As the number of coronavirus cases started spiking again this month, the White House keyed in on a different number — one that paints a more rosy picture of the pandemic: the case fatality rate.
When asked about rising cases at a recent briefing, press secretary Kayleigh McEnany quickly parried. “We’re seeing the fatality rate in this country come down,” said McEnany. “That is a very good thing.”
The case fatality rate is the result of a simple mathematical calculation: the number of deaths divided by the number of diagnosed coronavirus cases. But it’s also a moving target. Case numbers are rising fast; deaths are a lagging indicator, running several weeks behind.
“Measuring … mortality rates on any given day is not a reliable way of communicating about this pandemic,” said Dr. Tom Inglesby, director of the Johns Hopkins Center for Health Security.
It is possible that innovations in treatment methods and therapeutic drugs have helped improve the survivability of COVID-19. It is also possible that with more young people being infected in this latest round, they are less likely to die. But medical experts warn it is also just too soon to be sure. And, they say, it’s an unreliable and misleading metric.
But that hasn’t stopped President Trump from boasting about the figure.
“Our case fatality rate has continued to decline and is lower than the European Union and almost everywhere else in the world,” Trump said Tuesday at his first White House coronavirus briefing in nearly three months.
In his interview on Fox News Sunday with Chris Wallace, Trump asked his staff to bring him the “death chart.” He said “the death chart is much more important” as Wallace ticked through 75,000 daily cases and 1,000 daily deaths.
Trump had that chart displayed behind him during the briefing. But this isn’t a metric public health experts have been using.
Inglesby says that by a more direct measure (the sheer number of deaths), and even adjusted for population size, the U.S. is not doing well compared to other countries around the world.
“What national leaders have the obligation to tell people is just the direct truth,” Inglesby said. “If we give them a false sense that things are getting better when they’re not, then they’re going to make decisions that increase the risk of transmission. And they’re also going to stop having confidence in the information they’re being given.”
Focusing on the fatality rate also glosses over other serious problems with the coronavirus, says Dr. David Relman, who specializes in immunology and infectious diseases at Stanford. He says about 20% of people get really sick with potential long-term health consequences. Plus, he says, the coronavirus is stressing the medical system. And as long as it is uncontained, the virus is holding the economy back. So, as he sees it, talking about the case fatality rate is counterproductive.
“What you do instead when you pull out one little piece and dangle it in front of people is to confuse and distract and undermine the overall message,” said Relman.
He says people need to take this virus seriously and take precautions, and that is a sacrifice that requires leaders to get the public on board. For Trump, accentuating the positive might have short-term political benefits, but there are longer-term risks.
“I think it was a mistake early on to be dismissive of the seriousness of it and that it was just going to go away,” said Mike DuHaime, a Republican strategist.
DuHaime gives Trump credit for coming out this week and treating the coronavirus more seriously than he has in the past, telling people to wear masks and avoid crowds. But he readily acknowledges that Trump has gone through other brief spurts urging the public to sacrifice to slow the spread of the virus, only to reverse himself, downplay the severity and pressure states to reopen.
“In order for him to succeed here politically, his credibility has to be as strong as possible,” said DuHaime, who now works at the firm Mercury.
Trump’s credibility has taken a major hit through this crisis. According to the latest Pew Poll, only 30% of Americans trust Trump to get the facts right on the virus. And Trump’s approval rating has tanked too, something he is attempting to repair with the resumed daily briefings.
“At the end of the day, he just needs to do a good job. I know that sounds simplistic, but when you’re an incumbent running for reelection, doing a good job is really the most important thing,” said DuHaime. “And to this point people haven’t seen him do a good job on what they think is the greatest challenge of his presidency.”
DuHaime points out that people are checking the numbers every day — the number of new cases in their city and state, the number of hospitalizations and deaths. Those numbers are all readily available and easier to find than the case fatality rate.
On June 25, San Francisco Mayor London Breed was excited the city’s zoo would finally reopen after closing down for months in response to Covid-19. She visited the facilities, posting photos on social media with a mask on and giraffes in the background.
“I know people are eager to get back to some sense of normalcy, especially families and children,” she tweeted. And it looked like her city was taking a step toward it.
The day after the visit, Breed had to announce the sad news: San Francisco’s reopening plan — for the zoo and various other facilities, including hair salons and indoor museums — would have to be put on hold.
“COVID-19 cases are rising throughout CA. We’re now seeing a rise in cases in SF too. Our numbers are still low but rising rapidly,” she tweeted. “As a result, we’re temporarily delaying the re-openings that were scheduled for Monday.”
While state and local leaders nationwide were pushing ahead with reopening, Breed pulled back. “I listened to our public health experts,” she told me. “It’s hard. The last thing I want to do is go out there and say one thing and then have to say something else. But I think it’s important that people understand things can change. This is a fluid situation.”
The decision — taken weeks before California Gov. Gavin Newsom’s move to shut down risky indoor venues statewide in July — was emblematic of San Francisco’s cautious approach throughout the coronavirus crisis. The city joined a regional stay-at-home order in March, before the rest of the state and New York, which became a Covid-19 epicenter, imposed their own orders. It was also slower to reopen: When California started to close down indoor venues again, the order largely didn’t affect San Francisco — because the city never reopened bars and indoor dining, among other high-risk venues, in the first place.
By and large, the approach — aided by regional cooperation, with leadership from Santa Clara County Health Officer Sara Cody, and widespread social distancing and mask-wearing by the public — has kept cases of Covid-19 manageable. In the spring, California and the Bay Area saw some of the first coronavirus cases, but quick action since then has let San Francisco and the surrounding region avoid turning into a major hot spot.
The increase in cases this summer has exceeded the April peak and fallen particularly hard on marginalized groups, especially Latin communities. But that, too, seems to be turning around: New cases started to fall by July 20 — almost a week before the state as a whole began to plateau. San Francisco has maintained less than 60 percent the Covid-19 cases per capita as California, and less than 30 percent the deaths per capita. Its caseload and death toll are lower than other large cities, including Washington, DC, and Columbus, Ohio, and far lower than current hot spots like Arizona and Florida.
“It’s doing as well as it can, given what’s going on around it,” Peter Chin-Hong, an infectious disease expert at the University of California San Francisco, told me.
Experts and local officials say the summer increase in cases doesn’t take away from what San Francisco has done. What it shows, instead, is the limits of what a local government can do — and the risk of relying on a county-by-county, state-by-state approach to a truly national crisis.
“We have to accept that we are all interrelated in a pandemic,” Kirsten Bibbins-Domingo, an epidemiologist at UCSF, told me. “We have to help each other out.”
“We are not isolated; we are interconnected,” Grant Colfax, director of the San Francisco Department of Public Health, told me. “The virus exploits that very interconnectedness of our society. Without a consistent, robust, and sustained federal response that is driven by science … eventually things cannot be sustained.”
This is why, experts argue, federal leadership is so key: The federal government is the one entity that could address these problems on a large scale. But President Donald Trump has ceded his role to the states and private actors — what his administration called the “state authority handoff” and the New York Times described as “perhaps one of the greatest failures of presidential leadership in generations.”
That’s left cities and states to fend for themselves. San Francisco has made the best of it, with the kind of model that experts argued could have prevented the current coronavirus resurgence if it had been followed nationally.
“There’s a value to being cautious,” Bibbins-Domingo said. “Any type of reopening is going to come with some increase in cases. That’s what we are learning in the pandemic. That’s what the infectious disease experts told us was going to happen. Places that thought they could just reopen without caution have really paid the price for it.”
San Francisco’s leaders were ahead on Covid-19
Breed started to really worry about the coronavirus in February, when she saw a glimpse of the future.
Stories of overwhelmed hospitals in Wuhan, China, showed that Covid-19 could cripple health care systems. But Breed believed, she said, that San Francisco’s larger, more advanced health care system could handle the blow. Then her advisers and experts told her differently — that a situation like Wuhan’s really could happen in San Francisco if she didn’t act.
“The shock I got,” Breed said. “We have all these hospitals, all these places where we have some of the most incredible doctors and research institutions. So in my mind, I’ve always thought this is where you want to be if something happens. To be told that here’s what our capacity is, here’s what happens if we do nothing, and what we need to prepare for, it really did blow my mind.”
At that point, she concluded, “We need to shut the city down to make sure this doesn’t happen.”
The virus has been the biggest challenge yet for Breed, who first became mayor in 2017 when her predecessor died, before she was elected to the role in 2018, having previously served on the Board of Supervisors.
But Breed, with the guidance of the Bay Area’s public health officials, has consistently kept the city ahead on Covid-19. The day before Trump claimed, falsely, that coronavirus cases would go from 15 to nearly zero in the US, Breed on February 25 declared a local state of emergency over the virus. Three days before California imposed a stay-at-home order and nearly a week before New York state did, San Francisco County, with Breed’s full backing, on March 16 joined the five other Bay Area counties in issuing the country’s first regional stay-at-home order.
Breed was ahead of not just much of the nation, but her progressive peers as well. On March 2, she warned on Twitter that the public should “prepare for possible disruption from an outbreak,” advising people to stock up on essential medications, make a child care plan in case a caregiver gets sick, and plan for school closures. The same day, New York City Mayor Bill de Blasio, a fellow Democrat, tweeted that he was “encouraging New Yorkers to go on with your lives + get out on the town despite Coronavirus.”
New York City would go on to suffer one of the worst coronavirus outbreaks in the world, with its total death rate standing, as of July 29, at 272 per 100,000 people — more than 45 times as high as San Francisco’s rate of 6 per 100,000. (De Blasio’s office didn’t respond to a request for comment.)
San Francisco’s death toll is also fairly low compared to that of some other areas in California — a fraction of Los Angeles County’s 45 per 100,000 and Imperial County’s 103. San Mateo County, a Bay Area county that reopened more aggressively, has more than double the death rate, at 15 per 100,000. San Francisco looks even better compared to cities and counties beyond California — with less than a tenth the deaths per capita as Washington, DC, and about a sixth as many as Franklin County, Ohio, where Columbus is, and Fulton County, Georgia, where most of Atlanta is.
At the time of the initial stay-at-home order, Chin-Hong said, people wondered if Breed was overreacting. “Of course, in hindsight, she was very prescient. She knew what was coming.”
There’s good reason to believe that San Francisco’s early action, particularly its lockdown, helped. The research indicates that stay-at-home orders and similar measures worked, with one preliminary Health Affairsstudy concluding:
Adoption of government-imposed social distancing measures reduced the daily growth rate by 5.4 percentage points after 1–5 days, 6.8 after 6–10 days, 8.2 after 11–15 days, and 9.1 after 16–20 days. Holding the amount of voluntary social distancing constant, these results imply 10 times greater spread by April 27 without SIPOs (10 million cases) and more than 35 times greater spread without any of the four measures (35 million).
That’s not to say San Francisco performed flawlessly.
Even the experts who praised Breed simultaneously raised alarms about how the virus had disproportionately affected minority populations — with about half of confirmed Covid-19 cases affecting Latin people, even though they comprise about 15 percent of the local population. The city’s large homeless population is also a major point of concern, with a big outbreak at the largest local homeless shelter. These are the kinds of blind spots with Covid-19 that have shown up across the country — as minority groups, in particular, are more likely to work in the kind of job deemed “essential” — and San Francisco isn’t immune to them.
“Myself, just taking care of patients, I know that some of those patients are going back to work sick if they don’t have to be hospitalized,” Yvonne Maldonado, an infectious disease expert at Stanford, told me. “They can’t afford not to work.”
Local officials point out they have taken aggressive action to shield marginalized populations — creating support programs for them, fielding contact tracing calls in Spanish, and setting up more than 2,500 hotel rooms for the vulnerable, including homeless people. And the disproportionate case count for Latin people is from a baseline of cases that’s lower than other parts of the state and country with similar disparities. Out of 57 Covid-19 deaths in the city, only one was a homeless person.
Breed acknowledged the challenge, describing the city’s response to Covid-19 as a work in progress as she and other officials struggle with the uncertainty that surrounds a virus that’s still relatively new to humans.
“That’s hard,” Breed said. “We have to make the hard decisions. What we hope people will understand is why. We keep trying to call attention to what’s happening or could happen to any of us. It’s a constant struggle.”
That’s especially compounded by the massive sacrifices that people have to make as they’re forced to stay at home, potentially giving up income, child care, and social connections.
Breed is aware this is no easy task. On a personal level, she said, “I’m tired of being in the house. I’ll tell you that much.” She acknowledged that the shutdown has left many people struggling, “because their livelihoods are at stake, their ability to take care of themselves is at stake.”
But the alternative, she suggested, is much worse. It’s not just more Covid-19 cases, hospitalizations, and deaths — but harm to the economy if a major outbreak forces cities and states to shut down all over again. As a preliminary study of the 1918 flu pandemic found, the cities that came out economically stronger back then took more aggressive action that hindered economies in the short term but better kept infections and deaths down overall.
Experts echoed a similar sentiment. “Dead people don’t shop. They don’t spend money. They don’t invest in things,” Jade Pagkas-Bather, an infectious disease expert and doctor at the University of Chicago, told me. “When you fail to invest in the health of your population, then there are longitudinal downstream effects.”
Breed had a key ally in San Francisco: The public
Chin-Hong, who lives and works in the Bay Area, recalled a recent experience he had at the grocery store. With the place at full capacity, people were waiting outside the store in a line. One person joined the line without a mask on. People began to eye him disapprovingly. He grew visibly nervous, at one point pulling his shirt over his mouth. After a while, a store staff member came out and gave him a mask, which he quickly put on.
The story is emblematic of one of Breed’s key advantages as she has pushed forward with aggressive actions against the coronavirus: San Francisco’s public is by and large on board, with a lot of solidarity built around social distancing and masking.
“The politician is only as good as her constituents,” Chin-Hong said. “It’s a key factor in all of this.”
In some ways, the public was even ahead of Breed. In the weeks before Bay Area counties issued a stay-at-home order, major tech companies in the region, like Google and Microsoft, told employees to work from home. That partly reflects tech employees’ ability to work from home with fewer disruptions, but also a greater sense of vigilance for an industry with close ties to the countries in East Asia that saw Covid-19 cases earlier.
It wasn’t just the tech sector. Restaurant data from OpenTable shows San Francisco was starting to avoid dining out by the first week of March, while most other cities in the US saw at best small decreases, if any changes: On March 1, dining out via OpenTable was down 18 percent in San Francisco, compared to down 3 percent in Los Angeles, down 2 percent in New York City, up 2 percent in Houston, and up 21 percent in Philadelphia. From that point forward, San Francisco’s numbers steadily dropped, while much of the US fluctuated before the depth of the outbreak became clearer nationwide.
San Francisco has also been better than much of the country about mask-wearing. A New York Times analysis found there’s a roughly 60 to 90 percent chance, depending on the part of the city, that everyone is masked in five random encounters in San Francisco. In other parts of the US, including cities, the percent chance can drop to as low as 20, 10, or the single digits.
Even in California, it wasn’t guaranteed things would go like this. Orange County’s chief health officer resigned in June due to public resistance against a mask-wearing order. Sheriffs in Orange, Riverside, Fresno, and Sacramento counties said they wouldn’t enforce Gov. Newsom’s June order requiring masks in public and high-risk areas. With Trump and other Republicans suggesting that social distancing and masking requirements were part of a broader overreaction to the pandemic and an attempt at government overreach, and people genuinely suffering due to the economic downturn, San Francisco could have taken a very different direction.
We don’t know for certain why San Francisco’s public is more aggressive about precautions against Covid-19. One advantage San Franciscans have is many of them, particularly those in the tech sector and other office jobs, can work from home much more easily than, say, “essential” agricultural employees. The city also has close ties to East Asia, including China, potentially offering personal connections — and an early warning — to the first coronavirus outbreaks and the value of masking. San Francisco is also very progressive and Democratic, which helps as physical distancing, masking, and related measures have become politically polarized. Perhaps Breed’s more aggressive communication paid off.
Whatever the cause, there’s good reason to believe the public embrace of precautions helped the city. A review of the research published in The Lancet found that “evidence shows that physical distancing of more than 1 m is highly effective and that face masks are associated with protection, even in non-health-care settings.”
Again, it’s not perfect. Breed told me of a recent trip to a local store that was clearly far above the city’s reduced standards of capacity, with some of the staff and customers not wearing masks. “I was like, ‘What the heck is this? This is ridiculous,’” she said. “I called [the San Francisco Department of] Public Health, and they put a stop to it.”
More recently, Breed had to get tested for coronavirus after she went to an event attended by someone who reportedly knew they were positive. She used the moment to lightly admonish those who didn’t follow the recommended precautions: “I know people want to be out in public right now, but this disease is killing people. It’s simply reckless for those who have tested positive [to] go out and risk the lives of others,” she tweeted. “I cannot stress this enough: if you test positive, it’s on you to stay home and not expose others.” (Breed tested negative.)
But San Francisco’s public is seemingly better than much of the country at following the recommended precautions. Beyond Breed’s actions, that’s a potent explanation for why San Francisco has done relatively well — and why other parts of the state and country haven’t.
Local governments can only do so much about a pandemic
As successful as San Francisco has been relative to other parts of California and the US, it hasn’t escaped the recent rise in Covid-19 cases untouched. As of July 22 (the most recent reliable local data available), the city hit a seven-day average of 98 new cases a day — down from a peak of 120 several days prior but up from the previous peak of 48 in mid-April.
More than reflecting San Francisco’s own failures, experts said the upward swing in cases reflects the limits of what a local government can do when a virus spreads nationally and globally. When a virus can cross borders, there’s only so much San Francisco can do if its residents can drive an hour or two to a county where bars and indoor dining are open for service, or to meet with family members in an area that’s hit much harder by Covid-19.
“When you have different rules for different counties, it’s very confusing,” Maldonado said. “People lose the message.”
There are similar limitations to what even California can do. It can impose its own lockdown, but it has less control over cases from Arizona, Nevada, Mexico, or other parts of the globe. While the state has taken steps to build up its testing capacity — surpassing the benchmark of 150 tests per 100,000, which is the equivalent of 500,000 tests nationwide — it can only go so far if there are constraints around the country for testing.
The testing problem is especially acute now: With new outbreaks across the US, demand for tests climbed as supply constraints reappeared. That’s led to waiting periods of up to weeks for getting results back — making tests practically useless for confirming, tracing, and containing infections before they have time to spread.
But there are limits to what San Francisco or California can do if the bottlenecks for testing are originating in other parts of the country or world — whether they’re due to epidemics in Arizona and Florida, or because factories in the Northeast and South can’t produce enough swabs to collect samples or reagents to run tests.
“We need a national plan,” Cyrus Shahpar, a director at the global health advocacy group Resolve to Save Lives, told me. “In terms of the structures to improve the supply chain or procure more stuff for the whole country, that’s a federal level of support. You need that to be in place.”
The Trump administration, however, has explicitly left most of these issues for states to solve. The White House’s testing plan declared that the federal government is merely a “supplier of last resort,” leaving it to local and state governments and private actors to fix choke points along the testing supply chain. The New York Times explained this was part of a broader “state authority handoff” plan that would “shift responsibility for leading the fight against the pandemic from the White House to the states.”
To the extent the federal government has provided support, Trump has actively undermined it. When the federal government released a phased plan for state reopenings, Trump called on states to reopen faster — to supposedly “LIBERATE” them from economic calamity. After the Centers for Disease Control and Prevention recommended people in public wear masks, Trump said it was a personal choice, refused for months to wear a mask in public, and even suggested that people wear masks to spite him (although a recent tweet seemed to support masking). (The White House didn’t return a request for comment.)
In my interviews, local officials, health care workers, and experts repeatedly complained about the problems caused by federal inaction. Breed lamented that San Francisco, and California, couldn’t rely on federal support to get personal protective equipment for health care workers, particularly in the early stages of the pandemic. A San Francisco Department of Public Health spokesperson told me that testing took time to scale up while the federal government did little to address supply constraints, commenting that the mixed messaging and inaction from the federal government “are hampering local efforts to be as effective as we would like to be.”
Over time, even the once-proactive California let its guard down. As Gov. Newsom faced pressure from local governments and businesses to reopen the state quickly, he allowed counties to reopen at a quicker pace if they met certain metrics. That led to new outbreaks, particularly in Central and Southern California — each of which presented a risk of bleeding over to the Bay Area. As Bibbins-Domingo said, county-by-county variations “have not been helpful” for suppressing the virus in San Francisco or statewide.
California Health and Human Services Secretary Mark Ghaly said that, like everyone else, the state was still learning how to properly combat the pandemic. But he argued it does make sense to tailor local responses to Covid-19 to what’s happening locally — and that’s what the state tried to do as it let some counties move quicker than others, while keeping some oversight by enforcing certain criteria before counties moved ahead.
The state is still “figuring out … the balance between hundreds of different things,” Ghaly told me. That includes, he added, “how you support counties making local decisions while maintaining some level of cohesiveness at a regional and statewide level so we don’t erode gains.”
Still, the fractured nature of federalism doesn’t help for fighting a virus that ignores local, state, and national borders.
A recent study in Science backed that up. Running simulations for Europe, researchers concluded that better-coordinated action within the European Union can help suppress Covid-19 better than different countries acting in different ways. Drawing on that finding, the authors concluded:
The implications of our study extend well beyond Europe and COVID-19, broadly demonstrating the importance of communities coordinating easing of various [non-pharmaceutical interventions] for any potential pandemic. In the United States, [non-pharmaceutical interventions] have been generally implemented at the state-level, and because states will be strongly interconnected, our results emphasize national coordination of pandemic preparedness efforts moving forward.
That the US has by and large stuck to a state-by-state and county-by-county approach to public health — an approach that predates the coronavirus pandemic — can help explain, then, why the country has continued to fail to control Covid-19 in the same way countries with strong national plans and, in some cases, international cooperation haven’t. To this day, America reports among the highest rates of coronavirus cases and deaths in the world.
In that context, with outbreaks raging around San Francisco and California, there’s only so much any single local or state government could do. “When you look at success stories of countries on Covid, you had a strong central voice,” Chin-Hong said.
So while San Francisco has done a lot right, it will take the rest of the country adopting a similar approach for the city, the broader Bay Area, or anywhere else in the US to really be safe from the coronavirus.
Problems with the government’s rationale for authorizing use of convalescent plasma in COVID-19 patients go far beyond the dustup over the purported 35% survival benefit cited by top officials on Sunday, numerous researchers say.
That figure quickly came under fire, leading to an apology from Commissioner Stephen Hahn, MD — but that’s not the only criticism leveled at the FDA’s analysis of the available data.
Much of it came from the Mayo Clinic and FDA expanded access program (EAP), at this point published only as a preprint manuscript. Although a large number of patients were included, the study was observational only, with no untreated control group. That makes the findings merely hypothesis-generating, and can’t offer any firm conclusions.
That’s fine for issuing an emergency use authorization (EUA), but not so much for making claims about survival benefit, independent researchers said.
“It’s not even a question of overstating,” Adam Gaffney, MD, MPH, a critical care doctor and health policy researcher at Harvard Medical School, told MedPage Today. “You can’t state much at all when you don’t have a randomized controlled trial.”
“People have made a big deal of Hahn referring to relative versus absolute risk reduction, but I think that’s less of a big deal,” Gaffney said. “The biggest problem is that the data they are citing … is not randomized. That’s the source of all the problems.”
Hahn took heat for saying that a “35% improvement in survival is a pretty substantial clinical benefit” further explaining that of “100 people who are sick with COVID-19, 35 would have been saved because of the administration of plasma.”
Critics rapidly took to Twitter, stating that the interpretation was incorrect. Hahn was referring to relative risk reduction, not absolute risk reduction. Thus, calculating the number of lives saved — which isn’t something experts recommend doing based on observational data in the first place — would have translated to somewhere more in the ballpark of 5 out of 100.
Moreover, the “risk reduction” came from a comparison of patients treated with high-titer plasma versus those receiving lower-titer preparations. The study offered no basis for concluding how many patients may have been “saved” relative to standard care.
And the 35% reduction in that analysis was for 7-day mortality; the relative reduction at 30 days was only 23%.
Hahn’s recital of the 35% figure “was just PART of the error,” tweeted Vinay Prasad, MD, MPH, of the University of California San Francisco. “The entire comparison is flawed. It is not a suitable control. The data don’t show anything useful.”
“The much broader problem here is the lack of commitment to performing large, national randomized controlled trials,” Gaffney said. “We could have done it for convalescent plasma. Instead, we did the EAP. I understand why people wanted it, but now we don’t know [if convalescent plasma works]. We have a question mark instead of a period.”
Undermining Trust in FDA?
Critics have charged that serious mistakes like Hahn’s misstatement could undermine FDA’s credibility, especially as it faces challenging decisions about potentially approving a vaccine this fall.
“This is playing out in the context of a hyper-politicized moment,” Gaffney said. “It behooves everyone to be extremely cautious in speaking about these things to avoid the appearance of politicization.”
On CBS This Morning on Tuesday, Hahn addressed concerns about politicization by offering reassurance to the “American people that this decision was made based upon sound science and data.”
In response to questions about the timing of the EUA announcement — it came just a day after President Donald Trump tweeted allegations that the “deep state” was holding back access to COVID-19 treatments with Hahn’s Twitter handle cited, and a day before the Republican National Convention got underway — Hahn said the agency had been working on the application for 3 or 4 weeks and was waiting on additional validation data, which were received at the end of last week and over the weekend.
“We’re going to continue to get data and as we’ve done with any other authorization, we will update that decision as new data come,” Hahn said on the news program. His agency initially issued an EUA for hydroxychloroquine, for instance, but later revoked it when the negative randomized trial data became available.
Lack of Access to FDA’s Data Review
Whether the public will ever see the full convalescent plasma data underlying the EUA is another matter. The “Clinical Memorandum” issued as the evidence behind the FDA’s decision glossed over the statistical analysis conducted by the agency; in particular, it made no mention of the 35% relative reduction in deaths.
Another problem with that is the 35% figure’s source isn’t fully clear. Although the EAP preprint manuscript is the most obvious source, Gaffney noted that HHS Secretary Alex Azar said it referred to a subgroup of patients under age 80 who were not on a ventilator. That is not found in the publicly available data. He also pointed to a tweet by FDA spokesperson Emily Miller that contains an agency slide showing a 37% reduction in mortality for non-intubated patients age 80 or under treated within 72 hours who got high-titer convalescent plasma, compared with low-titer product. Neither of those figures is reflected in the EAP manuscript.
The FDA did not return a request by MedPage Today for the full summary of data reviewed by FDA and any independent statistical analysis done by the agency.
Shmuel Shoham, MD, of Johns Hopkins University in Baltimore, said during a press briefing organized by the Infectious Diseases Society of America that “enormous amounts of data have been generated” from the EAP, in which more than 70,000 patients have been treated.
“Some data have been reported in articles and at meetings, but that’s only part of what the FDA — this is their program — has access to,” he said. “The stuff in the public domain is only a fraction of the data they have collected.”
Shoham is on the scientific advisory board of the EAP and is involved in two convalescent plasma clinical trials at Johns Hopkins.
Gaffney said Mayo researchers and FDA reviewers have noted that physicians were blinded to the dose of antibody given in plasma infusions, which he described as a “pseudo-randomization effect. We could use that to make more causal inferences about the effectiveness of antibody titers.”
However, he said there were some significant differences between those who received high-titer versus low-titer antibody, including differences in P-to-F ratio (a measure of inhaled oxygen to blood oxygen) and in those with five or more severe risk factors, suggesting the low-titer group was sicker to begin with than the high-titer group.
Also, patients in the EAP received a variety of other treatments: about half got steroids and 40% were given remdesivir.
“This is why we do randomized controlled trials,” Gaffney said. “Without them it’s very difficult to ensure that the effect you see is the result of the drug, and not the result of patient characteristics.”
Is an Answer Forthcoming?
Several randomized controlled trials of convalescent plasma are underway in the U.S., but the big concern is that wider access to convalescent plasma will limit enrollment. Will clinicians recommend that their patients enroll in a trial in which they might receive placebo? Will patients agree?
For the Hopkins studies, the prevention trial has enrolled 25 people out of a goal of 500, and its outpatient trial has enrolled 50 people of its 600-patient goal.
Liise-anne Pirofski, MD, of Montefiore Medical Center in New York, started a study at the end of April, looking to enroll 300 people. She said the team enrolled the first 150 people quickly, but “then the pandemic began to wane in New York.” With subsequent funding from the NIH, the trial has managed to enroll 190 patients, and has now expanded to four additional sites: New York University, Yale, the University of Miami, and the University of Texas Houston.
Clifton Callaway, MD, PhD, of the University of Pittsburgh Medical Center and lead investigator on the C3PO trial looking at outpatient convalescent plasma, said he hopes the EUA doesn’t discourage participation.
“To the contrary, I believe it should reassure persons considering participation that the FDA feels that convalescent plasma is safe and potentially useful and that the FDA specifically comments: ‘Current data suggest the largest clinical benefit is associated with high-titer units of CCP administered early in the course of disease.’ Giving high-titer convalescent plasma earlier (before you are sick enough to be in the hospital) is exactly what C3PO is testing.”
In addition to determining whether earlier or prophylactic treatment works, Shoham said other unanswered questions include identifying whether other components in plasma are useful therapies and whether low-titer plasma can work at all.
“What everyone agrees on is that the gaps in knowledge that exist can best be addressed by high-quality randomized controlled trials,” he said.
Pirofski said the science and data should be the focus, “rather than the decision and what drove the decision…. I don’t think anyone knows what drove that decision other than the people in that room. Hopefully they know.”
Molina executives said it will likely experience a “significant” increase of Medicaid and exchange members as the pandemic continues to wash over the country and forces more out of work and job-based coverage, according to comments made during Friday’s first quarter earnings call.
The company reaffirmed its 2020 earnings outlook with “enhanced confidence” given the “net-positive” effects likely to stem from the impact of novel coronavirus, as executives noted a steep decline in elective procedures and utilization very late in March and the limited impact COVID-19 has had on costs so far.
Overall for the first quarter, Molina beat Wall Street expectations on earnings per share and revenue which increased to $4.5 billion. Yet, it was only one of two managed care organizations to miss on medical loss ratio targets, which increased to 86.3% due to higher costs in its marketplace business.
Dive Insight:
Another 3.8 million Americans filed for unemployment last week, bringing the total of out-of-work Americans to more than 30 million since the outbreak unfolded.
That presents an opportunity for insurers like Molina that are primarily positioned in Medicaid and Affordable Care Act exchange lines of business. Medicaid coverage is based on income and reserved for low-income Americans and the marketplace, or exchanges, tie coverage to income and financial help for those with incomes below a certain threshold.
Although its membership is likely to swell due to current economic conditions, Molina CEO Joe Zubretsky cautioned investors Friday by saying, “by how much we do not yet know.”
Zubretsky said Medicaid has proven it’s a stress-tested model that works in both robust economies and those in a recession.
So far, through April 27, 950 of Molina’s members have been hospitalized with COVID-19, a small fraction of Molina’s 3.4 million membership base. The average length of stay was about 10 days for these members, but they have not been able to assess the costs per episode yet, executives said Friday.
Its plans in Washington, California and Michigan were most affected. However, its Michigan plans have experienced the highest number of cases.
By business line, Medicare members have experienced the highest percentage of COVID-19 diagnoses followed by Medicaid and marketplace members, in line with reports of the disease disproportionately affecting older Americans.
Molina also said it had entered into a definitive agreement to acquire Magellan Complete Care for $820 million in cash. The deal is expected to close in the first quarter of 2021. The deal gives Molina about 155,000 more members. Last year, Magellan generated more than $2.7 billion in revenue, according to Molina.
Magellan operates in six states, three of which would be new for Molina, including Arizona, Virginia and Massachusetts.
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HENRY KOTULA 