JULY 2016
NICE TALKING TO YOU EARLY DIALOGUE WITH THE NATIONAL INSTITUTE FOR HEALTH AND CARE EXCELLENCE
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NICE TALKING TO YOU
TABLE OF CONTENTS
TABLE OF FIGURES
Executive Summary
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1: NICE standard scientific advice for pharmaceuticals process
Introduction
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2: Participation of HTA agencies in parallel EMA-HTA advice
Range of NICE advice has changed over 01 time Getting NICE scientific advice
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A popular choice in Europe Rising demand for NICE scientific advice
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3: Early dialogue with NICE, 2009/10 to 03 2015/16
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4: Number of companies seeking NICE scientific advice
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5: Number of staff providing scientific advice at NICE, Apr 09 to Mar 16
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NICE scientific advice sought across a range of therapy areas
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6: Income generated by NICE scientific 04 advice, 2009/10 to 2015/16
Impact of NICE scientific advice
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7: NICE scientific advice projects by year and therapy area, 2009/10 to 2015/16
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The future
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References
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8: NICE scientific advice projects by therapy area, 2009/10 to 2015/16 TABLE OF BOXES
1: NICE scientific advice services
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This report contains information from numerous sources that Leela Barham Economic Consulting Ltd believes to be reliable but for which accuracy cannot be guaranteed. Leela Barham Economic Consulting Ltd does not accept any responsibility for any loss incurred by any person who acts or who fails to act as a result of information published in this document.
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Executive Summary The National Institute for Health and Care Excellence (NICE) in the UK, is a globally recognised Health Technology Assessment (HTA) agency. This expert report focuses on NICE, using exclusive data from a freedom of information request response from NICE, to complement a separate expert report on early dialogue on HTA in Europe. [1] Since 2009, companies have been able to seek NICE advice early in development to help understand what evidence NICE would like to see to support future technology appraisals (TAs). Over time, the NICE scientific advice service has expanded, offering not only one-to-one advice but also advice in parallel with regulators and a special offering for small and medium sized companies (SMEs). NICE advice seems to be popular; they provided more advice than any other HTA agency in Europe involved in the European Medicines Agency (EMA) multi-HTA scientific advice service up to the end of 2015. Companies need to navigate a ten-stage process to receive confidential and non-binding NICE scientific advice, which builds on submission documents, a faceto-face meeting and a report from NICE over a 4 to 6 month time period. Companies need to plan for this; they need to come early, before Phase III, and ensure that they share submissions early enough for NICE to keep to the timetable. Companies can seek advice on both the clinical trial programme and economic evaluation; asking questions about everything from subgroups to resource use to modeling. Patients can also be invited to be part of the advice discussion too.
Demand for NICE to provide scientific advice has increased over time, with a peak of other 40 projects in 2014/15. There may a shift over time: fewer companies are seeking stand-alone advice with NICE and more are seeking NICE advice as part of the EMA-HTA scientific advice service. NICE has added staff to respond to this demand; almost 14 whole time equivalents are involved on the NICE side in Mar 2016. That compares to just three in April 2016 when they started the service. Scientific advice is a source of income to NICE, bringing in over £1million in 2015/16 alone. That implies that fees are also significant, although confidential, anecdotal estimates are from £30,000 to over £50,000 per project. Scientific advice has been sought across a variety of therapy areas, but it’s most often sought for treatments for the nervous system, antineoplastic and immunomodulating agents and treatments for the musculoskeletal system. Together they account for 61% of projects since 2009/10. It may be too soon to judge impact given the years needed to bring a new product to market. However, the positive impact of NICE scientific advice lies in its potential to generate the evidence that NICE would like to see. That in turn could lead to a positive appraisal and reimbursed patient access. Could it even offer a competitive advantage? With the UK’s position in Europe unclear as a result of the vote to leave the EU on the 23 June, there are questions about the role of NICE in European HTA, including early dialogue.
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Early dialogue (also referred to as scientific advice) between Health Technology Assessment (HTA) agencies and industry has been increasing over time, offering the opportunity for companies to seek advice on the evidence package that HTA agencies would like to see when appraising their new medicines. This report complements a report [1] on early dialogue with HTA agencies across Europe, and takes a closer look at early dialogue with the National Institute for Health and Care Excellence (NICE). It draws on exclusive data from a freedom of information response from NICE.
Range of advice has expanded over time NICE was the first agency to formally launch early scientific advice in Europe in 2009. [1] Now NICE offers a range of advice as set out in box 1. Box 1: NICE scientific advice services
For pharmaceuticals: Standard scientific advice - NICE-MHRA scientific advice (with the UK regulator) - HTA-EMA scientific advice (with the European regulator) - Advice for small and medium-sized companies (SMEs) -
For devices and diagnostics: Standard scientific advice - Advice for small and medium-sized companies -
Source: [2]
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However, the first option launched – standard scientific advice – has been the most popular choice with the later options being rarely used. For example, NICE and Medicines and Healthcare Regulatory products Agency (MHRA) parallel scientific advice was provided four times, advice for SMEs two times, and only once for a medical device/diagnostic up to end of March 2016. [3] NICE has provided scientific advice in 175 projects over the same time period. [3] The NICE scientific advice service also offers seminars and events too. [2] NICE does not generally give advice on generics, biosimilars, new formulations, HIV products and non-therapeutic vaccines. [4]
Getting NICE scientific advice NICE strongly encourages companies to seek their advice before the start of Phase III. Companies can then develop an understanding of what NICE expects to see at a time when changes can still be made.[5] Companies seeking scientific advice from NICE need to negotiate a ten step process (see figure 1). NICE provides a template for the briefing book as well as guidance on completing the briefing book. [4] Scientific advice from NICE can cover both the clinical trial programme and economic evaluation.[6] The service typically responds to questions on: [4] • The trial population and subgroups • Trial design • Relevant outcomes • Comparators • Health-related quality of life data collection • Economic analysis • Cost effectiveness modelling • Extrapolation • Resource use • Costs
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NICE TALKING TO YOU
Figure 1: NICE standard scientific advice for pharmaceuticals process
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The process takes around 4 to 6 months, with the ultimate output a report from NICE that builds on the submission documents and discussion at a 3 hour face -to-face meeting with the company. Their advice is kept confidential and is not shared with the Appraisal Committee who may subsequently appraise the product in the future, and is not legally binding on either party. [6] [7] Introduced in 2014, companies now have the opportunity to involve patients too as part of the service. By the end of 2014/15, NICE had run four projects that included patient representatives.[8]
A popular choice in Europe
Source: Based on [2] Note: Co = company, q's = questions, mtg = meeting
Figure 2: Participation of HTA agencies in parallel EMA-HTA advice
NICE is a globally recognised agency. It proved to be the most popular choice of HTA agency for the industry to talk to about their evidence generation plans as part of the European Medicines Agency (EMA) parallel scientific advice service up to the end of 2015 (see figure 2).
Source: Data from [9] Note: Excludes SEED NICE = National Institute for Health and Care Excellence (UK) G-BA = German Federal Joint Committee AIFA = Italian Medicines Agency TLV = Swedish Dental and Pharmaceutical Benefits Agency HAS = Haute Autorite de Sante (France) HVB = Main Association of Austrian Social Security Institutions ZIN = Dutch National Health Care Institute AEMPS = Spanish Medicines Agency AIAQS = Catalan Agency for Health Information, Assessment and Quality (Spain) NoMA = Norwegian Medicines Agency AOTMiT = Agency for Health Technology Assessment and Tariff System (Poland) INAMI = National Institute for Sickness and Invalidity Insurance (Belgium) IQWiG = Institute for Quality and Efficiency in Healthcare (Germany)
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Rising demand for NICE scientific advice NICE’s workload has seen a steady increase over time, peaking in 2014/15 (see figure 3). The number of projects just between NICE and companies has fallen, and the number of companies has correspondingly fallen too (see figure 4). Perhaps this suggests that companies are seeking NICE input via multi-HTA forums, and this has to some degree provided a substitute service? Figure 3: Early dialogue with NICE, 2009/10 to 2015/16
Source: Data from [3]
Figure 4: Number of companies seeking NICE scientific advice
Source: Data from [3]
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Advice is kept confidential so only NICE and the companies know the full details. However, NICE reports that many of the top 20 pharmaceutical companies have sought early scientific advice from them.[10] To respond to the overall increase in NICE workload, NICE has added staff to the scientific advice service (figure 5). The service began with three Whole Time Equivalents (WTEs) and expanding that to just under 14 WTEs by March 2016. [3] That increasing workload has also been accompanied by a corresponding increase in income as companies pay fees for NICE scientific advice (see figure 6). In 2015/16, NICE generated over a £1 million for scientific advice. The precise fee charged per project is not disclosed by NICE, however anecdotally fees can vary from £30,000 to over £50,000. Figure 5: Number of staff providing scientific advice at NICE. Apr 09 to Mar 16
Source: Data from [3] Note: Whole Time Equivalents (WTEs)
Figure 6: Income generated by NICE scientific advice, 2009/10 to 2015/16
Source: Data from [3]
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NICE scientific advice sought across a range of therapy areas Companies have been seeking NICE input on evidence generation plans across a variety of therapy areas; there can be considerable variation within years (see figure 7), however companies have been seeking advice most often for products to treat nervous system disorders, antineoplastic and immunomodulating agents, and treatments for the musculoskeletal system (see figure 8) accounting for 61% collectively of NICE scientific advice projects for pharmaceuticals. [3] Figure 7: NICE scientific advice projects by year and therapy area, 2009/10 to 2015/16
Source: Data from [3]
Figure 8: NICE scientific advice projects by therapy area, 2009/10 to 2015/16
Source: Data from [3]
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Impact of NICE scientific advice
The future
NICE promotes their scientific advice service and suggests that it can help companies generate relevant evidence for future evaluation by NICE. Dr Leeza Osipenko, Associate Director, Scientific Advice, at NICE, suggests that NICE SA increases the robustness of evidence, reduces uncertainty and delays in decisionmaking and increases access for patients.[6]
NICE is seen as a global leader on HTA. NICE’s scientific advice service is increasingly sought after, although the dynamic may have changed as companies can access their scientific advice via multi-HTA forums rather than seeking lone advice from them. However, those forums have in large part arisen out of European work. It remains to be seen whether NICE will still play such a strong role on the European stage in light of the vote to leave the EU on 23 June.
Many companies return again for advice from NICE [6], indicating that the advice is seen as valuable. NICE has also interviewed those using their advice service. They have had feedback that clients have believe that the service is valuable and that the advice report and feedback at the advice meeting is influencing their development plans.[6] However, not all requests lead to the provision of advice, with 17 requests from 60 requests received by NICE up to October 2013, subsequently withdrawn.[11] NICE analysis suggests that between 2009 and 2014, scientific advice had bought sought but then clinical development had subsequently been stopped for 19% of products where advice had been sought.[12] Given the time taken to bring a new product to market, it may also be too soon to be able to judge any impact on the ultimate goals of early dialogue: achieving speedy reimbursed patient access. It's too early to say if seeking scientific advice from NICE is able to confer a competitive advantage.
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References 1 Barham, L (2016) It’s good to talk: Early dialogue with Health Technology Assessment agencies, available at: https://tinyurl.com/EarlydialogueHTA [ ]
2 NICE Scientific Advice, available at: https://www.nice.org.uk/about/what-we-do/scientific-advice
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3 NICE response to Freedom of Information request
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4 NICE Scientific Advice, FAQs available at: https://www.nice.org.uk/about/what-we-do/scientific-advice/frequentlyasked-questions [ ]
5 TOPRA (2016) Why earlier access requires earlier dialogue
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6 Osipenko, L (2014) NICE Scientific Advice CADTH Symposium Presentation
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7 CB Partners (2014) A tale of two audiences Workshop ISPOR Europe Amsterdam Presentation
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8 NICE (2015) Review 2014/15 Available at: http://review2014-2015.nice.org.uk/scientific-advice/
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9 EMA (2016) Report of the pilot on parallel regulatory-health technology assessment scientific advice
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10] NICE (2014) Advice on generating relevant evidence NICE Review 2013/14
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11] Ciani, O and Jommi, C (2014) The role of health technology assessment bodies in shaping drug development Drug Design, Development and Therapy 8 2273-2281 [
12] Maignen, FM, Osipenko, L Gajraj, E and Chivers, R (2014) Trends in early engagement between industry and HTA: Analysis of scientific advice service provided by NICE since 2009 Value in Health 17 A323-A686 [
About the author
Leela Barham is an independent health economist and policy expert. You can contact her on
[email protected] or +44 (0) 777 927 9511 No funding was received for this work, it was motivated by just a little bit of spare time and curiosity. www.leelabarhameconomicconsulting.blogspot.com
