




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.”

Walmart plans to open a 6,500-square-foot standalone clinic in Middleburg, Fla., according to the Jacksonville Record & Observer, which cited plans filed with the local water management district.
The new clinic is part of the expansion Walmart Health announced July 22. The new health center will offer primary care, urgent care, labs, imagining, counseling, optical and hearing services, according to the report. A timeline for when the clinic will open has not been released.
In addition to expanding into Florida, Walmart Health is also planning to open a few clinics in the Chicago market. The company already has freestanding health centers in Georgia and Arkansas.

CMS recently released guidance that includes a new requirement for hospitals to get a Medicare payment boost for caring for patients diagnosed with COVID-19.
The Coronavirus Aid, Relief and Economic Security Act provided a 20 percent add-on payment to the inpatient prospective payment system diagnosis-related group rate for treating patients diagnosed with COVID-19. Until now, a physician’s documentation that a patient has COVID-19 was sufficient to receive the add-on payment. However, recent guidance from CMS adds the requirement to have a positive COVID-19 laboratory test documented in the patient’s medical record for the claim to be eligible for the add-on payment. The new requirement applies to admissions occurring on or after Sept. 1.
To receive the payment boost under the new guidance, the COVID-19 test must be taken within 14 days of the hospital admission. Only the results of viral testing that are consistent with CDC guidelines can be used. Tests performed by an entity other than the hospital, such as a local government-run testing center, can be manually entered into the patient’s medical record, CMS said.
Meeting the new requirement for the add-on payment could be difficult for hospitals, Ronald Hirsch, MD, vice president of the regulations and education group at R1 Physician Advisory Services, told Becker’s Hospital Review.
“There is no way to indicate on a claim for a hospital patient that a test was positive or negative,” he said. “First, the hospital will manually need to go into every record for a patient with U07.1 as a diagnosis and look for a positive test in their own lab system. If one is not found, they will need to search the notes to see if the patient had a test in the 14 days prior to admission and if that test was positive. If there is a note the patient self-reported that they had a positive test, the hospital must decide if they must go through due diligence and attempt to get that actual test result for their records.”
In cases where there isn’t a positive test noted in the medical record, hospitals would need to notify the Medicare audit contractor that they are submitting a claim for a COVID-19 diagnosis that was made clinically, Dr. Hirsch said. The MAC would need to make the appropriate adjustment to ensure the 20 percent add-on payment is not made.
The “undue burden” that the new requirement will place on hospitals was one of the concerns the American Hospital Association highlighted in an Aug. 26 letter to CMS Administrator Seema Verma. The group is also concerned that requiring a positive COVID-19 test will lead to unnecessary additional testing.
“Basing the COVID-19 diagnosis code on clinical judgment alone — in line with coding rules — continues to be an important approach given that test accuracy may not be reliable, re-testing is unnecessarily onerous, and some communities face persistent testing shortages.”
The AHA is urging CMS to drop the new requirement and allow provider documentation of a COVID-19 diagnosis to be sufficient for the add-on payment if the test result is unavailable.

https://unitedstatesofcare.org/resources/2020-health-care-legislative-guide/

ABOUT THE UNITES STATES OF CARE
United States of Care is a nonpartisan nonprofit working to ensure every person in America has access to
quality, affordable health care regardless of health status, social need or income. USofCare works with elected
officials and other state partners across the country by connecting with our extensive health care expert
network and other state leaders; providing technical policy assistance; and providing strategic communications
and political support. Contact USofCare at help@usofcare.org
Health care remains one of the most important problems facing America.
Voters are concerned about access to and the cost for health care and insurance.
Health Care During the COVID Pandemic
The COVID-19 pandemic has illuminated the need for effective solutions that address both the immediate
challenges and the long-term gaps in our health care systems to ensure people can access quality health care
they can afford. Americans are feeling a mix of emotions related to the pandemic, and those emotions are
overwhelmingly negative.*
In addition, the pandemic has illuminated deficiencies of our health care system.
People feel that the U.S. was caught unprepared to handle the pandemic and our losses have
been greater than those of other countries.
People blame government for the inadequate pandemic response, not health care systems.
The COVID-19 pandemic has illuminated the need for effective solutions that address both the immediate challenges and the long-term gaps in our health care systems to ensure people can access quality health care they can afford. In the wake of COVID, policymakers have a critical opportunity to enact solutions to meet their constituents’ short- and long-term health care needs. The 2020 Health Care Legislative Candidate Guide provides candidates with public opinion data, state-specific health care information, key messages and ideas for your health care platform.
Click to access USC_Generic_CandidateEducationGuide.pdf
Promising State Policies to Respond to People’s Health Care Needs
In the wake of COVID, policymakers have a critical opportunity to enact solutions to meet their constituents’
short- and long-term health care needs. Shared needs and expectations are emerging in response to the
pandemic, including the desire for solutions that:
Ensure individuals are able to provide for themselves and their loved ones, especially those worried about
the financial impact of the pandemic.
• Protect against high out-of-pocket costs.
• Expand access to telehealth services for people who prefer it to improve access to care.
• Extend Medicaid coverage for new moms to remove financial barriers to care to support healthier moms
and babies.
Ensure a reliable health care system that is fully resourced to support essential workers and available when
it is needed, both now and after the pandemic.
• Ensure safe workplaces for front-line health care workers and essential workers and increase the capacity to
maintain a quality health care workforce.
• Support hospitals and other health care providers, particularly those in rural or distressed areas.
• Expand mental health services and community workforce to meet increased need.
Ensure a health care system that cares for everyone, including people who are vulnerable and those who
were already struggling before the pandemic hit.
• Adopt an integrated approach to people’s overall health by coordinating people’s physical health, behavioral health
and social service needs.
• Establish coordinated data collection to quickly address needs and gaps in care, especially in vulnerable
communities.
Provide accurate information and clear recommendations on the virus and how to stay healthy and safe.
• Build and maintain capacity for detailed and effective testing and surveillance of the virus.
• Resource and implement contact tracing by utilizing existing programs in state health departments, pursuing
public-private partnerships, or app-based solutions while also ensuring strong privacy protections.
BY THE NUMBERS
The pandemic is showing different impacts for people across the country
that point to larger challenges individuals and families are grappling.
A disproportionate number of those infected by COVID-19 are Black, Indigenous, and people of color. According to recent CDC data, 31.4% of cases and 17% of deaths are among Latino residents and 19.9% of cases and 22.4% of deaths were among Black residents.ix They make up 18.5% and 13.4% of the total population, respectively.
Seniors are at greatest risk. According to a CDC estimate on August 1, 2020, 80% of COVID-19 deaths were among patients ages 65 and older. In 2018, only 16% of Americans were in this age range.
Access to health care in rural areas has only become more challenging during the pandemic and will likely have lasting impacts on rural communities.
The economic fallout of the pandemic has caused nearly 27 million Americans to lose their employer-based health insurance. An estimated 12.7 million would be eligible for Medicaid; 8.4 million could qualify for subsidies on exchanges; leaving 5.7 million who would need to cover the cost of health insurance policies (COBRA policies averaged $7,188 for a single person to $20,576 for a family of four) or remain uninsured.