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February 1 - February 10, 2022
Hong Kong had recently installed vending machines in its subway stations that dispensed rapid COVID tests right to consumers. In the US, the rapid antigen tests that Fauci envisioned wouldn’t be available until the fall of 2020. And
The application of public health requires public trust.
These case-based tactics are why New Zealand kept the virus out of their country and why the nations of the Pacific Rim got control of their outbreaks. When we finally lifted the stay-at-home order, we failed to transition from community-wide mitigation to tracking down individual cases because we didn’t have the testing and contact tracing systems to support it. So, the virus flared after we reopened. It was a continuous cycle of infection. We never escaped.
In many towns, local school boards felt compelled to adhere closely to the CDC’s recommendations, and they simply didn’t have enough space in their schoolhouses to keep students six feet apart. The federal government was working off a model for flu, and it was the wrong framework for COVID.
CDC’s output is more akin to the journal articles issued by an academic department of epidemiology than a battlefield report issued by the Joint Special Operations Command.
The CDC wasn’t just slow to develop this evidence, it also didn’t offer it in practical terms that made it actionable.
It turned out that the CDC wasn’t actually providing data that was being reported to the agency on real hospitalizations, but was instead posting an estimate derived from a predictive model. In other words, the number of hospitalizations that the CDC was reporting each day weren’t people who were actually being admitted to the hospital but were hypothetical patients being modeled off a small sample that the CDC was collecting.
Medicare has data on influenza hospitalizations for those over the age of sixty-five. Insurers will have this data for their beneficiaries, and they’ll often report these trends. However, for the CDC, aggregating this information seemed to be too difficult.
Deborah Birx convinced the Coronavirus Task Force to direct money to the CDC to modernize its reporting of the COVID hospital data, but the CDC said no.
Rather than try to cajole the CDC into fixing its reporting system, Ambassador Birx and Secretary Azar decided to re-create that structure outside the agency.
As Levin observed, “the simplest way to describe the CDC’s response to this binding legal mandate was that it just ignored it. It did nothing.”
In contrast to the US, the UK was able to detect the more contagious B.1.1.7 variant because it was sequencing about 10 percent of all patient samples. By the time the delta variant, B.1.617, emerged in May 2021, the UK was sequencing 60 percent of all patient samples.33 By comparison, the CDC had set as its initial goal getting five sequences from each state per week. When B.1.1.7 arrived in the US, the CDC was sequencing only 0.3 percent of patient samples. This
Epidemiologists Dr. Caitlin Rivers and Dr. Dylan George advocated the creation of a centralized system for disease forecasting. The idea is to have the epidemiological equivalent of the National Weather Service.
The South Korean CDC provided the manufacturers with early access to SARS-CoV-2 viral samples, making it easier for them to develop new tests,
after MERS the South Koreans also created a regulatory model that had their CDC and FDA working together to advance new tests in the setting of public health crises. Under the approach, the South Korean CDC would do its own clinical evaluation of new diagnostic kits to validate their accuracy using patient samples that the agency would have access to. It would then send the data it generated to the South Korean FDA to do an independent review and issue the equivalent of an emergency-use authorization. The key advance was the commitment by the South Korean CDC to use patient samples to do the
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in the first week two domestic manufacturers had produced 700,000 test kits.
South Korean FDA had only put the tests through a preliminary review. Regulators knew that the rapid development process left gaps in how the tests had been validated. So the South Korean FDA continued to evaluate the tests after they reached the market.
To support these efforts, South Korea records almost every credit card and bank transaction on government databases. Health agencies were able to legally access this information and combine it with closed-circuit television footage and data from mobile phones to track people’s movements.
Tracking and tracing didn’t need to identify every case, just some of them. In the US, even if we could find a fraction of the infections, and convince people to voluntarily self-isolate, it could delay the start of the epidemic, or reduce its severity.23
South Korea showed the importance of having in place the infrastructure that was required to respond to a pandemic.
Amgen’s efforts provide an instructive lesson for how we can harden ourselves in preparation for a pandemic and secure the capacity to expand diagnostic testing in a crisis.
core pillars of this new system. Under this approach, the federal government would subsidize these labs to build excess capacity inside their existing sites. The labs would also be paid to keep a fresh stockpile of testing consumables (reagents, swabs, etc.) to support a surge in testing demand.
Right now, the commercial labs might maintain about three thousand testing machines in their largest reference sites. They typically operate these facilities at 80 percent capacity for maximal productivity. Their present focus is to operate these facilities for maximum efficiency. That helps keep costs down. Instead, there needs to be an equal focus on operating these sites with greater resiliency. Some surge capacity needs to be built into the system as a hedge against a major crisis. This could mean, for example, operating five thousand machines but running each of them at 50 percent
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The federal government can pay the labs for the additional cost of maintaining this excess capacity, as part of our national security preparedness.
Commercial kit makers worried about how the CDC’s claims of intellectual property over the tests could impede the ability to market the tests, and get reimbursed. Negotiating the terms for licensure can eat up valuable time in a crisis. That’s precisely what occurred during COVID.
Through these regulatory measures, the CDC basically owned the entire market, essentially preventing manufacturers from developing their own inventions.
allow the agency to collect royalties on its diagnostics.
In 2004, the National Institute of Allergy and Infectious Diseases awarded $104.7 million in annual funding for coronavirus-related research. However, that funding fell to $14.9 million by 2010.
There were literally thousands of clinical trials under way with various drugs that doctors hoped could help treat COVID, though most of these drugs had dubious value. It was a therapeutic free-for-all.
about 90 percent of the COVID trials run during the pandemic were designed in a way that would never yield actionable results that could change medical practice.
Federal regulators at the FDA had no way to prioritize the conduct and completion of certain trials over others, or to steer enrollment toward higher-value studies. Researchers at the NIH could use their funding mechanisms to support high-priority studies, but they had limited ability to direct academic sites to prioritize enrollment in some clinical trials over others.
Instead of focusing on the limited number of variables that were most relevant to determining whether a drug was delivering a benefit, as RECOVERY did, many US trials tracked dozens and sometimes hundreds of different variables and required providers to input reams of sometimes marginally useful information.
Bend your principles a little, and you get pressured later to bend them a lot.
the FDA would be largely locked into the guidance that they had already issued where, as a practical matter, the agency’s criteria meant that they would have to wait for the conclusion of the trial, and couldn’t base an authorization on an interim analysis of that data. I couldn’t help but think: Would the agency’s bar have been set differently had the FDA constructed its framework with knowledge of how well the vaccines would pan out? Would the FDA have used its discretion to authorize the vaccines sooner for the highest risk patients, based on an interim analysis, if it knew how effective
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The story of how these COVID antibody drugs came about at once shows the benefits offered by nimble platforms that can be used to develop countermeasures to unpredictable threats, along with the opportunities that we missed by not securing these capabilities years in advance, as part of a comprehensive approach to pandemic preparedness that we never fully put in place.
Regeneron believed it was possible to develop a cocktail of antibodies that would be effective against any coronavirus. But the project couldn’t attract investment from federal agencies like BARDA that would have had to fund these sorts of countermeasures. In 2015, the head of BARDA, Robin Robinson, told the publication BioCentury that his agency didn’t have funding to develop coronavirus countermeasures. “We are funded for pandemic influenza and man-made threats like anthrax, smallpox, nuclear devices and chemical agents. If we had another emergency from another emerging infectious disease,
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The only way to secure more production capacity for the COVID drugs was to stop making other medicines and eat into stockpiles that companies had on hand.40 That was the only fix that we had in the short run. We didn’t pursue this, or other stopgap measures.
It turned out, however, that our distribution system for the drugs was so poor that we didn’t use even this small supply.
We also built a vaccine manufacturing facility in Maryland that was run by Emergent BioSolutions, and another one located in North Carolina that used a cell-based manufacturing process to make flu vaccine.43 These and other capabilities were constructed as a hedge against a pandemic strain of bird flu, to give us the capacities we would need to manufacture a new vaccine. All of these efforts ran into separate challenges.
We invested in the construction of the initial capacity and then didn’t keep it operating in a way that both maintained its readiness and guaranteed its availability for a crisis.
Instead, the contract manufacturers can be paid to operate plants that are oversized for their routine obligations. In an emergency, any one of these facilities could make its excess capacity available for the production of needed products.
To prepare for future threats, to have that capacity ready in the event of a crisis, we’ll have to pay for that spare volume, much as we’ll need to support the maintenance of some reserve testing capacity in the major diagnostic labs like Quest and LabCorp. We need to take new steps to make sure that the US will always have a surge capability in a crisis.
Instead of growing the protein in large bioreactors inside a manufacturing plant, our bodies are co-opted into becoming production facilities.
Pfizer and BioNTech were planning to start clinical trials with an experimental flu vaccine in 2020.22 Then COVID happened.
Pfizer had adapted the mRNA sequence to make the resulting spike protein it produced more easily recognized by our B cells so it would stimulate a more robust immune response.
The specially formulated mRNA used in the vaccine was produced by batteries of highly specialized mixing machines that Pfizer had custom-made for the purpose at a cost of $200 million each. I remember the board meeting when we voted to buy more of them. We initially purchased five of the batteries of machines in all, at a cost of $1 billion—before we even knew if the vaccine was going to work.
In contrast to antibody drugs and vaccines, which are specific to each individual strain and target precise proteins on a virus, the protease inhibitors can act on all coronaviruses, along with other related viruses.
To counter the unknowns, the most valuable capabilities are the ones that can be quickly adapted to novel threats, or countermeasures that can help defeat entire categories of pathogens—for example, a vaccine that will work against multiple strains of coronavirus.
Among the group’s recommendations was the establishment of a consolidated system for reporting information about potentially concerning pathogens and outbreaks.
The volatile nature of that NSC role was a leitmotif for the shifting focus on these dangers
