appreciated by the sites and research sponsor
- The extent to which the subject is well educated and informed about clinical trials in general and about the specifics of the given clinical trial as well as the expectations the subject has re: benefiting from the trial and the comfort and quality of the clinical research environment
- The credibility of the site staff conducting the trial (and interacting with the subject)
- The strength of the relationship the site has with the subject and how responsive they are to subject inquires and needs as well as the resources available (or impact on financial resources) to the patient/family
- The nature and frequency of communication between the subject and key site staff
- The amount of risk or peril and inconvenience associated with participation in the study as well as the strength and impact of key influencers (e.g., GP, family members) on the subject’s decision to participate
The formula helps you to understand the factors that influence a subject’s willingness and ability to participate in a trial. It also helps researchers anticipate potential challenges and the key “levers” or tactics that can be applied to enhance enrollment and minimize drop-outs.
The CTPQ Formula suggests that a subject’s willingness to participate is a function of many variables. There are a number of factors in the numerator of the equation (e.g., awareness, education and so forth as outlined in each of these “buckets” and this is divided by the amount of peril or risk in the study as well as the amount of inconvenience associated with participation. The Impact of Influencers who may be involved in the decision to participate or stay in the study also comes into play.
Reduce Peril and Inconvenience
In essence then, to get a patient to participate and stay in a trial, one must balance out all of these factors. Where possible, researchers should try to minimize the amount of peril, risk and inconvenience (as well as take steps to address concerns from potential influencers like other family members, primary care physicians, spiritual leaders or others). Since the “Peril/Inconvenience” factors are often based on the needs of the protocol or investigational drug/device (and harder to influence or control), it’s often necessary to do a lot more of the “Awareness/Education and Credibility/Relationships/Communication” to overcome the impact. So, for particularly challenging studies, you need to do more awareness building, more appreciating, more educating, more relationship building and so forth in order to ensure a subject will consider, enroll, as well as stay in the study.
One of the other important features of the CTPQ is to evaluate all of the elements for a given trial. It’s often tempting to solve the patient recruitment problem by just focusing on awareness building but in reality, this is only 1/7th of the equation. All of the other elements must be addressed to ensure recruitment and retention. The emphasis one places on each of the elements will vary by indication, protocol, site and patient population, but researchers should at least consider whether or not they need to address all or some of the elements by systematically going through and asking questions such as:
- How will participants be aware of the study?
- How well educated is our population about their disease and clinical research? Will we need supplemental educational materials?
- When, how and how often will our population want to be communicated with?
- What financial or other resource constraints or concerns might impact their willingness to participate?
- What kinds of things could we do to make the study less inconvenient (or what could we do to minimize the inconveniences)
The Recruitment Funnel or “Leaky Pipe” Framework
Another way to think about recruitment and retention planning is through visualizing the recruitment funnel. The “leaky pipe” framework comes from supply chain methodology, which describes inputs into a process and the outputs that are derived as a result of the process. In this case, the process is a clinical trial and the inputs into the system are the potential pool of subjects available. The output is ultimately the number of evaluable subjects who complete the trial and for whose data can be used in the analysis.
The “leaky pipe” process helps researchers to visualize where along the continuum they may lose patients so they can determine the overall conversion ratio from patients with a disease or condition versus those who are likely qualified, will enroll and stay in the trial. Gaining an understanding of the loss ratios and reasons helps researchers to plan to reach the appropriate number of subjects and/or identify opportunities to reduce the loss of patients through various strategies such as modifying inclusion/exclusion criteria, putting in place patient educational programs, providing transportation assistance and so forth.
The following graphic shows the overall visualization of the recruitment funnel:
Ideally, researchers capture the metrics in a systematic way so that they can apply lessons learned from one study to the next. If you don’t have access to historical performance data for a given therapeutic area, indication or phase of trial, then applying some of the typical benchmark information can be helpful as a starting point.
On average, a researcher must identify or reach about 10 times as many patients with a given condition in order to randomize one. So, if a site is planning to randomize 9 patients in a trial, they will need to reach about 90-100 at the “top of the funnel”. This is because about 69% or 2/3rds of the patients will fail to meet the pre-screening criteria (the criteria that can be determined through a database search (e.g., query of the EMR system). About 58% of the subjects will decline the opportunity to participate for various reasons and another 1/3rd will fail to meet the remaining eligibility criteria that can be evaluated at screening (post informed consent). From that conversion of 10:1, a further 18% of the patients on average will drop out of the trial leaving even fewer patients who make it all the way through the trial.
This framework helps explain why researchers are often overly optimistic about their enrollment potential; they fail to account for all of the areas where patients can be lost. By evaluating where and how many patients may be lost across the recruitment funnel, researchers can identify the specific methods to either “fill the funnel”, “manage the leaks” or both in order to maximize the overall conversion of subjects through the clinical trial process.
Recruitment Funnel Calculator
The recruitment funnel calculator (excel spreadsheet) is a practical tool that enable you to quickly run various scenarios to estimate (based on your own know data or the benchmark data) what the conversion ratio looks like for a particular trial. By running various scenarios based on different loss ratios and enrollment periods, you can develop a much more realistic sense of HOW many patients you can realistically enroll within a given time frame.
Example of Recruitment Funnel Calculations:
Recruitment Resource Plan
Recruitment Resource Plan (RRP) outlines your planned approach to recruiting and retaining subjects. This analysis will lead you to creating a recruitment budget. A snapshot of a sample RRP is included below and provides the basic areas to include in the plan. The plan can be shared with the research sponsor or submitted as part of a grant application to demonstrate that you have done due diligence and considered the realistic enrollment contribution and associated efforts and activities to fulfill the enrollment goal. The RRP answers some of the fundamental planning questions of where the patients will be identified and how, what materials and methods will be used and how much they will cost.
Recruitment Action Plan
Recruitment Action Plan (RAP), is a simple document that outlines the “who, what, when and where” aspects of the plan. When and where will specific tactics or initiatives be deployed and by whom? What is the outcome of the efforts and how is enrollment progressing? If the recruitment goal is not being achieved, then the form allows you to evaluate what is and isn’t working and make necessary adjustments.
There are many clinical research studies being conducted at UC San Diego that are seeking volunteers. All studies have guidelines for Inclusion/Exclusion criteria, which must be followed. When a research study is designed, it is necessary to control all factors that might influence the results. Guidelines are established to determine who should and should not be included in the research study. These might include age, gender, weight, race, existing diseases, medications, allergies, just to list a few. Please do not be discouraged if you volunteer to participate in a study and are not selected to be a full participant once you are screened. There are many studies looking at a large variety of wellness and disease issues, so if one isn't a good match, there are others that might be. We encourage you to volunteer!
Recruitment Materials & Strategy
Successful study recruitment involves development and implementation of a well-coordinated plan that may require the efforts of the entire research team. Once in place, subject recruitment efforts must be frequently assessed, with new strategies implemented as necessary. The study team must only use recruitment strategies and advertisements that have been approved by the UCSD IRB for that specific study.
Based upon the specific inclusion/exclusion criteria for a study, the study team should establish a suitable recruitment plan that is outlined and approved in the IRB application. Listed below are resources to assist with your recruitment efforts.
Recruitment Guidelines & Tools
- Recruitment Guidelines
- UCLA's example of How to Write Clear Advertisements to Recruit Research Participants
- FDA Direct Advertising Guidance
Accrual to Clinical Trials (ACT)
The ACT Network is a real-time, open access platform allowing researchers to explore and validate feasibility for clinical studies
UC San Diego Altman Clinical and Translational Research Institute (ACTRI) is pleased to announce that it has partnered with the Accrual to Clinical Trials (ACT) Network to bring real-time cohort exploration and discovery to its researchers. ACT was developed by members of the Clinical and Translational Science Awards (CTSA) Program consortium to enable cohort discovery using a web interface in a HIPAA-compliant manner, without requiring study-specific IRB approval. It offers open-access to a national network of leading academic medical research centers and generates aggregate patient count data from an investigator's real-time, iterative searches. Using ACT, UC San Diego Health researchers can explore patient populations, confirm and demonstrate study feasibility, and identify potential partners for multi-site studies. ACTRI is one of the first 21 CTSA hubs across the country to launch the ACT Network. Now linking 48 hubs and a Trial Innovation Network (TIN) resource, the ACT hubs share ontologies, governance and data use agreements. UCSD has performed cohort discovery searches for the TIN. Led by UCSD with University of Pittsburgh, UT Southwestern and Harvard, the NCATS ACT network is an important tool for research design to assure studies are performed at the appropriate hubs.
ACT is available to all UC San Diego Health researchers at no charge, but registration is required.