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

Abstract

Objectives Drug development trials must fulfill social value requirement but no estimates of value provided by pediatric Phase 1 trials in oncology exist. These trials involve a particularly vulnerable population. Our objective was to assess of surrogates of social value of Phase 1 trials performed in pediatric oncology: rates of approval of tested interventions, transition to further phases of testing and citation in subsequent primary research reports. Methods We performed an analysis on a subset of eligible trials included in a previous meta-analysis. That study systematically searched EMBASE and PubMed for small sample size, non-randomized, dose escalation pediatric cancer Phase 1 studies of any malignancy, assessing chemotherapy and/or targeted therapy and looked at risk and benefit. The current analysis assessed all studies in that review published between January 1st 2004 and December 31st 2013 for predictors of social value. This time range allowed for at least five years of subsequent development activity. Sources of data included FDA and EMA medicine databases (for approval), ClinicalTrials.gov and EU Clinical Trials Register (for transition) and Google Scholar (for citation). Results One hundred thirty-nine trials enrolling 3814 patients met the eligibility criteria. Seven trials (5%) led to drugs being registered for pediatric use in therapy of cancer. Fifty-two (37%) transitioned to later phases of pediatric oncology trials according to ClinicalTrials.gov and/or EU Register. Over 90% of trials were cited by at least one subsequent primary research report or systematic review. Most of the citations were preclinical studies.

Evolution of the Innovative Therapies for Children With Cancer Consortium Trial Portfolio for Drug Development for Children With Cancer

“…Seventeen of the 40 dose-finding studies transitioned from phase I to further stages (41%), similar to the 35% reported in other pediatrics reports, 43 and this proportion improved over time (33% v 45%).…”

“…9 In agreement with ITCC recommendations, the majority of dose-finding trials (62%) incorporated expansion phase cohorts where additional safety, pharmacologic, and preliminary efficacy data could be collected, enabling the evaluation of biomarkers and response and the selection of new drugs for subsequent randomized trials (Table 3, Data Supplement, Table S1). Seventeen of the 40 dose-finding studies transitioned from phase I to further stages (41%), similar to the 35% reported in other pediatrics reports, 43 and this proportion improved over time (33% v 45%).…”

Risk and benefit for umbrella trials in oncology: a systematic review and meta-analysis

“…Furthermore, early phases of clinical trials also poorly predict phase III success. Therefore, surrogate measures should be considered only hypothesis-generating and not a marker of true clinical benefit [74][75][76][77][78].…”

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

“…Globally, it is estimated that there will be 13.7 million new pediatric cancer cases by 2050 [ 2 ]. Hence, new therapeutics that meaningfully improve outcomes in pediatric cancers are needed [ 3 , 4 ].…”