Bill Hunter’s Post

Gait as a Biomarker Few things are more “human” than our ability to walk upright. Ever recognize your child at a distance by observing how an otherwise ill-defined figure was walking or running? Gait is like a fingerprint – completely unique to each of us. It is also extremely complex, requiring highly coordinated functioning of our musculoskeletal, nervous, cardiac and respiratory systems. Abnormalities in virtually any body system result in characteristic ambulatory changes that physicians can use to recognize and diagnose numerous medical maladies. The “shuffling gait” of Parkison’s Disease, the “foot drop” of L5 entrapment, Trendelenberg, hemiplegia, and dystonia have been taught to generations of medical students; there are scores of diseases that result in gait pattern changes (see attached figure). Although the clinical knowledge existed, doctors lacked precise tools to reproducibly identify, measure, and quantify pathognomonic gait changes for true “diagnostic” purposes. Gait labs aren’t widely accessible and wearables need to be worn. A recent article describes the use of wearables to diagnose subclinical heart failure (https://lnkd.in/gh5Q66qb) using a combination of activity and gait metrics. That makes perfect sense to me – poor cardiac function changes your exercise tolerance (activity levels) and gait (e.g. claudication). Persona IQ recently passed 10 BILLION data points and thousands of total knee patients are now generating continuous activity data and “gait lab quality” kinematic data several times per day, every day. Our patients are typically of the age where co-morbid conditions known to alter gait kinematics - neurologic (Parkinson’s Disease, ALS), vascular (CVA, Peripheral Vascular Disease / Claudication, DVT), TKA-related (contracture, loosening), infectious (Prosthetic Joint Infection, Septic Arthritis), metabolic (Diabetes, Gout), and respiratory (COPD) disorders – are developing or are already present. For example, statistically, hundreds of PIQ patients must also have diabetes and heart disease. We are hoping to capture, analyze, categorize, and quantify gait changes associated with non-TKA disorders as the PIQ database expands exponentially. Soon, Activity and Precision Gait Analysis could be used for the early diagnosis of a variety of ailments by identifying and quantifying characteristic gait pattern changes; kinematic data analysis could become a new method for evaluating and predicting disease progression. Vital signs, blood tests, and ECG have served that purpose for decades. Gait could become a “biomarker” in much the same way. Someday, your knee might alert your clinician to pending heart issues. We will be asking our doctors and patients to help us discover predictive gait biomarkers in the coming months. Thank you in advance!

I really enjoyed this interview. The focus was less upon Canary and the technical topics I usually discuss, and more about going from being a physician to working in industry. The decision to leave medicine was the hardest career decision of my life. It worked out well, but that doesn’t mean I don’t still think about it often. Good luck to those of you trying to decide which road to take - or how to stay on both at the same time!

Career Aging I have been following the explosion of science and literature regarding aging of the human body and brain. We must accept that our physical and cognitive functions change with age, but do our career paths have recognizable stages too? A career consumes an enormous part of our lives and is a significant contributor to our happiness. I present a completely unscientific retrospective of the decades of a career. 20’s – Where do I start? Fresh out of school, full of confidence and ambition; armed with peak book knowledge, you happen to the work world. The 20’s are the decade of finding out who you are and charting a course to what you will become. It may end by doing something completely different than what you started. Career changes are common, encouraged even. In the tech world, it is the most common age to start a company. I founded Angiotech. I had no idea what was coming. My carefully planned medical career would soon be in the rearview mirror. 30’s – What am I going to be? The decade of settling into a career, often by necessity. Changes, adjusted expectations. Experience blending with knowledge. The script flips - the work world happens to you. Segments of acceleration, periods of stagnation, steps backward. 40’s – What have I become? The decade that largely determines what you become. Family, friends, career, all compete for attention. Life balance is difficult. Changes in career trajectory are certain, their direction, less certain. The peak AND valley of my career. 50’s – What I thought I would be vs. what I became. The decade of reconciliation between what you imagined, and what you are. The bad news? The nadir of human happiness. The good news?  Acceptance of the good, the bad and the indifferent, finally reverses the happiness curve. As most cognitive skills are declining, one peaks – the ability to recognize patterns, anticipate problems, avoid mistakes. In healthcare, it is the most common age to start a company. I started Canary. I knew exactly what was coming. 60’s and Beyond – What will I leave behind? Planning to be President? You have 20 more years still to go. For the rest of us, the end, or at least a meaningful change, is inevitable. Those who want to retire, retire; those who love what they do, do it for as long as they can. I am in the later category – but only if I can do it at the highest level. Reality reminds you that the end is much closer than the beginning. Mindset shifts from growth to giving back. For a life’s work and knowledge to mean something, the learnings – and, most importantly, the failings – must be passed to the next generation. That’s still a work in progress.

On the first day of medical school (OK, maybe the second, after figuring out where all your classes are), you are taught about "SOAP" - Subjective, Objective, Assessment, and Plan - how to evaluate and treat a patient. This simple mnemonic will guide every patient note you will write for the rest of your career. The Patient history (Subjective) has always been the first step in any evaluation. Ask the patient what their problem is and how they are feeling. In TKA patients, PROMs (Patient Reported Outcome Measures) have become the gold standard of subjective assessment - how do you feel about your TKA results? The "O" - Objective data - is the second critical part of patient evaluation - the physical exam, diagnostic tests, radiographic imagining - objective, diagnostic information the clinician can collect and use to Assess the patient and formulate an appropriate treatment Plan. Charlie DeCook is the first orthopaedic surgeon to compare a TKA patient's Subjective experience to a smart implant's (Persona IQ) Objective assessment of post-operative TKA function. Unsurprisingly to any clinician, the two correlate, but don't perfectly overlap - validating what we were taught - both subjective and objective data are critical to assessing any patient. Who knew my professors were right all those years ago? As we learn more, PIQ can give surgeons a "second objective opinion" on the patient's function and recovery - combining subjective PROMs with objective PIQ activity and kinematic data to help Assess and Plan their patient's recovery. With even more data and the addition of AI, perhaps it will be possible to help with assessment and planning as well.

Healthcare Rainmakers Descend Upon Miami I spent last week at the Goldman Sachs Healthcare Conference in Miami held during the worst rainstorm I have ever witnessed – and I live in the Pacific Northwest. We are all grateful that miraculously no one was killed, and our hearts go out to Miami residents who suffered financial losses and property damage. Over 20 inches of rainfall fell in one day -the video was filmed from the car window as we made our way back to our hotel. Hooky at the beach wasn’t an option, so it was an excellent opportunity to take the pulse of CEOs and investors trapped in the convention center. I sat next to Goldman’s Chief Economist, Jan Hatzius, at Monday night’s CEO dinner, who described himself as “optimistic” about the remainder of 2024. Predicting the Fed would cut interest rates “a couple of times, but not the 4 or 5 times some were expecting,” macroeconomic trends are favorable, and inflation appears to be coming under control. The mood at the bar - where true impressions come out late in the evening – is dramatically improved. Many of our biotech brethren have successfully raised capital this year and IPO talk has gone from wistful in 2023, to confident in 2024. Money flows back into our industry from the top; the best companies are getting funded again. Tuesday morning, Canary was featured in a fireside chat hosted by one of my favorite people in medtech, Goldman partner Yassaman Salas. Interest in the digital transformation of medtech continues to gain momentum as more companies make strategic plays in the field, including our partner Zimmer Biomet, who announced a partnership with THINK Surgical that morning. CEO Ivan Tornos is building upon his vision of a fully integrated suite of robotics and “smart” implants that generate actionable data and clinical insights throughout the entire episode of care. In the hallways and one-on-one meetings is where real information changes hands. Despite being an illiquid, private company, Canary’s schedule was packed. Roll your eyes if you must, but Big Data and Generative AI are at the top of investor’s minds. Hang around healthcare long enough and you’ll see countless trends – combinatorial chemistry, high throughput screening, biologics, gene therapy, CRISPR, immunotherapy, cell therapy, robotics, and 50 more I can’t remember. Most of the companies come and go, but one or two winners from every trend join the ranks of the mega-successful; the diamonds every investor hunts for. Unique data sets create unique clinical insights. Big data sets can address big clinical problems. As a company mining for unique data captured from within the human body, Canary hopes to be one of those remaining after the AI wave recedes. 

A Marshmallow Day Many years ago, there was a famous psychology study conducted on delayed gratification. In it, children were left alone in a room with marshmallows. If they ate them, they didn’t get any more. However, if they were able to resist the temptation to eat them, they were given more marshmallows as a reward. I recall reading that when those children were followed into later life, the ones able to delay gratification tended to achieve greater things. Working in the field of health care startups and new product development can feel like a lifetime spent waiting for marshmallows. Decades or more pass while you experiment, fail, and change directions trying to determine if the technology works and if the product will succeed. Becoming a doctor is a similar pursuit - a four-year undergraduate degree, followed by four years of medical school, and five or more years of postgraduate specialty training. Many years spent, and many hours of effort expended, before the long-awaited, next batch of marshmallows is delivered. Twelve years ago, my tenure at Angiotech came to an unceremonious end, and a few colleagues and I founded Canary on the concept of “smart” medical devices. Twelve years ago, my daughter Olivia Hunter was a freshman in high school who showed no particular interest in medicine. One of those co-founders, Fred Cushner, helped us design a “smart” knee and took a position at the Hospital for Special Surgery – the hospital that would ultimately become the first in the world to implant Persona IQ. Olivia completed her undergraduate degree at Dartmouth College, then returned home to my alma mater, the The University of British Columbia, to attend medical school. Last week, during an elective at HSS, Olivia was in the operating room while Fred implanted Persona IQ in three different patients. For good measure, he closed using Quill, the barbed suture product developed at Angiotech. It was a once-in-a-lifetime experience, and an early Father’s Day present for Dad. It is mind boggling to me to contemplate how many separate, independent events needed to successfully transpire for that moment to occur. So, the next time you feel that a career in medical research or the practice of medicine is too hard, too long, too unpredictable, and requires too much delayed gratification to be worth the effort, remember, Marshmallow Days really do happen. When they do, they are well worth the wait.

Thanks Brian! A blast from the past - a video interview taken from before the launch of Persona IQ, the world’s first #smartknee. I think most of it still rings true! 🥵 Watching it made me realize just how much Canary has needed to learn in moving from a novel technology to a clinically useful product over the last 3 years. The (Bill) Gates Law states, “Most people overestimate what they can achieve in a year and underestimate what they can achieve in ten years.” In the life of a startup, a decade passes in 2-3 years! His comment is said to be based on Roy Amara, a Stanford computer scientist in the 1960s, who said, “we overestimate the impact of technology in the short-term and underestimate the effect in the long run.” When it comes to connected devices, I guess we’ll soon find out if that is true. Thank you to biofilm Media, yourself, Life Sciences BC, Ali Ardakani, Wendy Hurlburt, and the many others who work so hard to build our industry in British Columbia.

4 for 4 Since everything in life is best expressed as a baseball metaphor, yesterday’s announcement of Canary’s unprecedented fourth “Breakthrough” designation for “smart” interbody cages is the equivalent of having one fine day at the plate. It is a testament to the talent and dedication of Nora Y., Jeff Gross, Peter Schiller, and the team in Carlsbad. Great scientists are attracted to great projects. The video shows nicely their creation for spinal fusion surgery. As I write this, they are already working on breakthrough application #5. There are reasons why this has happened 4 times. FDA WANTS OBJECTIVE MEDICAL DEVICE DATA. It is no secret that medical products get approved by being studied under tightly controlled, optimized clinical trials. The real world is messier; real world clinical results differ; success rates are lower, complications are higher. Regulators, clinicians and patients want to know actual performance – that requires numbers. You can’t improve what you can’t measure. MONITORED PATIENTS GET BETTER RESULTS. Trial after trial demonstrates the obvious – engaged, informed, empowered patients have better outcomes than those handed an information sheet on the way out the door. Diabetics using CGM have better A1Cs – even if you don’t change their treatment/dosing. Monitored heart failure patients stay out of the ER and live longer. The list goes on and on. Facilitating patient involvement in their recovery is good medicine. BETTER.  That’s how Charlie DeCook describes using objective data to monitor his patient’s AND his performance. Show me a surgeon worried about liability, and I’ll show you a hundred who want objective data to improve their results. They are scientists – and pretty darn good ones too if they got into medical school and then into highly competitive residencies! Charlie compares it to training for a marathon (https://lnkd.in/gFc6q5YU). There is a running adage: you won’t race faster, if you don’t train faster. Progress is aided by feedback on heart rate, cadence, stride length; timed sprints, tempo runs, and long runs; improving VO2  Max, lactate threshold - all require data. Human performance in sport has exploded over the last 10-20 years due to data-driven training programs. Surgery is no different – patient reported outcome measures (PROMs) are simply not precise enough to differentiate between different surgical techniques or implant designs. It’s like training for a marathon using a sextant.  Continuous, objective, accurate data obtained directly from the site of surgery makes BETTER possible. Nowhere is the lack of objective data more evident than in spinal fusion surgery. One of the most common surgeries performed in the US, it is also among the highest in variability for patient satisfaction rates. “Smart” interbody cages might help improve that.

Canary chose Zimmer Biomet as our "smart" total joint program because they are the recognized market leader AND because they had an ambitious plan to bring objective data to the practice of orthopaedic surgery. If you want to learn how all the pieces fit together and the progress that has been made toward improving patient outcomes through data-driven surgical technique and device solutions, have a listen on May 29. Tell Ivan a little bird told you.