The journey from laboratory breakthrough to a new therapy in a patient’s hands is a marathon, but its first leg—clinical trial start-up—is increasingly becoming an obstacle course of its own.

Study start-up, encompassing feasibility assessments, site selection, contracting, and activation, is a critical gateway. Delays here cascade through the entire development timeline, postponing patient access to potential treatments and inflating costs in an industry where time is literally money. Recent analyses suggest that despite technological advancements, this phase is becoming more protracted, not less.

This trend raises urgent questions for the pharmaceutical and biotechnology sectors. Why, in an era of digital transformation and operational innovation, does it take longer to get a clinical trial off the ground?

To explore this paradox, we examine insights from a recent industry survey conducted by ICON, a global clinical research organization (CRO), and an exclusive interview with Brian Mallon, Executive Vice President of Sites, Patients & Study Start Up at ICON. The survey, capturing the voices of over 100 principal investigators and site personnel, paints a stark picture of persistent bottlenecks. Mallon, drawing on this data and ICON’s extensive operational experience, provides a nuanced diagnosis of the causes and points toward human-centric solutions for breaking the cycle of delay.

The State of Start-Up

ICON’s 2025 industry survey, designed to capture a generalized industry landscape beyond its own studies, quantifies the widespread sentiment of delay. The key finding is stark: 55% of site respondents reported that the time from site selection to full activation takes five months or longer. Furthermore, 39% indicated that activation timelines are longer now than they were two years ago, confirming a worrying trend of regression rather than improvement.

This elongation occurs despite sites being the operational engine of clinical research. As Mallon notes, the survey aimed to amplify “the voice of the site at a site level,” revealing that these crucial partners are facing “heavier operational burdens and more demanding requirements.” The data suggests that operational advances have not kept pace with the growing complexities placed upon trial sites, creating a system where delays are becoming embedded in the process.

Unpacking the Bottlenecks

The survey and Mallon’s commentary point to a confluence of factors, moving beyond simplistic explanations to reveal a multi-layered problem.

1. The Complexity Spiral

The nature of clinical science itself is a primary driver. The survey identified “complex or demanding protocol designs” and “narrowly defined patient populations” as the top two factors contributing to longer timelines, each cited by 50% of respondents. Modern trials, especially in oncology and rare diseases, are scientifically sophisticated but often operationally burdensome.

Mallon expands on this, pointing to “increasing protocol complexity, narrowing of eligibility criteria, [and] much more intensified competition for capable qualified sites and patients.” This creates a perfect storm: sites must navigate intricate protocols for a smaller pool of eligible patients, while competing with other sponsors for the same high-performing investigators. This competition has tangible consequences; pre-selection decline rates—where sites decline to participate before formal selection—rose from 35% in 2021 to 47% in 2023.

2. The Contractual Quagmire

If scientific complexity sets the stage, administrative and contractual hurdles frequently bring progress to a standstill. The survey is unambiguous: 66% of sites experience contract and budget delays “often” or “always,” and 92% cited this area as where sponsors and CROs most need to improve support. Budget negotiations (72%) were ranked the number one barrier to site initiation, with contract finalization close behind (60%).

Mallon acknowledges this as a critical industry-wide issue. “Prolonged contract and budget negotiations are one of the top barriers to site activation,” he states. The traditional process is often sequential and adversarial, treating contracts as “combative adversarial hurdles” rather than enablers. He illustrates a better approach with an anecdote about a major customer’s General Counsel: “What is more important to us is speed than anything else… culturally this is not a combative exercise for us.” This mindset shift, Mallon argues, is as important as technological solutions.

3. The Communication Gap

Closely tied to contractual delays is a failure in fundamental communication. Nearly half (47%) of survey respondents rated sponsor and CRO communication on start-up timelines and support as “average” or “poor”. This gap can erode site confidence and momentum.

Mallon offers a profound diagnosis, quoting George Bernard Shaw: “The single biggest problem in communication is the illusion that it has taken place.” He argues that industry communication has been too “extractive,” focused on what information can be gleaned from sites rather than what sites need from sponsors and CROs. This one-way dynamic fails to build the partnership necessary for efficient start-up. “Clear and consistent communication” was, however, the factor sites most associated with a smooth start-up process, highlighting the yawning gap between expectation and reality.

4. Attrition and the Momentum Paradox

Even after successfully selecting a site, the process remains fragile. ICON data shows that post-selection, approximately 16% of sites in large pharma studies and 23% in biotech studies drop out before activation. Reasons include staffing shortages, competing trials, and the very budget delays already discussed.

Mallon emphasizes that “momentum matters” intensely in study start-up. “If you don’t start with urgency and intentionality and maintain a positive momentum, apathy can creep in,” he warns. A site losing confidence due to slow communication or protracted negotiations is a prime candidate for attrition, forcing sponsors back to square one and compounding delays.

Navigating Imperfection

Both the survey and Mallon’s insights suggest that solving the start-up delay crisis requires moving beyond a purely technological fix to a more nuanced, human-centric operational philosophy.

1. Embracing “Smart” Standardization and Early Partnership

Addressing the contractual bottleneck requires standardization married with flexibility. Mallon points to tools like ICON’s AI-powered SmartDraft, which can learn from historical negotiations to streamline contracting, potentially cutting cycle times by up to 50%. Centralized site networks with pre-negotiated master agreements can also reduce friction.

More fundamentally, it requires engaging sites earlier and more thoughtfully. “We need to probably embrace more flexibility and engagement of sites earlier and probably much more fully,” Mallon advises. This means moving beyond generic feasibility questionnaires to probative conversations: “What do you need, site? What would help with your participation?”

2. Elevating Site-Centricity

For years, the industry mantra has been “patient-centricity.” Mallon and ICON advocate for a dual-focus model that places equal emphasis on “site-centricity.” “Sites are the Nexus by which physicians connect with patients,” Mallon states. Overlooking their experience undermines the entire trial.

ICON’s Accellacare site network exemplifies this. By providing dedicated support, centralized services, and integrated technology to a network of sites, they achieve site initiation visits 58% faster than non-network sites. This focus on reducing administrative burden allows investigators to focus on patient care and trial execution.

3. The Case for Strategic Over-Selection

Given high pre-selection decline and post-selection attrition rates, Mallon advocates for a pragmatic, data-informed strategy of over-selection. “The days of selecting 100% of the required sites rarely guarantees 100% full activation,” he notes. ICON employs a model of selecting roughly 20% more sites than the target, building contingency into the plan from the outset. This “buffer” absorbs attrition and maintains momentum, leading to more predictable and often accelerated delivery.

4. Meeting Sites Where They Are

Mallon’s “wish” for an industry-wide change is elegantly simple: a philosophy of “meeting the sites where they’re at.” This involves integrating sponsor and CRO processes more seamlessly into the existing ecosystems of tools and workflows that sites use daily, rather than forcing sites to adapt to new, additive systems for every trial. It represents a shift from a transactional relationship to a genuine partnership.

From Bottleneck to Launchpad

The data is clear: clinical trial start-up times are increasing under the weight of scientific complexity, administrative bottlenecks, and communication failures. However, as Brian Mallon’s analysis reveals, this is not an intractable problem. It demands a strategic reset that balances operational excellence with human understanding.

The solution lies not in seeking a perfect, frictionless system but in expertly navigating an imperfect one. This requires treating sites as strategic partners, not vendors; leveraging technology like AI to handle repetitive tasks while freeing humans for complex partnership and problem-solving; and, above all, maintaining the momentum that comes from clear communication and shared urgency. By adopting this human-centred approach, the industry can transform the start-up phase from its most stubborn bottleneck into a reliable launchpad, accelerating the delivery of new therapies to the patients who need them.