Clinical Trial Basics: Screen Failure
Screen failures can significantly increase the cost burden on both sponsors and sites, so it’s essential to understand how they arise and what can be done to minimize screen failure rate.
Subject screening definition
In clinical research, subject screening or patient screening is the process of reviewing a candidate against the inclusion and exclusion criteria of the trial to determine their eligibility. This includes asking demographic and general health questions, and may include performing physical exams, lab work, and diagnostics tests such as MRIs, CT scans, or x-rays. These latter screening processes can only start after a candidate gives their informed consent, whereas basic demographic factors can be established prior to consenting.
Definition of screen failure in clinical trials
A candidate who does not meet a clinical trial's inclusion or exclusion criteria is referred to as a screen failure. The definition of screen failure also includes eligible candidates who consent but then:
- Withdraw their consent
- Suffer an adverse event (e.g., death or accident)
- Relocate
- Prove to be non-compliant
It’s difficult to obtain consistent statistics on the prevalence of screen failures because there is no standardized definition of a failed screening, meaning there is also no uniform protocol for reporting screen failures.
How do you calculate screen failure rate?
The screen failure rate formula (in percentage) is given as the number of ineligible candidates divided by the number of screened candidates, multiplied by 100.
For example, a clinical trial that has 220 eligible candidates after screening 350 candidates would calculate the screen failure rate as: [(350-220)/350] x 100 = 37.1%
The screen failure rate for this hypothetical trial is 37.1%.
Is screening before or after informed consent?
Actual screening is only allowed after a candidate has given their informed consent.
However, clinical trial recruiters can pre-screen candidates based on certain inclusion or exclusion criteria such as age, diagnosis, comorbidities, and prior treatments. Using this information, they can determine eligibility for further screening.
Invasive procedures or interventions such as scans or lab work cannot be performed prior to consenting.
How much do screen failures cost sponsors?
There is no question that screen failures due to non-enrollments cost sites and sponsors, but the actual values are difficult to approximate as this information is not typically published. Screen failure costs also vary widely amongst different areas of clinical research. However, several industry factors influence the screen failure cost, such as:
- Fee arrangements between sponsors and enrollment sites
- The complexities of the clinical trial, e.g., multi-center or international trials
- The candidate population available
- The recruitment process and timeline
- The use of digital solutions for informed consent and pre-screening
What are the most common causes of screen failure?
The most common reason for screening failure is the ineligibility of the candidate. This is followed by an eligible candidate’s refusal to participate, which could be for several reasons such as lifestyle constraints, the trial duration, or learning about the potential adverse risks of the trial.
Another reason for exaggerated screen failures is working with enrollment sites according to a flat-fee payment model wherein the site is paid for the total number of screens, regardless of whether or not the candidate is eligible. This motivation to simply earn the screening fee can inflate the screen failure rate.
5 ways to reduce screen failure rate
There are several ways sponsors and sites can reduce their screen failure rate. Five strategies are listed below.
1. Perform thorough pre-screening
Take full advantage of the pre-screening process to filter candidates before calling them to your site and involving your research team. Look to digital solutions and online platforms such as Power that can streamline your clinical trial pre-screening process and send through only those most likely to pass the final screening process and enroll.
2. Design patient-centric protocols
The more flexible the trial is for patients, and the more consideration is given to patient experience, the more willing participants will likely be to enroll in the trial. If a trial is sufficiently enticing, interested candidates are less likely to choose not to participate. Focus on designing patient-centric trial protocols that take the burden off your candidates and help them feel seen and valued.
3. Leverage decentralized technologies
Decentralizing your pre-screening, consent and screening processes can lower screen failures. Technologies such as eConsent not only help to engage and educate candidates, but also enable remote enrollment, thus widening your potential trial population.
4. Monitor screen failure rate and address problems identified
Monitor your screen failure rate throughout the enrollment process and aim to rectify problems as they arise. High pre-screen failures can highlight a lack of specificity in your clinical trial marketing, while higher screen failures across all sites can indicate problems with your screening protocol or overly restrictive inclusion/exclusion criteria.
5. Establish an appropriate fee structure for screening
To avoid the issue of sites screening indiscriminately to obtain the screening fee, ensure an appropriate fee structure agreement with your enrollment site. Consider a performance-based payment scheme, then explicitly hash out the details and your expectations so you don’t end up paying more than you have budgeted and so the fee structure works out for the trial sites as well.
Conclusions
Screen failures are part of the clinical trial enrollment process and likely cannot be avoided completely. However, sponsors who are prepared with realistic expectations, well-designed protocols and eligibility criteria, and who leverage digital technologies to their advantage can minimize screen failure costs and keep their clinical trial recruitment on track.