Hermida 2003.

Methods	prospective, randomized, open‐label, blinded end point, parallel‐group trial. 2‐ to 4‐week washout period and 3 months timed active treatment . Baseline similarity: age, height, weight, BMI, waist and hip perimeters, SBP, and DBP, laboratory chemistry variables Sample size calculation: not reported
Participants	Country: Spain Number randomised:90 Mean age: 49.0±14.3(SD) years gender: 30 men, 60 women Ethnicity: White Inclusion Criteria: conventional SBP between 140 and 179 mm Hg, or DBP between 90 to 109 mm Hg, and ABPM 24 hour mean SBP/DBP > 130/80 mm Hg, diurnal mean >135/85 mm Hg, or the nocturnal mean > 120/70 mm Hg. Exclusion criteria: shift workers, heavy drinkers, smokers, and heavy exercisers, severe arterial hypertension, secondary arterial hypertension, cardiovascular disorders, including angina, heart failure, stroke, nephropathy, retinopathy, prior myocardial infarction or coronary revascularization.
Interventions	valsartan 160 mg/d awakening: N=46 valsartan 160 mg/d bedtime: N=44
Outcomes	Mortality: not reported Morbidity: not reported Blood Pressure data:24h BP change by 48h ABPM, data was obtained from graph and text (fig 3 on page 288) Adverse Events: not reported
Notes
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	computerized random‐number generator
Allocation concealment (selection bias)	High risk	"Assignment of subjects to treatment groups was done by 1 member of the research team, according to the order of recruitment, following an allocation table constructed by a computerized random‐number generator."
Blinding (performance bias and detection bias) All outcomes	Low risk	investigator obtaining the BP measurements and outcome assessors blinded. Benefits of the PROBE design and its validity compared with double‐blind, placebo‐controlled trials in assessing antihypertensive efficacy based on blinded ABPM measurements have been documented previously (Smith 2003).
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	All participants were reported. 6 subjects missing ABPM data were eliminated, 3 subjects discontinued timed treatment or they failed to return for the second ABPM at the end of treatment, but distribution according to group not reported
Selective reporting (reporting bias)	High risk	Morning SBP, DBP were not reported.
Other bias	Low risk	None identified