BPLTTC Methods

Methods

The principal hypotheses, criteria for trial eligibility and main outcomes to be studies were all pre-specified, prior to knowledge of the results of any individual trials. A protocol for the Collaboration was published in the Journal of Hypertension in 1998 (Resources).

Principal Hypotheses

•	That, compared with placebo, blood pressure lowering with newer antihypertensive drugs, such as ACE inhibitors, calcium antagonists and angiotensin II antagonists, would reduce major morbidity and mortality.
•	That, compared with less intensive strategies, blood pressure lowering regimens of greater intensity would reduce major morbidity and mortality.
•	That blood pressure lowering regimens based on different classes of antihypertensive drug would have different effects on cause-specific cardiovascular outcomes.

Criteria for eligibility of trials

•	Inclusion of a randomised comparison that addressed one of the pre-specified hypotheses.
•	A planned minimum of 1000 patient years of follow-up in each randomised group.
•	Main results not published or presented prior to finalisation of the Collaboration protocol in July 1995.

Primary outcomes

•	Stroke (non-fatal stroke or death from cerebrovascular disease).
•	Coronary heart disease (non-fatal myocardial infarction, death from coronary heart disease or sudden death).
•	Heart failure (causing death or requiring hospitalisation).
•	Death from any cardiovascular cause.
•	Major cardiovascular events (stroke, myocardial infarction, heart failure or any cardiovascular death).
•	Total mortality

Data collection

Both individual participant data and summary tabular data are sought from each completed trial. Data requested for each participant include baseline characteristics recorded at (or immediately prior to) randomisation, selected measurements made during follow-up, and details of the occurrence of all pre-defined study outcomes during the scheduled follow-up period.

Individual participant data extend the range of analyses that can be performed and, in particular, facilitate analyses among patient subgroups. The individual participant data files are carefully checked for completeness of patient records, for balance of randomised group sizes and for other indicators of possible anomalies. The internal consistency of the individual participant data is confirmed by direct comparison of the individual participant data sets with the summary data provided by each trial. This process helps to ensure that individual study results are correctly included in analyses and, hence, that the overview analyses are reliable.

Statistical issues

Analyses are performed using standard statistical software (STATA, Release 6.0). Relative risks and 95% confidence intervals for each outcome are calculated separately for each trial according to the principle of intention to treat. Overall estimates of effect are calculated using a fixed-effects model, whereby the log-relative risk for each trial is weighted by the reciprocal of the variance of the log-relative risk. The assumption of homogeneity of treatment effect between different trials and subgroups of trials is assessed using chi-square tests of homogeneity.