Large multicentre trials in anaesthesia: the ANZCA Clinical Trials Group.

Abstract

In the search for the best available evidence, large randomized clinical trials have much to offer1-7. First, large trials (often with more than 1000 patients) can study major endpoints such as death and permanent disability. second, large trials can be powered to detect, with precise 95% confidence intervals, the modest differences in hard endpoints that are important to clinicians, patients and their families. Third, large trials can come close to reflecting real world clinical practice if the protocol is simple and the broadest possible range of patients are included from many hospitals. Fourth, subgroups from large patient samples can be analysed to generate further hypotheses and subsequent targeted clinical trials. Fifth, while observational studies can provide important data, a randomized trial will minimize biases that may taint the results, such as patient characteristics or other confounding factors differing between treatment arms. Finally, recent guidelines have further improved the information provided in trial reports7.

There have been several large trials in anaesthesia and critical care medicine817. These include clear evidence of benefit for maintenance of normothermia and/or high inspired oxygen concentration in colorectal surgery8,9, intensive insulin therapy in critically ill patients10, bispectral index monitoring to prevent awareness", low-dose aspirin for hip surgery12, lowtidal volume ventilation in acute lung injury13, and recombinant human activated protein C for severe sepsis14. In contrast, there is no demonstrable benefit of low-dose dopamine or albumin in critically ill patients15'16.

Successful large trials conducted by informal networks of Australasian anaesthetists11,17, and in critical care medicine, the Clinical Trials Group of the Australian and New Zealand Intensive Care Society (ANZICS CTG)15,16,18, have led to publications in high profile general medical journals such as New England Journal of Medicine and Lancet. Following on from the success of our intensive care colleagues, the Australian and New Zealand College of Anaesthetists has formally created a Clinical Trials Group (ANZCA CTG).

The ANZCA CTG aims to promote, support, design, and conduct research in anaesthesia, perioperative medicine, and pain medicine. Further, the ANZCA CTG will work with the ANZICS CTG in designing and conducting trials of mutual interest. The ANZCA CTG reports to the College Research Committee, and through them to the College Council. The College Council has approved a constitution for the CTG and has funded a CTG Administrative Officer.

There are early signs of success for the ANZCA CTG: the most recent round of the Australian National Health and Medical Research Council project grants included a successful application from the group ($1.17 million), to fund a large trial testing the effectiveness of aspirin and/or tranexamic acid in coronary artery surgery ("The ATACAS Trial"). This trial will enrol 4,600 patients in about twelve centres over the next five years.

Those already involved in the ANZCA CTG hope that Fellows of the College will enthusiastically support the CTG through active participation in the CTG or as part of a participating centre in clinical trials. Further, it is hoped that Fellows with research hypotheses can use the CTG to develop and conduct trials and then be primary author of subsequent publications. For trainees, ANZCA guidelines now specifically include participation in multicentre trials as suitable for formal projects19.