Cost-effectiveness of droxidopa in patients with neurogenic orthostatic hypotension: post-hoc economic analysis of Phase 3 clinical trial data

Figures & data

Figure 1. Markov model structure. *State ‘all-cause death’ is not displayed.

Table 1. Summary of model assumptions.

Assumptions
1. The placebo arm of the droxidopa clinical trial, NOH306, represented standard of care for number of falls and improvement in nOH symptoms (treatment response).
2. After 6 months of treatment, patients in the droxidopa treatment group were assumed to switch to standard of care and its associated probability of fall estimates.
3. All patients initiated treatment in the ‘no fall’ state.
4. Probabilities of falling were assumed to be constant over time.
5. After a fall with major injury, recovery was associated with a period of bed rest and immobilization. Patients were considered to have zero risk of a fall or fall-related death during the recovery period.
6. A maximum of one fall per week was possible.
7. Patients purchased medication once a week, paying a fixed co-pay amount on each occasion.
8. nOH symptom improvement occurred in treatment responders only, after the treatment response assessment (8 weeks), and continued until the end of treatment.
9. Treatment responders had lower resource use (the same for both treatment arms) and a higher quality-of-life (gain in utility) from the moment of response to the end of treatment.
10. An average utility decrement was applied for falls with no injury, minor injury, or moderate injury; for falls with major injury, a utility decrement associated with fracture was assessed.
11. Each type of fall-related injury was associated with a different level of FoF; for each type of injury, the duration of FoF was the same.

FoF, fear of falling; nOH, neurogenic orthostatic hypotension.

Table 2. Key model inputs for base analysis and DSA analysis.

Parameter	Probability or value
	Base	DSA	Source
Time horizon, months	12	6	Assumption
Droxidopa treatment duration, months	6	3 or 12	Assumption
Post-droxidopa probability of fall	Same as standard of care	Same as droxidopa	Assumption
Weekly fall rates, %			Droxidopa RCTs4^,5*
Droxidopa	33.0	22.3–44.7
Standard of care	81.7	51.4–98.4
Treatment response rate, %†			Droxidopa RCT (nOH306B)5
Droxidopa	55.6	ND
Standard of care	38.2	ND
Fall severity, %			Base: Haines et al.8‡; DSA: Latimer et al.16$ or Wielinski et al.24¶
No injury	80.80	40.85 or 34.88
Minor injury	12.95	31.88 or 15.85
Moderate injury	3.09	17.93 or 27.37
Major injury	2.79	8.97 or 21.53
Death	0.37	0.37
Droxidopa acquisition, US$/week			Droxidopa RCTs (doses)4^,5 and manufacturer (pricing)
Titration period	796	ND
Maintenance	1141	ND
FoF duration, weeks	26	13–39	Base: Bertera and Bertera17, Delbaere et al.18, and Iglesias et al.15; DSA: assumption
Utility decrement due to FoF			Iglesias et al.15
No injury	0.04	0.03–0.07
Minor injury	0.08	0.06–0.10
Moderate injury	0.11	0.05–0.17
Major injury	0.25	0.10–0.45
Utility decrement due to falls and fractures			Iglesias et al.15
Fall	0.004	0.00–0.03
Fracture	0.021	0.00–0.11
Fall-related injury, US$
No injury	0	0	Assumption
Minor injury	111	63	Base: Haines et al.8**; DSA: cost of general practitioner visit
Moderate injury	12,742	319	Base: Davis et al.10††; DSA: Roudsari et al.9‡‡
Major injury	31,393	17,727	Base: Davis et al.10††; DSA: Roudsari et al.9‡‡
Death	22,413	ND	Stevens et al.11$$
nOH management
General practitioner visit, US$	63	ND	2012 MarketScan Medicaid database
Non-responder visits,¶¶ n/3 months	2	ND	Assumption
Responder visits,*** n/4 months	2	ND	Assumption
Neurologist visit, US$	71	ND	2012 MarketScan Medicaid database
Non-responder visits,¶¶ n/3 months	1	ND	Assumption
Responder visits,*** n/4 months	1	ND	Assumption

DSA, deterministic sensitivity analysis; FoF, fear of falling; ND, not done; nOH, neurogenic orthostatic hypotension; RCT, randomized controlled trial.

*Pooled data analyzed by Poisson-inverse Gaussian model.

†Treatment response was defined as a ≥50% improvement in item 1 (dizziness/lightheadedness) of the Orthostatic Hypotension Symptom Assessment from baseline to week 8 of treatment.

‡Recalculated to include the probability of fall-related death.

$Data from the general population.

¶Data from a Parkinson's disease population.

**Adjusted to 2014 costs calculated using the Australian healthcare Consumer Price Index and converted to US dollars.

††Adjusted to 2014 costs using the Consumer Price Index (restricted to medical care).

‡‡Moderate injury corresponds to emergency department costs; major injury corresponds to hospitalization costs.

$$Calculated from average cost and adjusted to 2014 costs using the Consumer Price Index (restricted to medical care).

¶¶During the period before treatment response assessment (8 weeks) and the period after the end of treatment.

***Occurring between treatment response assessment and end of treatment.

Table 3. PSA parameters and sources.

Parameter	Distribution	Base	σ/β/b	95% CI	Source
Weekly fall rates, %	Beta (µ, σ)
Droxidopa		33.0	0.06	22.3–44.7	β calibrated to fit in the 95% CI, estimated from droxidopa RCTs4^,5*
Standard of care		81.7	0.13	51.4–98.4
FoF duration, weeks	LogNormalY (µ, σ)	26	6.6	13–39		SD calibrated to fit in the assumed 95% CI
Costs, US$	Gamma (µ, σ)
Droxidopa, per mg		0.15	0.03	0.10–0.21	SD calibrated to fit in the assumed 95% CI
Fall with no injury		0	0	0	SD calibrated to fit in the assumed 95% CI
Fall with minor injury		111	0	60.89–175.90	Haines et al.8†
Fall with moderate injury		12,742	0	6990–20,193	SDs not reported in the base case; SD for fall with no injury applied as percentage
Fall with major injury		31,393	0	17,221–49,749	SDs not reported in the base case; SD for fall with no injury applied as percentage
Fall resulting in death		22,413	0	12,295–35,518	SDs not reported in the base case; SD for fall with no injury applied as percentage
General practitioner visit		63	12	41–89	2012 MarketScan Medicaid database
Neurologist visit		71	24	32–125	2012 MarketScan Medicaid database

PSA, probabilistic sensitivity analysis; RCT, randomized controlled trial.

*Pooled data analyzed by Poisson-inverse Gaussian model.

†Adjusted to 2014 costs calculated using the Australian healthcare Consumer Price Index and converted to US dollars.

Table 4. Number of falls per 10,000 patients by treatment group.

Fall severity	Droxidopa	Standard of care	Difference (Droxidopa vs Standard of care)
Total	258,776	365,419	−106,643
No injury	209,091	295,258	−86,168
Minor injury	33,516	47,329	−13,812
Moderate injury	7992	11,286	−3294
Major injury	7219	10,194	−2975
Death	957	1352	−395

Table 5. Total and incremental costs per patient by treatment group in US dollars.

Costs, US$	Droxidopa	Standard of care	Difference (Droxidopa vs Standard of care)
Total	66,414	50,827	15,587
Treatment	30,112	0	30,112
Routine care	938	889	49
Falls	35,364	49,938	−14,574

Figure 2. Deterministic sensitivity analyses for ICER per QALY (A), avoided fall with no/minor injury (B), and avoided fall with moderate/major injury (C). ICER, incremental cost-effectiveness ratio; QALY, quality-adjusted life-year.

Figure 3. Cost-effectiveness acceptability curve for ICER per QALY with droxidopa vs standard of care. ICER, incremental cost-effectiveness ratio; QALY, quality-adjusted life-year.

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