Categories

Above the Fold

The Next Steps in Parkinson’s Disease Research

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:

  1. 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”.
  2. NIH alludes to $74 million of the overall budget as indirect costs without an explanation of this distinction.
  3. 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”.
  4. 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:

CategoryNumberCosts ($000)
Explanatory5018,162
Exploratory3213,178
Diagnostic2111,499
Tools74,444
Biomarkers93,541
DBS133,598
Alpha-synuclein3816,642
Physical therapies1718,119
Indirect2718,975
Total214$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.

Continue reading…

A Health Economist to lead the NIH

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.

Continue reading…

Kris Engskov, Rippl

Kris Engskov is CEO of Rippl, a General Catalyst-funded company developing a wrap around care model around the primary care doctor for people with dementia. Their process is to help the family caregiver who is looking after the dementia patient and gives a ton of support to those caregivers which helps them be successful taking care of the patient at home. They start with diagnosis and use care navigators to build a care model face to face with patients. They’ve raised $52m and are nearly 2 years into serving a very neglected group of patients and caregivers–Matthew Holt

Colby Takeda, Pear Suite

Colby Takeda is CEO of Pear Suite which has developed a system that helps organizations employing community health workers to track and pay for their work. These community health workers are in multiple social and health organizations. Increasingly states Medicaid and health plans are paying directly to community organizations and Pear Suite is building the capacity for those organizations to contract and bill the plans and states. The community health workers are now out helping engage patients, particularly around preventative services, housing, food access and much more. This includes those people in the health system and is saving health care organizations money, and is improving HEDIA and Star scores. Pear Suite has been doing this since 2023 and has over 100 clients already, and has even built its own network of community health workers. A niche, but a very impactful one-Matthew Holt

Mental Health’s Unfinished Digital Revolution

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.

Investment in Digital Mental Health (2010-2023)
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.

Incubent Scale vs. Startup Scale
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.

Continue reading…

Shama Rathi, Co-Founder, LunaJoy

Shama Rathi MD is the co-founder of LunaJoy, a mental health company that works exclusively for women. It started with pregnancy (pre- and post- partum) and now is working with women in midlife for nearly a third of its cases. Shama believes that women have been ignored and LunaJoy has built out specific care pathways for women. They are moving into the market starting with Medicaid, the payer responsible for a large number of births, mostly doing it in conjunction with OBGYN clinics. It’s an interesting and necessary niche play for a large underserved group–Matthew Holt

Ten Shadowy Figures Who Shaped Our Health Care System

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 1994, a controversial figure.In the assessment of author and political journalist Elizabeth Drew, “Mrs. Lasker has been considered an able woman who has done good things but is too covetous of power, too insistent on her pursuits, too confident of her own expertise in the minutiae of medicine.”

William Menninger

During the first major WW II battle in North Africa, a startling number of soldiers were incapacitated with “Shell Shock.” One neurologist in North Africa, Frederick R. Hanson, discovered that a bit of kindness in the form of a hot shower and a warm meal, combined with sedation-induced rest, was remarkably successful in rehabilitating the majority of the “mentally incapacitated” men under his care.

Hanson’s success did not go unnoticed by the Army’s chief of the division of neuropsychiatry in the Office of the Surgeon General, William C. Menninger. After studying his results, he decided that if psychiatric casualties in a standard unit exceeded one mental casualty for every four wounded in action, this was a harbinger of broader problems—like a breakdown in morale, leadership issues, prolonged combat fatigue, or a policy breakdown in the evacuation scheme.

Continue reading…

Cancer’s Juvenescence: An Incoming Tide and the Urgent Need for a Paradigm Shift

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.

Continue reading…

THCB Gang Episode 147, Thursday December 5

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.

You Can’t Spell Fair Pay Without AI

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.

Continue reading…