The Value of Clinical Trial Liaisons in the Drug Development Lifecycle

Credit: Gorodenkoff | stock.adobe.com

The evaluation of the efficacy and safety of novel pharmacotherapeutic agents is contingent upon the careful execution of clinical trials, which relies heavily on the proficiency and expertise of qualified investigative sites. Sites assume a pivotal role not only in ensuring the protection of patient rights, safety, and welfare, but also in upholding the methodological integrity of the clinical investigation—conducting the trial according to the study’s protocol, ensuring the appropriate participants are enrolled, and generating data that are valid and reliable.

Over the past 15 years the number of industry-sponsored clinical trials has increased, with a corresponding increase in demand for patients.^1,2 Clinical trials have also become longer and more complex, often collapsing phases of development and including more sophisticated adaptive designs, interim analyses, intricate randomizations, and novel endpoints tailored to specific therapeutic areas.³

This increased complexity often translates to additional patient recruitment challenges, resulting in fewer eligible participants for a particular study but with no accommodation for enrollment timelines or the financial burden to enroll. Further, while there have been innovations in direct data capture and eClinical technologies that theoretically are meant to reduce site burden, those advances are often offset by the need to implement and integrate multiple clinical and outcome assessment systems within the same trial.

The same can be said for patients, who are asked to comply with longer and more frequent clinic visits as well as additional demands related to the use of technologies for reporting symptoms. All of these factors impact not only recruitment but also retention.

At the same time, the decade-long workforce shortage in clinical research, which peaked during the COVID-19 pandemic and is now at a crisis point,⁴ has affected not only site staffing but also the number of available sites. For example, for every experienced clinical research coordinator seeking work, seven jobs are posted.⁵

As many as 95% of cancer centers have reported staffing issues, and trial accrual rates are down 20% since January 2020.⁶ Constrained resources have adversely affected site ability to deliver clinical trial data for the expanding and increasingly complex pipeline, as evidenced by a 14% decline in the rate of recruitment of oncology and a 54% declined rate for non-oncology clinical trials since 2012.²

Even a decade ago, a staggering 80% of studies failed to meet their enrollment timelines⁷ and the situation has not improved. The multifaceted responsibilities for sites in delivering patients with valid and reliable data in a clinical trial requires substantial dexterity and coordination to navigate the complexities inherent in today's clinical research environment that were not present years ago. These factors clearly highlight an essential need for specialized support.

One example of this specialized support has historically come in the form of medical science liaisons (MSLs), leveraged by the pharmaceutical industry for nearly 60 years to support healthcare providers in the optimal use of marketed medicinal products. MSLs serve as pivotal scientific resources and experts to healthcare providers, functioning as a conduit between key opinion leaders (KOLs), healthcare providers, and the pharmaceutical company, playing a key role in driving scientific exchange that informs clinical practice and medical advancements.

These highly specialized professionals typically hold advanced degrees, with deep expertise in their specific therapeutic areas. The more recent establishment of the clinical trial liaison (CTL) role in the clinical trial setting was modeled after the successful use of MSLs, offering what is now considered important support to investigators.⁸

Therapeutically aligned CTLs mirror their MSL counterparts in their level of expertise and are uniquely positioned to offer expert guidance, help develop strategies, and deliver customized support tailored to each clinical research site and a study’s unique scientific and operational needs. In this capacity, a core strength of CTLs is the direct scientific engagement with study investigators and KOLs (as well as their respective clinical site team members) focused toward enhancing scientific understanding of an experimental therapy’s mechanism of action, its preclinical development background, and serving as subject matter experts for the study’s protocol.

CTLs facilitate peer-to-peer exchanges at the site level to enhance scientific and clinical understanding of complex study protocols, directly improving the identification and enrollment of the right patients. Through active site engagement across the clinical study’s lifecycle, CTLs bring highly specialized knowledge of clinical trial methodology paired with a broad understanding of the many operational details involved in the successful execution of the trial.

CTLs act as strategic intermediaries between multiple key stakeholders within and across trials, including the sponsoring pharma company(s), contract research organizations (CROs), site investigators and their respective site team members, and other potential clinical or diagnostic vendor service organizations. This multidirectional flow of information among all stakeholders facilitates rapid feedback and proactive resolution of issues including but certainly not limited to those related to patient recruitment and helps maintain a high degree of clinical and scientific excellence throughout the study’s lifecycle.

This specialized support goes beyond the role of the clinical research associate (CRA), whose focus is on maintaining regulatory compliance and detailed verification of data collected once subjects are enrolled. While CRAs routinely have patient recruitment discussions with sites, they often have limited time to address the nuanced, site-specific challenges that each trial can present. Specific contributions within and across clinical trials for individual studies and across drug development programs in a given therapeutic area stemming from this caliber of CTL expertise are detailed in the following sections.

Study Design and Feasibility

Therapeutically specialized CTLs offer valuable assessments of study protocol viability, ensuring studies are pragmatic and feasible within real-world clinical trial environments. This insight helps preempt the development of overly complicated or impractical protocols that could impede participant recruitment and study implementation, potentially reducing the need for protocol amendments.

Drawing on their expertise, CTLs can help refine study endpoints, anticipate obstacles, and propose adaptations aimed at enhancing the overall scientific rigor, efficiency, and success of the clinical program. Without a feasible approach to patient participation, trials may face significant hurdles, such as slow enrollment, escalating costs, and the risk of trial failure.

CTLs are also adept at putting protocols into practice within the framework of local standards of care, treatment guidelines, and the patient’s journey through healthcare systems. This proficiency is not only important for successful recruitment of patients but also in their ongoing retention in clinical trials. In this capacity, CTLs play a vital role in laying the groundwork for successful clinical trials and the eventual introduction of new therapies to the market.

Site Selection

Through their established relationships with leading investigators, KOLs, site teams, and clinical trial networks in their therapeutic area, CTLs are instrumental in thoroughly vetting potential sites through their knowledge of the site’s true operational capacity; their specific patient demographics and depth and accessibility of their internal and referral patient database; team proficiency; and past trial performance.

With knowledge of each site’s start-up processes, timelines, and their ability to ensure alignment with study requirements, they are also able to offer valuable input that will result in realistic enrollment forecasting and the scheduling of trial timelines. Following successes in the United Kingdom with introduction of a CTL role, Australia’s National Health and Medical Research Council found employment of CTLs to be a key contributor in reducing delays in clinical trial commencement at the site level.⁹

Enrollment of the Right Participants

Recruiting participants is crucial not only for adhering to study timelines, but also for maximizing signal detection (i.e., the ability to detect a difference between active drug and control). Enrolling the right participants is paramount for meeting objectives of the protocol and confidence of study endpoints—to conclusively ascertain whether the investigational drug demonstrates superior efficacy compared to the control and to accurately characterize safety.

Expert CTLs can function in both capacities, supporting site understanding of patient eligibility from a medical and scientific perspective and serving as strategists for recruitment at the individual site level. CTLs are at the forefront of addressing patient recruitment issues and their expertise in understanding operational workflows, patient pathways, and referral networks help keep investigators engaged with robust patient screening and retention.

Coordinating Trials Across Clinical Disciplines

There is an increasing need to coordinate clinical trials across multiple disciplines within the site due to diverse application of treatment paradigms. For example, chimeric antigen receptor (CAR) T-cell therapies have been approved since 2017 for oncology indications but are now also being developed for cardiometabolic disorders, autoimmune disease, infectious disease, and neurological indications.

While oncologists might be familiar with administering and overseeing the safety of CAR T-cell therapy, it is probable that physicians from other medical disciplines are not familiar with the operational characteristics of this type of treatment modality. Similarly, the management of rare diseases often demands a multifaceted approach involving expertise from various medical disciplines to provide comprehensive patient care.

Although physicians in their individual disciplines may possess experience in conducting clinical trials within their specific areas, there may be a lack of familiarity with cross-team coordination and adherence to the intricacies of protocol-specific procedures in a multidisciplinary setting. CTLs facilitate planning and coordination across clinical disciplines, helping to create new operational and patient workflows to enable successful patient care and protocol adherence during their time in the study.

Increasing Trial Awareness in the Community

Increasing public awareness about clinical trials is vital for advancing medical research and improving patient outcomes by boosting participant recruitment and ensuring diverse study populations.⁹ CTLs can be instrumental in increasing this awareness to further facilitate patient recruitment by addressing the general lack of public understanding of clinical research through connecting and forming relationships with patient advocacy groups (PAGs).

PAGs can be a key element for disseminating knowledge about the significance of clinical research and how trial participants may contribute to medical advancements and personalized treatment options. Through community outreach, CTLs also further foster inclusion, diversity, and broad patient outreach.

Summary

When utilized correctly, CTLs are much more than “recruitment ambassadors” for individual studies, but rather serve as experts in their therapeutic areas and as clinical trial specialists. Their advanced educational background and specialization enables CTLs to provide a suite of strategic advantages to benefit a study, including:

• More effective site identification and selection based on their knowledge of site capabilities and anticipated protocol challenges, as well as engaging a broader pool of potential sites and/or preparing research-naïve clinicians to undertake clinical research.
• Cultivation of deeper site relationships that extend beyond a single trial, serving as a strategic site relationship manager and an alternative and consistent contact point.
• Collection and assimilation of feedback and insights gained across multiple studies in a therapeutic area.
• Identification of challenges across sites and serving as a “problem solver” for sites.
• Improvement of project team and CRA readiness through enhanced protocol training.
• Strengthened collaboration and dialogue among different functional teams involved in trial management.
• Foreseeing and proactively managing site performance issues to maintain study timelines and quality.
• Providing scientific and operational input during protocol development given their strong understanding of clinical trial methodologies, regulatory feedback, and innovative designs within their therapeutic areas.
• Improved study planning through the use of their comprehensive understanding of the competitive landscape of clinical trials in their therapeutic area.
• Facilitation of patient recruitment through their understanding of local standards of care and the patient treatment journey within their specific areas of focus and geographic regions.

When taken together, CTLs support successful trial execution operationally and provide assurance of overall quality of study outcomes.

References

1. World Health Organization. Number of clinical trial registrations by location, disease, phase of development, age and sex of trial participants (1999-2024). December 2024. https://www.who.int/observatories/global-observatory-on-health-research-and-development/monitoring/number-of-trial-registrations-by-year-location-disease-and-phase-of-development.
2. Agrawal G, Kautzky J, et al. Accelerating clinical trials to improve biopharma R&D productivity.McKinsey & Company, 22 January 2024.https://www.mckinsey.com/industries/life-sciences/our-insights/accelerating-clinical-trials-to-improve-biopharma-r-and-d-productivity (accessed 30 Dec 2024).
3. Markey N, Howitt B, El-Mansouri I, Schwartzenberg C, Kotova O, Meier C. Clinical trials are becoming more complex: a machine learning analysis of data from over 16,000 trials. Sci Rep. 2024 Feb 12;14(1):3514.
4. Freel SA, Snyder DC, Bastarache K, Jones CT, Marchant MB, Rowley LA, Sonstein SA, Lipworth KM, Landis SP. Now is the time to fix the clinical research workforce crisis. Clin Trials. 2023 Oct;20(5):457-462.
5. Mills N, Vulcano D. Exploring the current clinical workforce. Society for Clinical Research Sites (SCRS). 22 July 2022.https://myscrs.org/resources/sites-now/exploring-the-current-clinical-workforce/ (accessed 30 Dec 2024).
6. Amorosi D. Cancer clinical research in crisis as staffing shortage hits ‘‘critical breaking point.’’HemOnc Today, 18 August 2022, https://www.healio.com/news/hematology-oncology/20220818/cancer-clinical-research-in-crisis-as-staffing-shortage-hits-critical-breaking-point (accessed 30 Dec 2024).
7. Danfield R. New role to improve clinical trial performance. Applied Clinical Trials, 19 October 2017, https://www.appliedclinicaltrialsonline.com/view/new-role-improve-clinical-trial-performance (accessed 30 Dec 2024)
8. Syneos Health. 2025 Health Trends Report.Syneos Health, 19 Dec 2024.https://www.syneoshealth.com/insights-hub/2025-health-trends (accessed 07 Jan 2025).
9. National Health and Medical Research Council. Streamlining the site assessment and authorization of clinical trials: final report.June 2017. https://www.nhmrc.gov.au/about-us/publications/nhmrc-good-practice-process-site-assessment-and-authorisation-clinical-trials (accessed 07 Jan 2025).