Table 1.

Clinical characteristics of the included subjects and precautionary drug exposure

Algorithm	CLEAR $C_l^{\text{DE pairs}}$	MetaLAB ${\text{ML}}_l^{\text{DE pairs}}$	MetaLAB ${\text{ML}}_L^{\text{RS}}$	MetaNurse ${\text{MN}}_N^{\text{RS}}$
Gold standard for ADRs	DE pairsa		RS-ADR
Type of ADR signals	Predefined laboratory abnormalities		MedDRA PTs
No. of target drugs	10		101
No. of ADR signals	47 (from 40 tests)		117 (from 48 tests)	757 (from 1357 SNSs)
No. of drug-ADR pairs	470		11 817	76 457
No. of positive pairsb	221		2210	34 857
No. of negative pairsc	249		9607	41 600
AUC, not integratedd,e	0.55 ± 0.06	0.61 ± 0.18	0.69 ± 0.11	0.62 ± 0.07
AUC, SOC-integratedf	–	–	0.84 ± 0.13	0.84 ± 0.09
No. of patients	68 769	88 038	215 088	220 954
No. of exposure casesg	90 804	127 171	1 028 724	1 187 037
Age (years)h	51.3 ± 18.9	50.7 ± 19.9	46.5 ± 23.0	46.22 ± 23.1
Female, n (%)i	38 290 (55.67)	47 470 (53.91)	108 410 (50.40)	110 864 (50.17)
Disease severity, n (%)j
1	22 755 (33.08)	29 706 (33.74)	106 997 (49.74)	111 410 (50.42)
2	29 225 (42.49)	37 611 (42.72)	82 306 (38.26)	83 422 (37.75)
3	10 485 (15.24)	12 619 (14.33)	19 238 (8.94)	19 824 (8.97)
4	3306 (4.80)	4167 (4.73)	4130 (1.92)	4025 (1.82)
5	2882 (4.19)	3747 (4.25)	2304 (0.01)	2174 (0.09)
6	116 (0.16)	188 (0.21)	113 (0.0005)	99 (0.0004)

^aPredefined DE pairs for 10 drugs and 47 laboratory abnormalities reported by Yoon et al.¹³

^bPositive pairs were established by expert review, and the remaining pairs were considered to be ^cNegative DE pairs.

^dAUCs were computed by considering all the drugs and ADRs as a single dataset.

^eCLEAR significantly outperformed MetaCLEAR (DeLong’s test for 2 ROC curves, P = .0137).

^fAUCs were computed for each MedDRA SOC by stratifying ADRs and then integrating.

^gNumbers of patient exposures to target drugs were summed by separately counting the exposures of each patient to different target drugs.

^hAge differed significantly between CLEAR and MetaLAB (P = .01) and between MetaLAB and MetaNurse (P = 4.68 × 10^–7) in Student t test.

ⁱGender did not differ significantly between the comparison groups (P = .89 and .93).

^jDisease severity did not differ significantly between CLEAR and MetaLAB (P = .029), but it did differ significantly between MetaLAB and MetaNurse (P = 3.09 × 10^–6) in Fisher’s exact test.