Mechanisms to expedite pediatric clinical trial site activation: The DOSE trial experience

Angelique E. Boutzoukas, Rachel Olson, Mary Ann Sellers, Gwenyth Fischer, Chi D. Hornik, Omar Alibrahim, Kelechi Iheagwara, Kamal Abulebda, Andora L. Bass, Katherine Irby, Anjali Subbaswamy, Elizabeth E. Zivick, Jill Sweney, Anne G. Stormorken, Erin E. Barker, Riad Lutfi, Michael C. McCrory, John M. Costello, Kate G. Ackerman, Jennifer C. Munoz ParejaJ. Michael Dean, Nael Abdelsamad, Daniel F. Hanley, W. Andrew Mould, Karen Lane, Mary Stroud, Bryan J. Feger, Rachel G. Greenberg, P. Brian Smith, Daniel K. Benjamin, Christoph P. Hornik, Kanecia O. Zimmerman, Mara L. Becker

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Background: Timely trial start-up is a key determinant of trial success; however, delays during start-up are common and costly. Moreover, data on start-up metrics in pediatric clinical trials are sparse. To expedite trial start-up, the Trial Innovation Network piloted three novel mechanisms in the trial titled Dexmedetomidine Opioid Sparing Effect in Mechanically Ventilated Children (DOSE), a multi-site, randomized, double-blind, placebo-controlled trial in the pediatric intensive care setting. Methods: The three novel start-up mechanisms included: 1) competitive activation; 2) use of trial start-up experts, called site navigators; and 3) supplemental funds earned for achieving pre-determined milestones. After sites were activated, they received a web-based survey to report perceptions of the DOSE start-up process. In addition to perceptions, metrics analyzed included milestones met, time to start-up, and subsequent enrollment of subjects. Results: Twenty sites were selected for participation, with 19 sites being fully activated. Across activated sites, the median (quartile 1, quartile 3) time from receipt of regulatory documents to site activation was 82 days (68, 113). Sites reported that of the three novel mechanisms, the most motivating factor for expeditious activation was additional funding available for achieving start-up milestones, followed by site navigator assistance and then competitive site activation. Conclusion: Study start-up is a critical time for the success of clinical trials, and innovative methods to minimize delays during start-up are needed. Milestone-based funds and site navigators were preferred mechanisms by sites participating in the DOSE study and may have contributed to the expeditious start-up timeline achieved. ClinicalTrials.gov

Original languageEnglish (US)
Article number107067
JournalContemporary Clinical Trials
Volume125
DOIs
StatePublished - Feb 2023

Bibliographical note

Funding Information:
This trial was funded by the Trial Innovation Network, supported by the National Center for Advancing Translational Sciences, National Institut2es of Health, under award numbers U24TR001608, U24TR001597, U24TR001609, and U24TR001579.MLB receives salary support from the National Institutes of Health (5R01HD089928–05, 5U24TR001608–4, HHSN275201800003I, 3U24TR001608-04S1), PCORI (PaCr-2017C2–8177), FDA Arthritis Advisory Committee, and the Childhood Arthritis and Rheumatology Research Alliance.JMC receives salary support from the National Institutes of Health (U24HL135691).CPH receives salary support for research from National Institute for Child Health and Human Development (NICHD) (R13HD102136; RL1HD107784; R01HD106588), the National Heart Lung and Blood Institute (NHLBI) (R61/R33HL147833), the US Food and Drug Administration (R01-FD006099, PI Laughon; and U18-FD006298), the U.S. government for his work in pediatric clinical pharmacology (Government Contract HHSN275201800003I, PI: Benjamin under the Best Pharmaceuticals for Children Act), the non-profit Burrhoughs Wellcome Fund, and other sponsors for drug development in adults and children (https://dcri.org/about-us/conflict-of-interest/).KOZ received salary support from NICHD (1K23HD091398; Zimmerman), Duke CTSA (KL2TR001115; Zimmerman), Pediatric Trials Network (NIH/HHSN-275201000003I), and FDA (UG3/UH3 FD 006797).Dr. Becker and DCRI coauthors eagerly acknowledge the tireless efforts of the DOSE Clinical Coordinating Center team: Suzanne Aycock, Elizabeth Mocka, Carrie Elliot, Theresa Jasion, Alexandra McCormick, Maya McKean-Peraza, and Grant Booth. They also gratefully acknowledge the Trial Innovation Network (TIN), a collaborative initiative supported by the National Center for Advancing Translational Research (NCATS), National Institutes of Health (NIH), under awards U24TR001608, U24TR001597, U24TR001609, and U24TR001579, which aims to both improve the execution of clinical trials and serve as a national laboratory to study, understand, and innovate the process of conducting clinical trials. Dr. Chi D. Hornik acknowledges the lead study coordinator at Duke, Melissa Harward. The JHU authors heartily acknowledge and thank the DOSE start-up navigators Sarah Lenington, Carolyn Koenig, Shannon Hillery, and Ryan Majkowski. Dr. Alibrahim acknowledges the PICU team (staff, faculty and fellows) at his previous institution at John R. Oishei Children's Hospital in Buffalo, NY, and his previous outstanding research coordinator Haiping Qiao for her selfless efforts during study initiation, patient enrollment, and others.

Funding Information:
Dr. Becker and DCRI coauthors eagerly acknowledge the tireless efforts of the DOSE Clinical Coordinating Center team: Suzanne Aycock, Elizabeth Mocka, Carrie Elliot, Theresa Jasion, Alexandra McCormick, Maya McKean-Peraza, and Grant Booth. They also gratefully acknowledge the Trial Innovation Network (TIN), a collaborative initiative supported by the National Center for Advancing Translational Research (NCATS), National Institutes of Health (NIH), under awards U24TR001608 , U24TR001597 , U24TR001609 , and U24TR001579 , which aims to both improve the execution of clinical trials and serve as a national laboratory to study, understand, and innovate the process of conducting clinical trials. Dr. Chi D. Hornik acknowledges the lead study coordinator at Duke, Melissa Harward. The JHU authors heartily acknowledge and thank the DOSE start-up navigators Sarah Lenington, Carolyn Koenig, Shannon Hillery, and Ryan Majkowski. Dr. Alibrahim acknowledges the PICU team (staff, faculty and fellows) at his previous institution at John R. Oishei Children's Hospital in Buffalo, NY, and his previous outstanding research coordinator Haiping Qiao for her selfless efforts during study initiation, patient enrollment, and others.

Funding Information:
This trial was funded by the Trial Innovation Network , supported by the National Center for Advancing Translational Sciences , National Institut2es of Health , under award numbers U24TR001608 , U24TR001597 , U24TR001609 , and U24TR001579 .

Publisher Copyright:
© 2022 Elsevier Inc.

Keywords

  • Clinical trial
  • Milestones
  • Pediatric trials
  • Study start-up

PubMed: MeSH publication types

  • Randomized Controlled Trial
  • Journal Article
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

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