Participant Protection in Phase 1 Pediatric Cancer Trials

Abstract

Advances in pediatric cancer treatment represent one of modern medicine's greatest achievements. This progress would not be possible without testing new therapies in children. However, pediatric research must satisfy stricter ethical and regulatory standards than research with adults, in light of children's inability to provide consent. We contend that current approaches to approving phase 1 pediatric cancer trials may inappropriately hinge on perceptions of therapeutic benefit without adequate consideration of the unlikelihood of such benefit in many cases and the magnitude of associated risks. Although such research is critically important, steps should be taken to maximize the prospect of direct benefit to enrolled children and to use alternative approval pathways for clinical trials that are socially valuable but unlikely to offer direct benefit to the pediatric participants.

Ethical Review and Methodologic Innovation in Phase 1 Cancer Trials—Reply

“…But in the presence of pharmacokinetic and pharmacodynamic heterogeneity, forbidding judicious titration appears on close examination both incoherent and unethical. 3 Consider that each new cohort in a dose-escalation trial is itself a first-inhumans mini-trial conducted at a never-before-tried dose. When intrapatient dose escalation is not allowed, each such mini-trial must enroll drug-naive participants.…”

Risk and Benefit for Targeted Therapy Agents in Pediatric Phase II Trials in Oncology: A Systematic Review with a Meta-Analysis

“…Cancer phase II studies are an important element of the drug development process designed to establish the shortterm activity of new treatments, further evaluate safety and toxicity and, if these treatments are sufficiently promising, advance them for evaluation in phase III trials [11]. To be considered as ethical, research involving pediatric participants must meet, among others, a favorable risk/benefit ratio criterion [12][13][14]. The determination of whether risks and potential benefits of research interventions are acceptable requires ethical and clinical expertise and scientific knowledge and data [15].…”

Clinical development success rates and social value of pediatric Phase 1 trials in oncology

“…Children are a unique group of participants and are considered vulnerable. Pediatric trials are evaluated with enhanced caution and must adhere to stricter standards than their counterparts with adult participants [7]. Most regulations allow only minimal risk or require the prospect of direct benefit for participants [8][9][10].…”