In preparation for our free February 14th webcast – The Joys and Woes of Clinical Trial Start-Up: A Global Perspective – I wanted to examine clinical research approval timelines to see whether centralized, parallel IRB/EC reviews were quicker.
Institutional review board (IRB) or ethics committee (EC) submission preparation, review and approval are several factors that commonly delay study starts.1 Domestically and internationally, timelines for regulatory approval vary from a few weeks to more than 12 months. IRBs and ECs are centralized nationally in some countries. In others, independent national and site-level IRB/ EC review and approval may be required. In theory, centralized IRB and EC review should shorten approval time, especially when done in parallel. However, a study evaluating the approval process at various locations in a global diabetes drug study found that centralized, parallel review does not guarantee expedience.
European Union Clinical Trials Directive
In 2001, the European Union adopted the European Union Clinical Trials Directive (EUCTD) to facilitate clinical drug research.2 To limit the duration of regulatory procedures for trial initiation, the EUCTD specified that each country should have a central, rather than site-based, ethics committee that provides a single opinion for that country. It was also suggested that the trial application could be simultaneously submitted to the country’s competent regulatory authority. The EUCTD specified that both ethics committees and competent authorities should give an opinion within 60 days from the receipt of the trial application.
Does Parallel Submission Speed Review?
A 2008 paper by Heerspink et al3 in the British Journal of Clinical Pharmacology compared submission to approval time in a study evaluating glycosaminoglycan sulodexide in patients with diabetic nephropathy in EUCTD regulated countries versus EU countries regulated by local legislation. Time to approval in Europe versus the United States and Australia was also compared. Applications were submitted to regulatory authorities in 14 European countries (10 regulated by EUCTD), to the United States, and to Australia.
Surprisingly, the median time for trial approval was 75 days in EUCTD countries compared to 59 days for EU countries following local legislation. The long timeframes in EUCTD countries were caused by EUCTD legislation not being followed properly ex. IRB and EC review being done sequentially rather than parallel and involvement of local ECs in central ECs procedures (review of protocol and investigational product). When the EUCTD countries not following parallel review were excluded, the median time to approval was similar between EUCTD countries (59 days) and non-EUCTD countries (61 days).
Following EUCTD procedures did have at least one benefit: it minimized the variation in time to review. However, it was noted the EUCTD countries that did comply with procedures used the maximum allotted time to give an opinion on a study application adding to the overall average time to approval. In countries following local legislation, time to approval ranged from 10 to 119 days, whereas in EUCTD countries, time to approval ranged from 43 to 67 days.
In Summary, approval was significantly longer in Europe (67 days) versus the United States (15 days). In the United States, following a central ethics procedure did result in shorter time to approval: a median of 9 days versus 44 days for local submission procedures. Time to approval was similar between Europe (67 days) and Australia (68 days).
- CenterWatch. Survey of Investigative Sites in the US; 2009.
- European Commission. Directive 2001/20/EC of the European Parliament and of the Council of 4 April 2001. Available at: http://www.eortc.be/services/doc/clinical-eu-directive-04-april-01.pdf Accessed 14 January 2013.
- Lambers Heerspink HJ, Dobre D, Hillege HL, Grobbee DE, de Zeeuw D. Does the European Clinical Trials Directive really improve clinical trial approval time? Br J Clin Pharmacol. 2008;66:546-550.