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Abstract
Childhood-onset systemic lupus erythematosus (cSLE) is rare in many regions of the world, including Europe. Access to approved medications for cSLE is currently limited, among others, due to a lack of high-quality evidence from clinical trials. The objectives of the study were to evaluate the current regulatory framework regarding medication approvals, delineate barriers to clinical trial conduct, and strategies to improve access to new medications for cSLE. Relevant methodological and regulatory aspects, epidemiological data, study designs and outcome measures are reviewed, and the results of a survey among Paediatric Rheumatology International Trials Organisation/Pediatric Rheumatology Collaborative Study Group investigators are presented. Laws and regulations in the USA and Europe necessitate that novel medicines are studied in paediatric populations, if similar or the same diseases in adults have been found to benefit from them. Regulatory agencies consider cSLE the paediatric form of SLE in adults. For medicines that have been found safe and effective in adult SLE, paediatric extrapolation strategies can limit the number and complexity of studies needed to support the labelling of these medicines for use in cSLE. In this setting, specialised research networks, validated outcome measures, stakeholder input, study designs as well as statistical methods successfully used in other uncommon diseases will help improve study efficiency in an effort to enhance the speed with which new drugs for cSLE can be studied. Open-label pharmacokinetic-pharmacodynamic studies are preferred by paediatric rheumatologists over double-blind parallel designs for cSLE trials. Appropriate infrastructure, outcome measures and sufficient numbers of patients are available for the testing of new medicines for children with cSLE.
- childhood-onset systemic lupus erythematosus
- European medicines agency
- US food and drug administration
- extrapolation
- clinical trials
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Footnotes
Handling editor Josef S Smolen
Collaborators The authors are officers of the PRINTO-PRCSG networks.
Contributors HIB generated the first draft of the manuscript. All four authors were involved in the feasibility survey (table 2), critically reviewed the manuscript and approved its final version.
Funding Drs. Brunner and Lovell are supported by endowments of the Cincinnati Children’s Research Foundation. Dr Ruperto and Prof Martini are full time employees of the Istituto G. Gaslini.
Funding HIB and DJL are supported by endowments of the Cincinnati Children’s Research Foundation. NR and AM are full-time employees of the Istituto Giannina Gaslini.
Competing interests DJL is chairman of PRCSG. HIB is scientific director of PRCSG. AM is chairman of PRINTO. NR is senior scientist of PRINTO. NR received honoraria (<US$10.000 each) for consultancies or speakers’ bureau from the following pharmaceutical companies since the last 5 years: Abbott, AbbVie, Amgen, Biogenidec, Astellas, Alter, AstraZeneca, Baxalta Biosimilars, Boehringer, BMS, CD-Pharma, Celgene, CrescendoBio, EMD Serono, Hoffman-La Roche, Italfarmaco, Janssen, MedImmune, Medac, Novartis, Novo Nordisk, Pfizer, Rewind Arms, R-Pharm, Sanofi Aventis, Servier, Sinergie, Takeda, Vertex and UCB Biosciences. IRCCS Istituto Giannina Gaslini, which is the public hospital where NR works as full-time public employee, has received contributions (>US$10.000 each) from the following industries: Abbott, BMS, 'Francesco Angelini', GlaxoSmithKline (GSK), Hoffman-La Roche, Italfarmaco, Janssen, Novartis, Pfizer, Sanofi Aventis, Schwarz Biosciences, Sobi, Xoma and Wyeth. The money was reinvested for the research activities of the hospital in a fully independent manner without any commitment with third parties. HIB is a consultant of AbbVie, Ablynx, Amgen, AstraZeneca, Baxalta Biosimilars, Biogen Idec, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Eli-Lilly, EMD Serono, Gilead Sciences, Janssen, MedImmune, Novartis, Pfizer, R-Pharm, Roche, Sanofi, Servier and Takeda; speakers’ bureaus: Genentech and Novartis. HIB receives grant support from Pfizer and Bristol-Myers Squibb. HIB is a full-time employee of Cincinnati Children’s Hospital which has received contributions from Bristol-Myers Squibb, Hoffman-La Roche, Janssen, Novartis and Pfizer for the coordination activity of the PRCSG network. AM has no conflicts of interest to declare since March 2016 when he became the scientific director of the Istituto Giannina Gaslini, because this role does not allow him to render private consultancy resulting in personal income. AM acted as a consultant on behalf of the Istituto Giannina Gaslini for AbbVie, Boehringer, Novartis and R-Pharm. IRCCS Istituto Giannina Gaslini has received contributions from Abbott, BMS, 'Francesco Angelini', GlaxoSmithKline (GSK), Hoffman-La Roche, Italfarmaco, Janssen, Novartis, Pfizer, Sanofi Aventis, Schwarz Biosciences, Sobi, Xoma and Wyeth for the coordination activity of the PRINTO network. DJL is a consultant of AbbVie, Ablynx, Amgen, AstraZeneca, Baxalta Biosimilars, Biogen Idec, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Eli-Lilly, EMD Serono, Gilead Sciences, Janssen, MedImmune, Novartis, Pfizer, R-Pharm, Roche, Sanofi, Servier and Takeda; speakers’ bureaus: Genentech and Novartis. DJL receives grant support from Bristol-Myers Squibb. DJL is a full-time employee of Cincinnati Children’s Hospital which has received contributions from Bristol-Myers Squibb, Hoffman-La Roche, Janssen, Novartis and Pfizer for the coordination activity of the PRCSG network.
Patient consent Not required.
Provenance and peer review Not commissioned; externally peer reviewed.