Modeling long-term health and economic implications of new treatment strategies for Parkinson’s disease: an individual patient simulation study

Figures & data

Figure 1. Model influence diagram

Outlines the key relationships captured in the Parkinson’s disease model.Abbreviations: HY = Hoehn and Yahr; MDS-UPDRS = Movement Disorder Society Unified Parkinson’s Disease Rating Scale; PD = Parkinson’s disease.

Table 1. Model inputs and sources

Parameter	Description	HY	Input Values	Source(s)
Population	Baseline individual profiles derived from studies on early PD		Supplement Table S1	[20]
Disease progression	Predictive equations from PD diagnosis (before and after initiating symptomatic therapy) and published transition probabilities HY 3+	HY <3 HY 3+	Predictors before initiation of symptomatic therapy: age, gender, disease duration, MDS-UPDRS (Supplement Table S2) Predictors on symptomatic therapy: age, gender, disease duration, UPDRS, LED and off-time (Supplement Table S3) Transitions between HY 3 to 4, 5 and five off-time categories (none, quartiles)	[20], [22], [26]
Mortality	Hazard ratios by HY adjust age- and gender-specific mortality for the UK general population	HY 1 to 3 HY 4 HY 5	UK life tables and hazard ratios 1.18 2.37 3.34	[30], [19]
Utilities	Patient EQ-5D estimated from predictive equation for HY <3 and published values for HY 3+	HY <3	Predicted adjusting for gender and UPDRS (Supplement Table S4)	[22]
		HY 3 HY 4 HY 5	Conditional on HY and five % off time categories None 0–25 26–50 51–75 76–100% 0.596 0.566 0.536 0.506 0.475 0.487 0.456 0.426 0.396 0.366 0.377 0.347 0.316 0.286 0.256	[28]
	Caregiver EQ-5D decrements conditional on patients’ HY	HY 2 HY 3 HY 4 HY 5	EQ-5D decrements -0.022 –0.120 -0.090 –0.120	[31]
Direct costs*	Direct medical and non-medical	HY 1 HY 2 HY 3 HY 4 HY 5	Annual costs (% in nursing home) £3,918 £7,417 £14,150 (4.1%) £28,660 (18.3%) £53,335 (61.9%)	[32]
Pharmaceutical costs	Symptomatic treatment costs reflect percent receiving each therapy and LED	HY <3 HY 3+	Percent on each dopaminergic/other over time^a,b £5 per LED mg/year^c £192/year non-dopaminergic £4,024/year	[20], [33], [21]
	Advanced therapies** costs reflect percent on each therapy (and co-medications) and average duration – weighted average cost applied for those who initiate an advanced therapy	HY 3+	Percent on each (average duration) None 59.1% DBS 23.3% (3.33 years) LCIG 15.9% (1.69 years) CSAI 3.3% (1.88 years) Weighted average initiation cost of £16,578 and ongoing cost of £22,942/year (applied for average duration of treatment); details are provided in supplement	[34], [29]

Abbreviations: CSAI = continuous subcutaneous apomorphine infusion; DBS = deep brain stimulation; HY = Hoehn and Yahr; LCIG = levodopa-carbidopa intestinal gel; LED = levodopa-equivalent dose; MDS-UPDRS = Movement Disorder Society Unified Parkinson’s Disease Rating Scale; ONS = Office for National Statistics; PD = Parkinson’s disease.

*Direct costs include inpatient and outpatient (excluding pharmaceutical costs), and direct non-medical services (nursing home, residential care, sheltered housing, home help, and respite care).

**Advanced therapies include continuous subcutaneous apomorphine infusion; deep brain stimulation; levodopa-carbidopa intestinal gel.

# Cost derivation details provided in supplement. Costs are reported in 2020 British pounds (GBP).

Table 2. Simulation base case results for a hypothetical DMT added to standard of care vs. standard of care over a lifetime horizon

Outcomes	Disease-Modifying Therapy Added to Standard of Care	Standard of Care	Incremental
Total costs (discounted)	£ 195,513.13	£ 232,619.02	-£ 37,105.89
Parkinson’s disease medications	£ 40,884.83	£ 39,473.57	£ 1,411.26
Advanced therapies	£ 12,584.05	£ 20,803.14	-£ 8,219.09
Direct medical	£ 33,877.07	£ 43,391.83	-£ 9,514.76
Direct non-medical	£ 108,167.18	£ 128,950.48	-£ 20,783.30
Health outcomes
Undiscounted
Life years	18.50	17.83	0.67
QALYs	12.28	10.41	1.87
Discounted (at 3.5% per year)
Life years	12.70	12.40	0.30
QALYs	8.81	7.69	1.12
Patient QALYs	9.40	8.45	0.95
Caregiver decrement in QALYs	0.59	0.76	−0.17

Abbreviations: QALY = quality-adjusted life year.

Figure 2. Simulation of movement disorder society unified Parkinson’s disease rating scale scores over time for a newly diagnosed cohort: comparison of simulated with observed outcomes

A) MDS-UPDRS I, B) MDS-UPDRS II, C) MDS-UPDRS III; Observed (grey): Mean observed data for each subscale derived from analyses of PPMI data; Simulated: Model outputs from simulation of a newly diagnosed cohort with PPMI-baseline characteristics, PPMI based equationsAbbreviations: MDS-UPDRS = Movement Disorder Society Unified Parkinson’s Disease Rating Scale; PPMI = Parkinson’s Progression Markers Initiative.

Figure 3. Deterministic sensitivity analysis results

Tornado diagrams for simulation of a DMT vs. standard of care over a lifetime horizonAbbreviations: DMT = disease-modifying therapy; HR = hazard ratio; HY = Hoehn and Yahr; MDS-UPDRS = Movement Disorder Society Unified Parkinson’s Disease Rating Scale; PD = Parkinson’s disease; QALY = quality-adjusted life year.

Parkinson’s Progression Markers Initiative. Home page. [ cited 2018 Jan]. Available from: www.ppmi-info.org

 Google Scholar

National Institute of Neurological Disorders and Stroke. Archived clinical research data (NET-PD LS-1 creatine in Parkinson’s disease; Karl Kieburtz, MD, MPH). [ cited 2021 Jan]. Available from: https://www.ninds.nih.gov/Current-Research/Research-Funded-NINDS/Clinical-Research/Archived-Clinical-Research-Datasets

 Google Scholar

Johnson SJ, Diener MD, Kaltenboeck A, et al. An economic model of Parkinson’s disease: implications for slowing progression in the USA. Mov Disord. 2013;28(3):319–326.

 PubMed Web of Science ®Google Scholar

Office for National Statistics. National life tables, UK: 2016 to 2018. Fit parametric distributions to reported survival data.

 Google Scholar

Kaltenboeck A, Johnson SJ, Davis MR, et al. Direct costs and survival of medicare beneficiaries with early and advanced Parkinson’s disease. Parkinsonism Relat Disord. 2012;18(4):321–326.

 PubMed Web of Science ®Google Scholar

Lowin J, Sail K, Baj R, et al. The cost-effectiveness of levodopa/carbidopa intestinal gel compared to standard care in advanced Parkinson’s disease. J Med Econ. 2017;20(11):1207–1215.

 PubMed Web of Science ®Google Scholar

Kalabina S, Belsey J, Pivonka D, et al. Cost-utility analysis of levodopa carbidopa intestinal gel (Duodopa) in the treatment of advanced Parkinson’s disease in patients in Scotland and Wales. J Med Econ. 2019;22(3):215–225.

 PubMed Web of Science ®Google Scholar

Findley LJ, Wood E, Lowin J, et al. The economic burden of advanced Parkinson’s disease: an analysis of a UK patient dataset. J Med Econ. 2011;14(1):130–139.

 PubMedGoogle Scholar

Kalilani L, Friesen D, Boudiaf N, et al. The characteristics and treatment patterns of patients with Parkinson’s disease in the USA and UK: a retrospective cohort study. PLoS One. 2019;14(11):e0225723.

 Web of Science ®Google Scholar

Writing Group for the NINDS Exploratory Trials in Parkinson Disease Investigators, Kieburtz K, Tilley BC, et al. Effect of creatine monohydrate on clinical progression in patients with Parkinson's disease: a randomized clinical trial. JAMA. 2015;313(6):584–593.

 Web of Science ®Google Scholar

Fasano A, Fung VSC, Lopiano L, et al. Characterizing advanced Parkinson’s disease: OBSERVE-PD observational study results of 2615 patients. BMC Neurol. 2019;19(1):50.

 PubMedGoogle Scholar

Walter E, Odin P. Cost-effectiveness of continuous subcutaneous apomorphine in the treatment of Parkinson’s disease in the UK and Germany. J Med Econ. 2015;18(2):155–165.

 PubMed Web of Science ®Google Scholar