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Safety should come first in children’s clinical trials

New recommendations for studying drugs in children issued this week by the American Academy of Pediatrics emphasized the ethical responsibilities of those who conduct trials in this vulnerable population.

Without pediatric-specific clinical trials, medication use in children is either off-label or based on data extrapolated from adults, resulting in greater potential risk for adverse events, committee members emphasized. “This situation imposes special considerations when inviting participation in studies, assessing risks and benefits and ensuring equitable participation in and benefits of clinical research,” they wrote.

Most of the guidelines remain unchanged from those published by the AAP in 1995; however, several key areas have been strengthened. The new framework focuses particularly on the necessity of a safety plan during all phases of the clinical trial and calls for independent data and safety monitoring committees to be in place for all phase-3 trials and some phase-1 and -2 trials, especially if they involve blinding.

The committee also called for study investigators to have “true uncertainty about which of the treatments being compared in the research study is superior” and made a case that all pediatric trials be registered and have results published to avoid repeating unnecessary — and therefore unethical — trials.

Additionally, due to the high risk-benefit ratio inherent in the early stages of the clinical trial process, the committee argued that pediatric studies should be deferred until a drug reaches phase-3 trials in adults, except in cases when a disease is severe or life-threatening and no other proven therapy is available.

Other changes included:

• Guidance for how to disclose potential conflicts of interest, including suggestions that institutions create conflict-of-interest committees separate from the institutional review board.
• A section detailing when requirements for informed permission can be waived, including situations where risk is minimal and also when getting permission does not function to protect the child, such as when the study involves neglected or abused children.
• Revisions to how clinical trial compensation is handled to ensure that payment is fair and does not “become an undue inducement for participation of the child.

“The AAP believes it is unethical to deny children appropriate access to existing and new therapeutic agents,” committee members wrote. “It is the combined responsibility of the pediatric community, pharmaceutical industry and regulatory agencies to design, approve and conduct high-quality studies in children,” the committee members wrote.

Shaddy RE. Pediatrics. 2010;125:850-860.

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