Economic evaluation of duloxetine as a first-line treatment for painful diabetic peripheral neuropathy in Mexico

Figures & data

Figure 1.  Structure of the model. PDPN: Painful diabetic peripheral neuropathy; AE: Adverse events. For simplicity, only branches for duloxetine are presented. All other strategies follow an identical pathway.

Figure 2.  Flowchart outlining steps in search strategy.

Table 1.  Pooled analysis of achieving good pain relief in placebo arms.

Source	Patients enrolled in placebo arms
	Patients	Response^a	Response (%)
Goldstein et al.22	115	35	30.4
Raskin et al.23	116	32	27.6
Wernicke et al.24	108	33	30.6
Lesser et al.46	97	23	23.7
Rosenstock et al.47	70	12^b	17.1
Tölle et al.42	96	35^b	36.5
Richter et al.45	85	24	28.2
Freynhagen et al.44	65	20	30.8
US FDA43	81	29^b	35.8
Arezzo et al.41	85	32	37.6
Backonja et al.51	81	25	30.9
Gorson et al.49	40	9	22.5
Simpson50	30	7	23.3
Backonja and Glanzman48	81	20	24.7
Pooled analysis	1150	336	29.2

^aGood pain relief: patient-reported subjective pain relief of ‘moderate’ or better; or ‘much improved’ or better on the Patient Global Impression of Change (PGIC) scale.

^bEstimated by using the conversion ratio derived by O’Connor et al.33.

Table 2.  Risk ratios of achieving good pain relief with active treatment.

Source	Number of patients		GPR		GPR (%)
	DUL 60 mg	PBO	DUL 60 mg	PBO	DUL 60 mg	PBO
Goldstein et al.22	114	115	64	35	56.1	30.4
Raskin et al.23	116	116	57	32	49.1	27.6
Wernicke et al.24	114	108	65	33	57.0	30.6
Pooled analysis	344	339	186	100	54.1	29.5
	Risk ratio [CI 95%] DUL 60 mg vs PBO 1.83 [1.51–2.22]
	PGB 300 mg	PBO	PGB 300 mg	PBO	PGB 300 mg	PBO
Lesser et al.46	81	97	44	23	54.3	23.7
Rosenstock et al.47	76	70	36^b	12^b	47.4	17.1
Tölle et al.42	99	96	39^b	35^b	39.4	36.5
Pooled analysis	256	263	119	70	46.5	26.6
	Risk ratio [CI 95%] PGB 300 mg vs PBO 1.75 [1.37–2.22]
	GBP^a	PBO	GBP^a	PBO	GBP^a	PBO
Backonja et al.51	84	81	47	25	56.0	30.9
Gorson et al.49	40	40	17	9	42.5	22.5
Simpson50	30	30	15	7	50.0	23.3
Backonja and Glanzman48	244	81	90	20	36.9	24.7
Pooled analysis	398	232	169	61	42.5	26.3
	Risk ratio [CI 95%] GAB vs PBO 1.61 [1.27–2.06]

^aDifferent doses; see text.

^bEstimated by using the conversion ratio derived by O’Connor et al.33

GPR, Good pain relief, defined as patient-reported subjective pain relief of ‘moderate’ or better; or ‘much improved’ or better on the Patient Global Impression of Change (PGIC) scale; DUL, Duloxetine; PGB, Pregabalin; GBP, Gabapentin; PBO, Placebo; CI, Confidence interval.

Table 3.  Model parameters values: base-case, ranges, and distributions.

Parameter	Base-case	Range	Distribution	Reference
Probability of good pain relief
Baseline risk (placebo)	0.292	0.266–0.319	–	Table 1
Duloxetine (RR)	1.83	1.51–2.22	LogNormal	Table 2
Pregabalin (RR)	1.75	1.37–2.22	LogNormal	Table 2
Gabapentin (RR)	1.61	1.27–2.06	LogNormal	Table 2
Probability of any adverse events
Baseline risk (placebo)	0.366	0.330–0.404	–	20
Duloxetine (RR)	1.45	1.29–1.63	LogNormal	22–24
Pregabalin (RR)	1.58	1.25–1.99	LogNormal	20
Gabapentin (RR)	1.80	1.50–2.17	LogNormal	20
Withdrawal owing to adverse events
Baseline risk (placebo)	0.076	0.064–0.091	–	20
Duloxetine (RR)	2.14	1.23–3.73	LogNormal	22–24
Pregabalin (RR)	2.34	1.76–3.10	LogNormal	20
Gabapentin (RR)	1.53	1.17–2.00	LogNormal	20
Probability of treatment adherence
Duloxetine	0.93	0.77–1.00	Beta	28
Pregabalin	0.87	0.74–0.97	Beta	28
Gabapentin	0.80	0.66–0.89	Beta	28
Probability of stopping drug because of poor pain relief	0.75	0.5–1.00	Uniform	33
Treatment stop timing (days)
Intolerable adverse events	7	0–14	Uniform	4
Lack of efficacy	28	21–35	Uniform	4
Pain-state utility values
Moderate-to-severe pain	0.64	0.59–0.70	Beta	11–14
Mild pain (good pain relief)	0.38	0.35–0.41	Beta	11–14
Disutility factor adjustment*
Tolerable adverse events	0.95	±0.025	Uniform	33
Intolerable adverse events	0.90	±0.05	Uniform	33
Daily treatment cost (MXN)
Duloxetine 60 mg/day	28.06	±10%	Gamma	38
Pregabalin 300 mg/day	49.00			38
Branded gabapentin 1800 mg/day	64.67			38
Generic gabapentin 1800 mg/day	16.26			37
Outpatient medical consultation cost
General medicine office visit (MXN)	535	±10%	Gamma	39
Specialty medicine office visit (MXN)	1362			39

*Pain-state utility values were multiplied by the disutility factor adjustment to create the utility of the combined health state (presence of adverse events along with the extent of pain).

Table 4.  Outcomes from the base-case analysis (per 1000 patients).

Model outcome	gen-GBP	DUL	PGB	Brand-GBP
Expected costs
Treatment cost (MXN)	$3,069,735	$3,561,411	$4,571,247	$5,303,382
Expected benefits
Patients with GPR	470	534	511	470
QALY	120.9	125.7	123.8	120.9
Incremental costs/benefits
ΔTreatment cost (MXN)	Reference	$491,676	$1,501,512	$2,233,647
ΔPatients with GPR	Reference	64	41	0
ΔQALY	Reference	4.8	2.9	0
ΔCost effectiveness ratios
Cost per additional patient with GPR (MXN)	Reference	$7647	$36,712	NC
Cost per additional QALY (MXN)	Reference	$102,433	$517,763	NC

GPR, Good pain relief, defined as patient-reported subjective pain relief of ‘moderate’ or better; or ‘much improved’ or better on the Patient Global Impression of Change (PGIC) scale; QALY, Quality adjusted life year; gen-GBP, Generic gabapentin 1800 mg/day; DUL, Duloxetine 60 mg/day; PGB, Pregabalin 300 mg/day; brand-GBP, Branded gabapentin 1800 mg/day; NC, Not calculable since incremental benefits are equal to zero.

Δdenotes ‘increment’. Rounded data.

Figure 3.  The tornado diagram: Painful diabetic peripheral neuropathy. The WTP for an additional QALY is set equal to 3 × GDP per capita in Mexico. RR: Risk ratio; GPR: Good pain relief; DUL: Duloxetine; GBP: Gabapentin; PGB: Pregabalin; AE: Adverse events; K denotes a thousand; WTP:Willingness to pay; GDP: Gross domestic product.

Figure 4.  Incremental cost-effectiveness scatter plot (DUL vs. gen-GBP). MXN: Mexican pesos; DUL:Duloxetine; gen-GBP: Generic gabapentin; QALY: Quality adjusted life year. Data per 1000 patients.

Figure 5.  Acceptability curves. QALY: Quality adjusted life years; brand-GBP: Branded gabapentin; gen-GBP: Generic gabapentin; DUL: Duloxetine; PGB: Pregabalin; K denotes a thousand.

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