Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Abnormal LFTs; Grade 3 or 4 toxicity	4		Risk Ratio (M-H, Fixed, 95% CI)	Subtotals only
1.1 Alanine aminotransferase (ALT)	4	3523	Risk Ratio (M-H, Fixed, 95% CI)	4.17 [1.38, 12.62]
1.2 Aspartate aminotransferase (AST)	4	3528	Risk Ratio (M-H, Fixed, 95% CI)	4.08 [1.17, 14.26]
1.3 Alkaline phosphatase (ALP)	3	2606	Risk Ratio (M-H, Fixed, 95% CI)	0.62 [0.15, 2.51]
1.4 Bilirubin	3	3067	Risk Ratio (M-H, Fixed, 95% CI)	1.92 [0.59, 6.24]
2 Combined abnormal LFTs	3		Risk Ratio (M-H, Fixed, 95% CI)	Subtotals only
2.1 ALT = 3 x ULN and Bilirubin = 2 x ULN (Hy's Law case)	3	3072	Risk Ratio (M-H, Fixed, 95% CI)	1.50 [0.30, 7.42]
3 Renal function tests	3		Mean Difference (IV, Fixed, 95% CI)	Subtotals only
3.1 Baseline	3	1878	Mean Difference (IV, Fixed, 95% CI)	-0.12 [-2.07, 1.84]
3.2 Day 3	2	1764	Mean Difference (IV, Fixed, 95% CI)	-1.72 [-3.54, 0.10]
3.3 Day 7	3	1808	Mean Difference (IV, Fixed, 95% CI)	-2.76 [-4.58, -0.94]
4 Haemoglobin	4		Mean Difference (IV, Fixed, 95% CI)	Subtotals only
4.1 Haemoglobin at baseline	4	3534	Mean Difference (IV, Fixed, 95% CI)	0.08 [-0.04, 0.21]
4.2 Haemoglobin day 3	4	3461	Mean Difference (IV, Fixed, 95% CI)	-0.12 [-0.20, -0.04]
4.3 Haemoglobin day 7	4	3394	Mean Difference (IV, Fixed, 95% CI)	-0.24 [-0.32, -0.16]
4.4 Haemoglobin day 28	4	3294	Mean Difference (IV, Fixed, 95% CI)	-0.09 [-0.19, 0.01]
5 Abnormal ECG findings	3		Risk Ratio (M-H, Fixed, 95% CI)	Subtotals only
5.1 ECG abnormalities	2	2543	Risk Ratio (M-H, Fixed, 95% CI)	0.80 [0.26, 2.43]
5.2 QT prolongation	3	2991	Risk Ratio (M-H, Fixed, 95% CI)	0.25 [0.07, 0.90]