Tackling High Screen Failure Rates and Boosting Diversity in CNS Clinical Trials
High screen failure rates in central nervous system (CNS), neurological, and psychiatric clinical trials are among the most significant barriers to efficient trial execution. For clinical sponsors and contract research organizations (CROs), these failures drive up costs, prolong timelines, and complicate recruitment strategies. Compounding this challenge is the lack of participant diversity, which limits the applicability of trial results and creates bottlenecks in recruitment. Amid these hurdles, however, innovative strategies and partnerships can pave the way for more inclusive, efficient, and successful trials.
Understanding and Addressing High Screen Failure Rates in CNS Trials
Screen failure rates in CNS trials regularly surpass those in other therapeutic areas. These failures often stem from the nature of neurological and psychiatric disorders. Diagnostic criteria are subjective, inclusion/exclusion requirements are stringent, and comorbidities or medication conflicts can further complicate recruitment.
Research conducted by the Tufts Center for the Study of Drug Development found:
- The average screen failure rate for clinical trials increased to 57 percent for neurological studies, up from 29.5 percent in 2012.1 For comparison, the overall average screen failure rate across all therapeutic areas was 36.3 percent.1
- In Alzheimer’s disease (AD) trials specifically:
- Mild AD trials have an average screen failure rate of 44 percent2
- Preclinical AD trials have a staggering average screen failure rate of 88 percent2
A combination of diagnostic, procedural, and participant-related challenges drives the high screen failure rates in CNS clinical trials. For example, trials for depression or dementia hinge on nuanced diagnostic assessments that do not always align with trial protocols. The subjective nature of CNS assessments and rating scales often leads to inconsistencies in patient selection.3 Stringent inclusion and exclusion criteria, such as requiring amyloid-beta PET positivity or specific neurocognitive benchmarks in AD studies, further narrow the pool of eligible participants, making it challenging to identify suitable candidates during pre-screening.2
Adding to these difficulties is the complexity and cost of screening procedures. Cognitive tests, MRIs, and amyloid-pathology assessments can amount to thousands of dollars per patient, inflating trial budgets. These processes also impose a high burden on patients, as do the frequent clinic visits, lengthy assessments, and intricate study designs typical of CNS trials.2
The high screen failure rates and complex nature of CNS clinical trials have profound implications for trial feasibility, creating a cascade of challenges that hinder progress. Patient-screening costs alone have been reported to account for 50 to 70 percent of total per-patient expenses in AD trials, making these studies among the most expensive in clinical research.2
Recruitment challenges further exacerbate the issue, often extending the duration of disease-modifying therapy trials far beyond those in other therapeutic areas. These recruitment barriers contribute to a discouraging statistic: the failure rate of CNS drugs in Phase 2 and 3 clinical trials exceeds 80 percent.4
The result? Sponsors are left scrambling to adjust strategies while attempting to meet regulatory and scientific standards. Such pressures create a challenging environment for both CNS trial sponsors and their CROs, emphasizing the need for careful planning and innovative approaches.
Diversity as a Catalyst for Accelerating CNS Clinical Research
One proven solution to the challenges in CNS clinical trials lies in fostering greater diversity among participants. By broadening the pool of eligible candidates and ensuring the inclusion of underrepresented populations, researchers can address recruitment logjams while enhancing the generalizability of trial outcomes – a critical priority in today’s regulatory and scientific landscape.
Historically, clinical trials have disproportionately enrolled white participants, with Caucasians comprising 83 percent of research participants despite representing only 67 percent of the U.S. population. In contrast, Black/African Americans and Hispanic/Latino populations are underrepresented, even as they bear disproportionate burdens of chronic and neurological diseases.5 This lack of diversity limits the applicability of trial results and exacerbates recruitment inefficiencies.
Increasing diversity is more than an ethical obligation – it is a pragmatic strategy. Diverse populations ensure trials produce results that better reflect real-world patient populations. FDA guidance on diversity action plans reinforces this priority, positioning inclusivity as both a moral and operational imperative for today’s clinical research.6
The Clinical Site Network Advantage in CNS Trials
Choosing the right clinical site network can be a key determinant in achieving greater diversity and improving CNS trial success. An innovative site partner can effectively translate these principles into practice in several ways. First and foremost, they can make a difference by maintaining and delivering proprietary patient databases that are uniquely qualified to meet screening requirements.
When evaluating a site network, in addition to the patient database, consider where the sites are located and how they are staffed. Placing trial sites in racially and ethnically diverse metropolitan areas and aligning staff demographics with those of the surrounding communities will ensure that trials are inclusive and representative across the relationship between patient and provider. Importantly, this relationship can aid participant compliance and retention – which is particularly essential in CNS trials.
One further consideration is that the right site network partner will understand how technological innovation is reshaping the landscape of CNS trials. In this regard, seek out sites using innovative tools like automated eSource exception reporting and real-time quality control to deliver an efficient trial startup process. These capabilities enable the swift identification and proactive scheduling of eligible candidates, reducing the time to first-patient-in and accelerating study progress.
Example in Practice: Enrollment Excellence in Neuropathy Trials
Alliance Clinical Network’s strategically placed sites in California, Nevada, and Texas contributed over 37 percent of total enrollment in a recent neuropathy study, earning recognition as the top enroller across all sites. Leveraging its 250,000+ prescreened participant database and efficient site activation, Alliance accelerated enrollment while maintaining audit-ready data through rigorous quality controls. With 85 percent of participants from underrepresented populations, Alliance’s diverse recruitment approach ensured equitable access to cutting-edge therapies and desired study outcomes. These results demonstrate the opportunity to exceed industry benchmarks and tackle the complexities of CNS trials.
Key Takeaway
High screen failure rates and limited diversity in CNS trials are significant challenges for sponsors and CROs, but they are solvable. Alliance Clinical Network offers proven strategies to help sponsors overcome these hurdles.
Contact Alliance Clinical Network today to learn how we can support your next study.
1 Getz, K. (December 1, 2019). Can Recruitment and Retention Get Any Worse? Applied Clinical Trials.
2 Goldman, D., Malzbender, K., Lavin-Mena, L., Hughes, L., Bose, N., & Patel, D. (August 17, 2020). Key barriers for clinical trials for Alzheimer’s disease.
3 Chen X, Chen J, Zhao X, Mu R, Tan H, Yu Z. Issues and Solutions in Psychiatric Clinical Trial with Case Studies. Neuropsychiatr Dis Treat. 2024;20:1191-1200
4 Turner, J. R. (2015). New drug development: An introduction to clinical trials (2nd ed.). Springer International Publishing.
5 Yates, I., Byrne, J., Donahue, S., McCarty, L., & Mathews, A. (2020). Representation in clinical trials: A review on reaching underrepresented populations in research. Clinical Researcher, 34(7).
6 U.S. Food and Drug Administration. (2024, June). Draft guidance for industry: Diversity action plans to improve enrollment of participants from underrepresented populations in clinical studies.