The Health Technology Assessment (HTA) of Cell

Therapies

ISCT industry roundtable 1: transition of products from the payer

perspective, 02 October 2016, Memphis

Nick Crabb, Programme Director, Scientific Affairs

• Review of clinical and economic evidence leading to

recommendations on the appropriate use of new and existing

medicines for the NHS in England

• Includes cost utility analysis

– Outcomes (length and quality of life) and costs (full care pathway costs) are

compared to those for the current standard of care

– Outcomes measured in quality adjusted life years (QALY) – a metric that

combines the impact of the treatment on both length and quality of life

– Cost per QALY considered in decision making

• Perspective:

– National Health Services and Personal Social Services for costs

– Direct health effects on patients and carers for outcomes

• Mandatory funding of medicines recommended in TA

NICE Technology Appraisals (TA)

Exciting Times!

• Very strong pipelines of pharmaceuticals, biopharmaceuticals and

advanced therapy medicinal products with the potential for major

patient benefits

• Patients and healthcare systems need these products

• Challenges

– High costs

– Timely patient access while the evidence is still emerging

Initiatives impacting patient access to

medicines • Policy landscape evolving with several initiatives aiming to ensure

timely patient access to products addressing unmet medical need:

– Accelerated access review (England)

– Changes to the Cancer Drugs Fund (England)

– Early Access to Medicines Scheme (UK)

– EMA adaptive pathways (Europe)

– EMA PRIME (Europe)

• These initiatives mean that products are likely to come to NICE and

other HTA agencies sooner in their development cycle with less

evidence

Managing access to promising new

health technologies • A key challenge is to work with partner and stakeholder organisations to find

a way to provide patients with access to promising new medicines while the

evidence is still emerging, in a financially sustainable way

• Developments include:

– Wider use of managed access arrangements to achieve fair sharing of risks

across stakeholders

– Post marketing authorisation “real world” evidence collection to reduce

uncertainty with time

– Increased emphasis on “recommended with research” type recommendations in

HTA/Payer decision frameworks

– Innovative pricing and payment methods

• New Cancer Drugs Fund arrangements in England address these issues for

cancer medicines

Cancer Drugs Fund

• NICE and NHS England undertook a joint public consultation on

proposals for a new Cancer Drugs Fund operating model from

November 2015 – February 2016

• Cancer Drugs Fund has become a “managed access fund” to

enable patient access to cancer drugs which appear promising but

where NICE indicates that there is insufficient evidence to support a

recommendation for routine commissioning

• Details from https://www.england.nhs.uk/cancer/cdf/

NICE methods research related to early

evaluation and managed access • Collaborating on international research into optimised drug

development and adoption pathways

– HTA elements of EMA adaptive pathways pilots

– IMI ADAPT-SMART project

• Research to support NICE’s ability to assess products and

interventions where evidence is limited

– use of real world evidence (IMI GetReal project)

– expert elicitation

• Research to support the analysis and presentation of uncertainty

and how managed access arrangements impact uncertainty

Engagement Opportunities • NICE Scientific Advice

– Dedicated team of 16 staff

– Advice on HTA aspects of prospective clinical trials

– Pharma, biotech, ATMPs and medical technologies

– Advice in collaboration with UK and European regulators and other European

HTA agencies

– Educational seminars

• NICE Office for Market Access

– New initiative – opened in October 2015

– Allows engagement on all dimensions of patient and market access

– High interest in managed access arrangements, including innovative pricing

methods

– Multi-stakeholder “safe harbour” discussions

NICE regenerative medicine study

• Study undertaken by NICE in collaboration with the Centre for

Reviews and Dissemination / Centre for Health Economics,

University of York

• Exercise prompted by a recommendation from the Department of

Health Regenerative Medicine Expert Group

• Study allowed detailed consideration of any specific challenges

associated with the evaluation of ATMPs including the interplay

between evidence maturity, price and payment methods

• Reports available from https://www.nice.org.uk/about/what-we-

do/science-policy-research/nice-research

Study design

• Much of the study concerned a hypothetical example product with

characteristics based on early clinical data for related real products

supplemented with hypothetical evidence

• Multiple scenarios were developed which were considered by an

Expert Panel experienced in NICE TA who were asked what

decisions they would make if the scenarios were encountered in real

appraisals

• Also included a broad exploration of the applicability of NICE TA

methods to regenerative medicines

• Supported by a Project Advisory Group

Hypothetical example product • CAR (chimeric antigen receptor) T-cell therapy specific to antigen CD19, for

treating relapsed or refractory B-cell acute lymphoblastic leukaemia (B-ALL) in

children and young adults

• Based on the available clinical evidence, two target product profiles (TPPs)

were developed,

– CAR T-cell therapy used “as a bridge” to hematopoietic stem cell transplantation (HSCT)

– CAR T-cell therapy used with “curative intent”

• To explore the impact of different levels of evidence, three hypothetical evidence

sets were constructed for each TPP (minimum, intermediate, mature) providing

six evidence scenarios

• Within each of the six evidence sets, cost effectiveness analyses explored the

impact of price discounts, payment models and discounting rates used in the

economic analyses

Hypothetical acquisition costs

• No commercially available product or published price

• Hypothetical price set such that economic analyses would give a

result close to NICE’s cost effectiveness threshold

• NICE “end of life” criteria considered applicable where a QALY

weighting equivalent to an appraisal threshold of £50,000 per QALY

applies

Note – end of life criteria will not apply to all regenerative medicines –

normally a cost per QALY under £20,000 - £30,000 would be required for a

product to be considered cost effective

Benefits and costs of the two TPPs

Bridge to HSCT TPP

Curative Intent TPP

Assumed Individual

patient level Incremental

QALY gain

7.46 10.07

Assumed Price

(acquisition cost of the

therapy)

£356,100 £528,600

Analysis and presentation of uncertainty • The product characteristics in the TTPs represent the potential for profound

patient benefits but there is also very high uncertainty around the actual

benefits that these products would deliver

• In analysing and presenting uncertainty, the York team determined:

– Incremental cost effectiveness ratio and probability of being cost effective at the

applicable threshold (as normally considered by Committees)

– Incremental Net Health Effect (NHE): Considers impact of recommending the therapy

on population level health. NHE is negative where ICERs are above the threshold and the

therapy not considered cost effective. May be expressed in QALY or financially

– Consequences of Decision Uncertainty: Reflects the potential magnitude of NHE that

could be gained if uncertainty surrounding potential decisions could be resolved. May be

expressed in QALY or financially

• NHE and Decision Uncertainty values in the following slides are based on 38

patients per year over a 10 year period

Bridge to HSTC TPP (minimum evidence set)

Scenario ICER Incremental NHE

QALY (£)

Probability

Cost Effective

Consequences of

decision uncertainty

QALY (£)

Expert Panel

“Decision”

Base case (£356,100

one-off acquisition cost

per patient)

£55,090 -216

(-£10,794,902)

26.1% 56.3

(£2,813,197)

No

Discount of 20% on

base case acquisition

cost (£320,490 per

patient)

£44,336 241

(£12,067,402)

76.5% 47.3

(£2,365,835)

Borderline

Lifetime leasing

method (£2,756 per

month)

£54,227 -180

(-£8,997,139)

22.1% 22.5

(£1,123,900)

No

Bridge to HSTC TPP (minimum evidence set)

Scenario ICER Incremental NHE

QALY (£)

Probability

Cost Effective

Consequences of

decision uncertainty

QALY (£)

Expert Panel

“Decision”

Payment for patients

with remission only

(approx. 35% reduction

in average cost per

patient)

£36,430 577

(£28,861,808)

96.8% 3.9

(£195,152)

Yes

Additional scenario modelled by the York team after the Expert Panel meeting

Discount of 20% on

base case with Lifetime

Leasing (£2,205 per

month)

£44,015 252

(£12,624,164)

87.4% 19.0

(£948,311)

Assumed

Borderline/Yes

Bridge to HSCT TPP (intermediate and

mature evidence sets)

• Increasing maturity of evidence had relatively low impact on the

consequences of decision uncertainty

• In this example, the key outcome from therapy is clinical remission

to allow HSCT

• Can be estimated with reasonable accuracy from even the minimum

evidence set

Curative intent TPP (minimum evidence set) Scenario ICER Incremental NHE

QALY (£)

Probability

Cost Effective

Consequences of

decision uncertainty

QALY (£)

Expert Panel

“Decision”

Base case (£528,600

one-off acquisition cost

per patient)

£50,906 -56

(-£2,902,629)

50.7% 304.6

(£15,229,786)

No

Discount of 10% on

base case (£475,740

per patient)

£45,131 306

(£15,293,860)

64.2% 209.1

(£10,456,541)

Borderline/No

Lifetime leasing

method (£3,283 per

month)

£50,618 -38

(-£1,910,653)

49.2% 65.6

(£3,227,969)

No

Payment for patients

with remission only

(approx.10% reduction

in average cost per

patient)

£45,708 267

(£13,325,042)

63.9% 236.1

(£11,803,131)

Borderline/No

Curative intent TPP (minimum evidence set)

Scenario ICER Incremental NHE

QALY (£)

Probability

Cost Effective

Consequences of

decision uncertainty

QALY (£)

Expert Panel

“Decision”

Additional scenarios modelled by the York team after the Expert Panel meeting

Discount of 10% on

base case price with

lifetime leasing (£2,955

per month)

£45,502 275

(£13,750,033)

87.2% 27.2

(£1,358,584)

Assumed

Borderline/Yes

Same pricing as

bridging to HSCT TPP

(£356,100 per patient)

£34,337 951

(£47,555,583)

85.6% 73.1

(£3,655,876)

Assumed Yes

Same total cost as

bridging TPP with

lifetime leasing (£2,221

per month)

£33,277 1050

(£52,500,851)

99.4% 2.3

(£112,597)

Assumed Yes

Curative intent TPP (intermediate and mature

evidence sets)

Scenario ICER Incremental NHE

QALY (£)

Probability

Cost Effective

Consequences of

decision uncertainty

QALY (£)

Expert Panel

“Decision”

Base case (minimum

evidence set)

£50,906 -56

(-£2,902,629)

50.7% 304.6

(£15,229,786)

No

Intermediate evidence

set

£43,344 486

(£24,311,227)

85.9% 40.6

(£2,031,623)

Borderline

Mature evidence set

£43,252 495

(£24,723,328)

91.5% 14.1

(£707,136)

Borderline/Yes

Curative intent TPP (intermediate and

mature evidence sets)

• Increasing maturity of evidence had a major impact on the

consequences of decision uncertainty

• The additional evidence increases the certainty around the curative

benefits and cost effectiveness of the treatment

Conclusions

• The NICE appraisal methods and decision frameworks are applicable to

regenerative medicines and cell therapies

• Quantifying and presenting clinical outcome and decision uncertainty

was key to the Expert Panel consideration of the hypothetical example

products

• Where there is a combination of great uncertainty but potentially

very substantial patient benefits, innovative payment methods

need to be developed to manage and share risk to facilitate timely

patient access while the evidence is immature

• The discounting rate applied to costs and benefits was found to have a

very significant impact on analyses of these types of technologies

Acknowledgements

• Cell and Gene Therapy Catapult

• Centre for Reviews and Dissemination / Centre for Health

Economics, University of York

• Department of Health Regenerative Medicine Expert Group

Secretariat

• Expert Panel

• Project Advisory Group