Table 2.

(a) Sample size calculations for a randomized, controlled trial and change in ppFEV₁. Note that standard deviation (SD) estimates for the change in ppFEV₁ are generally stable over time so these estimates apply independent of duration of the trial. Careful consideration will be necessary to inform the baseline lung function eligibility criteria for a given trial, balancing enrichment for a population that may have more perceived room for improvement with the need to enable a more expansive development population (e.g., by not having an upper limit of 90% for ppFEV₁ as an eligibility criteria). (b) Sample size calculations for a one-year randomized, placebo-controlled trial and reduction in rate of CF pulmonary exacerbations (PEx). PEx rate of 1.0/year reflects rates in the absence of CFTR modulators and 0.3 reflects expect rates in the presence of CFTR modulators. Sample size estimates based on ppFEV₁ variability and PEx rates from(9, 10).

(a)
	Total Sample Size – ppFEV1 Endpoint (assuming one-sided 0.025 α)
	80% Power		90% Power
Treatment Effect (Active – Control)	SD=6	SD=8	SD=6	SD=8
3%	126	224	170	300
4%	72	126	96	170
5%	46	82	62	108
7%	24	42	32	56
10%	12	22	16	28
(b)
	Total Sample Size – PEx Endpoint (assuming one-sided 0.025 α)
	80% Power		90% Power
Treatment Effect (Rate Ratio)	Placebo Rate 0.3/yr	Placebo Rate 1.0/year	Placebo Rate 0.3/yr	Placebo Rate 1.0/year
0.5	316	104	426	140
0.55	406	136	548	182
0.6	536	178	722	240
0.65	728	242	978	326
0.7	1028	344	1380	460
0.75	1532	514	2054	688