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Investigation programs needed for study of risks in use of pediatric anticoagulant drugs
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The International Society on Thrombosis and Haemostasis called for the development of pediatric investigative programs to study risks of anticoagulants in children and the establishment of a safety monitoring board for the development of new anticoagulant drugs for pediatric populations, according to a proposed guideline published in the Journal of Thrombosis and Haemostasis.
Recommendations
One recommendation of note was that pediatric investigation programs should include pediatric thrombosis experts who consider how thromboembolism differs in children vs. adults. The Society also recommended that an established safety monitoring board be involved through all stages of drug development.
In addition to preclinical data determining toxicology, the researchers considered a need for juvenile animal studies on toxicity, especially in relation to growth and development. They also recommended studies on age-appropriate formulations for all drugs.
Investigative studies
The document further outlined considerations and goals for the design and testing of the drugs during phase 1, 2, 3 and 4 studies.
During phase 1 of the study — primarily establishing basic safety, pharmacokinetic (PK) and pharmacodynamic (PD) parameters and dosing — the researchers recommended study participants only include children who completed their course of anticoagulation for a venous thromboembolism (VTE) and have a relatively high risk of recurrence.
A phase 2 study, which would further investigate the safety in a larger cohort and establish dosing practices, can be of various designs and may include a comparison arm using standard anticoagulants or placebo. The phase 2 study should be conducted in children who undergo late phase anticoagulant treatment for VTE following a period of standard anticoagulant treatment.
Establishing efficacy, safety and a positive benefit-to-risk ratio during phase 3 poses challenges in the pediatric population because this typically requires the enrollment of thousands of patients. The researchers said some data would have to be extrapolated from adult studies.
“For treatment of VTE, phase 3 studies should comprise the entire treatment period, with randomization occurring early, ie within 1 week of initiating anticoagulation. The assessment of primary outcome should be performed after 3 [to] 6 months of treatment, and patients requiring longer anticoagulation can be followed further for secondary outcomes. It is important that phase 3 studies continue to collect PK and/or PD data from children,” the researchers wrote.
In phase 4 studies, the researchers advised researchers to continue to assess outcomes such as bone density, neuropsychological development and growth following the approval of an anticoagulant for pediatric use.
Guy Young
Guy Young, MD, of the Hemostasis and Thrombosis Center, Children’s Hospital Los Angeles at the University of Southern California Keck School of Medicine, told HemOnc Today, “This important recommendation outlines the manner in which new anticoagulant drugs should be studied and developed in children. . . . Manufacturers and sponsors should use these as a guide in their pediatric drug development programs.” – by Suzanne Bryla Reist
Disclosures: Male reports membership in the Steering Committees for Bayer and Bristol-Myers Squibb outside of the submitted work. The researchers report no other relevant financial disclosures.
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