Reader Response: Clinical trials of disease-modifying agents in pediatric MS: Opportunities, challenges, and recommendations from the IPMSSG
KlausRose, MD, Chief Executive Officer, klausrose Consulting, Pediatric Drug Development & More, 4125 Riehen, Switzerland
LucioFumi, MD, Chief Executive Officer, Wyfold Medical Consultancy The Innovation Centre, Howbery Park Oxford, UK
Jane MGrant-Kels, Professor of Dermatology, Pathology, and Pediatrics Dermatology,, UConn Health, 263 Farmington Avenue, Farmington, CT 06030-6230 USA
Submitted May 31, 2019
Waubant et al. criticized placebo-controlled trials in pediatric multiple sclerosis (MS),1 but failed to address a core challenge. The terms “children” and “pediatrics” have 2 connotative considerations: legal/administrative and physiological. The American Academy of Pediatrics (AAP) defines pediatrics as patients <21-years-old; older with special needs.2 This is adequate to define administratively which patients pediatricians can/should treat, but inadequate as inclusion criterion for efficacy trials.3 MS and depression can emerge when the CNS reaches some maturity; epilepsy occurs at any age. There is no "pediatric" MS or depression. Both diseases begin sometimes in minors, but do not change fundamentally at Food and Drug Administration (FDA)/European Medicines Agency (EMA)-defined birthdays (17 years and 18 years, respectively).4 Separate pediatric drug development in non-neonatals emerged with the acceptance of the children-are-therapeutic-orphans concept by the AAP and FDA.5 The United States’ rewards for separate "pediatric" studies created conflicts of interest in regulatory authorities, academia, and pharmaceutical industry.3 Today, the FDA accepts adolescents in adult cancer studies and has partially relented to demands for separate "pediatric" studies in dermatology and epilepsy, while the EMA remains unfortunately adamant.4 Separate "pediatric" efficacy studies in minors with mature bodies are unethical. This challenge goes beyond individual clinical disciplines; but, without clinicians critically addressing it, it will never be resolved.
Disclosure
The authors report no relevant disclosures. Contact [email protected] for full disclosures.
References
Waubant E, Banwell B, Wassmer E, et al. Clinical trials of disease-modifying agents in pediatric MS: Opportunities, challenges, and recommendations from the IPMSSG. Neurology 2019;92:e2538–e2549.
Hardin AP, Hackell JM; COMMITTEE ON PRACTICE AND AMBULATORY MEDICINE. Age Limit of Pediatrics. Pediatrics 2017;140:e20172151.
Rose K, Neubauer D, Grant-Kels JM. Rational Use of Medicine in Children – The Conflict of Interests Story. A Review. Rambam Maimonides Med J (in press 2019).
Rose K, Grant-Kels JM. Pediatric melanoma—The whole (conflicts of interest) story. Int J Womens Dermatol 2018;5:110–115.
Ward RM, Benjamin DK Jr, Davis JM, et al. The Need for Pediatric Drug Development. J Pediatr 2018;192:13–21.
Waubant et al. criticized placebo-controlled trials in pediatric multiple sclerosis (MS),1 but failed to address a core challenge. The terms “children” and “pediatrics” have 2 connotative considerations: legal/administrative and physiological. The American Academy of Pediatrics (AAP) defines pediatrics as patients <21-years-old; older with special needs.2 This is adequate to define administratively which patients pediatricians can/should treat, but inadequate as inclusion criterion for efficacy trials.3 MS and depression can emerge when the CNS reaches some maturity; epilepsy occurs at any age. There is no "pediatric" MS or depression. Both diseases begin sometimes in minors, but do not change fundamentally at Food and Drug Administration (FDA)/European Medicines Agency (EMA)-defined birthdays (17 years and 18 years, respectively).4 Separate pediatric drug development in non-neonatals emerged with the acceptance of the children-are-therapeutic-orphans concept by the AAP and FDA.5 The United States’ rewards for separate "pediatric" studies created conflicts of interest in regulatory authorities, academia, and pharmaceutical industry.3 Today, the FDA accepts adolescents in adult cancer studies and has partially relented to demands for separate "pediatric" studies in dermatology and epilepsy, while the EMA remains unfortunately adamant.4 Separate "pediatric" efficacy studies in minors with mature bodies are unethical. This challenge goes beyond individual clinical disciplines; but, without clinicians critically addressing it, it will never be resolved.
Disclosure
The authors report no relevant disclosures. Contact [email protected] for full disclosures.
References