COVID-19 Data Dispatch

Tag: FDA

  • The data problem underlying booster shot confusion

    The data problem underlying booster shot confusion

    This is all the breakthrough case data that the CDC gives us. Screenshot taken on September 26.

    This past Thursday, an advisory committee to the CDC recommended that booster doses of the Pfizer vaccine be authorized for seniors and individuals with high-risk health conditions. The committee’s recommendation, notably, did not include individuals who worked in high-risk settings, such as healthcare workers—whom the FDA had included in its own Emergency Use Authorization, following an FDA advisory committee meeting last week.

    Then, very early on Friday morning, CDC Director Rochelle Walensky announced that she was overruling the advisory committee—but agreeing with the FDA. Americans who work in high-risk settings can get booster shots. (At least, they can get booster shots if they previously received two doses of Pfizer’s vaccine.)

    This week’s developments have been just the latest in a rather confusing booster shot timeline:

    Why has this process been so confusing? Why don’t the experts agree on whether booster shots are necessary, or on who should get these extra shots? Part of the problem, of course, is that the Biden administration announced booster shots were coming in August, before the scientific agencies had a chance to review all the relevant evidence.

    But from my (data journalist’s) perspective, the booster shot confusion largely stems from a lack of data on breakthrough cases.

    Let’s go back in time—back four months, or about four years in pandemic time. In May, the CDC announced a major change in its tracking of breakthrough cases. The agency had previously investigated and published data on all breakthrough cases, including those that were mild. But starting in May, the CDC was only investigating and publishing data on those severe breakthrough cases, i.e. those which led to hospitalization or death.

    At the time, I called this a lazy choice that would hinder the U.S.’s ability to track how well the vaccines are working. I continued to criticize this move, when researchers and journalists attempted to do the CDC’s job—but were unable to provide data as comprehensive as what the CDC might make available. 

    Think about what might have been possible if the CDC had continued tracking all breakthrough cases, or had even stepped up its investigation of these cases through increased testing and genomic sequencing. Imagine if we had data showing breakthrough cases by age group, by high-risk health condition, or by occupational setting—all broken out by their severity. What if we could compare the risk of someone with diabetes getting a breakthrough case, to the risk of someone who works in an elementary school?

    If we had this kind of data, the FDA and CDC advisory committees would have information that they could use to determine the potential benefits of booster shots for specific subsets of the U.S. population. Instead, these committees had to make guesses. Their guesses didn’t come out of nowhere; they had scientific studies to review, data from Pfizer, and information from Israel and the U.K., two countries with better public health data systems than the U.S. But still, these guesses were much less informed than they might have been if the CDC had tracked breakthrough cases and outbreaks in a more comprehensive manner.

    From that perspective, I can’t really fault the CDC and the FDA for casting their guesses with a fairly wide net—including the majority of Americans who received Pfizer shots in their authorization. There’s also a logistical component here; the U.S. has a lot of doses that are currently going unused (thanks to vaccine hesitancy), and may be wasted if they aren’t used as boosters.

    But it is worth emphasizing how a lack of data on breakthrough cases has driven a booster shot decision based on fear of who might be at risk, rather than on hard evidence about who is actually at risk. Other than seniors; the risk for that group is fairly clear.

    The booster shot decision casts a wide net. But at the same time, it creates a narrow band of booster eligibility: only people who got two doses of Pfizer earlier in 2021 are now eligible for a Pfizer booster. Recipients of the Moderna and Johnson & Johnson vaccines are still left in the dark, even though some of those people may need a booster more than many people who are now eligible for additional Pfizer shots. (Compare, say, a 25-year-old teacher who got Pfizer to a 80-year-old, living in a nursing home, with multiple health conditions who got Moderna.)

    That Pfizer-only restriction also stems from a data issue. The federal government’s current model for approving vaccines is very specific: first a pharmaceutical company submits its data to the FDA, then the FDA reviews these data, then the FDA makes a decision, then the CDC reviews the data, then the CDC makes a decision.

    By starting with the pharmaceutical company, the decision-making process is restricted to options presented by that company. As a result, we aren’t seeing much data on mixing-and-matching different vaccines, which likely wouldn’t be profitable for vaccine manufacturers. (Even though immunological evidence suggests that this could be a useful strategy, especially for Johnson & Johnson recipients.)

    In short, the FDA and CDC’s booster shot decision is essentially both ahead of evidence on who may benefit most from a booster, but behind evidence for non-Pfizer vaccine recipients. It’s kind-of a mess.

    I also can’t end this post without acknowledging that we need to vaccinate the whole world, not just the U.S. Global vaccination went largely undiscussed at the FDA and CDC meetings, even though it is a top concern for many public health experts outside these agencies.

    At an international summit this week, President Biden announced more U.S. donations to the global vaccine effort. His administration seems convinced that the U.S. can manage both boosters at home and donations abroad. But the White House only has so much political capital to spend. And right now, it’s pretty clearly getting spent on boosters, rather than, say, incentivizing the vaccine manufacturers to share their technology with the Global South.

    I can only imagine this situation getting messier in the months to come.

    More vaccine reporting

  • Boosters for the vulnerable: FAQs following the FDA advisory meeting

    Boosters for the vulnerable: FAQs following the FDA advisory meeting

    This past Friday, the Food and Drug Administration (FDA)’s vaccine advisory committee voted to recommend booster shots of the Pfizer-BioNTech vaccine for all Americans over age 65 and those who are particularly vulnerable to the virus, due to their health conditions and/or work environments. This was a notable recommendation because it went against the FDA’s ask: booster shots for everyone over the age of 16.

    Let’s walk through the data behind this decision.

    How is the current two-dose vaccine regimen faring against severe COVID-19 disease?

    Before we get into any numbers, it’s important to remember the initial goal of the COVID-19 vaccines: protect people against severe disease, hospitalization, and death, basically reducing the coronavirus’ power to cause deadly harm.

    On this front, all of the vaccines are performing well. Numerous papers cited during the advisory meeting, as well as the U.S.’s breakthrough case data, suggest that vaccination protects against severe COVID-19 disease for the vast majority of recipients. Among over 178 million people who had been fully vaccinated in the U.S. by mid-September, just 3,000 have died following a positive COVID-19 test. Those 3,000 deaths account for just about 1% of all COVID-19 deaths in the U.S. since January 2021.

    The numbers get a bit more complex, however, when you look at older adults and other vulnerable populations. Those who were more vulnerable to a severe COVID-19 case in the first place are also more vulnerable to having a severe breakthrough case, if they encounter the virus after vaccination. One chart, presented at the FDA meeting, provides a picture of this trend. From late January to mid-July, 2021, the hospitalization rate among younger adults (ages 18-49) was 23 times higher for the unvaccinated than for the vaccinated. For seniors (over age 65), however, the rate was 13 times higher for the unvaccinated.

    Seniors are more likely to experience a severe breakthrough case than younger adults, CDC data suggest.

    How is that current regimen faring against coronavirus infection?

    This is where we see a bigger drop in efficacy. Multiple studies point to the Pfizer and Moderna vaccines becoming less capable of protecting recipients against infection, over time; in other words, if you got your two shots in April 2021, you’re more likely to get a positive test result now, in September, than you were in May. (Though your case will likely be mild or asymptomatic!)

    While the vaccines are still highly effective against severe disease, their effectiveness against coronavirus infection appears to be waning.

    We can also see this in breakthrough case numbers when we look at all infections, as opposed to only those cases that lead to severe disease or death. This type of analysis is difficult to do in the U.S., as the CDC is only systematically tracking those severe cases, but we can see patterns in the data from local jurisdictions that are reporting their breakthrough cases more comprehensively.

    For example, let’s look at Washington, DC, which reports breakthrough cases in extensive detail:

    Washington, D.C. is seeing many more breakthrough cases now than it was earlier in 2021.

    During the week of March 8, DC reported 14 breakthrough cases. The district reported about 800 cases overall that week, meaning that breakthroughs accounted for 2% of all cases. 

    During the week of August 23, however, the district reported almost 500 breakthrough cases. In that week, the district reported about 1,400 cases overall—meaning that breakthrough cases have jumped from 2% of all weekly DC cases to 35% of all weekly DC cases.

    DC also reports a breakdown of breakthrough cases according to the time it’s been since residents were fully vaccinated. This reveals that most breakthroughs occur at least two months after an individual completed their dose series, with the highest number of breakthroughs in people who’d been vaccinated three to four months ago. We can assume that similar patterns are occurring elsewhere in the country.

    It’s also worth noting that we don’t have a great sense of how well the vaccines protect against Long COVID—though data thus far suggest that post-vaccination Long COVID cases are much rarer than non-breakthrough cases.

    Why are the vaccines appearing to lose their effectiveness?

    This was a big point of discussion for the FDA advisory committee. Are the Pfizer and Moderna vaccines appearing to lose their ability to protect us against coronavirus infection because Delta has a special ability to evade the vaccines or because the vaccines become less effective over time?

    One early-morning presenter at the FDA meeting, medical statistician Jonathan Sterne from the University of Bristol, dove into this issue. His presentation focused on confounders, a statistical term for an outside force that influences the question a researcher is trying to study. In the case of vaccine effectiveness, Sterne said, there are a lot of confounders; these include vaccine recipients’ ages, how long ago they were vaccinated, and when they were vaccinated (i.e. in which phase of the pandemic?).

    Sterne’s presentation focused on the confounders that make it difficult to estimate vaccine effectiveness.

    Sterne and other British researchers have taken advantage of the U.K.’s extensive electronic health records to analyze how well the vaccines are working, attempting to take these confounders into consideration. Overall, he said, it’s very challenging to get trustworthy effectiveness numbers—though the U.K. has approved boosters for residents over age 50, so it’s clear that the country’s public health agency does see some need for the additional shots.

    Sterne’s presentation, as did a presentation from Israeli public health officials, also underscored the need for the U.S. to collect more standardized data on breakthrough cases, among other things.

    Why did the FDA advisory committee vote against booster shots for everyone, ages 16 and over?

    When this advisory committee votes on a question regarding vaccines or another biological product, the committee is specifically asked to consider whether the benefits of the product outweigh the risks. In this case, do the benefits of widespread boosters outweigh the risks of potential side effects from those additional doses?

    When it comes to those risks of potential side effects, the committee had strikingly little data to evaluate. Pfizer did conduct a clinical trial of booster shots, but it only included 306 participants—an incredibly small number, when compared to the massive trials of the vaccine’s original two-dose regimen. The trial didn’t include any participants under age 18 or over age 55, which some advisory committee members found problematic, as they were being asked to consider approval for all Americans over age 16.

    Israel—which has now administered booster shots to over 2.8 million residents—provided some data on side effects, but their utility is limited. The country started giving boosters to older adults before moving to younger adults, limiting Israeli health officials’ ability to identify potential risk for myocarditis or other severe side effects that might be more common in the younger population.

    Israel has only identified 19 serious vaccine side effects from its booster shot rollout thus far, but the majority of the country’s young adults have yet to be vaccinated.

    While data from Israel do suggest that booster shots can bring down infection numbers in an overall population, the FDA advisory committee did not find that a sufficient argument to recommend boosters for all Americans. Not at this time, anyway.

    Why did the committee vote to support boosters for seniors and other vulnerable populations?

    The risks of booster shots may not be clear for younger adults, but the risks of a breakthrough COVID-19 case are clear for older adults and others with health conditions that make them more vulnerable to severe COVID-19 case. The committee’s vote to recommend boosters for vulnerable groups aligns with a growing scientific consensus: that the U.S. should protect seniors, nursing home residents, and others who are at higher risk for serious COVID-19 cases.

    What happens next?

    It’s important to underscore here that this booster shot recommendation came from a committee that advises the FDA, not from the FDA itself. The agency typically follows its committee’s recommendations, but it doesn’t have to. We can expect the FDA’s decision—approval of booster shots for vulnerable groups, for everyone over age 16, or something else—within a couple of days.

    Next week, on Wednesday and Thursday, a CDC advisory committee is set to meet to further discuss booster shots. If both the FDA and CDC approve boosters, health departments across the country are prepared to begin administering them to eligible Americans; this will likely include seniors and other vulnerable adults who previously got two shots of the Pfizer vaccine. 

    What about everyone who got the Moderna or Johnson & Johnson vaccines?

    Again, this decision focused on the Pfizer vaccine, so Moderna and J&J recipients will need to wait for more data and more deliberation. Moderna has formally applied to the FDA for authorization of its booster shot, so we may see a similar series of meetings about that vaccine in the coming weeks.

    J&J vaccine recipients will likely experience a longer wait as researchers collect data on the effectiveness of this one-shot vaccine. CNET has a good explainer of the situation.

    Also: If you’d like to read a more detailed breakdown of everything that happened at Friday’s advisory committee meeting, I highly recommend the STAT News liveblog by Helen Branswell and Matthew Herper, which I drew upon heavily in writing this post.

    More vaccines reporting

  • U.S. moves to approve booster shots despite minimal evidence

    U.S. moves to approve booster shots despite minimal evidence

    Timeline of the scientific results and policy moves leading up to Wednesday’s announcement. Chart via Your Local Epidemiologist.

    This week, the federal government announced that the U.S. intends to provide third vaccine doses to all Americans who received the Pfizer or Moderna vaccines. This booster shot distribution will start in September, with adults becoming eligible once they hit eight months after their second shot.

    While the booster shot regimen still must be approved by the FDA and CDC, federal officials are making it sound like a pretty sure thing—President Biden himself announced the decision at a press conference on Wednesday. However, many epidemiologists, vaccine experts, global health experts, and other scientists have criticized the decision.

    Here are three main criticisms I’ve seen in the past few days.

    First: Scientific evidence is lacking. As the booster shot decision was announced on Wednesday, the CDC published three new studies that appear to show a decline in the Pfizer and Moderna vaccines’ ability to stave off symptomatic COVID-19 infection after several months. One of these reports, from a network of U.S. nursing homes, suggests that efficacy among nursing home residents fell to just 53% by June and July 2021, many months after this vulnerable population was vaccinated. The other two reports show similar declines, though the CDC found that vaccination remains effective against severe disease, hospitalization, and death.

    The federal government—and others arguing in favor of booster shots—have also pointed to data from Israel, which appear to similarly demonstrate that the vaccines lose their effectiveness after several months. In Israel, where almost 80% of residents over age 12 are vaccinated, the majority of those hospitalized with COVID-19 are now fully vaccinated individuals.

    But the act of interpreting these data is more complicated than it first appears. In a blog post at COVID-19 Data Science, biostatistics professor Jeffrey Morris explains that, when the majority of a population is vaccinated, vaccination numbers will go up in this population simply because they are the majority. But the risk remains far higher for the unvaccinated. Plus, Morris explains, stratifying hospitalization numbers by age reveals that older adults are more likely to have a severe COVID-19 case regardless of vaccination status, while younger adults are less likely to be vaccinated (and thus have a non-breakthrough case).

    Simply put, the vaccines do still work well against severe COVID-19—you just need to be precise in calculating effectiveness. And yet, the U.S. government is saying that vaccine efficacy wanes so much, everyone’s going to need a third shot in the fall or early next year. This suggests that the federal government has more data that it is not sharing publicly, which leads us to the second criticism.

    Second: Transparency is also lacking. Typically, when the government makes a decision about approving a new medical product, this decision follows a series of prescribed steps: data submission from the company behind the product, review by FDA scientists, FDA approval, followed by more review by other agencies (such as the CDC or the Centers for Medicare & Medicaid Services) as needed. Review meetings are typically open to the public, with data shared in advance of a decision. In the case of these booster shots, however, the president has announced a specific rollout plan before full scientific review has taken place.

    As STAT’s Helen Branswell explains:

    To many experts, including Baylor, the sequencing of the decisions being made is also out of whack. While U.S. health officials said booster shots could start being offered the week of Sept. 20, the Food and Drug Administration has not even ruled yet on Pfizer’s application for approval of a third shot; it was filed only Monday. Moderna hasn’t yet asked the agency to authorize a third shot at all.

    Plus, remember that the CDC has not publicly shared any comprehensive data on breakthrough cases since the spring, before Delta became dominant.

    The FDA and CDC will certainly still be reviewing the need for booster shots, but the experts cited in Branswell’s piece are skeptical that any decision other than, “Yes, go ahead” will be considered. I, for one, will be very curious to see how the discussions proceed—and what data get cited—at the FDA and CDC committee meetings.  

    Third: We need to vaccinate the world. As I’ve explained in the CDD before, getting vaccines to the low-income nations that have yet to start their rollouts is not just a humanitarian priority. It also protects us, here in the U.S., because the longer the coronavirus circulates, the more opportunities it has to mutate into increasingly-dangerous variants.

    By moving to provide booster shots to everyone—not just the immunocompromised, the elderly, or the otherwise extra-vulnerable—the U.S. is likely delaying shots to other countries, prolonging the pandemic overall.

    As Dr. Michael Ryan, emergencies chief at the World Health Organization, told reporters last week: “We’re planning to hand out extra life jackets to people who already have life jackets, while we’re leaving other people to drown without a single life jacket.”

    More vaccine news

    • Sources and updates, November 12
      Sources and updates for the week of November 12 include new vaccination data, a rapid test receiving FDA approval, treatment guidelines, and more.
    • How is the CDC tracking the latest round of COVID-19 vaccines?
      Following the end of the federal public health emergency in May, the CDC has lost its authority to collect vaccination data from all state and local health agencies that keep immunization records. As a result, the CDC is no longer providing comprehensive vaccination numbers on its COVID-19 dashboards. But we still have some information about this year’s vaccination campaign, thanks to continued CDC efforts as well as reporting by other health agencies and research organizations.
    • Sources and updates, October 8
      Sources and updates for the week of October 8 include new papers about booster shot uptake, at-home tests, and Long COVID symptoms.
    • COVID source shout-out: Novavax’s booster is now available
      This week, the FDA authorized Novavax’s updated COVID-19 vaccine. Here’s why some people are excited to get Novavax’s vaccine this fall, as opposed to Pfizer’s or Moderna’s.
    • COVID-19 vaccine issues: Stories from COVID-19 Data Dispatch readers across the U.S.
      Last week, I asked you, COVID-19 Data Dispatch readers, to send me your stories of challenges you experienced when trying to get this fall’s COVID-19 vaccines. I received 35 responses from readers across the country, demonstrating issues with insurance coverage, pharmacy logistics, and more.
  • Pfizer for the whole pfamily (now CDC-verified!)

    Pfizer for the whole pfamily (now CDC-verified!)

    In case you missed it amidst the mask discourse: Pfizer was already the “vaccine for cool people,” but this week, it formally became the vaccine for teens. The FDA announced on Monday that it was expanding the Emergency Use Authorization for this vaccine to include children ages 12 to 15, and the CDC followed this up with an official recommendation on Wednesday.

    As Sarah Braner reported when the Pfizer adolescent trial results were released: “In the trial, no participants who received the vaccine contracted symptomatic COVID-19 out of a total of 2,260 participants, marking an efficacy rate of 100%.” So, this formal endorsement was a pretty foregone conclusion, but it’s still good news for the 17 million children ages 12 to 15 in the country.

    Here are a couple more statistics about the 12-15 age group, via the Kaiser Family Foundation:

    • This group accounts for 5% of the U.S. population and 27% of the population under age 16.
    • Nearly half of children in this age group are people of color, including: 25% are Hispanic, 13% are Black, and 5% are Asian.
    • 36% of children in this age group live in a family with incomes below 200% of the Federal Poverty Level.
    Vaccination coverage for the population ages 12 and up, as of May 15. The darker blue a state is, the better its coverage.

    And speaking of adolescent data: on Friday, the CDC diversified its vaccine tracker. In addition to state-by-state views of vaccination coverage for the overall population, adult population, and senior population, the Tracker will now show you vaccination coverage for each state’s population over age 12. Nationwide, 56% of this group has had at least one dose and 44% is fully vaccinated.

    The Vaccinations County View page will show you coverage over age 12 by county, but these data aren’t yet available for easy download in the Community Profile Reports.

    The CDC’s demographic vaccination data, meanwhile, groups adolescents in with (already eligible) 16 to 18-year olds in an under 18 category—so we aren’t yet able to see precisely how many children in this age group are getting vaccinated. This may become a concerning data gap as schools may seek to use 12-15 vaccination rates as an indicator for reopening next fall.

    More vaccine coverage

    • Sources and updates, November 12
      Sources and updates for the week of November 12 include new vaccination data, a rapid test receiving FDA approval, treatment guidelines, and more.
    • How is the CDC tracking the latest round of COVID-19 vaccines?
      Following the end of the federal public health emergency in May, the CDC has lost its authority to collect vaccination data from all state and local health agencies that keep immunization records. As a result, the CDC is no longer providing comprehensive vaccination numbers on its COVID-19 dashboards. But we still have some information about this year’s vaccination campaign, thanks to continued CDC efforts as well as reporting by other health agencies and research organizations.
    • Sources and updates, October 8
      Sources and updates for the week of October 8 include new papers about booster shot uptake, at-home tests, and Long COVID symptoms.
    • COVID source shout-out: Novavax’s booster is now available
      This week, the FDA authorized Novavax’s updated COVID-19 vaccine. Here’s why some people are excited to get Novavax’s vaccine this fall, as opposed to Pfizer’s or Moderna’s.

  • COVID source shout-out: FDA’s techies

    I watched a pretty significant quantity of the FDA’s vaccine advisory committee (or VRBPAC) meeting on Thursday. The meeting lasted nearly nine hours, from 9 AM to about 5:40 PM Eastern, and was plagued by top infectious disease experts who simply could not turn on their microphones.

    It was a typical Zoom meeting with a few older colleagues. But it was also a critically important meeting to discuss the safety of a novel biological product that might save thousands of lives. That’s why, this week, I am paying homage to the FDA tech people behind the scenes who needed to turn on and off those microphones, share those slides, and generally get all the VRBPAC information where it needed to go. As far as I could tell, they kept the meeting running smoothly without seriously angering any of the esteemed committee members. No small achievement!

    Also, the meeting had banger hold music during the breaks. (Disclaimer: I am a 23-year-old white girl who listens to indie instrumentals and the “How to Train Your Dragon” soundtrack while working. You might want to take my categorization of banger hold music with a grain of salt.)

    If you want to read actual, serious coverage of the VRBPAC meeting, STAT News kept a thorough liveblog.

    more source spotlights

  • Federal data source updates, Nov. 8

    As cases spike, the Department of Health and Human Services (HHS) is focusing on rapid testing as a means to control the pandemic. But data on this type of testing continue to be widely unavailable.

    • HHS funds new COVID-19 tests: On October 31, HHS and the Department of Defense announced a $12.7 million contract with InBios International, a Seattle-based diagnostic testing company. The contract aims to help InBios increase its production capacity for two COVID-19 tests: a rapid antigen test called the SCoV-2 Ag Detect Kit and an antibody test called the SCoV-2 Detect IgM/IgG Food & Drug Administration (FDA).
    • HHS distributes antigen tests to HBCUs: At the end of September, the Trump administration announced that Historically Black Colleges and Universities (HBCUs) would be one category of priority sites for the distribution of Abbott BinaxNOW antigen tests, of which the administration has purchased 150 million. This promise is now coming to fruition; HHS announced on October 31 that 389,000 BinaxNow tests have been distributed to 83 HBCUs in 24 states, at no cost to the schools. How these schools will use the tests and report their testing data, however, remains to be seen.
    • FDA reminds antigen test providers to use them properly: The FDA issued a letter to clinical laboratory staff and health care providers on November 3, reminding them that antigen tests may incur false positives when the instructions for these tests’ use are not correctly followed. FDA recommendations include using antigen tests for symptomatic individuals, handling tests correctly, and using PCR tests to confirm results in low incidence counties. As I’ve discussed in this newsletter before, incorrect use of antigen tests may lead to misleading results that waste clinical resources or instill false confidence in people who receive false negatives.
    • HHS needs better testing oversight and data: Two new articles in STAT News this past week have discussed COVID-19 test regulation and reporting. An investigation by Kathleen McLaughlin finds that laboratory developed tests, diagnostic tools developed by and for specific facilities, fall in a “regulatory gray area” which makes it easy for innacuracies to slip past the FDA and HHS. Meanwhile, an op-ed by OB-GYN Joia Crear-Perry points out the public health danger in allowing demographic data on testing to be lost when rapid tests are not incoporated into reporting pipelines.
    more federal data