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Insights from the trial innovation network’s initial consultation process

Published online by Cambridge University Press:  26 June 2025

Paul A. Harris Open the ORCID record for Paul A. Harris [Opens in a new window] ,
Nan Kennedy Open the ORCID record for Nan Kennedy [Opens in a new window] ,
Consuelo H. Wilkins ,
Karen Lane Open the ORCID record for Karen Lane [Opens in a new window] ,
Gordon R. Bernard ,
Jonathan D. Casey ,
Daniel E. Ford Open the ORCID record for Daniel E. Ford [Opens in a new window] ,
Salina P. Waddy ,
Ken L. Wiley Jr.  and
Terri L. Edwards
...Show all authors
Paul A. Harris*
Affiliation:
Vanderbilt Institute for Clinical and Translational Research, Nashville, TN, USA. Department of Biomedical Informatics, Vanderbilt University Medical Center, Nashville, TN, USA
Nan Kennedy
Affiliation:
Vanderbilt Institute for Clinical and Translational Research, Nashville, TN, USA.
Consuelo H. Wilkins
Affiliation:
Vanderbilt Institute for Clinical and Translational Research, Nashville, TN, USA. Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA. Department of Internal Medicine, Meharry Medical College, Nashville, TN, USA.
Karen Lane
Affiliation:
Johns Hopkins University School of Medicine, Baltimore, MD, USA
Gordon R. Bernard
Affiliation:
Vanderbilt Institute for Clinical and Translational Research, Nashville, TN, USA. Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
Jonathan D. Casey
Affiliation:
Vanderbilt Institute for Clinical and Translational Research, Nashville, TN, USA. Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
Daniel E. Ford
Affiliation:
Johns Hopkins University School of Medicine, Baltimore, MD, USA Johns Hopkins Institute for Clinical and Translational Research, Baltimore, MD, USA
Salina P. Waddy
Affiliation:
National Center for Advancing Translational Sciences, Bethesda, MD, USA
Ken L. Wiley Jr.
Affiliation:
National Center for Advancing Translational Sciences, Bethesda, MD, USA
Terri L. Edwards
Affiliation:
Vanderbilt Institute for Clinical and Translational Research, Nashville, TN, USA.
Nichol McBee
Affiliation:
Johns Hopkins University School of Medicine, Baltimore, MD, USA
Dixie D. Thompson
Affiliation:
University of Utah Health, Salt Lake City, UT, USA Utah Clinical & Translational Science Institute, Salt Lake City, UT, USA
Mary Stroud
Affiliation:
Vanderbilt Institute for Clinical and Translational Research, Nashville, TN, USA.
Emily S. Serdoz
Affiliation:
Vanderbilt Institute for Clinical and Translational Research, Nashville, TN, USA.
Sarah J. Nelson
Affiliation:
Vanderbilt Institute for Clinical and Translational Research, Nashville, TN, USA.
Michelle Jones
Affiliation:
Vanderbilt Institute for Clinical and Translational Research, Nashville, TN, USA.
Lindsay M. Eyzaguirre
Affiliation:
Johns Hopkins University School of Medicine, Baltimore, MD, USA
Leslie R. Boone
Affiliation:
Vanderbilt Institute for Clinical and Translational Research, Nashville, TN, USA.
Jessica Baird
Affiliation:
Johns Hopkins University School of Medicine, Baltimore, MD, USA
Colleen E. Lawrence
Affiliation:
Vanderbilt Institute for Clinical and Translational Research, Nashville, TN, USA.
Elizabeth Holthouse
Affiliation:
Johns Hopkins University School of Medicine, Baltimore, MD, USA
Sarah K. Cook
Affiliation:
Vanderbilt Institute for Clinical and Translational Research, Nashville, TN, USA.
Maeve Tischbein
Affiliation:
Vanderbilt Institute for Clinical and Translational Research, Nashville, TN, USA.
Natalya Amrine
Affiliation:
Vanderbilt Institute for Clinical and Translational Research, Nashville, TN, USA.
Tiffany Chen
Affiliation:
Vanderbilt Institute for Clinical and Translational Research, Nashville, TN, USA.
Jodie Cohen
Affiliation:
Vanderbilt Institute for Clinical and Translational Research, Nashville, TN, USA.
LaShondra Deyampert
Affiliation:
Vanderbilt Institute for Clinical and Translational Research, Nashville, TN, USA.
Natalie A. Dilts
Affiliation:
Vanderbilt Institute for Clinical and Translational Research, Nashville, TN, USA.
Delicia Burts
Affiliation:
Vanderbilt Institute for Clinical and Translational Research, Nashville, TN, USA.
Amna Baig
Affiliation:
Vanderbilt Institute for Clinical and Translational Research, Nashville, TN, USA.
Joseph G. Christodoulou
Affiliation:
Vanderbilt Institute for Clinical and Translational Research, Nashville, TN, USA.
Mariela Rodriguez
Affiliation:
Vanderbilt Institute for Clinical and Translational Research, Nashville, TN, USA.
Edgar R. Miller III
Affiliation:
Johns Hopkins University School of Medicine, Baltimore, MD, USA
James F. Casella
Affiliation:
Johns Hopkins University School of Medicine, Baltimore, MD, USA Johns Hopkins Institute for Clinical and Translational Research, Baltimore, MD, USA
W. Andrew Mould
Affiliation:
Johns Hopkins University School of Medicine, Baltimore, MD, USA
J. Michael Dean
Affiliation:
University of Utah Health, Salt Lake City, UT, USA
Daniel K. Benjamin
Affiliation:
Duke University School of Medicine, Durham, North Carolina, USA
Harry P. Selker
Affiliation:
Institute for Clinical Research and Health Policy Studies, Tufts Medical Center, Boston, MA, USA Tufts Clinical and Translational Science Institute, Tufts University, Boston, MA, USA
Marisha E. Palm
Affiliation:
Institute for Clinical Research and Health Policy Studies, Tufts Medical Center, Boston, MA, USA Tufts Clinical and Translational Science Institute, Tufts University, Boston, MA, USA
Lori Poole
Affiliation:
Duke Clinical Research Institute, Durham, NC, USA
Jeri S. Burr
Affiliation:
University of Utah Health, Salt Lake City, UT, USA
Sara Hassani
Affiliation:
National Center for Advancing Translational Sciences, Bethesda, MD, USA
Angeline Nanni
Affiliation:
Johns Hopkins University School of Medicine, Baltimore, MD, USA
Meghan Hildreth
Affiliation:
Johns Hopkins University School of Medicine, Baltimore, MD, USA
Daniel F. Hanley
Affiliation:
Johns Hopkins University School of Medicine, Baltimore, MD, USA Johns Hopkins Institute for Clinical and Translational Research, Baltimore, MD, USA
*
Corresponding author: P.A. Harris; Email: paul.a.harris@vumc.org
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Abstract

Multicenter clinical trials are essential for evaluating interventions but often face significant challenges in study design, site coordination, participant recruitment, and regulatory compliance. To address these issues, the National Institutes of Health’s National Center for Advancing Translational Sciences established the Trial Innovation Network (TIN). The TIN offers a scientific consultation process, providing access to clinical trial and disease experts who provide input and recommendations throughout the trial’s duration, at no cost to investigators. This approach aims to improve trial design, accelerate implementation, foster interdisciplinary teamwork, and spur innovations that enhance multicenter trial quality and efficiency. The TIN leverages resources of the Clinical and Translational Science Awards (CTSA) program, complementing local capabilities at the investigator’s institution. The Initial Consultation process focuses on the study’s scientific premise, design, site development, recruitment and retention strategies, funding feasibility, and other support areas. As of 6/1/2024, the TIN has provided 431 Initial Consultations to increase efficiency and accelerate trial implementation by delivering customized support and tailored recommendations. Across a range of clinical trials, the TIN has developed standardized, streamlined, and adaptable processes. We describe these processes, provide operational metrics, and include a set of lessons learned for consideration by other trial support and innovation networks.

Keywords

Multicenter studiesTrial Innovation NetworkTrial Innovation CenterRecruitment Innovation Centerscientific consultation

Information

Type
Special Communication
Information
Journal of Clinical and Translational Science , Volume 9 , Issue 1 , 2025 , e149
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 (https://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), 2025. Published by Cambridge University Press on behalf of Association for Clinical and Translational Science

Introduction

Clinical trials are essential for evaluating the safety and efficacy of new and existing treatments or interventions across appropriate and representative populations, ensuring findings are reproducible. Studies that generate evidence (e.g., early phase trials, management trials using drugs or devices, behavioral intervention trials, comparative effectiveness studies, decentralized trials) among specialized populations typically require multicenter recruitment and enrollment to attain a sample size sufficient to ensure generalizable results within a meaningful timeline. Multicenter trials can speed the pace of scientific discovery and translation, but face ongoing challenges to successful completion, such as complexities in study design, coordination, and data management across multiple sites; lengthy design-test-implement cycles; recruitment and retention of all populations, including those with limited representation in research; and divergent interpretations by local Institutional Review Boards [Reference Chung and Song1,Reference Harris, Dunsmore, Atkinson, Benjamin, Bernard and Dean2].

Expert scientific and operational input is needed during trial planning stages to optimize designs, address methodological challenges, and ensure robust protocol development. The Trial Innovation Network (TIN) was established by the National Institutes of Health’s National Center for Advancing Translational Sciences (NCATS) as a collaborative initiative that seeks to accelerate the translation of research into clinical practice [Reference Shah, Culp, Gersing, Jones, Purucker and Urv3]. As part of this effort, experts and scientists from the Trial Innovation Centers (TICs), the Recruitment Innovation Center (RIC) [Reference Wilkins, Edwards, Stroud, Kennedy, Jerome and Lawrence4], and Liaison Teams from >60 Clinical and Translational Science Awards (CTSA) Program Hubs across the country (Figure 1) collaborate in a multidisciplinary scientific consultation process to consider, plan, and conduct multicenter clinical trials while developing data-driven innovations and tools in trial design and operations.

Figure 1.

Trial Innovation Network partners, 2025. CTSA = Clinical and Translational Science Award.

Early network efforts and the original institutional configuration of innovation centers have been described by Bernard et al. [Reference Bernard, Harris, Pulley, Benjamin, Dean and Ford5], while the more mature network is discussed in recent publications [Reference Harris, Dunsmore, Atkinson, Benjamin, Bernard and Dean2,Reference Wilkins, Edwards, Stroud, Kennedy, Jerome and Lawrence4,Reference Palm, Edwards, Wieber, Kay, Marion and Boone6–Reference Cook, Kennedy, Boone, Drury, Rodweller and Stroud8]. The TIN’s freely available consultation process provides researchers access to a range of clinical trialists, methodologists, and disease domain experts, who offer feedback and guidance at various stages across the trial life cycle. By leveraging the multidisciplinary expertise of the TIN, and by extension the CTSA network writ large, investigators receive assistance in navigating the intricacies of study design and protocol development, multiple site coordination, regulatory variations, representative participant recruitment, quality data analysis, and broad dissemination of learned advances in science and medicine. Individual researchers, including both new and seasoned principal investigators, are empowered to optimize trial design and operational performance, understand and meet the needs of the patients at the core of their clinical question(s), and work together with TIN experts to accelerate the translation of promising scientific discoveries into real benefits for patients.

The TIN’s scientific consultations can include an Initial Consultation [Reference Harris, Wilkins, Lane, Bernard, Casey and Ford9], targeted resources, customized recommendations, and/or a Comprehensive Consultation for investigators who wish to have one of the TICs serve as the data coordinating center or clinical coordinating center. This paper, which focuses on the Initial Consultation and targeted resources, describes the TIN’s current structure and areas of innovative emphasis, showcases examples of a variety of Initial Consultations, and presents a set of lessons learned that may help other trial network leaders design consultative services.

Methods

History of the TIN Initial Consultation

The TIN’s iterative proposal submission process began with an initial call for proposals in October 2016, yielding 38 proposals. In July 2017, we honed the submission process, committing to a 5-working-day response window during which a TIC or RIC manager would contact the study investigator to set up an introductory call and discuss expectations for the consultation process. Our revised process also ensured every investigator (100%) who applied to the TIN was offered an Initial Consultation with recommendations. Rolling acceptance, review, and consultative processes were developed to enhance program flexibility [Reference Harris, Dunsmore, Atkinson, Benjamin, Bernard and Dean2,Reference Bernard, Harris, Pulley, Benjamin, Dean and Ford5].

Organizational structure

The guiding principle of the TIN Initial Consultation is to deliver early-stage, high-quality scientific consultations to investigators, tailored to address study-specific needs. To achieve this aim, the consultation process and governance structure have been standardized to enable rapid access to discussions among the principal investigator (PI) and study team, assigned TIC and RIC project leads, disease domain experts, CTSA members, and NIH program officers (Table 1), while also establishing connections with experienced TIN clinical trialists, biostatisticians, and recruitment experts. Consultative discussions may cover the study’s scientific premise, statistical design, recruitment and retention strategies, funding feasibility, and other support areas. In addition to fostering ongoing partnerships between the study team and consultation experts, the TIN encourages investigators to leverage the expertise and resources available within their own institutional CTSA program (when applicable) and promotes potential collaborations with external entities such as community hospitals and affiliated medical centers.

Table 1.

Initial Consultation – TIN roles and responsibilities

TIN = Trial Innovation Network; TIC = Trial Innovation Center; RIC = Recruitment Innovation Center; JHU = Johns Hopkins University; NIH = National Institutes of Health; sIRB = single Institutional Review Board; CTSA = Clinical and Translational Science Award.

The TIN prioritizes proposals that can potentially test an operational or design innovation to enhance efficiency or reduce clinical trial costs. Initial Consultations are a first step; through them, the TIN discovers shared interest in partnering on methods to improve performance. From the needs and experiences communicated during collaboration with research teams across a multitude of studies and domains, the TIN identifies gaps in design and implementation, integrates new insights, and generates new resources, methods, and tools [Reference Palm, Edwards, Wieber, Kay, Marion and Boone6,Reference Lane, Palm, Marion, Kay, Thompson and Stroud10]. Using this bidirectional approach, the TIN has developed innovations such as the ResearchMatch Expert Advice Tool [Reference Tischbein, Cook, Shyr, Benhoff, Baig and Quarles11]; the IRB Reliance Exchange (IREx) to operationalize single IRB review and communications [Reference Serdoz, Edwards, Pulley, Beadles, Ozier and Harris12]; a module in REDCap to facilitate real-time participant randomization in adaptive trials; a site assessment survey instrument (SASI) [Reference Lane, Hillery, Majkowski, Barney, Amirault and Nelson13]; and an accelerated trial start-up (ASU) program, among others [Reference Lawrence, Bruce, Salberg, Edwards, Morales and Palm14].

The TIN Initial Consultation process

A proposal to request a TIN consultation can be completed through the TIN website (trialinnovationnetwork.org) by any US-based investigator who is developing or conducting a multicenter study in any discipline and with any type of funding. The proposal captures the basic study design, objectives, endpoints, target population, intervention, study and participation duration, sites, requested resources (Table 2), funding source, and funding mechanism. If investigators are affiliated with a CTSA Hub, an acknowledgment or letter of support from their CTSA PI is required to ensure locally available resources (e.g., biostatistical support, study coordination support, and regulatory expertise) are leveraged when available. Following the review of the proposal, the TIN initiates and carries out the Initial Consultation. This process involves a series of consultative calls with the study investigator, domain experts, TIC or RIC lead, and relevant resource leads. Potential TIC/RIC resources (Table 2) that may be provided to the investigator are discussed, and those that are deemed appropriate and beneficial are implemented. The TIN provides a final Recommendations Report for all Initial Consultations, and if warranted by the needs of the study and approved by the Proposal Assessment Team (PAT), a TIN Comprehensive Consultation may follow.

Table 2.

Initial Consultation areas of innovative emphasis

TIN = Trial Innovation Network; sIRB = single Institutional Review Board; IREx = Institutional Review Board Reliance Exchange; FDP-CTSA = Federal Demonstration Partnership - Clinical Trials Subaward Agreement; CTSA = Clinical and Translational Science Award; PI = Principal Investigator; EHR = Electronic Health Record.

Results

Consultation reach

The TIN received 448 submissions requesting an Initial Consultation from October 2016 through June 1, 2024 (2016–44; 2017–42; 2018–78; 2019–67; 2020–78; 2021–46; 2022–41; 2023–34; 2024–20). Some proposals did not move forward or are in progress (n = 4) or were part of the TIN pilot/demonstration project (n = 13). In total, 431 TIN Initial Consultations were completed. Investigators receiving Initial Consultations are often from well-funded R1 institutions, as CTSAs are typically housed in large research centers (Figure 2). Nearly 20% of TIN Initial Consultations were delivered to junior investigators, including fellows, instructors, and assistant professors.

Figure 2.

TIN Initial Consultations metrics – distribution of institution funding/research activity classification and investigator roles. R1= research 1; R2 = research 2. *Based on the Carnegie Classification of Institutions of Higher Learning©.

Selected examples of Initial Consultations and outcomes

The following use cases present a range of studies with a variety of challenges, resources received, and outcomes that illustrate the possible progression of an Initial Consultation and its impact on a clinical trial.

BEACH (Biomarker and Edema Attenuation in IntraCerebral Hemorrhage) Trial: Johns Hopkins University (JHU), University of Kentucky and JHU TIC, and Vanderbilt University Medical Center (VUMC) RIC. Proposal for first-in-human evaluation of an anti-neuroinflammatory, small-molecule drug candidate in an adult acute trauma population, informed by evidentiary preclinical data. Initial Consultation design experts and content-specific physician scientists recommended shifting the focused population to one that is easier to assess, where factors influencing disease development are known and quantifiable. The TIN leveraged the CTSA program for EHR-based cohort assessments to identify optimal sites, assisted with establishing a Clinical Coordinating Center and Data Coordinating Center collaboration, and identified potential trial implementation innovations including automating near real-time brain CT scan measurement in screening and endpoint assessment. Consultation Outcome: Design strategies, site identification, collaborative structure. A subsequent TIN Comprehensive Consultation resulted in a successful collaborative grant proposal to the National Institute of Aging, which was funded on the first attempt. NCT05020535

Physical Activity in People with Multiple Sclerosis (MS) Study: Columbia University and VUMC TIC, VUMC RIC. Proposal for a Phase II, randomized, placebo-controlled trial in an adult autoimmune disease population, to evaluate medication dosing and physical activity levels. Initial Consultation design experts suggested expanding the intervention and designing a three-arm trial with placebo and recommended continuously monitoring activity levels rather than pre- and post-intervention. The ResearchMatch [Reference Harris, Scott, Lebo, Hassan, Lightner and Pulley23] Expert Advice Tool [Reference Tischbein, Cook, Shyr, Benhoff, Baig and Quarles11] collected pre-grant opinions from volunteers with appropriate lived experience. 61 volunteers responded, 72% said they would be “likely” or “extremely likely” to participate in the trial with continuous activity monitoring. The TIC recommended additional resources once funded: MyCap [Reference Harris, Swafford, Serdoz, Eidenmuller, Delacqua and Jagtap15] for remote capture of patient-reported outcomes and the Clinician Study App [Reference Wilkins, Edwards, Stroud, Kennedy, Jerome and Lawrence4] to facilitate provider referrals. Unsupportable budget impacts arose two weeks prior to grant submission, and were immediately addressed and mitigated by the VUMC TIC. The study PI was connected to an expert pharmacy resource; a revised quote was provided within 1 business day at <25% of the original pharmacy costs ($1M+ vs. $172K). Consultation Outcome: Design strategies. Recommendations Report and Resources. Ongoing team collaborations. Grant not yet funded.

REBIRTH (Randomized Evaluation of Bromocriptine in Myocardial Recovery Therapy for Peripartum Cardiomyopathy) Study: University of Pittsburgh and VUMC RIC, Duke University TIC. Proposal to evaluate the use of bromocriptine for myocardial recovery therapy in women living with peripartum cardiomyopathy at 50 recruitment sites. Anticipated challenges included: delayed care due to a lack of awareness of peripartum cardiomyopathy among providers; later diagnosis and care for Black women compared to white women; the need for genetic sample collection; and loss to follow-up. Hospitalization at enrollment was expected to be problematic if individuals were too sick or needed complex care that made them ineligible to participate. To support the grant submission, the RIC conducted a Community Engagement Studio [Reference Dilts, Harrell, Lindsell, Nwosu, Stewart and Shotwell16] with priority populations to illuminate potential barriers and enable creation of a Recruitment and Retention Plan to mitigate risks. The RIC also developed an electronic phenotype algorithm to identify sites with the relevant rare disease population. Consultation Outcome: Recommendations Report and Resources, Letter of Support for grant submission. Grant was funded. NCT05180773

WIRED UP Study: Johns Hopkins University and JHU TIC, VUMC RIC. Open-label randomized controlled trial to determine if specialized insoles with real-time feedback and remote monitoring can prevent recurrent diabetic foot ulcers in adults with recently healed ulcers. Also assessed were patient satisfaction, quality of life, and healthcare costs compared to standard non-interactive insoles. The investigator initially tested the device at a single site, but wanted to expand to a multicenter study. After an intensive learning experience on the many requirements (such as sIRB), investigator and site selection, length of time to conduct a multicenter trial, and most importantly, cost of conducting a multicentered trial, the investigator concluded her budget could not stretch to multiple sites without compromising quality, and decided instead to focus on strengthening single site data collection. Consultation Outcome: Recommendations Report. Investigator highly satisfied with the training and recommendations provided; plans to return to the TIN when transitioning to a multicenter trial.

Maternal and Infant Outcomes Study: Maternal and Infant Outcomes among Incarcerated Women Who Give Birth in Custody: University of Minnesota Twin Cities and University of Utah TIC. Proposal to conduct a multicenter study of perinatal support for incarcerated women in five geographically representative prisons. The study aims to provide actionable insights for prisons when implementing perinatal support and doula programs to improve maternal and infant health outcomes. With funding secured, the Utah TIC collaborated to execute a single IRB (sIRB). Each participating state prison required partnerships with an academic institution and/or a community-based nonprofit organization. This funded study enables the Utah sIRB to facilitate meaningful stakeholder engagement and address challenges in conducting research with pregnant, incarcerated women. The Utah team worked with the study team to secure sIRB approval, establish reliance partnerships between the nonprofits, and navigate the intricacies of the Department of Corrections review and approval processes in each state. Consultation Outcome: Approval for sIRB Support. Ongoing team collaborations.

Discussion

The low rate of successful completion of clinical trials in the United States constitutes an ongoing national research crisis. Recruitment and retention levels are suffering, costs continue to rise, and design issues produce uninformative data. These factors significantly curtail treatment advancement.

The Covid pandemic produced a dramatic negative impact on the viability of clinical trials for several years beginning in 2020, causing a reduction in the number of proposals for TIN Initial Consultations during that time period. The pandemic faded just as our TIN funding period began winding down. The uncertainty of award renewal for the RIC and TICs prevented us from aggressively promoting our services and likely caused investigators to hesitate in seeking out TIN resources. Since our funding was renewed in 2024, however, we have reinvigorated the dissemination and marketing of the TIN’s services. The number of TIN proposals received rose from 34 in 2023 to 55 in 2024, and we are on target to receive more than 55 in 2025.

The TIN provides scalable solutions to remediate these problems by providing timely advice and resources during initial clinical trial planning stages, at no cost to investigators. Its impact on clinical care is emerging: a recent analysis found that published articles from research supported by CTSAs were significantly more likely to be cited in health policy documents and clinical guidelines than the proportion expected [Reference Llewellyn, Weber, Pelfrey, DiazGranados and Nehl24]. The TIN contributes to this impact by accelerating clinical research so that research results can be more quickly translated into clinical practice.

As previously reported, investigators report high satisfaction with the consultation process and deliverables [Reference Harris, Wilkins, Lane, Bernard, Casey and Ford9]. The TIN’s guiding principle is delivery of high-quality consultations that add value to an investigator’s study via a standardized, yet adaptable process tailored to the needs of each research team. For each Initial Consultation, the TIN leverages CTSA program expertise that complements local institutional resources.

Lessons learned

Through experience, the TIN has learned that:

  • A successful consultation starts with a strong scientific hypothesis, preferably backed by preliminary, supporting data.

  • The TIN strongly recommends submitting a request for an Initial Consultation early in the grant proposal process (60–180 days before submission) to maximize consultation impact. Our consultations include experienced trialists who can often recommend funding sources or suggest strategies for funding submissions. Moreover, they can assist with proposal development, budget planning and resource allocation, and recruitment and retention planning to ensure that the trial is well-designed and appropriately resourced. Studies in need of “rescue” (i.e., studies already funded and in implementation needing additional assistance) often struggle to recruit individuals from populations with limited representation [Reference Peters-Lawrence, Bell, Hsu, Osunkwo, Seaman and Blackwood25].

  • Investigators may be approaching the TIN late in the process because of a lack of awareness. We have been expanding our marketing efforts through conference presentations, webinars, manuscripts, and word of mouth to inform investigators of the expertise freely available to them through a TIN consultation.

  • Ideally, most sites should be US-based to foster broad collaboration within the CTSA Program and NIH Institutes and Centers.

  • Consultations can prove especially beneficial for new investigators, newly organized consortia, or experienced investigators moving into new areas.

  • Successful funding and study completion are not the only measures of a TIN Initial Consultation’s value. In some cases, a proposed study’s design is underdeveloped or under-resourced for a multisite trial. In those cases, the TIN may recommend that a study not move forward, and in doing so, we are often able to educate investigators on the many aspects of the multisite clinical trial process (sIRB, budgeting, recruitment and retention, site selection, etc.), save the investigator time and energy, and reduce the burden of the grants review process, placing them in a position to create a better proposal later with greater chance for success.

  • Investigators at CTSA organizations should consult their local CTSA TIN Liaison to ensure a pragmatic consultation focus.

Limitations

Although potentially open to any trialist, TIN Initial Consultation requests have primarily come from CTSA institutions. For studies not advancing to a Comprehensive Consultation, the TIN has limited ability to track outcomes (e.g., implementation of recommendations provided during consultations) outside of its consultative engagement with study teams. In addition, we are not aware of similar disease-neutral consultation networks outside the TIN to which its process or results can be compared.

Future directions

The TIN will continue to develop new resources through iterative innovation discovery and development. We will continue to work to expand recruitment and retention to improve the representation of different patient groups, enhancing the likelihood of generating actionable and relevant results that benefit all patients. TIN’s Initial Consultation process awareness is being increased through seminars, conferences, and publications to attract new investigators and consortia. The TIN will continually refine its evaluation process to measure the impact of Initial Consultations and the effectiveness of tools and methods.

Conclusion

The TIN’s well-developed infrastructure and wealth of resources help investigators plan, enhance, and expedite their multicenter clinical trials, thereby advancing new healthcare treatments for various diseases more rapidly. This model has been validated through numerous successful Initial Consultations, each tailored to meet an investigator’s specific needs and to overcome identified obstacles. TIN leadership continuously identifies recurring issues that hinder the timely completion of clinical trials and develops new resources to mitigate them. These innovations, incorporated into the TIN’s toolbox of offerings to researchers, continue to expand as new challenges in the clinical research enterprise arise. TIN resources, many available at no cost to the broader research community, are communicated via the website, webinars, and publications. US-based investigators from CTSAs who are conducting or planning to conduct a multicenter study are encouraged to submit a proposal for a TIN consultation.

Acknowledgments

We acknowledge and are especially grateful for the contributions of previous TIN members from Duke University, the University of Utah, and Tufts University who helped develop the Initial Consultation structure. We gratefully acknowledge the contributions of the principal investigators of the case studies highlighted in this paper: Victoria M. Leavitt from Columbia University, New York, NY (Physical Activity in People with Multiple Sclerosis); Dr Linda Van Eldik from The University of Kentucky (BEACH Trial [NIH grants R01 AG069930 and UL1 TR001998]); Dr Dennis McNamara from the University of Pittsburgh, Pittsburgh, PA (REBIRTH Study [U24 HL153846]); Dr Caitlin Hicks from Johns Hopkins University, Baltimore, MD (WIRED UP Study [NIH grant UM1 TR004926]); and Dr Rebecca Shlafer from University of Minnesota Twin Cities, Minneapolis, MN (Maternal and Infant Outcomes Study [NIH grant R01HD103634]). We are also grateful for the partnership and engagement of the Hub Liaison teams from across the Clinical and Translational Science Award program hubs. We acknowledge and thank the NCATS program staff, principal investigator advisors, Clinical and Translational Science Award PIs, and investigative teams that have collaborated with the TIN. We acknowledge with appreciation the VUMC RIC Community Advisory Board for their many contributions to the work of the TIN. We also thank Meghan Vance at VUMC for graphics creation.

Author contributions

Paul A. Harris: Conceptualization, Data curation, Formal analysis, Funding acquisition, Methodology, Project administration, Resources, Software, Supervision, Writing – original draft, Writing – review & editing: Nan Kennedy: Methodology, Project administration, Visualization, Writing – original draft, Writing – review & editing: Consuelo H. Wilkins: Conceptualization, Data curation, Formal analysis, Funding acquisition, Investigation, Methodology, Project administration, Supervision, Writing – review & editing: Karen Lane: Conceptualization, Data curation, Formal analysis, Funding acquisition, Investigation, Methodology, Project administration, Supervision, Writing – original draft, Writing – review & editing: Gordon R. Bernard: Conceptualization, Data curation, Formal analysis, Funding acquisition, Investigation, Methodology, Project administration, Resources, Supervision, Writing – review & editing: Jonathan D. Casey: Conceptualization, Funding acquisition, Investigation, Methodology, Project administration, Resources, Supervision, Writing – review & editing: Daniel E. Ford: Conceptualization, Data curation, Formal analysis, Funding acquisition, Investigation, Methodology, Project administration, Resources, Supervision, Writing – review & editing: Salina P. Waddy: Conceptualization, Methodology, Resources, Supervision, Writing – review & editing: Ken L. Wiley: Conceptualization, Methodology, Resources, Supervision, Writing – review & editing: Terri L. Edwards: Conceptualization, Funding acquisition, Methodology, Project administration, Supervision, Writing – original draft, Writing – review & editing: Nichol McBee: Conceptualization, Funding acquisition, Methodology, Project administration, Supervision, Writing – original draft, Writing – review & editing: Dixie D. Thompson: Conceptualization, Funding acquisition, Methodology, Project administration, Supervision, Writing – original draft, Writing – review & editing: Mary Stroud: Conceptualization, Funding acquisition, Methodology, Project administration, Supervision, Writing – original draft, Writing-review & editing: Emily S. Serdoz: Conceptualization, Funding acquisition, Methodology, Project administration, Supervision, Writing – original draft, Writing – review & editing: Sarah J. Nelson: Conceptualization, Funding acquisition, Methodology, Project administration, Writing – original draft, Writing – review & editing: Michelle Jones: Conceptualization, Data curation, Methodology, Project administration, Writing – review & editing: Lindsay M. Eyzaguirre: Conceptualization, Funding acquisition, Methodology, Project administration, Writing – original draft, Writing – review & editing: Leslie R. Boone: Conceptualization, Investigation, Methodology, Project administration, Supervision, Writing – original draft, Writing – review & editing: Jessica Baird: Conceptualization, Data curation, Methodology, Project administration, Writing – review & editing: Colleen E. Lawrence: Conceptualization, Funding acquisition, Methodology, Project administration, Supervision, Writing – review & editing: Elizabeth Holthouse: Project administration, Writing – original draft, Writing – review & editing: Sarah K. Cook: Conceptualization, Data curation, Methodology, Project administration, Visualization, Writing – review & editing: Maeve Tischbein: Conceptualization, Data curation, Methodology, Project administration, Writing – review & editing: Natalya Amrine: Data curation, Project administration, Writing – review & editing: Tiffany Chen: Data curation, Project administration, Writing – review & editing: Jodie Cohen: Data curation, Methodology, Project administration, Writing – review & editing: LaShondra Deyampert: Data curation, Project administration, Writing – review & editing: Natalie A. Dilts: Conceptualization, Data curation, Methodology, Project administration, Visualization, Writing – review & editing: Delicia Burts: Data curation, Project administration, Writing – review & editing: Amna Baig: Data curation, Project administration, Writing – review & editing: Joseph G. Christodoulou: Data curation, Project administration, Writing – review & editing: Mariela Rodriguez: Data curation, Project administration, Writing – review & editing: Edgar R. Miller: Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Project administration, Supervision, Writing – review & editing: James F. Casella: Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Project administration, Supervision, Writing – review & editing: W. Andrew Mould: Conceptualization, Data curation, Methodology, Project administration, Writing – review & editing: J. Michael Dean: Conceptualization, Data curation, Funding acquisition, Investigation, Methodology, Supervision, Writing – review & editing: Daniel K. Benjamin: Conceptualization, Data curation, Funding acquisition, Investigation, Methodology, Supervision, Writing – review & editing: Harry P. Selker: Conceptualization, Data curation, Funding acquisition, Investigation, Methodology, Supervision, Writing – review & editing: Marisha E. Palm: Conceptualization, Data curation, Funding acquisition, Methodology, Project administration, Supervision, Writing – review & editing: Lori Poole: Data curation, Project administration, Writing – review & editing: Jeri S. Burr: Conceptualization, Funding acquisition, Methodology, Project administration, Supervision, Writing – review & editing: Sara Hassani: Methodology, Project administration, Resources, Supervision, Writing – review & editing: Angeline Nanni: Data curation, Project administration, Writing – review & editing: Meghan Hildreth: Data curation, Project administration, Writing – review & editing: Daniel F. Hanley: Conceptualization, Data curation, Formal analysis, Funding acquisition, Investigation, Methodology, Project administration, Resources, Supervision, Writing – original draft, Writing – review & editing.

Funding statement

This work is supported by the National Institutes of Health NCATS and the National Institute on Aging, in support of the TIN under grant numbers U24TR004432 and U24TR001579 (VUMC RIC), U24TR004437 (VUMC TIC), U24TR004440 and U24TR001609 (JHU TIC), U24TR001608 (VUMC/Duke TIC), U24TR001597 (University of Utah TIC), and UL1TR002544 (Tufts University).

Competing interests

Dr Benjamin reported personal fees from AbbVie, PPD, and Syneos Health outside the submitted work. No other disclosures were reported.

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Figure 0

Figure 1. Trial Innovation Network partners, 2025. CTSA = Clinical and Translational Science Award.

Figure 1

Table 1. Initial Consultation – TIN roles and responsibilities

Figure 2

Table 2. Initial Consultation areas of innovative emphasis

Figure 3

Figure 2. TIN Initial Consultations metrics – distribution of institution funding/research activity classification and investigator roles. R1= research 1; R2 = research 2. *Based on the Carnegie Classification of Institutions of Higher Learning©.