Conditional Coverage. Access with evidence development. Claire McKenna

Unifying research and coverage decisions: How the assessment required can be informed

Claire McKenna

K Claxton, S Palmer, L Longworth†, L Bojke, S Griffin, M Soares, E Spackman, J Youn†

Centre for Health Economics, University of York, UK

†Health Economics Research Group, Brunel University, UK

9th HTAi Annual Meeting Bilbao June 23-27, 2012

Allocation and research decisionsA number of conceptually distinct but simultaneous decisions must be made:

Which technology should be adopted into clinical practice given the existing evidence base and the uncertainty surrounding outcomes and resource use?

Is additional evidence required to support the use of the technology?- How uncertain are the expected benefits? - Does this uncertainty matter (will it change the adoption decision)?- How much does it matter (consequences of getting it wrong)?

What type of evidence would be most valuable? Which research designs would be worthwhile?

When to approve the technology?

- Early approval? Can the evidence be provided with approval?

Policy options: Approve, Reject, OIR, AWR

Approve

Reject

Only in research (OIR)

Approve with research (AWR)

Could impact the prospects of acquiring further evidence

Could restrict patient access to promising new technologies

Additional policies: overcomes the problems associated with making coverage decisions under uncertainty

‘Yes’ decision until further research is completed and guidance is established

‘No’ decision until further evidence establishes value - Only approved for use within the context of suitable research study

What assessments are needed?

Expected cost-effectiveness

Irrecoverable costs– Costs committed by approval that cannot be recovered

• Capital costs of long lived equipment (training and learning)• Initial losses (negative NHE) offset by later gains• Significance depends on whether initiation of treatment can be delayed

Value of additional evidence

The need for evidence, type of evidence, design of research

Uncertainty that cannot be resolved by research but only over time

Are the benefits of early approval greater than the opportunity costs?

Establish the circumstances when an OIR or AWR scheme may be an appropriate policy option

Checklist of assessmentThe sequence of assessment can be summarised as a simple 7-point checklist

†For technologies not expected to be cost-effective, point 4 becomes ‘Is the research possible without approval?’

Po

ssib

le p

ath

way

s:

Case study: EECP for chronic stable angina

Enhanced external counterpulsation (EECP) is a non-invasive procedure used to treat chronic stable angina

Primary outcome is the symptomatic relief of angina symptoms

EECP has large initial upfront costs of treatment (£4,347 per patient), which are irrecoverable once treated

EECP as adjunct to standard therapy vs. standard therapy alone

One RCT showed evidence of improved HRQoL at 12 months

Uncertain whether HRQoL benefits are sustained beyond 12 months

Long inflatable pressure cuffs are inflated and deflated to increase blood flow to the coronary arteries

Point 1 - Is the technology expected to be cost-effective?

Assessment of effectiveness, potential for harm and costs over a patient time horizon Assessment and judgement at points 1 and 2 of the checklist:

- Does not lead directly to guidance- Determines subsequent pathway

Cost-effectiveness at threshold (per QALY gained):

£10,000 £20,000 £30,000

Net health effects (NHEs): EECP Standard therapy

£70,071£72,369

£144,887£144,738

£219,702£217,107

Incremental mean costs £4,744

Incremental mean QALYs 0.2446

ICER for EECP £19,392

Treatment decision: maximum expected net health effects

Point 2 – Are there significant irrecoverable costs?Cumulative incremental NHE of EECP over the patient time horizon

-25,000

-20,000

-15,000

-10,000

-5,000

0

5,000

0 5 10 15 20 25 30 35 40 45 50

Cum

ulati

ve incr

emen

tal NHE a

t popul

ati

on

leve

l fo

r EECP,

QALY

Time, years

Technology time horizon

Point 2 – Are there significant irrecoverable costs?Cumulative incremental NHE of EECP over the patient time horizon

-25,000

-20,000

-15,000

-10,000

-5,000

0

5,000

0 5 10 15 20 25 30 35 40 45 50

Cum

ulati

ve incr

emen

tal NHE a

t popul

ati

on

leve

l fo

r EECP,

QALY

Time, years

Capital cost spread over 10 years

Capital cost incurred in year 1

Technology time horizon

Point 3 – Does more research seem worthwhile?

i. How uncertain is a decision to approve or reject ii. Do the likely consequences of uncertainty justify further research

• NHE that could be gained if it could be resolved immediately• Upper bound on potential benefits of more research• ‘No’ can lead directly to guidance

Cost-effectiveness threshold at £20,000 per QALY

TreatmentIncremental NHE

QALY (£m) Probability

cost-effectiveExpected

consequences, QALY (£m)

EECP 1,405 (28.1) 0.4289,287

(185.7)Standard care - 0.572

0.00

0.05

0.10

0.15

0.20

0.25

0.30

0.35

0.40

0.45

0 [0,5000] [5000,10000] [10000, 15000] [15000,20000] [20000,25000] [25000,30000] [30000,35000] [35000,40000] [40000,45000]

Pro

babilit

y

Consequences, QALY

Point 3 – Does more research seem worthwhile?

Probability of no losses = 0.43

Expectation across the distribution of consequences = 9,287 QALYs (£180m)

EVPI = Maximum value of research = £180m

Point 4 - Is research possible with approval?i. Type of evidence needed?ii. Can the research be conducted while approved?

• Importance of parameters (values that change the decision)• Uncertainty in possible values (how likely to change)• NHE that are to be gained (expected consequences)• Assessment and judgement at point 4

- Does not lead directly to guidance- Determines whether AWR or OIR are possibilities

8,127

3,860

0

9,287

0 1,000 2,000 3,000 4,000 5,000 6,000 7,000 8,000 9,000 10,000

(1) Incremental HRQoL benefits in first year

(2) Probability of sustaining HRQoL benefits insubsequent years (group of elicited parameters)

(3) 2-year probability of repeat EECP sessions

Overall decision uncertainty (EVPI)

Expected consequences (QALYs)

Point 5 – Will other sources of uncertainty resolve over time?

i. Other sources of uncertainty• Changes in price (technology and comparators)• New technologies entering• Other evidence becoming available

Assessment 1 2 3 4 5 6 7 Guidance

17 Yes Yes Yes Yes No Yes Yes AWR 4

18 Yes Yes Yes Yes No Yes No OIR 4

19 Yes Yes Yes Yes No No - Approve 6

24 Yes Yes Yes No No Yes Yes Approve 9

25 Yes Yes Yes No No Yes No OIR 6

26 Yes Yes Yes No No No - Approve 10

Types and categories of guidance for EECP that could ultimately result from assessments up to point 6

Point 6 – Are the benefits of research greater than the costs?i. Will the research be conducted?ii. When will it be available?

£0 £40,000,000 £80,000,000 £120,000,000 £160,000,000 £200,000,0000.00

0.10

0.20

0.30

0.40

0.50

0.60

0.70

0.80

0.90

1.000 2,000 4,000 6,000 8,000 10,000

Expected consequences, £

Pro

babilit

y of

res

earc

h

Expected consequences, QALY

1 year delay28 7

Costs of research, £1.5m (75 QALYs)

Research reports immediately3459 6

iii. How much uncertainty will be resolved?iv. Impact of other sources (point 5)

Point 7 – Are the benefits of approval greater than the costs?

The final point on the checklist requires a comparison of the benefits of approval and early access and the opportunity costs of approval

• Value of research forgone as a consequence• Irrecoverable costs committed by approval

- Capital costs (equipment, facilities, training and learning)- Initially negative NHE (when treatment decisions can be changed)






Types and categories of guidance for EECP that could ultimately result:











Is research possible with approval?











Is research possible with approval?

Technologies with significant irrecoverable costs - Research is not possible with approval

0.0

0.2

0.4

0.6

0.8

1.00 1 2 3 4 5 6 7 8 9

Pro

babilit

y that

rese

arc

h is

conduc

ted

Time for research to report, years

4-year design

3-year design

2-year design

1-year design

Necessary condition for OIR

Sufficient condition for Approve

An OIR or Approve boundary (EECP)

OIR AWRk = £20,000

Evaluation of alternative research designs

£0

£10,000

£20,000

£30,000

£40,000

£50,000

£60,000

£70,000

£80,000

£90,000

£100,000

0 200 400 600 800 10001200140016001800200022002400

Popu

lation

ENBS

x £1

,000

Sample size (n)

4-year follow-up

3-year follow-up

2-year follow-up

1-year follow-up

n*= 720

n*= 920

n*= 1,000

n*= 1,540

£0

£5,000

£10,000

£15,000

£20,000

£25,000

£30,000

£35,000

£40,000

0 200 400 600 800 1000 1200 1400 1600 1800 2000 2200 2400

Popu

lation

ENBS

x £1

,000

Sample size (n)

4-year follow-up

3-year follow-up

2-year follow-up

1-year follow-up

n*= 580

n*= 520

n*= 900

n*= 1,540

- Research is possible with approval

Conclusions

Policy analysis based on value of information analysis can be used to consider the value of:

i. being able to conduct research while a technology is approved;ii. the trade-off between the expected NHEs to current patients from early access and the NHEs to future patients from more research;

Understanding the relationship between the time taken for research to report and the value of the evidence can help inform:

i. investments which might make research findings available quicklyii. the trade-off implicit in the choice of alternative research designsiii. those areas where research must be reported quickly to be of value

Claxton et al. (2012) Uncertainty, Evidence and Irrecoverable Costs: Informing Approval, Pricing and Research Decisions for Health Technologies. CHE Research Paper 69.http://www.york.ac.uk/che/publications/in-house/

http://www.york.ac.uk/che/publications/in-house/

Health & Medicine

Conditional Coverage. Access with evidence development. Claire McKenna