Diabetes. Professor Philip Clarke Centre for Health Policy - PowerPoint PPT Presentation

Conducting economic analyses alongside clinical studies in Type 1 Diabetes. Professor Philip Clarke Centre for Health Policy Melbourne School of Population of Global Health

Inter-generational Report 2015 Does this make you “fall of your chair”? • Longer life expectancy: – Males 91.5 years at birth; – females 93.6 years • Australian Government real health expenditure per person is projected to more than double over the next 40 years ($2,800 to around $6,500). • Key drivers of health expenditure is not aging, but – demand from rising income, – technological change. How long will a child born today with Type 1 diabetes live?; How much will it cost to treat/ cure them?

Lung 2014 (PLOS One) • The relative mortality of people with Type 1 Diabetes has improved • Relative risk (pre-1971): 6 times general population • Relative Risk (post-1990) : 3 times general population • There is still a life expectancy gap of 11-13 years Lung PLOS One 2014

Current trends in mortality (unpublished) W o m e n M en A ll C a u s e M o rta lity A ll C a u s e M o rta lity 1 0 0 1 0 0 N D R 2 0 0 2 -0 6 P ro p o rtio n a liv e (% ) P ro p o rtio n a liv e (% ) N D R 2 0 0 7 -1 1 8 0 8 0 G e n e ra l p o p u la tio n 2 0 0 2 -0 6 6 0 6 0 G e n e ra l p o p u la tio n 2 0 0 7 -1 1 4 0 4 0 2 0 2 0 • Evidence of 0 0 2 0 4 0 6 0 8 0 2 0 4 0 6 0 8 0 A ge A ge LE gap closing in C V D M o rta lity C V D M o rta lity men due to 1 0 0 1 0 0 P ro p o rtio n e v e n t fre e (% ) P ro p o rtio n e v e n t fre e (% ) reductions in CVD 8 0 8 0 mortality 6 0 6 0 • No evidence in 4 0 4 0 2 0 2 0 women for 0 0 improvements in 2 0 4 0 6 0 8 0 2 0 4 0 6 0 8 0 A ge A ge Rel. Survival.

Case study: Insulin analogues Insulin analogues “afford more flexible treatment regimens with a lower risk of the development of hypoglycemia” (NEJM 2005) Benefits: • Rapid acting analogues reduce postprandial hyperglycemia (high blood sugar after meals) • Long acting analogues reduce the risk of hypoglycemia

Now a look at the cost… • Australian prices: INSULIN ISOPHANE HUMAN: $224 per script INSULIN GLARGINE: $433 per script • The increase in expenditure reflects: Expanded use for people with Type 2 Diabetes The higher price of insulin analogues

What are the benefits of reducing “hypos”? 1)Quality of life a) Patients value not having hypoglycemic episodes – they have reduced quality of life during an episode and long-term due to increased complications. b) Perhaps all people with Diabetes are affected by a “fear of hypos” 2) Clinical impact There is emerging evidence of increased mortality (particularly after cardiovascular events)

Recent evidence of survival post CVD event Lung et. al., Diabetes Care, 2014

Are Analogues “value for money”? • In Australia these decisions are made by the Pharmaceutical Benefits Advisory Council (PBAC) on the basis of cost-effectiveness. • Example of Insulin Glargine: – Considered 5 times by the economic sub-committee of the PBAC – First considered by the PBAC in 2003 – Finally listed in 2006 – Company projected to cost $145 million over first four years (actual cost $263million)

What the PBAC thought… Comments from Oct 2005 Meeting: “ A number of problems with this analysis were identified during the evaluation, and the PBAC considered that the trial-based incremental costs per extra hypoglycaemic event avoided could be higher than estimated in the submission” “The PBAC did not accept other assumptions in the economic model” Recommendation: Reject

Food for thought: health system performance Source: McKeon Review

UKPDS – Example of economic evaluation alongside an RCT

UKPDS overview • First of the large scale RCTs in Type 2 diabetes – involving 10 years of follow-up on 5102 patients • Economics integrated into the study prospectively • Included collection of cost and quality of life information • Data formed the basis of development of the UKPDS Outcomes model

UKPDS – intermediate outcomes • First major RCT in Type 2 diabetes • Intensive vs conventional Blood Glucose control • Very long term follow-up (median 10.3 years)

UKPDS – final outcomes At the end of follow-up At the end of follow-up

Example CEA

Blood Glucose & Blood pressure Study: Aims To determine the cost per Quality Adjusted Life Year (QALY) gained of three UKPDS policies: • Intensive blood glucose control: is intensive blood glucose control with sulphonylurea, or insulin, cost- effective in preventing clinical complications in people with Type 2 Diabetes? • Metformin: is intensive blood glucose control with Metformin in overweight patient cost-effective in preventing complications? • Tight blood pressure control: is tight blood pressure control cost-effective in preventing complications?

Main economic evaluation Comparison: intensive versus conventional blood glucose and blood pressure control policies in Type 2 diabetic patients Data: patient level data on costs and outcomes from UKPDS Outcome measure: Quality adjusted life years Time period: within trial effects extrapolated over lifetime (median follow-up 10 years for Blood Glucose and 8.4 years for Blood Pressure Trial) Perspective: UK health care system Result: Incremental cost per QALY gained in 2004 £s (£1 = 1.5 Euros)

Costs and resource use • Therapy: - drug doses (antidiabetic, antihypertensive, other) - tests (blood glucose, HbA 1C ) - standard practice (cost of implementing UKPDS policies in a general health care setting) • Complications: - hospital admissions: length of stay, diagnosis - non-inpatient services: home, clinic & telephone contacts with GPs, nurses, dieticians etc. Cost of complications is modelled over each patient’s lifetime

Unit costs

Costs: Blood pressure study

Total discounted costs Mean costs per patient over trial period, £s, 3.5% discount Item Mean (SD) Mean (SD) Mean difference conventional intensive (95% C.I.) Intensive BG 14,984 (17,888) 15,868 (14,465) 884(-483, 2250) 16,941 (23,193) 15,920 (13,678) Metformin -1021(-4291, 2249) 15,786 (16,378) 15,895 (16,025) Blood pressure 108(-2347, 2563)

Estimating Outcomes • Estimate QALYs for people with Type 2 diabetes, based on profile of complications of each patient over their remaining lifetime • Use UKPDS Outcomes Model which is based on an integrated set of parametric proportional hazard models to predict absolute risk of first occurrence of seven major diabetes-related complications, using: – patients’ characteristics (e.g. age and sex) – time varying risk factors (e.g. HbA 1c )

Model equations: Complications

Simulating lifetime outcomes Average QALY for UKPDS patients by blood glucose policy 0.9 0.8 Intensive Therapy QALY (Utility weight) Conventional therapy 0.7 Median duration of the trial 0.6 0.5 0.4 0.3 0.2 0.1 0 Maximum Minimum Years (from diagnosis of diabetes) follow-up follow-up

Total outcomes Mean QALYs per patient, undiscounted Item Mean (SD) Mean (SD) Mean difference conventional intensive (95% C.I.) Intensive BG 16.35 (8.36) 16.62 (8.35) 0.27 (-0.48, 1.03) 16.44 (8.49) 17.32 (7.94) Metformin 0.88 (-0.54, 2.29) 13.71 (8.00) 14.16 (7.81) Blood pressure 0.45 (-0.70, 1.60)

Cost-utility results £4,000 Tight blood Intervention less Intervention more pressure control effective, more costly effective, more costly £370 per QALY £2,000 Intensive blood glucose control with sulphonylurea/insulin £6000 per QALY INCREMENTAL QALYs £0 -2.0 -1.0 0.0 1.0 2.0 3.0 Intensive blood glucose control -£2,000 with metformin -£4,000 Intervention less Intervention more INCREMENTAL COST effective, less costly effective, less costly Costs & QALYs discounted at 3.5% p.a.

Development of a Type 1 diabetes simulation model

Rationale for a specific Type 1 Diabetes simulation model • Much longer durations of diabetes • Absolute risk is different • Different effect of risk factors on outcomes Figure 1: Risk of CVD event for two age Swedish NDR cohorts people with Type 1 diabetes: Person aged 35-45 years 50-60 years (Unpublished)

NHMRC Project Grant (2012-14): Collaboration to build a type 1 diabetes model • University of Melbourne • University of Tasmania (Prof Andrew Palmer) • DCCT/EDIC collaboration • Swedish National Diabetes Register • Glasgow University • Data sources: – Swedish National Diabetes Register (NDR) – DCCT/EDIC • US trial of intensive versus conventional control – Scottish SCI-Diabetes