Farahmand 2011.

Methods	Study design: randomized, controlled clinical trial. Method of randomization: randomization was performed on outpatients admitted for acute deep vein thrombosis between April 2005 and 2007 on the basis of a computer‐based randomization program; an Excel program was used for randomization of participants between two groups (García 2012a [pers comm]). Concealment of allocation: authors mentioned that investigators and coordinators were unaware of the group to which participants were allocated. They did not detail the concrete method that was used to conceal sequence. In light of the study conducted by Kovacs 2003, a specific nomogram was used in each group to determine the required warfarin dose on the basis of INR values reported during the study period. Blinded: double (physician–patient). Power calculation: the sample size was calculated to be about 63 participants in each treatment group, so that the study would have power of 95% to yield an SD of 1 for INR levels and an α level of 0.05. Because of the 95% sensitivity of Doppler ultrasound in detecting acute proximal DVT and possible dropouts, some three additional participants were recruited in each group. Number of participants randomly assigned: 132. Number of participants analyzed: 132. Number of withdrawals and reasons: none. Intention‐to‐treat analysis: yes. Source of funding: not stated. Potential financial conflicts of interest:none disclosed.
Participants	Country: Iran. Number of centers: 1. Location: emergency department (ED) of Imam Khomeini Hospital in Tehran, Iran. Source of participants: 10‐mg nomogram group: 66 participants. 5‐mg nomogram group: 66 participants. Age: mean ± SD, years. 10‐mg nomogram group: 45.8 ± 14.5 years (P = 0.07). 5‐mg nomogram group: 47.2 ± 17.5 years. Sex: men/women, n/n. 10‐mg nomogram group: 32/34. 5‐mg nomogram group: 40/26. Inclusion criteria: consecutive outpatients with suspected acute VTE (deep venous thrombosis) in whom the diagnosis was confirmed by color Doppler ultrasound. Exclusion criteria: participants with INR levels > 1.4 before initiation of treatment, platelet count < 50,000, severe hypertension (systolic blood pressure ≥ 200 mm Hg or diastolic blood pressure ≥ 120 mm Hg), and active bleeding, along with participants younger than 18 years of age; those with a positive history of ocular or neurosurgical surgery, intracranial hemorrhage in the past 10 days, documented liver disease, and bleeding disorders; and those who had used anticoagulants in the past 2 weeks.
Interventions	Treatment(s): Intervention: 66 participants were assigned to the 10‐mg nomogram group. Control: 66 participants were assigned to the 5‐mg nomogram group. Treatment was started with the subcutaneous injection of a single dose of enoxaparin (1.5 mg/kg) per day along with 5 or 10 mg warfarin, depending on the participant's group. The regimen was continued for 3 days; thereafter, the amount of prescribed warfarin was modified on the basis of INR levels. Throughout the study period, warfarin was prescribed early in the morning, and INR levels were evaluated at 10:00 AM. Duration: 14 days.
Outcomes	Outcomes: INR was checked daily on the first 7 days of the study and on the 14th day. During this time, participants were asked daily for possible signs of bleeding. Third day: mean of INR. 10‐mg nomogram group: 2.0636 ± 0.5979. 5‐mg nomogram group: 1.5667 ± 0.4145, P = 0.000. Fourth day: mean of INR, 10‐mg nomogram group: 2.7758 ± 0.7764. 5‐mg nomogram group: 1.8652 ± 0.6560, P = 0.004. Fifth day: mean of INR. 10‐mg nomogram group: 3.2742 ± 0.5936. 5‐mg nomogram group: 2.1561 ± 0.6805, P = 0.912. Seventh day: mean of INR. 10‐mg nomogram group: 3.2394 ± 0.3687. 5‐mg nomogram group: 2.6970 ± 0.6411, P = 0.024. Fourteenth day: mean of INR. 10‐mg nomogram group: 3.2467 ± 0.3170. 5‐mg nomogram group: 2.7773 ± 0.3062, P = 0.769. Proportions of participants whose INRs were within the therapeutic range (2.0 to 3.0) on the fifth day: n (%). Data were taken from the published table. 10‐mg nomogram group: 18 (27.27%). 5‐mg nomogram group: 31 (46.97%). Incidence of major bleeding within 14 days of follow‐up: n (%) 10‐mg nomogram group: 1 (1.52%). 5‐mg nomogram group: 1 (1.52%). Incidence of minor bleeding within 14 days of follow‐up: n 10‐mg nomogram group: 1 (1.52%). 5‐mg nomogram group: 0.
Notes	To add any information: Outcomes not included at protocol: Proportion of participants with 3 < INR < 5 on the seventh day: n (%) 10‐mg nomogram group: 38 (57.58%). 5‐mg nomogram group: 8 (12.12%). Proportion of participants with 3 < INR < 5 on the fourteenth day: n (%) 10‐mg nomogram group: 15 (22.73%). 5‐mg nomogram group: 7 (10.61%). Proportion of participants with INR > 5 on the seventh and fourteenth days: n (%) 10‐mg nomogram group: 0%. 5‐mg nomogram group: 0%. Mortality: It was not reported. The nomograms of 5 mg and 10 mg are similar to those in the study of Kovacs 2003. It should be stressed that this is the first of such a study conducted on outpatients referred to an ED. A significant difference was noted between INR levels of the 2 groups on the third, fourth, and seventh days; those reported on days 1, 5, and 14, however, were not statistically different. Invitation to authors to add and audit review data: yes, extra data provided. García 2012a [pers comm]: "We use Excel program for randomisation of participants between two groups. In 5‐mg group, we have one case of GI bleeding (24‐year‐old illegal drug user man) and in 10‐mg group one case of GI bleeding (68‐year‐old man suffering from GI malignancy) and one case of nose bleeding."
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	The study authors mentioned that participants were allocated to receive 5 or 10 mg warfarin on the basis of a computer‐based randomization program and used an Excel program for randomization of participants between two groups (García 2012a [pers comm]).
Allocation concealment (selection bias)	Unclear risk	The study authors mentioned that investigators and coordinators were unaware of the group to which participants were allocated. They did not detail the concrete method that was used to conceal sequence.
Blinding (performance bias and detection bias) All outcomes	Low risk	It is a double‐blind (physician‐patient) controlled trial.
Incomplete outcome data (attrition bias) All outcomes	Low risk	All participants were followed up for 14 days. Losses to follow‐up: none.
Selective reporting (reporting bias)	Low risk	The dates are objectively measured.
Other bias	Low risk	Probably free of other bias sources.