Setting the threshold for reimbursement of a treatment

Dr Paul Cornes

Conflict of interest

Salary received:

• United Kingdom National Health Service

Honoraria received:

• Roche

• Janssen

• Sandoz

• Lilly

• European Generics Association

• Teva

• Hospira

Strive not to be a success,

but rather to be of value

Setting the threshold for

reimbursement of a treatment

Comparative Outcomes Group

ESO Task Force Advisory Board on

Access to Innovative Treatment in

Europe

European School of Oncology

Piazza Indipendenza, 2

6500 Bellinzona - Switzerland

Dr Paul Cornes,

Consultant Oncologist,

Bristol Haematology & Oncology Centre

[email protected]



Setting the threshold for

reimbursement of a treatment

Of the 12 new cancer drugs approved by the Food and Drug

Administration in 2012

11 were priced above $100,000 annually.

Only three were found to improve patient survival rates

and, of these, two increased survival by less than two months.

Kantarjian H et al. Making cancer drugs less expensive. Washington Post. February 22, 2013.

http://www.washingtonpost.com/opinions/making-cancer-drugs-less-expensive/2013/02/22/d8c8983e-7795-11e2-aa12-

e6cf1d31106b_story.html Accessed Sept 22, 2014

The options for future health spending include

the following:

Carry on spending at current rates – postpone

the inevitable decision to contain spending

Carry on spending at current rates and improve

efficiency and productivity

• that is, buy extra time before confronting the

inevitable decision to contain spending

Align health spending growth to general, long-

term growth in the economy as a whole

• with possible adjustments to devote a

modestly greater share of GDP to health care

as GDP grows.

Untenable in the

medium term

Viable possibly

medium term

Only long term

viable option if

the state is to

provide health

care from

general

taxation

Appleby J et al. Spending on health care - How much is enough? Kings Fund 2006. URL: http://www.kingsfund.org.uk/sites/files/kf/SpendingonHealthCare.pdf. Accessed

Nov 2, 2014

Physician level rationing

Oncologists do ration expensive treatments

• But they are not transparent in telling the patients

German Society of Hematology and Oncology

• Two-thirds of 345 participating oncologists withold costly

treatments in at least some instances

Reasons given

• 70% evidence for costly intervention was not convincing

enough,

• 59% unfavorable cost/benefit calculation.

Transparency

• Only 29% reported being explicit about their rationing decision

if the patient did not know or inquire about the respective

intervention.

Krause SW et al. Rationing cancer care: a survey among the members of the german society of hematology and

oncology.J Natl Compr Canc Netw. 2013 Jun 1;11(6):658-65.

Physician level rationing – with a financial

incentive!

USA - medical bills for the average

patient on chemotherapy can top

$100,000 a year.

• two of the largest health insurers

in the nation, United Healthcare

and Aetna, are tightening their

oversight over the treatment of

cancer by offering physicians

extra money to avoid newer, less

proven treatments.

• Evidence based therapy for lung

cancer offers 8 different

potential therapies

Mathews AW. Wall St J. May 27, 2014Insurers Push to Rein In Spending on Cancer Care. http://online.wsj.com/articles/insurer-to-reward-cancer-doctors-for-adhering-

to-regimens-1401220033. Accessed Sept 29, 2014. Abelson R. Insurers Test New Cancer Pay Systems. N Y Times Oct 19, 2010.

http://www.nytimes.com/2010/10/20/health/policy/20cancer.html?hpw. Accessed Sept 29, 2014

treatment

costs over a

12-month

period were

35 percent

lower

Rationing

had no effect

on patients.

Neubauer MA. Cost

Effectiveness of Evidence-

Based Treatment Guidelines

for the Treatment of Non–

Small-Cell Lung Cancer in the

Community Setting. JOP

January 2010 vol. 6 no. 1 12-

18

$350 month bonus fee

Metrics for decisions

The aim of healthcare

Aim of healthcare

• To live longer

• To live better

Aim of the health care systems

• to maximise health outcomes using available resources

The aim of healthcare – and its measures

The aim of healthcare is to help people live longer and better

Aim of healthcare Metric for health intervention

• To live longer Added Life Years ALY

• To live better Quality Of Life QOL

Metric for the two parallel aims

• ALY x QOL = QALY Quality Adjusted Life Year

Aim of the health care system

• to maximise health using available resources

• To gain the maximum QALYs for the health budget

Metric: Cost/ALY or Cost/QALY


Not all policy initiatives appear not to be driven primarily by the

pursuit of QALY gain, but to focus instead on what might be

described as ‘process‐of‐care’ considerations.

For example -- Hospital waiting times targets

• While some health gain might arise from the quicker treatment

of patients, targets can also result in prioritising those who

have waited longest over those with the most severe health

problems

If Value based medicine is to be introduced – it should be part of

a drive for value in the whole health system

• And not just a mechanism to cap some budgets over others!

– Shah K et al. Is the aim of the English health care system to maximize QALYs?

Journal of Health Services Research and Policy.17(3), 157-164.

Choices in health economics

The Stockholm group asks us to consider new treatment options

Ref Stockholm Network Research Team. What Price for a Year of Life? The Threshold Discussion in Health Technology Assessment. 2008. URL:

http://www.stockholm-network.org/downloads/publications/HTA_4.pdf. Accessed Nov 2, 2014

Your Budget

is 3,750

million gold

coins


HTA model

Buy most cost

effective treatment

first, then next, until

the money is spent

RESULT

Fund treatments A,

B, C, D and E,

Total Cost 3,750

million gold coins

Do Not fund F,G,H

or I



Your Budget is 3,750 million gold coins


Political Equal

distribution model:

Buy all treatment

equally until the

budget is spent

RESULT

You could buy 1/3rd

of each treatment

option A B C D E F

G H 1

Total Cost 3,750

million gold coins





Political Interest

model:

Buy all treatment to

satisfy well

organised patient or

producer groups




The Austrian

Parliament during

breast cancer

awareness month


Political Interest

model:

Buy all treatment to

satisfy well

organised patient or

producer groups

RESULT

You could buy only

treatments C D and

H

Total Cost 3,750

million gold coins





The HTA model saves more QALYs for a given investment in

health care



Now – who wants to be the Minister of Health?

The most effective option may make you unpopular!


The threshold diagram

What are the metrics for the Economic Decision

Diagram?

Clinical Outcome

Bette

rW

ors

e

Cost difference

Less More

Length of Life = ALY

Quality of Life = Q

ALY x Q = QALY

Money The slope of the line is the

Incremental Cost Effectiveness

Ratio = ICER

ICER Unit = The extra money

required to improve health by 1

QALY

The greater the gain,

the more we should

be prepared to pay


Diagram? WHO advice

Clinical Outcome

Bette

rW

ors

e

Cost difference

Less More

<1 x per capita

GDP / QALY = very

good value

>3 x per capita

GDP / QALY = poor

value

Per capita GDP is the

average National Gross

Domestic Product

(Earnings) per citizen per

year


Diagram? WHO advice

Clinical Outcome

Bette

rW

ors

e

Cost difference

Less More

Per capita GDP is the

average National Gross

Domestic Product

(Earnings) per citizen per

year

Where is the dividing

line?

The slope of the line

is the Incremental

Cost Effectiveness

Ratio = ICER


Diagram? WHO advice

Clinical Outcome

Bette

rW

ors

e

Cost difference

Less More


line?

In a National Health System

this is decided by willingness

to pay

In a private health system this

is decided by ability to pay


Diagram? WHO advice

Clinical Outcome

Bette

rW

ors

e

Cost difference

Less More


line?



to pay



How much

should

taxpayers be

prepared to pay

for a QALY gain?What about

insurers?


Diagram? WHO advice

Clinical Outcome

Bette

rW

ors

e

Cost difference

Less More


line?



to pay



What about

insurers?

Would they be

more

generous

What are the metrics for the Economic Decision:

Key Questions for Malaysian Oncology

1. Is cancer a special case compared to other illnesses?

2. What is the cost/effectiveness threshold at which we should

approve a new treatment for reimbursement?

3. What is the cost/effectiveness threshold at which we should

Remove a current treatment from reimbursement?

Should cancer treatments be seen as more

deserving than treatment for heart disease?

How much

should

taxpayers be

prepared to pay

for a QALY gain?




The very simplest answer

How can we improve Malaysian Guidelines?

By being explicit about the clinical effectiveness of the

interventions

This enables us to rank the value of potential treatment options

Tier Impact

Extremely

effective

Significant prolongation of

survival or

long term significant increase

in tumour control

Moderate

efficacy

Intermediate between the two

Minimal

efficacy

“statistically significant”

survival benefits of only short

duration

we will need payer and stakeholder consensus to

agree the parameters for our decisions !

What is the

“minimum

clinical

benefit” to

justify

treatment

from

Malaysian

Societal

perspectives?

Valuing Innovation

2013: Drs Kantarjian, Fojo, Mathisen, and Zwelling

Proposed 3 tiers of value for a new treatment

Ref Kantarjian HM et al. Cancer Drugs in the United States: Justum Pretium—The Just Price. J Clin Onc 2013;31(28):3600. DOI:

10.1200/JCO.2013.49.184

Tier Impact

Extremely

effective

Moderate

efficacy

Minimal

efficacy

Will need societal and payers

consensus

Valuing Innovation


Proposed 3 tiers of value for a new treatment


10.1200/JCO.2013.49.184

Tier Impact

Extremely

effective

new drug prolongs survival by more than 6 months or by

more than one third of the life expectancy (eg, 12 months

becomes ≥16 months, or 30 months is increased to ≥40

months)

improves long-term survival or PFS by 10%

Moderate

efficacy

Intermediate

Minimal

efficacy

“statistically significant” survival benefits of 2 months or

prolong life by less than 15%

For debate – we propose this for the

2014-2015 guidelines

Valuing Innovation

Example: Mariotto AB, J Nat Ca Inst 2011;103:117

anti–vascular endothelial growth factor inhibitors in

metastatic colon cancer provide a median survival

advantage of 1.4 months over standard of care,

These drugs cost $5,000 to $11,000 per month.

With a median overall survival from start of second-

line therapy of 12 months, and a median duration of

therapy of 12 to 14 months, the total cost translates

into approximately $40,000 to $80,000 per patient per

additional month of life.


10.1200/JCO.2013.49.184 Mariotto AB, Yabroff KR, Shao Y, et al: Projections of the cost of cancer care in the United States:

2010-2020. J Natl Cancer Inst 103:117-128, 2011

Tier

Extremely

effective

Moderate

efficacy

Minimal

efficacy

We might chose reject reimbursement for this

treatment on both efficacy and value criteria

Valuing Innovation


Set a challenge to us

• “Researchers, academicians, and professional societies

should demand better results and discontinue the practice of

exulting marginal outcomes”.

• “The bar should be raised for expectations from new drugs,

and hyping minor benefits of newer (more expensive) drugs

over older (less expensive) ones should not be endorsed by

tumor experts or professional societies unless such benefits

truly reflect incremental value worth the differential price.”


10.1200/JCO.2013.49.184

“This will also alleviate the pressure community oncologists

feel to prescribe newer drugs promoted by experts at

professional meetings"


Add cost effectiveness

Cost/effectiveness

High

<1xGDP

Moderate

? X GDP

Poor

>?GDP

Clinical

effect

Extremely

effective

Moderate

efficacy

Minimal

efficacy

We hope to agree

MOH funding for

these

Push for generics, biosimilars, price

reductions or cheaper

dose/schedules to bring inside MOH

funding zone

Create value with generics,

biosimilars, or cheaper

dose/schedules to free-up resource



Cost/effectiveness

High

<1xGDP

Moderate

? X GDP

Poor

>?GDP

Clinical

effect

Extremely

effective

Moderate

efficacy

Minimal

efficacy

Will need stakeholder

consensus to decide

Will need societal and payers

consensus



Cost/effectiveness

High

<1xGDP

Moderate

1 <2 X GDP

Poor

>2GDP

Clinical

effect

Extremely

effective

Moderate

efficacy

Minimal

efficacy

For debate – we propose this for the

2014-2015 guidelines



Cost/effectiveness

High

<1xGDP

Moderate

1 <2 X GDP

Poor

>2GDP

Clinical

effect

Extremely

effective

Moderate

efficacy

Minimal

efficacy





Practical steps in guideline writing

Making reimbursement decisions

For our process to be reasonable and accountable, there are four

conditions that we must fulfil:

1. Transparency: the process must be fully transparent about

the grounds for/rationales behind a decision.

2. Relevance: the decision must rest on reasons that all those

affected by the decision can accept as relevant to meeting

health needs fairly, given the resource constraints.

3. Revisability: decisions should be revisable in light of new

evidence and arguments.

4. Enforcement/regulation: there must be some kind of

regulation guaranteeing the three conditions described

above.

Ref

The 3 step reimbursement decision process

Assessment Phase:

• Output: Assessment report

Appraisal phase

• Output: Reimbursement advice

Decision‐making phase

• Output: Reimbursement decision

Ref

Potential Answers

1. Yes

2. Yes with restrictions

3. Defer until more data

4. No

The 3 step reimbursement decision process

Assessment Phase:

• Assessment criteria: health related, measurable

• Objective reporting, no value judgement

• Output: Assessment report

Appraisal phase

• Appraisal criteria: assessment criteria + other socially relevant

health(care‐sector) related criteria

• Weighting criteria, value judgement

• Output: Reimbursement advice


• Decision criteria: appraisal criteria + other socially criteria

• Weighting appraisal outcome with other socially relevant

criteria, value judgement

• Output: Reimbursement decisionRef

The 3 step reimbursement decision process: suggested

schema if not clearly effective and very good value

Assessment Phase:

Appraisal phase

• Perform a very simple HTA and compare with published

ASK - Is it approval straightforward?

• High or moderate clinical benefit and <2x GDP

ANSWER

• Yes, well inside 2 x GDP

• close,

• No - >3xGDP


Ref

WAIT: Full HTA is commissioned

ADVISE: Reject reimbursement as

intervention is very unlikely to be

cost effective

ADVISE: approve

HTA in Malaysia

Ref MaHTAS – Health Technology Assessment Section, Ministry of Health Malaysia. URL: http://www.inahta.org/our-members/members/mahtas/

Accessed Oct 9, 2014

WAIT: Full HTA is commissioned

Reimbursement decisions

Framework to take into

account when discussing the

reimbursement of a drug:

• efficacy, effectiveness,

• side-effects & safety

• user-friendliness

• added therapeutic value,

cost-effectiveness,

• budget impact,

• therapeutic and social

needs.

Metrics to take into account

when discussing the


Ref









cost-effectiveness,

• budget impact,


needs.


when discussing the


Ref

Balance of risks and benefits = OS

x QoL = QALY

Will be discovered in the “utility”

or “preference” scores.

Example: Patients prefer oral vs

i.v. drugs

Patients will trade off survival to

have a less effective oral

treatment









cost-effectiveness,

• budget impact,


needs.


when discussing the


Ref

QALY difference

COST/QALY = I.C.E.R

Incremental Cost-Effectiveness

Ratio

Gain or Loss: Monetary value

Example: Paying more for locally

produced treatments to stimulate

the economy

HTA in Malaysia

Office established – MaHTAS

Mission - Our vision is to ensure appropriate use of health

technology by influencing dicision-makers through collection,

analysis, dissemination of information on safety, effectivenes,

cost-effectiveness and health impact of technologies.

Our mission is to provide evidence for informed decision making

to policymakers, health care providers and consumers.

Ref MaHTAS – Health Technology Assessment Section, Ministry of Health Malaysia. URL: http://www.inahta.org/our-members/members/mahtas/










cost-effectiveness,

• budget impact,


needs.


when discussing the


Ref









cost-effectiveness,

• budget impact,


needs.


when discussing the


Ref

Balance of risks and benefits = OS

x QoL = QALY

Will be discovered in the “utility”

or “preference” scores.

Example: Patients prefer oral vs

i.v.drugs

Patients will trade off survival to

have a less effective oral

treatment









cost-effectiveness,

• budget impact,


needs.


when discussing the


Ref

QALY difference

COST/QALY = I.C.E.R

Incremental Cost-Effectiveness

Ratio

Gain or Loss: Monetary value

Example: Paying more for locally

produced treatments to stimulate

the economy





What is a significant or minimal clinical effect?

• Length of life

What is a wonder drug?

Gillis B. Abiraterone Continues to Show Survival Benefit in Updated Interim Analysis. OncLive Feb 15, 2013. URL http://www.onclive.com/conference-coverage/gu-

2013/Abiraterone-Continues-to-Show-Survival-Benefit-in-Updated-Interim-Analysis#sthash.FGBsts9B.dpufAccessed October 7, 2014.

Mostly of reduced performance

status

Adds 5.2 months of life

But doesn’t cure

Is derived from Ketoconazole,

another CYP17 inhibitor that

blocks androgen biosynthesis

Delays deterioration in ECOG

performance status by 10.9 vs.

12.3 months = 43 days

cost per QALY = £63,200

Marginal benefits?

Randomised trial of CT

screening for lung cancer

Clinical benefit:

• 0.0316 life-years per person

(95% CI, 0.0154 to 0.0478)

• 365 x 0.0316 = 12 days extra

life

• 0.0201 QALYs per person

(95% CI, 0.0088 to 0.0314).

• 365 x 0.0201 = 7 Days of

good quality life

Ref: Black WC et al. Cost-effectiveness of CT screening in the National Lung Screening Trial.N Engl J Med. 2014 Nov

6;371(19):1793-802. doi: 10.1056/NEJMoa1312547

Is there a real minimum threshold for treatment?

Time-trade off studies

Silvestri G. BMJ. 1998;317:771

• U.S.A.: 81 patients previously treated with cis-platinum based

chemotherapy for advanced non-small cell lung cancer.

asked to indicate the minimum survival benefit required to

accept the side effects of chemotherapy

• chemotherapy with mild toxicity and

• chemotherapy with severe toxicity

asked to choose between chemotherapy and supportive care

• Benefit prolonged life by 3 months

• Benefit palliated symptoms, no survival gain

Silvestri G et al. Preferences for chemotherapy in patients with advanced non-small cell lung cancer: descriptive study based on scripted interviews.

BMJ. Sep 19, 1998; 317(7161): 771–775.


Silvestri G. BMJ. 1998;317:771

• U.S.A.: 81 patients previously treated with cis-platinum based

chemotherapy for advanced non-small cell lung cancer.

asked to indicate the minimum survival benefit required to

accept the side effects of chemotherapy RESULTS

• chemotherapy with mild toxicity and Median 4.5m

• chemotherapy with severe toxicity Median 9m

asked to choose between chemotherapy and supportive care

• Benefit prolonged life by 3 months 22%

• Benefit palliated symptoms, no survival gain 68%


BMJ. Sep 19, 1998; 317(7161): 771–775.

“Big Lung Trial” S Spiro. Thorax 2004;59:828

• 725 patients with un-resectable NSCLC

• randomised to receive supportive care alone (n = 361) or

supportive care plus cisplatin-based chemotherapy (n = 364).

• Results

• median survival 8.0 months v 5.7 months

• Chemotherapy improved OS by 9 weeks

Ref: S Spiro, et al. Chemotherapy versus supportive care in advanced non-small cell lung cancer: improved survival without detriment to quality of life.

Thorax. Oct 2004; 59(10): 828–836.



BMJ. Sep 19, 1998; 317(7161): 771–775.

Treatment preferences

for 81 patients who

had had

chemotherapy for lung

cancer.

Relation between

additional survival

offered and

percentage of patients

choosing

chemotherapy is

shown for mild toxicity

(scenario 1) and

severe toxicity

(scenario 2)

BIG

lung

trial 9

weeks


Kim M K et al. Jpn. J. Clin. Oncol. 2008;38:64-70

A decade later the

findings are similar

Treatment preferences

for Japanese cancer

patients

Relation between

additional survival

offered and

percentage of patients

choosing

chemotherapy is

shown for mild toxicity

(scenario 1) and

severe toxicity

(scenario 2)

BIG

lung

trial 9

weeks






• Length of life

• Quality of life

What is a “meaningful clinical difference?”

Overall survival is a simple end-point to evaluate

• Extra length of life = ALY gain

But what if only Quality of life is improved?

• And what it it has not been directly measured?

The “minimally important difference” (MID) is easy to define

• The MID has been defined as the smallest change in a Patient

Reported Outcome (PRO) measure that is perceived by

patients as beneficial or that would result in a change in

treatment

And what if you don’t have a

validated PRO recorded

Revicki DA, et al. Responsiveness and minimal important differences for patient reported outcomes. Health Qual Life Outcomes 2006, 4:70


A QOL change that turned a patient from dependent on others to

independent living would be seen as a real benefit to patients

and carers

ECOG/ WHO PS 3, to independent, WHO PS 0-1Revicki DA, et al. Responsiveness and minimal important differences for patient reported outcomes. Health Qual Life Outcomes 2006, 4:70




and carers

ECOG/ WHO PS 3, to independent, WHO PS 0-1Pickard SA et al. Estimation of minimally important differences in EQ-5D utility and VAS scores in cancer. Health and

Quality of Life Outcomes 2010, 8:4

PS Utility

for all

patients

For Lung

cancer

only

0 0.85 0.78

1 0.73 0.68

2 0.63 0.55

3 0.45 0.52

Improvement

from 3 to 1 =

0.73-0.45 =

0.28 gain

If OS is not improved

by a treatment, and

median OS was 6

months there is no

ALY gain

If it improved mean

PS from 3 to 1 it

would gain 0.5 years

x 0.28 QOL= 0.14

QALYs gained

UK Data from

Pickard 2010

can be useful




and carers

ECOG/ WHO PS 3, to independent, WHO PS 0-1Pickard SA et al. Estimation of minimally important differences in EQ-5D utility and VAS scores in cancer. Health and


PS Utility

for all

patients

For Lung

cancer

only

0 0.85 0.78

1 0.73 0.68

2 0.63 0.55

3 0.45 0.52

AS a simple

measure for

HTA

1 x WHO PS gain is

0.1 to 0.18 Utility gain

UK Data from

Pickard 2010

can be useful

2 x WHO PS gain is


3 x WHO PS gain is

0.4 Utility gain


The Minimum Utility Gain to make a

noticeable difference is usually 0.10

– Pickard SA, 2010

• For a simple estimate HTA. This

equates to improvement in 1

ECOG/WHO performance level

A truly impressive QALY gain requires

a 2-3 ECOG/WHO performance level

gain

• Or 0.22 to 0.4 difference in QoL

Pickard SA et al. Estimation of minimally important differences in EQ-5D utility and VAS scores in cancer. Health and


1 x WHO PS gain is


2 x WHO PS gain is


3 x WHO PS gain is

0.4 Utility gain

So – a truly impressive symptomatic response, of duration 6 months, if

OS was not changed …

…might gain perhaps 0.5 x 0.4 = 0.2 QALYs


For the best results in a full HTA, we need to measure QOL using

a validated scale

• AND understand how society rates each health state

The simplest is to use the EQ5D 5 question tool

• From which we know Malaysian preference scores

3 x WHO PS gain is

0.4 Utility gain

Collecting EQ5D as a routine

Helps you decide if there is a meaningful benefit or loss in QOL

over time for a patient

• Can let you audit a protocol outcome

• Compare treatments

• Drive improvements in performance

Is used in the UK

• for routine Patient reported Outcomes surveys – to assess

variation between hospitals

• Used for “payment by results”

• For population health surveys to assess needs-based

allocation of resources

• For NICE assessments of preference in treatment and so

cost/QALY estimates for Valuation of cost utility

Devlin NJ. NHS Experience with the EQ5D as an outcome measure. Health Quality Council of Alberta, Cranmore, Canada,

18-19 Oct, 2012. URL http://www.slideshare.net/OHENews/devlin-canada-2012. Accessed October 7, 2014.

EQ5D is simple to collect – about 3 minutes

EQ5D is simple to collect – about 3 minutes

This patient has

scored 2,2,2,3,1

And a Global Visual

Analogue Q.o.L.

score of 0.65

3x3x3x3x3=243

potential results

Use of EQ5D to assess variation in QALY gained

by hip surgery by hospital in the UK



Cost per QALY difference between 336 UK

Hospitals



EQ5D in Malaysia

Faridah Aryani Md Yusof et al. Estimating an EQ-5D Value Set for Malaysia Using Time Trade-Off and Visual Analogue

Scale Methods. Value in Health 2012;15(1) suppl:S85-90



3x3x3x3x3=243

potential results

All 243 are now

scored for

Malaysia, ready for

local HTAs using

Malaysian Societal

values

A year lived at an EQ5D score 1,1,1,3,3 is worth about half a

QALY in Malaysia societal values

• 0.453 QALYs by Time Trade Off

• 0.511 QALYs by VAS



Minimum therapeutic benefit

Harvard Study, 1991

Survey of 51 oncologists

Lind SE,et al. Oncologists vary in their willingness to undertake anti-cancer therapies. Br. J. Cancer 1991;64:391-395

Minimum therapeutic benefit

A follow-up survey was conducted in March 1997 at a session on

NCCN clinical practice guidelines

“You are a 60-year-old oncologist with non-small-cell lung

cancer, one liver metastasis, and bone metastases. Your

performance status is 1.

• Would you take chemotherapy? Yes or no?”

YES

64.5% Medical Oncologists/Hematologists

67% Nurses

33% Radiation oncologists and other types of physicians

0% Nonmedical administrators

Do Doctors Refuse Chemotherapy On Themselves? http://anaximperator.wordpress.com/2010/05/06/do-75-of-doctors-refuse-

chemotherapy-on-themselves/. Accessed Sept 4, 2014

Minimum therapeutic benefit –

how do you ask the question?

Patients need to have the information required to obtain

informed consent

“Chemotherapy halves the odds of death with a serious toxicity

rate of 3%”

Chao, C. Adjuvant Chemotherapy for Breast Cancer: How Presentation of Recurrence Risk Influences Decision-Making. J Clin

Oncol 21:4299-4305.

Relative risk

Absolute risk

Minimum therapeutic benefit –

how do you ask the question?

Chao, C. Adjuvant Chemotherapy for Breast Cancer: How Presentation of Recurrence Risk Influences Decision-Making. J Clin

Oncol 21:4299-4305.

Different chance of

accepting

chemotherapy when

results are expressed

in Relative risk vs

absolute numbers






Debate on the value of a QALY threshold

International Comparisons 2008

US Medicare $50,000 or £34,000 per QALY

Stockholm Network Research Team. What Price for a Year of Life? The Threshold Discussion in Health Technology Assessment. URL:


What should we pay for a year of life?

Options to set a threshold that have general support:

Affordability – a multiple of per-capita annual income

• WHO <1 x GDP; 1 to 3; >3

Equity for all patients

Gerber AM and CE Phelps. Economic Foundations of Cost-effectiveness Analysis. Journal of Health Economics 1997(16):1-31.

Ubel PA. What Is the Price of Life and Why Doesn’t It Increase at the Rate of Inflation? Arch Intern Med 2003(163):1640-41

McGregor M. Cost-utility Analysis: Use QALYs Only With Great Caution. CMAJ 2003(168)4:433-4

Options to set a threshold that have general

support:

Affordability

– Endorsed by the WHO CHOICE programme and Commission on

Macroeconomics and Health (CMH)

• No more than 2 x per capita annual income (PCI)

– Garber AM, Phelps CE. Economic foundations of cost-effectiveness analysis. J

Health Econ. 1997 Feb; 16(1):1-31

– Evans DB & WHO Choosing Interventions that are Cost Effective (CHOICE)

Millennium Development Goals Team. Evaluation of current strategies and future

priorities for improving health in developing countries. BMJ. 2005 Dec 17;

331(7530):1457-61

– Sachs J. Macroeconomics and health: investing in health for economic

development. World Health Organization; Geneva: 2001

Garber AM, Phelps CE. Economic foundations of cost-effectiveness analysis. J Health Econ. 1997 Feb; 16(1):1-31

Evans DB & WHO Choosing Interventions that are Cost Effective (CHOICE) Millennium Development Goals Team. Evaluation of current strategies and future priorities for improving health in developing countries. BMJ. 2005 Dec 17;

331(7530):1457-61

Sachs J. Macroeconomics and health: investing in health for economic development. World Health Organization; Geneva: 2001

The $US50 000 per QALY (1982

year values) threshold commonly

used in the USA is similar to 2 x

Annual PCI ($US46 040)

This level rises

as society

becomes

wealthier

So the 2011

level = $US

100,000 per

QALY

Is 3x GDP too high?

Options to set a threshold that have general

support:

But the US is an unequal society.

The median wage in the US per person was only $26,695 in 2011

– How much do Americans earn? What is the average US income and other

income figures. Fiscal cliff talks only useful in context of incomes. My Budget

360. URL: http://www.mybudget360.com/how-much-do-americans-earn-what-is-

the-average-us-income/ Accessed Oct 30, 2014.

Conversion performed Oct 30, 2014. URL:

https://www.google.co.uk/search?q=convert+53%2C390+USD+to+gbp&oq=convert+53%2C390+USD+to+gbp&aqs=chrome..69i57.5277j0j4

&sourceid=chrome&es_sm=91&ie=UTF-8

The $US50 000 per QALY (1982

year values) threshold commonly

used in the USA is similar to 2 x

Annual PCI ($US46 040)

This level rises

as society

becomes

wealthier

So the 2008

level =

$US101,295

per QALY

A better

estimate of

affordability

may be

2 x

26,695 =

53,390

USD

Almost

identical to

NICE’s

30,000

GBP/QALY


Options to set a threshold that have general support:

Affordability – a multiple of per-capita annual income

Equity for all patients

• Equivalent cost effectiveness of Dialysis

• Not significantly different from the current average cost

effectiveness of the health system





The first reported formal threshold

• The ‘Medicare Dialysis Standard’ – $50,000 (US) for a QALY.

Originates from a 1982 ruling by the US public health fund

Medicare that concerned a programme to treat patients with

chronic renal failure.

The ruling intended to make sure that the treatment was only

applied in serious cases, so that it resulted in the mentioned

cost-per-QALY number.

Equity of access to health care then suggests that all other

treatment options up to – $50,000 (US) for a QALY should also be

provided.

Stockholm Network Research Team. What Price for a Year of Life? The Threshold Discussion in Health Technology Assessment. URL:



One level that is often advised is to set it at the level for Dialysis

• So that cancer patients and renal failure patients could have

the same access to treatment

• USA suggests haemodialysis works out at about $50,000/year

Under Medicare rules, renal dialysis is a federal entitlement to all

United States citizens, and is thus considered cost-effective by

US standards.

• As such, any other treatment that costs $50,000 or less per

QALY is considered cost-effective as well.




Shows close

agreement

with UK

N.I.C.E.

30,000 GBP


One level that is often advised is to set it at the level for Dialysis

• So that cancer patients and renal failure patients could have

the same access to treatment

• USA suggests haemodialysis works out at about $50,000/year

Critique is that

• medical advances and rising costs have forced this higher

since the original $50,000 calculation




Shows close

agreement

with UK

N.I.C.E.

30,000 GBP


Critique is that

• medical advances and rising costs have forced this higher

since the original $50,000 / Year calculation

Stanford recalculation by Lee et al:

• computer analysis of more than half a million patients who

underwent dialysis, adding up costs and comparing that data

to treatment outcomes.

• Cost/QALY = $129,000

Lee CP et al. An Empiric Estimate of the Value of Life: Updating the Renal Dialysis Cost-Effectiveness Standard. Value in

Health 2009;12(1):80-87


Critique of the critique is that

• Dialysis costs have risen fast than any extra clinical benefits

Renal Week 2009 presentation:

• 2009 Costs for a year of dialysis = $73,000

• Even modest improvements in the survival of patients with

end-stage renal disease undergoing dialysis may lead to

billions of dollars in extra costs

• Paying for "new advances" will cost the USA and extra $14

billion each year

MacReady N. Skyrocketing Costs of Dialysis May Require Difficult Decisions. Medscape Medical News November 09, 2009.

http://www.medscape.com/viewarticle/712019. Accessed Aug 31, 2014

Lee CP et al. An Empiric Estimate of the Value of Life: Updating the Renal Dialysis Cost-Effectiveness Standard. Value in Health 2009;12(1):80-87

Will these extras be worth it

compared with other things that

could be done with $14 Billion?

Comparisons with dialysis

What is the cost/benefit of the Malaysian Dialysis programme?

Budget is under threat with annual rise of between 7%-13% of

new patients joining dialysis program in the last five years.

Costs include:

RM50mil was spent on medication after transplantation

Arukesamy K. Government funds almost 60% of all haemodialysis funding. The Sun Daily. Posted on 27 December 2011 - 05:24am. http://www.thesundaily.my/news/249349 Accessed Aug 31, 2014

Malaysian patients spend $286mil on kidney dialysis yearly. Star/Asia News Network Dec 14, 2011. http://news.asiaone.com/News/AsiaOne+News/Malaysia/Story/A1Story20111214-

316098.html#sthash.rIyeRX7R.dpuf. Accessed Aug 31, 2014


As in the USA – the Malaysian

Dialysis Programme is becoming

unaffordable

2012: there were 26,404 patients

on dialysis

National programme equivalent

cost = 873,233,088 RM per year

Malaysian Dialysis Cost is

33,072 RM per year per patient at

an NGO centre

Loh Foon Fong et al. Dialysis subsidy drying up. The Star. Thursday November 7, 2013 MYT 12:00:00 AM Updated: Friday November 8, 2013 MYT 9:37:24 AM. Accessed Aug 31, 2014

Arukesamy K. Government funds almost 60% of all haemodialysis funding. The Sun Daily. Posted on 27 December 2011 - 05:24am. http://www.thesundaily.my/news/249349 Accessed Aug 31,

2014

Threshold using the WHO 2 x

GDP criteria = 34,000 RM per

year (2 x 17,000 = 34,000)

Good

agreement

with the cost

of

haemodialysis

or peritoneal

dialysis for a

year in

Malaysian

public

hospitals =

RM33,000 per

patient,


As in the USA – the Malaysian

Dialysis Programme is

becoming unaffordable

2012: there were 26,404

patients on dialysis

National programme

equivalent cost = 873,233,088

RM per year

Malaysian Dialysis Cost is

33,072 RM per year per patient

at an NGO centre

Loh Foon Fong et al. Dialysis subsidy drying up. The Star. Thursday November 7, 2013 MYT 12:00:00 AM Updated: Friday November 8, 2013 MYT 9:37:24 AM. Accessed Aug 31, 2014

Arukesamy K. Government funds almost 60% of all haemodialysis funding. The Sun Daily. Posted on 27 December 2011 - 05:24am. http://www.thesundaily.my/news/249349 Accessed Aug 31, 2014

Faridah Aryani Md Yusof et al. Cost Utility Analysis of the Ministry of Health Dialysis Programme. iHEA 2007 6th World Congress: Explorations in Health Economics Paper. Available at

http://papers.ssrn.com/sol3/papers.cfm?abstract_id=993376. Accessed Aug 31, 2014

Threshold using the WHO 2 x

GDP criteria = 34,000 RM per

year (2 x 17,000 = 34,000)

Good

agreement with

the cost of

haemodialysis

or peritoneal

dialysis for a

year in

Malaysian

public hospitals

= RM33,000 per

patient,

Cost/QALY in

Malaysia

estimated at

RM43,000 for

haemodialysis

and RM41,000

for CAPD.

GDP for 2013 from - World Bank.

Malaysia Overview. Updated on

February 28, 2014. URL:

http://www.worldbank.org/en/countr

y/malaysia/overview. Accessed Oct

13, 2014. World Bank. Malaysia

Overview. Updated on February 28,

2014. URL:

http://www.worldbank.org/en/countr

y/malaysia/overview. Conversion

USD to MYR via Google Oct 13,

2014.

URL:https://www.google.co.uk/web

hp?sourceid=chrome-

instant&ion=1&espv=2&ie=UTF-

8#q=10500%20USD%20to%20MY

R. Accessed Oct 13, 2014.

Threshold for reimbursement in Malaysia

Cost/QALY Derived from

RM 31,195 Malaysian willingness to pay survey

RM 34,000 2 x per capita annual income

RM 43,000 Haemodialysis

RM 51,000 3 x per capita annual income

Suggests

that dialysis

may be just

at the edge

of

affordability

for

Malaysian

Healthcare.

Asrul Akmal Shafie et al. Exploring willingness to pay for a quality-adjusted life-year in Malaysia. Universiti Sains Malaysia, Penang, Malaysia. https://usmalaysia.conference-

services.net/reports/template/onetextabstract.xml?xsl=template/onetextabstract.xsl&conferenceID=3730&abstractID=754949. Accessed Sept 4, 2014. Loh Foon Fong et al. Dialysis subsidy drying

up. The Star 2013 Nov 7th. http://www.thestar.com.my/News/Nation/2013/11/07/Dialysis-subsidy-drying-up-Thousands-face-health-risk-as-govt-funding-is-not-approved/. Accessed Sept 4, 2014

Confirmed

by loss of

subsidy for

dialysis

The number of

approvals for

the RM600

monthly

subsidy began

to decrease in

2011, and

became minimal

from mid-2012.

Mean income was $49,855 in 2011

Critique of the USA $100,000 per QALY

With a single payer

National Health

Service that pools the

risk of ALL citizens

and taxation

proportionate to

wealth, the threshold

could be 2 x per capita

GDP = 2 x 49,855

• = about $100,000

However the USA is a

very unequal country

Most citizens had to

buy private insurance

weighted to individual

risk factorsHow much do Americans earn? My Budget 360. URL: http://www.mybudget360.com/how-much-do-americans-earn-what-is-the-average-us-income/. Accessed Nov 2, 2014

World Bank data for USA 2011. URL: http://data.worldbank.org/indicator/NY.GDP.PCAP.CD. Accessed Nov 2, 2014

Median income was $26,965 in 2011

The richest

got richer

But the

majority

are little

better off

than in the

1960s

Median Household income = $50,100 in 2011

Mean income was $49,855 in 2011

Critique of the USA $100,000 per QALY

With a single payer

National Health

Service that pools the

risk of ALL citizens

and taxation

proportionate to

wealth, the threshold

could be 2 x per capita

GDP = 2 x 49,855

• = about $100,000

However the USA is a

very unequal country

Most citizens had to

buy private insurance

weighted to individual

risk factorsHow much do Americans earn? My Budget 360. URL: http://www.mybudget360.com/how-much-do-americans-earn-what-is-the-average-us-income/. Accessed Nov 2, 2014

World Bank data for USA 2011. URL: http://data.worldbank.org/indicator/NY.GDP.PCAP.CD. Accessed Nov 2, 2014

Median income was $26,965 in 2011

Very Close in agreement with the

UK N.I.C.E £30,000/QALY

threshold !

What the typical US citizen

could actually afford was 2 x

Median Salary of 26,965

approximately $54,000/QALY

$54,000 = £34,000

Critique of the USA $100,000 per QALY: Explains

why US medicine has become unaffordable

Mangan D. Medical Bills Are the Biggest Cause of US Bankruptcies: Study. CNBC Jun 25, 2013. URL: http://www.cnbc.com/id/100840148#. Accessed Nov 2, 2014

Kane L. Nearly One-Third of Americans Can’t Afford Health Care. Learnvest.com. Dec 21, 2012. URL: http://www.learnvest.com/2012/12/nearly-one-third-of-americans-

cant-afford-health-care-123/. Accessed Nov 2, 2014

Very Close in agreement with the

UK N.I.C.E £30,000/QALY

threshold !

Strongly validates 2 x GDP as an

upper reimbursement threshold !

US & UK agreement?

The US $50,000 or £34,000 per QALY upper limit is also identical

to the upper routine threshold calculated for the UK

Martin et al (2008) examined variations in NHS local purchaser

spending and mortality by disease area for one year

– Martin S, Rice N and Smith P (2008) “Does health care spending improve health

outcomes? Evidence from English programme budgeting data.” Journal of Health

Economics Vol.27 (4): pp826-842.

Cost to “buy” an Added Life Year (ALY) in UK cancer medicine is

£13,100 in 2008

• About 1 x GDP

Upper 95% CI spend for a QALY is £34,099

• About 2 x GDP







Debate in Thailand

Development of Health Technology Assessment

in Thailand

Milestones

Sripen Tantivess, Health technology assessment and policymaking in Thailand.

http://www.worldhealthsummit.org/fileadmin/downloads/2013/WHSRMA_2013/Presentations/Day_3/Tantivess%20Sripen%20-

%20Health%20Technology%20Assessment%20and%20Policymaking%20in%20Thailand.pdf. Accessed Sept 17, 2014


in Thailand

Established standards, guidelines, tools:

• National Methodological Guidelines for HTA

• Cost-effectiveness threshold – 1 GNI per capita per QALY

gained (120,000 Baht)

• Thailand’s HTA database

• Standard Costs Menu





in Thailand

HTA are used to decide coverage by

Universal Health Coverage plan – benefit package

• UHC manager: National Health Security Office (NHSO)

• Literally, all services are covered, except those on ‘negative’

list

• Interventions: diagnosis, treatment, prevention, health

promotion, rehabilitation

• Focus: safety, effectiveness, cost-effectiveness, budget

impact





in Thailand

HTA are used to decide coverage by

National List of Essential Medicines (NLEM)

• Executive Committee, with support from technical working

groups

• National pharmaceutical benefit package

• Interventions: pharmaceuticals, vaccines and other biological

products

• Focus: safety, effectiveness, cost-effectiveness, budget

impact and others




If treatment is a drug


in Thailand





in Thailand




Recent examples of reimbursement decisions by HITAP


in Thailand





Renal Dialysis

• Was more expensive than 120,000 Baht/QALY

• Peritoneal dialysis for ESRD (ICER=435,000)

• Hemodialysis for ESRD (ICER=449,000)

Social considerations were included -

because this treated catastrophic diseases

with a life-saving intervention


in Thailand

ยามะเร็งสุดแพงเข็มละ 7 หม่ืนบาท รกัษาหายใชเ้งินกว่าลา้น สปส./30 บ.เขา้ไม่ถึง Submitted by ปารณีย์ จิรสัยจิ์นดา on 18 June 2012 22:30


Trastuzumab for breast cancer (August 2014)

HITAP report (http://hitap.net/en/node/11172)

• the cost of Trastuzumab - Herceptin was Priced at 98,340 USD

• Up to 60% price reductions required of the pharmaceutical

company

Thresholds to set reimbursement

Country GDP in USD in 2012

Singapore 51,162

Japan 46,735

S Korea 23,113

Taiwan 20,328

Malaysia 10,304

Thailand 5,678

UK 38,649 (23665 GBP)

Adapted from the IMF's World Economic Outlook Database (April 2013). http://www.imf.org/external/pubs/ft/weo/2013/01/weodata/weorept.aspx?sy=2010&ey=2012&scsm=1&ssd=1&sort=country&ds=.&br=1&

pr1.x=74&pr1.y=12&c=548%2C924%2C576%2C528%2C532%2C578%2C158%2C542&s=NGDPDPC%2CPPPGDP%2CPPPPC&grp=

0&a=

Thailand set a cost/QALY threshold

of 120,000 Baht/QALY ≈ 1 x GDP in

2009

Raised to 160,000 Baht/QALY in

2013 ≈ 1.2 x GDP

UK set a routine cost/QALY

threshold of 20,000 GBP ≈ 1 x GDP

Rising to 30,000 GBP after careful

economic assessment ≈ 1.3 x GDP

Rising to 50,000 GBP in very

selected situations (end of life)

≈ 2 x GDP




Raised to 449,000 Baht/QALY for

dialysis ≈ 2.8 x GDP







Debate in Thailand

Practical steps in guideline writing

How many treatment pathways are needed for

each cancer?

Ref: Hoppe RT . Patterns of Care Process Study Newsletter [Hodgkins disease]. 1990-1991. Philadelphia, American College of radiology, 1991

The value of

decision tree

diagrams

Key part of USA

Patterns of care

studies

Describes work

up and staging

This tree results

in 5 Treatment

Summary

groups (TS 1 to

5)

How many protocols do we need?

5 cancers in Malaysia account for more than half the burden,

2007 data

– National cancer Registry Report, 2007

Remember – it takes as long to write the guidelines for a rare

cancer as a common one!

58.4%

National Cancer Registry Report, Malaysia Cancer Statistics – Data and Figure 2007, Ariffin OZ, Saleha IT, Ministry of

Health, Malaysia, 2011.

How many guidelines for treatment are needed?

Despite there being >200 types of cancer

• Most countries need <20 guidelines to cover >70%

of the cancer population in men and women

Ref: Mary Chin. 64 oncologists and nearly half women. Daily Express Feb 25, 2012. URL: http://www.dailyexpress.com.my/read.cfm?NewsID=868.


71.9% of all

male cancer

77.6% of all

female cancer

10 Guidelines + 5 more

Guidelines

How many guidelines for cost-effective

treatment are needed?

Despite there being >200 types of cancer

• Most countries need <20 guidelines to cover >70%

of the cancer population in men and women

Ref: Mary Chin. 64 oncologists and nearly half women. Daily Express Feb 25, 2012. URL: http://www.dailyexpress.com.my/read.cfm?NewsID=868.


71.9% of all

male cancer

77.6% of all

female cancer

10 Guidelines + 5 more

Guidelines

2012: 64

Oncologists

were working

in Malaysia

If 4 Oncologists took a week of study leave to draft

each cost-effectiveness guideline, then Malaysian

Specific guidelines could be written in 1 year that

covered >70% of the national cancer incidence

Or the insurers and MoH

need to fund 15 weeks

study leave for a team of 4

Oncologists to create the

National guidelines

Once created,

annual updates

take far less

time &

resource

Why is it in the interests of the MoH and

Insurers to support such a policy?

Investing in systems to promote Cost-Effective care is good

value

Thailand

• Health Intervention and Technology Assessment Program

(HITAP) cost-effectiveness group set up 2007

• MoH Invests in a staff of 50, 1 Million USD/Year costs

• By 2013, had saved Thailland’s MoH >1000 Million Baht

Ref Sripen Tantivess, Health technology assessment and policymaking in Thailand. URL:


%20Health%20Technology%20Assessment%20and%20Policymaking%20in%20Thailand.pdf. Accessed Oct 15, 2014

>30 Million USD

>100 Million RM

A Five-fold return

on investment

DOI: http://dx.doi.org/10.1007/s11523-011-0196-3

Albert Einstein



Setting the threshold for reimbursement of a treatment

Health & Medicine

Transcript of Setting the threshold for reimbursement of a treatment