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. 2016 Jul;82(1):213-26.
doi: 10.1111/bcp.12940. Epub 2016 Apr 22.

Characteristics and follow-up of postmarketing studies of conditionally authorized medicines in the EU

Jarno Hoekman  1   2 , Thea T Klamer  1 , Aukje K Mantel-Teeuwisse  1 , Hubert G M Leufkens  1   3 , Marie L De Bruin  1   3
Affiliations

Characteristics and follow-up of postmarketing studies of conditionally authorized medicines in the EU

Jarno Hoekman et al. Br J Clin Pharmacol. 2016 Jul.

Abstract

Aim: The aim of the present study was to provide an insight into the characteristics and follow-up of postmarketing studies of medicines that were conditionally authorized in the European Union (EU).

Methods: We compiled a list of all postmarketing studies attached as specific obligations to the licence of medicines that were granted conditional marketing authorization from January 2006 to April 2014. Studies were characterized based on their objective, design, status upon marketing authorization (MA) and due data set by authorities. They were linked to online study registrations (Clinicaltrials.gov, ENCePP) to determine completion date. We described and associated characteristics of studies and medicines, and determined whether studies were completed on time.

Results: A total of 59 postmarketing studies were requested for 21 conditionally authorized medicines. Most studies had an interventional study design (73%), were ongoing upon MA (61%) and aimed to provide additional data on efficacy (45%). Interventional studies were more often ongoing and providing efficacy data, while observational and other studies were more often new and providing safety data. Frequent grounds for requesting postmarketing studies were 'long-term follow-up' and 'increase data on subpopulations'. Of the 34 studies eligible for follow-up analysis, 26 (76%) were completed and 17 (50%) completed on time. Actual completion time took a median (interquartile range) of 274 (-121 to 556) days longer than expected.

Conclusions: Our results indicated that most postmarketing studies attached to a conditional marketing authorization were eventually completed but that half were completed with a substantial delay. The observations suggest caution when broadening the use of postmarketing studies for resolving uncertainties about benefits and risks after MA.

Keywords: Benefit-risk assessment; drug; drug approval; legislation; postmarketing; product surveillance.

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Figures

Figure 1
Figure 1
Grounds for requesting post‐marketing studies (from top to bottom). (formula image) Long‐term follow‐up, (formula image) Additional endpoints, (formula image) (Additional) comparator, (formula image) Increase size of study population, (formula image) Quantification of specific risks, (formula image) Understanding posology and drug‐drug interaction, (□) Increase data on subpopulation(s)
Figure 2
Figure 2
Flowchart describing the identification and matching of postmarketing studies. CMA, conditional marketing authorization. (formula image) Analysis of characteristics (n = 59), (formula image) Analysis of follow‐up (n = 34)
Figure 3
Figure 3
Distribution of time to completion for postmarketing studies (upper panel) and time to conversion for medicines (lower panel). (formula image) Completion in time, (formula image) Completion delayed, (formula image) Expected completion delayed, (formula image) Conversion in time, (formula image) Conversion not in time
See this image and copyright information in PMC

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