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Cost Inputs Technical Report

IXA-001 Hypertension Microsimulation Model

Version: 1.0 Date: February 2026 Price Year: 2024 CHEERS 2022 Compliance: Items 15, 16, 17

Table of Contents

  1. Executive Summary
  2. Methodology
  3. Drug Costs
  4. Acute Event Costs
  5. Chronic Management Costs
  6. Indirect Costs (Societal Perspective)
  7. Laboratory and Monitoring Costs
  8. Country-Specific Cost Summary
  9. PSA Distributions
  10. Inflation and Currency Adjustments
  11. References

1. Executive Summary

This report documents all cost inputs used in the IXA-001 hypertension microsimulation model, including sources, price year, and probabilistic sensitivity analysis (PSA) distributions.

Cost Categories

Category US (2024 USD) UK (2024 GBP) Key Driver
Drug Costs $590-1,040/month £448-783/month IXA-001 vs Spironolactone
Acute Events $2,100-25,000 £850-9,000 MI, Stroke, HF admission
Chronic Management $1,200-90,000/year £350-35,000/year ESRD highest cost
Indirect (Societal) $1,680-14,400/event £2,240-28,800/event Stroke disability

Perspective Options

Perspective Included Costs
Healthcare System Drug costs, acute events, chronic management, laboratory
Societal All above + absenteeism + chronic disability

2. Methodology

2.1 Cost Identification

Costs were identified using a micro-costing approach for drugs and a gross-costing approach for healthcare resource use:

  1. Drug Costs: Unit costs from national pricing databases
  2. Acute Events: Hospital episode costs from administrative databases
  3. Chronic Management: Published literature with inflation adjustment
  4. Indirect Costs: Human capital approach

2.2 Data Sources by Country

Country Drug Pricing Hospital Costs Wage Data
US NADAC, SSR Health HCUP NIS 2022 BLS OEWS 2024
UK NHS Drug Tariff NHS Reference Costs 2022-23 ONS ASHE 2024

2.3 Price Year and Currency

Market Currency Price Year Inflation Index
US USD ($) 2024 Medical CPI
UK GBP (£) 2024 NHS Cost Inflation Index

2.4 CHEERS 2022 Compliance

CHEERS Item Requirement Compliance
15 Methods for estimating resource quantities ✓ Section 2.1
16 Unit costs, currency, price date ✓ All tables
17 Methods for productivity costs ✓ Section 6

3. Drug Costs

3.1 Investigational Product: IXA-001

Parameter US UK Source
Monthly Cost $500 £400 Manufacturer WAC (placeholder)
Annual Cost $6,000 £4,800 -
PSA Distribution Gamma(μ=500, σ=100) Gamma(μ=400, σ=80) ±20% range

Notes:

  • US price reflects anticipated Wholesale Acquisition Cost (WAC)
  • UK price assumes PPRS/VPAS agreement pricing
  • Prices are placeholders pending commercial launch

3.2 Comparator: Spironolactone

Parameter US UK Source
Monthly Cost $15 £8 NADAC 2024 / NHS Drug Tariff
Annual Cost $180 £96 -
Formulation 25mg tablets × 30 25mg tablets × 28 -
PSA Distribution Gamma(μ=15, σ=5) Gamma(μ=8, σ=2) Generic variability

Reference: NADAC (National Average Drug Acquisition Cost). Medicaid.gov. 2024.

3.3 Background Antihypertensive Therapy

All patients receive background therapy regardless of investigational treatment:

Component US Monthly UK Monthly Notes
ACE inhibitor/ARB $25 £15 Generic lisinopril/losartan
Calcium channel blocker $30 £15 Generic amlodipine
Thiazide diuretic $20 £10 Generic HCTZ/indapamide
Total Background $75 £40 -

Reference: Moran AE, et al. Cost-effectiveness of hypertension therapy. JAMA. 2015;312(20):2069-2082.

3.4 SGLT2 Inhibitors (Add-on Therapy)

Parameter US UK Source
Monthly Cost $450 £35 SSR Health / NHS Tariff
Products Empagliflozin, Dapagliflozin Dapagliflozin (generic) -
Annual Cost $5,400 £420 -

Notes:

  • US: Brand pricing (Jardiance®, Farxiga®) per SSR Health Net Price Report 2024
  • UK: Generic dapagliflozin available since 2022 patent expiry

3.5 Potassium Binders

For hyperkalemia management with MRA/ASI therapy:

Product US Monthly UK Monthly Source
Patiromer (Veltassa®) $500 £300 SSR Health / NHS Tariff
Sodium zirconium (Lokelma®) $400 £250 SSR Health / NHS Tariff
Model Input $500 £300 Higher cost (conservative)

Reference: Weir MR, et al. Patiromer in patients with kidney disease and hyperkalemia. NEJM. 2015;372(3):211-221.

3.6 Total Monthly Drug Cost by Treatment Arm

Treatment Arm US UK Components
IXA-001 $575 £440 IXA + background
IXA-001 + SGLT2i $1,025 £475 IXA + background + SGLT2i
Spironolactone $90 £48 Spiro + background
Spironolactone + SGLT2i $540 £83 Spiro + background + SGLT2i
Standard Care $75 £40 Background only

4. Acute Event Costs

4.1 Myocardial Infarction (MI)

Parameter US UK Source
Acute Hospitalization $25,000 £8,000 HCUP DRG 280-282 / NHS EB10A-C
Severity Range $22,000-28,000 £6,000-12,000 Without/with MCC
PSA Distribution Gamma(μ=25000, σ=5000) Gamma(μ=8000, σ=1600) -

Resource Bundle (US):

Resource Quantity Unit Cost Total
Coronary angiography 1 $4,500 $4,500
PCI (70% of patients) 0.7 $18,000 $12,600
ICU days 2 $2,500 $5,000
Ward days 3 $1,000 $3,000
Total - - $25,100

References:

  • Kauf TL, et al. The cost of acute myocardial infarction. Am Heart J. 2006;152(4):678-684.
  • HCUP National Inpatient Sample 2022. AHRQ.

4.2 Stroke

4.2.1 Ischemic Stroke

Parameter US UK Source
Acute Hospitalization $15,200 £6,000 HCUP DRG 61-63 / NHS AA22A-D
PSA Distribution Gamma(μ=15200, σ=3000) Gamma(μ=6000, σ=1200) -

Resource Bundle (US):

Resource Quantity Unit Cost Total
CT/MRI imaging 1 $1,200 $1,200
tPA (25% eligible) 0.25 $8,000 $2,000
Thrombectomy (15%) 0.15 $25,000 $3,750
Stroke unit days 5 $1,500 $7,500
Total - - $14,450

4.2.2 Hemorrhagic Stroke

Parameter US UK Source
Acute Hospitalization $22,500 £9,000 HCUP DRG 64-66 / NHS AA23A-C
PSA Distribution Gamma(μ=22500, σ=5000) Gamma(μ=9000, σ=2000) -

Notes: Higher cost due to ICU care, potential neurosurgical intervention, and longer length of stay.

References:

  • Wang G, et al. The cost of stroke in the United States. Stroke. 2014;45(1):29-35.
  • Qureshi AI, et al. Intracerebral haemorrhage. Lancet. 2009;373(9675):1632-1644.

4.3 Transient Ischemic Attack (TIA)

Parameter US UK Source
Acute Workup $2,100 £850 HCUP / NHS Rapid Access TIA
Setting Emergency Department TIA Clinic -
PSA Distribution Gamma(μ=2100, σ=500) Gamma(μ=850, σ=200) -

Resource Bundle (US):

Resource Unit Cost Total
ER visit $500 $500
CT/MRI brain $800 $800
Carotid doppler $400 $400
Labs (BMP, CBC, lipids) $200 $200
Neurology consult $200 $200
Total - $2,100

Reference: Johnston SC, et al. Short-term prognosis after emergency department diagnosis of TIA. JAMA. 2000;284(22):2901-2906.

4.4 Heart Failure Admission

Parameter US UK Source
Acute Hospitalization $18,000 £5,500 HCUP DRG 291-293 / NHS EB03A-D
Mean LOS 5.5 days 7.0 days -
PSA Distribution Gamma(μ=18000, σ=4000) Gamma(μ=5500, σ=1100) -

Resource Bundle (US):

Resource Quantity Unit Cost Total
Telemetry bed days 5 $2,200 $11,000
Echocardiogram 1 $1,500 $1,500
BNP testing 2 $150 $300
IV diuretics - $500 $500
Cardiology consult 1 $300 $300
Discharge planning 1 $400 $400
Total - - $14,000

Note: Actual billed costs typically higher due to facility fees; model uses mean DRG payment.

Reference: Heidenreich PA, et al. Forecasting the future of cardiovascular disease in the United States. Circ Heart Fail. 2013;126(5):1001-1010.

4.5 Atrial Fibrillation (New Onset)

Parameter US UK Source
Acute Hospitalization $8,500 £3,500 HCUP DRG 308-310 / NHS EB07A-C
PSA Distribution Gamma(μ=8500, σ=2000) Gamma(μ=3500, σ=700) -

Resource Bundle:

Resource Description
Admission Rate control, anticoagulation initiation
Cardioversion Electrical or pharmacological (50%)
TEE If cardioversion planned
DOAC initiation Education and monitoring

Reference: Kim MH, et al. Estimation of total incremental health care costs in patients with atrial fibrillation. Circ Cardiovasc Qual Outcomes. 2011;4(3):313-320.

4.6 Acute Event Cost Summary Table

Event US (2024 USD) UK (2024 GBP) US:UK Ratio
MI $25,000 £8,000 3.1:1
Ischemic Stroke $15,200 £6,000 2.5:1
Hemorrhagic Stroke $22,500 £9,000 2.5:1
TIA $2,100 £850 2.5:1
HF Admission $18,000 £5,500 3.3:1
New AF $8,500 £3,500 2.4:1

5. Chronic Management Costs

5.1 Hypertension Management

Controlled Hypertension (Resistant HTN, on stable therapy)

Parameter US UK Source
Annual Cost $1,200 £350 Sim JJ 2015 / NICE CG127
PSA Distribution Gamma(μ=1200, σ=240) Gamma(μ=350, σ=70) -

Resource Use (US):

Resource Frequency Unit Cost Annual
Primary care visits 3/year $150 $450
Specialist visits 1/year $250 $250
Routine labs 2/year $75 $150
ECG 1/year $100 $100
Home BP monitor 0.2/year $50 $10
Total - - $960

Note: Resistant HTN patients have ~1.5× higher costs than general HTN population.

Uncontrolled Hypertension

Parameter US UK Source
Annual Cost $1,800 £550 Valderrama 2014 / NICE CG127
PSA Distribution Gamma(μ=1800, σ=360) Gamma(μ=550, σ=110) -

Additional Resources vs Controlled:

  • More frequent visits (4-6/year vs 3/year)
  • Additional specialist referrals
  • Medication titration costs
  • Secondary HTN workup (if indicated)

References:

  • Sim JJ, et al. Resistant hypertension and healthcare costs. J Am Heart Assoc. 2015;4(12):e002404.
  • Valderrama AL, et al. Direct medical costs of uncontrolled hypertension. J Am Soc Hypertens. 2014;8(4):210-219.
  • Daugherty SL, et al. Incidence and prognosis of resistant hypertension. Circulation. 2012;125(13):1635-1642.

5.2 Post-Event Cardiac Management

Post-MI (Secondary Prevention)

Parameter US UK Source
Annual Cost $5,500 £2,200 Zhao 2010 / Luengo-Fernandez 2006
PSA Distribution Gamma(μ=5500, σ=1100) Gamma(μ=2200, σ=440) -

Resource Bundle (Annual):

Resource Frequency US Cost
Cardiology visits 2-4/year $600
Echo/stress test 1/year $1,200
Cardiac rehab 36 sessions $2,000
Dual antiplatelet 12 months $1,200
Statin (high-intensity) 12 months $300
Total - $5,300

Reference: Zhao Z, et al. Healthcare costs and utilization for Medicare beneficiaries with acute myocardial infarction. JMCP. 2010;16(8):601-610.

Post-Stroke

Parameter US UK Source
Annual Cost $12,000 £5,500 Luengo-Fernandez 2013
PSA Distribution Gamma(μ=12000, σ=3000) Gamma(μ=5500, σ=1375) -

Cost Drivers:

  • Rehabilitation (inpatient and outpatient)
  • Disability care (home health, assistive devices)
  • Anticoagulation (if cardioembolic)
  • Secondary prevention medications
  • Neurologist follow-up

Note: Costs highly variable by stroke severity (mRS 0-2 vs 3-5).

Reference: Luengo-Fernandez R, et al. A population-based study of costs of stroke care in England. Stroke. 2013;44(5):1287-1294.

Chronic Heart Failure

Parameter US UK Source
Annual Cost $15,000 £6,000 Dunlay 2011 / NICE TA388
PSA Distribution Gamma(μ=15000, σ=4000) Gamma(μ=6000, σ=1500) -

Resource Bundle (Annual):

Resource US Cost
HF clinic visits $1,500
Cardiology visits $600
BNP monitoring $600
Echo $1,200
GDMT medications $3,600
Hospitalizations (0.5/year) $9,000
Total $16,500

Note: HF patients average 0.5-1.0 hospitalizations/year; model uses 0.5 for prevalent HF.

Reference: Dunlay SM, et al. Lifetime costs of medical care after heart failure diagnosis. Circ Heart Fail. 2011;4(1):68-75.

Chronic Atrial Fibrillation

Parameter US UK Source
Annual Cost $8,500 £2,500 Kim 2011 / NHS Reference Costs
PSA Distribution Gamma(μ=8500, σ=2000) Gamma(μ=2500, σ=625) -

Cost Components:

Component US Annual UK Annual
DOAC therapy $6,000 £600
INR monitoring (warfarin) $1,500 £400
Cardiology visits $500 £300
Echo monitoring $1,000 £500
Rate/rhythm control meds $500 £200

Note: Model assumes DOAC as standard; warfarin would reduce drug cost but increase monitoring.

Reference: Kim MH, et al. Estimation of total incremental health care costs in AF. Circ Cardiovasc Qual Outcomes. 2011;4(3):313-320.

5.3 Chronic Kidney Disease Management

CKD Stage eGFR Range US Annual UK Annual Source
Stage 3a 45-59 $2,500 £1,200 Vupputuri 2014 / Kerr 2012
Stage 3b 30-44 $4,500 £2,200 Vupputuri 2014 / Kerr 2012
Stage 4 15-29 $8,000 £3,500 Smith 2004 / Kerr 2012
Stage 5/ESRD <15 $90,000 £35,000 USRDS 2023 / NHS Ref Costs

CKD Stage 3a

Resource Bundle:

Resource Frequency US Cost
Nephrology referral Once $400
Primary care visits 3/year $450
Labs (eGFR, uACR, K+) 3/year $225
ACEi/ARB optimization - $200
Total - $1,275

CKD Stage 3b

Additional vs Stage 3a:

  • More frequent nephrology visits
  • Anemia workup (iron, B12, EPO if indicated)
  • Bone mineral monitoring (Ca, Phos, PTH)
  • Dietary counseling

CKD Stage 4 (Pre-Dialysis)

Additional Resources:

  • Pre-dialysis education
  • Vascular access creation (fistula/graft)
  • Transplant evaluation (if candidate)
  • More frequent labs and visits

ESRD (Dialysis)

Parameter US UK Source
Annual Cost $90,000 £35,000 USRDS 2023 / NHS 2022-23
Modality Hemodialysis (in-center) Hemodialysis -
PSA Distribution Gamma(μ=90000, σ=15000) Gamma(μ=35000, σ=7000) -

US Cost Breakdown:

Component Annual Cost
Dialysis sessions (3×/week) $72,000
Vascular access maintenance $5,000
EPO and IV iron $8,000
Hospitalization (1/year) $5,000
Total $90,000

References:

  • USRDS Annual Data Report 2023. Chapter 9: Healthcare Expenditures for Persons with ESRD.
  • Vupputuri S, et al. The economic burden of CKD. Kidney Int. 2014;86(3):619-624.
  • Kerr M, et al. Estimating the financial cost of CKD to the NHS in England. Nephrol Dial Transplant. 2012;27(suppl_3):iii73-iii80.
  • Smith DH, et al. Cost of medical care for CKD and comorbidity among enrollees in a large HMO. Am J Kidney Dis. 2004;44(2):261-271.

5.4 Chronic Management Cost Summary

Condition US Annual UK Annual Monthly (US)
Controlled HTN $1,200 £350 $100
Uncontrolled HTN $1,800 £550 $150
Post-MI $5,500 £2,200 $458
Post-Stroke $12,000 £5,500 $1,000
Chronic HF $15,000 £6,000 $1,250
Chronic AF $8,500 £2,500 $708
CKD Stage 3a $2,500 £1,200 $208
CKD Stage 3b $4,500 £2,200 $375
CKD Stage 4 $8,000 £3,500 $667
ESRD $90,000 £35,000 $7,500

6. Indirect Costs (Societal Perspective)

6.1 Methodology

Indirect costs are estimated using the Human Capital Approach, which values productivity loss at market wages.

Assumptions:

  • Working age defined as <65 years
  • Working days per year: 250
  • Productivity loss = 0 for patients aged ≥65

Reference: Drummond MF, et al. Methods for the Economic Evaluation of Health Care Programmes. 4th ed. Oxford. 2015. Chapter 6.

6.2 Wage Data

Parameter US UK Source
Daily Wage (median) $240 £160 BLS OEWS / ONS ASHE 2024
Annual Wage (median) $60,000 £40,000 -
Working Days/Year 250 250 -

6.3 Acute Absenteeism (One-Time)

Event Days Lost (US) Days Lost (UK) US Cost UK Cost
Acute MI 7 14 $1,680 £2,240
Stroke 30 60 $7,200 £9,600
TIA 3 3 $720 £480
HF Admission 5 10 $1,200 £1,600

Note: UK estimates higher due to longer statutory sick leave provisions.

References:

  • Greiner W, et al. Productivity loss after acute coronary syndrome. Eur J Health Econ. 2004;5(4):324-330.
  • Dewilde S, et al. Work absence and return after stroke. BMJ Open. 2017;7(6):e014163.
  • Liao L, et al. Costs and resource use in heart failure. JACC Heart Fail. 2007;49(5):523-531.

6.4 Chronic Disability (Annual)

Condition Disability Multiplier (US) Disability Multiplier (UK) US Annual Loss UK Annual Loss
Post-Stroke 20% 30% $12,000 £12,000
Chronic HF 15% 20% $9,000 £8,000

Calculation:

Annual Disability Cost = Annual Wage × Disability Multiplier
US Post-Stroke = $60,000 × 0.20 = $12,000/year
UK Post-Stroke = £40,000 × 0.30 = £12,000/year

References:

  • Tanaka E, et al. Long-term economic impact of stroke in Japan. Stroke. 2011;42(11):3034-3039.
  • Heidenreich PA, et al. Economic impact of heart failure. Circulation. 2013;127(10):1132-1143.
  • Patel A, et al. Productivity costs of stroke in the United Kingdom. Stroke. 2020;51(5):1429-1436.

6.5 Total Indirect Cost by Event (Working-Age Patient)

Event Acute + Year 1 Chronic (US) Acute + Year 1 Chronic (UK)
MI $1,680 £2,240
Stroke $7,200 + $12,000 = $19,200 £9,600 + £12,000 = £21,600
HF $1,200 + $9,000 = $10,200 £1,600 + £8,000 = £9,600

7. Laboratory and Monitoring Costs

7.1 Potassium Monitoring

Parameter US UK Source
Serum K+ (BMP) $15 £3 Medicare CLFS / NHS DAPS08
PSA Distribution Gamma(μ=15, σ=5) Gamma(μ=3, σ=1) -

Monitoring Frequency by Treatment:

Treatment Frequency US Annual UK Annual
IXA-001 Monthly × 3, then quarterly $105 £21
Spironolactone Monthly × 3, then quarterly $105 £21
Standard Care Quarterly $60 £12

7.2 Other Laboratory Tests

Test US Cost UK Cost Frequency
Basic Metabolic Panel $15 £3 Per protocol
eGFR/Creatinine $10 £2 Per renal state
Lipid Panel $25 £5 Annual
HbA1c (diabetics) $20 £4 Quarterly

8. Country-Specific Cost Summary

8.1 US Costs (2024 USD)

Category Cost Notes
Drug Costs (Monthly)
IXA-001 + background $575
Spironolactone + background $90
SGLT2i add-on $450
Acute Events
MI $25,000
Ischemic stroke $15,200
Hemorrhagic stroke $22,500
HF admission $18,000
New AF $8,500
TIA $2,100
Annual Management
Controlled HTN $1,200
Post-MI $5,500
Post-stroke $12,000
Chronic HF $15,000
Chronic AF $8,500
CKD Stage 4 $8,000
ESRD $90,000
Indirect (working age)
Daily wage $240
Stroke disability $12,000/yr

8.2 UK Costs (2024 GBP)

Category Cost Notes
Drug Costs (Monthly)
IXA-001 + background £440
Spironolactone + background £48
SGLT2i add-on £35 Generic
Acute Events
MI £8,000
Ischemic stroke £6,000
Hemorrhagic stroke £9,000
HF admission £5,500
New AF £3,500
TIA £850
Annual Management
Controlled HTN £350
Post-MI £2,200
Post-stroke £5,500
Chronic HF £6,000
Chronic AF £2,500
CKD Stage 4 £3,500
ESRD £35,000
Indirect (working age)
Daily wage £160
Stroke disability £12,000/yr

9. PSA Distributions

9.1 Distribution Selection Rationale

Parameter Type Distribution Rationale
Costs Gamma Non-negative, right-skewed
Probabilities Beta Bounded 0-1
Days lost Uniform Range-based estimates
Disability % Beta Bounded 0-1

9.2 Gamma Distribution Parameterization

For costs with mean μ and standard deviation σ:

$$\alpha = \frac{\mu^2}{\sigma^2}, \quad \beta = \frac{\sigma^2}{\mu}$$

9.3 Complete PSA Parameter Table

Parameter Base Case Distribution α β (or SD)
Drug Costs (US)
IXA-001 monthly $500 Gamma 25 20
Spironolactone monthly $15 Gamma 9 1.67
SGLT2i monthly $450 Gamma 25 18
Background monthly $75 Gamma 9 8.33
K+ binder monthly $500 Gamma 25 20
Acute Events (US)
MI acute $25,000 Gamma 25 1,000
Ischemic stroke $15,200 Gamma 25.7 592
Hemorrhagic stroke $22,500 Gamma 20.25 1,111
HF admission $18,000 Gamma 20.25 889
AF acute $8,500 Gamma 18.06 471
TIA $2,100 Gamma 17.64 119
Annual Costs (US)
Controlled HTN $1,200 Gamma 25 48
Uncontrolled HTN $1,800 Gamma 25 72
Post-MI $5,500 Gamma 30.25 182
Post-stroke $12,000 Gamma 16 750
Chronic HF $15,000 Gamma 14.06 1,067
ESRD $90,000 Gamma 36 2,500
Indirect Costs
Daily wage (US) $240 Gamma 36 6.67
Absenteeism MI (days) 7 Uniform 5 14
Absenteeism stroke (days) 30 Uniform 14 60
Disability stroke 0.20 Beta 20 80
Disability HF 0.15 Beta 15 85

10. Inflation and Currency Adjustments

10.1 Inflation Indices

Country Index 2022→2024 Factor
US Medical CPI 1.08
UK NHS Cost Inflation Index 1.06

10.2 Historical Cost Adjustment

For costs from prior years:

$$Cost_{2024} = Cost_{original} \times \frac{Index_{2024}}{Index_{original}}$$

10.3 Currency Conversion (if needed)

Conversion Rate Source
USD → GBP 0.80 Average 2024 exchange rate
GBP → USD 1.25 Average 2024 exchange rate

Note: Country-specific costs are preferred over currency conversion to capture local practice patterns and pricing.

11. References

Primary Cost Sources

  1. HCUP National Inpatient Sample. Healthcare Cost and Utilization Project (HCUP). Agency for Healthcare Research and Quality. 2022.

  2. NHS Reference Costs 2022-23. NHS England. https://www.england.nhs.uk/costing-in-the-nhs/national-cost-collection/

  3. NADAC (National Average Drug Acquisition Cost). Medicaid.gov. 2024. https://data.medicaid.gov/nadac

  4. NHS Drug Tariff. NHS Business Services Authority. April 2024.

  5. USRDS Annual Data Report 2023. United States Renal Data System. Chapter 9: Healthcare Expenditures.

  6. Medicare Clinical Laboratory Fee Schedule. CMS. 2024.

Published Literature

  1. Moran AE, et al. Cost-effectiveness of hypertension therapy according to 2014 guidelines. JAMA. 2015;312(20):2069-2082.

  2. Sim JJ, et al. Resistant hypertension and healthcare costs. J Am Heart Assoc. 2015;4(12):e002404.

  3. Valderrama AL, et al. Direct medical costs of uncontrolled hypertension. J Am Soc Hypertens. 2014;8(4):210-219.

  4. Kauf TL, et al. The cost of acute myocardial infarction in the 1990s. Am Heart J. 2006;152(4):678-684.

  5. Wang G, et al. The cost of stroke in the United States. Stroke. 2014;45(1):29-35.

  6. Luengo-Fernandez R, et al. Population-based study of costs of stroke care in England. Stroke. 2013;44(5):1287-1294.

  7. Heidenreich PA, et al. Forecasting the future of cardiovascular disease. Circ Heart Fail. 2013;126(5):1001-1010.

  8. Dunlay SM, et al. Lifetime costs of medical care after heart failure diagnosis. Circ Heart Fail. 2011;4(1):68-75.

  9. Kim MH, et al. Estimation of total incremental health care costs in atrial fibrillation. Circ Cardiovasc Qual Outcomes. 2011;4(3):313-320.

  10. Vupputuri S, et al. The economic burden of chronic kidney disease. Kidney Int. 2014;86(3):619-624.

  11. Kerr M, et al. Estimating the financial cost of chronic kidney disease to the NHS in England. Nephrol Dial Transplant. 2012;27(suppl_3):iii73-iii80.

  12. Smith DH, et al. Cost of medical care for chronic kidney disease. Am J Kidney Dis. 2004;44(2):261-271.

Indirect Cost References

  1. Greiner W, et al. Productivity loss after acute coronary syndrome. Eur J Health Econ. 2004;5(4):324-330.

  2. Dewilde S, et al. Work absence and return to work after stroke. BMJ Open. 2017;7(6):e014163.

  3. Tanaka E, et al. Long-term economic impact of stroke. Stroke. 2011;42(11):3034-3039.

  4. Patel A, et al. Productivity costs of stroke in the United Kingdom. Stroke. 2020;51(5):1429-1436.

Methodology

  1. Husereau D, et al. Consolidated Health Economic Evaluation Reporting Standards 2022 (CHEERS 2022). BMJ. 2022;376:e067975.

  2. Drummond MF, et al. Methods for the Economic Evaluation of Health Care Programmes. 4th ed. Oxford University Press. 2015.

  3. NICE. Guide to the methods of technology appraisal 2013 (PMG9).

Appendix A: Code Reference

File: src/costs/costs.py

Function Purpose
get_drug_cost() Calculate monthly drug cost by treatment arm
get_total_cost() Sum chronic management costs by state
get_event_cost() Return one-time acute event cost
get_productivity_loss() Calculate chronic disability cost
get_acute_absenteeism_cost() Calculate one-time absenteeism cost

Appendix B: Cost Input Checklist for Model Updates

When updating cost inputs:

  • Verify price year matches model documentation
  • Update inflation factors if using historical data
  • Check NADAC/NHS Tariff for current drug prices
  • Verify HCUP/NHS Reference Cost codes still apply
  • Update PSA distributions if uncertainty changes
  • Document all sources in this report
  • Run model validation after cost updates

Document Version: 1.0 Last Updated: February 2026 Author: HEOR Technical Documentation Team