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

Autor: Wasylewski MT; Dept. of Philosophy and Bioethics, REMEDY, Research Ethics in Medicine Study Group, Jagiellonian University Medical College, Krakow, Poland., Strzebonska K; Dept. of Philosophy and Bioethics, REMEDY, Research Ethics in Medicine Study Group, Jagiellonian University Medical College, Krakow, Poland., Koperny M; Dept. of Philosophy and Bioethics, REMEDY, Research Ethics in Medicine Study Group, Jagiellonian University Medical College, Krakow, Poland., Polak M; Dept. of Philosophy and Bioethics, REMEDY, Research Ethics in Medicine Study Group, Jagiellonian University Medical College, Krakow, Poland.; Dept. of Epidemiology and Population Studies, Jagiellonian University Medical College, Krakow, Poland., Kimmelman J; Studies of Translation, Ethics and Medicine (STREAM), Biomedical Ethics Unit, McGill University, Montreal, Canada., Waligora M; Dept. of Philosophy and Bioethics, REMEDY, Research Ethics in Medicine Study Group, Jagiellonian University Medical College, Krakow, Poland.
Jazyk: angličtina
Zdroj: PloS one [PLoS One] 2020 Jun 24; Vol. 15 (6), pp. e0234911. Date of Electronic Publication: 2020 Jun 24 (Print Publication: 2020).
DOI: 10.1371/journal.pone.0234911
Abstrakt: 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.
Conclusions: Our analysis shows that treatments tested in pediatric Phase 1 trials in oncology have low rates of regulatory approval. However, a large proportion of Phase 1 trials inform further testing and development of tested interventions.
Competing Interests: Marcin Waligora reports personal fees from Advisory Bioethics Council, Sanofi outside the submitted work. This does not alter our adherence to PLOS ONE policies on sharing data and materials. Other authors have declared that no competing interests exist.
Databáze: MEDLINE
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