Table 2.

Parameters used for base case analysis

Parameters	Both	Ibrutinib	Comparator	Value	Reference	Comments
Health utilities (yearly), QALYs per life-year
PFS on initial therapy		0.71	0.67		29
PFS not on therapy after initial therapy			0.82		29
Progressed, awaiting second-line therapy	0.66				29
PFS on second-line therapy	0.55				29
PFS completed second-line therapy	0.71				29
Progressed, awaiting third-line therapy	0.59				29
PFS on third- or greater-line therapy	0.42				29
PFS completed third-line therapy	0.59				29
Receiving best supportive care/hospice	0.59				29
Drug cost-related
AWP for drugs on patent, %				64	25,26	VA HERC recommendations
AWP for drugs off patent, %				27	25,26	VA HERC recommendations
Ibrutinib per month, $				8 527.04	9	64% of AWP from Redbook Online; 420 mg/d
Comparator (obinutuzumab) month 1, $				17 227.50	50	Medicare Part B maximum payment allowance
					12	3000 mg (see supplemental Appendix for further details)
Comparator (obinutuzumab) months 2-6, $				5 742.50	50	Medicare Part B maximum payment allowance
					12	1000 mg/mo
Comparator (chlorambucil) per month, $				249.60	51	27% of AWP from RedBook Online
Administration costs comparator month 1, $				1 080.99		See supplemental Appendix for further details
Administration costs comparator months 2-6, $				263.07
Patients receiving ibrutinib as initial therapy at 29 months, %				79	6	Additional patients were modeled to come off therapy without progressing. At 28.5-mo median follow-up, 79% of patients were receiving ibrutinib. Seven of 22 go on to receive bendamustine plus rituximab (see supplemental Table 3 for further details).
Patients stopping oral salvage therapy in first 9 months, %				5.6	4	These patients were modeled to come off therapy without progressing; 11 of 195 patients stopped therapy for reasons other than progression or death at median follow-up of 9.4 months.
Patients experiencing grade 3 or 4 AEs during trial, %
Diarrhea		7	0
Anemia		6	4
Neutropenia		10	37
Thrombocytopenia		2	10
Infections (eg, pulmonary nodular amyloidosis)		10	12
Infusion-related reaction		0	20
Hyponatremia		3	0
Rash		3	0
Atrial fibrillation
Grade 3 or 4		4*	1.6†
Chronic		107	421

AEs were included for all drugs if the incidence was 3% or higher for any drug as reported in any trial used for this analysis. Ibrutinib AEs were modeled based on Burger et al,⁵ except atrial fibrillation, which was based on the incidence reported by Hillmen et al.⁷ For the comparator, atrial fibrillation was not reported as an AE in Goede et al,¹² so rates based on the age-matched general population were used.²¹ Probabilities for AEs were adjusted for median time on therapy for respective trial (see supplemental Figure 7). See supplemental Appendix for costs and dysutilities associated with AEs. Median time receiving therapy from respective trials was 18.4 months for ibrutinib and 6 months for the comparator. “Both” refers to ibrutinib and comparator.

PFS, progression-free survival; VA HERC, Veterans Affairs Health Economics Resource Center.

^*At 29-month follow-up.⁷

^†Per 29 months.