2 Materials and Methods
3.2 Risk of bias in included studies
3.2.1 Methodological quality of included studies (ordered by study ID) . 117
by study ID)
AASK 2002
Bias Authors'
judgement Support for judgement Random sequence
generation (selection bias) Low risk The randomisation was stratified by city using randomly permuted blocks
Allocation concealment
(selection bias) Unclear risk Method of allocation concealment was not described
Blinding of participants and personnel
(performance bias)
Low risk Participants and personnel blinded Blinding of outcome
assessment (detection bias)
Low risk Blind outcome assessment Incomplete outcome data
(attrition bias) Low risk Patients withdrawing from the study were accounted. ITT analysis was performed Selective reporting
(reporting bias) Low risk Outcomes listed in the methods section were all reported
Other bias Unclear risk
A number of BP-lowering agents were added to randomly allocated treatment to control BP. The observed effects could equally have resulted from the different additional drugs
ACCOMPLISH 2004
Bias Authors'
judgement Support for judgement Random sequence
generation (selection bias) Low risk Randomization scheme was generated by computer
Allocation concealment
(selection bias) Low risk Central randomisation Blinding of participants
and personnel (performance bias)
Low risk Participants and personnel blinded Blinding of outcome
assessment (detection bias)
Low risk Blind outcome assessment Incomplete outcome data
(attrition bias) Unclear risk It is unclear whether an ITT or PP analysis was used
Selective reporting
(reporting bias) Low risk Outcomes listed in the methods section were all reported
Other bias Unclear risk
A number of BP-lowering agents were added to randomly allocated treatment to control BP. The observed effects could equally have resulted from the different additional drugs
Alcocer 1995
Bias Authors'
judgement Support for judgement Random sequence
generation (selection bias) Low risk The randomisation was stratified by centres using randomly permuted blocks
Allocation concealment
(selection bias) Unclear risk Method of allocation concealment was not described
Blinding of participants and personnel
(performance bias)
Low risk Participants and personnel blinded
Blinding of outcome assessment (detection bias)
Low risk Blind outcome assessment Incomplete outcome data
(attrition bias) Low risk Patients withdrawing from the study were accounted. ITT analysis was performed Selective reporting
(reporting bias) Low risk Outcomes listed in the methods section were all reported
Other bias Low risk No other possible bias was found
ALLHAT 2002
Bias Authors'
judgement Support for judgement Random sequence
generation (selection bias)
Low risk Randomization scheme was generated by computer
Allocation concealment
(selection bias) Low risk Concealment scheme was implemented at the clinical trials centre and stratified by centre Blinding of participants
and personnel (performance bias)
Low risk Participants and personnel blinded Blinding of outcome
assessment (detection bias)
Low risk Blind outcome assessment
Incomplete outcome data
(attrition bias) Low risk
Two centres initially reported were excluded, due poor documentation of informed consent. ITT analysis was performed
Selective reporting
(reporting bias) Low risk Outcomes listed in the methods section were all reported
Other bias Unclear risk
A number of BP-lowering agents were added to randomly allocated treatment to control BP. The observed effects could equally have resulted from the different additional drugs
ALPINE 2003
Bias Authors'
judgement Support for judgement Random sequence
generation (selection bias) Unclear risk Method of sequence generation was not described
Allocation concealment
(selection bias) Unclear risk Method of allocation concealment was not described
Blinding of participants and personnel
(performance bias)
Low risk Participants and personnel blinded Blinding of outcome
assessment (detection bias)
Low risk Blind outcome assessment
Incomplete outcome data
(attrition bias) Low risk
Not indicated whether reasons for missing outcome data were similar across treatment groups. Modified ITT analysis was performed including all randomised patients who had completed the study and had taken at least one dose of study drug
Selective reporting
(reporting bias) Low risk Outcomes listed in the methods section were all reported
Other bias Low risk No other possible bias was found
ASCOT-BPLA 2005
Bias Authors'
judgement Support for judgement
Random sequence generation (selection bias)
Low risk Randomization scheme was generated by computer
Allocation concealment
(selection bias) Low risk Central randomisation Blinding of participants
and personnel (performance bias)
High risk Study drugs were administered open-label Blinding of outcome
assessment (detection bias)
Low risk A PROBE design was used.
Incomplete outcome data
(attrition bias) Low risk
Two centres with 85 patients initially reported were excluded, due data integrity concerns. ITT analysis was performed
Selective reporting
(reporting bias) Low risk Outcomes listed in the methods section were all reported
Other bias Low risk No other possible bias was found
Benetos 2000
Bias Authors'
judgement Support for judgement Random sequence
generation (selection bias) Unclear risk Method of sequence generation was not described
Allocation concealment
(selection bias) Unclear risk Method of allocation concealment was not described
Blinding of participants and personnel
(performance bias)
Low risk Participants and personnel blinded Blinding of outcome
assessment (detection bias)
Low risk Blind outcome assessment
Incomplete outcome data
(attrition bias) Low risk
Not indicated whether reasons for missing outcome data were similar across treatment groups. Modified ITT analysis was performed including all randomly assigned patients who received at least one dose of the study
medication, had one baseline BP measurement, and at least one subsequent BP measurement Selective reporting
(reporting bias) Low risk Outcomes listed in the methods section were all reported
Other bias Low risk No other possible bias was found
Black 1997
Bias Authors'
judgement Support for judgement Random sequence
generation (selection bias)
Unclear risk Method of sequence generation was not described
Allocation concealment
(selection bias) Unclear risk Method of allocation concealment was not described
Blinding of participants and personnel
(performance bias)
Low risk Participants and personnel blinded Blinding of outcome
assessment (detection bias)
Low risk Blind outcome assessment
Incomplete outcome data
(attrition bias) Low risk
Not indicated whether reasons for missing outcome data were similar across treatment groups. Modified ITT analysis was performed including all randomised patients with a baseline
measurement and at least one post treatment observation
Selective reporting
(reporting bias) Low risk Outcomes listed in the methods section were all reported.
Other bias Low risk No other possible bias was found.
Black 2001
Bias Authors'
judgement Support for judgement Random sequence
generation (selection bias) Unclear risk Method of sequence generation was not described
Allocation concealment
(selection bias) Unclear risk Method of allocation concealment was not described
Blinding of participants and personnel
(performance bias)
Low risk Participants and personnel blinded Blinding of outcome
assessment (detection bias)
Low risk Blind outcome assessment Incomplete outcome data
(attrition bias) Unclear risk It is unclear whether an ITT or PP analysis was used
Selective reporting
(reporting bias) Low risk Outcomes listed in the methods section were all reported
Other bias Low risk No other possible bias was found
Bremner 1997
Bias Authors'
judgement Support for judgement Random sequence
generation (selection bias) Unclear risk Method of sequence generation was not described
Allocation concealment
(selection bias) Unclear risk Method of allocation concealment was not described
Blinding of participants and personnel
(performance bias)
Low risk Participants and personnel blinded Blinding of outcome
assessment (detection bias)
Unclear risk It is unclear whether blinding was broken prior to making final decision to withdraw
Incomplete outcome data
(attrition bias) Low risk Patients withdrawing from the study were accounted. ITT analysis was performed Selective reporting
(reporting bias) Low risk Outcomes listed in the methods section were all reported
Other bias Low risk No other possible bias was found
CASE-J 2008
Bias Authors'
judgement Support for judgement Random sequence
generation (selection bias) Low risk Randomization scheme was generated by computer
Allocation concealment
(selection bias) Unclear risk Method of allocation concealment was not described
Blinding of participants and personnel
(performance bias)
High risk Participants and personnel were not blinded Blinding of outcome
assessment (detection bias)
Low risk A PROBE design was used.
Incomplete outcome data
(attrition bias) Low risk Patients withdrawing from the study were accounted. ITT analysis was performed
Selective reporting
(reporting bias) Low risk Outcomes listed in the methods section were all reported
Other bias Low risk No other possible bias was found
Chanudet 2001
Bias Authors'
judgement Support for judgement Random sequence
generation (selection bias) Unclear risk Method of sequence generation was not described Allocation concealment
(selection bias) Unclear risk Method of allocation concealment was not described
Blinding of participants and personnel
(performance bias)
Low risk Participants and personnel blinded Blinding of outcome
assessment (detection bias)
Low risk Blind outcome assessment Incomplete outcome data
(attrition bias) High risk Data of withdrawn patients were not included. PP analyses was used
Selective reporting
(reporting bias) Low risk Outcomes listed in the methods section were all reported
Other bias Low risk No other possible bias was found
CONVINCE 2003
Bias Authors'
judgement Support for judgement Random sequence
generation (selection bias) Low risk IVRS, for randomising, assigning, and tracking blinded medication was used
Allocation concealment
(selection bias) Low risk IVRS, for randomising, assigning, and tracking blinded medication was used
Blinding of participants and personnel
(performance bias)
High risk A number of patients discontinued blinded medication (administered open-label) Blinding of outcome
assessment (detection bias)
Low risk Blind outcome assessment
Incomplete outcome data
(attrition bias) Low risk
Participants from two centres with 126 patients were excluded, due to data integrity concerns.
ITT analysis was performed Selective reporting
(reporting bias) Low risk Outcomes listed in the methods section were all reported
Other bias Unclear risk
A number of BP-lowering agents were added to randomly allocated treatment to control BP. The observed effects could equally have resulted from the different additional drugs
Cremonesi 2002
Bias Authors'
judgement Support for judgement Random sequence
generation (selection bias) Unclear risk Method of sequence generation was not described
Allocation concealment
(selection bias) Unclear risk Method of allocation concealment was not described
Blinding of participants and personnel
(performance bias)
High risk Participants and personnel were not blinded Blinding of outcome
assessment (detection bias)
High risk Study drugs were administered open-label
Incomplete outcome data
(attrition bias) Low risk Patients withdrawing from the study were accounted. ITT analysis was performed Selective reporting
(reporting bias) Low risk Outcomes listed in the methods section were all reported
Other bias Low risk No other possible bias was found
CROSS 2003
Bias Authors'
judgement Support for judgement Random sequence
generation (selection bias) Unclear risk Method of sequence generation was not described
Allocation concealment
(selection bias) Unclear risk Method of allocation concealment was not described
Blinding of participants and personnel
(performance bias)
Low risk Participants and personnel blinded Blinding of outcome
assessment (detection bias)
Low risk Blind outcome assessment
Incomplete outcome data
(attrition bias) Low risk
Not indicated whether reasons for missing outcome data were similar across treatment groups. Modified ITT analysis was performed including all patients allocated randomly to groups, provided that they had received at least one dose of the study medication and had post- baseline data
Selective reporting
(reporting bias) Low risk Outcomes listed in the methods section were all reported.
Other bias Low risk No other possible bias was found
Cushman 1998
Bias Authors'
judgement Support for judgement Random sequence
generation (selection bias) Unclear risk Method of sequence generation was not described
Allocation concealment
(selection bias) Unclear risk Method of allocation concealment was not described
Blinding of participants and personnel
(performance bias)
Low risk Participants and personnel blinded Blinding of outcome
assessment (detection bias)
Low risk Blind outcome assessment Incomplete outcome data
(attrition bias) Low risk Patients withdrawing from the study were accounted. ITT analysis was performed Selective reporting
(reporting bias) Low risk Outcomes listed in the methods section were all reported
Other bias Low risk No other possible bias was found
Derosa 2013
Low risk Randomization scheme was generated by computer
Allocation concealment (selection bias)
Low risk Central randomisation Blinding of participants
and personnel (performance bias)
Low risk
Participants and personnel blinded
Blinding of outcome
Low risk Not indicated whether reasons for missing outcome data were similar across treatment groups. Modified ITT analysis was performed including patients who had received at least one dose of study medication and had a subsequent efficacy observation
Selective reporting (reporting bias)
Low risk Outcomes listed in the methods section were all reported
Other bias Low risk No other possible bias was found
Derosa 2014
Bias Authors'
judgement Support for judgement Random sequence
generation (selection bias) Low risk Randomization scheme was generated by computer
Allocation concealment
(selection bias) Low risk
Allocation concealment was done with envelopes containing randomisation codes prepared by statisticians
Blinding of participants and personnel
(performance bias)
Low risk Participants and personnel blinded Blinding of outcome
assessment (detection bias)
Low risk Blind outcome assessment Incomplete outcome data
(attrition bias) Unclear risk It is unclear whether an ITT or PP analysis was used
Selective reporting
(reporting bias) Low risk Outcomes listed in the methods section were all reported
Other bias Low risk No other possible bias was found
DETAIL 2004
Bias Authors'
judgement Support for judgement Random sequence
generation (selection bias) Unclear risk Method of sequence generation was not described
Allocation concealment
(selection bias) Unclear risk Method of allocation concealment was not described
Blinding of participants and personnel
(performance bias)
Low risk Participants and personnel blinded Blinding of outcome
assessment (detection bias)
Unclear risk It is unclear whether blinding was broken prior to making final decision to withdraw
Incomplete outcome data
(attrition bias) Low risk Patients withdrawing from the study were accounted. ITT analysis was performed Selective reporting
(reporting bias) Low risk Outcomes listed in the methods section were all reported
Other bias Low risk No other possible bias was found
ELLE 2003
Bias Authors'
judgement Support for judgement Random sequence
generation (selection bias) Unclear risk Method of sequence generation was not described
Allocation concealment
(selection bias) Unclear risk Method of allocation concealment was not described
Blinding of participants and personnel
(performance bias)
Low risk Participants and personnel blinded Blinding of outcome
assessment (detection bias)
Low risk Blind outcome assessment Incomplete outcome data
(attrition bias) High risk Data of withdrawn patients were not included.
PP analyses was used Selective reporting
(reporting bias) Low risk Outcomes listed in the methods section were all reported
Other bias Low risk No other possible bias was found
ELSA 2002
Bias Authors'
judgement Support for judgement Random sequence
generation (selection bias) Low risk Randomization scheme was generated by computer
Allocation concealment
(selection bias) Unclear risk Method of allocation concealment was not described
Blinding of participants and personnel
(performance bias)
Low risk Participants and personnel blinded Blinding of outcome
assessment (detection bias)
Low risk Blind outcome assessment
Incomplete outcome data
(attrition bias) Low risk
Not mentioned whether reasons for missing outcome data were similar between treatment groups. Modified ITT analysis was performed including all patients randomised to double blind medication who had the baseline ultrasound scan and at least one follow-up scan, including scans performed after withdrawal
Selective reporting
(reporting bias) Low risk Outcomes listed in the methods section were all reported
Other bias Low risk No other possible bias was found
ELVERA 2004
Bias Authors'
judgement Support for judgement Random sequence
generation (selection bias) Unclear risk Method of sequence generation was not described
Allocation concealment
(selection bias) Unclear risk Method of allocation concealment was not described
Blinding of participants and personnel
(performance bias)
Low risk Participants and personnel blinded Blinding of outcome
assessment (detection bias)
Low risk Blind outcome assessment
Incomplete outcome data
(attrition bias) Low risk
Not indicated whether reasons for missing outcome data were similar across treatment groups. Modified ITT analysis was performed including patients for whom there were valid readings at baseline and at least one valid observation after 1 and 2 years
Selective reporting
(reporting bias) Low risk Outcomes listed in the methods section were all reported
Other bias Low risk No other possible bias was found
FACET 1998
Bias Authors'
judgement Support for judgement Random sequence
generation (selection bias) Low risk Randomization scheme was generated by computer
Allocation concealment
(selection bias) Unclear risk Method of allocation concealment was not described
Blinding of participants and personnel
(performance bias)
High risk Study drugs were administered open-label Blinding of outcome
assessment (detection bias)
High risk Outcome assessment not blinded Incomplete outcome data
(attrition bias) Low risk Patients withdrawing from the study were accounted. ITT analysis was performed Selective reporting
(reporting bias) Low risk Outcomes listed in the methods section were all reported
Other bias Unclear risk
A number of BP-lowering agents were added to randomly allocated treatment to control BP. The observed effects could equally have resulted from the different additional drugs
Farsang 2007
Bias Authors'
judgement Support for judgement Random sequence
generation (selection bias) Unclear risk Method of sequence generation was not described
Allocation concealment
(selection bias) Unclear risk Method of allocation concealment was not described
Blinding of participants and personnel
(performance bias)
Low risk Participants and personnel blinded Blinding of outcome
assessment (detection bias)
Low risk Blind outcome assessment Incomplete outcome data
(attrition bias) Low risk Patients withdrawing from the study were accounted. ITT analysis was performed Selective reporting
(reporting bias) Low risk Outcomes listed in the methods section were all reported
Other bias Low risk No other possible bias was found
Fogari 2008
Bias Authors'
judgement Support for judgement Random sequence
generation (selection bias) Low risk Randomization scheme was generated by computer
Allocation concealment
(selection bias) Low risk Central randomisation Blinding of participants
and personnel (performance bias)
High risk Study drugs were administered open-label Blinding of outcome
assessment (detection bias)
Low risk A PROBE design was used.
Incomplete outcome data
(attrition bias) Unclear risk It is unclear whether an ITT or PP analysis was used
Selective reporting
(reporting bias) Low risk Outcomes listed in the methods section were all reported
Other bias Low risk No other possible bias was found
Freytag 2001
Bias Authors'
judgement Support for judgement Random sequence
generation (selection bias) Unclear risk Method of sequence generation was not described.
Allocation concealment
(selection bias) Unclear risk Method of allocation concealment was not described.
Blinding of participants and personnel
(performance bias)
Low risk Participants and personnel blinded.
Blinding of outcome assessment (detection bias)
Low risk Blind outcome assessment.
Incomplete outcome data
(attrition bias) Low risk Patients withdrawing from the study were accounted. ITT analysis was performed.
Selective reporting
(reporting bias) Low risk Outcomes listed in the methods section were all reported.
Other bias Low risk No other possible bias was found.
Giles 2007
Bias Authors'
judgement Support for judgement Random sequence
generation (selection bias) Unclear risk Method of sequence generation was not described
Allocation concealment
(selection bias) Unclear risk Method of allocation concealment was not described
Blinding of participants and personnel
(performance bias)
Low risk Participants and personnel blinded Blinding of outcome
assessment (detection bias)
Low risk Blind outcome assessment
Incomplete outcome data
(attrition bias) Low risk
Not indicated whether reasons for missing outcome data were similar across treatment groups. Modified ITT analysis was performed including patients who received at least 1 dose of study drug and had a baseline BP
measurement and at least one post baseline BP assessment
Selective reporting
(reporting bias) Low risk Outcomes listed in the methods section were all reported
Other bias Low risk No other possible bias was found
Grassi 2003
Bias Authors'
judgement Support for judgement Random sequence
generation (selection bias) Unclear risk Method of sequence generation was not described
Allocation concealment
(selection bias) Unclear risk Method of allocation concealment was not described
Blinding of participants and personnel
(performance bias)
Low risk Participants and personnel blinded Blinding of outcome
assessment (detection bias)
Low risk Blind outcome assessment Incomplete outcome data
(attrition bias) High risk Data of withdrawn patients were not included.
PP analyses was used Selective reporting
(reporting bias) Low risk Outcomes listed in the methods section were all reported
Other bias Low risk No other possible bias was found
Greathouse 2010
Bias Authors'
judgement Support for judgement Random sequence
generation (selection bias) Unclear risk Method of sequence generation was not described
Allocation concealment
(selection bias) Unclear risk Method of allocation concealment was not described
Blinding of participants and personnel
(performance bias)
Low risk Participants and personnel blinded Blinding of outcome
assessment (detection bias)
Low risk Blind outcome assessment
Incomplete outcome data
(attrition bias) Low risk
Not indicated whether reasons for missing outcome data were similar across treatment groups. Modified ITT analysis was performed including all randomised patients who received at least one dose of study medication.
Not indicated whether reasons for missing outcome data were similar across treatment groups. Modified ITT analysis was performed including all randomised patients who received at least one dose of study medication.