2024

THCB Gang Dec 16, 2024 Joining Matthew Holt on #THCBGang on Monday December 16 at 1pm PST 4pm EST are patient safety expert Michael Millenson, physician, entrepreneur and technologist Shantanu Nundy; and Digital Health and Emerging Med-Tech Practice Co-Founder at Marsh & McLennan, Beracah Stortvedt. You can see the video below live (and later archived) & if you’d rather listen than watch, the audio is preserved as a weekly podcast available on our iTunes & Spotify channels. 2024-12-16 20:21:10

“Stay in the moment. The practice of staying present will heal you. Obsessing about how the future will turn out creates anxiety. Replaying broken scenarios from the past causes anger and sadness. Stay here, in this moment.” ~Sylvester McNutt For two years, I studied and practiced meditation. I listened to podcasts, chanted mantras each morning, sat quietly while exploring my default mode network, and traversed Eastern mysticism under the guidance of a licensed clinical psychologist who taught me how to use deep diaphragmatic breathing to stimulate my vagus nerve and lower my resting heart rate. This helped me recover from panic attacks, which I started having as a result of existential dread. After a series of nights with intrusive thoughts about death and dying, and painful memories related to my childhood, I decided to learn how to meditate so my thoughts would bother me less. It’s important to examine our feelings and emotions in order to determine what to do with them. While meditating, as you nonjudgmentally observe your thoughts, the goal is to let the thought pass and then go back to the present moment with a mantra. However, after your meditation session is over, it’s also important to catalog for yourself if a thought or memory keeps surfacing, and what feelings or emotions might be present with that experience, so that you know what to work on in your personal development. For myself, I found that many of the childhood memories that kept surfacing during meditation were related to my mother. Not surprisingly, much of my early writing as a poet includes themes and ideas related to my mother and other family issues. It was only once I started to really tackle these memories that I realized that they were attached to painful emotions directly linked to my childhood. Once I gave myself the space I needed to examine my memories as artifacts from my life—ones to be accepted and not ones that I wanted to give power to—I was able to work through them and come out on the other side. In order to do this, I started journaling, speaking about my experiences more with trusted advisors and through my creative work, and keeping up with meditation practices, which I did judiciously for three to four hours every morning. One childhood memory that used to bother me a lot before I worked through it was from a time when I was about seven or eight years old. I remembered it vividly, as the memory would keep resurfacing each day. A friend of mine and I were sitting on the floor of my bedroom, talking, when my mother came into the room. She commented sternly about how my clothes weren’t put away yet, since she’d told me having my friend over was contingent on that. She then, without saying another word, picked up every article of clothing and proceeded to throw each of them at me while I was on the floor. My friend and I were speechless. Afterwards, when my mother left the room, my friend helped me pick them up. What I realized by nonjudgmentally accepting my memory is that this experience had become a trauma point for me, one that I carried with me into my adult life until I started dealing with the emotions that were hardwired into my brain related to the event. Only once I started meditating and kept seeing this memory resurface again and again—thereby noticing that I even had the memory and emotions in the first place—was I able to deal with the fact that this instance caused me to feel wronged because of how unfair it was. I felt humiliated. I felt ashamed. How could she have done something like this, I wondered? However, once I began naming my feelings one by one, I found that the bodily sensations and experiences of the emotions surrounding the memory began to fade. I even found the courage to speak with my mother about my childhood using nonviolent communication strategies as discussed in the book Nonviolent Communication, written by Marshall B. Rosenberg, PhD with a foreword by Deepak Chopra. The most rudimentary format of nonviolent communication entails communicating about conflict by saying, “When I hear you say X, I feel Y, because I need Z,” which makes the other person more likely to be able to receive your communication without being reactive or defensive. I found great success with this approach, and while my mother and I are not close by any means, this communication approach strengthened our relationship and my relationship with myself. Now, most, if not all, of my painful childhood memories are no longer traumatic for me, including the one about my clothing. This memory and the emotions that used to be attached to it are literally nonissues for me now, years later. And yet, the most important form of communication that I found for myself is the communication with the self, all brought on by a healthy meditation regimen. So, how does one meditate with the goal of nonjudgmentally observing one’s thoughts, letting them go, and returning to the present moment in order to be successful with processing painful childhood memories and to gain more self-awareness overall? The technique that my psychologist taught me is that, at the same time as doing deep diaphragmic breathing to stimulate the vagus nerve and promote inner calmness (eight seconds in, pause, then eight seconds out), it’s good to have an intention in mind that you can chant in your head as inner dialogue. He also suggested audiating for stronger results, or putting the mantra to music in your mind, which I found was even more intellectually stimulating and led to greater mental clarity. The idea is to try to clear your mind of all thoughts except the mantra, which you have going on repeat. I chose the mantra “Hamsa” for each breath, which means “I am that which I will become,” representing personal development. When my thoughts wandered while I

By STEVEN ZECOLA Steven Zercola is back with his latest insights into research in Parkinson’s disease. You can say previous part of this series here In its latest report, the National Institute of Health (NIH) references 508 active Parkinson’s disease (PD) projects as the recipients of $243M in grants. A few caveats are warranted about these numbers: The information is not as precise as it seems.  The NIH report states that: “NIH does not expressly budget by category”. Rather, it “categorizes diseases, conditions, and other research based on a computerized process that it uses at the end of each fiscal year”. NIH alludes to $74 million of the overall budget as indirect costs without an explanation of this distinction. Only about half of the aforementioned research grants are available to review. The NIH report specifies that “{t}he minimum reporting threshold for a specific disease/condition is $500,000”. NIH isn’t the only federal government agency providing grants for PD research.  For example, the Department of Defense also maintains a budget for PD research, albeit much smaller. Generally speaking, one can categorize basic research into having exploratory, explanatory or diagnostic objectives.  Given that basic research for PD has gained some important insights over the past several decades, I have added some PD-specific categories to the more general categories of research, as shown in the chart below. Once these additional categories were identified, I assigned each of the reported studies and associated costs to the corresponding categories as follows: Category Number Costs ($000) Explanatory 50 18,162 Exploratory 32 13,178 Diagnostic 21 11,499 Tools 7 4,444 Biomarkers 9 3,541 DBS 13 3,598 Alpha-synuclein 38 16,642 Physical therapies 17 18,119 Indirect 27 18,975 Total 214 $108,158 As you can see from the activity on explanatory and exploratory research, NIH is still very much in a discovery mode when it comes to PD research.  From my perspective as a patient, only about 25% of these identified grants are in a position to produce game-changing results within the 10-year window of the legislation (namely, tools, biomarkers and alpha-synuclein). In terms of clinical research, clinicaltrials.gov provides a listing of all trials, broken down into phases, including those that are completed, recruiting or terminated.  However, the inputs are not reviewed by an independent party, and the overall numbers are not reliable and do not reflect the funding status of the trials. Nevertheless, there are a series of individual trials that show promise. A dozen or so trials target alpha-synuclein either by 1) reducing alpha-synuclein by immunization; 2) blocking misfolding of alpha-synuclein; 3) blocking alpha-synuclein aggregation; or 4) reducing alpha-synuclein synthesis. For example, Prasinezumab is designed to block the transmission of the aggregated forms of alpha-synuclein. The PROPEL Study tests a one-time gene therapy drug for people with Parkinson’s disease and a GBA1 gene mutation. Johns Hopkins is studying the safety and tolerability of RO-7486967, a small molecule designed to inhibit inflammation in Parkinson’s disease. Ambroxol is in a phase 3 clinical trial to test its long-term efficacy in slowing the progression of the disease. The above examples are provided for illustrative purposes only and by no means are near complete. Nevertheless, the two most important areas for PD research right now are 1) finding an easily administered biomarker for the disease and 2) finding a way to stop or reverse the clumping of the alpha-synuclein protein in the brain.   Finding an easily administered biomarker would enhance the pursuit of a cure by providing a quick and definitive cause and effect relationship of certain approaches.  In the case of alpha-synuclein, research has shown a direct correlation between clumping of alpha-synuclein protein in the brain and the death of dopamine producing cells.  Therefore, if the effects of alpha-synuclein can be halted or reversed, the Holy Grail of PD research can be reached. Separately, Terazosin deserves a special mention.  Several scientists found that those people who took Terazosin over an extended period of time had a lower incidence of PD and a slower progression of the disease if it manifested itself.  The drug had been approved by the FDA thirty-five years ago for other uses.  Yet it has taken years and millions of dollars for the drug to go through a Phase 1 trial to determine if it is safe.  This is a good example of unnecessary regulation at its worst. A New Approach Significantly, in July of this year, the President signed into law the National Plan to Cure Parkinson’s Disease.  In essence, the legislation requires HHS and other funding federal agencies to become more efficient and effective with respect to PD research. The HHS Secretary with advice provided by an Advisory Council has been tasked by the legislation with sorting out the strategic direction for PD research. As this program kicks off, there are several steps that can be taken to improve the effectiveness of PD research. First, all federal PD grants should be administered under one agency and coordinated with oversight by one person/office on a dedicated basis. Second, at this point in the research cycle, grants for basic PD research should be more limited in scope and increased in dollar value.  For example, additional tools such as provided by Artificial Intelligence as well as having an easily-administered biomarker for the disease will have disproportionate positive effects.  Therefore, the amount and size of commitments to these projects should be increased provided that the specific project is not being pursued in the private sector. Third, grants for physical therapies such as exercises, music and various forms of brain or body stimulation should be wound down and left to the private sector. The payback period on this research is comparatively short and the potential benefits are more limited compared to the other categories. Fourth, unless the Advisory Council finds a high degree of uncertainty from the ongoing clinical trials, basic research in exploratory and explanatory matters should be scaled back while research for specific diagnostic efforts should continue, where such diagnostic research aims to understand “why” something is happening by

By KIM BELLARD Everything’s about AI these days. Everything is going to be about AI for a while. Everyone’s talking about it, and most of them know more about it than I do. But there is one thing about AI that I don’t think is getting enough attention. I’m old enough that the mantra “follow the money” resonates, and, when it comes to AI, I don’t like where I think the money is ending up. I’ll talk about this both at a macro level and also specifically for healthcare. On the macro side, one trend that I have become increasingly radicalized about over the past few year is income/wealth inequality.  I wrote a couple weeks ago about how the economy is not working for many workers: executive to worker compensation ratios have skyrocketed over the past few decades, resulting in wage stagnation for many workers; income and wealthy inequality are at levels that make the Gilded Age look positively progressive; intergenerational mobility in the United States is moribund. That’s not the American Dream many of us grew up believing in. We’ve got a winner-take-all economy, and it’s leaving behind more and more people. If you are a tech CEO, a hedge fund manager, or a highly skilled knowledge worker, things are looking pretty good. If you don’t have a college degree, or even if you have a college degree but with the wrong major or have the wrong skills, not so much.   All that was happening before AI, and the question for us is whether AI will exacerbate those trends, or ameliorate them. If you are in doubt about the answer to that question, follow the money. Who is funding AI research, and what might they be expecting in return? It seems like every day I read about how AI is impacting white collar jobs. It can help traders! It can help lawyers! It can help coders! It can help doctors! For many white collar workers, AI may be a valuable tool that will enhance their productivity and make their jobs easier – in the short term. In the long term, of course, AI may simply come for their jobs, as it is starting to do for blue collar workers. Automation has already cost more blue collar jobs than outsourcing, and that was before anything we’d now consider AI. With AI, that trend is going to happen on steroids; jobs will disappear in droves. That’s great if you are an executive looking to cut costs, but terrible if you are one of those costs. So, AI is giving the upper 10% tools to make them even more valuable, and will help the upper 1% further boost their wealth. Well, you might say, that’s just capitalism. Technology goes to the winners. We need to step back and ask ourselves: is that really how we want to use AI? Here’s what I’d hope: I want AI to be first applied to making blue collar workers more valuable (and I’m using “blue collar” broadly). Not to eliminate their jobs, but to enhance their jobs. To make their jobs better, to make their lives less precarious, to take some of the money that would otherwise flow to executives and owners and put it in workers’ pockets. I think the Wall Street guys, the lawyers, the doctors, and so on can wait a while longer for AI to help them. Exactly how AI could do this, I don’t know, but AI, and AI researchers, are much smarter than I am. Let’s have them put their minds to it. Enough with having AI pass the bar exam or medical licensing tests; let’s see how it can help Amazon or Walmart workers. Then there’s healthcare. Personally, I have long believed that we’re going to have AI doctors (although “doctor” may be too limiting a concept). Not assistants, not tools, not human-directed, but an entity that you’ll be comfortable getting advice, diagnosis, and even procedures from. If things play out as I think they might, you might even prefer them to human doctors. But most people – especially most doctors – think that they’ll “just” be great tools. They’ll take some of the many administrative burdens away from physicians (e.g., taking notes or dealing with insurance companies), they’ll help doctors keep current with research findings, they’ll propose more appropriate diagnoses, they’ll offer a more precise hand in procedures. What’s not to like? I’m wondering how that help will get billed. I can already see new CPT codes for AI-assisted visits. Hey, doctors will say, we have this AI expense that needs to get paid for, and, after all, isn’t it worth more if the diagnosis is more accurate or the treatment more effective? In healthcare, new technology always raises costs; why should AI be any different? Well, it should be. When we pay physicians, we’re essentially paying for all those years of training, all those years of experience, all of which led to their expertise. We’re also paying for the time they spend with us, figuring out what is wrong with us and how to fix it. But the AI will be supplying much of that expertise, and making the figuring out part much faster. I.e., it should be cheaper. I’d argue that AI-assisted CPT codes should be priced lower than non-AI ones (which, of course, might make physicians less inclined to use them). And when, not if, we get to the point of fully AI visits, those should be much, much cheaper. Of course, one assignment I would offer AI is to figure out better ways to pay than CPT codes, DRGs, ICD-9 codes, and all the other convoluted ways we have for people to get paid in our existing healthcare system. Humans got us into these complicated, ridiculously expensive payment systems; it’d be fitting AI could get us out of them and into something better. If we allow AI to just get added on to our healthcare reimbursement structures, instead of radically rethinking them,

THCB Gang Dec 5, 2024 Joining Matthew Holt (@boltyboy) on #THCBGang on Thursday December 5 at 1pm PST 4pm EST are patient safety expert Michael Millenson, patient advocate & entrepreneur Robin Farmanfarmaian; futurist Jeff Goldsmith; and employer & care consultant Brian Klepper. You can see the video below live (and later archived) & if you’d rather listen than watch, the audio is preserved as a weekly podcast available on our iTunes & Spotify channels. 2024-12-05 18:43:50

By GEORGE BEAUREGARD During my years in a bustling metropolitan primary care practice from 1992 to 2010, I recall only a handful of patients under 50 who developed cancer. Not surprisingly, these were mostly cases of Hodgkin’s and Non-Hodgkin’s lymphomas, myeloma, skin, and breast cancer. Fortunately, those few patients were wearing the mantle of cancer survivor by the time I left clinical practice. Since 2010, I’ve transitioned into physician executive roles across various U.S. markets, overseeing large physician networks and other health systems, including so-called Accountable Care Organizations (ACOs) that oversee the care of tens of thousands of attributed patients. My goal has been to help transform healthcare delivery to focus on consistently delivering high-value care–defined as being of high quality and cost effective. My engagement with cancer has mainly been through monitoring how our organization performs on established cancer screening measures for breast, colon, and cervical cancers, based on HEDIS guidelines for age ranges. During those two periods, my life took two profound turns. The first occurred in October 2005 when I was diagnosed at 49 with advanced-stage bladder cancer. The second, more devastating one, occurred on September 16, 2017, when my previously healthy 29-year-old son was unexpectedly diagnosed with stage 4 colon cancer. That shocking news came a month after his wedding. While I knew the grim 5-year relative survival rate for this stage was about 13 percent, I still hoped and prayed that he would somehow end up being on the positive side of that survival statistic. Throughout his three-year treatment at Dana Farber Cancer Institute (DFCI), in Boston, my son, while courageously fighting his battle—one he would eventually lose at 32—became a passionate advocate for raising early-onset colorectal cancer (CRC) awareness and the need for increased research funding. He played an important role in helping to launch DFCI’s Young Onset Colorectal Cancer Center, which has since treated over 1,500 patients. Many of those individuals are between the ages of 20 and 40. Six months before his death, my son made a memorable appearance on The Today Show. Fatherhood and medicine are deeply ingrained in my identity. After the initial shock of my son’s diagnosis, I delved into medical and scientific literature, seeking all relevant information. What I’ve discovered, and continue to learn, is that there’s been a global surge in early-onset cancers, defined as occurring in people under the age of 50. Between 1990 and 2019, early-onset cancer cases globally surged by nearly 80 percent, with related deaths increasing by around 30 percent. In the U.S., projections suggest that by 2030, one-third of colorectal cancer cases will be in individuals under 50. It’s already the leading cause of cancer deaths in men younger than 50. In women, it now trails only breast cancer. Since 2021, screening ages have been lowered; colon cancer screening now starts at 45 and breast cancer at 40 for average-risk individuals. Yet, given the trends, these starting ages might still be too high. The alarming early-onset cancer trend has led me to expand my work focus beyond improving screening rates, which remain significantly below national targets. Now, I am also concerned with addressing undiagnosed early-onset cancers that could become lethal if not caught early. It’s been well established that early detection of precursors to cancer and lower-stage disease improves outcomes. Enter the promise of emerging blood-based cancer tests, so-called liquid biopsies, that detect DNA fragment modifications, genomic alterations, aberrant methylation and certain biomarkers circulating in the bloodstream from cancer cells and tumors. Recently, the FDA approved Guardant’s SHIELD test, a blood-based screening test for colorectal cancer. Building on the promising results of the U.K.-based PATHFINDER study, which used the commercially available (but not yet FDA approved) GRAIL Galleri test capable of  detecting 50 types of cancer, a large-scale prospective trial involving 140,000 participants is underway in the U.K.; the results are expected in 2026. The trial’s primary endpoint is an absolute reduction of late-stage (stage 3 and 4) cancers diagnosed. Cancer-specific mortality will be analyzed after five years of surveillance. If the trial results are positive, the U.K.’s National Health Service intends to proceed with a large-scale pilot program involving the test’s use in clinical practice. People diagnosed with cancer obviously above all want to be cured. When that’s not possible, detecting cancers at an earlier stage (the so-called “stage shift”) can still offer such quality-of-life benefits as giving afflicted people a chance to witness their children graduate from high school or college, to attend their weddings, to be present for the birth of their children, to a hold their grandchildren for the first time and other memorable life events. There are no ways to measure economically those occasions. Among the five cancers with established evidence-based screening methods, screening rates fall short of national targets. Numerous factors contribute to this disparity, including limited access to healthcare providers, socioeconomic factors, insufficient knowledge about the occurrence and spread of specific cancers, the significance of screening in early cancer detection, and the preference for less invasive techniques. Additionally, for many cancer types, no screening tests are available. Innovative screening solutions are emerging, such as the blood-based single or multi-cancer early detection tests and multi-target stool DNA tests. Two of these have received FDA approval: GUARDANT’s Shield test–which has a 83 percent sensitivity and 90 percent specificity, and, Exact Sciences Cologuard Plus, urine- and breath-based tests have also been developed and are being investigated. Despite the increasing attention to early-onset cancers, public awareness remains limited. As awareness increases, clinicians—particularly community-based primary care providers—will undoubtedly encounter questions about abnormal early detection test results and whether patients should be tested in this manner. (I’m curious about how many of the 38.5 million people who watched the Thanksgiving Day NFL game between the Giants and the Cowboys on Fox noticed the mention and the conversation regarding the GRAIL Galleri test.) Early detection tests hold promise for addressing lagging screening rates, particularly in people who decline a stool-based test or a colonoscopy; socioeconomically disadvantaged populations that lack access to

By MIKE MAGEE The incoming Trump Administration nominees for positions in Health and Human Services (like RFK Jr. to direct the department and Mehmet Oz to head Medicare and Medicaid Services) are names you know and apparently many trust? In this morning’s New York Times, Dr. Ashish Jha, President Biden’s Covid lead, thinks he knows why. He says, “You have a large swath of the population facing a health crisis, and they feel like medicine and public health isn’t delivering…They’re much more open to people saying, ‘The whole system is corrupt and we have to blow the whole thing up.’”  As Ashish knows better than most, we didn’t arrive here out of the blue. Over the years, many of the players who had the greatest impact on America’s health care system as we know it, remain hidden in the historic shadows. Here (in no particular order) are 10 of the least known but most influential figures in shaping health policy in our lifetime. Sam Massengill In spring 1937, the head of sales for S.E. Massengill Company in Bristol, Tennessee, went to the company head, Samuel Evans Massengill, with an idea generated by customer feedback. Massengill salesmen were passing along reports from doctors that there was demand among parents of young children suffering from strep throat for a liquid version of their new sulfa drug. Massengill, charged the company’s chief chemist, Harold Cole Watkins, to find an effective solvent in which powdered sulfanilamide (an anti-biotic) could be dissolved. His choice was diethylene glycol, which smoothly dissolved sulfanilamide powder and led to a concoction that was 10 percent sulfanilamide, 72 percent diethylene glycol, and 16 percent water. Flavored with raspberry extract, saccharine, and caramel, it passed the taste and smell tests, but in keeping with then current federal regulations—or lack thereof—there was no test for safety. In fact, no one did even a rudimentary check of the literature on diethylene glycol, which would have quickly revealed that it was a highly toxic component of brake fluid, wallpaper stripper, and antifreeze that had caused a fatality in 1930. Instead, perhaps sensing that its competition would be right behind, Massengill rushed its “Elixir Sulfanilamide” into production, then shipped 240 gallons of the red liquid to 31 states through a network of small distributors in early September 1937. Within two weeks, children began to die. In all, more than 100 children died, but only after going through 7 to 21 days of wrenchingly painful illness including “stoppage of urine, severe abdominal pain, nausea, vomiting, stupor, and convulsions.” The whole disaster was vigorously reported in the press, and drug safety soon inched its way up the list of New Deal priorities. By June 11, 1938, bills from the Senate and House of Representatives had been reconciled, and on June 25, 1938, President Roosevelt signed into law the 1938 Federal Food, Drug, and Cosmetic Act. Samuel Massengill belatedly issued a statement on behalf of his company: “My chemists and I deeply regret the fatal results, but there was no error in the manufacture of the product. . . . I do not feel there was any responsibility on our part.” Unfortunately, Massengill’s morally blind position reflected the letter of the law at that time. In short, the absence of effective legal sanctions meant that a company or an individual could indeed sell a deadly medication and get away with it. Mary Lasker Born in 1900, Mary Lasker was the daughter of Frank Elwin Woodard, the head of the local bank in Watertown, Wisconsin, and a shrewd businessman with Chicago connections. By her own account, she was a campaigner almost from birth, and she traced her interest in promoting medical research back to an event she experienced at the age of three or four. Her mother, a local community supporter and civic activist, took Mary to see their ailing servant, a Mrs. Belter, who had undergone a double mastectomy as treatment for breast cancer. “I thought, this shouldn’t happen to anybody,” Mary Lasker later wrote. As a young adult, she began to focus on health policy issues and became a devotee to Margaret Sanger. Mary sought out financial support for the organization, turning to a dynamic advertising man, Albert Lasker, who had launched some of America’s most recognizable consumer brands, including Lucky Strike cigarettes. Known as the “father of modern advertising,” Lasker is credited for suggesting that the Control Federation of America be renamed the Planned Parenthood Federation. When Albert asked Mary what she wanted to accomplish, she listed reforms in health insurance, cancer research, and research against tuberculosis. Albert responded, “Well, for that you don’t need my kind of money. You need federal money, and I will show you how to get it.” When Mary and Albert married in 1940, the world was preparing for war. Beginning in 1942, the Laskers began to cultivate science luminaries who shared their commitment to maximizing government funding of applied research. The Laskers realized early that they would need a credible health-related national organization to anchor and launch their campaign and set their sights on the American Society for the Control of Cancer, an organization created in 1913 by 10 physicians meeting at the Harvard Club in New York City. The leadership was more than happy to grant the Laskers easy entry to their Board of Trustees in return for financial support. By 1944, the Laskers had seized control of the Board, largely dumped the doctors, and renamed the group the American Cancer Society (ACS). Its leadership was now composed of name-brand corporate heads, entertainment giants, and advertising executives. To add further glory to the idea of Big Science, Mary and Albert created the annual Lasker Awards, with the somewhat self-serving tagline “Sometimes called ‘America’s Nobels.’” She then began to collect academic researchers, promote their careers, injecting publicity and special placement on government bodies. Over a decade she was at the center of creating seventeen specialty Institutes within the new NIH, most built around her favored scientists. Mary Lasker died in

By TREVOR VAN MIERLO In 2021, digital mental health and substance use startups attracted a record-breaking $5.1 billion in funding. Despite the surge, the promise of scalable, transformative digital health platforms remains unfulfilled. Following the surge, investment plummeted. Unlike other industries that have been revolutionized by digital-first solutions, digital health struggles with models that fail to address cost, complexity, and access. What we’re left with entering into 2025 are a smorgasbord of solutions clamoring to attach themselves to traditional enterprise incumbents (Health Insurance Providers, Electronic Health Records, Hospital Systems). These incumbents have achieved scale – but not the type of scale that digital health needs to flourish. Digital Mental Health Investment (2010-2023) Incumbents Build Deep, Startups Go Wide Incumbent scale is infrastructure-heavy, slow, and linear, and focuses on deep integration within their established markets. In contrast, startups aim for technology-driven, exponential, and global scale, leveraging digital platforms to serve millions of users quickly. While startups have the speed advantage, achieving scale similar to incumbents requires win-win partnerships and fundamental shifts away from established business models. Incumbent Scale vs. Startup Scale The investment market does see the tremendous opportunity: a massive, growing global customer-base proactively demanding help as social stigma decreases. And as time passes, this customer-base grows exponentially with technology pervasiveness. What investors see is unmet demand for mental health and substance use treatment, and a historic opportunity for digital health to step up and deliver solutions that are scalable, accessible, and affordable. However, the delivery mechanism to these populations, though digital, is obfuscated through the blurred lens of incumbent purchasing power. We can’t get past incumbents’ size, their reach, and their connection to patients. In this common view, incumbents are the customer. This view is promoted by both industry and academia. A recent HLTH Inc. summary, titled Boston Think Tank: Event Takeaways – Scaling Digital Health: De-Risking Adoption summarizes this: “To effectively scale digital health solutions, a carefully crafted strategy is needed – one that meets the intricate demands of healthcare systems while navigating potential adoption hurdles“. Last April a JMIR Publications published Digital Health at Enterprise Scale: Evaluation Framework for Selecting Patient-Facing Software in a Digital-First Health System. It begins: “The digital transformation of our health care system will require not only digitization of existing tools but also a redesign of our care delivery system and collaboration with digital partners.“ Both will take decades to achieve, and the market won’t wait. The customer is not the incumbent. The customer is not even patients – it’s people. For now, demand surges, but digital health is stuck in the middle. Demand Surge: Mental Health & Substance Use TAM, SAM, and SOM To understand the scale of the opportunity in digital mental health and addictions, we turn to TAM (Total Addressable Market), SAM (Service Available Market), and SOM (Serviceable Obtainable Market)  – frameworks widely used by investors to evaluate market potential. The framework is summarized nicely by Ali Gamaleldin here. The TAM, SAM, and SOM in mental health and addictions represents an extraordinary, if not immense, business opportunity far surpassing many other industries in scope. The size of the market is a result of high prevalence (1 in 8 citizens), persistent demand, and global scalability after the proper solution is implemented. In North America and Europe alone, the annual TAM for mental health and substance use assistance is currently estimated at $1.2 trillion. TAM, SAM, and SOM for North America and Europe: Mental Health and Substance Use In Australasia the TAM, SAM, and SOM are estimated at $60, $15, and $3 billion, respectively. A lack of comprehensive epidemiological data prohibits the TAM, SAM, and SOM from being calculated for Asia, but growth opportunities are enormous. This is similar to Central and South America, which are further compounded by diverse economies and cultures, government-led healthcare systems, and cultural perceptions of mental health. But despite setbacks in Asia, Central, and South America, the diverse, multicultural societies in North America and Europe can actively test and validate these emerging markets. Those regions are ripe for follow-on expansion and digital scale. But has this been done before? What other industries have addressed opportunities with high TAM, SAM, and SOM? Is there a roadmap? The Current Market and Roadmaps Rock Health Capital appeared optimistic about 2024. However, in reality digital mental health companies only raised $682 million in the first half. MedTech Strategist reflect this cautious optimism, and Galen Growth | Insights You Can Trust states that digital health is poised to outperform 2023, but with the investment focusing on AI are these numbers indicative of digital health breakthroughs? There are several factors behind the rapid decrease in funding from 2021, including a correction due to pandemic-driven surge, overvaluations, and investor fatigue, but markets are opportunistic. But let’s face it – the primary reason is that despite the ongoing hype surrounding digital health, a clear winner – or winners – have not emerged. Worse – unlike other industries that have transformed to digital, we still haven’t seen a profitable business model. Looking to Other Industries In other industries, significant TAM, SAM, and SOM opportunities were leveraged to disrupt industry incumbents. Successfully Scaling TAM, SAM, and SOM In the above examples, each company disrupted incumbents by addressing problems like cost, complexity, or access. Those of us in the digital health industry need to honestly ask ourselves if any of the solutions we’ve created have: reduced costs (one could argue healthcare is more expensive than ever) made the help seeking process and access less complex (try to obtain immediate access to a digital health product) opened doors to non-traditional customers (e.g.  non-insured, minimally-insured, students, etc.) Substitutions & Supplements Digital health today is dominated by substitutes, like telehealth and digital therapeutics (mimicking traditional care), and supplements (engagement apps and wearables). These tools enhance failing models and do not address the TAM. Disruptions vs. Supplements vs. Substitutions Neither approach addresses the core challenges of cost, complexity, and access. True disruption is still missing. Digital Health: A Problem in Search

By SAURABH JHA Early on in the COVID-19 pandemic a seroprevalence study from Santa Clara indicated that the viral spread was far greater than was believed. The study suggested that the infection fatality rate (IFR) was much lower than the case fatality rate and perhaps even lower than the suspected IFR. The researchers estimated that 2.8% of the county had been infected by April 2020. The virus was contagious and, most importantly, caused many asymptomatic infections.   The study, released as a preprint within a month of the lockdown, should have been published by the NEJM or Lancet. The specificity of the immunoassay was a whopping 99.5% and could not have been lower than 98.5%. Instead, it was roundly criticized by born-again methodological purists. Noted statistician, Andrew Gelman, known expert at dealing with (very) imperfect statistical methods, wanted an apology from the researchers for wasting everyone’s time by making “avoidable screw ups.” Around the same time, a similar study published in JAMA came to similar conclusions. Researchers found that the seroprevalence COVID-19 antibodies in LA county was 4.65%, 367 000 adults had SARS-CoV-2 antibodies, substantially greater than the 8430 confirmed infections. They concluded that “contact tracing methods to limit the spread of infection will face considerable challenges.” No one asked the researchers for an apology, presumably because the study had passed anonymous peer review and had escaped the wrath of the medical commentariat. A few months later, a German study suggested that many infected with COVID-19 had myocarditis. This meant that the asymptomatic were not just reservoirs of viral transmission, but walking tombs of cardiac doom. By many, the researchers, who used cardiac MRI to look for myocarditis, put a figure at nearly 80%. That’s a lot. No virus had ever done that. That number itself should have invited scrutiny. The animated, born-again empiricists, who has been energized by the Santa Clara study into becoming methodological sleuths, went into hibernation after the German myocarditis study. The study was swallowed uncritically by many and was covered by the NY Times. If the rigor demanded of the Santa Clara study was that of a Pythagorean proof, the German myocarditis study received the scrutiny of a cult prophet. The burden of proof in them days was like shifting sand, which shifted depending on the implications of the research. The Santa Clara study suggested the test – isolate strategy was forlorn, as controlling the viral spread was akin to chasing one’s tail. The German myocarditis study was cautionary, emphasizing that that the virus should not be under estimated, as even asymptomatic infections could be deadly. The Santa Clara study challenged lockdowns, the German study supported lockdowns. The senior author of the Santa Clara study, Jay Bhattacharya, has been nominated by President Trump to be the next NIH director. His nomination has surprised a few, upset a few, irritated a few, shocked a few and, as befits a polarized country, pleased many. Bhattacharya may well have won the popular vote, though I’m uncertain he will win the institutional vote. Bhattacharya’s anti-lockdown views rapidly made him a persona non grata in academic circles. But he was no slouch, but a Stanford health economist, with an MD and a PhD, who had researched human behavior during pandemics, the sort of academic who makes health policy, who once advocated for improved access to Hepatitis C treatment. He believed that the lockdowns caused more harm than good. You may disagree with him and I certainly do – I believe early lockdowns did save lives ( I’m unsure of the efficacy of the later lockdowns). However, to hold Bhattacharya’s premise as fringe is itself a sign of how unhinged the medical fraternity became during the pandemic. Bhattacharya was guilty of thinking like an economist, of always asking about trade-offs, of weighing the harms against the benefits of public policies, including lockdowns. What was remarkable was that many public policy experts, such as the celebratory economist, Justin Wolfers, saw little trade-offs between lives and the economy in the early lockdown. I get the allure of that position. Once you deny trade-offs you don’t have to make hard decisions, even in thought experiments in your head. It’s cognitively appealing. I had a long conversation with Bhattacharya during the pandemic. There were many things we disagreed about. Bhattacharya viewed lockdowns as a black swan event. He believed that lockdowns could cause societal upheaval, a Hobbesian breakdown of the delicate forces which maintain social order. I have no idea if he was right. Thanks to Operation Warp Speed, which enabled vaccine development in record time and ended the pandemic, we never had to find out. But was Bhattacharya’s belief fringe, like “earth is flat” fringe, or was it “I don’t like your opinion and therefore I will call you a Nazi” type of fringe? His nomination is ironic, and certainly karmic, as there was a concerted effort to discredit Bhattacharya after he spoke against the lockdowns and was one of the signatories of the Great Barrington Declaration which advocated focused protection. Bhattacharya was shadow banned by Twitter’s moral police. The ham-fisted attempts to censor him backfired spectacularly. Instead, of being consigned to irrelevance, Bhattacharya’s fame grew – it was the Streisand Effect on steroids. He was not censored in the Stalin/ Mao/ Starmer version of censorship. But academia did something else. They ignored him, were unwilling to debate him, considered him beneath their dignity to engage respectfully, but spoke about him incessantly on Twitter. Alas, this was a missed teaching moment. A rigorous, moderated, structured scientific debate between Bhattacharya and a lockdown advocate, such as Ashish Jha, would have been valuable, mostly for Bhattacharya’s critics who now appear like that angry old man yelling at the clouds. The major criticism of Bhattacharya is that he under estimated the pandemic death count. Few academics emerged from the pandemic unblemished. If some made errors of underestimation, others made errors of over estimation. It is an odd morality where underestimating the virus is a vice but underestimating

“The only thing you sometimes have control over is perspective. You don’t have control over your situation. But you have a choice about how you view it.” ~Chris Pine I had a happy, carefree childhood up until a point. I remember lots of giggles, hugs, and playfulness. One summer, as we were sitting in my grandmother’s yard enjoying her homemade cake, my mum’s right hand started trembling. My worried grandmother encouraged her to eat, but her hand continued to tremble. I remember her troubled look. She must have sensed something was wrong. Just three months later, she was gone. Acute leukemia meant that on Monday she received the results of a worrying blood test, on Wednesday she was admitted to the hospital, and by Friday she had died. I was only ten years old. My aunt broke the news to us that Friday afternoon by saying, “Your mum has gone to the sky.” If I were to explain what the news of her passing felt like, I would say it was like being hit by lightning. I’ve read that in cases of sudden death, children can stay stuck in some sort of confusing reality: They hear what happened and react to the news, but they don’t quite comprehend it. Somehow, deep inside, they don’t really believe it. In my case, and for years following my mum’s death, I thought that she had gone to the sky, but that she would come back. It was just a trip, or a bad joke. She would most definitely come back. As you might be guessing, I did not get much support in dealing with my grief. On the contrary, the message I got was that life should go on. That a page had turned, but the preceding pages weren’t worth reading. This is also how all the adults around me acted. So, even though lightning had struck me, I simply stood up and continued to walk, despite all the invisible damage it had done. The wake-up call to locate that damage and try to repair it came years later when I started experiencing health issues that my doctors said were linked to chronic stress. That’s when I finally decided to face my grief. My young adult body was giving me a clear sign: There were too many unprocessed emotions, desperately needing to find a way out. Once I allowed myself to finally feel that my heart had been shattered in a million pieces, I started putting those pieces together and redefining who I was. If my life were a book, grief would be the longest chapter. When I meet someone for the first time, I almost feel like saying, “Hi, I’m Annie, and my mum suddenly died when I was ten.” That’s how much it defines who I am. Negatively, you might think. Indeed, her absence still causes tremendous pain. I never felt this more than when I had my own children a few years ago. Becoming a mother does not mean that you stop being a daughter who needs her mother. You also become a mother who would like her children to have a grandmother. My mother is not there to spoil my daughters, and they will never get to know her. There is no one I can ask to find out how I was as a baby. She isn’t there to listen to my worries or fears while I navigate parenthood. I still get a ping in my heart when I see ten-year-old girls with their mums, seeing myself in them and re-living the immensity of such a loss. And as I am approaching the age she was when she died, I’m terrified that I will share the same fate and that my girls will grow up without me. Nevertheless—and I know this might sound contradictory, but aren’t grief and life full of contradictions?—in many ways, her absence has also been a gift. Thanks to her: –I fully embrace the idea “live every day as if it is your last” because I know that there is a very real possibility that this day might indeed be my very last. While you might think this means living life with fear, quite the opposite is true. It means living life full of appreciation, gratitude, and love for this body that is still functioning, for the people around me, and for life itself. –I choose to be truly present with my children and close ones and cherish deep relationships because I want to make the time we spend together count. If the memories we are creating are shorter for whatever reason, let them be powerful. –I have a job that gives me a deep sense of purpose and meaning because anything else would make me feel like I am wasting precious time that I don’t necessarily have. I’m honored to be making a difference in other people’s lives by helping them think differently about their lives and helping them through their own grief. I make it my goal to share my gifts with the world while I live on this planet. –I am (relatively) comfortable with the challenges that life throws at me. When you survive after the tragedy of losing a parent, you don’t sweat the small stuff as much. I still find myself getting upset by little things like anyone else, but I’m able to quickly change my perspective and realize that many of the things that upset us are not as important as we first think. –I know that I cannot control life because life is utterly uncontrollable. In fact, I was a control freak for years, trying to make sure nothing tragic would ever happen to me or my loved ones again, until I realized that this was a reaction to my mum’s passing. I now know this isn’t a way to live life, and that is liberating. –I take care of my health to feel good in my body, not because I want to live until I’m 100,