WASHINGTON, D.C. – The Federation of American Scientists unveiled 23 actionable policy proposals developed by expert contributors. These recommendations were developed with the aim of contributing to a holistic, evidence-based approach to managing wildland fire in the United States and in response to the Wildland Fire Mitigation and Management Commission’s request for stakeholder input in its work to develop a report for Congress . 

In partnership with COMPASS, the California Council on Science and Technology (CCST), and Conservation X Labs, FAS hosted a Wildland Fire Policy Accelerator to collect, refine, and amplify actionable, evidence-based ideas to improve how we live with fire. 

The recommendations cover issues across the wildland fire policy spectrum, falling into four categories: Landscapes and Communities, Public Health and Infrastructure, Science, Data, and Technology, and Workforce. Contributors come from academia, the private sector, and nonprofits and have expertise in public health, fire intelligence, forestry, cultural burning, and more. 

“The ideas we are presenting showcase how the development of evidence-based policy can be inclusive of more diverse expert input and lead to better results. We are eager to see the final recommendations the Commission ultimately relays to Congress, and how they respond” says FAS Director of Science Policy Erica Goldman.

“These are urgent issues that can only be solved through cross-sectoral, multidisciplinary collaborations. We’re grateful to be at the table and excited to see how these bold ideas can evolve and inform public policy across local and state governments,” says CCST Senior Science Officer Teresa Feo.

The Federation of American Scientists (FAS) is a nonprofit policy research and advocacy organization founded in 1945 to meet national security challenges with evidence-based, scientifically-driven, and nonpartisan policy, analysis, and research. The organization works to advance progress on a broad suite of contemporary issues where science, technology, and innovation policy can deliver dramatic progress, and seeks to ensure that scientific and technical expertise have a seat at the policymaking table.

Just over a year ago, I found myself pausing during a research lab meeting. “Why were all the subjects in our studies of wearable devices white? And what were the consequences of exclusion?”

This question stuck with me long after the meeting. Digging into the evidence, I was alarmed to find paper after paper signaling embedded biases in key medical technologies. 

One device stuck out amongst the rest – the pulse oximeter. Because of its crucial role in diagnosing COVID-19, it had caught the attention of a diverse group of stakeholders: clinicians looking to understand the impacts on patient care, engineers working to build more equitable devices, social scientists tracing the history of device and examining colorism in pulse oximetry, policymakers seeking solutions for their constituents, and the FDA, which was examining racial bias in medical technologies for the first time. But what I found as I scoped out this policy area is that these stakeholders weren’t talking to one another, at the expense of coordinated progress towards equity in pulse oximetry. 

With all eyes directed towards the FDA’s Advisory Committee meeting on November 1st, 2022, FAS convened a half-day session of stakeholders on November 2nd to chart a research and policy agenda for near-term mitigation of inequities in pulse oximetry and other medical technologies. Eight experts from medicine, engineering, sociology, and anthropology shared insights with an audience of 60 participants from academia, the private sector, and federal government. Collectively, we developed several key insights for future progress on this issue and outlined a path forward for achieving equity now. You can access the full readout here. We’ll dive into the key highlights below:

Key Insights

Through discussions with experts during the forum, three key themes rose to the surface:

• Racial bias in pulse oximetry cannot be fixed by focusing on “race” alone. Existing evidence suggests reducing bias in pulse oximetry requires replacing devices with less-biased ones. This will take time as new devices are developed and will be a significant cost. 
• Better calibration for skin tone is vital, but measurement is complicated. The crux of the problem is a comprehensive standard for quantifying the full range of skin pigmentation. This is vital to understanding how pulse oximeter accuracy varies by melanin content.
• Proactively identifying and addressing bias in medical devices will require system-wide efforts. Identification of bias in medical devices has been piecemeal rather than the outcome of proactive, deliberative efforts. Further efforts to address bias in medical devices should engage diverse stakeholders to establish best practices for ensuring equity in medical devices.

Resolving the problem of bias in pulse oximeter devices will likely take several years. But in the meantime, this issue will continue negatively impacting patients. Our participants urged that we need to think about actions that can be initiated this next year that will advance more equitable care with existing pulse oximeters. 

In-person stakeholders convening a focused conversation on next steps

Motivating Action for Equity Now

While a daunting problem, a collaborative, multi-stakeholder effort can bring us closer to solutions. We can work together to advance equity in standards of care by:

• Gathering evidence on existing pulse oximeter devices and their use in care [ASAP, start early 2023]. More evidence is required to identify the best approaches to equitable care with existing devices. This evidence gathering process should be initiated over the next year to inform clinicians on 
• Establishing consensus to advance the standard of care [start early 2024]. After growing the body of evidence, there will be a need to convene around key conclusions derived from the evidence. Evidence synthesis will need to be generated and care societies will need to make decisions on how clinicians should use pulse oximeters in their care practice.
• Taking action to ensure equitable care nationwide [2024 onwards]. Once the care standards are changed, there is a need for system-wide efforts to communicate these to clinicians nationwide, inform procurement across federal hospitals, and re-evaluate insurance reimbursement standards.

Mapping out a plan of action towards equity

Looking Ahead

This won’t be easy, but it’s 30 years overdue. We believe correcting the bias will pioneer a model that can be readily applied to combatting biases across the medical device ecosystem, something already underway in the United Kingdom with their Equity in Medical Devices Independent Review. Through a systematic approach, stakeholders can work to close racial disparities in the near-term and advance health equity.

Poor diets present elevated health risks, and Americans need help finding the time and resources to eat nutritiously

Americans get bombarded with promotions for unsubstantiated diet fads on the internet, are exposed to dubious weight-loss branded foods in grocery stores, and often struggle to eat nutritiously. The Dietary Guidelines for Americans recommend a balanced diet of two and a half cups of vegetables, two cups of fruit, six ounces of grains, three cups of dairy, five and a half ounces of protein, and 27 grams of oil every day. This diet is well-balanced, but it is neither practiced by, nor accessible to, all Americans (Figure 1).

Increasing numbers of Americans do not eat healthful diets. In 2018, the National Health and Nutrition Examination Survey found that one in three Americans eats fast food on any given day. Moreover, both rural and urban Americans report that lack of time and access to nutritious foods prevents them from cooking healthy meals. Indeed, a 2017 study indicated that the higher prices of healthy foods – nearly double those of unhealthy foods – can play a role in the U.S. population’s failure to achieve a nutritious diet. When healthy food cost even 14 percent higher than unhealthy food, there was a 24 percent decrease in consuming a high-quality diet. Unfortunately, an unhealthy diet can lead to a variety of health issues, such as obesity, type-2 diabetes, heart disease, and an increased risk of some cancers. To reverse poor health metrics such as the 42.4% of American adults over 20 years of age who suffered from obesity in 2018, policymakers and health experts alike hope to make healthy diets more accessible to all Americans.

Figure 1.

On average, people in the U.S. score between 56 and 60 (out of 100) when evaluated for healthy eating. The maximum test score of 100 points indicates adherence to the American Dietary Guidelines. Figure reproduced from Dietary Guidelines for Americans, 2020-2025.

To empower people to develop more nutritious eating habits, some experts recommend:

• Teaching better practices for caloric intake, which can increase life expectancy;
• Incentivizing healthy eating with financial rewards, such as coupons, when purchasing fruits and vegetables;
• Teaching and encouraging adults to buy and prepare their own meals; and
• Enabling mutual aid initiatives such as community fridges, food banks, and free breakfast programs for those who are food insecure.

For some, the transition to eating a well-balanced diet will require learning how to cook, carving out time to prepare meals, or gaining an understanding of the nutritional value of various foods. In the U.S., there is no justifiable reason people should not be supported by their local, state, and federal governments in efforts to eat healthy.

To improve American dietary habits, policymakers can learn about and implement public health initiatives for nutritional education, as well as break down systemic barriers to healthy eating lifestyles.

This CSPI Science and Technology Policy Snapshot expands upon a scientific exchange between Congressman Bill Foster (D, IL-11) and his new FAS-organized Science Council.

Innovative manufacturing techniques can expand the production of drugs and medical supplies in the U.S.

The COVID-19 pandemic caused significant disruptions in global supply chains, and policymakers are now strategizing around how to ramp up U.S. supply chain resiliency. Everything from beef to toilet paper became more difficult to find in U.S. stores, and the pandemic also caused dire shortages of medical supplies and lifesaving treatments. The shortages were caused by the closure of many manufacturing plants in countries like China, and our domestic supply chain was not sufficient to meet the demand gap. In fact, it is estimated that China exports more respirators, surgical masks, and other personal protective equipment than the rest of the world combined. The limited capacity of domestic supply chains – particularly for pharmaceuticals and medical supplies – was a focus for Chair Tammy Baldwin (D, WI) during last week’s Senate Appropriations Subcommittee hearing featuring testimony from Dr. Janet Woodcock, acting commissioner of the Food and Drug Administration (FDA).

The distributed nature of modern manufacturing

The production of goods such as smartphones, medical therapeutics, or kitchen appliances is complex. Manufacturers rely on highly-trained specialists to make different components that are eventually combined into a single product. For example, the manufacture of LCD displays requires obtaining the raw materials, like glass sheets, films, semiconductor chips, and circuit connectors, from other manufacturers around the world, and assembling components inside multi-billion-dollar factories. Specialization in manufacturing allows businesses to develop new, lower-cost technologies, and more easily scale production and design processes. Unfortunately, specialization also results in a layered network of manufacturers relying on yet other manufacturers, and so on, and it becomes very difficult to determine where each component is coming from in the supply chain. The lack of visibility into this process then exacerbates disruptions in manufacturing during crises, such as the COVID-19 pandemic.

Federal partnerships to strengthen the domestic manufacturing base

To protect against future disruptions, implementing advanced manufacturing practices in domestic facilities, and encouraging businesses, particularly those that make critical drugs and medical supplies, to set up new advanced manufacturing plants in the U.S., can make a substantial impact. During last week’s hearing, Senate Appropriations Subcommittee on Agriculture, Rural Development, FDA, and Related Agencies Chair Baldwin began by asking (33:05 mark in video) FDA Acting Commissioner Woodcock about how the agency is helping to strengthen domestic pharmaceutical supply chains with advanced manufacturing.

The implementation of advanced manufacturing is a top priority for the Biden Administration, and earlier this year, the FDA partnered with the National Institute of Standards and Technology (NIST) to develop an advanced manufacturing regulatory framework. The partnership aims to “increase U.S. medical supply chain resilience and advanced domestic manufacturing of drugs, biological products, and medical devices through adoption of 21st century manufacturing technologies.” One emerging technology that will be explored by the partnership is the modularization of manufacturing processes. Modularization refers to structuring discrete parts of the manufacturing process in a way that they can be plugged into each other in different combinations and still function properly. With modular processes, reconfiguring the manufacturing floor to produce a different medicine or device could take just hours or days, instead of months. Another example is using artificial intelligence to track production, tweak settings to increase efficiency, and schedule maintenance to reduce the amount of downtime necessary.

In addition to FDA and NIST efforts to implement advanced manufacturing for medical supplies, two Manufacturing USA Institutes – the National Institute for Innovation in Manufacturing Biopharmaceuticals (NIIMBL) and the Bioindustrial Manufacturing and Design Ecosystem (BioMADE) – are pursuing new advanced biomanufacturing solutions. NIIMBL is a public-private partnership supported by industry and NIST to “accelerate biopharmaceutical innovation,” develop standards, and educate the biomanufacturing workforce. Advances in manufacturing processes developed by NIIMBL aid in the production of treatments for debilitating diseases like cancer, autoimmune disorders, microbial infections, and diabetes. BioMADE is one of the newest Manufacturing USA institutes, supported by the Department of Defense and industry partners. It will promote the commercialization of new biomanufacturing technologies by (i) developing predictive models to move products from the lab to production, (ii) de-risking new technologies, and (iii) manufacturing products at pilot and intermediate scales before they are produced at full scale. BioMADE would also help establish best practices for the biofabrication of novel chemicals, enzymes, and other useful biological products.

Advanced manufacturing for on-demand pharmaceuticals

There are already numerous advanced manufacturing technologies that could be leveraged to boost domestic capacity and improve U.S. self-sufficiency in the production of high-priority medicines, such as anesthetics. Building on work that is underway at the federal level, there are additional opportunities for the Executive Branch to form cross-cutting, productive partnerships. A proposal from Dr. Geoffrey Ling – former founding director of the Biological Technologies Office at the Defense Advanced Research Projects Agency, CEO of On Demand Pharmaceuticals, and Day One Project contributor – suggests that the U.S. Government could launch a national adaptive pharmaceutical manufacturing initiative. This initiative would aim to achieve self-sufficiency for the production of medicines in the U.S. by implementing new technologies to establish high-quality and automated systems readily deployed across the country. Action steps would include fostering:

• “Targeted synthetic biology research and development to enable faster manufacturing of low-cost, on-demand vaccines and precision immunotherapies;”
• “Advanced development of green, modular, on-demand small-molecule manufacturing technologies;” and
• “New business models to support the economically sustainable domestic adoption and deployment of new manufacturing technology.”

By convening experts from the public and private sectors, as well as academia, to craft a national strategy for advanced manufacturing, and then supporting its execution, the federal government could help reduce U.S. dependence on foreign pharmaceutical and medical supply manufacturing.

Fundamental research setting the stage for advanced manufacturing

While much of the focus to implement advanced manufacturing technologies is on later-stage experimental development and commercialization, fundamental research is critical to launching these cutting-edge systems. For instance, the National Science Foundation (NSF) spent an estimated $318 million on basic manufacturing research in fiscal year 2021, and is requesting an additional $100 million in funding for its work in fiscal year 2022. In the coming fiscal year, NSF plans to sponsor research in scientific disciplines vital to advanced manufacturing, such as:

• “Highly-connected, adaptable, resilient, safe, and secure cyber-physical systems;”
• “New methods, processes, analyses, tools, or equipment for new or existing manufacturing products, supply-chain components, or chemicals and materials, including replacements for mainstay materials such as plastics that cause environmental harm;”and
• “Next-generation manufacturing infrastructure as part of a broader effort to design and renew national infrastructure.”

Today’s investments in fundamental research into manufacturing are expected to catalyze tomorrow’s breakthrough advanced manufacturing technologies.

Looking ahead

The full implementation of new developments in advanced manufacturing has the potential to ensure the resilience of U.S. medical supply chains in future crises. It can also provide other significant benefits, such as improvements in the quality of critical treatments and therapies, the creation of new jobs, and strengthening the economy. As the FDA, NIST, and other federal agencies work together, and Congress explores ways to continue supporting advanced manufacturing, we encourage the CSPI community to continue to serve as a resource to federal officials.

Each year about 700 women die from pregnancy or birth complications in the U.S., the worst maternal mortality rate out of all industrialized countries. The need to improve U.S. rates of maternal mortality, as well as bolster research on the safety of prescription drugs for the health of pregnant and lactating women, were both raised during last week’s House Appropriations Committee hearing about the National Institutes of Health (NIH) future research and funding priorities.

The maternal mortality crisis

The rate of maternal deaths has been rising in the U.S. since 2000, taking a serious toll on families from all different backgrounds. Maternal mortality is defined as any deaths during a pregnancy or within 42 days of the end of the pregnancy from “any cause related to or aggravated by the pregnancy or its management.” More than half of maternal deaths occur after the day of birth, and one third occur during the pregnancy. The most common causes of death are cardiomyopathy (weakened heart muscles), blood clots, hypertension (high blood pressure), stroke, infection, and hemorrhage (heavy bleeding). This crisis is also exacerbated by disparities experienced by people of color: Black women are 2.5 times more likely to die than White women and three times more likely to die than Hispanic women.

Reducing maternal deaths, particularly among communities of color, is a top priority for  Diana Bianchi, the director of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD). Just last year, the NIH established the Implementing a Maternal health and PRegnancy Outcomes Vision for Everyone (IMPROVE) Initiative. It aims to “mitigate preventable maternal mortality… and promote health equity” by using “an integrated approach to understand biological, behavioral, sociocultural, and structural factors.” The IMPROVE initiative has already awarded over $7 million in grants to address disparities in maternal mortality.

The lack of knowledge about safe drugs for pregnant and lactating women

While there are several active efforts to address maternal mortality, one aspect of women’s health that has not received as much attention: there is a significant lack of knowledge as to which drugs are safe for pregnant and lactating women to use. While this problem has existed for a long time, it is brought into clear focus when examining the recent clinical trials for COVID-19 treatments. Out of 927 clinical trials worldwide, only 16, less than 2%, evaluated the effectiveness of a treatment on pregnant women and their fetuses. More than half of the clinical trials excluded pregnant women specifically. Both Representatives John Moolenaar (R-MI) and Lois Frankel (D-FL) raised the knowledge gap in safe treatments for pregnant and lactating women during the hearing. 

The exclusion of pregnant women from clinical trials largely stems from the thalidomide and diethylstilbestrol (DES) tragedies in the mid-1900s. DES entered the market in 1938 and was promoted as a way to prevent miscarriages and premature births, but almost 40 years later, researchers found the drug actually caused rare cancers in the daughters born to mothers who took it, as well as structural changes to the reproductive tract, and infertility. It also elevated risks of breast cancer in the mothers. Thalidomide was used during the late 1950s and early 1960s to treat morning sickness. Researchers found, however, that the drug caused devastating birth defects in babies. After these tragedies, the Food and Drug Administration (FDA) published guidelines in 1977 that prevented pregnant women from participating in phase I and phase II clinical trials.

Though it is now possible for pregnant women to enroll in clinical trials due to the passage of the NIH Revitalization Act of 1993, the researchers may only recruit them if the clinical trials adhere to strict regulations. Current regulations require conducting preclinical studies with pregnant animals and clinical studies with nonpregnant women prior to enrolling pregnant women. The clinical trials must also ensure the “least possible” risk to achieve objectives of the research, among other obligations. Because these requirements add time and cost to clinical trials, as well as necessitate the recruitment of sufficient numbers of pregnant women, many researchers opt not to include them. The Centers for Disease Control and Prevention estimate that 70% of pregnant women take at least one prescription drug. Nevertheless, the fact that researchers rarely include pregnant women in clinical trials results in these women not having clear information about what drugs are safe for them and their babies. One study found that 90% of drugs approved by the FDA between 1980 and 2000 had no data about the drugs’ potential effects on pregnant women and their fetuses. Drug manufacturers now choose to track possible side effects after a drug’s release via self-reported registries. However, the requirement for pregnant women to report their own symptoms can skew the data toward only severe reactions, and omit any milder, but still clinically important, symptoms.

As part of the 21st Century Cures Act, NIH established the Task Force on Research Specific to Pregnant Women and Lactating Women (PRGLAC) to provide recommendations and an implementation plan on how to integrate pregnant and lactating women into drug safety research. The task force has already had a positive effect on the work at NIH, and helped launch the Maternal and Pediatric Precision in Therapeutics (MPRINT) Hub. The goal of the hub is to establish a center of knowledge  that explains what drugs pregnant and lactating women can take safely, and the effects of medicines on babies.

More to be done

The initiatives NIH has launched so far are vital to reduce maternal mortality and support the health of pregnant and lactating women. These topics will likely continue to be priorities of the Biden Administration and Congress. If you have ideas on how the federal government can support further research in maternal health, we encourage you to serve as a resource for Members of Congress and their staff.

To help catalyze innovation in the health and biomedical sciences, research and development (R&D) paradigms with a track record of producing ‘moonshot’-scale breakthroughs – such as the Advanced Research Projects Agency (ARPA) model – stand at the ready. The Biden Administration has recognized this, proposing the establishment of an ARPA for health (ARPA-H) as part of its fiscal year 2022 budget request. Done right, ARPA-H would be created in the image of existing ARPAs – DARPA (defense), ARPA-E (energy), and IARPA (intelligence) – and be capable of mobilizing federal, state, local, private sector, academic, and nonprofit resources to directly address the country’s most urgent health challenges, such as the high cost of therapies for diseases like cancer, or antimicrobial resistance. During a recent House Energy and Commerce Committee hearing, Chairwoman Anna Eshoo (D-CA) raised the Administration’s proposal for ARPA-H with Department of Health and Human Services (HHS) Secretary Xavier Becerra, expressing her interest in exploring how to best position a potential ARPA-H for success.

Keys to the ARPA model

The success of the ARPA model is attributed in part to the high level of autonomy with which its program leaders select R&D projects (compared to those at traditional federal research agencies), a strong sense of agency mission, and a culture of risk-taking with a tolerance for failure, resulting in a great degree of flexibility to pursue bold agendas and adapt to urgent needs. Policymakers have debated situating a potential ARPA-H within the National Institutes of Health (NIH), or outside of NIH, elsewhere under the umbrella of HHS. Regardless, it is essential that ARPA-H retain an independent and innovative culture.

The first ARPA – DARPA – was established in 1958, the year after Sputnik was launched, and is credited with developing GPS, the stealth fighter, and computer networking. DARPA continues to serve its customer – the Department of Defense – by developing groundbreaking defense technologies and data analysis techniques. Nevertheless, DARPA operates separately from its parent organization. This is also true of ARPA-E, which was launched in 2007 based on a recommendation from a National Academies consensus study report which called for implementing the DARPA model to drive “transformational research that could lead to new ways of fueling the nation and its economy,” and IARPA, created in 2006, to foster advances in intelligence collection, research, and analysis.

If ARPA-H is organized within NIH, it is essential that it maintain the innovative spirit and independence characteristic of established ARPAs. NIH already has some experience overseeing a partially independent entity: the National Cancer Institute (NCI). Compared to other NIH institutes, NCI’s unique authorities include:

• Direct access to the president;
• A requirement to submit a completely separate budget proposal to the president each year without getting approval from NIH or HHS; and
• The ability of the NCI director to form new cancer centers and training programs, establish advisory committees, and independently collaborate with other federal, state, and local entities.

This level of independence has contributed to NCI achieving a number of significant milestones in cancer treatment, including developing a chemotherapy treatment to cure choriocarcinoma (a rare type of cancer that starts in the womb), publishing the now-widely-used Breast Cancer Risk Assessment Model, and creating an anticancer drug for ovarian cancer that was unresponsive to other treatments.

If the NCI model were to be used as the foundation for the launch of ARPA-H, insulation from political considerations, whether those of Congress or the Executive Branch, would be critical. With DARPA-like autonomy, a potential ARPA-H could help push the boundaries of enrichments to human health.

Antimicrobial resistance as a case study for an ARPA-H

An example of a grand challenge that an ARPA-H could take on is addressing antimicrobial resistance, a worsening situation that, without intervention, will lead to a significant public health crisis. Antimicrobial resistance occurs when “bacteria, viruses, fungi, and parasites change over time and no longer respond to medicines, making infections harder to treat and increasing the risk of disease spread, severe illness, and death.” Microbes have the potential to gain resistance to drugs when not all of the pathogens or parasites are killed by a treatment, either because the treatment was the not correct option for the illness (like using antibiotics for viruses), or refraining from completing a prescribed course of an antimicrobial drug. The organisms that are not killed, presumably because they harbor genetic factors that confer resistance, then reproduce and pass along those genes, which make it harder for the treatments to kill them.

The most immediate concerns regarding antimicrobial resistance come from bacteria and fungi. The CDC considers some of the biggest threats to be Acinetobacter, Candida auris, and C. difficile, which are often present in healthcare and hospital settings and mainly threaten the lives of those with already weakened immune systems. Every year in the U.S., almost 3 million people are infected with antimicrobial-resistant bacteria or fungi, and as a result, more than 35,000 people die. While the toll of antibiotic resistance in the U.S. is devastating, the global outlook is perhaps even more concerning: in 2019, the United Nations warned that if no action is taken, antimicrobial resistance could cause 10 million deaths per year worldwide by 2050.

Developing new and effective antibiotics can help counter antimicrobial resistance; however, progress has been extremely slow. The last completely new class of antibiotics was discovered in the late 1980s, and developing new antibiotics is often not profitable for pharmaceutical companies. It is estimated that it takes $1.5 billion to create a new antibiotic, while the average revenue is about $46 million per year. In addition, while pharmaceutical companies receive an exclusivity period during which competitors cannot manufacture a generic version of their drug, the period is only five to ten years, which is too short to recoup the cost of research and development. Furthermore, doctors are often hesitant to prescribe new antibiotics in hopes of delaying the development of newly drug-resistant microbes, which also contributes to driving down the amount pharmaceutical companies earn for antibiotics.

Early last year, the World Health Organization reported that out of 60 antibiotics in development, there would be very little additional benefit over existing treatments, and few targeted the most resistant bacteria. Moreover, the ones that appeared promising will take years to get to the market. This year, Pew Research conducted a study on the current antibiotic development landscape and found that out of 43 antibiotics under development, at least 19 have the potential to treat the most resistant bacteria. However, the likelihood of all, or even some of these products making it to patients is low: over 95 percent of the products in development are being studied by small companies, and more than 70 percent of these companies do not have any other products on the market.

There is both a dire need for new innovations in the space, such as using cocktails of different viruses that attack bacteria to treat infections, and a gap between the research into and commercialization of new antibiotics – a perfect opportunity for a potential ARPA-H to make an impact. With this new agency, experimental treatments could be supported through the technology transfer process and matured to the point that the private sector is able to take the baton and move a new antimicrobial to market. This would be revolutionary for public health, and, combined with improved messaging around best practices for the use of antibiotics, save many lives.

Moving forward

The need for, structure, and possible priorities of a potential ARPA-H will continue to be discussed over the course of the congressional appropriations process, with consultation between the Legislative and Executive Branches. We encourage the CSPI community to serve as a resource for Members of Congress and their staffs to ensure that the new agency will be properly positioned to contribute to significant advances in human health and biomedical technologies.

As the U.S. continues to grapple with the pandemic, there are growing concerns about the risks posed by variants of SARS-CoV-2 – the coronavirus that causes COVID-19. Recent data have shown that at least one SARS-CoV-2 variant is more transmissible than the original, and there are questions as to whether any variants could be more deadly. The main way to detect emerging variants is to perform widespread genome sequencing, but the sequencing infrastructure in the U.S. is struggling to keep up with demand. This issue was a major focus of the Centers for Disease Control and Prevention’s (CDC) briefing to the House Appropriations Subcommittee on Labor, Health and Human Services, Education and Related Agencies this week.

Origin of variants and their detection

Viruses replicate by taking advantage of a person’s own cells, and each replication introduces small changes into a virus’ genetic code. Usually, these mistakes either have no impact, or are harmful to the virus. Sometimes, though, these errors give the virus an advantage, like increased ability to infect other people. Besides increased transmissibility, it is possible that variants could also cause more severe disease, evade detection by diagnostic tests, reduce the effectiveness of treatments, escape infection-induced immunity, or render vaccines less effective.

These risks are why it is imperative that public health officials track the emergence of variants around the country, and around the globe. Variants are found by extracting genetic material from patient samples, using sequencing equipment to read the virus’ genetic code, and comparing it with other known samples. When increasing numbers of cases of disease are found to have been caused by a virus with a genetic signature that is only slightly different from that of the known samples, scientists can estimate that they may have found a new variant. For SARS-CoV-2 specifically, there are a few variants that appear to have an advantage and are able to spread much more easily than the original strain. These variants include the UK and South African strains. There are also some early data that a variant discovered in California is more contagious than the original.

Challenges for genome sequencing of viruses in the U.S.

Public health officials use genomic sequencing to monitor for a variety of viruses, but the increased demand during the COVID-19 pandemic has put the U.S.’ sequencing infrastructure under strain. Though the U.S. has over 28 million COVID-19 cases, or about one-fourth of the total number of cases in the world, only about 96,000 samples, or around 0.3 percent, have been sequenced. For U.S. labs, the sequencing process can be costly and time-consuming, taking 48 hours to readout a virus’ genome in the best case scenario, though typical turnaround times stretch up to seven days. The cost of just one virus genome sequence can be anywhere from $80 to $500.

The country’s current genomic sequencing infrastructure has not been prioritized as a public health need and, in the past, sequencing was typically performed only by research universities. In 2014, the CDC started funding public health labs to track foodborne illnesses with genomic sequencing. By 2017 every state had labs which could perform genome sequencing, but obtaining funding is still difficult.

Current efforts and the road ahead

The CDC has been working to form various partnerships to boost the U.S.’ capacity for virus genome sequencing. According to its website, CDC has focused on several activities to increase genomic sequencing capacity, including:

• Leading the National SARS-CoV-2 Strain Surveillance (NS3) system;
• Partnering with commercial diagnostic laboratories;
• Collaborating with universities;
• Supporting state, territorial, local, and tribal health departments; and
• Leading the SARS-CoV-2 Sequencing for Public Health Emergency Response, Epidemiology, and Surveillance (SPHERES) consortium.

CDC Director Rochelle Walensky echoed this during Tuesday’s briefing and noted that under her leadership, the agency has scaled from 250 SARS-CoV-2 sequences per week to 14,000 per week. She hopes to scale up enough that the CDC can sequence 25,000 samples per week, which is close to about 5% of positive cases. To do this, the White House announced last week it would provide $200 million to support more genomic sequencing, and the U.S. Congress is considering adding almost $2 billion to that effort in the next economic relief package.

This funding is also intended to sustain the U.S.’ genomic sequencing infrastructure for the future. Senator Tammy Baldwin (D-WI), who introduced the legislation to support further sequencing, said the federal government should establish “the basis of a permanent infrastructure that would allow us not only to do surveillance for COVID-19, to be on the leading edge of discovering new variants, but also…have that capacity for other diseases.” During Tuesday’s briefing, Ranking Member Tom Cole (R-OK) affirmed this idea, saying that the House Appropriations Committee needs to think about establishing long-term funding streams to ensure that infrastructure developed during this crisis can last well in the future.

The COVID-19 pandemic has highlighted gaps in U.S. infrastructure for the genomic sequencing of pathogens, and the importance of tracking virus variants for our public health. While the CDC works with its partners to rapidly scale up sequencing capacity, lawmakers need to consider how to sustain it for future outbreaks. As the Biden Administration and Congress consider scaling and sustainment, we encourage the CSPI community to serve as a resource to federal officials on this topic.

Given the pervasiveness of COVID-19 throughout the U.S., the risk of infection to transportation workers and passengers is significant. For instance, in a survey of over 600 bus and subway workers in New York City, almost one quarter reported contracting COVID-19, and 76 percent personally knew a coworker who had died from the disease. During last week’s hearing, the House Transportation and Infrastructure Committee discussed best practices for protecting transportation workers and passengers from COVID-19, with a particular focus on preventing the spread of the coronavirus through the air.

Transmission of COVID-19 via aerosols

In early October 2020, the Centers for Disease Control and Prevention (CDC) updated its guidance, confirming that COVID-19 can be transmitted via aerosols in addition to larger respiratory droplets. When an individual with COVID-19 coughs, speaks, or breathes, tiny coronavirus-carrying droplets can travel over distances longer than six feet and stay suspended in the air for up to several hours. For the coronavirus, most transmission via aerosols occurs in enclosed, poorly ventilated spaces, when a person is exposed to respiratory particles for an extended period of time. Mass transit vehicles can be one such pathway for infection since people from different households share the same spaces while either working or riding to their destinations.

Protecting people from COVID-19 involves implementing measures to keep virus particles from entering individuals’ noses and mouths. Scientists have found that wearing a face covering can limit the amount of droplets an individual releases, and thus also reduce the amount of virus particles in the air. Masks can also provide some degree of protection to the wearer by providing a barrier between coronavirus-carrying droplets and the person’s nose and mouth. The CDC also suggests that buildings and transportation systems examine the quality of their ventilation and filtration systems to reduce spread of COVID-19. Effective ventilation quickly dilutes the amount of virus particles in the air and allows clean air to quickly circulate in enclosed spaces. Advanced filtration systems can help catch and retain virus-carrying particles on tightly woven inserts, keeping them from reentering the space. While any one of these methods alone is not sufficient to protect people from the coronavirus, a layered approach that combines many safeguards can reduce the ability of respiratory diseases like COVID-19 to spread.

Using advanced filters to remove coronavirus-carrying particles from enclosed spaces

Several Members of the Committee noted the importance of developing and implementing advanced filtration technologies on transportation systems and in buildings. Scientists estimate that the coronavirus can spread even via airborne particles under 5 microns in diameter. (For comparison, a single raindrop is typically about 2,000 microns in diameter.) Most buildings have filters with a Minimum Efficiency Reporting Value (MERV) rating of between 7 and 8, which means they can filter up to 84.9 percent of particles between 3 and 10 microns in diameter. Subway cars also use these filters. The highest rated filters (MERV 16 to 20) can capture over 75 percent of particles that are between 0.3 and 1 micron in diameter, and high efficiency particulate air (HEPA) filters, which are used on airplanes, can theoretically remove at least 99.97 percent of particles 0.3 microns in diameter and larger. To better protect workers and passengers, transportation systems like Washington, DC’s Metro and the Bay Area Transit system in San Francisco are already testing out more advanced filtration technologies through pilot programs funded by the Federal Transit Administration.

Benefits of advanced filters beyond reducing spread of COVID-19

Widespread adoption of advanced filtration technologies can be beneficial not only to reduce the amount of coronavirus-carrying particles in the air, but also to trap other harmful aerosols. During the hearing, Dr. David Michaels from George Washington University and Dr. William Bahnfleth from Penn State University both noted that investing in better filters now can also protect people from inhaling harmful particulate matter from other sources. For example, wildfires contribute about 30% of all fine particulate emissions in the U.S., with many of these being 2.5 microns or smaller. Inhaling these harmful particles can be associated with cardiovascular and respiratory issues, as well as premature mortality, particularly in vulnerable groups such as the elderly, children, and pregnant women.

Enhanced air filtration is a useful tool to help slow the spread of COVID-19, especially when used alongside other measures like wearing masks, improving ventilation, social distancing, and hand washing. As the new administration and Congress work toward ending the pandemic, practices such as the widespread adoption of more robust filters are likely to be examined in more detail. We encourage our community to get involved in the effort to counter COVID-19 by engaging in future congressional hearings through our Calls to Action.

There has been a surge of public interest in the drug fluvoxamine as a potential treatment for individuals with mild COVID-19, and Congressional offices are receiving many questions about the possibility of using the drug to counter COVID-19 from constituents. This brief outlines what is known to date about fluvoxamine in the context of the coronavirus pandemic in order to help both policymakers and scientists discuss this issue with those in their communities.

Fluvoxamine is a long-used drug that showed promising preliminary results in a small, well-controlled COVID-19 patient study

The generic drug fluvoxamine (also referred to by the brand name Luvox) was first synthesized in 1971, and is used to treat anxiety, depression, and obsessive-compulsive disorder. Fluvoxamine blocks serotonin reuptake in the brain, but it is chemically unrelated to other selective serotonin reuptake inhibitors that are used to treat anxiety or depression, like fluoxetine (Prozac) or sertraline (Zoloft). Studies have demonstrated that fluvoxamine also binds a protein in mammalian cells called the sigma-1 receptor. One of this receptor’s functions is to regulate cytokine production; cytokines cause inflammation. When fluvoxamine has been used in the laboratory, it results in a dampened inflammatory response in human cells in the test tube, and protects mice from lethal septic shock, which is an out-of-control immune response to infection, causing massive inflammation that can impede blood flow to major organs, and result in organ failure. Notably, retrospective analyses have indicated that COVID-19 patients given antipsychotic drugs that target the sigma-1 receptor were less likely to require mechanical ventilation than COVID-19 patients given other antipsychotic drugs, and some drugs that bind the sigma-1 receptor also have antiviral activity against SARS-CoV-2 in the petri dish.

Researchers reasoned that fluvoxamine may be able to stave off the “cytokine storm” that can lead to the out-of-control inflammatory response that appears to cause severe respiratory and blood-clotting issues for some people infected with the coronavirus, and tested the drug in a pilot study to gauge whether it has potential as a treatment for COVID-19. The study was a small, double-blind, placebo-controlled, randomized clinical trial of 152 non-hospitalized adults with mild COVID-19. Treatment of symptomatic, confirmed COVID-19 patients started within 7 days of their diagnosis. None of the 80 patients treated with fluvoxamine experienced clinical deterioration, compared to 6 of 72 patients treated with placebo who experienced both “1) shortness of breath or hospitalization for shortness of breath or pneumonia and 2) oxygen saturation less than 92%.” While this amounted to a statistically significant difference, the study serves as only preliminary evidence for the efficacy of fluvoxamine as a therapy to counter COVID-19, and a much larger clinical trial has been initiated to pursue conclusive results.

Summary of the 152-participant fluvoxamine/COVID-19 clinical trial. Image source: The Journal of the American Medical Association

Further study of treating many more COVID-19 patients with fluvoxamine is required before the drug should be used outside of clinical trials as a therapy to counter COVID-19

While the double-blind, placebo-controlled, randomized design of the clinical trial does minimize bias and provide the opportunity to identify a causal relationship between treatment and patient outcome, larger randomized trials with more definitive metrics in place for assessing patients’ health status are necessary in order to reach a conclusion about whether fluvoxamine should be used to treat patients with COVID-19 outside of clinical trials. The findings of this single, small study are a launching point for larger clinical trials, and “should not be used as the basis for current treatment decisions.”

The limitations of the study include the small number of COVID-19 patients involved and the low number of patients in the placebo group whose conditions worsened – only six. And while fluvoxamine is safe, easily accessible, administered orally, and inexpensive, it may interact with other drugs, and does have some side effects, such as nausea, diarrhea, loss of appetite, increased sweating, dizziness, drowsiness, insomnia, or dry mouth.

The researchers who performed this pilot study are currently conducting a larger clinical trial to conclusively determine whether fluvoxamine is an advisable treatment for mild COVID-19. The trial is expected to be watched closely since the identification of drugs – in addition to the monoclonal antibody treatments developed by Regeneron and Eli Lilly – that could be used to reduce the likelihood of progression from mild to more severe COVID-19 would greatly improve health outcomes for people infected by the coronavirus, as well as reduce the burden on the US healthcare system.

–

This briefing document was prepared by the Federation of American Scientists along with Professor Alban Gaultier at the University of Virginia and Professor David Boulware at the University of Minnesota.

The limited science and technology (S&T) resources available to policymakers in Congress and state legislatures have compounded the severity of the COVID-19 pandemic. To help meet legislators’ S&T needs, the Federation of American Scientists (FAS) organized more than 60 specialists with expertise in all the different aspects of the pandemic to serve on the COVID-19 Rapid Response Task Force. In addition to providing many written briefings to Congressional and state legislative offices, members of the Task Force have so far provided three oral briefings to Congress, including one about the promise of monoclonal antibody (mAb) therapies for COVID-19.

Monoclonal antibodies to counter COVID-19

Many experts believe that mAb therapies have a major role to play in protecting people from COVID-19, serving as a bridge to a vaccine, and safeguarding groups that potentially would not respond to a vaccine, for example, an aged population or immunocompromised individuals. There is certainly precedent for mAb therapies helping people survive deadly diseases; for instance, mAb therapies resulted in statistically significant survival benefits for Ebola patients.

Therapeutic mAbs against COVID-19 are intended to stick to the spike proteins of SARS-CoV-2, which are on the outside of the virus, and block them from being able to attach to receptor proteins on the outside of human cells, which would be needed for viral entry and infection. Most focus has been on the spike protein interaction with the human cell surface receptor ACE2, and recent work shows that the human cell surface protein Neuropilin-1 also has a role in facilitating SARS-CoV-2 entry and infectivity in some human cell types. Designing mAb therapies that interfere with either one or both of these interactions could help explore the range of efficacies of COVID-19 mAbs.

This image was adapted from the San Diego Union-Tribune.

An experimental mAb from Eli Lilly being tested in early-stage clinical trials, while not appearing to help COVID-19 patients who are hospitalized (that testing has been stopped), has shown promise for people with mild or moderate COVID-19 who receive the treatment early and who are not hospitalized, reducing viral load, symptom severity, and eventual hospitalizations. The Food and Drug Administration (FDA) recently granted an Emergency Use Authorization (EUA) for Eli Lilly’s antibody. Under the EUA, the treatment, called bamlanivimab, is supposed to be given to patients as soon as possible after a positive coronavirus test, no more than 10 days after developing symptoms. The treatment should not be used for patients who are hospitalized. It is intended for individuals 12 and older and at risk for developing a severe form of COVID-19 or being hospitalized.

This image was adapted from Eli Lilly

Regeneron has also developed a mAb treatment, and has, like Eli Lilly, stopped its clinical trial in hospitalized patients – in Regeneron’s case, “an independent data monitoring committee warned that the risks might outweigh the benefits for hospitalised patients on high levels of oxygen.” Like Eli Lilly’s drug, Regeneron has reported that its mAB cocktail reduces virus levels in the body and improves symptoms for individuals with COVID-19 who are not hospitalized. Regeneron has also applied to the FDA for an EUA of their mAB therapy, and overall, at least ten COVID-19 antibodies are being tested in clinical trials, with many more under development.

While EUAs can serve to get drugs to patients more rapidly than going through full FDA approval, the use of mAbs outside of clinical trials can make it more difficult to ascertain the therapies’ true effectiveness in different age groups. Furthermore, it could make it harder to enroll volunteers in future clinical trials for alternative therapies, since people may want to take a drug that appears to work, rather than risk possibly getting placebo. Authorizing a low-impact therapeutic could be counterproductive. FDA must take care to only grant EUAs for mAb therapies where the data show they are potent, and clearly delineate the circumstances in which they should be administered to help patients.

Antibodies are expensive and difficult to make, and they are administered at relatively high levels. These factors conspire to limit the number of doses that are produced. By the end of the year, Regeneron is expected to have produced up to 300,000 doses of its cocktail, and Eli Lilly greater than one million. More doses are needed; experts estimate that each day, 10,000 to 15,000 people in the US would be indicated for the drugs based on age and risk factors, even if there’s no further surge of infection.

A major challenge is that manufacturing capacity for monoclonal antibodies is limited, generally actively being used to produce treatments that are needed by patients as therapies for conditions such as cancer, multiple sclerosis, or osteoporosis. Globally, bioreactor capacity for producing mAbs from mammalian cells is spread across 200 facilities, with a total capacity of about 1,500,000 gallons. Constructing new manufacturing capacity requires years, with different types of facilities taking anywhere from 18 months to 7.5 years to come online. Bringing inactive facilities back online is a possibility, but how available such facilities are, and what would be needed to update them for operation, is unclear, and unlikely to happen in the near future. So, COVID-19 mAb manufacturing will need to rely on facilities either in use or in development, at least in the near-term.

Possible roles for government include helping to coordinate the construction of new mAb manufacturing capacity, or the repurposing of existing sites that could serve as bioreactors. Non-traditional mammalian cell lines could be tested to see which produce the highest levels of these mAbs to make the best use of the bioreactor capacity. Also, there are techniques for producing mAb therapies in bacterial or fungal (like brewer’s yeast) cells, in addition to mammalian cells, which could take advantage of existing capacity for microbial fermentation. And regulatory agencies like the Environmental Protection Agency and FDA could help expedite actions like repurposing bioreactor sites or deploying new bioproduction technologies by prioritizing the evaluation of these activities without harming the environment or sacrificing drug safety or efficacy.

Government could also assist with coordination between companies, providing a framework and forum for sharing information about or partnering on manufacturing capacity, or discussing approaches to COVID-19 mAb design that may have already been attempted and that did not pan out. This coordination could even extend to facilitating international collaborations, as COVID-19 mAb development efforts are taking place in countries all around the globe.

Considering COVID-19 is a deadly disease that can also have long-term health impacts for those who survive, the development and deployment of mAb therapies that can be administered soon after infection is detected and reduce the severity of disease are expected to contribute to countering the health effects of the pandemic.

Briefers

The experts who briefed Congress were Megan Coffee, MD/PhD, Clinical Assistant Professor at New York University; Erica Ollmann Saphire, PhD, Professor at the La Jolla Institute for Immunology and lead of the Coronavirus Immunotherapy Consortium; Jill Horowitz, PhD, Executive Director of the Strategic Operations Laboratory of Molecular Immunology at Rockefeller University; John Cumbers, PhD, CEO of SynBioBeta; Eric Hobbs, PhD, CEO of Berkeley Lights; Jake Glanville, PhD, CEO of Distributed Bio; Mike Fisher, PhD, Senior Fellow at the Federation of American Scientists; and Ali Nouri, PhD, President of the Federation of American Scientists.For more information about FAS’ work with Congress, visit our Congressional Science Policy Initiative website.

Categories: Public Health

The disconnect between assurances from federal health and science agencies and President Trump’s words continues. Before Wednesday’s hearing in the Senate Health, Education, Labor, and Pensions (HELP) Committee, news broke that the Food and Drug Administration (FDA) has plans to implement special Emergency Use Authorization (EUA) requirements for COVID-19 vaccine candidates. The vaccine EUA requirements proposed by FDA are reported to be more stringent than those for non-vaccine products like hydroxychloroquine or COVID-19 convalescent plasma. FDA Commissioner Hahn alluded to the application of the more stringent standards in his testimony during the hearing, but later in the day the president indicated that his administration may decide to reject the FDA’s proposal.

President Trump may reject FDA COVID-19 vaccine candidate guidelines

On Wednesday, President Trump cast doubt on whether the White House would greenlight FDA’s proposed rules for evaluating COVID-19 vaccine candidates that pharmaceutical companies could submit for approval via the EUA mechanism. An EUA is a temporary clearance for medical products that can be conferred more rapidly and with less documentation than a full approval, which can take six to nine months. Standard EUAs require only that a product “may be effective,” and that the likely benefits to people outweigh the harms. In 2005, the anthrax vaccine was granted an EUA so military personnel considered at high risk of anthrax attack could receive the product, the only instance of an EUA being issued for a vaccine.

Because the vaccine would be administered to a broad population to prevent illness, as opposed to patients suffering from COVID-19, FDA has proposed to strengthen the EUA process. That proposal is now awaiting review in the White House Office of Management and Budget. In a shocking televised press conference, the president characterized the FDA proposal as a “political move.” FDA officials believe a different standard for EUAs for vaccine safety and efficacy, as opposed to EUAs for medical products like hydroxychloroquine (since revoked) and convalescent plasma, is appropriate since vaccines are given to healthy people, not to those who are sick. To earn an EUA, reports indicate the FDA plans to require clinical trial data for COVID-19 vaccine candidates that are close to what is required for a full approval. Specifically, the standards would require monitoring participants in late-stage clinical trials for a median of at least two months, starting after they receive a second vaccine shot (if the vaccine requires two shots), as well as reaching at least five severe cases of COVID-19 in the placebo group for each trial, and some cases of the disease in the elderly. Regardless, any EUA would be based on less safety data than the standard approval track, so clinical trial participants would be monitored well after an EUA, if one were to be issued.

The public will be able to evaluate FDA-reviewed COVID-19 vaccine candidates

As part of its COVID-19 vaccine candidate evaluation process, FDA plans to get the advice of the Vaccines and Related Biological Products Advisory Committee (VRBPAC), made up of experts in “immunology, molecular biology, recombinant DNA, virology, bacteriology, epidemiology or biostatistics, vaccine policy, vaccine safety science, federal immunization activities, vaccine development including translational and clinical evaluation programs, allergy, preventive medicine, infectious diseases, pediatrics, microbiology, and biochemistry.” These experts are screened for ethical conflicts, and are independent of both the US Government and vaccine-making companies. Notably, the VRBPAC chair recently recused herself from the review of COVID-19 vaccine candidates because she is running Moderna’s COVID-19 vaccine candidate clinical trial.

FDA Commissioner Hahn, pressed by Senator Maggie Hassan (D, NH; 2:29:32 mark in video), made it clear that when a vaccine-making company either submits a COVID-19 vaccine candidate application for full approval or requests an EUA, clinical trial data and the FDA summary assessing the data will be provided to VRBPAC as well as to the entire American public. Dr. Hahn also noted that VRBPAC’s discussion, vote, and recommendations will all be public. The public will then have an opportunity to provide comments. FDA will incorporate feedback from VRBPAC into its process, and make a final decision on approval or EUA.

It is important to note, however, that the VRBPAC recommendations are not binding. In other words, the FDA commissioner, Department of Health and Human Services secretary, or possibly even the president have the authority to grant an EUA, irrespective of VRBPAC’s recommendations.

Even so, the opportunity for the entire science and medical community to review COVID-19 vaccine candidate data should help ensure that the public can learn the extent to which COVID-19 vaccine candidates are known to be safe and effective.

The outlook for COVID-19 vaccine availability

At Wednesday’s hearing, Dr. Anthony Fauci, the director of the National Institute of Allergy and Infectious Diseases, told the Committee (2:37:41 mark in video) that if all goes well with vaccine-makers’ COVID-19 vaccine candidate clinical trials, that in November, there possibly could be 50 million doses available, about 100 million more doses in December, and roughly 700 million total doses by April. He said that the vaccines will likely be given to healthcare providers and those who are vulnerable due to underlying conditions first. However, Paul Offit, director of the Vaccine Education Center at Children’s Hospital of Philadelphia and a member of VRBPAC, recently told the Washington Post that “It’s hard to imagine how an [emergency use authorization] could possibly occur before December,” indicating the availability of COVID-19 vaccines in November is not certain.

FAS is tracking this situation closely; for an opportunity to contribute to oversight over the COVID-19 vaccine candidate evaluation process, click here.

Additional hearing highlights

Senators seek answers about the guidance on airborne transmission of COVID-19 that was posted and then removed from the CDC website

Dr. Fauci pushes back on Senator Rand Paul in an exchange about herd immunity

Attention called to head of Operation Warp Speed’s potential conflicts of interest

More than 90 percent of Americans remain susceptible to the coronavirus

To review the entire hearing, click here.

The Oval Office, biopharmaceutical executives, and federal agencies have signaled that COVID-19 vaccines could be ready to go this fall; however, leading experts believe that proof of a safe and effective vaccine before Election Day is unlikely. President Trump has said that “we can probably have [a COVID-19 vaccine] sometime in October.” Pfizer and BioNTech executives think they could know whether their joint COVID-19 vaccine candidate works by the end of October, and that the Food and Drug Administration (FDA) will grant it an Emergency Use Authorization (EUA). The Centers for Disease Control and Prevention (CDC) wants states ready to distribute a COVID-19 vaccine as soon as late October, with distribution sites operational by November 1st. While it is certainly important to be primed to distribute life-saving vaccines, a more realistic scenario is that thorough analyses determining the safety and efficacy of COVID-19 vaccine candidates should be possible at the very end of this year, or beginning of next year.

Nevertheless, extremely optimistic COVID-19 vaccine approval timelines that converge with Election Day are being broadcast to the American public, and during Wednesday’s Senate Health, Education, Labor, and Pensions (HELP) Committee hearing, lawmakers demanded assurances that scientific data, not political agendas, will drive the COVID-19 vaccine approval process.

The path forward for phase III COVID-19 vaccine candidates

Three COVID-19 vaccine candidates that could be made available to Americans are currently in phase III clinical trials, and their paths forward rely on the actions that are taken by the vaccine-makers, FDA, the Department of Health and Human Services (HHS, FDA’s parent agency), and the President.

Whereas vaccine candidate clinical trials have historically been designed and executed by biopharmaceutical companies alone, COVID-19 vaccine candidate trials have been overseen by the US Government. To gauge if any of the vaccine candidates prevent or decrease the severity of disease with at least 50 percent efficacy – the bar FDA set at the end of June – tens of thousands of people are being enrolled in each COVID-19 vaccine candidate phase III clinical trial. In fact, on Saturday, Pfizer proposed to FDA that it enroll up to 44,000 participants, almost 50 percent more than the initial target of 30,000. Half are dosed with the vaccine candidate, the other half are dosed with placebo, and, to prevent bias, only a select group of experimentalists – not the trial participants, not the professionals administering the doses – know who gets what. During Wednesday’s hearing, Dr. Francis Collins, the director of the National Institutes of Health, asserted (2:26:10 mark in video) that once 150 people in the entire trial have developed symptomatic disease, it should be possible to determine whether a vaccine candidate is 50 percent effective. However, some experts say that even the point at which the trial reaches 150 cases of disease is unlikely to provide enough time to prove vaccine candidate safety.

Each individual COVID-19 vaccine candidate trial is tracked by a unique Data Safety and Monitoring Board (DSMB). DSMBs are multidisciplinary groups, independent of both the vaccine-maker and the federal government, composed of clinical trials specialists, biostatisticians, bioethicists, immunologists, vaccinologists, and virologists. As trials progress, DSMBs regularly review the data as they accumulate, and make recommendations to the company and to FDA about whether a vaccine has met safety and efficacy standards. Ultimately, DSMBs are only advisory groups, and it is up to the company as to whether it submits a Biologics License Application (BLA) to FDA for their COVID-19 vaccine candidate.

FDA will review the clinical trial data in the BLA for safety and efficacy. Following FDA’s review, the company and the FDA have the option of presenting their findings to FDA’s Vaccines and Related Biological Products Advisory Committee (VRBPAC), another expert body independent of both the federal government and the vaccine-maker. If consulted, VRBPAC would provide advice to FDA regarding the safety and efficacy of the vaccine. Regardless, FDA could then approve or deny the vaccine candidate for use.

Alternatively, a vaccine-maker could request an EUA from FDA, which opens up the possibility of a vaccine being approved for use before the conclusion of the clinical trial, which could complicate the trial’s full evaluation of safety and efficacy. Another tool FDA could possibly use is Accelerated Approval, a process that could base vaccine approval only on antibody levels or another surrogate biochemical marker produced in trial participants, rather than measuring actual protection from disease. Notably, HHS, or possibly President Trump, could even overrule an FDA rejection of a request for an EUA.

Dr. Anthony Fauci, the director of the National Institute of Allergy and Infectious Diseases, believes there would be a moral obligation to end a trial early and make a vaccine accessible if the data from the trial were to be overwhelming that the vaccine candidate is safe and effective.

Federal officials testify that COVID-19 vaccine decisions will be based only on science

During the hearing, Senator Bernie Sanders (D, VT) pressed (1:14:27 mark in video) the witnesses to affirm that the COVID-19 vaccine approval process will only be driven by science. Dr. Collins pledged that he and all US Government scientists will be basing COVID-19 vaccine candidate evaluations and assessments only on science, or else he would have no part in the process. He also expressed cautious optimism that the US will produce a safe and effective vaccine by the end of the year, adding “certainly to try to predict whether it happens on a particular week before or after a particular date in early November is well beyond anything that any scientist right now could tell you and be confident that they know what they’re saying.”

Vice Admiral Jerome Adams, the US Surgeon General, concurred with this sentiment, stating that a COVID-19 vaccine will not be moved along unless it is proven to be safe and effective, that shortcuts will not be taken, and that once approved or authorized by FDA, he and his family would not hesitate to receive the vaccine.

Will words translate into action as Election Day approaches?

Dr. Collins and Vice Admiral Adams are not the only ones giving assurances that science, not political influence, will drive COVID-19 vaccine approval. Career civil servants at FDA reiterated their resolve to working “with agency leadership to maintain FDA’s steadfast commitment to ensuring our decisions will continue to be guided by the best science.” The head of Operation Warp Speed (the US effort to accelerate COVID-19 vaccine development), Dr. Moncef Slaoui, says he will “immediately resign if there is undue interference in this process.” And nine COVID-19 vaccine-making companies have pledged to “uphold the integrity of the scientific process as they work towards potential global regulatory filings and approvals of the first COVID-19 vaccines.”

We will be tracking this issue closely as Election Day nears, and will be sure to alert the community to new developments. To review the entirety of this week’s hearing, click here.