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For Peer Review Only BMJ Open BMJ Open: first published as 10.1136/bmjopen-2014-006235 on 24 October 2014. Downloaded from How innovative are new drugs? A retrospective study of new drug launches in the UK, 2001-2012 ForJournal: peerBMJ Open review only Manuscript ID: bmjopen-2014-006235 Article Type: Research Date Submitted by the Author: 28-Jul-2014 Complete List of Authors: Ward, Derek; University of Birmingham, NIHR Horizon Scanning Centre Slade, Angharad; University of Birmingham, NIHR Horizon Scanning Centre Genus, Tracey; University of Birmingham, NIHR Horizon Scanning Centre Martino, Orsolina; Coventry City Council, Public Health Stevens, Andrew; University of Birmingham, Department of Public Health, Epidemiology and Biostatistics <b>Primary Subject Pharmacology and therapeutics Heading</b>: Secondary Subject Heading: Health policy Pharmaceuticals, Innovation, New drug launches, time trends, United Keywords: Kingdom http://bmjopen.bmj.com/ on September 25, 2021 by guest. Protected copyright. For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 1 of 28 BMJ Open BMJ Open: first published as 10.1136/bmjopen-2014-006235 on 24 October 2014. Downloaded from 1 2 3 How innovative are new drugs? A retrospective study of new drug launches 4 5 6 in the UK, 2001-2012 7 8 9 10 1 11 Derek J Ward, MD FFPH 12 13 Angharad Slade, BMedSc1 14 15 For1 peer review only 16 Tracey Genus, MPhil 17 18 Orsolina I Martino, PhD2 19 20 Andrew J Stevens, MBBS FFPH3 21 22 23 24 25 1. NIHR Horizon Scanning Centre, School of Health and Population Sciences 26 27 University of Birmingham, Edgbaston, Birmingham, B15 2TT, United Kingdom 28 29 2. Coventry City Council, Council House, Earl Street, Coventry, CV1 5RR, United Kingdom 30 31 3. Department of Public Health, Epidemiology and Biostatistics, 32 33 School of Health and Population Sciences, University of Birmingham, Edgbaston, http://bmjopen.bmj.com/ 34 35 36 Birmingham, B15 2TT, United Kingdom 37 38 39 40 Corresponding author: 41 42 Dr Derek Ward [email protected] on September 25, 2021 by guest. Protected copyright. 43 44 45 46 Key words 47 48 49 Pharmaceuticals, innovation, new drug launches, time trends, United Kingdom 50 51 52 53 54 55 56 57 58 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open Page 2 of 28 BMJ Open: first published as 10.1136/bmjopen-2014-006235 on 24 October 2014. Downloaded from 1 2 3 Abstract 4 5 6 Objectives: Innovative new drugs offer potential benefits to patients, healthcare systems, 7 8 governments, and the pharmaceutical industry. Recent data suggest the annual number of new 9 10 drugs launched in the UK has increased in recent years, and we sought to understand whether this 11 12 represents increasing numbers of highly innovative new drugs being made available or the 13 14 introduction of increasing numbers of new drugs with limited additional therapeutic value. 15 For peer review only 16 Design and setting: Retrospective observational study of new drug entries in the British National 17 18 19 Formulary (BNF). 20 21 Primary and secondary outcome measures: Number of new drugs launched in the UK each year 22 23 (based on first appearance in the BNF) from 2001 to 2012, including new chemical entities and new 24 25 biological drugs, categorised by degree of innovativeness according to published criteria that 26 27 incorporate a broad perspective of innovation. 28 29 Results: Highly innovative, moderately innovative and slightly innovative drugs made up 26%, 18% 30 31 32 and 56% of all newly launched drugs, respectively for the study period (n=290). There was an 33 2 34 upward trend in annual numbers of slightly innovative drugs from 2004 onwards (R =0.44), which http://bmjopen.bmj.com/ 35 36 aligned closely with the recovery in total numbers of new drugs launched each year since that time. 37 38 There were no discernable time trends in the highly or moderately innovative categories. New drugs 39 40 for malignancy and skin disease were most likely to be characterised as highly innovative (44% and 41 42 on September 25, 2021 by guest. Protected copyright. 57% respectively). 43 44 45 Conclusions: Highly innovative new drugs comprise only around a quarter of all new drug launches 46 47 in the UK. In contrast, drugs categorised as only slightly innovative comprised well over half of all 48 49 new drugs and annual numbers in this category are increasing. Current policy initiatives that seek to 50 51 increase the supply of innovative new drugs have long-lead times to impact, and will need careful 52 53 assessment to ensure they deliver their aims without unintended consequences. 54 55 56 57 58 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 3 of 28 BMJ Open BMJ Open: first published as 10.1136/bmjopen-2014-006235 on 24 October 2014. Downloaded from 1 2 3 Article summary 4 5 Strengths and limitations of this study 6 7 This is the most up to date and complete study that considers the innovativeness of new drug 8 • 9 10 introductions into the UK. 11 12 13 14 • The study used published criteria that adopt a broad perspective of innovation, and incorporate 15 For peer review only 16 novelty, clinical usefulness, cost-effectiveness, and the degree to which innovation arises 17 18 through a revolutionary or disruptive transformation. 19 20 21 22 23 • However, the criteria used to categorise innovativeness do not take into account the public 24 25 health need, health service impact, or commercial success of newly launched drugs. 26 27 28 29 • This study did not consider new indications for existing licensed and marketed drugs. 30 31 32 33 34 http://bmjopen.bmj.com/ 35 36 37 38 39 40 41 42 on September 25, 2021 by guest. Protected copyright. 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open Page 4 of 28 BMJ Open: first published as 10.1136/bmjopen-2014-006235 on 24 October 2014. Downloaded from 1 2 3 Introduction 4 5 6 Innovative new drugs offer potential benefits to patients, healthcare systems, governments, and the 7 8 pharmaceutical industry.1 However, during the first decade of the new millennium, many 9 10 commentators noted an apparent lack of pharmaceutical innovation and a reduction in new drug 11 12 launches, despite increasing research and development (R&D) spending.2-5 Within the context of 13 14 drug development, innovation is generally defined as the discovery, development and bringing to 15 For peer review only 16 the market of a new chemical entity6 (NCE); “an active ingredient that has never been marketed…in 17 18 7 19 any form”. The most straightforward way to measure innovation is to separate drugs into ‘first in 20 21 class’ and ‘me-too’ or ‘follow-on’ drugs, those which largely duplicate the action of existing drugs 22 23 and are chemically similar.8 Ferner et al (2010)9 have proposed a more sophisticated classification, 24 25 which identifies a range of features related to a drug’s molecular structure, synthesis, 26 27 pharmacodynamics, pharmacokinetics, delivery, pharmacogenetics, and application. However, this 28 29 does not account for all possible aspects of innovativeness, in particular therapeutic advantage over 30 31 32 existing drugs. In considering how the National Institute for Health and Care Excellence (NICE) 33 34 should incorporate innovation into UK decision making, Kennedy (2009) proposed that an innovative http://bmjopen.bmj.com/ 35 36 medicine should offer improvements over existing therapies and a “step-change in terms of 37 38 outcomes for patients”.10 Building on these approaches, Aronson et al1 (2012) defined 39 40 innovativeness using a broad perspective of innovation, including health and non-health elements, 41 42 on September 25, 2021 by guest. Protected copyright. that incorporate novelty, clinical usefulness, cost-effectiveness, and the degree to which innovation 43 44 45 arises through a revolutionary or disruptive transformation. In this approach, a new drug may be 46 47 considered “highly innovative” if it has “a new target or novel mechanism”, “improved identification 48 49 of patients…likely to benefit or be harmed”, or a “novel application of an existing compound”. 50 51 52 53 A recent systematic review by Kesselheim et al (2013)11 sought to identify the range of approaches 54 55 used to determine trends in pharmaceutical innovation. They developed a taxonomy of assessment 56 57 58 strategies, and considered the conclusions drawn when using these differing definitions. They 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 5 of 28 BMJ Open BMJ Open: first published as 10.1136/bmjopen-2014-006235 on 24 October 2014. Downloaded from 1 2 3 determined four main categories of study: “counts of new drugs approved, assessments of 4 5 therapeutic value, economic outcomes and patents issued”.11 Studies based on counts of new drug 6 7 approvals reported both positive and negative temporal trends in innovation, depending on the 8 9 definitions used, geographical locations, and time periods studied. However, studies published in the 10 11 12 last decade that define innovativeness on the basis of therapeutic value all report a negative trend in 13 14 the innovativeness of new drugs, despite using different approaches to measurement and reporting 15 For peer review only 16 time periods varying from 1990-2003 to 2001-2010. The varied approaches to measuring therapeutic 17 18 value included: the results from pre- and post-marketing trials; pharmaceutical or technical 19 20 innovation; comparison with available marketed alternatives or therapeutic novelty (giving greater 21 22 weight to drugs for conditions with no existing effective treatment); and more general public health 23 24 25 measures.
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