Schmieder 2009.

Study characteristics
Methods	Randomized, double‐blind, active‐controlled, dose‐titration trial followed by an extension phase
Participants	1124 patients from 6 European countries with hypertension (SBP 140 to 179 mmHg and/or DBP 90 to 104 mmHg), no severe concomitant disease and no diabetes Mean age 56 years 505 F:618 M
Interventions	Aliskiren 150 mg to 300 mg daily Hydrochlorothiazide 12.5 mg to 25 mg daily Optional add‐on treatment of amlodipine 5 mg to 10 mg daily
Outcomes	AEs Potassium, creatinine, BUN BP at 1 year Duration: 1 year
Notes	—
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "Randomization by centre was performed by the interactive voice response system provider with the use of a validated system that automates the random assignment of patients to randomisation numbers." Unclear if patients who were initially randomized to placebo treatment were then assigned to aliskiren or hydrochlorothiazide at 6 weeks in a randomized manner.
Allocation concealment (selection bias)	Low risk	Quote: "Randomization data were kept strictly confidential until the time of unblinding."
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	Study was described as double‐blind, but no additional details provided.
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	No description of outcome assessment blinding was provided.
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	An intention‐to‐treat analysis was used. Quote: "[During the 26‐week double‐blind period] the overall number of discontinuations was significantly higher with the hydrochlorothiazide regimen than with the aliskiren regimen (15.8% versus 10.2%, respectively)." Quote: "[During the 26‐week extension] the proportion of patients discontinuing in this phase of the study was higher with the hydrochlorothiazide regimen than with the aliskiren regimen (6.7% versus 3.2%, respectively)."
Selective reporting (reporting bias)	Unclear risk	Unable to fully assess (no available protocol listing prespecified outcomes).
Use of supplemental drugs	Low risk	Only amlodipine permitted as add‐on therapy. Quote: "For patients not achieving the target BP of less than 140/90 mmHg, addition of amlodipine 5 mg was permitted from week 12, with titration to 10 mg from week 18."
Industry sponsorship	High risk	Quote: "This study was supported by Novartis Pharmaceuticals Corporation, East Hanover, New Jersey, USA."