We had an overwhelming response to our May 2014 webinar on the topic of Strategic Patient Screening. As a follow up, here are answers to some of the most popular questions related to study feasibility and budgets.
Q: When you are developing a recruitment funnel, how do you estimate the percentages that will screen fail at each stage?
One of the reasons capturing the recruitment funnel data is so important is that you can then create a benchmark for what the average loss ratios (pre-screening, consent declines, screen failures and drop-outs) look like for various indications and phases of trials. You may find, for example, that if you do a lot of work in dermatology (or any indication), you might notice trends where on average you lose 50% of the patients at pre-screening and 22% at screening. These ratios can then be applied to a future dermatology trial for the purposes of study planning and budget development.
If, however, you have no historical data available, then you can start with some industry benchmark data as a reference point. I have been monitoring the recruitment funnel data for some 15 years, and across all therapeutic areas and indications we generally see the following pattern:
- 69% of patients will fail to meet the pre-screening criteria
- 58% of patients will decline the opportunity to participate in a trial
- 32% will fail the screening criteria
- 18% will drop out of the trial for preventable or unpreventable reasons
On average, the data suggests that the typical conversion ratio is about 10:1. For every patient to be randomized, the site (or the study overall) will need to identify or reach about 10 patients.
While the conversion ratio and losses will vary for a particular indication or phase, this benchmark data (which has not changed dramatically over the years) provides a good reference point. If in doubt, plan to be more conservative in your estimates to ensure a realistic recruitment funnel.
Q: What is the threshold (quantitative) of potential contribution of patients from your own pool of patients that you should use to determine whether or not to accept to participate in a potential study?
As a general rule of thumb, I like to suggest that sites should be able to enroll at least 70% (or 2/3’rds) of the enrollment goal from within their known patient population base and plan to supplement only 30% with additional outreach or awareness activities. For example, if the sponsor’s goal is for a site to enroll 20 patients in 6 months, then, based on the enrollment validation assessment, the site should have access to at least 14 enrollable subjects within the database (or know, based on the influx of new patients, that it is reasonable to recruit 14 patients from their practice). This, of course, must account for the “top of the funnel” calculations. Applying the 10:1 conversion ratio, the site then would need access to about 140 subjects with the indication of interest to achieve the enrollment goal of 14 patients. The remaining 6 patients would need to be recruited through some type of outreach and awareness initiatives.
That said, the site would also need to have a well-developed Recruitment Action Plan (RAP) with the appropriate materials, methods, tactics and budgets for implementing the initiatives to ensure the remaining 30% of the subjects could be recruited. Knowing how challenging it is to recruit subjects in general, if a site has to rely on external sources of patients to supplement more than 30% of the intended enrollment goal, they may be setting themselves up for failure if they do not have the resources available to successfully implement the RAP.
In the case of dedicated research sites who do not necessarily have access to patients within a known database (and rely entirely on outside referrals), they would need a much more sophisticated and robust RAP to ensure they could achieve the enrollment goals.
Q: When we are approached by a sponsor, who has the responsibility to conduct the recruitment funnel analysis and cost evaluation even before we do any feasibility questionnaires – a research coordinator or budgeting department?
This is really a function of how the site is organized. Centers who have separate budgeting departments or central clinical trial offices are encouraged to work jointly between the coordinator/recruitment specialist and finance experts to evaluate the cost implications of the recruitment funnel (and associated planned pre-screening and screen-failure reimbursement rates). In other cases, a site director or lead coordinator may play multiple roles and they can conduct the analysis by themselves.
In general, I like to say that any trial is ultimately feasible given enough time, money and resources. So in the case of industry-sponsored trials, I like to advocate that sites request preliminary financials from the sponsors as part of the feasibility assessment as it’s nearly impossible to commit to a given enrollment contribution without knowing the funds available. Or, suggest that they re-visit the enrollment estimates as additional protocol and financial information becomes available.
Q: Our site routinely prescreens, but even with documentation sponsors are notoriously unwilling to pay for the activities. Do you have any recommendations for strategies to address this?
In my experience, more and more sponsors are gaining an appreciation for the fact that the majority of patient recruitment work and evaluation happens during the pre-screening process. Sometimes it is a matter of additional education, documentation and patience.
Providing documentation of the enrollment validation and recruitment funnel calculations provides the “evidence” that the sponsors need to understand how difficult the conversion of patients will be from diagnosis to qualification and enrollment and the impact that protocol complexity will have not only on the eligibility criteria but the willingness of the patient to agree to participate.
Using the detailed segmentation process and capturing the key criteria that is driving the biggest loss of patients by using the excel analysis (or other CTMS report) demonstrates that the site has done a reasonable due diligence effort to validate their enrollment potential and shows where and when patients are going to fall out of the recruitment “pipeline.” Adding in the financial analysis that we discussed in the webinar further shows the true site cost of all of the work effort involved in doing the chart reviews and so forth. This also highlights that paying for screen failures doesn’t account for all of the upfront work effort and sometimes it’s a matter of visually representing the information in a different way so that sponsors really understand and distinguish what you mean by pre-screening vs. screening. This has not been something that the industry has necessarily done in a systematic way and people often use the terms interchangeably, so ensuring that you are “speaking the same language” is particularly important during the budget negotiation process.
Q: Reimbursement for screen fails ratio are often a non negotiable item according to sponsors; how do you go about negotiating for more reasonable screen-failure payments?
As discussed above, it’s really a combination of semantics, evidence, documentation and education. Everything in life is negotiable so it’s a matter of understanding WHY they feel their budget and estimates are fair, HOW their assumptions compare to your evidence, and understanding how big the gaps are and what the gaps consist of. In my experience, sponsors are willing to revisit this with enough data from the sites to help them “see” and understand the pre-screening and screening process and work effort. If you have determined that the sponsor, for whatever reasons, is truly unwilling to negotiate and the gap in reimbursement vs. work effort is too great, then you may need to respectfully decline the study opportunity. Or, at least accept this with eyes wide open knowing that you will need to cover your costs through other avenues.
Want to learn more?
To learn more best practices for improving clinical trial patient recruitment at your research institution, view the free, on-demand recording of the presentation by Beth Harper, President, Clinical Performance Partners, Inc. and Kelly Anastasio, Associate Director of Clinical Trial Resources, Yale University: How to improve your clinical trial patient recruitment.