These biannual reviews will include data on number and causality of deaths, number of treatment failures and serious adverse events.
The DSMB can recommend to modify or stop the study prematurely, if number and causality of deaths, number of treatment failures and serious adverse events are significantly greater than was foreseen in the literature.
Probably, the observed difference in deaths occurred by chance, but irrespective of the causality of the deaths, these negatively affected the number of QALYs gained in the intervention group.
ICMR's director general, microbiologist Vishwa Mohan Katoch, categorically rejects a connection: "Based on the enquiry, it is certain that causality of the seven deaths was not at all related to the HPV vaccine," he insists.
However, unequivocally demonstrating causality of such infections to death is difficult in critically ill patients because of potential confounding and competing events.
In general, as individuals reporting a prevalent condition at recruitment (either cancer, diabetes, heart attack or stroke) were excluded from the analysis in an effort to minimise reverse causality, our estimates of absolute risks of death are possibly underestimated.
However, it is very difficult to determine the causality between MSOF and infection, and both are important predictors of death.
Causality of neonatal deaths is thus, mainly based on estimations and most causes of death are unknown.
Because of the observational nature of this study, our findings of increased risk of death related to tight control of systolic and diastolic blood pressure do not imply causality.
The defective lung development of the RASSF9−/− mice is likely the major causality of their failure to thrive and premature death.
