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

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.

Using single IRB consultations to meet the educational needs of investigative teams.

Single IRB (SIRB) consultation resources were established by the Utah Trial Innovation Center to assist and educate investigative teams prior to the submission of funding applications for multisite, cooperative research. Qualitative analysis of the written consultation materials and meeting minutes revealed the most common areas of education needed by investigative teams, including (a) the differences and relationships between the IRB and a Human Research Protection Program (HRPP); (b) the main phases of the SIRB process; and (c) the use of technology platforms for documentation of SIRB review processes. For investigative teams who are inexperienced with using a SIRB, such consultation in the pre-award period is likely to fill in knowledge gaps and improve the study start-up process.

Diabetic muscle infarction: often misdiagnosed and mismanaged.

A patient with type 2 diabetes, retinopathy, neuropathy, and nephropathy presented with severe right distal thigh pain, which awoke him from sleep. He was diagnosed with musculoskeletal pain and discharged home. Two days later, the severity of pain increased in his right thigh and, subsequently, he developed pain in the proximal lateral aspect of his left thigh, for which he returned to hospital. He had elevated creatine kinase and myoglobin levels. An ultrasound of the right thigh identified a loss of definition of the normal muscular striations and subcutaneous edema. On MRI, the axial STIR image demonstrated extensive T2 hyperintensity in the right vastus medialis and left vastus lateralis, consistent with the diagnosis of diabetic muscle infarction (DMI). This presentation emphasizes the need for a thorough patient history and physical examination, and the importance of directed imaging for the prompt diagnosis of DMI.