Clinical trials are vital for medical advancement, but a major challenge is non-enrolling sites—locations that are activated yet fail to enrol participants. This delays important research and incurs significant costs. We will examine the impact of these non-enrolling sites and discuss strategies to address the issue.
The Scale of the Problem
The prevalence of non-enrolling sites is alarming. Nearly one-third of sites in clinical trials fail to enrol a single patient, with some regions seeing non-enrollment rates as high as 40%[1]. This inefficiency leads to significant financial losses, as the cost of initiating a site ranges from $20,000 to $30,000, with an additional $1,500 per month for maintenance[1].
The Financial Burden
The financial implications of non-enrolling sites extend far beyond the initial setup costs. Studies have shown that 80% of trials experience delays of at least a month, resulting in potential losses of approximately $600,000 to $8 million per day[4]. These delays not only increase direct costs but can also lead to:
- Wasted drug supplies
- Loss of clinical sites due to competing studies
- Delayed access to treatment for patients
Moreover, the cost of replacing patients lost due to non-compliance is substantial. While it costs an average of $6,533 to recruit one patient to a clinical study, the cost of replacing a patient is nearly triple at $19,533[4].
The Ripple Effect on Trial Efficiency
Non-enrolling sites contribute to a broader issue of decreased trial efficiency. Recent data shows a concerning trend:
- Recruitment duration for industry-sponsored phase III clinical trials has increased significantly from an average of 13 months in 2008-2011 to 18 months in 2016-2019[5].
- The number of registered sites per clinical trial has increased by more than 30% during the last 12 years, from a median of 43 sites in 2012-2015 to 64 sites in 2016-2019[5].
- Despite the increase in sites, the number of participants enrolled in clinical research has decreased significantly[5].
These findings suggest that recruitment for phase III clinical trials is less effective today compared to 12 years ago, highlighting the need for more efficient site selection and management strategies.
Factors Influencing Site Performance
Understanding the factors that contribute to site performance is crucial for addressing the issue of non-enrolling sites. The Survey of Attitudes towards Trial sites in Europe (SAT-EU Study) revealed some interesting insights:
- Investigator-dependent, environment-dependent, and hospital-dependent factors were rated as highly important in site selection[2].
- Within environment-driven criteria, the pool of eligible patients, speed of approvals, and presence of disease-management networks were significantly more important than costs or government financial incentives[2].
- Costs were considered less important in site selection, contrary to common belief[2].
Strategies to Overcome Non-Enrolling Sites
1. Data-Driven Site Selection
Use analytics and machine learning to identify sites with higher enrollment potential based on historical performance and relevant factors.
2. Early Identification of At-Risk Sites
Implement real-time monitoring systems to detect underperforming sites early, allowing for timely interventions.
3. Personalized Site Support
Provide tailored assistance to sites based on their specific challenges, including additional training or recruitment strategy adjustments.
4. Streamlined Approval Processes
Harmonize and expedite approval processes across regions to enhance site efficiency and attractiveness.
5. Enhanced Visibility of Centers of Excellence
Promote and support high-performing centers to attract investigators and patients.
6. Patient-Centric Trial Design
Incorporate patient perspectives in trial design to improve recruitment and retention, such as minimizing visit burden and offering virtual options.
Cost of Delays (Tufts CSDD Studies) [4]
According to Tufts Center for the Study of Drug Development (CSDD), delays in clinical trials can result in significant financial losses:
- Phase II trials: $600,000 per day in lost opportunity costs.
- Phase III trials: Up to $8 million per day in lost opportunity costs.
These figures underscore the critical importance of addressing non-enrolling sites and improving overall trial efficiency. The substantial daily losses emphasize the need for proactive strategies to minimize delays and optimize site performance throughout the clinical trial process.
The Future of Clinical Trial Site Management
As the clinical trial landscape continues to evolve, the ability to manage and optimize site performance becomes increasingly critical. The traditional reactive approaches to non-enrolling sites are no longer sufficient in today's complex and competitive environment.
By leveraging innovative technologies, data-driven insights, and patient-centric approaches, the industry can work towards more efficient and effective clinical trials. This not only reduces the financial burden associated with non-enrolling sites but also accelerates the development of new treatments, ultimately benefiting patients who are waiting for these potentially life-changing therapies.
Sources
[1] Understanding site variability in a multisite clinical trial of a ... https://pmc.ncbi.nlm.nih.gov/articles/PMC8459398/
[2] Factors influencing clinical trial site selection in Europe - PubMed https://pubmed.ncbi.nlm.nih.gov/24240138/
[3] How to Proactively Overcome Issues of Non-Enrolling Sites - PPD https://www.ppd.com/blog/overcome-issues-non-enrolling-clinical-research-sites/
[4] The True Cost Of Patient Drop-outs In Clinical Trials - mdgroup https://mdgroup.com/blog/the-true-cost-of-patient-drop-outs-in-clinical-trials/
[5] Changes in key recruitment performance metrics from 2008–2019 in ... https://pmc.ncbi.nlm.nih.gov/articles/PMC9321424/
[6] 7 factors that impact clinical trial patient recruitment - Antidote.me https://www.antidote.me/blog/7-factors-that-impact-patient-recruitment
[7] Non-Adherence: A Direct Influence on Clinical Trial Duration and Cost https://www.appliedclinicaltrialsonline.com/view/non-adherence-direct-influence-clinical-trial-duration-and-cost
[8] The Cost of Delaying A Trial | Pharmasols https://pharmasols.com/news/april-2021/the-cost-of-delaying-a-trial/
[9] Sites per clinical trial started worldwide by phase 2015-2020 - Statista https://www.statista.com/statistics/1249066/average-number-sites-per-drug-trial-started-by-phase-worldwide/
[10] Factors influencing clinical trial site selection in Europe - BMJ Open https://bmjopen.bmj.com/content/3/11/e002957
