Trial design

Bringing research directly to families in the era of COVID-19

Posted on by Kayla Korzekwinski

Pediatric Research • November 2020

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Balevic SJ, Singler L, Randell R, Chung RJ, Lemmon ME, Hornik CP

In order to optimize direct-to-family trials, investigators should seek early feedback from regulatory authorities about proposed safety and follow-up procedures, and feedback from family and other stakeholders on study schedules and interventions. Pediatric clinical research must adapt to be more flexible, efficient, and cost effective to increase access to clinical trials both during the COVID-19 pandemic and beyond.

Innovative Study Designs Optimizing Clinical Pharmacology Research in Infants and Children

Posted on by Kayla Korzekwinski

The Journal of Clinical Pharmacology • October 2019

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Balevic SJ, Cohen-Wolkowiez M

Almost half of recent pediatric trials failed to achieve labeling indications, due in large part to inadequate study design. Therefore, innovative study methods are crucial to optimize trial design while also reducing the potential harms inherent with drug investigation. New and innovative study designs are imperative to address current clinical pharmacology gaps and to ensure future therapeutics are safe and effective for children.

Creation of a Multicenter Pediatric Inpatient Data Repository Derived from Electronic Health Records

Posted on by Kayla Korzekwinski

Applied Clinical Informatics Journal • March 2019

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Hornik CP, Atz AM, Bendel C, Chan F, Downes K, Grundmeier R, Fogel B, Gipson D, Laughon M, Miller M, Smith M, Livingston C, Kluchar C, Heath A, Jarrett C, McKerlie B, Patel H, Hunter C; Best Pharmaceuticals for Children Act Pediatric Trials Network

Integration of electronic health records (EHRs) data across sites and access to that data remain limited. This study developed an EHR-based pediatric inpatient repository using nine U.S. centers from the National Institute of Child Health and Human Development Pediatric Trials Network.

A pharmacokinetic model for amiodarone in infants developed from an opportunistic sampling trial and published literature data

Posted on by Kayla Korzekwinski

Journal of Pharmacokinetics and Pharmacodynamics • June 2018

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Dallefeld SH, Atz AM, Yogev R, Sullivan JE, Al-Uzri A, Mendley SR, Laughon M, Hornik CP, Melloni C, Harper B, Lewandowski A, Mitchell J, Wu H, Green TP, Cohen-Wolkowiez M.

Amiodarone is a first-line antiarrhythmic for life-threatening ventricular fibrillation or ventricular tachycardia in children, yet little is known about its pharmacokinetics (PK) in this population. We developed a population PK (PopPK) model using samples collected via an opportunistic study design of children receiving amiodarone per standard of care supplemented by amiodarone PK data from the literature.

Perceived barriers to pediatrician and family practitioner participation in pediatric clinical trials: Findings from the Clinical Trials Transformation Initiative

Posted on by Kayla Korzekwinski

Contemporary Clinical Trials Communications • November 2017

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Greenberg RG, Corneli A, Bradley J, Farley J, Jafri HS, Lin L, Nambiar S, Noel GJ, Wheeler C, Tiernan R, Smith PB, Roberts J, Benjamin DK Jr.

Despite legislation to stimulate pediatric drug development through clinical trials, enrolling children in trials continues to be challenging. Non-investigator providers are essential to recruitment of pediatric patients, but little is known regarding the specific barriers that limit pediatric providers from participating in and referring their patients to clinical trials. This study conducted an online survey of pediatric providers from a wide variety of practice types across the United States to evaluate their attitudes and awareness of pediatric clinical trials.

Pharmacologic studies in vulnerable populations – using the pediatric experience

Posted on by Kayla Korzekwinski

Seminars in Perinatology • November 2016

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Zimmerman K, Gonzalez D, Swamy GK, Cohen-Wolkowiez M
Historically, few data exist to guide dosing in children and pregnant women. Multiple barriers to inclusion of these vulnerable populations in clinical trials have led to this paucity of data. Given the similar barriers to drug research and development in pediatric and pregnant populations, the route toward success in children may serve as a model for the advancement of drug development and appropriate drug administration in pregnant women.

Optimizing operational efficiencies in early phase trials: The Pediatric Trials Network experience

Posted on by Kayla Korzekwinski

Contemporary Clinical Trials • March 2016

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England A, Wade K, Smith PB, Berezny K, Laughon M; Best Pharmaceuticals for Children Act — Pediatric Trials Network Administrative Core Committee.

Performing drug trials in pediatrics is challenging. In support of the Best Pharmaceuticals for Children Act, the Eunice Kennedy Shriver National Institute of Child Health and Human Development funded the formation of the Pediatric Trials Network (PTN) in 2010. Since its inception, the PTN has developed strategies to increase both efficiency and safety of pediatric drug trials. Through use of innovative techniques such as sparse and scavenged blood sampling as well as opportunistic study design, participation in trials has grown. The PTN has also strived to improve consistency of adverse event reporting in neonatal drug trials through the development of a standardized adverse event table. We review how the PTN is optimizing operational efficiencies in pediatric drug trials to increase the safety of drugs in children.

Dosing in neonates: Special considerations in physiology and trial design

Posted on by Kayla Korzekwinski

Pediatric Research • January 2016

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Ku LC, Smith PB
Determining the right dose for drugs used to treat neonates is critically important. Neonates have significant differences in physiology affecting drug absorption, distribution, metabolism, and elimination that makes extrapolating dosages from adults and older children inappropriate. Fortunately, specialized analytical techniques, such as the use of dried blood spots, scavenged sampling, population pharmacokinetics analyses, and sparse sampling, have helped investigators better define doses that maximize efficacy and safety. Through the use of these methods, successful clinical trials have resulted in recent changes to drug dosing in this population.

Innovative clinical trial design for pediatric therapeutics

Posted on by Kayla Korzekwinski

Expert Review of Clinical Pharmacology • September 2011

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Laughon MM, Benjamin DK Jr, Capparelli EV, Kearns GL, Berezny K, Paul IM, Wade K, Barrett J, Smith PB, Cohen-Wolkowiez M.

Until approximately 15 years ago, sponsors rarely included children in the development of therapeutics. US and European legislation has resulted in an increase in the number of pediatric trials and specific label changes and dosing recommendations, although infants remain an understudied group.