Industry Perspective of Pediatric Drug Development in the United States: Involvement of the European Union Countries

T, Onishi; Tsukamoto, Katsura; Matsumaru, Naoki; Waki, Takashi

doi:10.1177/2168479017716718

Cited by 4 publications

(2 citation statements)

References 17 publications

(19 reference statements)

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“…56 Many general updates on pediatric research are good overviews. 9,[57][58][59][60][61][62][63][64] However, decoding is required to understand their true meaning. They do not describe/discuss research for clinical improvement, but use pediatric labels as endpoints.…”

Section: Triggered Studiesmentioning

confidence: 99%

The Meanings of “Pediatric Drug Development”

Rose¹,

Grant‐Kels

2019

Ther Innov Regul Sci

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Pediatric drug development (PDD) became an industry goal when the Food and Drug Administration (FDA) granted patent extensions. This was later expanded to obligations for pediatric studies and to the European Medicines Agency’s (EMA’s) strict pediatric investigation plans (PIPs). Industry now sponsors many often international studies in young patients that are difficult or impossible to recruit. PDD’s intellectual foundations characterize children as “therapeutic orphans,” allegedly discriminated in drug treatment and development. While toxicities occured in newborns, demanding separate efficacy and safety (E&S) studies in all age groups is wasteful and reflects hidden conflicts of interest. The American Academy of Pediatrics (AAP) successfully procured pediatric research funds; the FDA dislikes pediatric off-label use and envisions labels as instructions for physicians. Pediatricians have continuously improved child health care by careful use of available drugs. Instead of physiologically defining children vis-à-vis drug treatment, the FDA defines children as ≤16 years old, offering convincing pretense for the need for mostly senseless “pediatric” studies in young adults, adolescents, and children. Although these studies may help advance pediatric academic careers, they do not improve pediatric health care. The EMA defines children as <18 years old and demands even more senseless and potentially harmful “pediatric” studies. Young patients need pharmacokinetic/pharmacodynamic and dose finding, but not separate E&S, studies. Institutional review boards and ethics committees should suspend or reject questionable FDA/EMA-demanded “pediatric” studies. Industry and science need repositioning towards “PDD”; US/EU pediatric laws need revision. We hope this will not take decades.

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Section: Triggered Studiesmentioning

confidence: 99%

The Meanings of “Pediatric Drug Development”

Rose¹,

Grant‐Kels

2019

Ther Innov Regul Sci

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“…Pediatric drug development (PDD) is a term being misused in the title of several books,1, 2 in US Food and Drug Administration (FDA) 3 and International Conference on Harmonisation 4 documents, in academic publications,5, 6, 7, 8, 9 in articles by pharmaceutical industry employees,10, 11 and by regulatory authorities 12, 13. The term pediatric development is also being used with the same meaning 14, 15.…”

Section: Introductionmentioning

confidence: 99%

The Challenges of Pediatric Drug Development

Rose¹

2019

Current Therapeutic Research

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Introduction and Background “Pediatric Drug Development” is being used to describe not the development of drugs for children, but rather the planning & conducting separate efficacy and safety (E&S) studies requested/demanded by regulatory authorities designed to produce pediatric labels. Pediatric studies required for drug approval enroll “children”; defined as <17 years of age (US Food and Drug Administration [FDA])/ <18 years (European Union [EU]). The medical rationale for study designs was examined. Material & Methods International industry-sponsored pediatric E&S studies registered in www.clinicaltrials.gov were analysed along with the history of US/EU laws, published literature, internet-retrieved regulatory documents, and regulatory/ American Academy of Pediatrics (AAP) justifications for doing separate pediatric E&S studies. Results US/EU regulators utilize an official, but non-physiological definition of childhood based on an age limit of 17/18 years. This definition, which blurs the interface between medicine and law, emerged after clinical studies became required for drug approval in 1962 prompting drug manufacturers to insert pediatric warnings into product information. Intended largely as legal protection against liability, they were interpreted medically. Absorption, distribution, metabolism, excretion mature rapidly. Drug toxicities seen in newborns during the first months of life were cited by AAP/FDA in warnings of dangers of drugs in all "children" including in adolescents who are physiologically no longer children. Warnings were/are exaggerated, exploit/ed parents' protective instincts and fears, and increase/d pediatric clinical trial activity. Conflicts of interest created by this increased activity involve research funding, career status & advancement, commercial profits. Discussion FDA/EMA-requested/demanded "pediatric" studies were identified which lack medical sense at best, others actually harm young patients by impeding use of superior, effective treatments. Separate labels for different indications make medical sense; separate approval in persons above/below 17/18 years of age does not. Conclusions Pediatric medical research should be restricted to studies which meet important medical needs of all recruited young patients, which generate information that cannot be obtained by other study designs, and do not limit access to superior alternative therapies. Clinical centers, investigators, and IRBs/ECs should more carefully examine studies for unjustified regulatory demands, prevention of subjects' access to superior treatments, and undeclared COI's. Questionable studies should not be approved and ongoing ones should be suspended.

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