Dehydrated human amnion and chorion allograft versus standard of care alone in treatment of Wagner 1 diabetic foot ulcers: a trial-based health economics study

Figures & data

Figure 1. Health states used in the Markov microsimulation model.

Table 1. Direct costs based on time-based activity-based costing (2019; US dollars).

Category	Item	Cost ($)	Source
Personnel	(a) Hourly cost (physician)	124.75	SalaryExpert^18
	(b) Hourly cost (nurse)	41.67	Indeed^19
Consumables	(a) Walker offloading boot	79.99	Orthotape.com
	(b) Debridement kit	8.99	Woundcareshop.com
	(c) Non-adherent primary dressing, 3” × 3”	0.68	Woundcareshop.com
	(d) Hydrogel-impregnated dressing 2” × 2”	1.11	Woundcareshop.com
	(e) Calcium alginate dressing 2” × 2”	6.67	Woundcareshop.com
	(f) Compression system	25.00	Woundcareshop.com
	(g) dHACA (per cm^2), ASP Q4151	155.61	CMS^20
Infection and cellulitis management	Bacterial organism identification
	(a) Culture, disk method	7.66	CMS^21
	(b) Nucleic acid, quantification, each organism	47.60	CMS^21
	Antibiotics (outpatient management):
	(a) Cephalexin, 500 mg capsule	1.24	Red Book
	(b) Amoxicillin clavulanate, 500 mg tablet (+125 mg clavulanic acid]	3.77
	(c) Levofloxacin, 500 mg	18.75
	(d) Topical metronidazole cream or gel	269.97
Osteomyelitis management	Diagnostics, bone debridement, and IV antibiotics (hospital)	18,129	See (Osteomyelitis section)
Amputation	Minor (e.g. toe, or transmetatarsal)	21,301	Barshes et al.^22
	Major (e.g. trans-tibial)	34,441	Barshes et al.^22

Table 2. Calculation of ASP cost for different sizes of dHACA. Cost is $155.61 per square centimeter.

dHACA Description	Area (cm^2)	ASP Cost ($)
1 cm disk	0.79	122.15
1.4 cm disk	1.54	239.42
1.8 cm disk	2.54	395.78
2 × 2 cm	4	622.44
2 × 4 cm	8	1,244.88
3 × 4 cm	12	1,867.32
4 × 4 cm	16	2,489.76

Table 3. Example of resource items, resource units, and calculation of costs for cycle 0 for both treatment groups. Totals ±$0.01 due to rounding errors.

Resource item	Cost ($)	Resource units dHACA	Resource units SOC	Cost component dHACA	Cost component SOC
Initial visit cost	83.21	1 unit	1 unit	83.21	83.21
Initial debridement cost	71.37	1 unit	1 unit	71.37	71.37
Collagen alginate dressing	6.67	–	7 units	0	46.69
Non-adherent primary dressing	0.68	7 units	–	4.76	0
Hydrogel-impregnated dressing	1.11	7 units	–	7.77	0
Compression system	25.00	1 unit	–	25.00	0
Offloading device	79.99	0.725 units*	0.775 units*	57.99	61.99
dHACA cost	609.24**	1 unit	–	609.24	0
dHACA application cost	31.19	1 unit	–	31.19	0
Sub-total	—	–	–	890.53	263.26
Indirect cost	—	1 unit	1 unit	Subtotal × 1.3	Subtotal × 1.3
TOTAL				1157.69	342.24

*Equates to the fact that not all DFUs are offloaded; multiply by 100 to obtain percentage of DFUs offloaded. **Mean cost for all DFUs adjusted for healing rate.

Table 4. Cycle costs ($) for model states.

Cycle Number	Group 1	Group 2
Unhealed non-infected ulcer
0	1157.68	342.23
1	542.56	128.33
2	509.10	180.56
3	423.41	128.33
4	380.57	180.56
5	380.57	128.33
6	285.49	180.56
7	294.88	128.33
8	242.65	180.56
9	294.88	128.33
10	242.65	180.56
11	294.88	128.33
12	85.94	85.94
52	85.94	85.94
Infected non-healed ulcer or cellulitis*
$636.21
Osteomyelitis
$18,129
Amputation
$24,586

*Per 2-week episode.

Table 5. Variables used in sensitivity analysis, rationale for using them, and values used in the analysis.

Variable	Rationale	Values
Costs
(1) Overall wound healing cost	Represents scenarios of overall lower/higher direct/indirect costs	±50%
(2) Infection episode cost*	Represents scenarios of overall lower/higher direct/indirect costs	±50%
(3) Amputation cost	Represents scenarios of overall lower/higher direct/indirect costs	±50%
(4) dHACA cost	Represents smaller or larger wounds (having to use smaller/larger sizes of dHACA), or lower/higher cost scenarios	±50%
Probabilities
(5) Healing rates	Represents uncertainty for smaller or larger wounds or factors that impact wound healing	±25%
(6) Infection rate**	Represents more or less severe infections on average (more severe: hospitalization) or lower or higher rates	±50%
(7) Amputation rate	Represents lower or higher rates of amputations or lower or higher proportion of major amputations	±50%
Utility values
(8) Change in utility value on healing	Represents uncertainty of assigned utility value based on method (differences between healed and unhealed states; other states adjusted proportionately)	±50%***

*Includes infection, cellulitis, and osteomyelitis costs. **Includes infection, cellulitis, and osteomyelitis rates. ***Change in utility value for healing a wound.

Table 6. Cycle probability rates for healing rates for both study groups. Note cycle 0 corresponds to the day of randomization in the trial; cycle 12 corresponds to week 12 in the trial.

Cycle	Group 1	Group 2
0	0.0195	0.0011
1	0.1156	0.0274
2	0.1294	0.0000
3	0.1820	0.1130
4	0.2164	0.0625
5	0.1603	0.0329
6	0.0618	0.0691
7	0.3274	0.0362
8	0.0000	0.0000
9	0.0000	0.0373
10	0.0916	0.0395
11	0.0000	0.0406
12	0.338	0.114
14	0.092	0.092
16	0.096	0.096
18	0.096	0.100
20	0.096	0.105
22	0.096	0.110
24	0.096	0.115
26	0.096	0.120
28	0.096	0.126
30	0.096	0.132
32	0.096	0.138
34	0.096	0.144
36	0.096	0.149
38	0.096	0.153
40	0.096	0.154
42	0.096	0.150
44	0.096	0.140
46	0.096	0.120
48	0.096	0.088
50	0.096	0.044
52	0.096	0.018

Figure 2. Tornado diagram showing influence of increasing or decreasing key cost and health state transition rate variables over the base case ICER using units of $/QALY (group 1 versus group 2). Note. units are expressed as the relative expected change in ICER.

Figure 3. ICE scatterplot. ICE scatterplot of group 1 versus group 2. The ellipse represents 95% confidence intervals (CI).

Figure 4. Willingness to pay curve with cost/QALY thresholds: £20,000/QALY based on June 2020 exchange rates (dotted vertical line) and $50,000/QALY (dashed line).

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