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Site readiness practices for clinical trials – considerations for CTSA hubs

Published online by Cambridge University Press:  29 June 2023

Laura Viera*
Affiliation:
University of North Carolina School of Medicine, Chapel Hill, NC, USA
Laura James
Affiliation:
University of Arkansas for Medical Sciences, Little Rock, AR, USA
Anantha Shekhar
Affiliation:
University of Pittsburgh, Pittsburgh, PA, USA
Octavian C. Ioachimescu
Affiliation:
Medical College of Wisconsin, Milwaukee, WI, USA
John B. Buse
Affiliation:
University of North Carolina School of Medicine, Chapel Hill, NC, USA
*
Corresponding author: L. Viera, MA, CCRP; Email: laura_viera@med.unc.edu
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Abstract

Type
Perspective
Creative Commons
Creative Common License - CCCreative Common License - BY
This is an Open Access article, distributed under the terms of the Creative Commons Attribution licence (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted re-use, distribution and reproduction, provided the original article is properly cited.
Copyright
© The Author(s), 2023. Published by Cambridge University Press on behalf of The Association for Clinical and Translational Science

It has been widely recognized that site-specific attributes such as infrastructure, personnel, and participant recruitment-related factors are critical to effective and successful conduct of clinical trials [Reference Mehta, Goyal and Singh1Reference Dombernowsky, Haedersdal, Lassen and Thomsen4]. Industry, federal, and foundation sponsors consider these factors in their assessment of site readiness when selecting sites to execute clinical trial protocols. While site selection factors vary somewhat depending on sponsor and trial type, “A Framework for Assessing for Clinical Trial Site Readiness” has identified a core set of site readiness practices that are recommended for all sites interested in initiating and executing clinical trials [Reference Buse, Austin and Johnston5]. The site readiness practices include factors spanning domains of research team, infrastructure, study management, data collection and management, quality oversight, and ethics and safety (Table 1).

Table 1. List of site readiness practices for clinical trials, organized by domain

Adoption of site readiness practices aims to improve sites’ success in initiating and sustaining clinical trials and streamlining operations. Nevertheless, there are several potential challenges sites could face in implementing the site readiness practices. With robust centralized infrastructure and sophisticated personnel expertise, Clinical and Translational Science Awards (CTSA) hubs are well-positioned to lead the adoption, documentation, maintenance, and further evaluation of site readiness practices. Furthermore, the framework defines three cross-cutting principles essential for site readiness: a culture of quality, clinical research literacy, and person-centeredness. The work of the CTSA hubs inherently encompasses these qualities, further priming them for leading these efforts in their institutions. In this paper, we highlight several anticipated challenges, opportunities, and recommendations to assist CTSA hubs in planning for and implementing site readiness practices for clinical trials.Footnote 1

Challenges and Opportunities for CTSA hubs

The process of standardizing operations as required to implement the site readiness practices will present challenges and is likely to face adoption delays and covert or frank opposition. Often, at large academic medical centers — where CTSA hubs are typically based — there is variability in standards and processes between various clinical units, departments, and locations. This variability is even greater in healthcare systems that often have multiple facilities and practices, sometimes with distinct governance. However, the CTSA hubs’ focus on innovation, efficiency, and quality, as well as experience in enabling enterprise-wide collaborations, allows them to understand existing differences in processes and to identify optimal local standards. Additionally, CTSA personnel are likely to be viewed as more neutral than personnel affiliated with a specific department or practice, and therefore potentially more successful in identifying suitable standards and subsequently implementing standardized processes that have historically been characterized by wider variability.

Implementing the site readiness practices may cause some disruption for site personnel as operations are standardized and processes change. CTSA hubs can minimize this disruption through their leadership across institutions, education, celebration of local successes, engagement of early adopters, and through the expansion and dissemination of existing resources or via training programs developed and vetted as part of the CTSA infrastructure.

The process of working across complex organizations to identify and define promising approaches to adoption will require significant and persistent effort. Simply documenting information from various units or locations will require coordinated effort, while working to establish (i.e., adopt, implement, maintain, and disseminate) new standards will require considerably more. CTSA hubs can leverage the advantage of existing personnel resources and technical infrastructure to refine approaches to adoption and document the site readiness practices in a centralized and accessible location, according to a set of defined organizational standards and principles of team science, including stakeholder engagement and shared decision-making.

Recommendations for CTSA hubs

Most of the recommended site readiness practices are policies and standardized procedures based on regulatory requirements. Some of the site readiness practices likely already exist (e.g., record retention policies and disaster recovery plans), but may need to be harmonized across locations or units. Other site readiness practices may need to be established de novo (e.g., research teams’ utilization of standard operating procedures and adoption of prompt study initiation processes). Once identified or established, the site readiness practices will need to be documented and continually reviewed for appropriateness, accuracy and optimal use, especially given the rate of change across the national clinical research enterprise and local conditions. In order to realize optimal efficiency and ease in developing and maintaining site readiness practices, we make the following recommendations for CTSA hubs:

  • Develop institutional standard operating procedures (SOPs) based on federal and local regulations according to the domains defined in the site readiness practices;

  • Create a standardized template for work instructions that individual units or locations may implement to supplement institutional SOPs;

  • Develop a robust SOP implementation plan that includes access to resources and trainings beneficial to study teams as they transition to new standard procedures;

  • Establish a rigorous review schedule and plan to appropriately update and maintain the SOPs; and

  • Harmonize documentation of and access to the site readiness practices across the institution.

Given that CTSA hubs are established and supported in various manners across institutions, some may be better-positioned to lead this charge. There are several factors that we believe will bolster the ability of CTSAs wishing to implement the site readiness practices across large and complex institutions:

  • Close engagement with leadership of the University, healthcare system, and/or School of Medicine

  • Alignment with institutional compliance offices (e.g. contracting, regulatory)

  • Collaboration with the healthcare system, especially spanning distinct sites

Call to Action

Implementation of the site readiness practices to demonstrate a site’s ability to conduct a clinical trial may be challenging for diverse and complex institutions. However, the anticipated benefits of increased engagement with clinical trial sponsors, greater trial opportunities for patients and communities, reduced burden for study teams related to initiating and executing clinical trials, and improved efficiency and quality are substantial.

Given the collaborative nature of the CTSA consortium and its rich expertise in all aspects of clinical trial design and conduct, implementation of the site readiness practices by CTSA hubs offers the unique opportunity of additional value and efficiency through sharing methods and feedback over time. With engagement from CTSA hubs, the site readiness practices may be further refined, and novel methods and processes for demonstrating and maintaining the readiness factors may be developed and shared across institutions.

Acknowledgments

The authors are grateful for project management and editorial support from the National Academies of Science, Engineering, and Medicine staff, Andrew N. March and Carolyn K. Shore. The authors thank Joni Rutter, director of the National Center for Advancing Translational Sciences (NCATS) at the National Institutes of Health, for her thoughtful feedback on the concept and content of this perspective. We also thank members of the Association for Clinical and Translational Science’s Clinical Research Professionals Taskforce Special Interest Group for their review and input.

Funding statement

The authors effort was supported by the University of North Carolina School of Medicine’s Clinical Research Support Office (LV, JBB), grants from the National Institutes of Health’s National Center for Advancing Translational Sciences UM1TR004406 (LV, JBB) and UL1 TR003107 (LJ).

Competing interests

LV and OI report no dualities of interest. LJ reports grant support to Acetaminophen Toxicity Diagnostics from DK079387. AS reports the following disclosures that are unrelated to the subject of this article. He is a scientific cofounder or owns stocks as a scientific contributor for the following biotech companies: Karuna Therapeutics, Gate Neurosciences, Anagin Inc., Monument Biosciences, MindX, Vasculonics and Aardwolf Therapeutics. JBB reports contracted fees and travel support for consulting work paid to the University of North Carolina by Novo Nordisk; grant support by Dexcom, NovaTarg, Novo Nordisk, Sanofi, Tolerion and vTv Therapeutics; personal compensation for consultation from Alkahest, Altimmune, Anji, AstraZeneca, Bayer, Biomea Fusion Inc., Boehringer-Ingelheim, CeQur, Cirius Therapeutics Inc., Corcept Therapeutics, Eli Lilly, Fortress Biotech, GentiBio, Glycadia, Glyscend, Janssen, MannKind, Mellitus Health, Moderna, Pendulum Therapeutics, Praetego, Sanofi, Stability Health, Terns Inc., Valo and Zealand Pharma; and stock/options in Glyscend, Mellitus Health, Pendulum Therapeutics, PhaseBio, Praetego, and Stability Health.

Disclaimer

The views expressed within this article do not necessarily represent the views of the National Academies of Sciences, Engineering, and Medicine, the National Research Council, or any of their constituent units. AS and JBB are current members of the Forum on Drug Discovery, Development, and Translation, a standing body of the National Academies.

Footnotes

1 This article provides additional context and commentary for CTSA sites regarding the implementation of a set of site readiness practices identified in the article, “A Framework for Assessing Clinical Trial Site Readiness.” That article, which is cited in the references of this publication, describes the full set of site readiness practices, the methods for their selection, and a rationale for their use by clinical trial sites. The article also includes supplementary material, including guidance and resources for implementing and documenting the site readiness practices.

2 For more information on who qualifies as a responsible party, see https://www.ecfr.gov/current/title-42/chapter-I/subchapter-A/part-11 (accessed August 15, 2022).

References

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Table 1. List of site readiness practices for clinical trials, organized by domain