Table 2.

Estimated group sizes required to detect cytokine release with different CRA methods with a power of 90%: Group size requirements for human PBMC SP, PBMC HDC, WB and 10% (v/v) WB CRA, WB SP and 10% (v/v) WB SP were calculated for paired t-tests on log transformed data to compare each therapeutic mAb against IgG1 isotype control, with the exception of TGN1412 which was compared to IgG4κ isotype control and a CD28 agonist*. All therapeutic mAb and cytokine response combinations were assumed to have equally variable responses for each CRA method and the standard deviations used for the calculations were pooled standard deviations (all 6 cytokine responses for the different therapeutic mAbs). The group sizes given for each therapeutic mAb would detect the difference observed in cytokine release for each CRA method with a power of 90% at the 5% significance level.

CRA method	Power analysis	Alemtuzumab	Muromonab-CD3	TGN1412	TGN1412*
PBMC SP	Relative mean	1.2	32.9	110.9	71.8
Group size required	180	4	4	5
PBMC HDC	relative mean	1.5	4.0	4.4	6.7
Group size required	341	31	27	19
WB	Relative mean	5.5	0.9	2.2	1.7
Group size required	8	4519	52	117
10% (v/v) WB	Relative mean	1.5	13.7	2.1	0.7
Group size required	114	9	79	284
WB SP	Relative mean	0.9	3.4	3.4	4.3
Group size required	5069	43	13	13
10% (v/v) WB SP	Relative mean	1.8	24.3	2.4	1.4
Group size required	66	8	46	313