SVMPharma Real World Evidence (RWE) – In this article we examine the benefits of RWE in support of HTA submissions and re-submissions, and ask whether RWE is something you can afford to pass up. For more resources RWE visit us at svmpharma.com

1. SVMPharma Ltd,
Landmark House
Station Road, Hook,
Hampshire, UK,
RG27 9HA
CONTACT US
enquiry@svmpharma.com
+44(0) 1256 962 220www.svmpharma.com
Real World Evidence as a
driver of HTA approval:
Can you afford to miss out?

2. Patient level data access in the
NHS: Generating positive outcomes
through Real World Evidence
Health economies use technology appraisals
(HTAs) to assess the value of new technologies.
Many positive HTA submissions require a
follow up review 2-4 years later, so planning
sources of new data has to come almost as
soon as the drug gets out the gate. Generation
of new data in support of such HTA submission
re-reviews is vital to maintaining access to a
drug. Further RCTs can be beneficial, but costly
and hard to launch on a reduced timescale.
Real World Evidence offers an exceptional
alternative; after all what could be more
supportive than real clinical outcomes,
generated from within the patient population?
We examine the benefits of RWE in support of
HTA submissions and re-submissions, and ask
whether RWE is something you can afford to
pass up.
1. HTA: the path to market access
Health Technology organisations such as the
UK’s NICE, Scotland’s SMC, Canada’s CADTH,
Australia’s PBAC, France’s HAS and Germany’s
AMNOG assess and give guidance on health
technologies to evaluate their clinical and cost
effectiveness.
In addition to the promotion of good health
indicated by HTA approval, funding
opportunities are also available to drugs with
receiving positive submissions. Since January
2002, it has been compulsory for NHS
organisations in England and Wales to provide
funding for medicines and treatment
recommended by NICE.
Overall, HTA submissions have become an
essential part of European market access and
the established norm in the pharmaceutical
industry, with positive submissions generally
leading to successful uptake of new drugs.
2. Re-reviews: the new standard
for HTA submissions?
Increasingly, positive HTA submissions are
subject to re-review, and often within just a few
years. Since January 93% of new and positive
NICE submissions had assigned re-reviews, and
all of those were within three years (at time of
writing). Of all published technology appraisals
(TAs; n=19), three were themselves updates on
previously published guidance, one was unable
to be reviewed due to a lack of evidence, and
only one was approved with no re-review date
stipulated. However, in this case a re-review
was recommended should there be any changes
resulting from a review of another appraisal. Of
the remaining 14 with mandated review dates,
three were recommended within just two years
with the 11 remaining within three years [1].
2
Real World Evidence as a driver
of HTA approval: Can you afford to
miss out?
www.svmpharma.com
©2016 SVMPharma Ltd. All rights reserved
16%
5%
5%
16%
58%74%
Published NICE TAs in 2016
Updates to previously published guidance
New & negative
New & no review*
New & positive - Review in 2 years
New & positive - Review in 3 years

3. RCT data enable many new drugs to gain HTA
approval but are not without their own
limitations; in particular, whilst good at
illustrating clinical outcomes, RCTs are
constrained by their cohort and are difficult to
extrapolate economic data from. NICE has
published guidelines on how it selects
interventions for review [2]:
At the time of writing, of the ten most recently
published positive NICE submissions with
upcoming re-reviews, only one has an RCT
planned at the time of writing [1,3]. What are
these companies doing to resubmit? A
separate evaluation of global HTA submissions
looked at 1,840 HTA decisions across multiple
agencies (NICE, SMC, CADTH, PBAC, HAS and G-
BA). Only 6% incorporated observational data,
however of these submissions, 77% resulted in
positive decisions, compared with 67% in the
former group [4].
When it comes to generating new data in
support of a review, and within such an
accelerated timeframe, RWE typically holds a
number of advantages relative to RCTs:
1. Lower cost
2. Speed to set up and run
3. Ease to plan and carry out
4. Numerous data types available for review
5. See how the drug is actually performing in
the patient population
So it is easy to see how RWE offers an attractive
alternative to running another RCT, but how do
the results stack up? A recent evaluation of
NICE submissions that utilised RWE in support
of their application revealed that:
 Can you afford not to consider RWE for your
HTA submissions and resubmissions?
3. Real World Evidence: the future
of HTA approval?
According to the International Society for
Pharmaeconomics Outcomes Research (ISPOR)
Real-World Data Task Force, “data used for
decision-making that are not collected in
conventional randomised controlled trials
(RCTs)… are essential for sound coverage,
payment, and reimbursement decisions” [5].
HTA success is driven by multiple factors and
RCTs may not be reflective of the full picture.
For example, if no new clinical outcomes
are presented by RCT, how do you show
value to the healthcare system? RWE
employs a wealth of data already existing in
patient notes that can be utilised to support a
range of criteria assessed by HTA bodies.
3
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©2016 SVMPharma Ltd. All rights reserved
Can you demonstrate the following
for your re-submission?
• Is the technology likely to result in a
significant health benefit, taken across
the NHS as a whole, if given to all
patients for whom it is indicated?
• Is the technology likely to result in a
significant impact on other health
related government policies (e.g.
reduction in health inequalities)?
• Is the technology likely to have a
significant impact on NHS resources
(financial or other) if given to all
patients for whom it is indicated?
• Is the Institute likely to be able to add
value by issuing national guidance?
• Is there significant inappropriate
variation in the use of the technology
across the country?
REAL WORLD EVIDENCE DRIVES
HTA APPROVAL IN 86% OF
SUBMISSIONS!

4. 4 ©2016 SVMPharma Ltd. All rights reserved
www.svmpharma.com
SVMPharma re-submission case study[6]
With an SMC resubmission looming and no new RCTs, the only route was patient access scheme
(PAS) or PAS+RWE. The study aimed not to replicate the original RCT, and so primary outcomes
looked at hospitalisations, exacerbations and IV antibiotics. Secondary outcomes collected were
the primary outcomes of the RCT. By judicious selection of these parameters from patient case
notes and Hospital Episodes Statistics (HES) data, the drug was approved for a positive
resubmission using data from just 113 patients across 14 sites in the UK and Ireland. Proof that
good quality real world data, even in small cohorts, can drive positive HTA outcomes.
NICE rare disease case study[7]
NICE has announced that it can approve BioMarin’s rare drug treatment Vimizin, but has
proposed RWE collection and a price cap to overcome doubts about the drug’s value. The move
shows NICE is developing a new model for rare disease drugs which can transform the health of
patients, but carry a very high price tag.
HTA success is driven by multiple factors and
RCTs may not be reflective of the full picture.
For example, if no new clinical outcomes
are presented by RCT, how do you show
value to the healthcare system? RWE
employs a wealth of data already existing in
patient notes that can be utilised to support a
range of criteria assessed by HTA bodies.
RWE needn’t be a complex process involving
hundreds of patients, innumerable records
across a myriad of data sources. See the
SVMPharma re-submission case study below
for details on how a small number of patients
reflecting good quality data is sufficient to
strengthen a submission and gain HTA approval.
The feasibility of large-scale trials within a
pipeline that is ever more focused on niche and
personalised medicines is decreasing,
particularly in the fields of rare diseases and
oncology. Within the changing landscape of
drug development, payers continue to demand
robust evidence to assess the value and
effectiveness of innovative treatments for both
smaller patient populations and increasingly
expensive medicines. In these situations, RWE
has proven to be a strong alternative to RCTs.
See the NICE rare disease case study below for
more information on how HTA bodies such as
NICE are actively encouraging RWE to widen
accessibility for limited access drugs.
REAL WORLD EVIDENCE DRIVES
HTA APPROVAL IN 86% OF
SUBMISSIONS!

5. 5
1. National Institute for Health and Care Excellence Guidance
and advice list. 2016. Available from
https://www.nice.org.uk/guidance/published?type=ta
Accessed June 2016
2. National Institute for Health and Care Excellence NICE
technology appraisal guidance. 2016. Available from
https://www.nice.org.uk/about/what-we-do/our-
programmes/nice-guidance/nice-technology-appraisal-
guidance Accessed June 2016
3. UK Clinical Trials Gateway Clinical Trial search. Available
from https://www.ukctg.nihr.ac.uk/home/ Accessed June
2016
4. Van Engen, A. Achieving HTA success with real world
evidence. 2016. Available from
http://www.quintiles.com/blog/achieving-hta-success-with-
real-world-evidence#sthash.3a7oLy76.dpuf Accessed June
2016
5. International Society for Pharmacoeconomics ISPOR global
healthcare systems roadmap. 2008. Available from
http://www.ispor.org/htaroadmaps/uk.asp Accessed June
2016
6. SVMPharma & Scottish Medicines Consortium
SVMPharma’s RWE behind a successful re-submission to the
SMC. 2015. Available from
http://www.svmpharma.com/svmpharma-smc-cayston/
Accessed June 2016
7. National Institute for Health and Care Excellence NICE draft
guidance conditionally recommends elosulfase alfa
(Vimizim) for treatment of very rare life-threatening genetic
disorder. 2015. Available from
https://www.nice.org.uk/Contents/Item/Display/27268
Accessed June 2016
Health technology assessment organisations want robust effectiveness and cost-effective data
for more definitive proof that a product provides added value over existing care. When
pharmaceutical industry can’t provide the outcomes data to validate these claims, they are
facing lower prices and more restricted access than they would like [4].
HTA success is driven by multiple factors and RCTs may not be reflective of the full picture.
Demonstration of clinical effectiveness isn’t the only string to the RWE bow, so even if an RCT
is commissioned in support of an HTA review, RWE can complement the clinical data
generated in powerful ways that RCTs may not. A small number of patients reflecting good
quality RWE data can be sufficient to gain approval in HTA submissions and resubmissions.
Positive HTA submissions ensure continued access and funding, and are vital for modern
European market access.
 Can you afford not to consider RWE for your HTA submissions and resubmissions?
SVMPharma is a RWE agency with experience of working on successful HTA
resubmissions for NICE and SMC that can help gather the right RWE data and
ease the RWE process to ensure your best chance of gaining positive HTA
submissions.
SVMPharma is an innovative strategic consultancy, specialising in Real World Evidence (RWE) for
the pharmaceutical industry. SVMPharma generates RWE within UK and Europe through bespoke
online Real World Treatment Evaluators, leading to successful health technology appraisal (HTA)
submissions. Clinical trial programmes do not reflect real-world clinical practice and outcomes,
RWE supplements and enhances clinical datasets. SVMPharma’s specialist teams focus on
delivering the outcomes that matter to your brand. SVMPharma also provides Global RWE, Patient
Real World Outcomes, and Big Data Analytics.
To find out more call +44 (0) 1256 962 220
www.svmpharma.com
Written by Dr Harrison Davis
©2016 SVMPharma Ltd. All rights reserved

6. CONTACT SVMPHARMA
Vaneet Nayar
Director SVMPharma
enquiry@svmpharma.com
Tel: +44 (0) 1256 962 220
SVMPharma Ltd
Landmark House
Station Road
Hook, Hampshire
RG27 9HA
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