| Boccardo 2005 | Fradet 2007 | Perdona 2005 | Saltzstein 2005 |
---|---|---|---|---|
Design | RCT, three arms | RCT, six armsb | RCT, three arms | RCT, three arms |
Intervention | tamoxifen 20 mg/d (37 patients) | tamoxifen 20 mg/d (35 patients) | tamoxifen 10 mg/d (50 patients) | tamoxifen 20 mg/d (35 patients) |
Control |    - anastrozole 1 mg/d (36 patients); |    - placebo (60 patients)b |    - radiotherapy (single fraction of 12 Gy, (50 patients); |    - anastrozole 1 mg/d (36 patients); |
 |    - placebo (40 patients) |  |    - no additional therapy (51 patients) |    - placebo (36 patients) |
Assessment of gynecomastia | by breast ultrasound or caliper. ("Severity was scored on the basis of the largest diameter as follows: grade 1, ≤ 2 cm; grade 2, more than 2 to ≤ 4 cm; grade 3, more than 4 to ≤ 6 cm; and grade 4, more than 6 cm.") | by patient questioning and calipers ("recorded in centimeters to the nearest 0.5 cm") | by calipers ("Severity was scored on the basis of the largest diameter: grade 1 (≤ 2 cm); grade 2 (from 2 to ≤ 4 cm); grade 3 (from 4 cm to ≤ 6 cm); and grade 4 (> 6 cm))" | by physical examination and direct patient questioning ("Criteria for a response to randomized therapy was the complete absence of gynecomastia and/or breast pain.") |
Assessment of breast pain | by direct patient questioning at each visit ("scored according to severity as none, mild to moderate, or severe")a | by direct patient questioning ("rated as mild (awareness of signs or symptoms but easily tolerated), moderate (discomfort sufficient to cause interference with normal activities), or severe (incapacitating resulting in an inability to perform normal activities") | by direct patient questioning at each visit ("scored as none, mild, moderate, or severe") | by direct patient questioning ("Criteria for a response to randomized therapy was the complete absence of gynecomastia and/or breast pain.") |
Random sequence generation | randomization lists for each center | computer random number generator | permuted randomization algorithm | sequential order, numbers were not reused, schedule prepared at each center |
Allocation concealment | unclear | central allocation | central allocation | central allocation |
Blinding of participants/personnel | double-blind, placebo-controlled | double-blind, placebo-controlled | no | double-blind, placebo-controlled |
Blinding of outcome assessment | double-blind, placebo-controlled | double-blind, placebo-controlled | no or not mentioned | double-blind, placebo-controlled |
Incomplete outcome data | low risk of biasc | low risk of biasc | low risk of biasc | low risk of biasc |
Selective reporting | low risk of biasd | low risk of biasd | low risk of biasd | low risk of biasd |
Other remarks | recruitment was stopped early because of planned interim analysis, research funding by AstraZeneca (no role in study design, analysis or interpretation of data) | co-author is an employee of AstraZeneca, writing support funded by AstraZeneca | authors declared no conflict of interest | co-authors are employees of AstraZeneca, no conflict of interest mentioned in manuscript |