Clinical Researcher—October 2025 (Volume 39, Issue 5)
PEER REVIEWED
Justin Scott Brathwaite, MBA; Nirmal Rajasekaran, PhD;
Milan Sheth, MS
The Growing Demands of Modern Clinical Research
Clinical trials have become more complex, due to myriad factors including rising protocol demands, the adoption of decentralized models, and the integration of artificial intelligence.{1} While these innovations promise greater personalization and operational efficiency, they also introduce new layers of logistical and regulatory complexity. For instance, a 2021 analysis by the Tufts Center for the Study of Drug Development highlighted key shifts in trial design between 2015 and 2021. During that span, the average number of endpoints in Phase III trials rose by nearly 40% to 25.8 per study.{2} This additional complexity places heavier demands on already resource-constrained clinical trial sites, which must manage patient screening and enrollment while maintaining strict adherence to the study protocol.{3}
Moreover, clinical trials have also become longer, with the most substantial increases occurring during study startup—specifically within the duration from protocol approval to first patient enrolled.{2} Protracted study timelines—driven partly by increasing clinical trial complexity—elevate operational costs and intensify pressure on sponsors and contract research organizations (CROs) to meet key milestones. Hence, sponsors and CROs should collaborate to design site-centric processes that reduce operational burden, streamline communication, and allow research teams to focus more on patient care and data quality.
Strategic Sponsor-CRO Partnerships: The Key to Addressing Clinical Development Challenges
In today’s complex pharmaceutical landscape, the relationship between sponsors and CROs has evolved significantly. It is no longer a simple vendor-client transaction, but rather a strategic alliance that plays a crucial role in shaping the success or failure of the clinical trial. As clinical development becomes more demanding, many sponsors are turning to CROs not just for execution, but for their specialized knowledge and strategic capabilities.{4}
Today’s CROs offer expertise in therapeutic areas, regulatory navigation, and global operations—skills that can be challenging and costly for certain sponsors to sustain internally.{5} Increasingly, sponsors are seeking partners who can deliver fully integrated, end-to-end solutions, particularly in the development of advanced or cell-based therapies that require customized support from early-phase research through market readiness.{6} This shift has led to a greater emphasis on strategic collaboration and early engagement. Rather than viewing CROs purely as vendors, sponsors are involving them earlier in the drug development lifecycle—sometimes as early as the discovery phase.{7,8}
Whether an emerging biotech or a global pharmaceutical leader, selecting the right CRO partner is among the most critical decisions in clinical development. Such partnerships must be grounded in mutual trust, shared objectives, and a commitment to patient welfare, all while striving to drive operational efficiency, maintain scientific rigor, and ensure timely trial completion.{9}
Modern clinical trials have grown increasingly sophisticated—often spanning global regions, involving multisite coordination, and integrating complex protocols with advanced digital technologies. These dynamics underscore the importance of early and strategic alignment between sponsors and CROs, fostering partnerships that go beyond traditional contractual relationships. Early collaboration may include joint efforts in protocol development, site feasibility assessments, and risk mitigation planning, all of which can contribute to more efficient trial activation and execution. Still, the degree of early involvement varies, shaped by each sponsor’s internal capabilities, therapeutic focus, and broader development strategy.
Another core element of successful partnerships is establishing strategic alignment from the outset, with clear agreement on core objectives such as accelerating time-to-market, managing costs efficiently, and ensuring regulatory compliance. Creating this shared vision is vital to guarantee that both sponsor and CRO are focused on the same goals. This alignment is strengthened by clearly defined roles, specific milestones, and measurable accountability throughout the trial’s entire duration.
Equally critical is the implementation of robust communication and comprehensive risk mitigation strategies. Effective partnerships incorporate structured protocols for regular progress reviews, early risk identification, and dedicated liaison teams, and collaborative governance structures like steering committees are essential. Because clinical trials are often unpredictable, with mid-study protocol amendments, evolving regulatory requirements, and inconsistent patient enrollment, having structured processes in place is essential to protect study integrity, ensuring adherence to timelines and maintaining continuous strategic alignment with sponsor goals.
From a sponsor’s perspective, high-performing CROs are highly valued because they offer a strategic edge in managing the growing complexity of today’s clinical trials. These CROs distinguish themselves by actively adopting scientific and technological innovations, such as artificial intelligence (AI)–driven analytics to optimize patient recruitment and risk monitoring and real-time data integration to enhance oversight and decision-making.
At the same time, regulatory compliance remains non-negotiable, with strict adherence to the International Council for Harmonization’s (ICH’s) Good Clinical Practice guideline, U.S. Food and Drug Administration and European Medicines Agency standards, implementation of risk-based monitoring, and enforcement of robust data integrity protocols to minimize the risk of costly errors and delays. Financial transparency further strengthens sponsor confidence, with models that incorporate performance-based contracting and cost optimization strategies, including efficient site selection and resource allocation.{10,11}
The financial stakes for sponsors are significant. Poor CRO selection can result in delays costing more than $500,000 daily in lost revenue and jeopardize regulatory approvals, while competitors advance on expedited timelines.{12} Conversely, high-performing CRO partnerships accelerate enrollment, enhance data quality, and improve return on investment by streamlined operational execution. Hence, the most successful collaboration lies in partnerships that function as true extensions of the sponsor’s internal team, emphasizing shared risk ownership, fostering long-term relationships, adopting innovative contracting models such as gain-sharing, and prioritizing patient-centric trial designs.
Adapting the Workforce: How ICH E6(R3) is Reshaping Clinical Roles and Sponsor-CRO Synergy
Recent updates found in the ICH E6(R3) Good Clinical Practice guideline catalyze the ongoing technological transformation in clinical trials by explicitly recognizing and encouraging the judicious integration of digital tools within trial design and execution. We suspect these changes will have downstream effects that may influence how clinical research roles are conducted. For instance, CRO teams are increasingly expected to achieve more with fewer resources, requiring both operational agility and technical fluency.
Given these variables, it is plausible that hybrid roles may become more prevalent in clinical operations, blending traditional responsibilities with advanced data analysis and AI-driven insights. Moreover, it is even conceivable that new roles will emerge, combining expertise in data science, regulatory strategy, and patient engagement to drive smarter, faster, and more patient-centered research.
This shift will inevitably require sponsors and CROs to collaborate more closely, ensuring that technology platforms, data pipelines, and operational frameworks are seamlessly integrated. Strategic partnerships will need to prioritize workforce upskilling and cross-functional training, enabling teams to harness AI-generated insights effectively. Moreover, the increased reliance on real-time data and predictive analytics will encourage CRO-sponsor alliances to move from reactive problem-solving to proactive decision-making, further strengthening their role as innovation partners rather than transactional vendors.
From the Ground Up: A Site Perspective on Enabling Trial Excellence
At the site level, sponsor-CRO collaboration plays a critical role in driving trial efficiency, data quality, and patient care—particularly in high-acuity fields like oncology. Drawing on experience within academic research environments, the following site-level perspective highlights where sponsor-CRO partnerships add value, where operational gaps persist, and what is needed to support high-performing, patient-centered trials.
Within leading academic institutions, sponsor-CRO partnerships have a direct and measurable impact on how effectively trials are conducted at the site level. Nowhere is this more evident than in oncology, where protocols are not only highly complex but often emotionally and logistically demanding. The strength and structure of sponsor-CRO relationships can determine whether a trial is managed with efficiency and integrity—or weighed down by friction and inefficiencies.
In studies ranging from advanced immunotherapy regimens for breast and lung cancers to novel targeted therapies in pediatric sarcomas, it has been observed firsthand how evolving trial complexity—longer startup windows, frequent amendments, and tighter data locks—requires CROs to operate not just as vendors, but as proactive partners. When these partnerships are well-executed, with continuity in personnel, clear lines of communication, and an understanding of institutional workflows, research teams are empowered to focus on what matters most: timely enrollment, data fidelity, and compassionate patient care.
Some partnerships have excelled. For instance, in a multisite oncology study, early alignment with the CRO through protocol walkthroughs, real-time query support, and assignment of a consistent clinical research associate (CRA) reduced fragmentation and allowed for seamless trial conduct, even amidst high volume. This kind of site-centric collaboration is critical—particularly when coordinators are balancing additional responsibilities across other complex therapeutic areas like CKD, diabetes, or spina bifida.
However, challenges persist. High turnover among CRO personnel—especially CRAs—often leads to inconsistent oversight, repetitive data queries, and lost institutional knowledge. Additionally, rigid startup processes that fail to adapt to site-specific institutional review board pathways or pediatric regulatory requirements can stall activation timelines. In pediatric oncology, where trials require coordination across multiple ancillary departments and heightened ethical review, one-size-fits-all approaches rarely serve the site’s needs.
What consistently makes a difference is early, respectful collaboration. When CROs treat sites as operational stakeholders with valuable frontline insights, trial execution improves across the board. Conversely, when sponsor and CRO teams neglect site realities—such as staff bandwidth, electronic medical record limitations, or competing priorities—they risk compromising both quality and speed.
As oncology trials become more adaptive, biomarker-driven, and digitally integrated, sustainable success will depend on a three-way partnership: sponsor, CRO, and site. When aligned effectively, this alliance is not merely transactional—it’s translational. It enables trials that are not only scientifically rigorous, but also operationally feasible and centered around patient outcomes.
Concluding Remarks
The evolving landscape of clinical trials demands a departure from traditional, transactional sponsor-CRO-site relationships toward a model defined by collaboration, flexibility, and shared strategic vision. Rising protocol complexity, the integration of technologies like AI, and the implementation of ICH E6(R3) are reshaping how trials are designed and executed. These shifts require all stakeholders—sponsors, CROs, and research sites—to adapt by embracing transparent communication, joint planning, and site-centric processes that reduce operational burden while maintaining data integrity.
Strategic partnerships foster not only operational efficiency but also greater alignment with patient-centric objectives and regulatory expectations. While needs will vary across programs, early engagement, thoughtful technology adoption, and a culture of mutual trust can improve resilience in the face of growing challenges. The future of clinical research will depend on these stronger, interconnected partnerships that prioritize innovation and flexibility while maintaining focus on quality and patient outcomes.
References
- Markey N, Howitt B, El-Mansouri I, Schwartzenberg C, Kotova O, Meier C. 2024. Clinical trials are becoming more complex: A machine learning analysis of data from over 16,000 trials. Scientific Reports 14 (Article 53211). https://doi.org/10.1038/s41598-024-53211-z
- Favaro MA, Sassano C. 2024. Enabling evidence-based study endpoint selection. Applied Clinical Trials 33(4). https://www.appliedclinicaltrialsonline.com/view/enabling-evidence-based-study-endpoint-selection
- Association of Clinical Research Professionals. 2024. Discover the top site challenges of 2024: Data and insights on site barriers and trial efficiency [Sponsored article]. https://acrpnet.org/2024/10/22/discover-the-top-site-challenges-of-2024-data-and-insights-on-site-barriers-and-trial-efficiency
- Segurado O. 2023. Assessing specialized services provided by CROs [Guest column]. Clinical Leader. https://www.clinicalleader.com/doc/assessing-specialized-services-provided-by-cros-000
- Marmen S. 2025. What is a contract research organization (CRO), and how do you choose the right one? CellCarta Science Hub. https://cellcarta.com/science-hub/contract-research-organization/
- Grand View Research. 2025. Cell & gene therapy contract research organizations market size, share & trends analysis report by type (drug discovery, preclinical, clinical), by service (regulatory strategy, clinical monitoring), by indication, by modality, by region, and segment forecasts, 2025–2033. https://www.grandviewresearch.com/industry-analysis/cell-gene-therapy-contract-research-organizations-market-report
- Steadman VA. 2018. Drug discovery: Collaborations between contract research organizations and the pharmaceutical industry. ACS Medicinal Chemistry Letters 9(7) 581–583. https://doi.org/10.1021/acsmedchemlett.8b00236
- John M, Hop CECA. 2015. Brothers in arms: Biopharma and CROs collaborating in early drug discovery. Drug Discovery World. https://assets.www.criver.com/storage-account-container/resources/doc_a/BrothersinArmsBioPharmaandCROscollaboratinginearlydrugdiscovery.pdf
- TransCelerate BioPharma. 2019. Improving site-sponsor collaboration through shared commitment and efficiency. https://www.transceleratebiopharmainc.com
- U.S. Food and Drug Administration. 2013. Guidance for industry: Oversight of clinical investigations — A risk-based approach to monitoring. https://www.fda.gov/media/116754/download
- International Council for Harmonization (ICH). 2016. ICH E6(R2) good clinical practice: Integrated addendum. https://database.ich.org/sites/default/files/E6_R2_Addendum.pdf
- Getz K. 2024. How much does a day of delay in a clinical trial really cost? Applied Clinical Trials. https://www.appliedclinicaltrialsonline.com/view/how-much-does-a-day-of-delay-in-a-clinical-trial-really-cost
Justin Scott Brathwaite, MBA, is a PhD student in Clinical Research at the University of Jamestown and a Senior Site Readiness and Regulatory Startup Specialist at Fortrea, a contract research organization.
Nirmal Rajasekaran, PhD, is a Project Lead/Clinical Trial Manager at Abion Inc, where he oversees the end-to-end execution of clinical development programs, with a particular focus on early- and mid-phase oncology trials.
Milan Sheth, MS, is a Clinical Research Coordinator specializing in oncology trials at Houston Methodist Neal Cancer Center.
