Why Site-CRO Relationships Are So Strained — And How To Fix Them
By Denise Bronner, founder, Empacftul Ventures
CROs have become integral to the pharma industry by providing a wide range of services that span the entire life cycle of clinical trials. As of 2023, close to 50% of clinical trial expenditures were allocated to outsourced services1. From study design to regulatory submissions, CROs play a vital role in ensuring that trials are conducted in compliance with global standards and regulations. Their expertise allows pharma companies to focus on drug development while outsourcing the complex operational aspects of running a clinical trial.
One of the key benefits of working with CROs is their ability to scale resources quickly. This is particularly valuable for pharma companies running multiple trials across different geographies. CROs also bring specialized knowledge in navigating regulatory landscapes, streamlining processes, and optimizing trial timelines. Their global networks enable sponsors to reach diverse patient populations, a necessity in today’s regulatory climate that emphasizes the need for more inclusive trial populations.
Despite these advantages, the increasing reliance on CROs has led to new challenges, particularly in their relationships with clinical trial sites. The imbalance between CROs' alignment with sponsor interests and site needs often fuels conflict, hindering trial progress and effectiveness. Understanding the root causes of these strained relationships is essential for rebuilding trust and improving collaboration.
Why Relationships Between CROs And Sites Have Become Strained
Relationships between CROs and clinical trial sites have become increasingly strained due to operational, communication, and support challenges. A significant source of tension stems from complicated and time-consuming contracting processes. A 2022 study conducted by ZS Associates on Site & Patient Voice found that 59% of sites expressed that contracting processes are often delayed and inefficient, largely because of the involvement of too many third parties, including CROs2. The complexity of this process can lead to frustration, especially when multiple intermediaries add layers of bureaucracy that slow down trial progress.
Communication breakdown is another critical issue, with 52% of sites dissatisfied with how communication is handled2. Sites often find themselves repeating the same information to multiple contacts from the same sponsor or third-party vendor, a practice that results in confusion and inefficiency. This fragmented communication, driven by the multiple layers of CRO management and sponsor oversight, leaves sites feeling unsupported and disconnected from the core decision-making processes of the trials.
Operational pressures further exacerbate these tensions. CROs, operating under strict deadlines from sponsors, frequently pass this pressure down to the sites, often without providing adequate support. Over 50% of sites report frustration with the lack of support and the complexity of challenging protocols imposed by sponsors2, which can make adhering to study requirements more difficult. These burdens can lead to inefficiencies in patient recruitment, data collection, and adherence to protocols, further straining the relationship between sites and CROs.
Compounding these issues is the misalignment of priorities between CROs and clinical sites. CROs are primarily accountable to sponsors and are driven by the need to meet sponsor timelines and budgets. On the other hand, clinical trial sites are more focused on patient care and data integrity, often perceiving that CROs prioritize sponsor demands over the quality of patient care and trial outcomes. This divergence in priorities can lead to mistrust and reduced cooperation, especially when sites feel their needs are secondary to the CRO's objectives.
High staff turnover and inexperience among CRO personnel contribute to further strain. The constant rotation of staff members within CROs results in inconsistencies in trial management and communication. New or inexperienced staff may be less familiar with the specific requirements or protocols of the trials, leaving sites to compensate for these gaps in knowledge, which can cause delays and errors. Sites may feel burdened by the need to correct these mistakes, further damaging the relationship.
Finally, CROs may set unrealistic expectations for sites in areas like patient recruitment or protocol adherence, often without considering the unique challenges individual sites face, such as staffing issues or regional differences in patient populations. When sites are unable to meet these expectations, it can lead to frustration and blame-shifting, with both parties feeling that the other is responsible for delays or inefficiencies. These unrealistic demands only deepen the disconnect between CROs and the sites, further complicating an already fragile relationship.
The Role Of Bias & Heuristics In CRO-Site Tensions
In addition to operational and communication challenges, unconscious biases3,4 play a significant role in shaping the dynamics between CROs and clinical trial sites. These biases can affect how CROs and sites perceive one another, leading to misunderstandings, misjudgments, and tensions that hinder collaboration. Here are some key unconscious biases that contribute to these issues:
1. Confirmation Bias – Enrollment Performance & Legacy Sites
CROs may exhibit confirmation bias by favoring sites that have previously performed well in patient enrollment, assuming that their past success guarantees future results. This bias can lead to an over-allocation of resources to larger or historically high-enrollment sites, while smaller or newer sites are overlooked. Even if these less experienced sites have the potential to perform well in the current trial, they may not receive the necessary support or attention. This selective focus on past performance can create imbalances and cause smaller sites to feel undervalued.
Another example is when sponsors continue to recommend legacy sites that have been involved in previous trials, despite CROs suggesting more suitable or capable sites for the current study. Sponsors might default to legacy sites out of loyalty or habit, even if those sites do not align with the trial's specific needs or enrollment targets. This can lead to tensions between CROs and sponsors, as the CRO may feel that the sponsor’s preferences are hindering trial efficiency.
2. Base Rate Neglect – Site Attributes
Base rate neglect occurs when CROs ignore the overall likelihood of site performance across various types or regions. For instance, CROs may overestimate the competence of academic sites, viewing them as more prestigious or capable, while underestimating non-academic sites or those located in less familiar geographies. This bias leads to unequal treatment, where academic or well-known sites receive more resources, training, and trust, even if the actual performance of non-academic or geographically diverse sites matches or exceeds expectations. The CRO’s focus on affiliation or location overshadows the broader evidence of these sites' capabilities.
3. Outgroup Bias – Perception of CROs
From the perspective of clinical trial sites, CROs are often seen as an outgroup, while the sponsor represents the ingroup. Sites may trust sponsors more due to long-standing relationships or shared objectives, perceiving the sponsor as more authoritative and aligned with their goals. Conversely, CROs are viewed as external intermediaries with less understanding of the site's specific needs. This outgroup bias can lead to sites being less cooperative with CROs, resisting their oversight or disregarding their requests, potentially slowing down trial progress.
4. Authority Effect – Perception Of Pharma Sponsors
Authority bias refers to the tendency to favor instructions or input from perceived authorities. In the context of clinical trials, sites often view the sponsor as the ultimate authority, valuing their guidance more than that of the CRO. Sites may be more responsive to the sponsor's requests, even when the CRO is tasked with managing day-to-day operations. This bias can undermine the CRO’s role and lead to inefficiencies, as sites may bypass CRO processes or delay responses, waiting for direction from the sponsor.
5. Availability Heuristic – Historical Experiences With CROs
Sites may exhibit availability heuristic by placing disproportionate weight on previous negative interactions with a CRO, such as delays, miscommunications, or perceived micromanagement. Even if the CRO has improved its processes or is performing well in the current trial, sites might still view them with skepticism and assume future issues will arise. This bias can strain relationships and reduce trust, as sites remain focused on past grievances rather than current performance or improvements.
Strategies For Rebuilding Trust And Improving Collaboration
Rebuilding trust between CROs and sites is critical for advancing the success of clinical trials. Sponsors are uniquely positioned to help create emotionally significant, positive examples that shift perceptions. One key approach is strengthening communication and ensuring transparent, consistent dialogue through frequent updates. This not only counteracts confirmation bias but also makes room for memorable positive interactions. Implementing robust feedback systems allows sites to feel heard and engaged, enhancing trust through responsive and efficient communication.
CROs and sponsors can combat confirmation and outgroup bias by shifting their focus from familiar high-enrollment sites to embracing the potential of new or smaller sites. Countering stereotypes with real examples — such as a new site delivering exceptional results in its first year — helps reframe assumptions. Providing all sites with equal access to resources like training, technology, and staffing sends the message that any site can be successful, regardless of past performance. Additionally, emphasizing shared goals, such as a passion for advancing science and improving patient outcomes, helps bridge gaps and foster collaboration.
Addressing base rate neglect and authority effect requires sponsors to ensure that CROs and sites are aligned on shared goals like high-quality patient care and accurate data collection. Probing questions, such as “How many sites have historically achieved these outcomes?” can help combat base rate neglect by promoting realistic expectations instead of relying on biases tied to site affiliation or geography. Additionally, sponsors must address the authority effect, where sites may see sponsors as more authoritative than CROs. Emphasizing collaboration and equality between CROs and sites ensures mutual respect and helps create a more balanced working relationship. By setting clear expectations and highlighting the importance of each party, sponsors can mitigate friction and encourage stronger, more cohesive trial operations.
Encouraging stability and consistency in CRO staffing helps address both availability heuristic and outgroup bias. High turnover rates within CROs can lead to negative perceptions of their competence, especially if sites have experienced issues in the past. By investing in staff retention and ensuring well-trained personnel, sponsors can help CROs build stronger, more consistent relationships with sites, reducing the likelihood of errors or miscommunications that fuel negative biases. This consistency fosters familiarity and reduces the perception of CROs as an external, unfamiliar entity (the outgroup), instead positioning them as trusted partners in the trial.
Finally, sponsors fostering a culture of collaboration with CROs can encourage sites to embrace a more open, collaborative engagement approach. Sponsors can promote joint training sessions, workshops, and team-building activities that bring CRO staff and site personnel together, helping to break down barriers and foster a true sense of partnership. By encouraging collaboration and teamwork, sponsors can address the entrenched bias of relying on familiar sites or routines, making way for more innovative and inclusive trial operations.
A Path Forward For Stronger CRO-Site Collaborations
Collaboration between CROs and sites is essential for the future of inclusive and efficient clinical research. As the FDA emphasizes the importance of diversity in clinical trials, particularly for underrepresented groups, it becomes clear that strong partnerships between CROs and sites are key to achieving this goal5. CROs, with their global reach and patient recruitment expertise, play a vital role in reaching these diverse populations, but their success hinges on close cooperation with sites. Sites, often embedded in local communities and healthcare networks, are uniquely positioned to recruit patients from underrepresented populations. When CROs collaborate with these sites, leveraging their local relationships and respecting their expertise, they open the door to more effective and inclusive recruitment efforts.
Rebuilding trust between CROs and sites is not only an operational need but a strategic imperative for ensuring the success of clinical trials. Miscommunication, lack of support, and operational pressures have strained these relationships, yet overcoming these issues is critical as the pharma industry faces growing demands for efficiency, regulatory compliance, and diverse patient participation. Sponsors are uniquely positioned to serve as the bridge between CROs and sites, fostering a culture of collaboration that can rebuild trust. By ensuring that CROs provide equitable support to all sites — regardless of size or location — sponsors can counteract biases that favor legacy sites and larger institutions. Open, consistent communication channels must be established to address the frustrations that arise from repeated information sharing and fragmented decision-making. Regular, transparent updates and feedback mechanisms can give sites a greater voice in trial operations, shifting the dynamic from one of frustration to one of partnership.
Ultimately, building stronger ties between CROs and sites is not just about improving trial efficiency — it is about fostering a collaborative environment where all parties feel respected, supported, and aligned toward the same goal: delivering lifesaving treatments to diverse patient populations. As the industry moves forward, this spirit of partnership will be critical to overcoming both the logistical and perceptual barriers that have long hindered clinical trials. With a renewed commitment to collaboration, the future of clinical research can be more inclusive, more effective, and better equipped to meet the challenges of a rapidly evolving healthcare landscape.
References:
- How Clinical Trial Trends are Redefining Drug Development
- 2022 ZS Associates Voice of Sites & Patients Report
- List of cognitive biases
- Raymond, J. Most of us are biased. Nature (2013)
- Updated FDA Guidance on Diversity Action Plans (June 2024)
About The Author:
Denise N Bronner, Ph.D. has roughly 15 years of organizational thought leadership experience within the global healthcare space and has held various roles in academia, consulting, pharma, and venture capital. During her career, she has specialized in health equity, data-driven global therapy program strategy development, pitch and storytelling refinement, and identifying business opportunities within pharma. Beyond her professional endeavors, she's passionate about enhancing diversity in STEM fields, serving on advisory boards, participating as a judge in pitch/business competitions, and mentoring young professionals. She holds a bachelor’s degree in Biological Sciences from Wayne State University, a Ph.D. in Microbiology & Immunology from the University of Michigan - Ann Arbor, and certification from the Venture Capital Executive Program from UC Berkeley Haas School of Business. She is the founder of Empactful Ventures which currently consults healthcare-focused startups and venture funds, and she is a member of the Clinical Leader editorial board.