(This is excerpted from a story from The Mercury News.)

Long motorcades of volunteers converged at three Stanford University research sites this week, donating blood for a new test that identifies the prevalence of coronavirus in our community – and could help reveal the full scope of Santa Clara County’s epidemic.

The 2,500 test slots on Friday and Saturday filled up within hours, as news of the project — the first large scale study of its type in the U.S. — spread quickly through the county, according to this Mercury News story.

The test detects protective antibodies to the virus rather than the virus itself. This gives scientists a snapshot of how many people in the county have already been infected, but weren’t seriously sick and didn’t realize it. And it tells residents whether they carry potentially protective antibodies – so may be immune to future infection.

“This is critical information,” said principal investigator Eran Bendavid, an infectious disease specialist and associate professor of medicine with Stanford Health Policy. “We will show the country what to do and how to do it,” he said.

The project, coordinated with the Santa Clara County Department of Health, was applauded by Gov. Gavin Newsom during a Saturday press conference in Sacramento, who called it “the first home-grown serum test in the state of California.”

Read The Mercury News Story

As we watch President Trump tell the states they have to do more to find their own personal protective equipment for their health-care workers, governors lash back with demands for a national leader who will unlock the emergency powers of the federal government.

The response to the COVID-19 pandemic has exposed major weaknesses in the federalist system of public health governance, which divides powers among the federal, state and local governments, argues SHP’s Michelle Mello in this New England Journal of Medicine commentary.

The coronavirus, she writes, “is exactly the type of infectious disease for which federal public health powers and emergencies were conceived: it is highly transmissible, crosses borders efficiently, and threatens our national infrastructure and economy.”

“Strong, decisive national action is therefore imperative,” writes Mello, a professor of medicine and a professor of law, and Rebecca L. Haffajee, a policy researcher at the RAND Corporation. “Yet the federal response has been alarmingly slow to develop, fostering confusion about the nature of the virus and necessary steps to address it.”

The authors warn this “lack of interjurisdictional coordination has and will cost lives.”

Though states must respect constitutionally protected individual rights — such as due process, equal protection and freedom of travel and association — the Constitution puts primary responsibility for public health with the states, cities and counties. It gives them the right to exercise broad police powers to protect their citizens’ health during ordinary times.

In extraordinary times — like the one we’re experiencing now — states and the federal government can activate emergency powers to expand their abilities to act swiftly and protect human life and health. All 50 states and dozens of localities and the federal government have declared emergencies.

“The resulting executive powers are sweeping: they can range from halting business operations, to restricting freedom of movement, to limiting civil rights and liberties, to commandeering property,” Mello and Haffajee write in the NEJM Perspective.

This emergency legal framework has led to too few checks-and-balances on poor decisions—historically, in the direction of being overly aggressive, write the authors. They note a good example is when New Jersey’s governor ordered a nurse returning from Sierra Leone during the 2014 Ebola outbreak into quarantine, contrary to Centers for Disease Control and Prevention guidelines.

Too Little Too Late? 

“Today, we find ourselves in the opposite situation: the federal government has done too little,” the authors write. “Perhaps because of misleading early statements from federal officials about the gravity of the COVID-19 threat, public sentiment has weighed against taking steps that would impose hardships on families and businesses.”

The tumbling stock market and unprecedented 10 million unemployment claims last month also have created further pressure by the federal government to project a sense of calm.

“The resulting laconic federal response has meant that a precious opportunity to contain COVID-19 through swift, unified national action has been lost — a scenario that mirrors what occurred in Italy,” they write.

So the states had to pick up where the federal government fell short, the authors note. Many jurisdictions issued stay-at-home orders; others did not. As of March 31, more than a dozen governors had yet to issue statewide stay-at-home orders and eight had only ordered partial measures. Yet many jurisdictions turn a blind eye, they note, to noncompliance with social-distancing recommendations issued by the CDC, as evidenced by crowded beaches and children congregating in public parks.

“This is the dark side of federalism: it encourages a patchwork response to epidemics,” the authors write.

“A federal takeover of all public health orders would be out of step with our federalist structure,” the authors state, but there remain three good options:

• “The White House must reverse its current trajectory toward prematurely weakening existing federal measures and the resolve of governors who are enforcing stay-at-home orders and school closures.” Trump said last week he wanted the United States “opened up and raring to go by Easter.” A few days later, he heeded the call of medical experts and extended social-distancing guidelines until the end of April, but public health experts believe the crisis will likely be with us longer.
• Congress should “use its spending power to further encourage states to follow a uniform playbook for community mitigation that includes measures for effective enforcement of public health orders.” It could threaten to withhold some federal funds from states that do not comply.
• “Congress could leverage its interstate-commerce powers to regular economic activities that affect the interstate spread” of COVID-19, such as restricting large businesses from traveling and operating across state lines in ways that expose workers to risk.

The White House could also make further use of the Defense Production Act (DPA) to direct private companies to produce badly needed ventilators and personal protective equipment for health-care workers, the authors write. Trump has ordered General Motors to manufacture ventilators and the $2 trillion stimulus package includes $1 billion for DPA projects.                                                                     

“Learning is difficult in the midst of an emergency, but one lesson from the COVID-19 epidemic is already clear: when epidemiologists warn that a pathogen has pandemic potential, the time to fly the flag of local freedom is over,” the authors conclude. “Yet national leadership in epidemic response works only if it is evidence-based. It is critical that the U.S. response to COVID-19 going forward be not only national, but rational.”

Stanford Health Policy's Eran Bendavid and Jay Bhattacharya write in this Wall Street Journal editorial that current estimates about the COVID-19 fatality rate may be too high by orders of magnitude.

"If it’s true that the novel coronavirus would kill millions without shelter-in-place orders and quarantines, then the extraordinary measures being carried out in cities and states around the country are surely justified. But there’s little evidence to confirm that premise—and projections of the death toll could plausibly be orders of magnitude too high.

"Fear of Covid-19 is based on its high estimated case fatality rate — 2% to 4% of people with confirmed Covid-19 have died, according to the World Health Organization and others. So if 100 million Americans ultimately get the disease, 2 million to 4 million could die. We believe that estimate is deeply flawed. The true fatality rate is the portion of those infected who die, not the deaths from identified positive cases."

"The latter rate is misleading because of selection bias in testing. The degree of bias is uncertainbecause available data are limited. But it could make the difference between an epidemic that kills 20,000 and one that kills 2 million. If the number of actual infections is much larger than the number of cases—orders of magnitude larger—then the true fatality rate is much lower as well. That’s not only plausible but likely based on what we know so far."

Read the Editorial 

As the deaths and detected cases from the COVID-19 epidemic continue to rise globally, government planners and policymakers require projections of its future course and impacts. They also need to understand how potential interventions might “flatten the curve.”

“It’s important to understand these overall effects by geographic area, demographic group, and for special populations like health-care workers,” says Stanford Health Policy’s Jeremy Goldhaber-Fiebert, who will be teaching a new class in the spring on infectious disease modeling with Stanford Medicine’s Jason Andrews. “Doing this requires mathematical models that incorporate the best available clinical, epidemiological, and policy data along with their associated uncertainties — the state-of-the-art of infectious disease modeling.”

Goldhaber-Fiebert and Andrews will debut the new course, Models for Understanding and Controlling Global Infectious Diseases (HUMBIO 154D for undergrads and HRP204 for graduate students) in the upcoming spring quarter. Stanford Provost Persis Drell announced last week that all spring courses at the university will now be taught online and pushed the start of the new quarter April 6.

Andrews is an infectious disease physician and assistant professor of medicine and Goldhaber-Fiebert, an associate professor of medicine, is a decision scientist.

The class will enable students to become critical consumers of studies using infectious disease modeling and to learn the building blocks for constructing infectious disease models themselves.

Despite the course being new and listed in the middle of winter quarter, they have seen enrollment rise from eight — prior to the rise of COVID-19 in the U.S. and its direct impacts on Stanford’s operations — to nearly 30 students as of March 22.

“Together Jason and I are leading one of several efforts on COVID-19 modeling here in Stanford,” said Goldhaber-Fiebert. “And we anticipate that the course will increase the number of Stanford students with the necessary skills to contribute to Stanford’s leadership in this area.”

Most Americans don’t realize there are silent brokers helping to fix the price of their prescription drugs — or that it’s a $100 billion annual business accounting for half of Big Pharma sales.

They’re called pharmacy benefit managers (PBMs), with CVS Caremark, Express Scripts and Optum RX dominating the market. Their chief function is to develop and maintain a list called the “formulary,” a list of drugs that will be covered by health-care plans. The formulary groups drugs into tiers with different levels of patient cost sharing.

They also pool volume across health plans to negotiate with drug manufacturers and retailers on prescription drug pricing. And PBMs reap rewards from rebates and fees that drug manufacturers pay them, as well as from a ‘pharmacy spread’ where PBMs bill health plans more than they reimburse pharmacies.  

All of this comes at a cost to patients.

“Patients typically only think about what they pay out-of-pocket at the pharmacy counter,” said Alex Chan, a PhD candidate in health economics at Stanford Health Policy. He and Kevin Schulman, a professor of medicine and professor of economics, by courtesy, at the Stanford Graduate School of Business, have just published a paper in JAMA Health Forum that examines these silent and powerful intermediaries.

“As PBMs leverage the formulary design to secure more and more rebates and fees from manufacturers, these drug manufacturers raise the list price in response,” Chan said. “The patients’ out-of-pocket cost at the counter would increase but at a less noticeable rate given that they co-pay are just a percentage of the list prices.”

Unless these rebates are passed along to consumers as reduced premiums, the net effect is an increase in premiums. Furthermore, if formulary design is used to help PBMs secure better rebates, PBMs may prioritize expensive drugs over more cost-effective drugs.

Transparency

These pharmacy benefit managers have come under scrutiny as health policy experts learn more about the scale of prescription drug rebates and other questionable practices used by these intermediaries in the prescription drug market. For example, PBMs can include “gag clauses” that prohibits pharmacists from telling customers about cheaper drug options.

They ask themselves: What is the underlying value of PBMs for both payers and patients?

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“They create value by providing information on the quality and value of products and services and by providing negotiation leverage as they amass scale by aggregating smaller buyers (or sellers),” they write. “Consumers can be sure to share in this value under three conditions: when there is competition among intermediaries, when pricing is transparent, and when it is clearly defined who is negotiating on whose behalf.”

But when these conditions are not met, they add: “We can find that intermediaries can hold a powerful and self-serving position in a market.”

Chan and Schulman found that in the drug prescription market, there are significant concerns about the value of these PBMs:

1. Rather than a market where there is competition among PBMs, consolidation has resulted in a situation in which the three largest PBMs have about 80% of market share. There are significant barriers to competition among PBMs. If a health system wants to switch PBMs, it requires a significant investment in a “request-for-proposal” process.
2. Drug-specific rebates are kept confidential between PBMs and drug manufacturers, and health plans have little ability to clearly assess the cost-savings for their members or to gauge the appropriateness of the rebate passthroughs.
3. Under the rebate model, the role of the PBM has evolved to serving as an agent of both the payer and the manufacturer. The interests of payers and manufacturers are often in conflict, especially with respect to expenditures.

"One of the largest criticisms of PBMs is the lack of transparency surrounding the structure and scale of payments from manufacturers to the PBM,” the authors write. “The current PBM business is shrouded in secrecy.”

Only the PBM knows the actual scope of payments from drug manufacturers, such as rebates and service fees. They note that in 2016, for 13 pharmaceutical companies, payments to PBMs and other intermediaries (such as wholesalers) were $100 billion — or 50% of gross sales.

 “Without transparency, a PBM might develop formularies that maximize payments to the PBM rather than maximize value to patients,” Chan and Schulman write.

Suspicion over just that led health insurance company Anthem to sue Express Scripts for $15 billion in 2016 for overpayments on drug pricing. In the end, Anthem cut ties with Express Scripts to develop its own PBM.

“The PBMs have grown out of sync with what we can reasonably expect to be a value-adding intermediary,” Chan said. “It is hard to really tell how much inefficiencies have been created due to this lack of transparency.”

Legal Solutions

The authors note that Congress has taken steps to shed light on PBMs through the Patient Right to Know Drug Prices Act and the Know the Lowest Price Act, both adopted in 2018. These laws outlaw PBMs gag clauses that forbid pharmacists from telling consumers that their price through a PBM was higher than the as price for the same product.

Chan said these laws are a move toward the direction of providing patients with more transparency about their options.

“An even more promising direction would be for legislation to make a stronger push towards public disclosure of rebates, discounts, and price concessions, along with lower barriers to entry to the PBM market,” he said.

Controversies over the lack of diagnostic testing for the COVID-19 virus have dominated U.S headlines for weeks. Technical challenges with the first test developed by the Centers for Disease Control and Prevention (CDC) left the nation with minimal diagnostic capacity during the first few weeks of the epidemic, according to a new paper published today in the Journal of the American Medical Association by Michelle Mello, a professor of medicine at Stanford Health Policy and professor of law at Stanford Law School.

On February 29, the Food and Drug Administration (FDA) began allowing high-complexity labs across the country to use tests they developed in-house. On March 5, the Stanford Clinical Virology Lab deployed its own test for patients at Stanford Health Care and Stanford Children’s Health.

We asked Mello to answer some questions about the federal rollout of diagnostic testing.

You write that in the early stages, COVID-19 “spread beyond the nation’s ability to detect it.” Is there anything the U.S. government could or should have done weeks ago to get out ahead of the spread?

Adopting broader testing criteria and allowing use of a wider range of tests would have been helpful in identifying the first U.S. cases and containing the spread. Manufacturing problems like the one that arose with CDC’s test are always a risk, but the fact that CDC put all its eggs in that one basket made the manufacturing snafu highly consequential.

Also, the public messaging from Washington about the seriousness of the problem has been neither consistent nor accurate, and I worry it may have led Americans to take fewer steps to prevent community transmission than we should have. Containment was not “pretty close to airtight.” A vaccine was never going to be ready in “three to four months,” as the Trump administration claimed. The case fatality rate is not “way under 1 percent.” Part of the problem here is that as the stock market continues to plunge, the president and the task force he appointed appear to be more concerned about calming investors than stopping the virus.

We seem to be between a rock and a hard place: You write that remedying gaps in testing is imperative, yet “more testing is not always better.” How do we determine the happy middle ground?

First, the testing criteria have to be calibrated to our actual testing capacity. You can’t announce that any American who wants a coronavirus test can get one and then, within hours, announce that there aren’t enough test kits to make that possible. High priorities for testing include patients with serious, unexplained respiratory illness and contacts of known cases. From there, testing can be expanded, beginning with other high-risk groups, as capacity permits.

Second, we should consider unintended side effects of mass testing. The problem with this virus is that it doesn’t have signature symptoms. It looks like the common cold or the flu. If everyone with a cough or fever, or who has been around someone with a cough or fever, shows up in their doctor’s office demanding a test, it will quickly overwhelm care facilities that should be focusing on patients with a higher likelihood of being infected or and those who are infected and are seriously ill. It may also work against the social distancing measures that public health officials are trying to encourage, because crowded waiting rooms may spread the virus.

The CDC announced Monday it now has the testing capacity in 78 state and local public health labs across 50 states to test for the virus. There are now 75,000 lab kits cumulatively to test for COVID-19 with more coming on board by mid-March. But is there anything we could have done to roll this out earlier?

The alternative would have been to allow laboratories to deploy their own tests from the beginning, using the primers and protocols made publicly available by the World Health Organization. That’s what other countries have done. RT-PCR is a mature technology and high-complexity labs around the country are well-qualified to conduct this type of testing.

There is a public health argument for not going that route: perhaps those labs wouldn’t have done as good a job as CDC’s own lab and the state labs that it handpicked early in the outbreak. What if there were erroneous test results? We could miss cases, or we could put people into isolation, with huge social consequences, based on false-positive results. There is also a worry that some labs aren’t consistent about reporting positive test results to CDC, and underreporting could compromise disease surveillance efforts.

The counterargument is that high-complexity labs have that certification for a reason—they’re good at what they do. And of course, surveillance is also compromised when you miss cases because you don’t test.

You write in your paper that testing for COVID-19 “highlights a controversial area of public policy—the regulation of laboratory-developed tests—in which there has long been tension between the goals of access and quality.” Who should be in charge of regulating these tests?

Laboratory-developed tests are largely unregulated outside of emergencies. The FDA proposed draft guidance in 2014 that, if implemented, would have required labs to make certain showings to FDA about tests they developed in-house, with the particular evidence calibrated to the risks involved in having a wrong test result. Contrary to President Trump’s claim that an Obama-era policy constrained coronavirus testing, the guidance did not relate to emergency situations. During declared emergencies, another statute and set of regulations apply, and the FDA has broad discretion to allow or disallow use of novel diagnostics and therapies as emergency countermeasures.

As a general matter, it makes good sense to require labs to submit evidence that their in-house tests work. It’s odd that laboratory-developed tests are carved out of requirements that apply to other kinds of medical devices. It’s also sensible that our legal framework allows FDA’s regular rules to be relaxed during emergencies so we can tailor our response to the difficult and changing circumstances.

You write that diagnostic testing is critical to an effective response to the novel coronavirus. What sort of policies and guidelines should be put into place to prevent such a sluggish rollout during an emerging epidemic the next time one comes around?

The legal framework for an effective emergency response is in place. Because giving agency heads the discretion to act as potentially unforeseeable circumstances require is a linchpin of this legal framework, it only works if leaders make smart choices. Every emergency is different, and there is a danger of Monday-morning quarterbacking. But we should learn from every misstep we make, and I think the lesson here is to make better use of already developed networks of highly qualified labs to make sure we have adequate testing capacity to isolate cases and trace their contacts very early in an outbreak.

What are some innovative approaches we could be taking to speed up testing for those who really need it?

The South Koreans have set up drive-through testing stations in parking lots to avoid concentrating crowds of people indoors. Of course, that requires that you have plenty of test kits, which we don’t yet – but we should also be thinking about creative ways to address the epidemic. For example, how could video calls be used to monitor the health of people confined at home after being exposed to the virus? How can social media be used to connect neighbors to help one another when some are isolated at home? Hopefully we can find new ways for technology to bring us together when pathogens drive us apart.

A task force of national health experts recommends clinicians screen all adults 18 to 79 for the hepatitis C virus (HCV), noting that the viral infection is now associated with more deaths in the United States than the top 60 reportable infectious diseases combined.

Many people are unaware they are carrying the viral infection.

“People with hepatitis C do not always feel sick and may not know they have it,” says chair of the U.S. Preventive Services Task Force Douglas K. Owens, M.D, M.S. “Screening is key to finding this infection early, when it’s easier to treat and cure, helping reduce illnesses and deaths.”

Screening involves testing a blood sample to see whether it contains antibodies (disease-fighting proteins) that react specifically to the hepatitis C virus. This test is followed by a second test that determines the level of virus in the blood. When used together, these two tests accurately identify whether a person has hepatitis C infection, according to the Task Force.

An estimated 4.1 million people in the United States are carrying HCV antibodies; about 2.4 million are living with the virus, according to the Task Force. The HCV infection becomes chronic in 75% to 85% of cases and some of those people develop symptoms such as chronic fatigue and depression, and liver diseases that can range from cirrhosis to liver cancer.

Approximately one-third of people ages 18 to 30 who inject drugs are infected with the virus; 70% to 90% of older injection-drug users are infected.

Owens, who is the director of Stanford Health Policy and the Henry J. Kaiser, Jr., Professor of Medicine, said the opioid epidemic now plays an important role in the prevalence of HCV. There are more than three times the number of acute HCV cases than a decade ago, particularly among young, white, injection drug users who live in rural areas. Women aged 15 to 44 have also been hit hard by the virus that is spread through contaminated blood.

“The opioid epidemic has added fuel to the HCV fire, substantially increasing transmission,” said Owens. “HCV is now an enormous public health problem, affecting a much broader age range of people than before. Fortunately, we have the tools to identify people and treatment is now successful in the vast majority of patients, so screening can prevent the mortality and morbidity from HCV.”

The U.S. Preventive Services Task Force is an independent panel of national experts in prevention and evidence-based medicine whose recommendations are followed by primary care clinicians nationwide. It has recommended people who are at high risk be tested for hepatitis C, as well as “baby boomers” born between 1945 and 1965, but now recommends screening all adults age 18 to 79, and younger or older patients if they are at high risk of acquiring HCV.

Hepatitis C is primarily spread when blood from an infected person enters the body of someone who is not infected. There currently is no vaccine for hepatitis C although research in the development of a vaccine is underway. But there are effective oral direct-acting antiviral (DAA) medications that can clear the virus from the body, particularly if caught early.

“Hepatitis C affects millions of people across the country,” says Task Force member Michael J. Barry, M.D. “We recommend screening all adults regardless of their risk because new evidence shows that more people can benefit from this service than even before.”

The Task Force’s final recommendation statement and corresponding evidence summary have been published online in the Journal of the American Medical Association, as well as on the Task Force website at http://www.uspreventiveservicestaskforce.org.