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Randomized Controlled Trial
. 2023 Feb:125:107067.
doi: 10.1016/j.cct.2022.107067. Epub 2022 Dec 25.

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

Angelique E Boutzoukas  1 , Rachel Olson  2 , Mary Ann Sellers  2 , Gwenyth Fischer  3 , Chi D Hornik  1 , Omar Alibrahim  4 , Kelechi Iheagwara  5 , Kamal Abulebda  6 , Andora L Bass  7 , Katherine Irby  8 , Anjali Subbaswamy  9 , Elizabeth E Zivick  10 , Jill Sweney  11 , Anne G Stormorken  12 , Erin E Barker  13 , Riad Lutfi  6 , Michael C McCrory  7 , John M Costello  10 , Kate G Ackerman  13 , Jennifer C Munoz Pareja  14 , J Michael Dean  15 , Nael Abdelsamad  15 , Daniel F Hanley Jr  16 , W Andrew Mould  16 , Karen Lane  16 , Mary Stroud  17 , Bryan J Feger  2 , Rachel G Greenberg  1 , P Brian Smith  1 , Daniel K Benjamin Jr  1 , Christoph P Hornik  1 , Kanecia O Zimmerman  1 , Mara L Becker  18
Affiliations
Randomized Controlled Trial

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

Angelique E Boutzoukas et al. Contemp Clin Trials. 2023 Feb.

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 #: NCT03938857.

Keywords: Clinical trial; Milestones; Pediatric trials; Study start-up.

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Conflict of interest statement

Declaration of Competing Interest AEB receives salary support through the US government National Institute of Child Health and Human Development T32 training grant (1T32HD094671). 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. CDH has performed consulting services for Tellus Therapeutics and Amarin Pharma, Inc. unrelated to the content of this article. JMC receives salary support from the National Institutes of Health (U24HL135691). RGG and KGA have provided consulting services for industry unrelated to the content of this article. 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).

Figures

Figure 1.
Figure 1.. Example Timeline for Activation Milestone-driven Reimbursements.
Four potential reimbursement milestones were offered as part of DOSE. Note: Because the regulatory packets and CTAs were received on different dates, Day 0 had to differ for certain milestones, represented by the different colors of shading on the top and bottom half of the figure. Abbreviations: CTA, clinical trial agreement; DOSE, Dexmedetomidine Opioid Sparing Effect in Mechanically Ventilated Children; IRB, institutional review board.
Figure 2.
Figure 2.. Distribution of Key Start-up Activities by Site.
Probability density plot of time to start-up activities from n=19 sites. Time from regulatory packet completion (blue) was measured from the date that the regulatory packet was sent. The remainder of milestones shown were measured starting from the date that the clinical trial agreement (CTA) was sent. The dashed lines represent the median time for each milestone. Abbreviations: CTA: Clinical trial agreement.
See this image and copyright information in PMC

References

    1. Fogel DB. Factors associated with clinical trials that fail and opportunities for improving the likelihood of success: A review. Contemp. Clin. Trials Commun. 11 (2018) 156–164. doi:10.1016/j.conctc.2018.08.001 - DOI - PMC - PubMed
    1. Krafcik BM, Doros G, Malikova MA. A single center analysis of factors influencing study start-up timeline in clinical trials. Future Sci. OA. 3 (4) (2017) FSO223. doi:10.4155/fsoa-2017-0025 - DOI - PMC - PubMed
    1. Schimanski C. Streamline and improve study start-up. Appl. Clin. Trials. 22 (9) (2013).
    1. Lai J, Forney L, Brinton DL, Simpson KN. Drivers of start-up delays in global randomized clinical trials. Ther. Innov. Regul. Sci. 55 (1) (2021) 212–227. doi:10.1007/s43441-020-00207-2 - DOI - PMC - PubMed
    1. Lamberti MJ, Wilkinson M, Harper B, Morgan C, Getz K. Assessing study start-up practices, performance, and perceptions among sponsors and contract research organizations. Ther. Innov. Regul. Sci. 52 (5) (2018) 572–578. doi:10.1177/2168479017751403 - DOI - PubMed

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