Palumbo 2011.

Study characteristics
Methods	Trial acronym: substudy of GIMEMA MM‐BO2005 and GIMEMA‐MM‐03‐05 Design: randomised, open‐label, multicentre study; modified intention‐to‐treat analysis, including participant receiving ≥ 1 study dose The trial sampled participants from 2 distinct RCTs, of which participants who received thalidomide‐based regimens were eligible to the substudy randomising antithrombotic prophylaxis treatments Median follow‐up time: 24.9 months
Participants	Patients with previously untreated myeloma who received thalidomide‐containing regimens and had no clinical indication or contraindication for a specific antiplatelet or anticoagulant therapy Median age: 61 (range 55–66) years in aspirin group; 60 (range 54–66) years in warfarin group; 62 (range 55–66) years in heparin group Gender, n (%) males: 117 (53%) in aspirin group; 115 (52%) in warfarin group; 130 (59%) in heparin group Metastatic disease: not reported Previous VTE: none
Interventions	Intervention 1: aspirin 100 mg/day Intervention 2: low‐dose warfarin (1.25 mg/day) Intervention 3: LMWH (enoxaparin 40 mg/day) Prophylaxis was administered during the 3 cycles of induction therapy in participants aged ≤ 65 years and during the first 6 cycles of induction therapy in participants aged > 65 years. Median treatment duration: 2.6 months in aspirin group; 2.4 months in low‐dose warfarin group; 2.6 months in LMWH group
Outcomes	Primary outcomes: a composite measure of a first episode of objectively confirmed symptomatic DVT, PE, arterial thrombosis, acute myocardial infarction or stroke, or sudden, otherwise‐unexplained death during the first 6 months from random assignment Secondary outcomes: each component of the composite primary endpoint; long‐term cumulative incidence of the primary endpoint; major and minor bleeding events; any toxicity that required interruption of study prophylaxis
Notes	Funding: none reported Disclosure of potential conflicts of interest: several authors reported paid consultant or advisory roles, honoraria, and research funds that were relevant to the subject matter under consideration in their trial report. Publication format: full‐text publication
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "A simple random assignment sequence was generated by a centralized computer." Comment: adequate method of sequence generation.
Allocation concealment (selection bias)	Low risk	Quote: "After registration in a centralized database through the Internet and validation of eligibility, patients were randomly allocated to treatments using an automated assignment procedure concealed to the investigators." Comment: adequate method of allocation concealment.
Blinding (performance bias and detection bias) All outcomes	High risk	Quote: "open‐label." Comment: this was an open‐label study. It is not reported whether outcomes were assessed blindly.
Incomplete outcome data (attrition bias) All outcomes	High risk	Comment: for effectiveness and safety, 220/224 (98.2%) participants in aspirin group, 220/222 (99.1%) participants in warfarin group, and 219/221 (99.1%) participants in LMWH group were analysed. In addition, 1 participant was not randomised by "clinician mistake."
Selective reporting (reporting bias)	High risk	Comment: the outcome "any toxicity that required interruption of study prophylaxis" was not reported in the final report.