Improving Study Start-Up Efficiency to Accelerate the Clinical Trial Timeline

Clinical Researcher—February 2026 (Volume 40, Issue 1)

PEER REVIEWED

William Bryant III, MPH; Amanda Martin, ACRP-PM; Justin Scott Brathwaite, MBA, PMP

 

Study start-up (SSU) is a vital phase in clinical trial execution, bridging the gap between project approval and the first patient enrolled. Delays in SSU can significantly impact trial costs, timelines, and competitiveness. This article explores strategies to improve SSU efficiency, including best practices in site feasibility, regulatory submissions, contract negotiations, and communication. It also examines the use of performance metrics, parallel processing, and technology-driven solutions to accelerate trial initiation without compromising quality. By adopting these approaches, sponsors, contract research organization (CROs), and investigative sites can reduce start-up times, improve predictability, and ultimately deliver new treatments to patients faster.

The Critical Role of Study Start-Up in Clinical Trials

In today’s competitive research environment, the ability to start a clinical trial quickly and efficiently can mean the difference between being first to market or falling behind. SSU refers to all activities that occur between receiving the green light to proceed and enrolling the first participant. Every day gained during this phase not only accelerates data collection, but can also significantly reduce costs, increase competitiveness, and improve patient access to potentially life-saving therapies.{1}

SSU inefficiencies can delay regulatory submissions, site activation, and recruitment, often causing ripple effects across the entire trial timeline.{2} Streamlining the process is therefore essential for sponsors, contract research organizations (CROs), and investigative sites.

The SSU process typically follows a sequence of interdependent phases. It begins with protocol finalization and regulatory planning to ensure all study documents are complete and ready for submission. This is followed by site feasibility and selection, where the most suitable sites are identified based on capability, patient population, and resources.{3}

Ethics committee or institutional review board (IRB) submissions follow, requiring the preparation of comprehensive packages for approval. In parallel, contract and budget negotiations take place to reach agreements that are both timely and mutually beneficial.

The final phase involves site initiation and activation, where all pre-study visits, training, and documentation are completed to open sites for enrollment. Because these steps are interconnected, delays in one can quickly cascade into others, thus making clear timelines, defined responsibilities, and proactive issue resolution critical to success.{4}

In this article, we integrate recent multisite IRB timing data and site activation benchmarks into a practical SSU playbook, translating established principles into concrete, measurable steps for sponsors, CROs, and sites.

Common Delays and Their Impact on Study Start-Up

Bottlenecks in SSU are common and can significantly impact timelines. These delays can stem from incomplete or late documentation, such as missing forms, outdated CVs, or incomplete protocols or regulatory packets. Extended contract negotiations over payment terms, indemnification, or intellectual property rights can also slow progress. Moreover, slow ethics or regulatory reviews, often due to long review cycles or requests for additional information, can add weeks to the process.{5} Clear and timely communication between stakeholders must also be prioritized to avoid exacerbating the kinds of delays that all of these issues may engender.

Documentation and Negotiations

Using standardized agreement templates that have been pre-approved by legal teams reduces the documentation review burden as paperwork moves back and forth between the stakeholders.{6} Developing clear and transparent payment schedules can minimize disputes, while initiating negotiations in parallel with regulatory submissions helps ensure that both are ready at the same time.{1}

For multisite studies, leveraging master agreements or centralized reviews can further streamline the process. Well-prepared contracts with clear, fair terms tend to be finalized faster, helping to keep activation on schedule.{2}

Site Feasibility and Selection

Meanwhile, site capacity issues, such as inadequate staff size or overextended facilities, limited availability of study team leaders, and inefficient communication between stakeholders can contribute to delays.{6} The result is often weeks or months added to trial initiation, creating a direct impact on recruitment timelines and trial costs.

One of the most effective ways to prevent these delays is to strengthen the site feasibility and selection process. Data-driven feasibility assessments that leverage historical performance metrics, recruitment rates, and protocol-specific experience help identify the most capable sites.{1}

Assessing resource availability early ensures that sites have the necessary staff, equipment, and bandwidth to take on the study. Also, engaging sites during protocol development allows investigators and site teams to provide feedback on potential challenges, while increasing buy-in and readiness. Standardizing feasibility questionnaires can further reduce completion time while improving data quality.

Selecting the right sites from the outset reduces the likelihood of underperformance and costly replacements later.{7}

IRB and Ethics Submissions

As mentioned, another critical area for efficiency is optimizing IRB and ethics submissions. These approvals can be one of the longest milestones in SSU. To expedite this stage, submission packages should be complete and comprehensive from the outset, including all required documents and study-specific details. Where possible, aligning submission timelines across sites helps avoid staggered approvals that can disrupt launch plans.{3}

Understanding local regulatory requirements is vital, especially in global trials, as these can vary significantly by country or region.{8} Maintaining a robust tracking system ensures submission status is monitored closely, allowing for proactive follow-up on pending approvals. Proactive engagement with ethics committees and regulatory authorities can help avoid resubmissions and additional review delays.{5}

Communication Between Stakeholders

Also touched on earlier is the essential nature of effective communication throughout the SSU process between the sponsor, CRO, and sites. Centralized communication platforms allow all stakeholders to access documents, track status updates, and address queries in one place.{8}

Regular status meetings, whether weekly or bi-weekly, keep all parties aligned and aware of upcoming deadlines. Clearly defining roles and responsibilities helps avoid duplication of effort and confusion, while encouraging transparency about challenges enables teams to address issues before they escalate.{7} Strong communication not only speeds decision-making but also fosters trust and collaboration among stakeholders.

Shared Characteristics of Efficient Study Start-Up

Metrics and Relationships That Matter

Tracking SSU performance using meaningful metrics is key to ongoing improvement. Common indicators include cycle times from green light to site activation, contract and budget turnaround times, regulatory approval timelines, and site activation rates.{4} Early screening and enrollment rates also serve as valuable indicators of site readiness and recruitment potential.{5}

By analyzing these metrics over time, organizations can identify trends, pinpoint bottlenecks, and implement targeted process improvements.{6} Early parallel processing—such as initiating contracts, regulatory submissions, and feasibility assessments simultaneously rather than sequentially—can shave weeks off the timeline.{1}

Pre-study site engagement, where relationships are built with sites before protocol finalization, improves readiness and enthusiasm. The use of technology platforms for e-signatures, online document sharing, and automated tracking tools increases efficiency and reduces administrative delays.{8} In regions where available, centralized ethics reviews or central IRBs eliminate duplicate reviews, shortening regulatory pathways.

Organizational culture also contributes. Teams that emphasize collaboration, accountability, and transparency build stronger sponsor, CRO, and site relationships, which foster greater engagement and enthusiasm. This translates into faster document turnaround, improved responsiveness to queries, and fewer errors requiring rework. Sponsors and CRO teams that communicate study objectives clearly and maintain open dialogue with investigators are often regarded as a “sponsor of choice,” making sites more willing to prioritize their studies.

Governance, Risk Management, and Coordination

Beyond these enablers, effective SSU requires strong governance and proactive risk management. Governance frameworks that clearly define decision-making authority, escalation pathways, and vendor performance expectations help avoid unnecessary delays. Risk-based approaches, such as prioritizing high-recruiting regions for early activation or identifying potential regulatory hurdles in advance, allow teams to allocate resources strategically. Predefined mitigation strategies for common bottlenecks (e.g., protracted contract negotiations or ethics review delays) help maintain momentum.

Another hallmark of an efficient start-up is cross-functional alignment and site-level cooperation. SSU activities involve multiple stakeholders, including clinical operations teams across sponsor and CROs, legal, regulatory, finance, and medical teams. Without coordination, interdependencies among these groups can create delays. Organizations that establish dashboards and integrated project plans, hold joint kick-off meetings, and align milestone accountability across functions typically achieve smoother execution. Likewise, proactive vendor oversight ensures CROs or site management organizations remain fully aligned with sponsor priorities and timelines.

Putting it All into Practice

The impact of these principles is evident across very different contexts. During the COVID-19 pandemic, the United Kingdom’s RECOVERY trial demonstrated the power of parallel activation at scale. By streamlining ethics and regulatory approvals, standardizing contracts, and leveraging the National Health Service hospital network, the trial enrolled its first patient within nine days of protocol finalization and randomized more than 11,000 patients within three months.{9} This unprecedented efficiency allowed researchers to identify dexamethasone as the first therapy to reduce mortality in severe COVID-19, reshaping global treatment guidelines.{10,11}

Further, lest we forget it amongst all this focus on the work of clinical research professionals, patient advocacy can be equally powerful in driving momentum. For example, the Saving Eliza campaign, launched in 2014 by family of a rare disease patient, leveraged grassroots awareness and crowdfunding to generate more than $500,000 in just 15 days and ultimately more than $1.5 million to fund gene therapy research for Sanfilippo syndrome.{12,13}. Beyond raising funds, the campaign created urgency and visibility that accelerated trial readiness, culminating in Eliza O’Neill becoming the first patient to receive intravenous gene therapy for the condition in 2016.{14}

While RECOVERY highlighted centralized efficiency and underscored infrastructure readiness, Saving Eliza illustrated how motivated patient communities can directly shape the pace and feasibility of study start-up.

Lessons from Site Analyses: Reducing Start-up Delays

From our experience, we have witnessed significant variability in how sites conduct SSU, especially across academic medical centers. This variation partly stems from differing requirements and specific institutional nuances and processes, such as the number of scientific review committees.{15} Moreover, the discrepancy reflects the more complex administrative, legal, and compliance processes at academic medical centers and hospitals that often contribute to longer start-up timelines.{2}

A deeper understanding of these site-specific challenges offers sponsors and CROs opportunities to optimize processes for all stakeholders, which raises an important question about whether SSU best practices can also be identified at the site level that could be leveraged to improve cycle times.

For instance, leveraging a central IRB can greatly improve start-up cycle times. A 2021 cohort study examined nine large cardiovascular randomized controlled trials (RCTs) conducted between 2004 and 2017 coordinated by the Duke Clinical Research Institute. The researchers measured site start-up performance, defined as the time from protocol delivery to first patient enrollment. Regulatory analysis included 2,225 sites, with 35.9% using a central IRB and 54.3% a local IRB. Sites leveraging a central IRB took a median 78 days to reach regulatory approval, twice as fast as the 165 days for sites utilizing a local IRB; moreover, central IRB sites had significantly shorter SSU times of 199 days versus 287 days for local sites (see Table 1).{16}

Table 1: Impact of IRB Type on Study Start-Up Timelines{16}

IRB Type	Median IRB Review Duration (Days)	Median SSU Duration (Days)	% of Sites
Central IRB	78 (IQR 45-124)	199 days (IQR 140–292)	35.9
Local IRB	165 (IQR 112-244)	287 days (IQR 205–390)	54.3
Unknown/Not Specified	___	___	9.8

Median study start-up and IRB review timelines (days) with interquartile ranges (IQRs) for North American research sites participating in large cardiovascular RCTs, stratified by IRB type.

Another relevant, though smaller-scale, study at a physician-owned cardiovascular hospital reviewed 10 prior clinical trials conducted at the institution to identify study start-up delays. The findings emphasized the importance of streamlining feasibility from the site perspective, recommending the use of a structured feasibility tool that incorporates at least three years of patient history, and a dedicated Feasibility Committee to provide objective and thorough evaluations outside routine meetings.

The study also recommended centralizing coverage analysis with Centers for Medicare & Medicaid Services coding experts as a strategy to give local site staff greater capacity for budget negotiations and to limit extended administrative back-and-forth. To further streamline the process, the study’s author proposed standardizing start-up costs by trial complexity, using fixed tiers to reduce disputes and accelerate approvals.{17}

Taken together, these insights show that adopting centralization, standardization, and technology can streamline SSU, minimize delays, and speed patient access to trials; however, it also highlights that CROs and sponsors must tailor their support to the operational realities of research sites.

Implementations and Tradeoffs

Implementing parallel workflows and standardized study start-up tools requires thoughtful upfront investment in resources, training, and oversight. Dedicated time must be allocated for staff training on new templates and dashboards, as well as legal and compliance review of master documents to ensure broad applicability across sites and sponsors.

Equally important is establishing clear governance structures to monitor adoption and resolve issues as they arise. To mitigate operational and regulatory risks, we recommend a phased roll-out strategy—beginning with one or two high-enrollment sites to test feasibility and refine processes before wider implementation. Predefined escalation pathways should also be in place for tasks that stall beyond a set threshold (e.g., >14 days), ensuring accountability and timely resolution.

Finally, routine monitoring through monthly reviews of key metrics, supported by a red-amber-green (RAG) status system, provides transparency and promotes proactive course correction. Together, these guardrails accelerate timelines while maintaining quality and regulatory compliance. (See the Sidebar for a summary of recommendations.)

Concluding Thoughts

Ultimately, accelerating SSU is not about cutting corners but about optimizing processes, improving communication, and leveraging technology and data to work smarter. Building a sustainable model for faster start-up requires realistic timelines, early and ongoing engagement with all stakeholders, and standardized processes that still allow for site-specific flexibility.{7}

Continuous measurement and improvement based on key metrics ensure that efficiency gains are maintained and enhanced over time. By embedding these principles into organizational culture, sites, sponsors, and CROs can consistently reduce start-up times, improve predictability, and bring treatments to patients faster.{3}

Now is the time to act by adopting standardized feasibility, running contracts and regulatory in parallel, tracking cycle times visibly, enabling 14-day escalations, and using central IRB wherever possible to cut study start-up timelines without sacrificing quality.

Sidebar: Study Start-Up Quick Wins and Key Takeaways
·       Standardize feasibility assessments with templates and multi-year patient volume data.
·       Run regulatory and contract processes in parallel using master templates.
·       Implement dashboards with RAG (red-amber-green) status and day targets for each milestone.
·       Prioritize central IRBs (reduces approval from ~165 → ~78 days; SSU from ~287 → ~199 days) and align submissions to avoid staggered approvals.{16}
·       Define clear escalation paths (e.g., 14 days) for stalled tasks or bottlenecks.
·       Track cycle times monthly and benchmark against top-performing sites (~106 days in the best quartile).{16}

Acknowledgments

The lead author thanks the reviewers and Managing Editor for Clinical Researcher for their thoughtful input on earlier drafts of this manuscript. He also acknowledges the contributions of his coauthors and Michele Martin Rowe, Joretta Wong, and mentors in clinical research operations whose insights and collaborations have informed the perspectives shared here.

Disclosures

Funding: This work received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

Conflicts of Interest: The authors declare no conflicts of interest related to this manuscript.

References

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William Bryant III, MPH, is a clinical research professional with more than 20 years of experience in study start-up, clinical operations, and global trial management. He has led initiatives across multiple therapeutic areas and is passionate about improving operational efficiency in clinical research to accelerate patient access to innovative therapies.

Amanda Martin, ACRP-PM, is a senior clinical research leader with more than 24 years of global experience in clinical operations and project management. She has directed multi-regional trials across multiple therapeutic areas, including but not limited to oncology, neuroscience, immunology, and rare diseases.

Justin Scott Brathwaite, MBA, PMP, is a Site Readiness and Regulatory Senior Specialist at Fortrea and a PhD student in Clinical Research at the University of Jamestown. He has five years of experience in study start-up operations and is a two-time finalist in the PharmaTimes Clinical Researcher of the Year (Study Start-Up category) competition.