Table 2.

Clinical inputs in the simulation model.

Clinical inputs	Time period	Initiate LUM/IVA + SC at:		SC	Source
		Aged 6–11 years	Aged⩾12 years
Treatment effects
ppFEV1 mean change from baseline	Weeks 1–24	2.4	2.8*	0.0	Wainwright et al.;10 Ratjen et al.18
PEx event rate ratio versus SC	Lifetime	1.00 for aged 6–11; 0.44 for aged ⩾12	0.44	–	Assumption, Wainwright et al.10
Weight-for-age Z score mean change from baseline	Weeks 1–104	0.066**	0.066**	−0.060**	Konstan et al.13
Annual change in absolute ppFEV1 by age, years$	Weeks 24+
6–8		−0.65	N/A	−1.12	Konstan et al.22
9–12		−1.39	−1.39	−2.39	Konstan et al.22
13–17		−1.36	−1.36	−2.34	Konstan et al.22
18–24		−1.11	−1.11	−1.92	Konstan et al.23
25+		−0.84	−0.84	−1.45	Konstan et al.23
Treatment discontinuation
LUM/IVA discontinuation rate‡	Weeks 1–24	0.13	0.15	–	VX14-809-109 and Wainwright et al.10
LUM/IVA discontinuation rate‡	Weeks 24–96	0.14	0.14	–	VX14-809-109 and Konstan et al.13
Lung transplant
ppFEV1 threshold	Lifetime	30	30	30	American Thoracic Society guidelines33
Eligible patients who receive transplant, %	Lifetime	26.8	26.8	26.8	US CFFPR report2
Postlung-transplant annual mortality risk, %	First year following transplant	15.2	15.2	15.2	ISHLT34
	Subsequent years	5.7	5.7	5.7	ISHLT34

^*Applied at week 16 and held constant through week 24.

^**Patients receiving LUM/IVA + SC increase 0.033 per year for 2 years, whereas patients on SC decline by 0.030 per year for 2 years.

^$LUM/IVA treatment effect on ppFEV₁ decline (i.e. 42% reduction) was reported by Konstan et al.¹³

^‡Rate was measured as event rate per patient-year.

CFFPR, Cystic Fibrosis Foundation Patient Registry; ISHLT, International Society for Heart and Lung Transplantation; LUM/IVA, lumacaftor/ivacaftor; N/A, not applicable; PEx, pulmonary exacerbation; ppFEV₁, percent predicted forced expiratory volume in 1 second; SC, standard care.