Setting the Stage for Pragmatic Trials in Anesthesiology to Make an IMPACT: Key Insights from Trialists, and Awardees’ Proposals

By Michael Mathis, MD, from the IARS, AUA and SOCCA 2019 Annual Meetings*

As collaboratively endorsed by the AUA, eSAS, FAER, IARS, MPOG, PACT, and SOCCA, the 2^nd annual Initiative for Multicenter Pragmatic Anesthesiology Clinical Trials (IMPACT) calmly has taken major steps towards a framework for executing high-impact, transformative research within perioperative medicine. The session, introduced by thought leaders Dr. Michael Avidan, MBBCh, FCA SA, Washington University in St. Louis, and Dr. Jeanine Wiener-Kronish, MD, Massachusetts General Hospital and held on Sunday, May 19 during the IARS 2019 Annual Meeting, featured insights from a diverse panel of anesthesiologists with complementary experiences in prospective clinical trial design. The session additionally unveiled plans for three promising pilot prospective research grants, as competitively judged and awarded by a panel of representatives from the endorsing agencies, and with the intent of catalyzing subsequent large-scale, high-impact major grant awards.

Importantly noted by Dr. Avidan, there currently exists a deficiency of pragmatic clinical trials executed within the perioperative setting in the United States. Present are great opportunities to learn from – and collaborate with – global allies including Canada (Perioperative Anesthesia Clinical Trials Group; PACT), Australia and New Zealand (Australia and New Zealand College of Anaesthetists; ANCZA), Africa (African Surgical Outcomes Study; ASOS), and others.

A major obstacle to achieving such transformational research in the U.S. historically has been the lack of a prerequisite infrastructure, including data coordinating centers and core clinical trial support. Answering calls to action have been agencies such as the Multicenter Perioperative Outcomes Group (MPOG) led by Dr. Sachin Kheterpal, MD, MBA, University of Michigan; and the Duke Clinical Research Institute (DCRI) directed by Dr. Paul Wischmeyer, MD, EDIC, Duke University.

The first half of the IMPACT session featured a panel of exemplars of success in perioperative clinical trial design from across the globe: this included work presented by Drs. Jessica Spence, Bruce Biccard, and David Mazer. All panelists provided primers on pragmatic clinical trial design, including how and why such studies are critically needed to advance perioperative care. Panelists additionally discussed obstacles and opportunities encountered during their own execution of perioperative clinical trials, as a valuable substrate for evaluation and discussion of IMPACT proposals presented during the second half of the session.

Jessica Spence, MD, PhD candidate, McMaster University, Hamilton, Ontario, kicked off the panel, highlighting her work in developing the Benzodiazepine-Free Cardiac Anesthesia for Reduction of Delirium (B-Free) Trial. Through funding support from a highly competitive Canadian Institutes of Health Research (CIHR) award, Dr. Spence detailed her story of designing a pragmatic, cluster-randomized, step-wedge trial to be executed across 16 centers in Canada. Critical to successfully securing this trial funding was Dr. Spence’s ability to demonstrate feasibility in an elegant pilot study involving two of the 16 now participating centers.

Bruce Biccard, MBChB, FCA(SA), FFARCI, MMedSci, PhD, University of Cape Town and Groote Schuur Hospital, South Africa, next provided an enlightening perspective on what it takes to make a pragmatic trial truly lean and agile. Through inspirational work as Chief Investigator for the African Surgical Outcomes (ASOS) and now currently the ASOS-2 Trials, Dr. Biccard directs 664 hospital clusters across 25 countries in Africa, to determine whether increased postoperative surveillance reduces in-hospital mortality in high-risk adult surgical patients. In his work, Dr. Biccard stressed the importance of humanism and “social contracts” in driving forward research collaborations, often hinging on single opportunities for one-on-one voice communications to potential sites with limited resources. Dr. Biccard also acknowledged a need for site recognition as critical to the success of health research pursuits, regardless of perceived size or scope of contributions.

C. David Mazer, MD, FRCPC, St. Michael’s Hospital, University of Toronto, concluded the panel through illustrating the variety of ways a pragmatic clinical trial may be designed, and detailing his compelling work as lead investigator for the Transfusion Requirements in Cardiac Surgery (TRICS III) trial. In this trial, he compared outcomes following restrictive versus liberal transfusion strategies in moderate-to-high risk cardiac surgical patients at 74 sites across 19 countries.

During the second half of the IMPACT session, pilot grant awardees, as judged and selected by a committee directed by Duminda Wijuysundera, MD, PhD, FRCPC, St. Michael’s Hospital, Toronto, and Hannah Wunsch, MD, MSc, Sunnybrook Health Sciences Center, Toronto, shared presentations of their proposed work.

Grant awardees included Dr. Robert Schonberger, MD, MHS, Yale New Haven Hospital, describing his proposal, “Improving Population Health via the Surgical Encounter: Targeting Underuse of Statins;” Karim Ladha, MD, University Health Network, Toronto General Hospital, describing his proposal, “The Comparison of Analgesic Regimen Effectiveness for Surgery (CARES) Trial;” and David Mazer, MD, FRCPC, St. Michael’s Hospital, University of Toronto, describing an expansion of his work in the “Transfusion Requirements in Cardiac Surgery (TRICS)-IV Trial: Restrictive versus Liberal Transfusion in Younger Patients Undergoing Cardiac Surgery.”

The panel concluded with remarks from Dr. Wiener-Kronish, who made clear that anesthesiology research collaborators in the U.S. are rapidly approaching a tipping point: opportunities for participating in deeply impactful research – comparable to trials such as ARDSNET and TRICC achieved by other specialties – may soon become a reality for anesthesiologists in the U.S.

For more information on IMPACT, visit https://iars.org/impact-award.

*Coverage from the AUA, eSAS, IARS, FAER, MPOG, PACT, and SOCCA Initiative for Multicenter Pragmatic Anesthesiology Clinical Trials (IMPACT) Program during the IARS 2019 Annual Meeting