DOI QR코드

DOI QR Code

Regulatory innovation for expansion of indications and pediatric drug development

  • Park, Min Soo (Department of Clinical Pharmacology, Severance Hospital, Yonsei University College of Medicine)
  • Published : 2018.12.15

Abstract

For regulatory approval of a new drug, the most preferred and reliable source of evidence would be randomized controlled trials (RCT). However, a great number of drugs, being developed as well as already marketed and being used, usually lack proper indications for children. It is imperative to develop properly evaluated drugs for children. And expanding the use of already approved drugs for other indications will benefit patients and the society. Nevertheless, to get an approval for expansion of indications, most often with off-label experiences, for drugs that have been approved or for the development of pediatric indications, either during or after completing the main drug development, conducting RCTs may not be the only, if not right, way to take. Extrapolation strategies and modelling & simulation for pediatric drug development are paving the road to the better approval scheme. Making the use of data sources other than RCT such as EHR and claims data in ways that improve the efficiency and validity of the results (e.g., randomized pragmatic trial and randomized registry trial) has been the topic of great interest all around the world. Regulatory authorities should adopt new methodologies for regulatory approval processes to adapt to the changes brought by increasing availability of big and real world data utilizing new tools of technological advancement.

Keywords

References

  1. E11(R1) Addendum: Clinical Investigation of Medicinal Products in the Pediatric Population. https://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Efficacy/E11/E11_R1_GuidelineWithAddendum_Step4.pdf. Accessed 3 Dec 2018
  2. New Pediatric Labeling Information Database. https://www.accessdata. fda.gov/scripts/sda/sdNavigation.cfm?filter=&sortColumn=1d&sd=labelin gdatabase&page=1. Accessed 3 Dec 2018
  3. Eguale T, Buckeridge DL, Verma A, Winslade NE, Benedetti A, Hanley JA, et al. Association of Off-label drug use and adverse drug events in an adult population. JAMA Intern Med 2016;176:55-63. doi: 10.1001/jamainternmed.2015.6058.
  4. Gupta SK, Nayak RP. Off-label use of medicine: Perspective of physicians, patients, pharmaceutical companies and regulatory authorities. J Pharmacol Pharmacother 2014;5: 88-92. doi: 10.4103/0976-500X.130046.
  5. Mulugeta LY, Yao L, Mould D, Jacobs B, Florian J, Smith B, et al. Leveraging big data in pediatric development programs. Proceedings from the 2016 American college of clinical pharmacology annual meeting symposium. Clin Pharmacol Ther 2018;104:81-87. doi: 10.1002/cpt.975.
  6. US FDA Guidance for Industry- General Clinical Pharmacology Considerations for Pediatric Studies for Drugs and Biological Products 2014, available at https://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM425885.pdf. Accessed 30 Nov, 2018
  7. Frieden TR. Evidence for health decision making - Beyond randomized, controlled trials. N Engl J Med 2017;377:465-475. doi: 10.1056/NEJMra1614394.
  8. US Food and Drug Administration. FDA D.I.S.C.O.: Avelumab in Merkel cell carcinoma transcript. https://www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm559876.htm. Accessed 30 Nov, 2018
  9. Alexion Receives Approval for Important Updates to the European Label for Soliris (eculizumab). Business Wire. http://www.businesswire.com/news/home/20150409006360/en/Alexion-Receives-Approval-Important-Updates-European-Label. Accessed 30 Nov, 2018
  10. Califf RM, Sugarman J. Exploring the ethical and regulatory issues in pragmaticclinicaltrials. Clin Trials2015;12:436-441. doi: 10.1177/1740774515598334.
  11. Dreyer NA. Advancing a framework for regulatory use of real-World evidence: When real is reliable. Ther Innov Regul Sci 2018;52:362-368. doi: 10.1177/2168479018763591.
  12. Liu JB, D'Angelica MI, Ko CY. The randomized registry trial: Two birds, One stone. AnnSurg2017;265:1064-1065. doi: 10.1097/SLA.0000000000002166.
  13. Lauer MS, D'Agostino RB, Sr. The randomized registry trial -- the next disruptive technology in clinical research? N Engl J Med 2013;369:1579-1581. doi: 10.1056/NEJMp1310102.
  14. James S, Rao SV, Granger CB. Registry-based randomized clinical trials--a new clinical trial paradigm. Nat Rev Cardiol 2015;12:312-316. doi: 10.1038/nrcardio.2015.33.
  15. Frobert O, Lagerqvist B, Gudnason T, Thuesen L, Svensson R, Olivecrona GK, et al. Thrombus Aspiration in ST-Elevation myocardial infarction in Scandinavia (TASTE trial): a multicenter, prospective, randomized, controlled clinical registry trial based on the Swedish Angiography and Angioplasty Registry (SCAAR) platform: study design and rationale. Am Heart J 2010;160:1042-1048. doi: 10.1016/j.ahj.2010.08.040.