Health Policy – The Health Care Blog

Harnessing Digital Innovation to Unlock Cancer Discoveries

matthew holt — Fri, 19 Apr 2024 06:05:00 +0000

By DOUG MIRSKY & BRIAN GONZALEZ

What if digital innovations could be the key to reducing the burden of cancer? CancerX was founded in 2023 as part of the Cancer Moonshot to achieve this goal. By uniting leading minds across industries such as technology, healthcare, science, and government, we are breaking down silos and leveraging digital innovation in the fight against cancer. With ambitious goals to cut the death rate from cancer by at least 50% and to improve the experience of people who are affected by cancer, digital innovation is critical.

As a public-private partnership co-hosted by Moffitt Cancer Center and the Digital Medicine Society, CancerX has created a unique ecosystem and community of public and private innovators. We are focused on fostering innovation and collaboration to accelerate the pace of digital tools to help patients across their entire cancer journey. We unite experts across industries and the government, leveraging the success of the Department for Health and Human Services’ InnovationX model; a public-private partnership approach that has driven breakthroughs in kidney care, Lyme disease and COVID-19. In collaboration with the Office of the National Coordinator for Health Information Technology (ONC) and the Office of the Assistant Secretary for Health (OASH), CancerX is in sync with the US government in our common Cancer Moonshot goals to boost government-wide engagement with industry muscle. This type of multidisciplinary partnership is necessary to change the landscape of cancer treatment and care.

At the one year anniversary of CancerX, we look back on a very fast pace in building up our three pillars of work, demonstrating the ways that digital innovation is contributing to fighting cancer:

Pre-Competitive Evidence Generation – A rolling series of multi-stakeholder initiatives to develop evidence, best practices, toolkits, and value models to drive the success of the mission.
Demonstration Projects – These implementation projects pilot novel, mission-aligned approaches to demonstrate their value and sustainability for scale to drive broad adoption.

Startup Accelerator – This program provides mentorship, education, and exposure to funding and clinical partnership opportunities to a start-up cohort aligned with the mission.

And we are already deeply underway with efforts across each of the three pillars.

With our inaugural effort, a pre-competitive evidence generation project, we initially set out to identify and demonstrate how health systems might derive the most value from digital solutions as part of their oncology strategies to support patients facing financial distress or access issues. In November, 2023 we released:

A Core Competencies guide for health system use in designing a digital strategy to improve patient access and reduce patient cost
A Financial Navigation guide for support service divisions and nurse navigators to use as a guide for intervening along the patient journey with the use of digital health tools to reduce out-of-pocket cost
A Solutions Catalog showcasing tools available off the shelf to support the implementation of a digital oncology strategy

The final two workstreams currently underway are focused more narrowly on defining and maximizing the benefit of digitally-enabled patient navigation programs for health systems, as well as the patients and care partners they serve. Resources from these workstreams will be released in the summer of 2024.

In our initial demonstration project, the CancerX community sprinted into action to support the collective efforts of the Center for Medicare and Medicaid Innovation (CMMI), the National Cancer Institute (NCI), the US Food and Drug Administration (FDA) and the Office of the National Coordinator for Health Information Technology (ONC) to advance cancer-related data standards.

Specifically, we provided additional support and insights into the ongoing collaboration between the CMMI’s Enhancing Oncology Model (EOM) and the development of ONC’s United States Core Data for Interoperability (USCDI+) – Oncology extension, which aims to support the establishment of domain-specific data element lists as extensions to the existing USCDI.

The CancerX Startup Accelerator is the first-ever innovation accelerator focused on the intersection of digital innovation and cancer. We have brought together champions, innovators, and expert users of oncology digital technology to help boost the development of these promising startups that

have strong potential to solve unmet needs in cancer care.

Out of more than 100 startups, 16 were competitively selected for this first CancerX Startup Accelerator cohort. These startups are focused on one of five aspects of oncology: clinical research, screening and diagnosis, treatment and management, clinical operations, and patient/survivor/caregiver experience. They include:

By the end of the cohort, these startups will have received in-person and online mentorship from experienced innovators, insights from subject matter experts, connections with potential investors, and networking with other oncology digital technology startups, giving them a jumpstart on bringing their products and services into the lives of those who are fighting cancer.

Doug Mirsky, PhD is Vice President of the Digital Medicine Society. Brian D. Gonzalez MD is the Associate Center Director of the Moffitt Cancer Center.

And Now For Something Completely Different

matthew holt — Tue, 16 Apr 2024 05:26:47 +0000

By KIM BELLARD

The most interesting story I read in the past week doesn’t come from the more usual worlds of health and/or technology, but from sports. It’s not even really news, since it was announced last fall; it’s just that it wasn’t until last week that a U.S. publication (The New York Times) reported on it. In a nutshell, a Paris football (a.k.a. soccer) club is not charging its fans admission during the current season.

Since last week I wrote about medical debt in the U.S. healthcare system, you might guess where this is going. The club is Paris FC. Last November it announced:

For the first time in history, Paris FC is offering free tickets for all home matches at the Stade Charléty, starting from the 11 November until the end of the 2023-2024 season from its Bastia reception, in a bid to offer a new and innovative vision of football by welcoming as many people as possible.

The policy includes the men’s second division team and the woman’s first division team. The NYT article clarifies that fans supporting the visiting team might be charged a “nominal” fee, and that hospitality suites still pay market rates.

Pierre Ferracci, Chairman of Paris FC, said: “We are proud to support this ambitious and pioneering project, which goes beyond the simple framework of sport in terms of the values it conveys. We want to bring people together around our club and our teams, while committing ourselves with strength and conviction. In a context of difficult purchasing power, we are confident that a club can be an ideal tool for bringing together people of goodwill and engage with societal issues.”

Fabrice Herrault, Paris FC’s general manager told NYT: “It was a kind of marketing strategy. We have to be different to stand out in Greater Paris. It was a good opportunity to talk about Paris F.C.” The club estimates it might cost them $1 million.

It seems to be working. The NYT reports:

Months later, most metrics suggest the gambit has worked. Crowds are up by more than a third. Games held at times appealing for school-age children have been the best attended, indicating that the club is succeeding in attracting a younger demographic.

The idea is not entirely de novo; last spring Fortuna Düsseldorf, a German second division football club, announced it would offer free admission for at least three matches this season, with the intent that eventually all home matches. “We open up football for all. We will have free entry for league games in this stadium,” Alexander Jobst, the club’s chief executive, said at the time. “We call it ‘Fortuna for all’ which can and will lead us to a successful future.”

In a NYT interview last spring, Mr. Jobst added: “We think it is completely new. We were trying to think about how we could do the soccer business completely different from before.”

I’m always a sucker for efforts to think about a business completely different than before.

Fortuna has now had two of its three free matches, and Mr. Jobst told NYT last week: “Our average attendance has gone from 27,000 to 33,000. Our merchandise sales are up by 50 percent. Our sponsorship revenue is up 50 percent. We have reached a record number of club members.”

Sure sounds like a success.

Keep in mind that for most professional sports, ticket and concession revenues are gravy; the real money is from TV deals, as well as sponsorships. The NFL, for example, only gets 17% of its revenue from fans, the NBA 26%, and MLB 31%, while MLS and NHL need over 40% (not such good TV deals!). Fortuna, in case you’re interested, only gets 20% of its revenue from tickets, even though it is only in the second division.

Meanwhile, Paris FC only gets 4% of its budget from ticket sales. “We’re not taking a big risk, and we won’t lose out,” Mr. Feracci told Le Monde. “The balance will be positive, thanks to new sponsorship income and the arrival of new shareholders who have shown themselves to be keen on our vision.

Spectators matter, not just as a revenue source. We all remember American professional sports during the early days of the pandemic. The NBA finished its 2019-2020 season in a bubble, with players, staff, and media quarantined, playing in empty arenas. Most of the NFL and MLB games that year were also without fans. Players and television viewers hated the experience; it just didn’t seem real without actual fans in attendance.

“Since the pandemic, there has been a growing awareness of the role of spectators in the ‘production’ of sporting events,” Luc Arrondel, a professor at the Paris School of Economics, told NYT. “The presence of supporters in the stadium increases the desirability of the television product, and therefore, possibly, the value of television rights,”

Professor Arrondel has even made the case in a paper (“Faut-il payer les supporters?”) that it might actually make sense for professional teams to pay the most ardent fans to attend in-person.

Yes, all that is thinking about the business completely differently.

=========

Meanwhile, there’s the U.S. healthcare system, which treats its “fans” – i.e., patients – as revenue from whom every dollar should be squeezed. E.g., ever pay a facility fee for a doctor’s visit, or pay the inflated U.S. prices for prescription drugs? It’s not surprising that we end up with all that medical debt. As I wrote last week: “why are so many charges so high, why aren’t people better protected against them, and why don’t more Americans have enough resources to pay their bills, especially unpredictable ones like from health care services?”

So here’s a thought” out-of-pocket spending is “only” 11% of national health expenditures. What if we just abolished it? Healthcare’s version of not making fans pay to attend football matches.

Now you might say – that’s crazy, how would the health care system make up that 10%? I’d say two things: first, we all know that there’s 10% of savings to be had in our bloated system; what better to use them for than this? Second, and more importantly, we need to admit that the current business model in the U.S. healthcare system does not work.

It’s time to think of ways to do the business of healthcare “completely different than before.”

Not making patients pay out-of-pocket might not be the “right” way to do that, although we could do worse, but, in any event, we better think of something completely different before the system crashes.

Kim is a former emarketing exec at a major Blues plan, editor of the late & lamented Tincture.io, and now regular THCB contributor

If data is the new oil, there’s going to be war over it

matthew holt — Mon, 15 Apr 2024 07:53:00 +0000

By MATTHEW HOLT

I am dipping into two rumbling controversies that probably only data nerds and chronic care management nerds care about, but as ever they reveal quite a bit about who has power and how the truth can get obfuscated in American health care.

This piece is about the data nerds but hopefully will help non-nerds understand why this matters. (You’ll have to wait for the one about diabetes & chronic care).

Think about data as a precious resource that drives economies, and then you’ll understand why there’s conflict.

A little history. Back in 1996 a law was passed that was supposed to make it easy to move your health insurance from employer to employer. It was called HIPAA (the first 3 letters stand for Health Insurance Portability–you didn’t know that, did you!). And no it didn’t help make insurance portable.

The “Accountability” (the 1st A, the second one stands for “Act”) part was basically a bunch of admin simplification standards for electronic forms insurers had been asking for. A bunch of privacy legislation got jammed in there too. One part of the “privacy” idea was that you, the patient, were supposed to be able to get a copy of your health data when you asked. As Regina Holliday pointed out in her art and story (73 cents), decades later you couldn’t.

Meanwhile, over the last 30 years America’s venerable community and parochial hospitals merged into large health systems, mostly to be able to stick it to insurers and employers on price. Blake Madden put out a chart of 91 health systems with more than $1bn in revenue this week and there are about 22 with over $10bn in revenue and a bunch more above $5bn. You don’t need me to remind you that many of those systems are guilty with extreme prejudice of monopolistic price gouging, screwing over their clinicians, suing poor people, managing huge hedge funds, and paying dozens of executives like they’re playing for the soon to be ex-Oakland A’s. A few got LA Dodgers’ style money. More than 15 years since Regina picked up her paintbrush to complain about her husband Fred’s treatment and the lack of access to his records, suffice it to say that many big health systems don’t engender much in the way of trust.

Meanwhile almost all of those systems, which already get 55-65% of their revenue from the taxpayer, received additional huge public subsidies to install electronic medical records which both pissed off their physicians and made several EMR vendors rich. One vendor, Epic Systems, became so wealthy that it has an office complex modeled after a theme park, including an 11,000 seat underground theater that looks like something from a 70’s sci-fi movie. Epic has also been criticized for monopolistic practices and related behavior, in particular limiting what its ex-employees could do and what its users could publicly complain about. Fortune’s Seth Joseph has been hammering away at them, to little avail as its software now manages 45%+ of all encounters with that number still increasing. (Northwell, Intermountain & UPMC are three huge health systems that recently tossed previous vendors to get on Epic).

Meanwhile some regulations did get passed about what was required from those who got those huge public subsidies and they have actually had some effect. The money from the 2009 HITECH act was spent mostly in the 2011-14 period and by the mid teens most hospitals and doctors had EMRs. There was a lot of talk about data exchange between providers but not much action. However, there were three major national networks set up, one mostly working with Epic and its clients called Carequality. Epic meanwhile had pretty successfully set up a client to client exchange called Care Everywhere (remember that).

Then, mostly driven by Joe Biden when he was VP, in 2016 Congress passed the 21st Century Cures Act which among many other things basically said that providers had to make data available in a modern format (i.e. via API). ONC, the bit of HHS that manages this stuff, eventually came up with some regulations and by the early 2020’s data access became real across a series of national networks. However, the access was restricted to data needed for “treatment” even though the law promised several other reasons to get health data.

As you might guess, a bunch of things then happened. First a series of VC-backed tech companies got created that basically extract data from hospital APIs in part via those national networks. These are commonly called “on-ramp” companies. Second, a bunch of companies started trying to use that data for a number of purposes, most ostensibly to deliver services to patients and play with their data outside those 91 big hospital systems.

Which brings us to the last couple of weeks. It became publicly known among the health data nerd crowd that one of the onramp companies, Particle Health, had been cut off from the Carequality Network and thus couldn’t provide its clients with data.

The supposed reason was that they were getting data without a “treatment” reason.

Now if you really want to understand all this in detail, go read Brendan Keeler’s excellent piece “Epic v Particle”. Basically Particle cried foul and unusually both Michael Marchant, a UC Davis Health employee & the Chair of the big health systems on the ”Care Everywhere Committee” (remember that from earlier?) and then Epic itself responded. Particle’s founder Troy Bannister in a linkedin post and an official release from Particle said that they had not received notice or any evidence of what they’d done wrong. Michael said they had. I started quoting the Dire Straits line “two men say they’re Jesus, one of them must be wrong.” (FD. Troy was briefly an intern at Health 2.0 long, long ago).

Then Epic publicly released a letter to its clients explaining that, contrary to what Troy & Particle said, it had been discussing this with Particle for months and had had several meetings before and after it cut them off. So unless Particle’s legal counsel was parsing its words very very carefully, they knew Epic and its clients were unhappy, and it was unlikely Troy was Jesus. Michael might still be, of course. (Update: as of 4/15/23 Particle says only some feeds were cut off not all of them as Epic suggested)

In the letter Epic named 4 companies who were using Particle’s data in a way it didn’t like– Reveleer and MDPortals (who are one not two companies as they merged in 2023 before this issue started), Novellia and Integritort.

So what do they do with the data. Reveleer says that “leveraging our AI-enabled platform with NLP and MDPortals’ sophisticated interoperability allows us to deliver providers a pre-encounter clinical summary of patients within their EHR workflow at the point of care.” Sounds like treatment to me. But Reveleer also does analysis for health plans. You can see why hospitals might not like them.

Novellia is a PHR company, presumably using “treatment” to enable consumers to access their data to manage their own care. This was EXACTLY what Joe Biden wanted the 21st Century Cures Act to give patients the right to do and what Epic CEO Judy Faulkner told him he shouldn’t want (depending exactly who you believe about that conversation). But it’s probably not a particular “treatment” under HIPAA, because who believes patients can treat themselves or need to know about their own data anyway? (I’ll just lock you all in a room with Dave deBronkart, Susannah Fox and Regina Holliday if you want the real answer). This is apparently the line where ONC folded in its ruling to the vested interests that providers (and their EMR vendors) didn’t have to provide data to patient requests.

Finally, Integritort does sound like it’s looking for records so it (or its law firm customers) can sue someone for bad treatment (or as it turns out defend them for it). Is that “treatment” under the HIPAA definition? Almost certainly not. On the other hand, do the providers cutting them off have a vested interest in making sure no outside expert can review what they’ve been up to? I think we all know the answer to that question.

But anyway it looks like Particle switched off Integritort’s access to Carequality on March 22nd before Particle was entirely switched off by Carequality sometime around April 1.

What is not answered in the letter is why, if Carequality can identify who these records are going to, it needed to switch all Particle’s access off. Additionally, you would think that Particle’s path of least resistance would be to cut off the named clients Epic/Carequality was concerned about and try to sort through things while keeping its system running–which it seems it did with Integritort. Whatever happened, instead of this negotiation continuing behind the scenes, we all got to witness a major power play–with clearly Epic & its big customers winning for now.

I think most people who are interested in getting access to data for patients are all agreed on the need for new “paths” which were already defined in the regulations but not implemented, and also presumably for agreed standards (with associated liability) of “know your customer laws” for the onramps like Particle to make sure that the clients using them are doing the right things vis a vis confirming patient identity et al.

Slight digression: I am confused about why identity proofing is such a big deal. In recent weeks I have had to prove my identity for the IRS, for a credit union, and for the TSA. Not to mention for lots of other websites. There are companies like IDme, Clear and many others that do exactly this. I don’t see anything so specific about health care that is different from credit cards, bank accounts, airport safety, etc. Why can those agencies/organizations access all that data online but for some reason it’s a bridge too far for health care?

However you can see where the fault lines are being drawn. There are a lot of organizations, many backed by rich VCs or huge quasi-tech corporations, that think they can do a much better job of caring for Americans than the current incumbents do. (Whether they can or not is another matter, but remember we are spending 18% of GDP when everyone else spends 10-12%). Those organizations, which include huge health plans, tech cos, retail clinics, startup virtual care clinics, and a whole lot more, need data. Not everything they or the intermediaries they do will fit the “treatment” definition the current holders of that data want to use. On the other hand, the current incumbents and their vendors are extremely uninterested in any changes to their business model.

Data may be the new oil but, like oil, data needs refining to power economies and power health care services. We spent much of the last century fighting about access to oil, and we’re going to spend a lot of this one fighting about data. Health care will be no exception.

Matthew Holt is the publisher of The Health Care Blog

Health Care’s Debt Problem

matthew holt — Wed, 10 Apr 2024 17:27:05 +0000

By KIM BELLARD

Among the many things that infuriate me about the U.S. healthcare system, health systems sending their patients to collections – or even suing them – is pretty high on the list (especially when they are “non-profit” and./or faith-based organizations, which we should expect to behave better).

There’s no doubt medical debt in the U.S. is a huge problem. Studies have found that more than 100 million people have medical debt, many of whom don’t think they’ll ever be able to pay it off. Kaiser Family Foundation estimates Americans owe some $220b in medical debt, with 3 million people owing more than $10,000. It’s oft cited that medical debts are the leading cause of bankruptcy, although it’s quite not clear that is actually true.

So you’d think that helping pay off that debt would be a good thing. But it turns out, it’s not that simple.

A new study from the National Bureau of Economic Research (NBER) by Raymond Kluender, et. alia, found that, whoops, paying off people’s medical debt didn’t improve their credit score or financial distress, made them less likely to pay future medical bills, and didn’t improve their mental health.

“We were disappointed,” said Professor Kluender told Sarah Kliff in The New York Times. “We don’t want to sugarcoat it.”

The researchers worked with R.I.P. Medical Debt, a non-profit that buys up medical debt “at pennies on the dollar,” to identify people with such debt, and then compared people whom R.I.P. Medical Debt had helped versus those it had not. One set of people had hospital debts that were at the point of being sold to a collection agency, and another had debts that had already been sent to collection. And, perhaps to highlight how little we understand our healthcare system, they asked experts in medical debt what their expectations for the experiment were.

Much to everyone’s surprise, having debt paid off made no difference between control and debt-relief groups. I.e.,

“We find no average effects of medical debt relief on the financial outcomes in credit bureau data in either of our experiments.
We similarly estimate economically small and statistically insignificant effects on other measures of financial distress, credit access, and credit utilization.
We find that debt relief causes a statistically significant and economically meaningful reduction in payment of existing medical bills.
We estimate statistically insignificant average effects of medical debt relief on measures of mental and physical health, healthcare utilization, and financial wellness, with “opposite-signed” point estimates for the mental health outcomes relative to our prior.”

In short:

Our findings contrast with evidence on the effects of non-medical debt relief and evidence on the benefits of upstream relief of medical bills through hospital financial assistance programs. Our results are similarly at odds with views of the experts we surveyed, pronouncements by policymakers funding medical debt relief, and self-reported assessments of recipients of medical debt relief.

Amy Finkelstein, a health economist at the MIT and a co-director of J-PAL North America, a nonprofit group that provided some funding for the study, told Ms. Kliff: “The idea that maybe we could get rid of medical debt, and it wouldn’t cost that much money but it would make a big difference, was appealing. What we learned, unfortunately, is that it doesn’t look like it has much of an impact.”

If only it was that easy.

To be clear, there were three key statistically significant effects:

“small improvements in credit access for the subset of persons whose medical debt would have otherwise been reported to the credit bureaus,
modest reduction in payments of future medical bills, and
worsened mental health outcomes, concentrated among those who had the largest amount of debt relieved and those who received phone calls to raise awareness and salience of the intervention.”

The authors admitted they had not expected the mental health results and had no good explanation, but their “preferred interpretation is that recipients of the cash payments viewed the transfers as insufficient to close the gap between their resources and needs, raising the salience of their financial distress and harming their mental health.”

As Neale Mahoney, an economist at Stanford and a co-author of the study, told Ms. Kliff: “Many of these people have lots of other financial issues. Removing one red flag just doesn’t make them suddenly turn into a good risk, from a lending perspective.”

The authors concluded:

Nonetheless, our results are sobering; they demonstrate no improvements in financial well-being or mental health from medical debt relief, reduced repayment of medical bills, and, if anything, a perverse worsening of mental health. Moreover, other than modest impacts on credit access for those whose medical debt is reported, we are unable to identify ways to target relief to subpopulations who stand to experience meaningful benefits.

On the other hand, Allison Sesso, R.I.P. Medical Debt’s executive director, told Ms. Kliff that study was at odds with what the group had regularly heard from those it had helped. “We’re hearing back from people who are thrilled,” she said.

As statisticians would say, anecdotes are not data.

————-

Removing medical debt seems like a can’t-lose idea. A number of states and local governments have passed programs to pay off medical debt (most working with R.I.P. Medical Debt) and a number of others are considering it.

Last fall the Consumer Financial Protection Bureau initiated rulemaking that would remove medical bills from credit reports. It has also, according to NPR, “penalized medical debt collectors, issued stern warnings to health care providers and lenders that target patients, and published reams of reports on how the health care system is undermining the financial security of Americans.”

Director Chopra admits: “Of course, there are broader things that we would probably want to fix about our health care system, but this is having a direct financial impact on so many Americans.”

If nothing else, the new study should remind us that our health system is best at putting band-aids on problems rather than solving them. The problems we should be addressing include: why are so many charges so high, why aren’t people better protected against them, and why don’t more Americans have enough resources to pay their bills, especially unpredictable ones like from health care services?

I’m glad R.I.P. Medical Debt is doing what it is doing, but let’s not kid ourselves that it is solving the problem.

Kim is a former emarketing exec at a major Blues plan, editor of the late & lamented Tincture.io, and now regular THCB contributor

An Urgent Call to Raise Awareness of Heart Disease in Women

matthew holt — Fri, 05 Apr 2024 22:46:23 +0000

By KELLY CARROLL

There is a dire need to raise awareness about heart disease in women. It is the number one killer of American women, and key data points reveal a lack of cognizance among doctors and women.

An assessment of primary care physicians published in 2019 revealed that only 22% felt extremely well prepared to evaluate cardiovascular disease risks in female patients. A 2019 survey of American women showed that just 44% recognized heart disease as the number one cause of death in women. Ten years earlier, in 2009, the same survey found that 65% of American women recognized heart disease as the leading cause of female death, revealing an alarming decline in awareness.

Recent evidence suggests that many adults don’t know the important health numbers that can help identify heart disease risk factors, like their blood sugar and cholesterol. A 2024 survey of American adults conducted by The Ohio State University Wexner Medical Center found that only 35% of adults knew their blood pressure and 16% of adults knew their cholesterol levels. In comparison, the study reported that 58% knew their childhood friend’s birthday.

Heart Disease Risk Factors in Women

Women have specific risk factors for heart disease that don’t pertain to men. Nanette Wenger, M.D., a cardiologist and researcher, said in an American Heart Association (AHA) statement, “For most of the last century, heart disease was considered a problem for men, and women were believed to have cardioprotective benefits from female sex hormones such as estrogen. However, emerging evidence shows that there are a substantial number of heart disease risk factors that are specific to women or predominant in women.” Some gender-specific risk factors outlined by the AHA are early onset of menstruation, early menopause, autoimmune disease, anxiety, depression, and pregnancy complications.

Bethany Barone Gibbs, Ph.D., an associate professor at West Virginia University, emphasized in an email that pregnancy is a “critical window” for women’s cardiovascular health. She said, “The cardiovascular and metabolic challenge of pregnancy may unmask risk for conditions like hypertension and diabetes, but it is also possible (though not yet clear) that experiencing an adverse pregnancy outcome may independently contribute to the development of maternal cardiovascular disease.” A history of adverse pregnancy outcomes can be associated with more than two times the risk of cardiovascular disease later in life, she explained.

Filling in knowledge gaps regarding the connections between pregnancy and long-term cardiovascular health is important to improving outcomes.

One knowledge gap is effective strategies to reduce future cardiovascular disease risk among people who experience adverse pregnancy outcomes. “Though we know these individuals are at much higher risk for poor outcomes, evidence-based approaches that are tailored to the postpartum years (which often includes subsequent pregnancies) are lacking,” Gibbs said.

Gibbs is working to identify the optimal physical activity, sedentary behavior, and sleep patterns during the postpartum years that may reduce cardiovascular risk. “We are hopeful that we can identify which behaviors are most important for cardiovascular recovery following pregnancy and we can work with these populations to prioritize the most potent interventions to support heart health during the postpartum period,” she said.

Signs of Heart Disease in Women

Knowing the signs of heart disease in women is an important part of saving lives. Men and women both commonly experience chest pain during a heart attack, but women are more likely than men to have other symptoms unrelated to chest pain. These symptoms include shortness of breath, nausea, vomiting, perspiration, indigestion, atypical fatigue, faintness and pain in the torso, neck, jaw, shoulders and arms.

A February 2020 study reported that women under age 55 display different heart attack symptoms and a wider variety of symptom combinations than men. The study’s lead author, John Brush, Jr., M.D., said in an AHA statement, “As a physician, if you’re looking at a woman, you need to think more expansively. She might not have the prototypical combination of features of chest pain, radiating pain down the arm, shortness of breath and sweating, which are often the examples given in textbooks.”

It is also common for women to attribute their heart disease symptoms to another ailment, such as the flu, acid reflux or aging. Failure to recognize the symptoms of heart disease can cause women to delay seeking treatment. While chest pain is still the most common symptom of heart disease in both men and women, awareness of other heart disease symptoms can help women get treatment faster.

Heart Disease Prevention

Most heart disease cases are preventable. Wenger said in an AHA statement, “About 80-90% of cardiovascular disease is preventable. Implementing preventative strategies early could have a significant impact on reducing premature cardiovascular disease, stroke and related mortality for women.”

Lifestyle choices like maintaining a healthy diet and prioritizing physical activity can help prevent heart disease. Keeping a healthy weight and steering clear of tobacco products also support cardiovascular health. A person understanding her individual risks of heart disease and factors that may put her at higher risk, such as high blood pressure and diabetes, is also helpful. The AHA has outlined the top 8 factors for cardiovascular health, called Life’s Essential 8. They are: Eat Better, Be More Active, Quit Tobacco, Get Healthy Sleep, Manage Weight, Control Cholesterol, Manage Blood Sugar, and Manage Blood Pressure.

Efforts to Raise Awareness and Understanding

National efforts are being made to raise awareness of heart disease in women. The AHA hosts the Go Red for Women campaign to fight cardiovascular disease in women. Circulation published the eighth yearly Go Red for Women issue featuring new cardiovascular research in women in 2024. The National Heart, Lung and Blood Institute also hosts a cardiovascular health education program called The Heart Truth.

While these efforts are underway to improve heart disease outcomes for women, women need more. AHA laid out a constellation of strategies to improve women’s heart health in a May 2022 publication, and several deserve further emphasis here. To make progress, we need more and improved gender-specific cardiovascular disease training for healthcare providers. We need more collaboration between cardiologists, obstetricians-gynecologists, primary care physicians and other healthcare providers to improve the prevention and treatment of cardiovascular disease in women. We need more research on gender-specific cardiovascular disease to fill in knowledge gaps and improve prevention and treatment strategies.

We also need more awareness. Spreading awareness of the risk factors and symptoms of heart disease in women can help save lives. Campaigns can help spread this message, and men and women sharing this information with other men and women can also help. If we all know the risk factors and symptoms of heart disease in women, all our mothers, sisters, daughters, neighbors and friends will be better off.

More than 300,000 women in the U.S. died from heart disease in 2021. Let’s make sure that number is much lower in 2031 and beyond.

Kelly Carroll is a freelance health writer based in Kentucky. More at her site

Optum: Testing Time for an Invisible Empire

matthew holt — Tue, 02 Apr 2024 08:43:00 +0000

By JEFF GOLDSMITH

Years ago, the largest living thing in the world was thought to be the blue whale. Then someone discovered that the largest living thing in the world was actually the 106 acre, 47 thousand tree Pando aspen grove in central Utah, which genetic testing revealed to be a single organism. With its enormous network of underground roots and symbiotic relationship with a vast ecosystem of fungi, that aspen grove is a great metaphor for UnitedHealth Group. United, whose revenues amount to more than 8% of the US health system, is the largest healthcare enterprise in the world. The root system of UHG is a vast and poorly understood subsidiary called Optum.

At $226 billion annual revenues, Optum is the largest healthcare business in the US that no-one knows anything about. Optum by itself has revenues that are a little less than 5% of total US healthcare spending. An ill-starred Optum subsidiary, Change Healthcare, which suffered a catastrophic $100 billion cyberattack on February 21, 2024 that put most of the US health system on life support, put its parent company Optum in the headlines.

But Change Healthcare is a tiny (less than 2%) piece of this vast new (less than twenty years old) healthcare enterprise. If it were freestanding, Optum would be the 12^th largest company in the US: identical in size to Costco and slightly larger than Microsoft. Optum’s topline revenues are almost four times larger than HCA, the nation’s largest hospital company, one third larger than the entirety of Elevance, United’s most significant health plan competitor, and more than double the size of Kaiser Permanente.

If there really were economies of scale in healthcare, they would mean that care was of demonstrably better value provided by vast enterprises like Optum/United than in more fragmented, smaller, or less integrated alternatives. It is not clear that it is. If value does not reach patients and physicians in ways that matter to them—in better, less expensive, and more responsive care, in improved health or in a less hassled and more fulfilling practice—ultimately the care system as well as United will suffer.

What is Optum?

Optum is a diversified health services, financing and business intelligence subsidiary of aptly named UnitedHealth Group. It provides health services, purchases drugs on behalf of United’s health plan, and provides consulting, logistical support (e.g. claims management and IT enablement) and business intelligence services to United’s health plan business, as well as to United’s competitors.

Of Optum’s $226 billion topline, $136.4 billion (or 60% of its total revenues) represent clinical and business services provided to United’s Health Insurance business. Corporate UnitedHealth Group, Optum included, generated $29 billion in cashflow in 23, and $118.3 billion since 2019. United channeled almost $52 billion of that cash into buying health-related businesses, nearly all of which end up housed inside Optum.

Source: 2023 UNH 10K

For most of the past decade, Optum has been driving force of incremental profit growth for United. Optum’s operating profits grew from $6.7 billion in 2017 (34% of UHG total) to $15.9 billion in 2023 (55% of total). However, the two most profitable pieces of Optum by operating margin—Optum Health and Optum Insight—have seen their operating margins fall by one third in just four years. The slowing of Optum’s profitability is a huge challenge for United.

Gaul Had Three Parts, So Does Optum

The largest and least profitable (by percent margin) piece of Optum is its giant Pharmacy Benefit Manager, Optum Rx, the third largest PBM in the US.

Optum Rx is more than half of Optum by revenue ($116.1 billion) but less than a third of its profits. The core of its profit comes from rebates from drug companies for featuring their drugs on OptumRx’s formulary- which governs which drugs United Healthcare subscribers get access to and how much they pay for them. Optum Rx derives almost 62% of its revenues from managing pharmaceutical spending for United’s health plan, but the remainder for servicing both health plan competitors of United and self-funded employers. It is the most “vertical” piece of Optum—in that it has the highest share of its revenues coming from United out of all of Optum’s major segments.

The accounting for these rebates is, to put it gently, less than transparent. Some of these rebates are returned to UHG customers (such as self-funded employers). Some are returned to insurers other than United for which Optum Rx processes pharmaceutical claims. And some are kept as profit inside either Optum Rx or United’s health insurance business. Optum Rx does not disclose the ultimate destination of many billions in rebates.

This lack of transparency is, understandably, a subject of political controversy. Congress is considering tightening PBM disclosures and possibly redirecting the flow of rebates back to health-plan customers and, gasp, potentially to patients themselves. Given the widening political controversy about whether PBMs actually save consumers money, Optum Rx’s business model is a major strategic vulnerability for UHG.

The second major piece of Optum, OptumInsight, has been in the glare of public controversy since its Change Healthcare subsidiary was hacked by the mysterious Russian hacker collective BlackCat in February. Its main business lines are: business intelligence, consulting, IT enablement, and business process outsourcing to non-UHG health enterprises. OptumInsight is the smallest of Optum’s three pieces at $18.9 billion, but the most profitable—22.5% profit margin—$4.3 billion in operating earnings. I have written extensively about OptumInsight, almost 42% of whose revenues derive from servicing United’s other businesses, but will not repeat that analysis here.

Optum Health

The piece we want to focus on here is the largest generator of profits for Optum, Optum Health, a diversified healthcare services enterprise. Optum Health is a $95.3 billion business, which makes it the second largest care enterprise in the US after Kaiser Permanente. It generates nearly $6.6 billion in operating profit for United. However, Optum Health’s profit margin declined from more than 10% in 2018 to about 6.6% in the third quarter of 2023. If not turned around, Optum Health’s declining profitability is a threat to United’s enterprise valuation and reputation. This is why when Optum reported disappointing 3Q23 earnings, United’s Chairman Steven Hemsley cleaned house at Optum Health, installing new leadership.

Since United is not required to disclose acquisitions that are not “material”, there is no way of knowing what United has actually bought and what it presently owns. But Optum Health is home to an enormous collection of physician groups, surgicenters, a large urgent care network, and two of the largest home health agencies in the US. It is a sprawling nationwide roll-up of healthcare assets.

Optum claims 90 thousand physicians in its networks but is cagey on how many are actually employed by Optum and how many are independent physicians in Independent Practice Associations that wrap around the employed groups and are common in the West and Southwest. An educated guess would be that Optum employs from 45 to 60 thousand physicians. If true, this would still be between double and triple the size of Permanente Medical Groups. Optum’s profitability dwarfs that of Kaiser (see below), perhaps a function of Kaiser operating 39 hospitals and Optum not operating a single one.

Source: UNH 10K, Kaiser Annual Report

Optum Health receives $57.7 billion (or 60% of its total revenues) from United’s health plan—the vertical part. But it also claims $21.8 billion in premium income, e.g. capitation, from “non-affiliated” customers, namely health plan competitors of United’s health plans. That capitation represents almost 23% of Optum Health’s total revenues. In addition, Optum Health reports $14.1 billion in services income, almost certainly “fee-for-service” based income from other health plans. What share of Optum Health’s $6.6 billion in profits come from these contracts with United’s competitors is a compelling mystery, since this is not reported in United’s financial disclosures.

Whatever the profit split, Optum Health is very much dependent not merely on the kindness of strangers, but of competitors of United’s core business. An important and unknowable question is whether Optum’s contract renewals with those competitors have enabled it to recover the soaring costs of nursing coverage, temporary physician coverage, turnover and retirements, and other labor factors that have exploded in the wake of the COVID pandemic. Every care delivery enterprise in the US has faced rising people costs, as the largest care delivery enterprise in the US, these forces have not spared Optum.

Optum’s medical group acquisition strategy to date has targeted independent (e.g. non-hospital) medical groups with significant at-risk (e.g. “capitated”) populations, mainly in Medicare Advantage plans. These included the original asset, the Nevada based Sierra Medical Group which United acquired when it purchased the Sierra Health Plan in 2007, but also Healthcare Partners, Monarch and North American Medical Management (based in Los Angeles), WellMed in central Texas, Atrius and Reliant in Massachusetts, Everett and PolyClinic in Seattle and Kelsey Seybold Clinic in Houston Texas. It is a growing presence in Oregon, New York and Connecticut through mainly smaller acquisitions. The map below showed where Optum Health’s assets were as of 2022.

The Vertical Integration Conundrum

Healthcare strategists have touted the idea of vertical integration –pioneered by Kaiser Permanente—which offers a comprehensive healthcare service experience—pretty much soup to nuts—through its health plan. The only way to access Kaiser physicians and hospitals is by enrolling in their health plan. Vertical integration has been viewed as a way of reducing health cost (by eliminating middlemen’s profits) and procuring products and services more efficiently, though actual evidence that it does so is scarce upon the ground.

With United, the health plan preceded the health services. In the first thirty years of its existence, United was a “network” plan, which contracted with independent hospitals and doctors for care. With the Sierra acquisition in 2007, United embarked on an adventure in strategic ambiguity—owning physician clinics which provided care to United customers as well as those of competing health plans. After Sierra and WellMed, a large capitated medical group in central Texas that Optum acquired in 2011, Optum’s medical group acquisitions have been, at best, loosely tied to United’s health plan enrollment. A 2018 analysis showed at best modest overlap between United’s Medicare Advantage market presence and the Optum Health network.

Making United “more vertical” in Optum markets would be complicated. Offering financial incentives to the Optum Health patients presently enrolled in competing plans to switch to United would pose two challenges. One is that this would damage Optum Health’s contracts with competing health plans. And sharing savings (e.g. some of United’s profits) with patients to redirect their care or lowering their rates would reduce health plan profit margins.

Conversely, telling Optum patients that they could only get care if they enrolled in United’s health plan would trigger a firestorm of negative publicity not to mention retaliation and cancelled contracts by United’s health plan competitors. Telling United subscribers they could only get care from Optum physicians and facilities would overwhelm them in volume and trigger longer waiting times and provider burnout. In sum, it does not appear to make business sense for United to make Optum more “vertically aligned” with its health plans. So straddling competitors in local markets seems to be an ambiguity with which United will have to cope going forward.

How much unregulated and invisible profit United’s health plans can generate “inside” United’s visible and highly regulated medical loss ratio (MLR) by selectively and generously compensating Optum’s physicians, surgical facilities, etc. is the most compelling mystery of this business model. Matthew Holt, a veteran industry observer, has termed this strategy of maximizing enterprise profit through contracting favorably with yourself “provider fracking.” Companies that control both insurance and care delivery have a great deal of flexibility in what the accountants term “transfer pricing”. This flexibility is valuable and would be lost were Optum to be spun off in a future United restructuring.

Two Big Risks for the Partially Integrated Optum Health

There are two other major clouds on the horizon for Optum Health. One is the Federal Trade Commission’s proposal to ban of non-compete clauses for corporate employees, including physicians. Non-compete clauses effectively make the patient populations of acquired physician groups the property of Optum. If physicians leave Optum, they are required to move out of the community to practice, surrendering their patients to the company.

Many of the senior physicians who were equity holders in the large practices acquired by Optum departed millionaires with United’s cash, leaving behind junior colleagues to suffer through both Optum system conversions and leadership changes that affected their daily lives as practitioners. Outlawing non-competes would enable disgruntled Optum physicians to remain in their home communities and take their patients with them.

If FTC precedents hold, the non-compete clause prohibition might not apply to non-profit hospitals (80% of all hospitals are non-profit), putting Optum and other corporate employers of physicians at a competitive disadvantage. In my opinion, entities that rely on coercive measures like non-competes to assure physician loyalty need to take a long hard look at their corporate culture.

The FTC’s proposed ban on non-competes is a major enterprise risk for Optum Health’s vast agglomeration of medical groups. If enacted, it would force Optum management directly to address physician working conditions, values, and priorities. United does have the potential for markedly reducing the documentation burden for Optum physicians that take care of United patients by selectively altering its claims review strategies. It will be interesting to see if they do so.

E Pluribus Unum

The other major cloud on the horizon is the unionization of physicians. According to AMA, some 67 thousand practicing physicians (e.g. not interns, residents or fellowship trainees) are members of labor unions. There are been several recent high profile instances where disillusioned hospital-employed physicians elected union representation (Allina in Minneapolis/St Paul, Providence St. Vincent and Legacy Health in Portland OR, are recent examples).

Unionization is often not motivated directly by compensation issues but rather by a sense of powerlessness and a feeling that core issues that affect the employee are not being addressed. Unionization would both increase Optum’s operating costs and reduce its management’s flexibility. Optum Health’s groups are by far the largest and most lucrative target of physician unionization in the United States.

Down in the Valley

The emerging market risks for Optum can be seen in two medium sized cities in Oregon’s Willamette Valley. During the early pandemic, Eugene-based Oregon Clinic encountered terminal operating difficulties and sold to Optum in late 2020. In March of this year, Optum sent letters to patients of departing Oregon Clinic physicians that they would have to find care elsewhere because they were unable to recruit replacements for their physicians. These 32 physicians resigned, apparently, because they were unhappy with working conditions at Oregon Clinic after the Optum takeover. Reading between the lines, due to non-competes, the departing physicians were unable to remain the Eugene area and thus unable to continue seeing long-standing patients.

Meanwhile, up the road forty miles in Corvallis, Optum requested that the State of Oregon expedite review of its proposed acquisition of the Corvallis Clinic due to accelerating cash flow difficulties that made it impossible for the Clinic to meet its payroll. The State ultimately acceded to Optum’s request. The apparent cause of the cash flow problem: the Change Healthcare cyberattack, which made it impossible for Change, an Optum subsidiary to accept or pay claims from its provider networks, including, most likely Corvallis Clinic. In other words, the catastrophic system failure of one piece of Optum likely accelerated another piece of Optum’s acquisition of the largest physician group in town.

Taken together, these simultaneous problems have not served to enhance Optum’s image as a care provider in the southern Willamette Valley. They make the company appear as a cold and exploitative outsider capitalizing on problems it helped create. These events will not enhance the likelihood of United growing its core insurance business in the area or endear the company to Oregon’s health system regulators, or its state managed Medicaid program, the Oregon Health Plan.

Outgrowing Its Nervous System?

Optum Health has almost quadrupled in size in the past six years, but its profit margin has fallen by a third. Given the explosive pace of acquisitions and the cost pressures on physician practices during and after the COVID pandemic, this margin deterioration is not surprising. However, if Optum Health’s new management does not stabilize its operating performance, margins could deteriorate further, putting pressure on United’s earnings.

There are no evident economies of scale or co-ordination in physician services. How Optum can recruit and retain high quality motivated physicians and advanced practice nurses to its vast care system is a major challenge to the enterprise. They will need a compelling answer to the question: “Why work for Optum?” The answer cannot be: we are huge and you don’t have a choice. How the company creates value for its tens of thousands of physicians and nurses will be the central management facing United, or indeed any large-scale employer of these complex professionals.

There is growing evidence that there are diseconomies both of scale and co-ordination in health services generally. Those diseconomies manifest themselves in the vast empty space between the giant enterprise and the physicians and patients who rely on them. Every denial of care by United’s AI-driven claims management system makes a tiny dent in the company’s consumer image. Patient anger over arbitrary and self-interested health plan meddling in care decisions resulted in first managed care backlash in the late 1990’s. United’s recent Net Promoter Score of -5 suggests that it has a long way to travel to regain customer confidence and loyalty.

The physician-patient relationship remains the bedrock of the health system. If the nerve endings of an enterprise do not reach out and sense the effect it is having on that relationship, it isn’t going to be very long before it either ceases to grow or ceases to be profitable or, likely, both. United and Optum have reached that tipping point right now. Follow Optum’s physicians and their patients and see the future.

Acknowledgements: Trevor Goldsmith provided research and technical support for this piece. The author appreciates Ian Morrison, Andrew Mueller and Jamie Robinson for reading and commenting on this piece.

Jeff Goldsmith is a veteran health care futurist, President of Health Futures Inc and regular THCB Contributor. This comes from his personal substack

The Long and Tortured History of Alpha-Synuclein and Parkinson’s Disease

matthew holt — Fri, 29 Mar 2024 15:21:19 +0000

By STEVEN ZECOLA

This study tracks the decades-long journey to harness alpha-synuclein as a treatment for Parkinson’s disease. Steven Zecola an activist who tracks Parkinson’s research and was on THCB last month discussing it, offers three key changes needed to overcome the underlying challenges.

A Quick Start for Alpha-Synuclein R&D

In the mid-1990’s, Parkinson’s patient advocacy groups had become impatient by the absence of any major therapeutic advances in the 25 years since L-dopa had been approved for Parkinson’s disease (PD).

The Director of National Institute of Neurological Disorders and Stroke (NINDS) set up a workshop in August 1995 that featured scientists with expertise in human genetics who might open novel avenues for PD research.

One such scientist, Robert Nussbaum, made the following remarks at the workshop:

“…finding genes responsible for familial Parkinson’s should be helpful for understanding all forms of the disease. Techniques now available should allow researchers to find the genes responsible for familial Parkinson’s disease in a relatively short time.”

Two years later in 1997, Spillantini et al. showed that alpha-synuclein (A-syn) was a major contributor of abnormal clusters of proteins in the brain, not only in patients with synuclein mutations but, more importantly, in patients with sporadic Parkinson’s disease as well.

As Nussbaum had predicted, progress had occurred rapidly. President Clinton in his 1998 State of the Union address, said:

“Think about this, the entire store of human knowledge now doubles every 5 years. In the 1980’s, scientists identified the gene causing cystic fibrosis. It took 9 years. Last year scientists located the gene that causes Parkinson’s disease in only 9 days.”

The NIH is Asked to Take a Leadership Role

Shortly after President Clinton’s call to action, a Senate Committee asked the National Institutes of Health (NIH) to develop a coordinated effort to take advantage of promising opportunities in PD research.

In response, the NIH and the National Institute of Neurological Disease and Stroke (NINDS) held a major planning meeting that included all components of the PD community. The group’s recommendations formed the basis of a five-year PD Research Agenda.

The Research Agenda was codified in a comprehensive 42-page report that covered all aspects of research from better understanding the disease, to creating new research capabilities, to developing new treatments, and to enhancing the research process.

Noting the “remarkable paradigm shift in Parkinson’s disease research” from the discovery of the effects of alpha-synuclein, the report stated that:

“New insights into the role of synucleins in the pathobiology of Parkinson’s disease would accelerate discovery of more effective therapies and provide fresh research opportunities to advance our understanding of Parkinson’s disease”.

NIH invested nearly $1 billion from FY 2000 to FY 2004 to implement the PD Research Agenda. A-syn research would be funded out of the funds allocated to the categories of Genetics and Epidemiology, with both categories targeted to receive about 15% of the overall spending.

Overall, there were 19 broad categories with spending authorizations, including $32.7 million allocated to Program Management and Direction.

When the PD Research Agenda reached the end of its 5-year span, NINDS sponsored a second PD Summit which was held in June 2005. It brought together an industry-wide consortium to assess the progress over the previous five years and to develop future directions for PD research.

The participants generated more than fifty specific recommendations. NIH considered these plans and the unmet goals from previous efforts and developed a 3-year Plan.

A major focus of that Plan was to identify and intervene with the causes of PD.

As reiterated in the 2006 Plan:

“…Understanding the role of alpha-synuclein may enable strategies to selectively block the harmful effects associated with this protein as a novel approach to treatment of PD”.

NINDS noted that:

“While PD is not a rare or orphan disease, other more prevalent diseases such as stroke, obesity and diabetes offer considerably larger “markets” for drug therapies than does PD. Thus, pharmaceutical companies have primarily focused on medicinal chemistry and alterations of existing PD or other neurological drugs (e.g., dopamine agonists) rather than investing in new drugs.”

In essence, NINDS recognized the financial conundrum of drug development for A-syn and other PD therapies, but looked to academia to solve the problem through its grant program.

Lacking success from the efforts of the 2006 Plan, NINDS organized another conference in January 2014 called: Parkinson’s Disease 2014: Advancing Research, Improving Lives. The purpose of this initiative was to identify significant challenges and to highlight the highest priorities for advancing research.

Thirty-one recommendations were provided. The summary of the conference included the Top 3 priorities for clinical research, translational research, and basic research. Under basic research, priorities 1 and 2 related to alpha-synuclein.

Given that the work specified for A-syn research was still at an early stage of basic research in 2014, it is clear that a large gap existed between the previous NINDS priorities for A-syn and what was delivered.

Private Interests Finally Move Forward with Alpha-Synuclein

Recognizing the continuing lack of progress and the need for funding, the Michael J. Fox Foundation announced a $10-million “Ken Griffin Alpha-synuclein Imaging Competition” in 2019 to spur development of a critical and elusive imaging research tool for Parkinson’s disease.

In March 2023, MJFF announced that the three initial Alpha-synuclein imaging competition teams — AC Immune, Mass General Brigham and Merck— made tremendous advancements in the development of different alpha-synuclein tracer methods.

MJFF awarded Merck an additional $1.5 million to continue the work and bring its tool to life. The first-in-human clinical trial of its alpha-synuclein PET tracer began in 2023.

Additionally, after more than two decades of basic research, five private research companies filed applications with the FDA and have initiated early-stage PD trials.

Neuropore Therapies and UCB are collaborating on an oral small molecule, which aims to prevent the formation of alpha-synuclein clusters.
Prothena Biosciences, in conjunction with Roche, is testing a humanized anti-alpha-synuclein antibody.
Biogen is investigating another monoclonal antibody against alpha-synuclein.
AFFiRiS, an Austrian biotech company, is testing an alpha-synuclein vaccine. AC Immune has recently announced the acquisition of all of AFFiRiS’ assets and underlying intellectual property related to its vaccine candidates targeting a-syn.
Vaxxinity uses an immunotherapy candidate codenamed UB–312 to target toxic forms of aggregated α-synuclein in the brain to fight Parkinson’s. Its Chairman recently said that: “Our findings suggest UB-312 could transform Parkinson’s care, offering hope for improved outcomes with a disease-modifying treatment”.

As with all R&D projects, there are many remaining challenges in the development of A-syn therapies before reaching the market. Nevertheless, assuming that at least one of the five on-going trials will be successful, we can expect a therapy utilizing A-syn will be approved by the FDA within the next 5-8 years. The net effect is that the overall development window between A-syn’s discovery in 1997 and its application to patients would be approximately 35 years – assuming that the research goes relatively smoothly from here.

Given its performance to date, the view from NIH regarding PD research is:

“… Our failures in bringing treatments to the goal line are due to remaining large gaps in knowledge of the underlying biology that causes and drives the disease. As we fill in these gaps, the chances of success will increase. Some of the gaps we know about, others we only find out about when the science opens another door”.

Why Has This Research Taken So Long?

With the benefit of hindsight, we can point to two areas that accounted for the greatest obstacles to progress – focus and resources.

In reading the PD research plans and reports from 2000, 2006 and 2014, it appears that NINDS threw everything it knew about PD into the hopper. There were hundreds of recommendations, projects and so-called priorities. But a key factor of success in research is having a team of motivated scientists with the necessary skills, knowledge and thinking ability to solve a finely-honed question.

There simply are not enough great minds to track down all of the “to do’s” in the three NINDS PD research plans. Also, communications and networking are important components of scientific advancement, yet the capability to network with the widespread participation in the small grants program was lacking.

The implication of using the term “focus” is that it comes with the assignment of responsibility and accountability if the priority doesn’t get done. There appears to be little outside oversight of the efficiency and effectiveness of the research dollars that were utilized on A-syn or other PD research projects. If anything, NIH seems content with the output.

Finally, NIH/NINDS knew there was a funding problem in crossing the Valley of Death from basic research to clinical trials, but these organizations fell back to their comfort zone, namely small grants to academicians. This strategy did not produce the necessary results.

A Better Approach

In 1998 and thereafter, alpha-synuclein needed a swat team of top-flight researchers along with a commitment for additional funds as the project progressed out of basic research and through the requisite clinical trials.

To address the shortcomings to date, the Department of Health and Human Services (HHS) should step in and 1) narrow the PD research priority list to the top candidates, 2) require the establishment of a robust communications network for sharing information and 3) relax the FDA regulations for PD to help level the fund-raising playing field.

In particular, HHS/NIH/NINDS must recognize that investments in new healthcare therapies such as A-syn come with very high risks and those risky investment dollars get to choose between healthcare therapies that go through 15+ years of basic research and expensive clinical trials and other opportunities that can be launched in less than a year.

Of paramount concern, the FDA’s regulatory scheme has had two deleterious effects on fund-raising. First, the FDA overhang has dried up interest in angel and venture capital investing in potential therapies such as A-syn. The result has been a Valley of Death between basic research and drug development. Second, even if the initial Valley can be crossed through government grants or non-profit donations, the FDA regulatory scheme puts an enormous burden on companies to raise scores of millions of dollars for lengthy clinical trials that face an uncertain regulatory outcome.

NIH/NINDS have not recognized that even without any direct role in fundraising, the FDA dominates the fund-raising process. For example, approximately 90% of fundraising for R&D is based on claims tied to regulatory milestones. Investors are well-aware of the challenges of the FDA approval process and it curbs investor interest.

Even in basic research, the FDA has had a large influence on scientific progress. For the academic entrepreneur, early development of an effective regulatory plan can be the difference between success and failure. Therefore, regulatory strategy becomes a critical component of the innovation process.

HHS must also recognize that the FDA has safety-first culture and a not-invented-here syndrome when it comes to any proposed changes to its processes.

The solution to these challenges, in part, entails HHS imposing a relaxed regulatory scheme for PD. For example, the FDA should be excludedfrom Phase 1 and Phase 2 trials and from providing any guidance to researchers prior to Phase 3 clinical trials. Such a change will speed development, unleash innovation, and improve early-stage fund-raising.

Second, to improve performance of the research endeavors, NINDS should be tasked to develop and manage a formal, hub-and-spoke, communications network among all stakeholders involved in PD research. ClinicalTrials.gov does not satisfy this requirement because it contains misleading information.

Facilitating regular exchanges of information, data sharing, and collaboration should help to maximize the impact of research efforts and avoid duplication of work. For the investment community, a partition in the hub with investment-related information would help to build a bridge over the Valley of Death and bring more funding to potential therapies such alpha-synuclein.

This investor-related partition of the communications office should generally be housed by MBAs (rather than by Ph.D.’s) who are focused on communicating high value research endeavors with the not-so-subtle intent of fomenting an interest in investments. NIH should consider hiring an investment banking firm to assist in setting up the investor-related component of this information network.

The third recommendation for change is that NIH should convene a very small group of experts working on PD research to identify the three most-likely-to-succeed paths to a cure. It should ensure that those paths have adequate personnel and sufficient research dollars for completion. Progress should be monitored on a regular basis.

Lastly, I should mention that the Michael J. Fox Foundation has done an excellent job on a number of important issues and should be a major part of any restructure going forward. For example, HHS could outsource the communications hub to MJFF.

The bottom line is that all components of the PD industry, including the FDA, must be on the same page in terms of finding a cure for PD within a reasonable amount of time given existing resources whether it be with alpha synuclein or other therapies. Such has not been the case with A-syn to date, and similarly, we have witnessed that the entire research effort for PD has underperformed – and will continue to underperform – in the absence of corrective action.

The Long and Tortured History of Alpha-Synuclein and Parkinson’s Disease

Preface

This study tracks the decades-long journey to harness alpha-synuclein as a treatment for Parkinson’s disease. The author offers three key changes needed to overcome the underlying challenges.

A Quick Start for Alpha-Synuclein R&D

One such scientist, Robert Nussbaum, made the following remarks at the workshop:

As Nussbaum had predicted, progress had occurred rapidly. President Clinton in his 1998 State of the Union address, said:

The NIH is Asked to Take a Leadership Role

Noting the “remarkable paradigm shift in Parkinson’s disease research” from the discovery of the effects of alpha-synuclein, the report stated that:

Overall, there were 19 broad categories with spending authorizations, including $32.7 million allocated to Program Management and Direction.

The participants generated more than fifty specific recommendations. NIH considered these plans and the unmet goals from previous efforts and developed a 3-year Plan.

A major focus of that Plan was to identify and intervene with the causes of PD. As reiterated in the 2006 Plan:

“…Understanding the role of alpha-synuclein may enable strategies to selectively block the harmful effects associated with this protein as a novel approach to treatment of PD”.

NINDS noted that:

In essence, NINDS recognized the financial conundrum of drug development for A-syn and other PD therapies, but looked to academia to solve the problem through its grant program.

Private Interests Finally Move Forward with Alpha-Synuclein

MJFF awarded Merck an additional $1.5 million to continue the work and bring its tool to life. The first-in-human clinical trial of its alpha-synuclein PET tracer began in 2023.

Additionally, after more than two decades of basic research, five private research companies filed applications with the FDA and have initiated early-stage PD trials.

Neuropore Therapies and UCB are collaborating on an oral small molecule, which aims to prevent the formation of alpha-synuclein clusters.
Prothena Biosciences, in conjunction with Roche, is testing a humanized anti-alpha-synuclein antibody.
Biogen is investigating another monoclonal antibody against alpha-synuclein.
AFFiRiS, an Austrian biotech company, is testing an alpha-synuclein vaccine. AC Immune has recently announced the acquisition of all of AFFiRiS’ assets and underlying intellectual property related to its vaccine candidates targeting a-syn.
Vaxxinity uses an immunotherapy candidate codenamed UB–312 to target toxic forms of aggregated α-synuclein in the brain to fight Parkinson’s. Its Chairman recently said that: “Our findings suggest UB-312 could transform Parkinson’s care, offering hope for improved outcomes with a disease-modifying treatment”.

Given its performance to date, the view from NIH regarding PD research is:

Why Has This Research Taken So Long?

With the benefit of hindsight, we can point to two areas that accounted for the greatest obstacles to progress – focus and resources.

A Better Approach

HHS must also recognize that the FDA has safety-first culture and a not-invented-here syndrome when it comes to any proposed changes to its processes.

Steve Zecola sold his web application and hosting business when he was diagnosed with Parkinson’s disease twenty three years ago. Since then, he has run a consulting practice, taught in graduate business school, and exercised extensively

Gen Z’s Mid-Life Crisis

matthew holt — Wed, 27 Mar 2024 05:11:36 +0000

By KIM BELLARD

These are not happy times in America.

Now, I’m not thinking about the increasing cultural wars, the endless political bickering, the troubles in the Med-East or Ukraine, the looming threat of climate crisis, or the omnipresent campaigning for the November 2024 elections, although all those play a part. I’m talking about quantifiable data, from the latest World Happiness Report. It found that America has slipped out of the top 20 countries for the first time, falling to 23^rd – behind countries like Slovenia and the U.A.E. and barely ahead of Mexico or Uruguay.

Even worse, the fall in U.S. scores is primarily due to those under 30. They ranked 62^nd, versus Americans over 60, who ranked 10^th. A decade ago those were reversed. Americans aged 30-44 were ranked 42nd for their age group globally, while Americans between the ages 45-59 ranked 17^th.

It’s not solely a U.S. phenomenon. Overall, young people are now the least happy, and the report comments: “This is a big change from 2006-10, when the young were happier than those in the midlife groups, and about as happy as those aged 60 and over. For the young, the happiness drop was about three-quarters of a point, and greater for females than males.”

“I have never seen such an extreme change,” John Helliwell, an economist and a co-author of the report, told The New York Times, referring to the drop in happiness among younger people. “This has all happened in the last 10 years, and it’s mainly in the English-language countries. There isn’t this drop in the world as a whole.”

Jan-Emmanuel De Neve, director of the University of Oxford’s Wellbeing Research Center and an editor of the report, said in an interview with The Washington Post that the findings are concerning “because youth well-being and mental health is highly predictive of a whole host of subjective and objective indicators of quality of life as people age and go through the course of life.”

As a result, he emphasized: “in North America, and the U.S. in particular, youth now start lower than the adults in terms of well-being. And that’s very disconcerting, because essentially it means that they’re at the level of their midlife crisis today and obviously begs the question of what’s next for them?”

Gen Z is having a mid-life crisis.

The researchers speculate that social media, political polarization, and economic inequality between generations contribute to the low scores for younger Americans. Jon Clifton, CEO of Gallup, believes: “Young people have more social interactions, but feel more lonely,” and that they aren’t as connected to their job, churches, or other institutions.

“One factor, which we’re all thinking about, is social media,” Dr. Robert Waldinger, the director of the Harvard Study of Adult Development, said in a NYT interview,. “Because there’s been some research that shows that depending on how we use social media, it lowers well-being, it increases rates of depression and anxiety, particularly among young girls and women, teenage girls.”

Others note the impact of the pandemic. Professor De Neve said: “general negative trend for youth well-being in the United States [was] exacerbated during covid, and youth in the U.S. have not recovered from the drop.” Similarly, Lorenzo Norris, an associate professor of psychiatry at George Washington University, who was not part of the World Happiness study, told NYT:

The literature is clear in practice — the effect that this had on socialization, pro-social behavior, if you will, and the ability for people to feel connected and have a community. Many of the things that would have normally taken place for people, particularly high school young adults, did not take place. And that is still occurring.

“It’s a very complex time for youth, with lots of pressures and a lot of demands for their attention,” Professor De Neve diplomatically observed. It was not true in all countries that younger people were the unhappiest, and Professor De Neve suggests: “I think we can try and dig into why the U.S. is coming down in terms of wellbeing and mental health, but we should also try and learn from what, say, Lithuania is doing well.”

Did you ever expect Lithuania might be a role model for our young people?

Professor Helliwell told CNN that young people are reflecting what is going on around them: “Almost whatever institution you’re in, people in North America seem to be fighting over rights, responsibilities and who should be doing what to improve things and who is to blame for things not going well in the past.”

Amidst all the gloomy findings, the report did say: “The COVID crisis led to a worldwide increase in the proportion of people who have helped others in need. This increase in benevolence has been large for all generations, but especially so for those born since 1980, who are even more likely than earlier generations to help others in need.” They may be less happy, but Gen Z and millennials aren’t less charitable.

So there’s that.

Honestly, if young people aren’t depressed, they’re not paying attention. Social media is dominating their lives, whether Instagram is making them feel depressed or TikTok is driving them to harmful mental health content. They can see the impacts of climate change but not any sign that their elders plan to do anything about it. Their jobs are neither satisfying nor economically viable enough to allow them to build wealth, especially when suffering from crushing student loans. They don’t expect Social Security to help with their retirement, whenever that may be and whatever that might look like. They have no reason to think that the largely geriatric politicians understand them or their needs.

And when it comes to health care, they can see the attacks on women’s health, the inadequate support for mental health, and the gap in technology versus in the rest of their lives.

They have every reason not to be happy.

The thing about mid-life crises is that they’re supposed to happen, you know, mid-life. Youth is supposed to be a time of optimism and exploration, of wanting to change the world. If current youth is already unhappy, we can’t assume they will grow happier, like those of us over 60 seem to have. This is the America we’re bequeathing them; the question is, are we OK with that?

Maybe a trip to Lithuania isn’t a bad idea after all.

Kim is a former emarketing exec at a major Blues plan, editor of the late & lamented Tincture.io, and now regular THCB contributor

Disability Activist: Take Great Care When Seeing Bias Toward Disabled Citizens

matthew holt — Wed, 20 Mar 2024 07:56:00 +0000

By RANDY SOUDERS

During the years I served as Chairman of the Board for Jean Kennedy Smith’s Arts and Disability program, Very Special Arts (VSA at the Kennedy Center), I had there opportunity to meet a wide range of remarkable and courageous disabled Americans. Among the lasting friendships is a painter and visual artist, Randy Souders, who was rendered quadriplegic at the age of 17 in a 1972 accident. His concerns of late have been heightened by Trump and MAGA Republicans. I share his communication with his permission here in the hope that tech designers and others will be alert to the fact that great care is required at this point, lest history repeat. — Mike Magee MD

When I was injured at the age of 17 the world was still quite closed for people like me. That was a year before passage of HR 504 of the Rehabilitation Act of 1973. As I recall that law was the first to mandate access to public places that received federal funds. A year later Jean Kennedy Smith founded VSA (Very Special Arts) which has provided important arts opportunities to literally millions of people with disabilities around the globe. It was a very different world back then and artistic achievement was an important way people such as myself could prove their worth to a society that still saw little evidence of it.

It’s unbelievable to think there are serious threats to roll back many of those hard won gains in the name of deregulation and profitability. Disability is costly and people with disabilities are still woefully underemployed. So when a billionaire presidential candidate repeatedly mocks people with disabilities, how long till the “useless/ unworthy” excuses rise again? The old term describing a person with a disability as an “invalid” has another meaning. The adjective use is defined as “Not valid; not true, correct, acceptable or appropriate.”

Few today are aware that the first victims of the Holocaust were the mentally, physically and neurologically disabled people. They were systematically murdered by several Nazi programs specifically targeting them. The Nazi regime was aided in their crimes by perverted “medical doctors and other experts” who were often seen wearing white lab coats in order to visually reinforce their propaganda.

Branded as “useless eaters” and existing as “lives not worthy of life,” people with disabilities were declared an unbearable burden both to German society and the state. As Holocaust historians have documented, “From 1939 to 1941 the Nazis carried out a campaign of euthanasia known as the T4 program (an abbreviation of Tiergartenstrasse 4 which itself was a shortened version of Zentral Dienststelle-T4: Central Office T4) the address from which the program was coordinated.”

These most vulnerable of humans were reportedly the first victims of mass extermination by poison gas and cheaper CO2 from automobile exhaust fumes. But first “a panel of medical experts were required to give their approval for the euthanasia/ ‘mercy-killing’ of each person.”

In the end an estimated quarter million people with disabilities were killed in gas chambers disguised as shower rooms. This model for killing disabled people was later applied to the industrialized murder within Nazi concentration and death camps such as Auschwitz-Birkenau.”

Much has been written on this topic but few seem to know the chronology and diabolical history of how these “beneficial cleansings” of undesirables often start. The Nazi’s enlisted medical doctors to provide them with a veneer of moral justification for their atrocities.

Throughout history, authoritarian political despots have also worked diligently to silence dissent and co-opt religion in order to assist in their mutual quests for total control and dominance of others.

And theocrats are convinced their particular splinter of a schism is the ultimate authority on earth as well as the entire universe. Stoning, beheadings and the hanging of transgressors and non-believers are arbitrarily justified by interpretations of their particular holy book.

There is much to fear when politicians exploit the religious beliefs of medical professionals in order to pass laws denying the rights of others to control their own bodies. This blatant pandering for votes by promising to deliver on religious wedge issues creates a positive feedback loop resulting in politicians being deified by their religious influencers. This is aided by a campaign of rationalization absolving them of their obvious failings. Such a campaign of apologetics by religious leaders is active and widespread in America as I type.

Examples include “God doesn’t call the qualified…He qualifies the called” (Exodus Chapter 4) and “God calls imperfect men to do His perfect will.” Is there even a red line where such “imperfect men” becomes an existential threat? Apparently not. I’m sure most citizens of the Third Reich didn’t think so until everything imploded.

The current Republican candidate for President is on the record as being a believer in the “racehorse theory” – the idea that selective breeding can improve a country’s performance, which American eugenicists and German Nazis used in the last century to buttress their goals of racial purity. On September 18, 2020 he told a mostly white crowd of supporters in Bemidji, Minn. “You have good genes. A lot of it is about the genes, isn’t it? Don’t you believe? The racehorse theory. You think we’re so different? You have good genes in Minnesota.”

This is one of many such statements he has made regarding genetics that has resulted in his personal superiority and that of his family. The New York Times reports “Mr. Trump was talking publicly about his belief that genetics determined a person’s success in life as early as 1988, when he told Oprah Winfrey that a person had ‘to have the right genes’ in order to achieve great fortune.”

These statements combined with those “about undocumented immigrants poisoning the blood” of America should equate to a 100 alarm fire.

Randy Souders is a Professional Artist, an Arts & Disability Advocate and has been Quadriplegic since 1972

What could we do if GLP-1 weight loss drugs were free? Would our obesity epidemic be solved for good?

matthew holt — Wed, 13 Mar 2024 15:19:37 +0000

By CECI CONNOLY and SAMI INKINEN

Unless you have been living under a rock, you likely have heard the names Ozempic, Wegovy or Mounjaro. Or perhaps been humming the jingle. Rarely has a class of drugs (in this case, GLP-1s) achieved such widespread attention in popular culture and the media, which has people clamoring for them in every doctor’s office in the nation.

And for good reason. What we know is that the efficacy and safety profile of these medications is substantially better than any weight loss drug in the past, while our obesity epidemic has only ballooned. As organizations committed to sound science and holistic patient care, we are encouraged by the benefits of these new therapies for diabetes. The clinical evidence shows that GLP-1s are highly effective for controlling blood glucose levels among patients living with Type 2 diabetes and certain co-morbidities. GLP-1s may even improve heart health for high-risk patients.

To date, the biggest worry with these weight loss therapeutics has been the hefty price tag, ranging from $800 to $1700 per person, per month. Conservatively, these weekly injections could cost the nation more than $100 billion dollars annually. Already, state Medicaid budgets are sagging under the financial burden. In North Carolina, for example, officials dropped coverage of GLP-1s for obesity, noting that two drugs alone would cost about $1 billion over 6 years, and that’s with a nice discount.

As troubling as the cost is, what we don’t know is what should really worry us. Amidst the excitement over patients rapidly shedding up to 15% of their body mass, fundamental questions remain about who should be taking GLP-1s, at what dosages and what the long-term health and economic consequences will be for patients and society. Ultimately, the price paid to people’s long-term health may be more concerning than the price paid out-of-pocket.

With the recent release of the SELECT trial data highlighting limitations of existing published studies of GLP-1s, it is now even clearer that the public isn’t getting the full picture.

Calls for widespread adoption are clearly premature. The stories touting GLP-1s clinical weight loss benefits often leave out that the studies are limited and based on a homogenous population, likely to further exacerbate existing inequities. For example, only 27.7% of the patients in the SELECT trial were women, compared with other trials in which they represented 74.1%. This smaller patient population rightfully leads to questions about the effectiveness in women and others not included in the trial. By only seeing part of the puzzle, we’re left to worry about the missing pieces such as what the GLP-1 cardiovascular benefit for people who are obese but without a prior heart condition could be.

Even more troubling are the unknown long-term effects. In people with diabetes, studies have found an increased risk of pancreatitis for some patients. For individuals taking GLP-1s for weight loss, usually at much higher dosages than for treating diabetes, we simply don’t know what the long-term implications, both positive and negative, will be because few longitudinal studies exist. Too many patients are prescribed GLP-1s for a lifetime without thought as to what comes next.

Pharmaceutical manufacturers will argue that anyone concerned about their weight would benefit from GLP-1s. However, based on the published evidence on weight re-gain, GLP-1s likely require a lifetime commitment to maintain weight loss and associated benefits. Many patients must contend with well-documented side effects such as nausea, diarrhea or the significant loss of lean body mass (ie. muscle) and bone density. Again, those are lifetime side effects. and some patients simply tire of giving themselves a weekly injection.

In a July 2023 study of real-world claims data from 16 million commercially insured members, Prime Therapeutics and MagellanRx researchers found that almost 70% of patients stopped GLP-1 treatment less than one year after starting. When you combine that data with the findings from a recent Journal of the American Medical Association study (in which patients regained two-thirds of the lost weight after switching to a placebo) you have the makings of a dangerous rollercoaster ride. We must consider whether the rider is prepared for the physical and mental implications of a weight-loss rollercoaster. The short-term benefit isn’t worth the long-term costs.

What we do know is that GLP-1s work best in combination with lifestyle modification and that clinicians need flexibility to determine the right combination for each individual. We can scale evidence-based nutrition treatments with proper support to deliver long-lasting results. Health plans, clinical teams, patients and – more broadly – society must deploy a full range of comprehensive population health tools to get the nation back to a healthy weight.

With so many unknowns about GLP-1s, a cautious approach is needed with continued focus on the evidence-based strategies that tackle root causes of obesity, including nutrition and socioeconomic factors. The work of population health is not as sexy as the slender models posting videos on Tik Tok, but it is the proven approach for many struggling with weight issues.

Clinicians and policy makers must resist the seeming quick fix of GLP-1s. Greater attention and resources must be devoted to treating the whole person and patiently evaluating the right and wrong candidates for GLP-1s.

A healthy lifestyle is likely the only sustainable, affordable and safe way to address our obesity epidemic and to deliver long-lasting results. By focusing on the drivers of obesity, we’re focusing on what we do know rather than being surprised by the unknowns.

Even if GLP-1s were free, they are not the magic pill to solve our obesity epidemic.

Ceci Connolly is the president and chief executive officer of the Alliance of Community Health Plans. Sami Inkinen is co-founder & CEO of Virta Health, a telemedicine and behavior treatment company focused on solving our T2 diabetes and obesity epidemic.