COVID-19 vaccine: More good news as Moderna releases results

Looks like more good news on the COVID-19 vaccine front. Dr. Fauci’s prediction that the Pfizer/BioNTech foreshadowed positive news for future vaccines appears to have come true. Stat News reports:

The Moderna vaccine reduced the risk of Covid-19 infection by 94.5%. There were 95 cases of infection among patients who received placebo in the company’s 30,000-patient study. There were only five infections in patients who developed Covid-19 after receiving Moderna’s vaccine, mRNA-1273…
Moderna also released data about the number of patients who had severe Covid-19. There were 11 cases of severe disease, all of them in the placebo group — another point of encouragement for Fauci.
“There was always the concern … since the primary endpoint [of the trial] is just clinically apparent disease, how do we know it’s going to have an impact on severe disease? And the results with severe disease were striking — 11 to zero is very impressive,” he said. At the time of their data release, Pfizer and BioNTech had no severe cases in their study.

Very exciting news!

COVID-19, nursing home quality and vaccination

Interesting findings from an NBER working paper by Cronin and Evans (2020):

Higher-quality nursing homes, as measured by inspection ratings, have substantially lower COVID-19 mortality. Quality does not predict the ability to prevent any COVID-19 resident or staff cases, but higher-quality establishments prevent the spread of resident infections conditional on having one. Preventing COVID-19 cases and deaths may come at some cost, as high-quality homes have substantially higher non-COVID deaths, a result consistent with high excess non-COVID mortality among the elderly since March. 

Recent positive news of a potential COVID-19 vaccine is welcome news. However, will people actually take it if the vaccine proves safe and effective? The answer likely depends if your proximate peers are pro-vax or anti-vax. A paper by Estep and Greenberg (2020) argues that:

…residential and school selection processes create “pockets of homogeneity” attracting parents inclined to opt out of vaccines. Structural features of these enclaves reduce the likelihood of harsh criticism for vaccine refusal and foster a false sense of protection from disease, making the choice to opt out seem both safe and socially acceptable. Examination of quantitative data on personal belief exemptions (PBEs) from school-based vaccination requirements in California schools and districts, as well as findings from parent interviews, provide empirical support for the theory. 

Hat tip: Kevin Lewis.

Positive news on a COVID-19 vaccine

Great news on progress for a COVID-19 vaccine from Pfizer. From their press release:

  • Vaccine candidate was found to be more than 90% effective in preventing COVID-19 in participants without evidence of prior SARS-CoV-2 infection in the first interim efficacy analysis
  • Analysis evaluated 94 confirmed cases of COVID-19 in trial participants
  • Study enrolled 43,538 participants, with 42% having diverse backgrounds, and no serious safety concerns have been observed; Safety and additional efficacy data continue to be collected
  • Submission for Emergency Use Authorization (EUA) to the U.S. Food and Drug Administration (FDA) planned for soon after the required safety milestone is achieved, which is currently expected to occur in the third week of November

The Phase 3 clinical trial of BNT162b2 began on July 27. Pfizer expects to produce o produce globally up to 50 million vaccine doses in 2020 and up to 1.3 billion doses in 2021. Note that since this is a two-dose regimen, this would be sufficient capacity for 25 million people this year and 650 million people next year.

Will fighting COVID-19 disrupt progress against malaria?

That is the key question explored in a recent article from The Economist titled “Masked up, ready to battle bugs“. As individuals in developing nations leave crowded cities for fear of COVID, they may be at more risk for malaria due to the presence of more standing water (which attracts malarial mosquitos) used for irrigation in rural areas. Additionally, COVID has disrupted supply chains for the distribution of mosquito nets. COVID-19 also makes treating malaria more complicated.

Governments in rich countries have pushed a consistent message for COVID-19. If you children have a fever, keep them at home. “That message would be an unmitigated disaster in countries with high malaria transmission, because a child with a fever can die from malaria in 24 hours,” says Melanie Renshaw of the African Leaders Malaria Alliance….Such a child must quickly be tested for malaria and, if the test is positive, be given anti-malarial drugs.

One can clearly see how the COVID-19 pandemic affects not only people who suffer from the disease, but also affects the treatment of other conditions–like malaria. The interplay of COVID-19 with other diseases is an area which requires more studies and more solutions.

Pandemic comparison: COVID-19 vs. London Plague

Dasgupta et al. (2020) compares individual behavior in the COVID-19 pandemic with the 1665 London plague outbreak based on the descriptions by Daniel Defoe in A Journal of the Year of the Plague. The historical comparison is interesting throughout and merits a full read. Some excerpts are below.

On the failure to recognize the disease’s severity:

Given their relative disbelief in the severity of the outbreak, in the early days people in every country or borough of London believed that there really was no cause for concern. Those in London believed it might affect other parts and maybe it existed in the outskirts but had not arrived in the city. For Covid often people believed it to be no more fatal than the flu or an infection that was present elsewhere. As a result, they did not take adequate measures to protect themselves. 

In both COVID-19 and the London plague, consumer hoarded goods. In the case of COVID-19, it was food, masks and toilet paper; in the London plague hoarding household goods was common. The hoarding is due to the uncertain nature of the duration of the pandemic. In addition:

…sellers too react to such episodes in very predictable ways. A very pointed instance of hoarding that Defoe describes in the book is when trying to escape the city to Lincolnshire, he witnesses an acute shortage of horses for hire even though most people were not moving around the city. There are other instances where he talks about theft—for instance of an unnecessary item like women’s hats from an unguarded warehouse in London, as well as frequent descriptions of food shortages. Similar instances of opportunistic market behavior can be found in the current pandemic…a seller in Florida was offering 15 N95 face masks on Amazon for $3,799, milk was being sold at $10 per gallon in a convenience store in Massachusetts, and of course the most curious of case where toilet rolls were vanishing from stores and being offered at exorbitant prices

With prices fluctuating frequently during a pandemic, opportunism is common.

Increased faith in “miraculous cures” also commonly occurs.

As Defoe notes “…they were as mad upon their running after quacks and mountebanks, and every practicing old woman, for medicines and remedies.” Models of herding behavior of the type developed by Banerjee (1992) and Bikhchandani, Hirshleifer, and Welch (1992) can be used to explain such behavior. Imagine that each person receives a private signal about the effectiveness of the miracle cure. However, if they observe other people believing in such a cure (since there is no known cure), an individual might ignore their private signal and follow the herd…Waiting to learn about the effectiveness of a cure during a pandemic can be costly (strategic delay), and this in itself can lead to herding.

On the positive side, necessity is the mother of invention. While remote working, teleconference, and contactless technology grew out of COVID-19, innovation also occured during the time of the plague.

Defoe notes the example of a waterman who took up the job of delivering water when he realized that there was a huge demand for such basic necessities stuck in the anchored ships in the nearby docks, which in turn provided him “… a great sum, as things go now with poor men”

Do read the entire article as there are many more interesting examples.

What is the “reputational value” of developing a COVID vaccine?

COVID-19 is a global pandemic and finding a vaccine for COVID-19 would be a boon to societal. The value would be enormous. One study found that the value would be more than 1.1% of GDP. Since global GDP is $87.7 trillion, the value of a vaccine would be nearly $1 trillion.

In a recent colloquium on from ICER on “Pricing in a Pandemic“, Peter Bach argued that the reputational benefits of developing a COVID vaccine would be large. Dr. Bach argued that social value of a COVID-19 vaccine is the maximum that should be paid for a vaccine, and one should likely pay less because of reputational benefits the pharma firm developing a vaccine would receive.

But are the reputational benefits of developing a vaccine likely to be large? I would argue ‘no’.

Consider the case of what would happen if Apple developed a vaccine. There likely would be a positive brand effect and Apple could charge more for their other products (e.g., iPhones) or even if they didn’t charge more they could sell more iPhones.

In pharmaceutical markets, however, neither of these benefits is likely to appear. First, dosing is regulated by the FDA. Even if that wasn’t the case, individuals typically don’t consume more of a medication conditional on taking them. Second, it is unlikely that reputational effects will allow a pharmaceutical firm to increase drug prices. Pharmaceutical prices are highly regulated and health insurers, payers and pharmacy benefits managers–rather than patients–negotiate prices and rebates. Thus, any reputational benefits that could accrue to patients, likely wouldn’t have much influence on these third party stakeholders.

Admittedly, There could be a positive effect in competitive markets where people may shift from one firms medication to the medication of the firm that developed a vaccine. This phenomenon, however, is only likely to have a major impact if the company has a large portfolio of treatments and if patients and physicians make treatment decisions of a current drug based on a drug company’s reputation rather than a specific drug’s safety and efficacy. This is not very likely.

In addition, the drug company’s reputation could actually be hurt from developing a vaccine. While some people would be very happy and appreciative of the company that develops a COVID-19 vaccines, others would argue that the pharmaceutical company is charging too much for the vaccine, even if the prices charged are modest and the cost/risks incurred to develop the vaccine are large.

A tangible benefit to pharmaceutical manufacturers is in employee recruitment. Individuals may be excited to work for a pharmaceutical firm that developed a COVID vaccine. It is unclear, however, how large a discount in salary workers would accept to work at a the firm that developed a COVID vaccine compared to one who did not develop a vaccine. Certainly there would be some benefit, but the magnitude is likely to be modest.

Conclusion

In short, while there clearly will be reputational implications for whichever firm (hopefully) discovers a COVID-19 vaccine, it is not at all clear that the reputational benefits will be large in magnitude or even positive in direction. Regardless, if one wants to price drugs based on value, reputational effects should not be incorporated into any value assessment for COVID treatment or prophylactic vaccines. Instead, the COVID vaccine’s estimated value to societal should determine the price under a value-based reimbursement scenario.

Masks work

That is based on an event study approach from a recent Health Affairs article by Lyu and Wehby (2020). Specifically,

Mandating face mask use in public is associated with a decline in the daily COVID-19 growth rate by 0.9, 1.1, 1.4, 1.7, and 2.0 percentage points in 1–5, 6–10, 11–15, 16–20, and 21 or more days after state face mask orders were signed, respectively. Estimates suggest that as a result of the implementation of these mandates, more than 200,000 COVID-19 cases were averted by May 22, 2020.

As of the end of July, we are still at peak levels in the US for new COVID-19 cases. Thus, if you go out side where you are around others, wear a mask.

LA: Distance learning only

The New York Times reports:

California’s two largest public school districts said on Monday that instruction would be online-only in the fall, in the latest sign that school administrators are increasingly unwilling to risk crowding students back into classrooms until the coronavirus is fully under control.
The school districts in Los Angeles and San Diego, which together enroll some 825,000 students, are the largest in the country to abandon plans for even a partial physical return to classrooms when they reopen in August.
The decision came as Gov. Gavin Newsom announced some of the most sweeping rollbacks yet of California’s plans to reopen. Indoor operations for restaurants, bars, wineries, movie theaters and zoos were shut down statewide on Monday, and churches, gyms, hair salons, malls and other businesses were shuttered for four-fifths of the population.

Is this a good decision? The decision likely will help limit the spread of the disease, but also put a significant burden on working parents with school-age children. Further, children’s learning, likely will not be the same with distance compared to in-person learning. A difficult decision to make for any politician.

Some good news

As COVID-19 cases continue to rise in the US, there was some good news last week from this year’s AIDS conference. Due to COVID-19, the conference had to be held remotely. One policy goal is known as the 90:90:90, which means to identify 90% of HIV cases, treat 90% of those identified and supress viral load to undetectable levels for 90% of those treated. The Economist reports:

Fourteen countries, including Botswana, Cambodia, Rwanda, Zambia and Zimbabwe, report that they have reached the 90:90:90 goal. Two of them, Switzerland and Eswatini (formerly Swaziland) report 95:95:95—which is actually the target for 2030.

One can see the general trends is positive around the world as well.

https://www.economist.com/science-and-technology/2020/07/08/this-years-aids-conference-has-brought-snippets-of-good-news

While COVID-19 has interrupted the supply chain somewhat for antiretroviral drugs, new preventative treatments, such as Truvada (emtricitabine/tenofovir) and cabotegravir have been shown to be highly effective pre-exposure prophylaxis (PrEP) treatments.

While the global burden of HIV is still high, the AIDS Conference highlights that for this disease at least, things are at least trending in the right direction.

What explains the decline in COVID deaths despite the rising number of cases?

Take a look at these two graphs. The first gives the number of new COVID-19 cases from John Hopkins University. It is a scary graph.

https://coronavirus.jhu.edu/data/new-cases

The second graph is the number of COVID deaths from IHME. Not nearly as bad.

https://covid19.healthdata.org/united-states-of-america

CDC reported death numbers are similar. In fact, the number of deaths in recent weeks is no different from normal according to the CDC.

https://www.cdc.gov/nchs/nvss/vsrr/covid19/excess_deaths.htm

One reason for rising cases is that we are doing more testing. Thus, we are catching more cases. People who are hospitalized with critical illness are more likely to be tested and thus as we expand the number of tests, we are now catching more of the less severe cases with the additional testing.

However, testing does not explain everything. We see that as cases are rising, so is the number of hospitalizations. Thus, this is not just a testing story. Real–not just detected–cases are rising.

https://twitter.com/Trinhnomics/status/1279948543684313088/photo/2

Most likely, the existence of more effective treatments (e.g., remdesivir and dexamethasone) and physicians gaining experience treating the disease is responsible. Among hospitalized individuals, death rates have been falling dramatically in recent weeks.

https://www.bbc.com/news/health-53192532

There is much still to be learned about the causes of these divergent trends and much more research is needed.

Disparities in COVID-19 hospitalization rates

Azar et al. (2020) use electronic health record data to examine differences in COVID-19 hospitalization rates by patient characteristics. The authors find that:

…compared with non-Hispanic white patients, nonHispanic African American patients had 2.7 times the odds of hospitalization, after adjustment for age, sex, comorbidities, and income.

These findings echo similar COVID-19-related conclusions across California.

California’s [COVID-19] death rate among African Americans is higher than that group’s representation in the population (10 percent mortality versus 6 percent population) and even more disproportionate in some counties. Recent data from Los Angeles County show a 14 percent mortality rate among African Americans, who make up 9 percent of that county’s population.

The authors hypothesize that barriers to access to care or delays in seeking care may lead to African-Americans having more advanced or severe illness at the time of presenting for COVID-19 testing and medical care. One finding that may confirm this suggestion is that African-American patients were more likely to have been tested at a hospital than in the ambulatory care setting. Restricted access to care, however, is likely not due to differences in insurance status as African-American insurance rates are relatively high in California. However, higher cost-sharing may delay access to care as may prior negative interactions with the health care system.

As we continue to fight COVID-19 throughout the country, outreach to encourage early testing for all Americans is vital to insure all patients get the treatment they need.