Serjeant 1977.

Methods	Design trial: parallel (two groups). Study phase: III. Baseline observation period: no (Dr Graham Serjeant, interviewed by one author of this review (JKM), on February 4, 2011). Follow‐up period: 6 months. Randomisation unit: patients. Unit of analysis: ulcers. Intention‐to‐treat analysis: no (information was supplied by Dr Graham Serjeant, interviewed by one author of this review (JKM), on February 4, 2011).
Participants	Enrolled: not described. Randomised: 40 (unclear). This number was confirmed by Dr Graham Serjeant, interviewed by one author of this review (JKM), on February 4, 2011. 1. Reported patients: 40 2. Loss patients: 25% (10/40) (isoxuprine hydrochloride group: 4/ placebo group: 6) (This number was supplied by Dr Graham Serjeant, interviewed by one author of this review (JKM), on February 4, 2011). 3. Reported leg ulcers at the start trial: 63 3.1. 1 ulcer reported by 23 patients: 23 ulcers. 3.2. 2 ulcers reported by 12 patients: 24 ulcers. 3.3. 3 ulcers reported by 4 patients: 12 ulcers. 3.4. 4 ulcers reported by 1 patient: 4 ulcers. Total: 63 ulcers. 4. Ulcers developed during trial: 9 (# patients: no reported). 5. Total ulcers: 72 (63 + 9): 72. 6. Reported leg ulcers completing trial: 46 (75% 30/40 patients). 7. Ulcers developed during trial which completed trial: 8 (# patients: no reported). 8. Number of ulcers completing trial: 54 (isoxuprine: 32; placebo: 22). 9. Duration (median): Isoxuprine group: 3.6 years (range: 0.3 to 15). Placebo group: 3.5 years (range: 0.3 to 12). Allocated group: not mentioned. Information about haemoglobin disorder type: Homozygous sickle cell disease "Diagnosed by haemoglobin electrophoresis on cellulose acetate and agar gel, and quantification of A2 levels": 38. Sickle cell‐haemoglobin C disease: 1. Sickle cell‐haemoglobin O (Arab) disease: 1. Age (years): 17 to 67. Gender (% male): 52.5 (21/40). Inclusion criteria: information was not supplied. Exclusion criteria: information was not supplied.
Interventions	Experimental group: Isoxuprine hydrochloride: 40 mg, per oral (bd). Control group: Placebo: 40 mg, per oral (bd). Co‐interventions: Local ulcer therapy: dressings plus mild antiseptic agent (not named): bd.
Outcomes	Outcomes were not describe as primary or secondary. They were reported into 'results' section: Variation ulcer size; healed. According with Dr Graham Serjeant, interviewed by one author of this review (JKM), 'ulcer area‐change' was the primary outcome (February 4, 2011).
Notes	Centre and Country: Medical Research Council Laboratories, University of West India, Jamaica. Sample size estimation a priori: no. Support: Mead Johnson and Company. Founder role: it supplied isoxsuprine hydrochloride and financial assistance.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Quote " patients were allotted serial numbers in a code..." (page 164). Insufficient information about the sequence generation process to permit judgement of ‘low risk’ or ‘high risk’.
Allocation concealment (selection bias)	Unclear risk	Insufficient information to permit judgement of ‘low risk’ or ‘high risk’.
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	Insufficient information to permit judgement of ‘low risk’ or ‘high risk’ Comment: Dr Searjent referred this paper as blinded (Interviewed by one author of this review (JKM), on February 4, 2011).
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Insufficient information to permit judgement of ‘low risk’ or ‘high risk’.
Incomplete outcome data (attrition bias) All outcomes	High risk	The number or reasons for dropouts and withdrawals were not described. Comments: this RCT loss 25% (10/40) of the patients and 27% (17/63) of the leg ulcers.
Selective reporting (reporting bias)	High risk	One or more clinically relevant and reasonably expected outcomes were not reported on; data on these outcomes were likely to have been recorded.
Other bias	High risk	Quote "The code was kept by the producing company". Comments. 1. Characteristic baseline table: not shown. 2. It is unclear data on randomisation unit reported by the authors. Dr Graham Serjeant pointed out unit of randomisation were the patients, and unit of analysis were the ulcers (Interviewed by one author of this review (JKM), on February 4, 2011). 3. Ulcers developed during trail were included which were analysed. 4. There is inconsistency regarding numbers of the total ulcers. 5. Ascertaiment bias and bias in the presentation of data (Appendix 2). 6. The inconsistency between 'Randomisation unit: patient' and 'Unit of analysis: ulcers' could generate the design and confusion bias (Appendix 2).