• No results found

Policy change: System change to support practice of AR

7.0 Further work

As the review of international cost-effectiveness literature did not yield useful evidence with which to compare the new guidelines, specific cost modelling of the recommendations using Australian data has also been undertaken by external consultants as part of the guidelines development process.

This process included cost effectiveness modelling for various drugs, which was used to inform the development of the recommendations. Further modelling was done after completion of the recommendations, to determine the total costs and the cost effectiveness of the finalised recommendations.

Target Population

Author Publication

year Intervention Comparator Study setting

Type of

evaluation Gender Age Risk factor/

co-morbidity

Analytic

horizon Discounting Perspective Compliance Annemans

et al

2006 Low-dose aspirin Placebo UK Germany Spain and Italy

Cost utility Both 50, 55,

60 Patient groups at 2%, 3%, 4%, 5% risk of a fatal coronary heart disease event in 10 years using SCORE algorithm

10 yrs Country-specific rates for both costs and benefits applied. The rates vary from 3% to 5%

Health care

payer No statement

Ara et al 2008 Ezetimibe in combination with statins

Statin

monotherapy UK Cost utility Both 40 Individuals who have not achieved cholesterol control with statins

Lifetime 3.5% National

Health Service Discussed

Earnshaw

et al 2011 Low dose aspirin

with omeprazole 20 mg/d

Low dose

aspirin alone. US Cost utility Men 45, 55, 65

A range of underlying 10 year CHD risk (2.5%, 5%, 7.5%, 10%, 15%, 25%)

Lifetime 3% Third-party

payer 100%

assumed

Franco et al 2007 Smoking cessation to smokers, aspirin given to all, BP-lowering drugs given to people with SBP>140 mmHg and statins given to all

No intervention Netherlands Cost

effectiveness Men 45-55 &

55-65 Framingham study participants meeting age and risk thresholds (low moderate and high)

10 years 4% Third-party

payer No statement

Gaziano

et al 2006 Aspirin, CCB,

ace inhibitor and statins for primary prevention

No treatment Developing country regions (WHO)

Cost utility Both 35-74 Multiple levels of 10-year risk for CHD

Lifetime 3% Societal Sensitivity analysis

Greving et al 2008 Low-dose aspirin

no quantity listed No aspirin Netherlands Cost utility Both 45, 55,

65, 75 At various levels of 10 year cardiovascular disease risk based on number of risk factors

10 yrs 4% for costs

& 1.5% for benefits

Health care

payer No statement

Grover et al 2008 Lipid treatment or hypertension management

Not stated Canada Cost effectiveness (averages)

Both 40–74 2,121 participants surveyed from the Canadian heart health survey without CVD who qualify for lipid treatment or hypertension management

Not stated 3% Health care

system No statement

Jonsson

et al 2003 Anti hypertensive

treatment with felodipine

The lowest

change in BP 26 countries Cost

effectiveness Both 50–80 18,790 trial patients with hypertension

Trial length of 3.8 yrs

None Societal No statement

Lamotte

et al 2006 Low-dose aspirin No aspirin Europe, 4

countries Cost utility Both Not spe

cified 1.5% 10-year risk of a coronary heart disease event

10 yrs Country

specific Public healthcare payer

No statement

Lungkvist

et al 2005 Candesartan

anti hypertensive treatment

Placebo Europe Cost utility Both 70–89 Elderly patients with mild to moderate hypertension

Lifetime 3% Societal No statement

Marshall 2006 Treatment with aspirin or up to 4 BP-lowering drugs and statins

Do nothing UK Cost

effectiveness Both Not spe

cified Taken from the Health Survey for England of 1998 using eligibility criteria for treatments with joint British recommendations

10 yrs 3% Health

services 100%

assumed

Montgomery

et al 2003 Hypertensive

medication not specified clearly

No treatment not further specified

UK Cost utility Both 30-70 Low- and high-risk groups defined with smoking, BP, diabetes, etc

Lifetime 6% for costs and 1.5% for benefits

Health

services Discussed

Table 1. Analysis of studies

Target Population

Author Publication

year Intervention Comparator Study setting

Type of

evaluation Gender Age Risk factor/

co-morbidity

Analytic

horizon Discounting Perspective Compliance Murray et al 2003 Statin, diuretic,

BP-lowering drug and aspirin

No intervention 3 World

regions Cost utility Both

30-100 People with an estimated combined risk of cardiac event over the next decade above a given threshold.

Thresholds reported as 35%, 25%, 15%, 5%

100 yrs 3% Decision

makers not further specified

Discussed

Newman et al 2008 Polypill combination therapy of simvastatin, captopril, hydrochlorthiazide and atenolol

Current standard care

US Cost utility Men >55

yrs Regardless of baseline risk factors

Not stated 3% Not stated 100%

Neyt et al 2009 Low dose

pravastatin Smoking cessation, or aspirin interventions

Belgium Cost

effectiveness Men 50 &

60yrs Moderate and high risk of coronary heart disease

10 yrs 3% for costs

& 1.5% for benefits

Belgian decision makers

Discussed

Nordman et al 2003 ACE inhibitors

to all Conventional

therapy US Cost utility Men 40yrs Requiring antihypertensives but no other comorbidity

Lifetime 5% Third-party

payer Sensitivity analysis

Pignone et al 2006 Low-dose aspirin, a statin, both drugs as a combination

No therapy US Cost utility Men 45 yrs

old Various levels of 10-year risk for CHD

Lifetime 3% Third-party

payer 100%

assumed

Pignone et al 2007 Aspirin No therapy US Cost utility Women 65 yrs 7.5% 10-year risk of a coronary heart disease event

Lifetime 3% Third-party

payer 100%

assumed

Pilote et al 2005 Lipids to people

w/o CVD Lipids to people with CVD

Canada Cost outcome with sub group analysis

Both 30-74 Population surveyed with Canadian Heart Health Survey

Lifetime 5% Societal No

statement

Pletcher et al 2009 ATP III guidelines and a number of risk based and age-based strategies

Current

practice US Cost utility Both 35-85 10-year CHD risk varying from > 0 to >15%

30 years 3% Healthcare

system 100%

assumed

Ramsay et al 2008 10mg/day

atorvastatin No HMG-CoA reductase inhibitor (statin) therapy

US Cost utility Both >20yrs People with type 2 diabetes, and one additional risk factor (retinopathy, albuminuria, current smoking or hypertension), but no CVD history

5,10,25

years 3% US payer No

statement

Schwander

et al 2009 eprosartan enalapril 6 countries

within Europe

Cost utility Both Adult Populations of 6 European countries

Lifetime Country-specific rates for both costs and benefits applied. The rates vary from 3% to 5%

European health care-payer perspective

Compliance is entered to the model

Ward et al 2007 Statins for primary and secondary prevention of CHD or CVD

Non use of

statins UK Cost utility Both 45-85 Multiple levels of risk for CHD in next 10 years

Lifetime 6% for costs and 1.5% for benefits

National Health Service

Accounts for increasing non-compliance for 5 years and holds constant from then on

Study Base year/

currency Cost-effectiveness results Relevance/quality/

comments

Annemans et al 2006 2003

Euros Low-dose aspirin is dominant in all countries at all levels of risk except for Italy due to the higher cost of a gastrointestinal bleed there.

Not relevant

Aspirin not relevant to the guidelines

Compared to placebo Sponsorship from Bayer Ara et al 2008 2006 British

pounds The lifetime results for treatment Scenario 1 (ezetimibe 10 mg plus current weighted statin versus current weighted statin titrated by one dose) range from £24,000 per QALY for males aged 45 years with a baseline LDL-C of 3.5mmol/L and no history of CVD to £62,000 per QALY for females aged 75 years with a baseline LDL-C of 2.5 mmol/L and no history of CVD.

Relevant study

Well-designed cost-utility study that acknowledges limitations in the source data

National Institute for Health Research HTA Programme sponsored

Earnshaw et al 2011 2009

US$ Treatment with aspirin for CHD prevention is less costly and more effective than no treatment in men

> 45 years with > 10-year, 10% CHD risks.

Not relevant

Aspirin not relevant to the guidelines

Sponsorship from Bayer Franco et al 2007 2003

Euros The most cost-effective treatment is smoking cessation therapy, representing savings in all situations. Statin therapy is the least cost-effective treatment (ranging from €73,971 to €19,027 per YLS). Aspirin was the second most cost-effective intervention (ranging from €2,263 to €16,949 per YLS) followed by antihypertensive treatment (ranging from Euros 28,187 to Euros 79,843 per YLS). These rankings were maintained for all age group/risk group categories analysed.

A cut-off value for the ICER of Euros 20,000 per YLS was chosen

Limited relevance

Some quality considerations including: Not a cost-utility study, limited to males, initial comparator is no intervention, 10-year time horizon, adverse events not included

Sponsorship from the Netherlands Heart Foundation

Gaziano et al 2006 2001

US$ Across six developing World Bank regions, primary prevention yielded ICERs of US$746–890/QALY gained for patients with a 10-year AR of CVD greater than 25%, and US$1039–1221/QALY gained for those with an AR greater than 5%.

Not relevant

Conducted for developing countries

Sponsorship from Fogarty International Centre, National Institutes of Health

Greving et al 2008 2005

Euros Aspirin treatment for primary prevention is cost-effective for men with a 10-year CVD risk of >10%

and for women with a risk of >15%. This occurs much later in life for women than men.

Not relevant

Aspirin not relevant to the guidelines

Sponsorship from Netherlands Organization for Health Research and Development

Grover et al 2008 2002

Canadian $ The average cost-effectiveness of lipid therapy would be approximately CA$16,700 per YOLS while hypertension therapy would be approximately CA$37,100 per YOLS

Limited relevance Not a cost-utility study

Incremental results not presented Sponsorship from Astra Zeneca

Table 2. An overview of economic evaluation study results

Study Base year/

currency Cost-effectiveness results Relevance/quality/comments

Gumbs et al 2007 Review Policymakers who want to use economic evaluations should use those that employed appropriate methodology and produced valid results. In that regard it seems that policymakers are better informed using recent publications, as the quality of considered studies appears to have increased over time. However policymakers should remain critical regarding the methodology employed as the overall quality of the policy context economic evaluations is disappointing.

This review focused on the methodology

employed by the studies but policymakers should also consider whether the results are applicable to their own setting.

Focussed on quality of the economic evaluations

Not included in Table 1 Sponsorship not stated

Jonsson et al 2003 1995 Swedish Krona

The CV-related health care cost per patient during 3.8 years of follow-up was SEK32, 000 and SEK35,000 for the target groups 90 and 80 DBP, respectively.

Not relevant.

Cost-effectiveness study of cost per reductions in BP

Some quality considerations including:- no discussion of compliance issues

Sponsorship from Astra Zeneca Lamotte et al 2006 2003

Euros In patients at low risk of CHD and low risk of gastrointestinal bleed, low-dose aspirin is cost-effective.

For patients with an annual risk of CHD of 1.5%, the model resulted in 10-year savings with low-dose aspirin of on average €201, 281, 797, and 427 per patient in UK, Germany, Spain and Italy respectively.

Not relevant

Aspirin not relevant to the guidelines Compared to placebo

Sponsorship from Bayer

Lundkuist et al 2005 2001 Euros Candesavtan-based antihypertensive treatment was associated with 0.0289 additional QALY per patient and an incremental cost per QALY gained of approximately €13,000.

Not relevant

Compared to placebo Sponsorship not stated

Marshall 2006 1996

British Pounds

Cost per cardiovascular event prevented is strongly determined by cardiovascular risk. For any treatment it is over £45 000 in an individual at

<10%, 10-year CVD risk and under £30 000 for any treatment in a patient at over 45%, 10-year CVD risk.

Not relevant

Cost-effectiveness evaluation per change in risk category.

Some quality considerations including:-the costs of coronary events is not included in the comparisons of health states, age not specified, short 10-year time horizon, comparator is do nothing.

Sponsorship not stated Montgomery et al

2003 2002

British Pounds

In terms of cost-effectiveness, treatment was more effective, but also cost more than non-treatment for all age, sex, and risk strata except the oldest high-risk men and women. Incremental cost per QALY among low-risk groups ranged from £1030 to £3304. Cost-effectiveness results for low-risk individuals were sensitive to the utility of receiving antihypertensive treatment. Treatment of high-risk individuals was highly cost effective, such that it was the dominant strategy in the oldest age group, and resulted in incremental costs per QALY ranging from £34 to £265 in younger age groups.

Relevant study

Some quality considerations including:

differential discount rates applied to costs and benefits, no adverse events were included, the treatment intervention was not described in detail, only strokes and myocardial infarctions considered, Framingham equations applied without calibration to the population under study Sponsored by UK Medical Research Council Training fellowship and UK NHS Primary Career Scientist Award

Murray et al 2003 2000 International dollars using purchasing power parity exchange rates

Combination treatment for people whose risk of a cardiovascular event over the next 10 years is above 35% is cost effective leading to substantial additional health benefits by averting an additional 63 million DALYs per year worldwide.

The absolute-risk approach at a threshold of 35% is always more cost effective than treatment based on either the measured systolic BP or the measured cholesterol concentration.

From the perspective of how best to achieve the best population health for the available resources, the optimum overall strategy is a combination of the population-wide and individual-based interventions.

Relevant study

Some quality considerations including:

Comparator was no intervention, no cost offsets were included for cardiac events prevented

Sponsorship not stated

Newman et al 2008 2003/04

US$ Under baseline assumptions, combination polypharmacy was less expensive and more effective than the current standard, namely, no treatment. Thus, the use of combination polypharmacy was a dominant strategy

Relevant study

Some quality considerations including: limited to males ≥55 years, the analytic time horizon and perspective not stated

Sponsorship not stated Neyt et al 2009 2007

Euros The results showed that smoking cessation is an intervention that should be encouraged. Low-dose aspirin was more cost-effective ranging from €3.854/LYG to €29.509/LYG compared to smoking cessation for smokers and ranging from

€401/LYG to €13.451/LYG compared to no-treatment for non-smokers. The results for statin treatment are less cost effective. Only for the high risk group aged 60, the cost-effectiveness was about €30,000/LYG under the assumption that the cheapest alternative statin would be prescribed. For other subgroups the ICER for statin treatment was about €50,000/LYG

Limited relevance

Some quality considerations including: limited to males, aged 50 and 60, the analytic time horizon was only 10 years, differential discounting applied to costs and benefits, the comparator interventions are less relevant than current practice

Sponsorship stated as ‘no external funding’

Nordmann et al 2003 1999

US$ The cost-effectiveness ratios are unattractively high: US$200,000 per QALY gained for the echocardiography strategy (compared with ECG), and US$700,000 for the ‘ACE inhibitor for all’

strategy (compared with ECG). The incremental cost effectiveness of prescribing ACE inhibitor therapy to everybody was never less than US$100,000/QALY in the sensitivity analysis.

Relevant study

Some quality considerations including:

40-year-old males only.

Sponsorship not stated

Pignone et al 2006 2003

US$ For 45-year-old men who do not smoke, are not hypertensive and have a 10-year risk for CHD of 7.5%, aspirin was more effective and less costly than no treatment. The addition of a statin to aspirin therapy produced an incremental cost-utility ratio of US$56,200 per quality-adjusted life-year gained compared with aspirin alone. The addition of a statin is more cost-effective as risk increases.

Relevant study

Some quality considerations including: limited analysis of 45 year old males, the comparator is aspirin and no therapy

Sponsorship from Bayer Pignone et al 2007 2005

US$ Aspirin use cost US$13,300 per additional QALY gained in the base case. Results were sensitive to age, CVD risk, relative risk reductions with aspirin for ischaemic strokes and MI, excess risk of haemorrhagic stroke and gastrointestinal bleeding, and the disutility of taking medication.

Probabilistic sensitivity analysis for 65-year-old women at moderate CVD risk found a 27%

chance that aspirin produces fewer QALYs than no treatment, a 35% chance that the cost-utility ratio was less than US$50,000 per QALY gained, and a 37% probability that it was greater than US$50,000 per QALY gained.

Not relevant

Aspirin not relevant to the guidelines Sponsorship from Bayer

Study Base

year/

currency Cost-effectiveness results Relevance/quality/comments

Study Base year/

currency Cost-effectiveness results Relevance/quality/comments

Pilote et al 2005 1996

Canadian$ Among the surveyed individuals with a TC level higher than 6.2mmol/L the proportions of individuals for which lipid-lowering therapy was cost-effective (at a threshold level of CA$50,000/

year of life saved) were 85.6% of men and 28.7%

of women for primary prevention.

Limited relevance.

Average cost effectiveness only. Not a cost-utility study.

Sponsorship provided by a grant from the Fonds de la Recherché en Santé de Quebec.

Pletcher et al 2009 2006

US$ Full adherence to ATP III primary prevention guidelines would require starting (9.7 million) or intensifying (1.4 million) statin therapy for 11.1 million adults and would prevent 20 000 myocardial infarctions and 10 000 CHD deaths per year at an annual net cost of US$3.6 billion (US$42 000/QALY) if low-intensity statins cost US$2.11 per pill. The ATP III guidelines would be preferred over alternative strategies if society is willing to pay US$50,000/QALY and statins cost US$1.54 to US$2.21 per pill. At higher statin costs, ATP III is not cost-effective; at lower costs, more liberal statin-prescribing strategies would be preferred; and at costs less than US$0.10 per pill, treating all persons with low-density lipoprotein cholesterol levels greater than 3.4 mmol/L (130 mg/dL) would yield net cost savings.

Relevant study

Some quality considerations including: Study included unrelated health care costs. Shorter than lifetime horizon analysed

Sponsorship from Flight Attendants Medical Research Institute and Swanson Family Fund

Ramsey et al 2008 2005

US$ Within the time horizon of the trial (5 years), the cost effectiveness of atorvastatin was US$137,276 per QALY. At 10 years, the incremental cost per QALY improved to US$

3,640 per QALY. At 25 years, the overall costs were lower and QALYs higher in the atorvastatin arm. Costs of managing CV events were lower after five years for patients treated with atorvastatin. For patients with type 2 diabetes and one additional risk factor for CV disease, normal LDL-cholesterol and no history of a CV event, primary prevention with atorvastatin appears to be cost saving and improve outcomes over 25 years although it is costly from a short-term US-payer perspective.

Relevant study

Some quality considerations including: Cost of adverse events not included

No statement on compliance Sponsored by Pfizer

Schwander et al

2009 2007

Euros Comparing eprosartan to enalapril in a primary prevention setting the mean costs per quality adjusted life year (QALY) gained were highest in Germany (€24,036) followed by Belgium (€17,863), the UK (€16,364), Norway (€ 13,834), Sweden (€ 11,691) and Spain (€ 7,918).

Relevant study

Some quality considerations including: no adverse events included, utility weights applied may not be appropriate, Framingham equations applied without calibration to the population under study, effectiveness data taken from one small trial (n=59)

Sponsored by Solvay Pharmaceuticals Ward et al 2007 2004

British Pounds

The cost-effectiveness of statins depends on the CHD risk in the population treated and the age and gender of the population under consideration. In primary prevention the discounted cost per QALY estimates for primary prevention at the age of 45 range between

£9,500 and £30,500 for men and women as annual CHD risk levels fall from 3% to 0.5%. By the age of 85 years the corresponding values are

£36,800 and £110,600

Relevant study

High-quality study except for differential discount rates applied to costs and benefits National Institute for Health Research HTA Programme sponsored