Cost-effectiveness analysis of pancreatin minimicrospheres in patients with pancreatic exocrine insufficiency due to chronic pancreatitis

Figures & data

Figure 1.  Core model structure (right) and treatment algorithm (left) for patients with uncontrolled PEI in the pancreatin MMS treatment arm.

Table 1.  Treatment effect from identified clinical trials.

Reference	Countries	Treatment duration (days)	Number of patients per treatment arm	Mean fat excretion (g/day)^a	CFA (%)^a
Safdi et al.40	US	14	PMM = 12	PMM = 22.9	PMM = 86.6
			P = 14	P = 51.8	P = 68.00
Halm et al.41^b	Germany	14	PMM = 11	PMM = 17.3	PMM = 77.2
O’Keefe et al.39	South Africa	14	PMM = 15	PMM = 19.6	PMM = 81.5
			P = 16	P = 43.3	P = 60.3
Whitcomb et al.42	Bulgaria, Poland, Russia, Serbia, Ukraine, US	7	PMM = 24	PMM = 67.3	PMM = 86.1
			P = 28	P = 165.8	P = 66.90
Thorat et al.43	India	7	PMM = 32	PMM = 16.2	PMM = 86.1
			P = 24	P = 30.0	P = 72.9
		365	PMM = 47	PMM = 12.2	PMM = 88.91

CFA, Coefficient of fat absorption; P, Placebo treatment group; PMM, Pancreatin minimicrospheres treatment group.

^aThe reported treatment effect refers to the assessment at the end of the treatment duration.

^bOnly data from the first treatment period from the MMS treatment arm were included due to the model design. Only patients with a post-efficacy measurement were taken into account.

Table 2.  Model input parameters.

Parameter	Base case value	Values used in SA (range)	PSA distribution (PSA parameters)		Source
Model Horizon
Discount rate for costs	5.0%	0–5%	None		ATOM51
Discount rate for outcomes	3.5%	0–5%	None
Utilities
Mild pancreatitis (controlled PEI)	0.95	0.85–0.95	Beta	19.02; 2.11	Poulose et al.49
Severe pancreatitis (uncontrolled PEI)	0.71	0.18–0.71	Beta	24.25; 9.91
Mortality
5-year death rate	15%	3–18%	Beta	235 (1565)	Lowenfels et al.44
10-year death rate	30%	14–34%	Beta	292 (973)
15-year death rate	45%	20–48%	Beta	246 (547)
20-year death rate	55%	37–62%	Beta	112 (204)
Dosing Regimen of Pancreatin MMS
Time at which pts receive increased dose	2 weeks	2–52	None		Clinical experts7
% pts with increased dosing	100%	0–100%	None
Dose increase rate	2	0–3	None
Time at which pts discontinue	26 weeks	2–260	None		Assumption
% pts who discontinue	100%	0–100%	None		Assumption
Medication Costs
Conversion rate Złoty to Euro	0.2413	0.217–0.265	None		Oanda54
Cost per capsule (Pancreatin MMS 40,000 lipase units)	€0.61	–	None		Provided by Abbott
Cost per capsule (Pancreatin MMS 25,000 lipase units)	€0.28	–	None		Wykaz Leków Refundowanych50
Transition Probabilities
First cycle*					O’Keefe et al.39
No PERT treatment: Uncontrolled to controlled	27%	18–37%	Beta	21 (79)	Safdi et al.40 Halm et al.41
Pancreatin MMS: Uncontrolled to controlled	69%	59–79%	Beta	59 (85)	Whitcomb et al.42 Thorat et al.43
Next cycles					Thorat et al.43
No PERT treatment: Remaining in controlled	100%	81–100%	Beta	27 (27)
Pancreatin MMS: Remaining in controlled	100%	81–100%	Beta	27 (27)
No PERT treatment: Uncontrolled to controlled	0%	0–10%	None
Pancreatin MMS: Uncontrolled to controlled	35%	12–66%	Beta	4 (7)

MMS, Minimicrospheres; PEI, Pancreatic exocrine insufficiency; PERT, Pancreatic enzyme replacement therapy; PSA, Probabilistic sensitivity analysis; SA, Sensitivity analysis.

*For the short-term treatment effect, the table only shows the per-cycle probability to move from one health state to another. The chance of remaining in the present health state is 1 minus the transition probability of moving away.

Table 3.  Results for 5-, 10-, and 20-year cost-effectiveness analysis.

	SA, 5 years		SA, 10 years		Base case analysis, 20 years
Treatment arm	Pancreatin MMS	No PERT treatment	Pancreatin MMS	No PERT treatment	Pancreatin MMS	No PERT treatment
Controlled PEI	78%	23%	64%	19%	41%	12%
Uncontrolled PEI	7%	62%	6%	51%	4%	33%
Died	15%	15%	30%	30%	55%	55%
Costs (€)	3473	0	5816	0	8223	0
QALYs	3.64	3.15	6.36	5.49	9.45	8.14
Cost (€) difference	3473		5816		8223
QALY difference	0.49		0.87		1.31
ICER (€)	7036		6666		6312

ICER, Incremental cost-effective ratio; MMS, Minimicrospheres; PEI, Pancreatic exocrine insufficiency; QALY, Quality-Adjusted Life Year; SA, Sensitivity analysis.

Table 4.  One-way sensitivity analysis results.

Parameter	SA value	ICER (€)
	Min	Max	Run 1	Run 2
Base case	–	–	6,312	6,312
Pancreatin MMS; Controlled to controlled after 1 year	81%	100%	−84,299	6,312
No PERT treatment; Uncontrolled to controlled after 1 year	0%	10%	6,312	28,422
Utility uncontrolled PEI	0.18	0.71	1,654	6,312
Utility controlled PEI	0.85	0.95	8,567	4,997
No PERT treatment; Controlled to controlled after 1 year	81%	100%	4,704	6,312
Conversion rate	0.208	0.255	5,681	6,944
Dose increase (same for Pancreatin MMS 40,000 and 25,000 lipase units)	0	3	5,700	6,619
Pancreatin MMS; Uncontrolled to controlled after 1 year	12%	66%	6,801	5,892
Time at which uncontrolled patients receive increased dose	2	52	6,804	6,006
Time after which uncontrolled Pancreatin MMS patients discontinue	2	260	6,250	6,609
% uncontrolled patients receiving increased dose after 26 weeks	0%	100%	6,006	6,312
% uncontrolled patients discontinuing Pancreatin MMS after 52 weeks	0%	100%	6,614	6,312
Mortality	37%	62%	6,237	6,334
Discounting on cost and outcome	0%	5%	6,918	6,970

ICER, incremental cost-effectiveness ratio; MMS, Minimicrospheres; PEI, Pancreatic exocrine insufficiency; PERT, Pancreatic enzyme replacement therapy; SA, Sensitivity analysis.

The minimum (Min) and maximum (Max) values used for each model input parameter in the SA as well as the resulting ICERs of the analysis are provided in the table. Run 1 ICER results correspond to minimum value input parameters whereas Run 2 outcomes correspond to maximum value input parameters. Parameters are ordered from most influential (top) to least influential (bottom) based on SA results.

Table 5.  Probabilistic sensitivity analysis results.

Result	Incremental cost (€)	Incremental QALYs	ICER (€)
Base case	8223	1.30	6,312
PSA mean	8025	1.43	13,425
PSA median	8392	1.39	5,659
SD	769	0.81	115,363
95% CI	5830–8652	1.08–1.67	Dominated – 2,258
Min/max	4390–8809	−2.07–4.61	Dominated – 1,824

CI, confidence interval; MMS, Minimicrospheres; QALY, Quality-Adjusted Life Year; PSA, Probabilistic sensitivity analysis; SD, Standard deviation.

Table 6.  Scenario analysis results based on stool fat excretion below 10 g/day.

Stool fat below 10 g/day	Pancreatin MMS	No PERT treatment
Controlled PEI	0%	0%
Uncontrolled PEI	45%	45%
Dead Patients	55%	55%
Costs (€)	1,616	0
QALYs	7.70	7.61
Cost (€) difference	1,616
QALY difference	0.09
ICER	17,443

ICER, Incremental cost-effective ratio; MMS, Minimicrospheres; PEI, Pancreatic exocrine insufficiency; QALY, Quality-Adjusted Life Year.

Controlled CP-related PEI was defined as stool fat excretion < 10 g/day.

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