Risk-reward tolerance standing in way of underperforming trials for sponsors.
Sponsors are losing ground to study sites: “We will deprioritize your study.” Sponsors expend a tremendous amount of resources identifying and initiating new sites for their studies; however, these investments are wasted when a study site deliberately diverts study resources away from studies that are operational failures—or, in essence, when the site quietly quits your trial.
"There is too much risk to prescreen subjects compared to the amount we receive after they enroll," "the protocol is too strict," and "patients aren't enrolling because their stipend is too low" are common reasons why sites deprioritize studies. In this article, I will share my experience and provide recommendations.
What is study deprioritization, and why do they get deprioritized?
After site initiation, study deprioritization occurs when a site deliberately diverts resources away from your trial. The typical cycle begins with the hope that the clinical trial will enroll patients; once initiated, the site attempts to enroll patients but fails (for a variety of reasons), then realizes that the recruitment effort was not worth the risk, and they refocus their resources on studies that are more likely to enroll patients.
Common causes of deprioritization of clinical trials include the following:
Insufficient or No Patient Recruitment Resources: Many sponsors erroneously rely solely on the patient volume at the study site to meet enrollment goals without supplementing recruitment with a recruitment campaign. When sites no longer have patients in their database, they begin to forget about your study. In addition, a lack of prescreening services to sift through hundreds (and sometimes thousands) of patient leads will quickly overwhelm sites, who will realize the effort is too resource-intensive and deprioritize your trial.
No Prescreening Budget: We are all aware that protocols have become increasingly complex, requiring sites to screen numerous patients before enrolling a single participant in your trial. A screen fail-to-enrollment ratio is no longer an effective strategy (since it works against the site regarding risk/reward). In addition, once a patient is prequalified, obtaining medical records post-pandemic has proven to be a significant obstacle for study sites, exhausting site resources.
Competing Study Budgets: The most frequent question on a site feasibility questionnaire is whether the study site is conducting clinical trials competing for the same patient populations; however, sponsors and CROs rarely, if ever, inquire about whether the site is conducting clinical trials with high study visit or patient stipend compensation. If your budget per patient or patient stipend is too low, sites will deprioritize your study.
Why is it important to prevent deprioritization?
Deprioritization of your trial is the worst possible outcome. Not only do you waste capital and resources on initiating the site, but you also miss your target enrollment numbers due to missed expectations and, as a result, delayed study completion timelines, continue to spend capital maintaining the site with regular monitoring visits, and pay closeout visits and fees—all of which result in a negative return on investment.
Tips on preventing clinical trial deprioritization
Optimize Protocols Using RWE: To increase the likelihood of successful enrollment, you may want to optimize your protocol using real-world evidence (RWE) data. By comparing your protocol's inclusion/exclusion criteria to RWE, you can modify your inclusion/exclusion criteria to maximize enrollment potential and reduce the likelihood of study deprioritization at sites.
Offer Site Resources for Patient Recruitment and Prescreens: Even with RWE-optimized protocols, they will remain complex, and it is essential to remember that site staff spends a substantial amount of time prescreening patients before enrolling the one patient who qualifies for your trial. Launching a patient recruitment campaign and providing prescreening support (i.e., phone screening patients and referring only those who prequalify or providing financial support for study site prescreening activities) would prevent deprioritization of the study.
Don’t Skimp on Your Study Budget: Patients are becoming more knowledgeable about clinical trials, and many expect compensation and reasonable compensation; giving patients $200 for five study visits totaling 14 hours of their time will cause them to flee. Moreover, cutting costs on research budgets gives sites an advantage. They would sign a contract to earn site startup fees, but they would deprioritize your trial once they realized the amount of risk required to enroll patients about the reward of enrolling them. Utilize coverage analyses and consider covering patient costs for standard-of-care (SOC) (as some health insurance may not always accept SOC procedures determined by you). Consider the cost of inflation, which has increased by approximately 10%.
Pay Your Sites on Time: Clinical trial payment delays are common for sites. Ensure that your sites are paid on time, and if you outsource site payments to a CRO or vendor, implement an oversight process to ensure that they are paid on time. Failure to pay sites on time results in legal issues and will cause sites to deprioritize your trial.
The deprioritization of clinical trials seems to be primarily related to risk-reward tolerance, and study sites are adept at measuring this tolerance, leaving sponsors with underperforming trials. Despite this, sponsors ignore the realities of complex protocol design, poor protocol optimization, substandard recruitment and prescreening support, and limited study budgets. By addressing these issues, sponsors could prevent sites from deprioritizing their trials.