Fred J Boyd Oration 2021

Mr. President, Peter Fowler, Mr. Jahrmarley Dawson, Distinguished Guests, and my Pharmacy Colleagues.

It is an honour to stand before you and accept the 2021 Fred J Boyd Award from the Society of Hospital Pharmacists of Australia (SHPA).

I am a student of history, and I believe history still has much to teach us, just as science is our best guide into the future. Indeed, the history of this award is poignant for me, as it is for all SHPA members and fellows. Mr. Frederick John Boyd, who made his mark a hundred years ago, was a pioneer in every sense. A hospital pharmacist, he ascended to Chief Pharmacist of Mont Park Mental Hospital. His commitment to the pharmacy profession became clear in subsequent years when he took on numerous service roles with the Pharmaceutical Society of Victoria. Recognising that hospital pharmacists would benefit from a professional society that served their specific needs, in 1941 Boyd formed the Society of Hospital Pharmaceutical Chemists with support from Mr. Charles B Macgibbon. His leadership role among hospital pharmacists was then cemented when he became the first national president of SHPA. Mr. Boyd then went on to become the first editor of what is now SHPA's flagship journal, the Journal of Pharmacy Practice and Research (JPPR). Mr. Boyd served in many community-facing volunteer roles and held lifetime memberships in at least two sporting clubs.

What can we learn about Mr. Boyd and his legacy? Many things, in my view. I'd like to highlight here a couple that I feel are worth reflecting on.

Firstly, Mr. Boyd taught us that service to your community creates a better community — this is clear when you see Mr. Boyd's legacy that is SHPA, a professional society that now guides a community of fundamental importance to the Australian healthcare system and a profession whose research and advocacy influence global health care.

Secondly, Mr. Boyd taught us about being creative and cultivating a pioneering mindset to create new entities and opportunities. Mr. Boyd established himself within pharmacy and then created meaningful institutions. I believe he did this through an understanding of the organisational and political opportunities available to him and then made wise decisions that dynamic and influential managers would support.

Thirdly, Mr. Boyd was committed to the long-term success of his initiatives with professional societies (as well as cricket and football clubs) and spent years of his life to ensure his vision would translate into a sustained and successful endeavour. As we reflect on SHPA, I'm sure we are all grateful for his unparalleled commitment and impact.

Of course, while this is not an award for Fred J Boyd, it is an award in his name and, as he clearly did, I believe in the power of both history and science.

As I hope I was able to convey, Mr. Boyd possessed key traits that led to his success. Reflecting on my own career, I feel that any success I have had comes back to some of these same attributes. Of course, I have been supported and mentored by amazing people in pharmacy and medicine, from Andrew McLachlan, Jacqui McInerney, and Tim Chen to Karen Allen, Jeff Lipman, Carl Kirkpatrick, and, more recently, William Hope, Ian Coombes, Michael Barras, Andrew Hale, Sonya Stacey, Michael Dooley, David Paterson, Roslyn Boyd, Karen Moritz, and Geoff McColl, not to mention an amazing Pharmacy Department at the Royal Brisbane and Women's Hospital (RBWH) and research group at The University of Queensland — a luxury that I'm not sure was enjoyed by Mr Boyd. However, by virtue of their support, I have been able to achieve more than I could have hoped for. I will acknowledge my family later, but all I am is a product of a nurturing environment with deeds that reflect upon everyone who has supported me.

I consider service to the profession and a willingness to collaborate with others to be a very important quality that I take great pride in. I have lost count of the number of people who have helped me along the way, but by understanding the legacy created by such generosity, I have now lost count of the number of people that I feel I have helped in some way, even if I will never forget their names and faces. I know that all of those people also see the benefit of giving and service and help many others themselves. In terms of service to SHPA, I was honoured to serve for many years on the Queensland Branch, including as Chair. I was honoured to co-convene a national conference. I'm particularly honoured to have served on leadership committees for Critical Care and Infectious Diseases for over 10 years and to be able to contribute to Standards of Practice in both areas. I am very proud of my long-term stint as Associate Editor of JPPR. In this sense, I hope that my service to my profession, via my professional society, has benefited others. It is said that ‘it is the little things that make the biggest impact’ and I feel that the biggest impacts that people have had on my career stemmed from interactions with mentors which I'm sure were considered small to them.

I also see the benefit of having a pioneering mindset and seeing problems as things waiting for solutions and not just things that block progress. Many of the steps I have taken in my career are not entirely unique or original, but they were not a curated pathway and so always took some courage and, more importantly, encouragement and support, which are yet one more benefit of my amazing support network.

I also believe in seeing initiatives through to the end, just as Mr. Boyd believed in sustaining his. My commitments to SHPA, to hospital pharmacy, and to academic research are all long-term because each is important to me, and they are causes I believe in and want to see succeed.

This is why I believe history is important. The behaviours of those who have achieved success will still be successful behaviours in the future, and I see value in understanding how their actions are creating opportunities for us now.

What about science? As we all know, science has perhaps never been more important and influential in the consciousness and behaviour of society. COVID-19 and climate change pose challenges to humankind that have shaped and continue to shape local and international policy informed by science. Of course, I study neither of these, but each has ensured a greater awareness in the community of the value of science.

My research program seems relatively specific from a clinical practice perspective, but it actually seeks to address many individual clinical practice questions. Antibiotic dosing in challenging patients is something I know to be important from my clinical experience and I know is subject to significant uncertainty for most clinicians. We know that effective antibiotic dosing saves lives, but the question is: What is that dose? What should the dose be with 1-year-old patients? With hundred-year-old patients? If their BMI is 20 or 60? If they have severe renal failure or augmented renal clearance? If the site of infection is a pus collection in the brain or a burn wound? If they receive one of a myriad of different forms of RRT (or dialysis)? Or ECMO? Or plasma exchange? If the patient is critically ill on triple inotropes? Or is receiving IV infusions at home as part of a HITH program? What if we do not know what pathogen is causing the infection? Or we do and it is extremely drug resistant? I've been fortunate enough to establish a research group and international network that can efficiently study these real-world clinical problems. We have now done that hundreds of times. We are fortunate to have the network we do of like-minded clinician-researchers who donate their time and expertise to help us solve problems. Our network covers all continents of the globe, and this means I now have new friends all around the world, friends I would not have had without these opportunities. Studies like the DALI Study (68 ICUs in 10 countries),¹ ASAP ECMO (6 ICUs in 4 countries),² SMARRT (29 ICUs in 14 countries)³ and SAFE-ICU (30 ICUs in 12 countries)⁴ are jewels in our research crown. These studies, among others, have changed international clinical practice guidelines and are referenced in leading publications, including the Therapeutic Guidelines⁵ and UpToDate⁶ — quite humbling achievements.

However, I'd like to share the story of my PhD work as it illustrates a fascinating learning curve for me and one which has helped me immeasurably in my career. My PhD involved studying the subcutaneous interstitial fluid exposures of piperacillin-tazobactam and meropenem in critically ill sepsis patients comparing administration by short 30-min infusions with continuous infusions.⁷ As most of you will know, beta-lactams have time-dependent pharmacodynamics, meaning that sustained rather than high peak concentrations have been demonstrated in laboratory studies to deliver more rapid and extensive bacterial killing. Extensive clinical literature confirms how important optimised antibiotic dosing is for maximising survival in sepsis, and we wanted to determine whether we could get better antibiotic exposures and patient outcomes with continuous infusions of beta-lactams. I remember quite a few nights in the RBWH ICU after midnight taking samples from patients and then, in the ensuing days, working in the chromatography laboratory to assay those samples. The excitement of later developing my first population pharmacokinetic models left me with very happy memories. Nevertheless, my PhD studies demonstrated more favourable interstitial fluid exposures of beta-lactams with continuous infusion, meaning that infection site exposures were also likely better. These data allowed our group to progress to a multicentre clinical trial feasibility study. This double-blinded, double-dummy RCT in three countries finished very well and confirmed our study design was robust and feasible to conduct in a multicentre format. We called that study BLING 1, where BLING stands for Beta-Lactam INfusion Group.⁸ Next, we conducted BLING 2 in 420 sepsis patients across 26 ICUs with the same study design and funded by NHMRC and New Zealand's equivalent funding body. This was also completed successfully and demonstrated some interesting clinical outcomes, which helped us learn more about the intervention, enabling us to enrich the design of the final BLING 3 study.⁹ BLING 3 is evaluating 90-day mortality rates between sepsis patients randomised to continuous or short infusions of meropenem or piperacillin/tazobactam. It is no longer double-blind or double dummy because of the nature of the primary endpoint.^{10, 11} We have now recruited >7000 patients in >100 ICUs in three continents and by the middle of next year should have results which will change global practice one way or another. This research program highlights that nurturing small things allows them to become big things, and the team of Jeff Lipman and myself has grown into a much bigger team which includes local key figures, like Joel Dulhunty, Os Cotta, John Myburgh, and Dorrilyn Rajbhandari. This team has allowed such a big undertaking to succeed, and it is an honour to be part of that, just as I am honoured to enjoy the support of Metro North Health and the RBWH as well as The University of Queensland. It is an important message for all — start with small and achievable goals and bigger impacts will follow.

I said I would comment more on my family, and I would like to close by acknowledging all of them. My brothers and sister have all been part of my journey, and each played a key supportive role in my life. My mother has never wavered in her support, nor has my father ever been unwilling to carve out some time to share some scientific, professional, or personal guidance. However, my wife Alison deserves special mention. She's made many sacrifices for me that allowed me to take advantage of all the opportunities that came my way. She is very much my partner in all my professional achievements, just as she is in my life. Our amazing girls, Evie, Lucy, and Isabelle, bring me joy and remind me why we all do the things we do.

I thank SHPA for this amazing honour. I pay tribute to Mr. Boyd for his legacy, and I hope that one day I can reflect on my own legacy with pride, and for all of those who have helped me achieve the things I have, I hope that they too will be proud of the product of their kindness and support. I also thank all of the research funding agencies that have made my research possible.