Supplemental digital content-Figure 1



Supplemental digital content-Figure 1. Evaluation of consistency for the network meta-analysis. The plot of posterior mean deviance of the individual data points in the consistency model against that of unrelated mean effects model for the network meta-analysis of IPSS (A) and PUF(B).

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Supplemental digital content-Figure 2. Evaluation of the risk of publication bias.

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Supplemental Digital Content-Table 1. Characteristics of included studies.

|Study |Intervention,dose (number of patients) |Cou|Mean age(year) |

| | |ntr| |

| | |y | |

| |Pairwise meta-analysis | |Network meta-analysis | |Pairwise meta-analysis | |Network meta-analysis |

| |Studies(Patients), MD(95%CI) | |MD(95%CI) | |Studies(Patients), MD(95%CI) | |MD(95%CI) |

|Placebo | | | | | | | |

|Alfuzosin |5(2627), -1.71(-2.14 to -1.29) | |-2.07(-2.66 to -1.49) | |9(3195), 1.09(0.81 to 1.36) | |1.07(0.78 to 1.38) |

|Doxazosin |3(1639), -2.83(-3.60 to -2.07) | |-3.67(-4.33 to -3.02) | |7(1983), 1.89(1.53 to 2.25) | |1.95(1.61 to 2.30) |

|Tamsulosin |9(4161), -2.09(-2.60 to -1.59)a | |-2.13(-2.56 to -1.71) | |9(4596), 0.95(0.69 to 1.20) | |1.07(0.83 to 1.32) |

|Terazosin |2(2489), -3.76(-4.30 to -3.22) | |-3.37(-4.24 to -2.50) | |6(1185), 0.97(0.20 to 1.75) | |1.21(0.74 to 1.66) |

|Silodosin |2(1479), -2.60(-3.18 to -2.01) | |-2.44(-3.24 to -1.64) | |2(1479), 0.96(0.57 to 1.35) | |0.93(0.45 to 1.42) |

|Naftopidil |NA | |-2.03(-3.02 to -1.04) | |NA | |1.05(0.29 to 1.80) |

|Finasteride |10(10 672), -1.09(-1.44 to -0.74) | |-1.35(-1.87 to -0.83) | |14(7064), 1.03(0.77 to 1.29) | |0.85(0.61 to 1.10) |

|Dutasteride |4(14 266), -1.93(-2.17 to -1.68) | |-1.82(-2.51 to -1.12) | |4(9277), 1.29(0.92 to 1.67) | |1.43(1.05 to 1.82) |

|Tolterodine |1(419),-0.60(-1.56 to 0.36) | |-0.86(-2.20 to 0.48) | |2(654), -0.24(-1.06 to 0.58) | |-0.02(-1.06 to 1.03) |

|Solifenacin |1(215),-0.30(-1.72 to 1.12) | |-0.30(-2.50 to 1.92) | |NA | |NA |

|Tadalafil |9(6436), -2.09(-2.40 to -1.78) | |-1.87(-2.44 to -1.29) | |11(4875), 0.23(-0.04 to 0.51) | |0.43(0.06 to 0.79) |

|Sildenafil |1(336), -4.40(-6.93 to -1.87) | |-3.15(-5.29 to -1.01) | |1(366), 0.15(-0.87 to 1.17) | |0.52(-0.50 to 1.54) |

|Vardenafil |1(214), -2.20(-3.94 to -0.46) | |-2.18(-4.61 to 0.25) | |1(214), 0.60(-1.01 to 2.21) | |0.58(-1.18 to 2.38) |

|Alfuzosin | | | | | | | |

|Doxazosin |1(179), -1.70(-3.36 to -0.04) | |-1.60(-2.43 to -0.78) | |1(146), 0.10(-1.15 to 1.35) | |0.87(0.44 to 1.31) |

|Tamsulosin |4(683), -0.09(-0.74 to 0.56) | |-0.06(-0.71 to 0.59) | |4(687), 0.39(-0.14 to 0.92) | |0.00(-0.35 to 0.35) |

|Terazosin |NA | |-1.30(-2.30 to -0.26) | |NA | |0.14(-0.40 to 0.66) |

|Silodosin |NA | |-0.37(-1.33 to 0.58) | |NA | |-0.14(-0.70 to 0.42) |

|Naftopidil |NA | |0.04(-1.07 to 1.17) | |NA | |-0.02(-0.82 to 0.77) |

|Finasteride |1(684), 0.90(0.04 to 1.76) | |0.72(-0.01 to 1.47) | |1(702), -0.45(-1.07 to 0.17) | |-0.22(-0.59 to 0.15) |

|Dutasteride |NA | |0.25(-0.63 to 1.15) | |NA | |0.36(-0.13 to 0.84) |

|Tolterodine |NA | |1.21(-0.25 to 2.67) | |NA | |-1.09(-2.16 to -0.01) |

|Solifenacin |NA | |1.77(-0.53 to 4.07) | |NA | |NA |

|Tadalafil |1(37), 3.90(1.03 to 6.77) | |0.20(-0.59 to 1.01) | |1(37), -0.50(-3.59 to 2.59) | |-0.65(-1.13 to -0.18) |

|Sildenafil |1(336), -0.20(-2.65 to 2.25) | |-1.08(-3.23 to 1.08) | |1(41), -0.50(-2.50 to 1.50) | |-0.55(-1.59 to 0.49) |

|Vardenafil | | |-0.11(-2.62 to 2.39) | |NA | |-0.49(-2.28 to 1.32) |

|Doxazosin | | | | | | | |

|Tamsulosin |7(912), 2.41(1.27 to 3.55)b | |1.54(0.89 to 2.19) | |4(548), -0.83(-1.40 to -0.26) | |-0.88(-1.25 to -0.49) |

|Terazosin |1(50), 0.70(-2.01 to 3.41) | |0.30(-0.71 to 1.33) | |1(50), -0.90(-2.30 to 0.50) | |-0.73(-1.30 to -0.19) |

|Silodosin |NA | |1.23(0.27 to 2.20) | |NA | |-1.01(-1.60 to -0.43) |

|Naftopidil |NA | |1.64(0.54 to 2.75) | |NA | |-0.90(-1.72 to -0.07) |

|Finasteride |1(489), 1.70(0.59 to 2.81) | |2.32(1.54 to 3.10) | |2(2013), -1.22(-2.19 to -0.25)d |-1.09(-1.48 to -0.71) |

|Dutasteride |NA | |1.85(0.92 to 2.79) | |NA | |-0.51(-1.03 to 0.00) |

|Tolterodine |NA | |2.81(1.36 to 4.29) | |NA | |-1.97(-3.07 to -0.88) |

|Solifenacin |NA | |3.37(1.06 to 5.70) | |NA | |NA |

|Tadalafil |NA | |1.80(0.96 to 2.66) | |NA | |-1.52(-2.02 to -1.02) |

|Sildenafil |NA | |0.52(-1.72 to 2.73) | |NA | |-1.42(-2.51 to -0.36) |

|Vardenafil |NA | |1.49(-1.03 to 4.03) | |NA | |-1.36(-3.15 to 0.44) |

|Tamsulosin | | | | | | | |

|Terazosin |4(398), -0.90(-3.21 to 1.41)c | |-1.24(-2.13 to -0.34) | |4(369), -0.25(-0.98 to 0.49) | |0.14(-0.35 to 0.61) |

|Silodosin |5(1195), -0.42(-1.18 to 0.35) | |-0.31(-1.06 to 0.44) | |4(1113), -0.10(-0.73 to 0.53) | |-0.14(-0.63 to 0.36) |

|Naftopidil |7(562), 0.45(-0.50 to 1.41) | |0.10(-0.81 to 1.02) | |6(451), 0.01(-0.53 to 0.54) | |-0.02(-0.75 to 0.70) |

|Finasteride |2(605), 0.72(-0.25 to 1.68) | |0.78(0.17 to 1.40) | |2(605), -0.21(-0.91 to 0.49) | |-0.22(-0.54 to 0.10) |

|Dutasteride |1(3174), 0.30(-0.12 to 0.72) | |0.31(-0.45 to 1.10) | |2(411), 0.76(0.04 to 1.47) | |0.36(-0.08 to 0.79) |

|Tolterodine |1(403), 1.00(0.22 to 1.78) | |1.27(-0.07 to 2.61) | |1(413), -0.38(-1.19 to 0.43) | |-1.09(-2.17 to 0.00) |

|Solifenacin |NA | |1.83(-0.43 to 4.10) | |NA | |NA |

|Tadalafil |2(645), 0.16(-1.20 to 1.53) | |0.26(-0.41 to 0.93) | |1(296), -0.50(-1.61 to 0.61) | |-0.64(-1.09 to -0.21) |

|Sildenafil |NA | |-1.02(-3.21 to 1.16) | |1(40), 0.80(-1.53 to 3.13) | |-0.55(-1.58 to 0.47) |

|Vardenafil |NA | |-0.05(-2.52 to 2.43) | |NA | |-0.49(-2.26 to 1.34) |

|Terazosin | | | | | | | |

|Silodosin |NA | |0.93(-0.21 to 2.09) | |NA | |-0.28(-0.92 to 0.37) |

|Naftopidil |NA | |1.34(0.06 to 2.63) | |NA | |-0.16(-1.01 to 0.73) |

|Finasteride |1(535), 2.80(1.79 to 3.81) | |2.02(1.07 to 2.98) | |1(527), -1.10(-1.61 to -0.59) | |-0.36(-0.84 to 0.14) |

|Dutasteride |NA | |1.55(0.46 to 2.65) | |NA | |0.22(-0.36 to 0.83) |

|Tolterodine |NA | |2.51(0.94 to 4.07) | |NA | |-1.23(-2.39 to -0.08) |

|Solifenacin |NA | |3.07(0.68 to 5.45) | |NA | |NA |

|Tadalafil |NA | |1.50(0.48 to 2.54) | |NA | |-0.79(-1.36 to -0.21) |

|Sildenafil |NA | |0.22(-2.10 to 2.51) | |NA | |-0.69(-1.79 to 0.45) |

|Vardenafil |NA | |1.19(-1.37 to 3.78) | |NA | |-0.63(-2.46 to 1.21) |

|Silodosin | | | | | | | |

|Naftopidil |1(91), -1.20(-4.07 to 1.67) | |0.41(-0.64 to 1.46) | |1(91), 0.70(-1.27 to 2.67) | |0.12(-0.73 to 0.95) |

|Finasteride |NA | |1.09(0.16 to 2.01) | |NA | |-0.08(-0.62 to 0.46) |

|Dutasteride |NA | |0.62(-0.40 to 1.67) | |NA | |0.50(-0.11 to 1.11) |

|Tolterodine |NA | |1.58(0.08 to 3.11) | |NA | |-0.95(-2.09 to 0.19) |

|Solifenacin |NA | |2.14(-0.23 to 4.48) | |NA | |NA |

|Tadalafil |NA | |0.57(-0.37 to 1.53) | |NA | |-0.51(-1.12 to 0.11) |

|Sildenafil |NA | |-0.71(-3.01 to 1.60) | |NA | |-0.41(-1.54 to 0.72) |

|Vardenafil |NA | |0.26(-2.29 to 2.83) | |NA | |-0.35(-2.17 to 1.52) |

|Naftopidil | | | | | | | |

|Finasteride |NA | |0.68(-0.41 to 1.78) | |NA | |-0.20(-0.98 to 0.58) |

|Dutasteride |NA | |0.21(-0.97 to 1.39) | |NA | |0.38(-0.44 to 1.24) |

|Tolterodine |NA | |1.17(-0.43 to 2.76) | |NA | |-1.07(-2.34 to 0.23) |

|Solifenacin |NA | |1.73(-0.71 to 4.16) | |NA | |NA |

|Tadalafil |NA | |0.16(-0.96 to 1.28) | |NA | |-0.62(-1.48 to 0.20) |

|Sildenafil |NA | |-1.13(-3.46 to 1.25) | |NA | |-0.53(-1.79 to 0.70) |

|Vardenafil |NA | |-0.15(-2.76 to 2.50) | |NA | |-0.47(-2.38 to 1.50) |

|Finasteride | | | | | | | |

|Dutasteride |1(1590), -0.30(-0.98 to 0.38) | |-0.47(-1.28 to 0.35) | |1(1573), 0.30(-0.25 to 0.85) | |0.58(0.14 to 1.02) |

|Tolterodine |NA | |0.49(-0.95 to 1.90) | |NA | |-0.87(-1.96 to 0.18) |

|Solifenacin |NA | |1.05(-1.25 to 3.34) | |NA | |NA |

|Tadalafil |NA | |-0.52(-1.28 to 0.25) | |NA | |-0.43(-0.85 to 0.00) |

|Sildenafil |NA | |-1.81(-4.01 to 0.41) | |NA | |-0.33(-1.40 to 0.71) |

|Vardenafil |NA | |-0.83(-3.31 to 1.66) | |NA | |-0.27(-2.06 to 1.54) |

|Dutasteride | | | | | | | |

|Tolterodine |NA | |0.96(-0.54 to 2.46) | |NA | |-1.45(-2.57 to -0.34) |

|Solifenacin |NA | |1.52(-0.83 to 3.84) | |NA | |NA |

|Tadalafil |NA | |-0.05(-0.94 to 0.84) | |NA | |-1.01(-1.54 to -0.47) |

|Sildenafil |NA | |-1.33(-3.58 to 0.90) | |NA | |-0.91(-1.99 to 0.18) |

|Vardenafil |NA | |-0.36(-2.88 to 2.18) | |NA | |-0.85(-2.70 to 0.98) |

|Tolterodine | | | | | | | |

|Solifenacin |NA | |0.56(-2.08 to 3.15) | |NA | | |

|Tadalafil |NA | |-1.01(-2.45 to 0.44) | |NA | |0.44(-0.68 to 1.56) |

|Sildenafil |NA | |-2.29(-4.83 to 0.20) | |NA | |0.54(-0.90 to 2.01) |

|Vardenafil |NA | |-1.32(-4.11 to 1.45) | |NA | |0.60(-1.46 to 2.69) |

|Solifenacin | | | | | | | |

|Tadalafil |NA | |-1.57(-3.87 to 0.76) | |NA | |NA |

|Sildenafil |NA | |-2.86(-5.93 to 0.25) | |NA | |NA |

|Vardenafil |NA | |-1.88(-5.19 to 1.44) | |NA | |NA |

|Tadalafil | | | | | | | |

|Sildenafil |NA | |-1.29(-3.49 to 0.93) | |NA | |0.10(-0.99 to 1.20) |

|Vardenafil |NA | |-0.31(-2.81 to 2.21) | |NA | |0.16(-1.65 to 2.01) |

|Sildenafil | | | | | | | |

|Vardenafil |NA | |0.98(-2.27 to 4.21) | |NA | |0.06(-1.96 to 2.10) |

|Heterogeneity identified: a. P=0.01 to I2= 58%; b. P 15 mL/s: Normal); MD to |

|Mean Difference; CI to Confidence Interval; NA to Not Available |

Supplemental Digital Content-Table 4. Meta-regression testing the similarity of network meta-analysis

|　 |IPSS | | |PUF | |

| |Regression coefficient |P-value | |Regression coefficient |P-value |

| |Mean(95%CI) | | |Mean(95%CI) | |

|Dosage |-0.08(-0.29 to 0.13) |0.43 | |0.00(-0.10 to 0.09) |0.95 |

|Age |0.07(-0.14 to 0.29) |0.52 | |-0.04(-0.10 to 0.02) |0.19 |

|Baseline IPSS |0.11(-0.07 to 0.29) |0.24 | |-0.14(-0.27 to 0.00) |0.05 |

|Baseline PUF |-0.07(-0.40 to 0.28) |0.71 | |0.16(-0.02 to 0.34) |0.07 |

|Treatment Duration |0.00(0.00 to 0.00) |0.82 | |0.00(0.00 to 0.00) |0.28 |

|Prostate-specific antigen |-0.66(-1.68 to 0.38) |0.21 | |0.07(-0.35 to 0.49) |0.75 |

|Prostatic volume |0.07(-0.14 to 0.29) |0.52 | |-0.04(-0.10 to 0.02) |0.19 |

|IPSS, International Prostate Symptom Score; PUF, Peak Urinary Flow Rate; CI, Confidence Interval. |

Supplemental Digital Content- Table 5. Evaluation of consistency between direct comparisons and indirect comparisons.

| |IPSS | | |PUF | |

| |Consistent model |Unrelated mean effects model |　 |Consistent model |Unrelated mean effects model |

|totresdev |212.9 |217.4 | |232.8 |231.9 |

|pD |170.2 |170.5 | |166.8 |168.2 |

|DIC |440.0 |445.3 | |411.9 |412.4 |

|totresdev: mean of the residual deviance; pD: effective number of parameters; DIC: deviance information criterion. |

Supplemental Digital Content-Table 6．Sensitivity analyses according to dosage and study quality.

| |Changes in IPSS, MD(95%CI) | |Change in PUF, MD(95%CI) |

| |Dosage |Study quality | |Dosage |Study quality |

| | | | | | |

|Placebo |Reference |Reference | |Reference |Reference |

|Alfuzosin |-2.06(-2.65 to -1.49) |-1.97(-2.56 to -1.39) | |1.07(0.76 to 1.38) |1.06(0.77 to 1.36) |

|Doxazosin |-3.63(-4.28 to -2.96) |-3.63(-4.30 to -2.95) | |1.95(1.60 to 2.30) |1.80(1.44 to 2.16) |

|Tamsulosin |-2.07(-2.52 to -1.63) |-2.16(-2.60 to -1.72) | |1.07(0.83 to 1.32) |1.05(0.81 to 1.28) |

|Terazosin |-3.24(-4.17 to -2.28) |-3.23(-4.13 to -2.32) | |1.19(0.73 to 1.64) |1.20(0.74 to 1.64) |

|Silodosin |-2.40(-3.21 to -1.61) |-2.44(-3.25 to -1.65) | |0.93(0.42 to 1.43) |0.93(0.44 to 1.42) |

|Naftopidil |-1.97(-2.95 to -0.97) |-1.95(-2.99 to -0.87) | |1.03(0.28 to 1.78) |1.02(0.29 to 1.75) |

|Finasteride |-1.33(-1.84 to -0.81) |-1.33(-1.85 to -0.81) | |0.85(0.60 to 1.09) |0.83(0.59 to 1.07) |

|Dutasteride |-1.81(-2.50 to -1.13) |-1.83(-2.53 to -1.14) | |1.43(1.04 to 1.82) |1.42(1.05 to 1.79) |

|Tolterodine |-0.84(-2.17 to 0.53) |-0.89(-2.23 to 0.44) | |-0.05(-1.11 to 0.98) |0.20(-194.40 to 196.00) |

|Solifenacin |-0.30(-2.53 to 1.91) |-0.31(-2.52 to 1.95) | |NA |NA |

|Tadalafil |-1.87(-2.44 to -1.30) |-1.99(-2.58 to -1.41) | |0.42(0.06 to 0.79) |0.41(0.05 to 0.78) |

|Sildenafil |-3.08(-5.21 to -0.97) |-3.08(-5.20 to -0.97) | |0.54(-0.45 to 1.53) |0.51(-0.47 to 1.52) |

|Vardenafil |-2.23(-4.68 to 0.22) |-2.21(-4.68 to 0.21) | |0.65(-1.10 to 2.45) |0.60(-1.17 to 2.39) |

|IPSS, International Prostate Symptom Score; PUF, Peak Urinary Fow Rate; MD, Mean Difference; CI, Confidence Interval. |

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