Microbiome startups have been alternately hailed for health breakthroughs and indicted for fraud.

This article was published on Wednesday, August 25, 2021 in Kaiser Health News.

By Hannah Norman   

After Russell Jordan sent a stool sample through the mail to the microbiome company Viome, his idea of what he should eat shifted. The gym owner in Sacramento, California, had always consumed large quantities of leafy greens. But the results from the test — which sequenced and analyzed the microbes in a pea-sized stool sample — recommended he steer clear of spinach, kale and broccoli.

"Things I've been eating for the better part of 30 years," said Jordan, 31. "And it worked." Soon, his mild indigestion subsided. He recommended the product to his girlfriend.

She took the test in late February, when the company — which sells its "Gut Intelligence" test for $129 and a more extensive "Health Intelligence" test, which requires a blood sample, for $199 — began experiencing hiccups. Viome had promised results within four weeks once the sample arrived at a testing facility, but Jordan said his girlfriend has been waiting more than five months and has submitted fresh blood and stool samples — twice.

Other Viome customers have flocked to social media to complain about similar problems: stool samples lost in the mail, months-long waits with no communication from the company, samples being rejected because of shipping or lab processing snafus. (I, too, have a stool sample lost in transit, which I mailed after a first vial was rejected because it "leaked.") The company's CEO, Naveen Jain, took to Facebook to apologize in late July.

Viome's troubles provide a cautionary tale for consumers in the wild west of microbiome startups, which have been alternately hailed for health breakthroughs and indicted for fraud.

The nascent industry offers individualized diet regimens based on analyzing gut bacteria — collectively known as the gut microbiome. Consumers pay hundreds of dollars for tests not covered by insurance, hoping to get answers to health problems ranging from irritable bowel syndrome to obesity.

Venture capitalists pumped $1 billion into these kinds of startups from 2015 to 2020, according to Crunchbase, buoyed by promising research and consumers' embrace of at-home testing. PitchBook has identified more than a dozen direct-to-consumer gut health providers.

But not all the startups are equal. Some are supported by peer-reviewed studies. Others are peddling murky science — and not just because poop samples are getting lost in the mail.

"A lot of companies are interested in the space, but they don't have the research to show that it's actually working," said Christopher Lynch, acting director of the National Institutes of Health Office of Nutrition. "And the research is really expensive."

With nearly $160 million in government funding, the NIH Common Fund's Nutrition for Precision Health research program, expected to launch by early next year, seeks to enroll 1 million people to study the interactions among diet, the microbiome, genes, metabolism and other factors.

The gut microbiome is a complex community of trillions of bacteria. Research over the past 15 years has determined that these microbes, both good and bad, are an integral part of human biology, and that altering a person's gut microbes can fundamentally change their metabolism, immune function — and, potentially, cure diseases, explained Justin Sonnenburg, a microbiology and immunology associate professor at Stanford University.

Metagenomic sequencing, which identifies the unique set of bugs in someone's gut (similar to what 23andMe does with its saliva test), has also improved dramatically, making the process cheaper for companies to reproduce.

"It's seen as one of the exciting areas of precision health," said Sonnenburg, who recently co-authored a study that found a fermented food diet increases microbiome diversity — which is considered positive — and reduces markers of inflammation. That includes foods like yogurt, kefir and kimchi.

"The difficulty for the consumer is to differentiate which of these companies is based on solid science versus over-reaching the current limits of the field," he added via email. "And for those companies based on solid science, what are the limits of what they should be recommending?"

San Francisco-based uBiome, founded in 2012, was one of the first to offer fecal sample testing.

But as uBiome began marketing its tests as "clinical" — and seeking reimbursement from insurers for up to nearly $3,000 — its business tactics came under scrutiny. The company was raided by the FBI and later filed for bankruptcy. Earlier this year, its co-founders were indicted for defrauding insurers into paying for tests that "were not validated and not medically necessary" in order to please investors, the Department of Justice alleges.

But for Tim Spector, a professor of genetic epidemiology at King's College London and co-founder of the startup Zoe, being associated with uBiome is insulting.

Zoe has spent more than two years conducting trials, which have included dietary assessments, standardized meals, testing glycemic responses and gut microbiome profiling on thousands of participants. In January, the findings were published in Nature Medicine.

The company offers a $354 test that requires a stool sample, a completed questionnaire, and then a blood sample after eating muffins designed to test blood fat and sugar levels. Customers can also opt in to a two-week, continuous glucose monitoring test.

The results are run through the company's algorithm to create a customized library of foods and meals — and how customers are likely to respond to those foods.

Screenshots from Zoe's app show how my gut health and blood sugar and fat levels may react to eating my breakfast one day, a Nature's Bakery Fig Bar. The 1-to-100 scale is based on the company's analysis of my stool and blood tests. (Hannah Norman / KHN)

DayTwo, a Walnut Creek, California, company that recently raised $37 million to expand its precision nutrition program, focuses on people with prediabetes or diabetes. It sells to large employers — and, soon, to health insurance plans — rather than directly to consumers, charging "a few thousand dollars" per person, said Dr. Jan Berger, chief clinical strategist.

Based on a decade of research, DayTwo has worked with nearly 75,000 people. It sends participants a testing kit and survey, and arranges for them to chat with a dietitian while their stool sample is processing. Then, when the results come in, it makes recommendations, Berger said.

"I can still eat two scoops of ice cream, but I need to add walnuts in it to regulate my blood sugar," she offered as an example.

Viome says it has tested more than 200,000 customers and has published its methodology for analyzing stool samples, which is different from other gut health companies. But the paper does not address Viome's larger claims of connecting the microbiome to dietary advice, and researcher Elisabeth Bik called the claims "far-fetched" in a 2019 review of the preprint version.

Viome makes additional money by selling supplements, probiotics and prebiotics based on consumers' test results. It has also rebranded as Viome Life Sciences, expanding into precision diagnostics and therapeutics, such as saliva tests to detect throat cancer. Meanwhile, its gut health program has been mired in logistical missteps.

One customer who posted on Facebook tracked her sample through the U.S. Postal Service as it boomeranged between Los Alamos, New Mexico, and Bothell, Washington, where it was supposed to be picked up. Another fought for a refund after waiting six weeks to hear her sample was not viable and learning a second attempt had expired after spending too long in transit. The company's expected lab processing time jumped from four weeks in February, when Jordan said his girlfriend took her first test, to six in summer. (Three weeks after I mailed my second sample in July, it still hadn't made it to the lab, so I called it quits and asked for a refund.)

In CEO Jain's July apology posted to the private Facebook group for Viome users, he said the company recently moved its lab from New Mexico to Washington state, close to its headquarters, which prompted a mail-forwarding fiasco. It bought new robotics that "refused to cooperate," he wrote. "Many things didn't go as planned during the move."

Spokesperson Kendall Donohue said Viome has been working on the problems but laid much of the blame on the Postal Service.

She also said Viome has been notifying customers — even though many (including myself) had not been contacted.

It is Viome's "top priority right now to ensure complete customer satisfaction, but unfortunately USPS needs to sort the issue internally for further action to be taken," she said.

She also offered me a free "Health Intelligence" test. I declined.

Hannah Norman: hannahn@kff.org, @hnorms

Despite widespread consensus on the importance of addiction treatment in the ER, many hospitals fail to screen for substance use.

This article was published on Wednesday, August 25, 2021 in Kaiser Health News.

By Aneri Pattani  

For years, Kayla West watched the opioid epidemic tear through her eastern Tennessee community. As a psychiatric nurse practitioner, she treated people with mental illness but felt she needed to do more to address addiction.

So in 2020, when the state created a position to help hospitals improve addiction care in the emergency room, West jumped at the opportunity.

She knew that many people with substance use disorders land in the ER, and that starting medications for opioid use — like buprenorphine (often known by the brand name Suboxone) — could double a person's chance of staying in treatment a month later.

Yet she also knew that providing the medication was far from standard practice.

A recent report from the Legal Action Center and the Bloomberg American Health Initiative found that despite widespread consensus on the importance of addiction treatment in the ER and an unprecedented rise in overdose deaths, many hospitals fail to screen for substance use, offer medications to treat opioid use disorder or connect patients to follow-up care.

Many patients who don't receive those services die shortly after discharge or within a year of their ER visit, the report said.

But a growing number of emergency rooms and health professionals are trying to change that by developing new approaches to address the missed treatment opportunity in ERs.

"We know it's possible because others have done it," said Sika Yeboah-Sampong, an attorney with Legal Action Center and co-author of the report. "You have a combination of levers and kinds of structures of how different cities, counties, states and even independent hospitals adopt these practices."

These models have already been put in place in some big hospitals and small hospitals, rural areas and urban centers, those with ample resources and those on tight budgets, she said.

In Tennessee, West looked to several of them for helpful guidance as she developed a pilot program with one hospital she advises. "It's like looking at a smorgasbord of options of where you can implement change," she said. Here are just a few of the different strategies emerging from ERs across the United States:

Advocating for the Patient in California

Daniel Browne started drinking alcohol and using prescription opioids at age 14. By the time he was 24, he was on the verge of losing his job, his car and his apartment.

"I didn't know where else to go to get treatment other than the ER," he said.

In May 2020, Browne drove 15 minutes from his home to Adventist Health Howard Memorial Hospital in Willits, California, where he was immediately met by Mary Anne Cox Gould. At the time, Cox Gould was a substance use navigator for a program called CA Bridge. She championed addiction treatment in the hospital and helped connect patients from the ER to clinics in the community. (Cox Gould is now a supervisor of other navigators in Adventist Health hospitals.)

"She met me in the parking lot even before I went into the ER," Browne recalled.

She stayed with him as he received his first dose of buprenorphine, which provided immediate relief from withdrawal symptoms. "Once you're not facing the crippling detoxification, it's much easier to not relapse," Browne said.

Cox Gould then walked him over to the hospital's outpatient clinic and helped him schedule recurring appointments. When Browne ran into obstacles filling his buprenorphine prescription at a local pharmacy, she made all the necessary arrangements for him to get it from the hospital.

Now more than a year into recovery, Browne said he's become a more reliable employee and has reconnected with his parents and younger brother — successes he credits partly to the medication and consistent support he's received.

Those are hallmarks of the CA Bridge program, said executive director Serena Clayton. Medication is considered a key element of treatment. Connecting patients with a navigator helps them in long-term recovery. And having navigators in the ER creates a more welcoming environment for patients, and gives ER staff a chance to learn more about addiction, she said.

The model is currently used by about 130 hospitals in California, and the state has allotted $40 million to expand the program to more than 100 others. The funds cover the salaries of substance use navigators, training for ER staff on prescribing buprenorphine and other technical assistance.

"This doesn't have to be a one-off story about a really special hospital," Clayton said. "It can happen at scale."

Removing Obstacles for Patients and Doctors in New York

Patients with addiction face many barriers to recovery, said Dr. Joshua Lynch, an associate professor of emergency medicine at the University at Buffalo. But doctors who want to help them also encounter hurdles, he said.

ER physicians are short on time, often lack training for addiction-related issues and don't know where to refer the patients for follow-up care. To improve the situation, both sets of barriers — for patients and for doctors — must be addressed, Lynch said.

That was his goal in creating New York MATTERS, a program that gives patients access to buprenorphine and links them to addiction clinics to continue treatment. It also provides pharmacy vouchers that cover 14 days of medication and Uber vouchers to cover transportation to the clinic — all through an electronic referral system.

"Being able to offer all of this without having to make any phone calls is probably what makes the doctors most likely to use it," Lynch said.

The program, partially funded by the state Department of Health, includes 38 hospitals and 94 clinics across New York that are vetted to ensure they provide buprenorphine to those who want it and accept patients regardless of insurance status. Providers in any participating ER can bring up a map of the clinics on a tablet and let patients choose where they'd like to be referred.

"This patient population is used to being told 'no' or 'that's not possible' or 'you have to go to this place,'" Lynch said. "We want to inspire them by giving them these choices."

Most patients pick a clinic close to home or where they know a friend had a good experience, Lynch said.

He estimated about 55% of patients in the program make it to their first appointment, where they can receive medication and therapy. National figures suggest fewer than 10% of patients addicted to opioids receive similar treatment.

Lynch said the cost for any hospital or clinic to join the program is minimal, since it mostly leverages existing resources, and the state hosts the data for the referral platform. Expanding the program to facilities across the entire state would cost less than $4 million a year, he said.

Training Everyone in North Carolina

Dr. Blake Fagan is chief education officer at the Mountain Area Health Education Center in Asheville, North Carolina. For years, when he approached hospital ERs to offer addiction training, he heard a common refrain.

"We don't have any place to send patients afterwards," he said doctors told him.

Without a clear place for patients to continue treatment, the doctors were reluctant to even start medications for opioid use. That's when Fagan and his colleagues realized their training had to extend beyond hospitals.

They reached out to federally qualified health centers, which treat people regardless of insurance status. In a state without Medicaid expansion and with large rural expanses, these centers serve many people with addiction.

Using just over $1 million in grant funding from two foundations, the Mountain Area Health Education Center trained 11 health centers and two local health departments over the past year and a half to provide medications for opioid use disorder. From March 2020 to May 2021, those centers treated more than 400 patients with the disorder.

Dr. Shuchin Shukla, who heads the program alongside partners at the University of North Carolina- Chapel Hill, said the centers have become obvious referral spots for doctors who start patients on medication in the ER.

"We consider ourselves a model for how to do this in a Medicaid non-expansion state," Shukla said.

North Carolina also has programs to train medical students, residents, nurse practitioners and physician assistants in addiction care.

Dr. Sara McEwen, executive director of the nonprofit Governor's Institute, which has helped to incorporate the training into medical school curricula, said students who see addiction prevention and treatment as a routine part of medicine will naturally apply that when they reach the ER or other clinical settings.

In fact, a recent study at Wake Forest School of Medicine found 60% of medical students who received the education reported using it during their internships.

"The learning is coming from med students to residents, up the chain," said Paige Estave, a co-author of the study and a doctor of medicine/Ph.D. candidate at the school. "Students bringing it up will cause doctors to start thinking, talking and finding resources. … Hopefully, those little pieces of change will add up cumulatively to something more."

Measuring Success

Across these varied models, one essential question remains: Do they work?

Unfortunately, it's also one of the most challenging to answer, according to addiction researchers and those who run the programs. Many projects are still in the early phases and won't be able to measure success for another few years. Others are struggling to gather long-term data that's necessary for evaluation.

In North Carolina, for instance, McEwen knows more than 500 medical students receive the addiction training each year, but until they complete residency and practice on their own, it's difficult to gauge how many will prescribe buprenorphine to their patients. In New York, Lynch can estimate how many patients make it to their first appointment at a clinic, and a recent study of the CA Bridge program tracked how many patients were given buprenorphine across 52 hospitals. But those numbers don't indicate how many patients achieved long-term recovery. That would require tracking patients for months and years.

In the meantime, people like West who are looking to these models as guideposts must operate with a level of uncertainty. But she said she'd rather get started now than wait for the perfect solution.

"Any movement on this is a step in the right direction," West said. "I've learned that no matter how varied your resources are, there are options for change in your ER."

Aneri Pattani: apattani@kff.org, @aneripattani

Eager to find new sources of revenue, hospital systems of all sizes have been experimenting as venture capitalists for healthcare startups.

This article was published on Tuesday, August 24, 2021 in Kaiser Health News.

By Jordan Rau August 24, 2021

Cone Health, a small not-for-profit healthcare network in North Carolina, spent several years developing a smartphone-based system called Wellsmith to help people manage their diabetes. But after investing $12 million, the network disclosed last year it was shutting down the company even though initial results were promising, with users losing weight and recording lower blood sugar levels.

The reason did not have to do with the program's potential benefit to Cone's patients, but rather the harm to its bottom line. Although Cone executives had banked on selling or licensing Wellsmith, Cone concluded that too many competing products had crowded the digital health marketplace to make a dent.

"They did us a tremendous favor in funding us, but the one thing we needed them to be was a customer and they couldn't figure out how to do it," said Jeanne Teshler, an Austin, Texas-based entrepreneur who developed Wellsmith and was its CEO.

Eager to find new sources of revenue, hospital systems of all sizes have been experimenting as venture capitalists for healthcare startups, a role that until recent years only a dozen or so giant hospital systems engaged in. Health system officials assert many of these investments are dually beneficial to their nonprofit missions, providing extra income and better care through new medical devices, software and other innovations, including ones their hospitals use.

But the gamble at times has been harder to pull off than expected. Health systems have gotten rattled by long-term investments when their hospitals hit a budgetary bump or underwent a corporate reorganization. Some health system executives have belatedly discovered a project they underwrote was not as distinctive as they had thought. Certain devices or apps sponsored by hospital systems have failed to be embraced by their own clinicians, out of either skepticism or habit.

"Even the best healthcare investors can't reliably get their health systems to adopt technologies or new innovations," said James Stanford, managing director and co-founder of Fitzroy Health, a healthcare investment company.

Some systems have found the business case for using their own innovations is weaker than anticipated. Wellsmith, for instance, was premised on a shift in insurance payments from a fee for each service to reimbursements that would reward Cone for keeping patients healthy. That change did not come as fast as hoped.

"The financial models are so much based on how many patients you see, how many procedures you do," said Dr. Jim Weinstein, who championed a health initiative similar to Cone's when he was CEO of the Dartmouth-Hitchcock health system in New Hampshire. "It makes it hard to run a business that is financially successful if you're altruistic."

Though their tax-exempt status is predicated on charitable efforts, nonprofit health systems rarely put humanitarian goals first when selecting investments, even when sitting on portfolios worth hundreds of millions of dollars or more, according to a KHN analysis of IRS filings. Together, nonprofit hospital systems held more than $283 billion in stocks, hedge funds, private equity, venture funds and other investment assets in 2019, the analysis found. Of that, nonprofit hospitals classified only $19 billion, or 7%, of their total investments as principally devoted to their nonprofit missions rather than producing income, the KHN analysis found.

Venture capital funds are a potentially lucrative but risky form of investment most associated with funding Silicon Valley startup companies. Because investors seek out companies in their early stages of development, a long-term horizon and tolerance for failure are critical to success. Venture capitalists often bank on a runaway success that ends up on a stock exchange or in a sale to a larger company to counterbalance their losses. As an asset class, venture capital funds assets annually return between 10% and 15% depending on the time frame, according to PitchBook.

While they lack the experience of longtime venture capitalists, health systems posit that they have advantages because they can invent, incubate, test and fine-tune a startup's creations. Children's Hospital of Philadelphia, for instance, parlayed a $50 million investment into a return of more than $514 million after it spun off its gene therapy startup Spark Therapeutics.

Many hospital-system venture capital funds, both established and new entrants, have grown rapidly. The largest, run by the Catholic hospital chain Ascension, has been in business for two decades and this year topped $1 billion, including contributions from 13 other nonprofit health systems eager to capture a piece of the returns.

Providence, a Catholic health system with hospitals in seven Western states, launched its venture capital fund in 2014 with $150 million and now has $300 million.

Cleveland-based University Hospitals launched its own fund, UH Ventures, in 2018. "We were candidly late to the game," said David Sylvan, president of UH Ventures.

UH Ventures yielded $64 million in profits in 2020, Sylvan said, which pushed University Hospitals' net operating revenue from the red to $31 million. Sylvan said the largest income contributor from UH Ventures was its specialty pharmacy, UH Meds, which provides medications to people with complex chronic conditions and helps them manage their ailments.

Another UH-supported startup, RiskLD, uses algorithms to monitor women and their babies during delivery to alert clinicians of sudden changes in conditions. It is used in UH's labor and delivery units. Sylvan said it is being marketed to other systems. UH Ventures' webpage touts the financial advantages for avoiding lawsuits, calling RiskLD "the first and only labor and delivery risk management tool designed to address birth malpractice losses."

But sustained commitment is harder when the return on investment is not clear or immediate. In 2016, Dartmouth-Hitchcock, which operates New Hampshire's only academic medical center, tested its remote monitoring technology, ImagineCare, on 2,894 employee volunteers. ImagineCare linked a mobile app and Bluetooth-enabled devices to a health system support center staffed by nurses and other Dartmouth-Hitchcock workers. The app tracked about two dozen measurements, including activity, sleep and, for those with chronic conditions, key indicators like weight and blood sugar levels. Worrisome results triggered contact and behavioral coaching from the Dartmouth-Hitchcock staff.

Dartmouth-Hitchcock found healthcare expenditures for the people with chronic conditions dropped by 15% more than matched controls. Nonetheless, in 2017, with the product facing unexpected technology challenges and the health system saddled with a short-term deficit, Dartmouth-Hitchcock scrapped the experiment and sold the technology to a Swedish company in return for potential royalties.

"We didn't have the capital as a small health system," said Weinstein, now senior vice president of innovation and health equity for Microsoft. "It wasn't a venture investment to make money; in fact, we probably would have lost revenues on admissions. But it was the right thing to do."

ImagineCare has found a more receptive home in Sweden. Two regions of the public healthcare system as well as a private healthcare organization have decided to deploy it as their remote monitoring service, according to ImagineCare's CEO, Annette Brodin Rampe. The company expects to have 10,000 patients enrolled by year's end.

Wellsmith, Cone Heath's diabetes platform, suffered an even rockier trajectory. The concepts were similar, but Wellsmith was initially tailored to people with Type 2 diabetes. Data on weight, activity, blood sugar and patients' compliance on taking medication was uploaded manually or through Bluetooth-enabled devices and sent to a small team of nurses and health coaches at Cone, who would contact those with disquieting signs.

Cone tested Wellsmith on 350 employees with Type 2 diabetes and reported encouraging results in 2018. Users' physical exercise had increased on average by 24% and their A1c levels, which measure the percentage of red blood cells with sugar-coated hemoglobin, had dropped by 1 point on average. "We believe that the future will be carried by those who can invest in and create models of care like Wellsmith," said Terry Akin, Cone's CEO at the time.

But Cone grew apprehensive about Wellsmith's commercial prospects, especially when other companies started pitching similar products. In its 2018 financial statement, Cone wrote that "management has determined that the existing technology will not be marketed for sale and licensing." In October 2020, Cone decided to end its relationship with Wellsmith and shut it down this year, according to its financial statement.

Cone declined requests for interviews. In an email, Cone spokesperson Doug Allred wrote: "Unfortunately, a number of well-funded competitors established similar platforms. This has made it difficult to scale our platform to more customers and develop more partnerships. Due to these factors we made the difficult decision to sunset the Wellsmith platform."

In interviews, Teshler said Cone had originally viewed the product as complementary to its efforts to move away from a traditional fee-for-service payment system. But she said alternative models — such as those in which insurers pay a set fee for each patient, providing doctors and hospitals with an incentive to keep spending low — remained the arrangement for a minority of Cone's patients: those enrolled in Cone's Medicare Advantage plans and accountable care organizations.

"The problem with these kinds of solutions — not just us — is it requires people to have digital devices that aren't normally covered by health insurance," she said.

Wellsmith's business plan was to charge a per-member monthly fee to organizations using it. Teshler said Cone did not want to pay Wellsmith a fee when it had already lent it millions, since it couldn't bill insurers for the service.

Other obstacles arose as well, according to Teshler. She said Wellsmith's development was delayed when the second version of the software was a "dismal failure" and needed to be revamped. To further complicate matters, Cone began entertaining a merger with another health system, making the long-term financial commitment to Wellsmith uncertain. "And then we hit COVID and it was game over," Teshler said.

Teshler said she is still developing her concept, though, under her contract with Cone, Wellsmith's software had to be destroyed when they split ways. She wants to market Wellsmith's successor to primary care medical practices that contract directly with employers — groups that benefit when medical claims are reduced. She does not see other hospital systems as viable customers.

"It's very simple for their attention to be diverted by the fact that their job is to keep people alive," she said. Also, unless an innovation is unique, she said, "everybody's got a fund, and nobody is going to buy anyone else's product."

Jordan Rau: jrau@kff.org, @JordanRau