Impact of patient adherence on the cost-effectiveness of noninvasive tests for the initial diagnosis of Helicobacter pylori infection in the United States

Figures & data

Figure 1 Decision-tree model.

Abbreviations: adh, adherence; erad, eradication; FN, false negative; FP, false positive; p, probability; prev, prevalence; QALYs, quality-adjusted life-years; TN, true negative; TP, true positive; Tx, treatment.

Table 1 Population characteristics, treatment attributes, and data for diseases related to Helicobacter pylori infection

Parameter	Value	Variability (range)	Source
Population
H. pylori prevalence, %	37.4	33.32–41.55	Point estimate based on Cardenas et al;^Citation19 range for SA based on ±20% (assumption)
Expected life-years at age 35 years*	43.6	34.86–52.28	Point estimate from Arias et al;^Citation20 range for SA based on ±20% (assumption)
Treatment attributes
First-line triple therapy for 14 days
Efficacy, %	81	77–85	Calvet et al^Citation18
Cost, US$	205.85	164.68–247.02	Truven Health Analytics^Citation26 for omeprazole, amoxicillin, and clarithromycin for 14 days
Physician visit cost (CPT codes 99214+99244), US$
PCP visit	107.83	86.26–129.4	Point estimate from OptumInsight;^Citation25 range for SA based on ±20% (assumption)
GI visit	185.92	148.74–223.1	Same as PCP visit
H. pylori-related disease parameters
Lifetime H. pylori-positive outcome probability, %
Gastric cancer	1	0.5–1.5	Point estimate from Kuipers;^Citation27 range for SA based on ±50% (assumption)
PUD	15	10–20	Point estimate from Peterson et al;^Citation4 range for SA based on ±33.33% (assumption)
Dyspepsia	100	80–100	Clinical expert’s input
Lifetime H. pylori-negative outcome probability, %
Gastric cancer	0.1	0.08–0.12	Point estimate based on Kuipers^Citation27 and Kusters et al;^Citation3 range for SA based on ±20% (assumption)
PUD	3.8	3–4.5	Point estimate based on Laine et al^Citation28 and Peterson et al;^Citation4 range for SA based on ±20% (assumption)
Dyspepsia	16.5	6–24	Point estimate based on Kusters et al;^Citation3 range for SA based on range reported in Kusters et al^Citation3
Median survival, years
Gastric cancer	2	1.37–2.05	Point estimate based on Davies et al;^Citation29 range for SA based on ±20% (assumption)
Disease duration
Average time elapsed between diagnosis of	H. pylori	infection and diagnosis of:
Gastric cancer, years	15	12–18	Estimated based on Asaka et al^Citation30 and Davies et al^Citation29
Dyspepsia, years	1.55	1.24–1.86	Point estimate based on Chiba et al;^Citation31 range for SA based on ±20% (assumption)
PUD, years	0.5	0.25–0.75	Assumption based on discussion with clinical consultant
Hospitalization due to PUD, days	4.3	3.44–5.16	HCUP with an ICD-9 code of 578.9 (hemorrhage of gastrointestinal tract); range for SA based on ±20% (assumption)
Utility values
Gastric cancer	0.49	0.17–0.79	Yeh et al;^Citation32 range for SA reported in Yeh et al^Citation32
PUD	0.92	0.81–0.96	Howard et al;^Citation33 range for SA reported in Howard et al^Citation33
GI hospitalization due to PUD	0.50	0.4–0.6	Point estimate from Erstad;^Citation34 range for SA based on ±20% (assumption)
Chronic dyspepsia	0.97	0.74–0.98	Point estimate from You et al;^Citation35 range for SA reported in You et al^Citation35
Associated costs, US$
Gastric cancer	48,159	44,141–52,086	Estimated based on Yabroff et al^Citation36 and Davies et al;^Citation29 range based on 95% CI reported in Yabroff et al^Citation36
PUD (managed with medication)	481	385–578	Estimated based on Slawsky et al;^Citation37 range for SA based on ±20% (assumption)
Hospitalization due to PUD	8,896	7,117–10,675	HCUP with an ICD-9 code of 578.9; range for SA based on ±20% (assumption)
Dyspepsia	481	385–578	Estimated based on Slawsky et al;^Citation37 range for SA based on ±20% (assumption)
Reduced QALYs and excess lifetime costs
Estimated reduced QALYs	6.79	3.82–9.44	Point estimate derived using the H. pylori-related disease parameters listed (gastric cancer, PUD and dyspepsia); range for SA estimated from Monte Carlo simulations (generated by sampling from intervals of uncertainty around H. pylori-related disease parameters)
Estimated excess LTCs, US$	965	685.51–1,128.21	Same as estimated reduced QALYs

Note:

* Life expectancy at age 35 years, which was approximately the midpoint of the age-range of the patient population.

Abbreviations: CI, confidence interval; CPT, Current Procedural Terminology; GI, gastrointestinal; HCUP, Healthcare Cost and Utilization Project; ICD, International Classification of Diseases; LTCs, lifetime costs; PCP, primary care physician; PUD, peptic ulcer disease; QALYs, quality-adjusted life-years; SA, sensitivity analysis.

Table 2 Test characteristics

Parameter	Value	Variability (range)	Source
UBT (CPT codes 83013+83014)
Sensitivity, %	97.3	77.86–100	Point estimate based on Gisbert and Pajares;^Citation16 range for SA based on ±20% (assumption; upper bound truncated at 100%)
Specificity, %	96.7	77.37–100	Same as UBT sensitivity
Adherence, %	86.2	68.96–100	Point estimate based on Cullen et al;^Citation13 range for SA based on ±20% (assumption; upper bound truncated at 100%)
Cost, US$	102.81	82.25–123.37	Point estimate derived from OptumInsight;^Citation25 range for SA based on ±20% (assumption)
Monoclonal FAT (CPT code 87338)
Sensitivity, %	96	76.8–100	Point estimate from Gisbert and Pajares;^Citation12 range for SA based on ±20% (assumption; upper bound truncated at 100%)
Specificity, %	97	77.6–100	Same as monoclonal FAT sensitivity
Adherence, %	48.3	38.64–57.96	Point estimate based on Cullen et al;^Citation13 range for SA based on ±20% (assumption)*
Cost, US$	19.7	15.76–23.64	Point estimate derived from OptumInsight;^Citation25 range for SA based on ±20% (assumption)
Polyclonal FAT (CPT code 87338)
Sensitivity, %	91	90–91	Point estimate from Gisbert and Pajares;^Citation12 range for SA reported in Gisbert and Pajares^Citation12
Specificity, %	93	93–94	Same as polyclonal FAT sensitivity
Adherence, %	48.3	38.64–57.96	Point estimate based on Cullen et al;^Citation13 range for SA based on ±20% (assumption)*
Cost, US$	19.7	15.76–23.64	Point estimate derived from OptumInsight;^Citation25 range for SA based on ±20% (assumption)
Serology (CPT code 86677)
Sensitivity, %	85	68–100	Point estimate from Loy et al;^Citation17 range for SA based on ±20% (assumption; upper bound truncated at 100%)
Specificity, %	79	63.2–94.8	Same as serology sensitivity
Adherence, %	86.2	68.96–100	Point estimate based on assumption and range for SA based on ±20% (assumption; upper bound truncated at 100%)
Cost, US$	19.7	15.7–23.64	Point estimate derived from OptumInsight;^Citation25 range for SA based on ±20% (assumption)

Note:

* For the purposes of scenario analysis we describe how the incremental cost-effectiveness ratio changes across a monoclonal and polyclonal FAT adherence range of 0.2–0.8 to provide a more complete assessment of the effects of adherence.

Abbreviations: CPT, Current Procedural Terminology; FAT, fecal antigen test; SA, sensitivity analysis; UBT, urea breath test.

Table 3 Base-case economic and health outcomes

Outcome	UBT	Monoclonal FAT	Serology
Economic outcomes/patient, US$
Total costs	424.99	466.41	404.98
Tests	88.62	9.52	16.98
Physician visits	146.88	146.88	146.88
First-line eradication therapy	79.25	77.85	92.55
Excess lifetime costs	110.24	232.17	148.57
Incremental outcomes
Costs/accurately diagnosed case, US$	508.58	999.38	578.25
ICER, US$/QALY gained, UBT vs test*	–	UBT dominant	74.20
UBT cost-effective in comparison with test?	–	Yes	Yes
Health outcomes/patient
Cases accurately diagnosed as positive (n)	0.31	0.17	0.27
Cases accurately diagnosed as negative (n)	0.52	0.29	0.43
Reduced QALYs due to continued H. pylori infection	0.78	1.63	1.05

Notes:

* In cases where the UBT was both less costly and more effective than another test (ie, FAT), the UBT was considered “dominant”; in cases where the UBT was more costly and more effective than another test (ie, serology), the ICER was below the commonly cited threshold for willingness to pay US$50,000/QALY gained.

Abbreviations: FAT, fecal antigen test; ICER, incremental cost-effectiveness ratio; QALY, quality-adjusted life-year; UBT, urea breath test.

Figure 2 Effect of adherence and prevalence.

Abbreviations: FAT, fecal antigen test; ICER, incremental cost-effectiveness ratio; QALY, quality-adjusted life-year; UBT, urea breath test.

Figure 3 Cost-effectiveness scatterplots for comparisons of urea breath test with (A) monoclonal fecal antigen test and (B) serology.

Abbreviations: PSA, probabilistic sensitivity analysis; QALYs, quality-adjusted life-years.

Table S1 Estimation of excess lifetime costs associated with peptic ulcer disease

Calculation step	Equation	Estimate
Excess lifetime costs associated with PUD due to continuing H. pylori infection, US$	(LTCPUD=(p)PUD[w] − pPUD[w])*CPUD	28.09
Expected cost/patient with PUD	CPUD=Cmed+Chosp	249.65
Expected cost/patient of PUD-related hospitalization	Chosp=PPUD[hosp]*CPUD[hosp]	8.9
Cost of GI hospitalization event due to PUD	CPUD[hosp]	8,896
Probability of GI hospitalization event due to PUD, %	pPUD[hosp]	0.1
Expected cost/patient of PUD regardless of hospitalization (managed by medication), US$	Cmed = tPUD[med]*CPUD[med]	240.75
Duration of PUD, years	tPUD[med]	0.5
Cost/year of managing PUD with medication, US$	CPUD[med]	481.5
Excess lifetime risk of PUD due to continuing H. pylori infection, %	pPUD[w] − pPUD[wo]	11.25
Lifetime risk of developing PUD with continuing H. pylori infection	pPUD[w]	15
Lifetime risk of developing PUD without continuing H. pylori infection	pPUD[wo]	3.75

Abbreviations: C, cost; GI, gastrointestinal; hosp, hospitalization; LTC, lifetime cost; med, medication; P, patient; PUD, peptic ulcer disease; t, duration; w, with H. pylori; wo, without H. pylori.

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