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Regulatory approval of pharmaceuticals without a randomised controlled study: analysis of EMA and FDA approvals 1999-2014.
BMJ Open. 2016 06 30; 6(6):e011666.BO

Abstract

INTRODUCTION

The efficacy of pharmaceuticals is most often demonstrated by randomised controlled trials (RCTs); however, in some cases, regulatory applications lack RCT evidence.

OBJECTIVE

To investigate the number and type of these approvals over the past 15 years by the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA).

METHODS

Drug approval data were downloaded from the EMA website and the 'Drugs@FDA' database for all decisions on pharmaceuticals published from 1 January 1999 to 8 May 2014. The details of eligible applications were extracted, including the therapeutic area, type of approval and review period.

RESULTS

Over the period of the study, 76 unique indications were granted without RCT results (44 by the EMA and 60 by the FDA), demonstrating that a substantial number of treatments reach the market without undergoing an RCT. The majority was for haematological malignancies (34), with the next most common areas being oncology (15) and metabolic conditions (15). Of the applications made to both agencies with a comparable data package, the FDA granted more approvals (43/44 vs 35/44) and took less time to review products (8.7 vs 15.5 months). Products reached the market first in the USA in 30 of 34 cases (mean 13.1 months) due to companies making FDA submission before EMA submissions and faster FDA review time.

DISCUSSION

Despite the frequency with which approvals are granted without RCT results, there is no systematic monitoring of such treatments to confirm their effectiveness or consistency regarding when this form of evidence is appropriate. We recommend a more open debate on the role of marketing authorisations granted without RCT results, and the development of guidelines on what constitutes an acceptable data package for regulators.

Authors+Show Affiliations

Department of Statistical Science, University College London, London, UK.Department of Statistical Science, University College London, London, UK.Johnson & Johnson, Titusville, New Jersey, USA.Department of Pharmacology, University of Tartu, Tartu, Estonia.Department of Primary Care & Population Health, University College London, London, UK.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

27363818

Citation

Hatswell, Anthony J., et al. "Regulatory Approval of Pharmaceuticals Without a Randomised Controlled Study: Analysis of EMA and FDA Approvals 1999-2014." BMJ Open, vol. 6, no. 6, 2016, pp. e011666.
Hatswell AJ, Baio G, Berlin JA, et al. Regulatory approval of pharmaceuticals without a randomised controlled study: analysis of EMA and FDA approvals 1999-2014. BMJ Open. 2016;6(6):e011666.
Hatswell, A. J., Baio, G., Berlin, J. A., Irs, A., & Freemantle, N. (2016). Regulatory approval of pharmaceuticals without a randomised controlled study: analysis of EMA and FDA approvals 1999-2014. BMJ Open, 6(6), e011666. https://doi.org/10.1136/bmjopen-2016-011666
Hatswell AJ, et al. Regulatory Approval of Pharmaceuticals Without a Randomised Controlled Study: Analysis of EMA and FDA Approvals 1999-2014. BMJ Open. 2016 06 30;6(6):e011666. PubMed PMID: 27363818.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Regulatory approval of pharmaceuticals without a randomised controlled study: analysis of EMA and FDA approvals 1999-2014. AU - Hatswell,Anthony J, AU - Baio,Gianluca, AU - Berlin,Jesse A, AU - Irs,Alar, AU - Freemantle,Nick, Y1 - 2016/06/30/ PY - 2016/7/2/entrez PY - 2016/7/2/pubmed PY - 2017/12/6/medline KW - CLINICAL PHARMACOLOGY KW - Regulatory SP - e011666 EP - e011666 JF - BMJ open JO - BMJ Open VL - 6 IS - 6 N2 - INTRODUCTION: The efficacy of pharmaceuticals is most often demonstrated by randomised controlled trials (RCTs); however, in some cases, regulatory applications lack RCT evidence. OBJECTIVE: To investigate the number and type of these approvals over the past 15 years by the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA). METHODS: Drug approval data were downloaded from the EMA website and the 'Drugs@FDA' database for all decisions on pharmaceuticals published from 1 January 1999 to 8 May 2014. The details of eligible applications were extracted, including the therapeutic area, type of approval and review period. RESULTS: Over the period of the study, 76 unique indications were granted without RCT results (44 by the EMA and 60 by the FDA), demonstrating that a substantial number of treatments reach the market without undergoing an RCT. The majority was for haematological malignancies (34), with the next most common areas being oncology (15) and metabolic conditions (15). Of the applications made to both agencies with a comparable data package, the FDA granted more approvals (43/44 vs 35/44) and took less time to review products (8.7 vs 15.5 months). Products reached the market first in the USA in 30 of 34 cases (mean 13.1 months) due to companies making FDA submission before EMA submissions and faster FDA review time. DISCUSSION: Despite the frequency with which approvals are granted without RCT results, there is no systematic monitoring of such treatments to confirm their effectiveness or consistency regarding when this form of evidence is appropriate. We recommend a more open debate on the role of marketing authorisations granted without RCT results, and the development of guidelines on what constitutes an acceptable data package for regulators. SN - 2044-6055 UR - https://neuro.unboundmedicine.com/medline/citation/27363818/Regulatory_approval_of_pharmaceuticals_without_a_randomised_controlled_study:_analysis_of_EMA_and_FDA_approvals_1999_2014_ L2 - https://bmjopen.bmj.com/lookup/pmidlookup?view=long&pmid=27363818 DB - PRIME DP - Unbound Medicine ER -