Haas 2012.

Study characteristics
Methods	Trial acronym: TOPIC‐1 and TOPIC‐2 Design: multicentre RCTs, intention‐to‐treat analysis for effectiveness and modified intention‐to‐treat analysis for safety outcomes. TOPIC‐1 was prematurely halted after an interim analysis. Median duration of follow‐up: not reported
Participants	Patients with metastatic breast cancer (n = 353) or non‐small‐cell lung carcinoma (n = 547) receiving first‐ or second‐line chemotherapy. Mean age in TOPIC‐1 study (participants with breast cancer): 54.6 (SD 10.3) years in certoparin group; 56.6 (SD 11.0) years in placebo group Mean age in TOPIC‐2 study (participants with lung cancer): 60.8 (SD 9.5) years in certoparin group; 60.3 (SD 10.0) years in placebo group Gender, n (%) males: TOPIC‐1: 0 (0%); TOPIC‐2: 227 (83.2%) overall Metastatic disease: not reported Previous VTE: 0/900
Interventions	Intervention: LMWH, certoparin 3000 IU SC, once daily Control: placebo Study treatment given for 6 months.
Outcomes	Primary outcomes: symptomatic or incidental VTE, major bleeding Secondary outcomes: symptomatic VTE, overall thrombosis rate (to include arterial thrombotic events, superficial venous thrombosis, and central‐line thrombosis), minor bleeding, thrombocytopenia, heparin‐induced thrombocytopenia, osteoporotic fractures, survival Post hoc: mortality, symptomatic or incidental VTE according to tumour stage
Notes	Funding: grant from Novartis Pharma, Nuremberg, Germany. Quote: "The TOPIC studies were supported by an unrestricted grant from Novartis Pharma GmbH, Germany." Disclosure of potential conflicts of interest, quote: "The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article." Publication format: full‐text publication
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "Using a computer‐generated randomisation list" and "Randomization was block‐stratified according to treatment with hormone‐based chemotherapy." Comment: adequate method of sequence generation.
Allocation concealment (selection bias)	Unclear risk	Quote: "Randomization numbers were allocated sequentially as patients were enrolled at each center." Comment: concealment of allocation was poorly reported. It was not reported if sealed, opaque, and consecutively numbered envelopes, coded syringes, or other methods were used. In addition, it remains unclear what is meant by randomisation number in "Patients were allocated to the lowest available randomisation number available for each study center."
Blinding (performance bias and detection bias) All outcomes	Low risk	Quote: "Efficacy outcomes were validated by a blinded, independent Central Thrombosis Evaluation Team; safety end points were validated by a Data Safety Monitoring Committee consisting of 2 clinicians (blinded to treatment) and an independent statistician with access to the treatment assignments." and "Only the external statistician from the Safety Committee had access to the randomization codes." Comment: double‐blind, placebo‐controlled RCT with blinding of participants, physicians, and outcome assessors#.
Incomplete outcome data (attrition bias) All outcomes	High risk	Comment: for effectiveness, 442/447 (98.9%) in LMWH group and 441/453 (97.4%) in placebo group were analysed. For safety, 447/447 (100%) in LMWH group and 451/453 (99.6%) in placebo group were analysed.
Selective reporting (reporting bias)	Low risk	Comment: all outcomes reported in the methods section were addressed in the results or discussion section. However, the outcome osteoporotic fracture was incompletely reported; it remained unclear in which of the TOPIC‐2 trial arms the single event occurred. Post hoc analyses were reported transparently.