Applying results from clinical trials: tranexamic acid in trauma patients

Ian Roberts, David Prieto-Merino, Ian Roberts, David Prieto-Merino

Abstract

This paper considers how results from clinical trials should be applied in the care of patients, using the results of the Clinical Randomisation of an Antifibrinolytic in Significant Haemorrhage (CRASH-2) trial of tranexamic acid in bleeding trauma patients as a case study. We explain why an understanding of the mechanisms of action of the trial treatment, and insight into the factors that might be relevant to this mechanism, is critical in order to properly apply (generalise) trial results and why it is not necessary that the trial population is representative of the population in which the medicine will be used. We explain why cause (mechanism)-specific mortality is more generalizable than all-cause mortality and why the risk ratio is the generalizable measure of the effect of the treatment. Overall, we argue that a biological insight into how the treatment works is more relevant when applying research results to patient care than the application of statistical reasoning.

Keywords: Clinical trials; Evidence-based medicine; Generalizability; Tranexamic acid; Trauma.

Figures

Figure 1
Figure 1
Two hypothetical trials: the risk ratio is the generalizable measure of the effect of treatment. In both trials, the biological effect of the treatment is the same, corresponding to a one third reduction in the risk of death. The relative risk is the same in both trials and reflects the biological effect of the treatment. However, the risk difference is not the same. The relative risk is a generalizable measure of the biological effect of a treatment, whereas the risk difference is not generalizable.
Figure 2
Figure 2
Hypothetical trial: effect on all-cause mortality is a weighted average of effect on cause-specific mortality. The treatment reduces the risk of death due to bleeding by one third (RR = 0.67) but has no effect on other causes of death (RR = 1.0). The effect on all-cause mortality (RR = 0.8) is a weighted average of its effect on deaths due to bleeding and on other causes of death, weighted according to the relative contributions of the different causes.

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Source: PubMed

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