The following Insight is a featured article from WCG’s 2025 Trends & Insights Report. If you would like to read more insights from this report, please click here.
As we enter 2025, clinical research sites face an increasingly dynamic and complex environment. In the recently released WCG 2024 Clinical Research Site Challenges Report, we collected data from a variety of sites on the headwinds and obstacles they faced in 2024. Notably, the operational challenges sites face due to the increasing complexity of studies and the obstacles in the study start-up process, resulting in lengthy timelines, emerged among the top five trends. The operational and strategic choices sites make this year will define their ability to thrive in an era of adaptive trial designs, cutting-edge therapies, and heightened expectations for efficiency.
Study Activation: Breaking the Barriers
For many sites, the gold standard of study activation is the National Cancer Institute’s recommended 90-day “time to activation,” which is defined a bit differently by each institution. Even for sites not conducting a large volume of oncology studies, most sites target 90-120 days for their end-to-end start-up timeline. Often, looking at the median time to activation can be most helpful when understanding where a site currently stands but may lead to further investigation into outliers in the upper range, dragging down the overall average. So, how does a site prepare for a high degree of accountability in this ever-changing landscape?
When it comes to complexity within the start-up process, few trials set the bar higher for sites than cell and gene therapy (CGT) studies. In the coming year, clinical trials involving CGT products are expected to play an important role in the development of new therapies in an expanding range of therapeutic areas. For example, some CD19-directed therapeutic approaches developed for hematology/oncology indications are being repurposed for the treatment of autoimmune diseases, such as lupus, and many of these clinical trials will begin in 2025.
Sites wishing to prepare for CGT research can take a variety of approaches. Any sites looking to become involved in CGT clinical trials should have an Institutional Biosafety Committee (IBC) registered with the NIH. Although approaches involving the manufacture of autologous cellular products can require a large investment in facilities, staffing, and training, many other CGT approaches can be undertaken with relatively small changes to equipment and procedures. For trials involving complex manufacturing and clinical management, new sites may wish to partner with larger, more experienced sites to enroll subjects in a “hub-and-spoke” model.
Aside from the regulatory consequences, we have repeatedly seen the impact these challenging trial designs, like cell and gene therapies, can have on study start-up. A seemingly straightforward schedule of events can cascade into a web of extensive start-up tasks that impact the overall activation timeline.
The operational complexity of CGT trials, for instance, often requires large, multi-disciplinary teams with expertise in areas like advanced storage solutions, patient-specific customization, and specialized clinical protocols. This complexity can lead to longer trial start-up times as every step builds on prior activities, impacting the activation timeline and trial readiness. And in advanced therapeutic trials, start-up challenges are compounded by regulatory hurdles and site selection requirements. CGT trials in particular are known for their lower throughput compared to traditional trials due to the bespoke nature of the therapies.
For example, a single line item in the schedule of events, such as “patient assessment,” can expand into numerous detailed entries in a Medicare Coverage Analysis (MCA). When closely examined, this single procedure can encompass a wide array of specific tasks and requirements. For instance, a “patient assessment” could be parsed into distinct components like physical examinations, laboratory tests, imaging studies, and specialist consultations. Each of these components then needs to be analyzed in terms of cost, frequency, whether it qualifies as routine clinical care or a research-specific expense, specific billing codes, compliance with Medicare regulations, and which entity — sponsor or payer — bears the financial responsibility.
Often, however, the sponsor-provided budget aligns differently from this detailed breakdown, as sponsors typically base budgets on overarching categories, overlooking the specifics uncovered during the MCA process. This budgetary misalignment can necessitate additional financial negotiations and adjustments, complicating the initial planning phase and extending activation timelines by weeks or even months.
Integrating the MCA and final approved budget/Clinical Trial Agreement (CTA) into a Clinical Trial Management System (CTMS) presents another layer of complexity. Harmonizing the study calendar with the financials becomes a meticulous task, requiring an accurate reflection of every line item to ensure clinical and financial schedules match. Any discrepancies in the system can lead to budget inaccuracies, compliance risks, and logistical challenges. Consequently, this rigorous process underscores the necessity for meticulous coordination and continuous communication among all stakeholders to achieve a seamless start without significantly impacting study activation timelines.
Budget Negotiations: The Hidden Bottleneck
One specific piece of the process we’ve identified as typically having some of the greatest flexibility — for better or worse when it comes to the overall timeline — is budget negotiations. They are often the rate limiting step that extends start-up timelines beyond intended targets. Given the total dollar figures represented in many clinical trial budgets, this isn’t a surprising fact on its own.
The “white space,” which we define as the unproductive time spent between active review, is a significant factor in extending the budget timelines. This is the time spent with any party waiting for approval, sitting in someone’s queue for review, or waiting to schedule a follow-up call.
We see that negotiations take 5-10 hours of active effort for a site negotiator. Allowing for a similar amount on the sponsor’s side, that is 10-20 hours of total effort for a process that can often extend 9+ weeks. In that scenario, the budget is actively being worked on for less than 6% of the time over those 9 weeks.
For organizations looking to reduce start-up timelines, the goal becomes clear: focus on reducing the white space. Each party can control a portion of this by limiting their own response timelines. Beyond that, you can influence white space on the other end by making it as easy as possible for the other party to review. Providing upfront justification, using standard editing practices like color coding, and employing a clean-as-you-go approach can all help eliminate confusion and prioritize your budget in what is often a large queue.
Most importantly, know your limits and communicate that early. It’s common to see parties prolong negotiations but then agree to a budget on day 100 that isn’t materially different from the budget offer on day 50.
The intricate network of activities involved in clinical trial start-up highlights the importance of meticulous planning, detailed analysis, and ongoing coordination among all stakeholders. Successfully navigating these complexities is essential for timely study activation and overall trial success. Through continued process reviews, stakeholder collaboration, and effective communication, the potential delays in study activation can be mitigated, paving the way for a seamless and efficient trial.
The Human Side of Research: Supporting Teams
Though we focus heavily on the metrics and data of what we do as an industry, we’d be remiss not to acknowledge the softer side of research. While serving participants and prioritizing their health is the north star of our work, so must be the wellness and health of our colleagues. While the impact of the Great Resignation has diminished, the risk of site staff burnout is real so supporting and equipping a high-performing team for success is critical to site excellence and individual motivation.
Developing team camaraderie requires taking the time to develop an environment of trust where members feel valued and connected to each other and the goals of clinical research. This is the “secret sauce” that can propel a site from being adequate to high performing. All too often it is expected that as professionals we will naturally come together as a team and foster motivation in each other. Yes, sometimes that occurs organically and with a little extra work, but attention is generally required. This means having meetings with explicit discussions about building mutual trust – based on open and honest communication. The leaders at the site need to share challenges and mistakes and be willing to seek help and ideas from staff. This type of vulnerability demonstrates from the top down that team members are valuable. This type of safe environment will empower your team to act decisively and collaborate.
Making sure there are some enjoyable “outside work” activities for team members to enjoy will also help to create a strong team. These activities do not have to be grand in nature. More casual outings can accomplish the goals of increased social interaction and recognition of team member accomplishments. The very nature of our work in helping to develop medicines, devices, and other treatments for diseases is compelling and should be reinforced as a part of your team’s development plan.
High-functioning teams deliver better results and enhance a site’s reputation, making it more attractive to sponsors and top talent. Ultimately, this balance between operational excellence and human connection will define the most successful sites in the evolving clinical research landscape.
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