Clinical effectiveness in cardiovascular trials in relation to the importance to the patient of the end-points measured.

BACKGROUND

In order to increase the statistical power of a trial design, it is common practice for trialists to place a strong emphasis on end-points other than mortality. To assess the validity of this practice, the aim of this study was to investigate the relationship between the effectiveness of cardiovascular interventions in clinical trials and the importance to the patient of the end-point used to measure this effectiveness.

METHODS

A reanalysis of a database of cardiovascular trials used in an earlier study. This database consists of all randomized controlled trials published in six leading journals for cardiovascular research between January 2002 and June 2003 that involve the exposure of humans to any therapeutic or primary preventive intervention for cardiovascular disease and report at least one composite end-point.

RESULTS

On the basis of analysing the study data using a statistical modelling approach, the best estimate of the percentage of trials that have a true (not estimated) relative risk of less than 0.8 for the end-point of moderate outcome, major outcome and death are 63%, 39% and 0% respectively, and the upper 95% confidence limits on these three percentages are 73%, 43% and 15% respectively.

CONCLUSIONS

The proportion of interventions tested in the cardiovascular trials considered in this study that have a substantial beneficial effect relative to the control decreases as the end-point used to measure this effect becomes more important to the patient, that is, as the end-point severity increases from minor outcome to major outcome to death. Also, the analysis presented in this study strongly suggests that most of these interventions are likely to have close to no genuine effect on mortality relative to the control. Overall, this study substantially strengthens the empirical basis for the belief that the actions of trialists in choosing to study and heavily emphasize end-points other than mortality in cardiovascular trials and in particular end-points that are of only moderate or major importance to patients, may mislead practitioners and policy-makers about the overall effectiveness of the intervention concerned.