Sandra Smith, RN, MSN, AOCN, Senior Vice President, Clinical Solutions and Strategic Partnerships at WCG.
Site activation of new clinical trials remains a top priority at most clinical research sites. But there is a disparity in median time for trial activation, defined as time from site selection to completion of contract, across all therapeutic areas. For the past three years, the median timeframe for trial activation for Phase I-III trials at academic medical centers (AMCs) and hospitals was 8.12 months vs. 4.37 months at independent sites/physician practices.1
In a 2018 Association of American Cancer Institutes benchmarking survey on clinical trial operations, 61 cancer center members reported a median trial activation time of 167 days. Guidance from the National Cancer Institute (NCI) suggests a target activation timeline of 90 days.2 Anecdotal reports of trial activation times in 2024 from NCI-designated cancer centers have ranged from 78 days to 313 days.3
Some research sites have unique infrastructure and process requirements for trial activation and they should be specified in the site’s quality management plan. This plan describes the point in time when all requirements have been satisfied and a site may begin to enroll participants in the study. This includes the processes to ensure compliance with trial participant safety, quality, and integrity of the clinical trial data, and compliance with all protocol requirements.
What is included in the site activation time?
This can vary from organization to organization, so sites should be specific when defining what is included to enable fair comparisons with other sites’ reported metrics. AMCs and institutions generally conduct a scientific review of the clinical trial protocol before expending efforts on budgets and contracts.
Scientific Review Committees evaluate new clinical trial opportunities to assess their scientific caliber, study design, and accrual feasibility. Once this determination is made, ancillary review(s) may be required.
Ancillary reviews permit individuals, institutional departments, or other organizationally defined reviewers to give feedback, approval, and/or provide documentation on the protocol. Ancillary reviews may occur in parallel with the ethical review process.
Once a determination is made to proceed with a trial, preparation for ethical and financial administrative reviews begins. Some research sites employ concurrent processes for ethical review, institutional biosafety review (when needed), and financial and contract administration.
Other sites follow a more linear approach. Time also needs to be allocated to create study calendars, budgets, and drug regimens in the site clinical trial management system (CTMS) and/or electronic health record (EHR) before enrolling the first trial participant, often referred to as “first patient/participant in.”
What influences activation time?
Many sites conduct an assessment of available staff time prior to opening a new trial. Some sites use one of a variety of trial complexity tools to assess staff time requirements or make a judgment based on the number of vacant positions.
Staffing challenges have been the number one concern for research sites from 2021-2023.4 All types of positions within clinical research have been impacted from those specializing in regulatory functions to research coordinators and data managers.
Open trials are also taking an average of 10 months longer to close.5 As a result, some sites managing a full trial portfolio may prioritize trials and have one open only after another one closes. The bottom line is that they must ensure they have sufficient staff availability to conduct the trial safely.
In addition to the research team, the identification and/or availability of a principal investigator may contribute to delays in opening a new trial. Recent data has shown a 55% reduction in US investigators from 2018 to 2023.6 In addition, approximately 66% of principal investigators participate in only one clinical trial, often referred to as the “one and done” phenomenon.7
The issue of staff shortages also extends to the specialized functions of creating and executing research budgets and contracts. Research finance competencies differ significantly from traditional healthcare revenue cycle competencies.
Knowledge of how to extract information from the trial protocol to perform a detailed coverage analysis, often referred to as a Medicare coverage analysis, is necessary to parse out elements of the protocol that may be considered routine or standard of care from those that are unique to the research protocol and thereby billable to the clinical trial sponsor. The coverage analysis informs the creation of the clinical trial budget.
Beyond procedures specified in the protocol and protocol-associated documents (exams, pharmacy, imaging, laboratory, etc.), any other required service costs, such as facility overhead and participant stipends, will be detailed in preparation for budget negotiations. With the recent impact of inflation and changing cost structure to conduct clinical trials, the length of time to complete budget negotiations has increased, averaging eight business days longer in 2023 than the previous year.8 Legal departments have also experienced staff shortages, but often the contract language has been agreed to prior to the completion of the budget negotiations, thus delaying the execution of the clinical trial agreements.
Using Lean Six Sigma techniques to process map current state workflows has educated and enlightened many organizations on the complexities of opening a clinical trial. The further application of Lean principles to remove unnecessary steps or waste from the process can significantly reduce the number of days in the start-up process.
Thoroughly documenting tasks and workflows, engaging and gaining buy-in from all teams, and managing the change process are worth the effort, but require time and discipline. Enabling technology (CTMS, eRegulatory binders, eConsent, eIRB, EHR, among others) to support clinical trial processes continues to improve, but there is no magic button (yet) to fully automate the activation process.
Conclusion
The activation of each clinical trial involves hundreds of tasks, along with many dependencies and handoffs, some of which may be automated, but many require manual processes. Research personnel with multiple specialized skill sets are required and must work in an environment of open communication and with an awareness and appreciation of how their role and work impacts the contributions of others in the overall trial activation process. Think of clinical trial activation as a symphony, with each research team (orchestra) member and section contributing to the overall delivery.
“No one can whistle a symphony. It takes an orchestra to play it.” (Halford Luccock)
About the Author
Sandra Smith, RN, MSN, AOCN, Senior Vice President, Clinical Solutions and Strategic Partnerships at WCG.
References
1.WCG Data Intelligence, 2023
2. American Association of Cancer Institutes, April 2023
3. WCG Data Intelligence, 2024
4. WCG Data Intelligence, 2021, 2022, 2023
5. WCG Data Intelligence, 2023
6. WCG Data Intelligence, 2024
7. Tufts CSDD, 2021
8. WCG Data Intelligence, 2024