Trends in clinical development timeframes for antiviral drugs launched in the UK, 1981–2014: a retrospective observational study

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Abstract

Objectives

Recent decades have witnessed the development of highly innovative new antiviral drug therapies. However, there are concerns that rising costs and lengthening development times could have implications for future patient access to innovative new drugs. We sought to establish whether the time taken for the clinical development of new antiviral drugs launched in the UK had increased since the 1980s.

Design and setting

Retrospective observational study of all new antiviral drugs licensed for use in the UK.

Primary and secondary outcome measures

Duration of clinical development (from initiation of studies in humans to receipt of Marketing Authorisation), subdivided into clinical trial and regulatory approval periods by the date of Marketing Authorisation Application.

Results

48 new antiviral drugs were licensed for use in the UK between 1981 and 2014 (inclusive), over half (54%) initially for HIV infection. The overall mean duration of clinical development was 77.2 months, of which 64.6 months was spent in clinical trials before regulatory submission. The total time in clinical development increased from 41.7 months for drugs licensed 1981–1992 to 91.7 months for drugs licensed 2004–2014. This increase was accounted for by an increase in the clinical trials period and not the regulatory approval period, for which there was no observable trend. Drugs initially licensed to treat hepatitis C had a longer duration of clinical development than those indicated for other viral infections. However, the, initially shorter clinical development durations of drugs indicated for HIV infection increased more rapidly across the study period than those indicated for other viral infections.

Conclusions

The time spent by antiviral drugs in clinical development has increased markedly in recent decades despite many initiatives to speed access to innovative new drugs. However, this represents only one part of the translational research pathway, and a complete picture of development timeframes is lacking.

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Most cited references 15

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The productivity crisis in pharmaceutical R&D.

Fabio Pammolli, Laura Magazzini, Massimo Riccaboni (2011)

Advances in the understanding of the molecular basis of diseases have expanded the number of plausible therapeutic targets for the development of innovative agents in recent decades. However, although investment in pharmaceutical research and development (R&D) has increased substantially in this time, the lack of a corresponding increase in the output in terms of new drugs being approved indicates that therapeutic innovation has become more challenging. Here, using a large database that contains information on R&D projects for more than 28,000 compounds investigated since 1990, we examine the decline of R&D productivity in pharmaceuticals in the past two decades and its determinants. We show that this decline is associated with an increasing concentration of R&D investments in areas in which the risk of failure is high, which correspond to unmet therapeutic needs and unexploited biological mechanisms. We also investigate the potential variations in productivity with regard to the regional location of companies and find that although companies based in the United States and Europe differ in the composition of their R&D portfolios, there is no evidence of any productivity gap.

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How long does biomedical research take? Studying the time taken between biomedical and health research and its translation into products, policy, and practice

Stephen R Hanney, Sophie Castle-Clarke, Jonathan Grant … (2015)

Background The time taken, or ‘time lags’, between biomedical/health research and its translation into health improvements is receiving growing attention. Reducing time lags should increase rates of return to such research. However, ways to measure time lags are under-developed, with little attention on where time lags arise within overall timelines. The process marker model has been proposed as a better way forward than the current focus on an increasingly complex series of translation ‘gaps’. Starting from that model, we aimed to develop better methods to measure and understand time lags and develop ways to identify policy options and produce recommendations for future studies. Methods Following reviews of the literature on time lags and of relevant policy documents, we developed a new approach to conduct case studies of time lags. We built on the process marker model, including developing a matrix with a series of overlapping tracks to allow us to present and measure elements within any overall time lag. We identified a reduced number of key markers or calibration points and tested our new approach in seven case studies of research leading to interventions in cardiovascular disease and mental health. Finally, we analysed the data to address our study’s key aims. Results The literature review illustrated the lack of agreement on starting points for measuring time lags. We mapped points from policy documents onto our matrix and thus highlighted key areas of concern, for example around delays before new therapies become widely available. Our seven completed case studies demonstrate we have made considerable progress in developing methods to measure and understand time lags. The matrix of overlapping tracks of activity in the research and implementation processes facilitated analysis of time lags along each track, and at the cross-over points where the next track started. We identified some factors that speed up translation through the actions of companies, researchers, funders, policymakers, and regulators. Recommendations for further work are built on progress made, limitations identified and revised terminology. Conclusions Our advances identify complexities, provide a firm basis for further methodological work along and between tracks, and begin to indicate potential ways of reducing lags. Electronic supplementary material The online version of this article (doi:10.1186/1478-4505-13-1) contains supplementary material, which is available to authorized users.

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Regulatory review of novel therapeutics--comparison of three regulatory agencies.

Nilay Shah, N Downing, Harlan M. Krumholz … (2012)

The upcoming reauthorization of the Prescription Drug User Fee Act focuses on improving the review process for new drug applications at the Food and Drug Administration (FDA). Using publicly available information from the FDA, the European Medicines Agency (EMA), and Health Canada, we compared the time for completion of the first review and the total review time for all applications involving novel therapeutic agents approved by the three regulatory agencies from 2001 through 2010 and determined the geographic area in which each novel therapeutic agent was first approved for use. There were 510 applications for novel therapeutic agents approved from 2001 through 2010--225 by the FDA, 186 by the EMA, and 99 by Health Canada; among the applications, there were 289 unique agents. The median length of time for completion of the first review was 303 days (interquartile range, 185 to 372) for applications approved by the FDA, 366 days (interquartile range, 310 to 445) for those approved by the EMA, and 352 days (interquartile range, 255 to 420) for those approved by Health Canada (P<0.001 for the comparison across the three agencies). The median total review time was also shorter at the FDA than at the EMA or Health Canada (P=0.002). Among the 289 unique novel therapeutic agents, 190 were approved in both the United States and Europe (either by the EMA or through the mutual recognition process), of which 121 (63.7%) were first approved in the United States; similarly, 154 were approved in both the United States and Canada, of which 132 (85.7%) were first approved in the United States. For novel therapeutic agents approved between 2001 and 2010, the FDA reviewed applications involving novel therapeutics more quickly, on average, than did the EMA or Health Canada, and the vast majority of these new therapeutic agents were first approved for use in the United States. (Funded by the Pew Charitable Trusts.).

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Author and article information

Journal

Journal ID (nlm-ta): BMJ Open

Journal ID (iso-abbrev): BMJ Open

Journal ID (hwp): bmjopen

Journal ID (publisher-id): bmjopen

Title: BMJ Open

Publisher: BMJ Publishing Group (BMA House, Tavistock Square, London, WC1H 9JR )

ISSN (Electronic): 2044-6055

Publication date Collection: 2015

Publication date (Electronic): 16 November 2015

Volume: 5

Issue: 11

Electronic Location Identifier: e009333

Affiliations

[1 ]NIHR Horizon Scanning Research & Intelligence Centre, School of Health and Population Sciences, University of Birmingham , Birmingham, UK

[2 ]Department of Public Health, Epidemiology and Biostatistics, School of Health and Population Sciences, University of Birmingham , Birmingham, UK

Author notes

[Correspondence to ] Dr Derek Ward; d.j.ward@ 123456bham.ac.uk

Article

Publisher ID: bmjopen-2015-009333

DOI: 10.1136/bmjopen-2015-009333

PMC ID: 4654359

PubMed ID: 26576812

SO-VID: 8ab91e4d-9b51-441c-99f8-c3b80d23a03a

Copyright © Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

License:

This is an Open Access article distributed in accordance with the terms of the Creative Commons Attribution (CC BY 4.0) license, which permits others to distribute, remix, adapt and build upon this work, for commercial use, provided the original work is properly cited. See: http://creativecommons.org/licenses/by/4.0/

History

Date received : 7 July 2015

Date revision received : 28 August 2015

Date accepted : 4 September 2015

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Trends in clinical development timeframes for antiviral drugs launched in the UK, 1981–2014: a retrospective observational study

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Abstract

Objectives

Design and setting

Primary and secondary outcome measures

Results

Conclusions

Related collections

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Most cited references 15

The productivity crisis in pharmaceutical R&D.

How long does biomedical research take? Studying the time taken between biomedical and health research and its translation into products, policy, and practice

Regulatory review of novel therapeutics--comparison of three regulatory agencies.

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Cited by 6

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