|Professor Paul Myles|
Professor Paul Myles, Head of the Department of Anaesthesia and Perioperative Medicine in CCS and Alfred Health will be presenting at the event. Professor Myles has just been awarded Clinical Trial of the Year for his work on coronary artery surgery.
Professor Myles will be presenting on "Large Clinical Trials and Reverse Translation". Abstract below:
Clinical practice should be guided by medical research, typically starting with basic science, then small studies in humans – translation from bench to bedside – and finally large clinical trials. Yet most clinical trials do not change practice (1); this suggests that their results are either unreliable or that such trials are irrelevant to clinical practice. The use of surrogate, or intermediate, outcome measures in surgery and anaesthesia is widespread (2). Such surrogate markers are of questionable significance and often have no convincing relationships with patient outcome. Severe complications leading to death or chronic disability are rare, but it is these that patients (and doctors!) are concerned about. Such low event rates have important implications for trial design.
Because most improvements in medicine are modest and incremental, large numbers of patients need to be studied in order to have adequate statistical power to detect a clinically important difference in serious adverse outcomes (3,4). Such studies require a sample size in the many 1,000s to provide sufficient statistical power and reliable estimates of effect. Large trials with straightforward requirements reflecting standard practice are sometimes called effectiveness, pragmatic, or practical trials. They thus optimize generalisability and so are clinically relevant.
But it must be kept in mind that large clinical trials are focused on the question, “Does this intervention work” (i.e. improve outcome)? They are not designed to investigate how or why a drug or techniques does or doesn’t work – that is, underlying mechanisms and explanations often remain unclear.
Large trials offer two key, frequently under-utilised benefits for those engaged in basic science. First, they offer a great opportunity to embed one or more substudies, with additional blood and other sampling in a subgroup of patients, to provide mechanistic insights. Second, there are often unexpected findings in large clinical trials, and these can inform the design of follow-up secondary studies to investigate how or why such effects occur. That is, reverse translation. It should be kept in mind that most medical discoveries are serendipitous, identified through the inquisitive minds of attentive investigators.
I will outline examples from some of our large, high-impact clinical trials (5-8).
We look forward to welcoming Professor Myles for the Symposium!
Translational Research Symposium
- Date: Monday 31 July, 2017
- Time: 8:30 for 9:00am start - 7:00pm close
- RSVP here
If you are a graduate student or early career researcher, you may be interested in the Young Investigator poster competition. See here for more details and to RSVP.
1. Kelly MJU, Wadsworth J. What price inconclusive clinical trials? Ann R Coll Surg Eng 1993; 75:145-6.
2. Fisher DM. Surrogate outcomes: meaningful not! Anesthesiology 1999; 90:355-6.
3. Myles PS. Why we need large randomised studies in anaesthesia. Br J Anaesth 1999; 83:833-4.
4. Collins R, MacMahon S. Reliable assessment of the effects of treatment on mortality and major morbidity, I: clinical trials. Lancet 2001; 357:373-80.
5. Myles PS, et al. Bispectral index monitoring to prevent awareness during anaesthesia: the B-Aware randomised controlled trial. Lancet 2004; 363:1757-63.
6. Myles PS, et al. The safety of addition of nitrous oxide to general anaesthesia in at-risk patients having major non-cardiac surgery (ENIGMA-II): a randomised, single-blind trial. Lancet 2014; 384:1446-54.
7. Myles PS, et al. Tranexamic acid in patients undergoing coronary artery surgery. N Engl J Med 2017; 376: 136-48.
8. Myles PS, et al. Restrictive versus liberal fluid therapy in major abdominal surgery (RELIEF): rationale and design for a multicentre randomised trial. BMJ Open 2017. doi:10.1136/bmjopen-2016-015358