Want to Motivate Vaccinations? Message Optimism, Not Doom
After COVID-19 was declared a worldwide pandemic by the World Health Organization on March 11, 2020, life as we knew it altered dramatically and millions went into lockdown. Since then, most of the world has had to contend with masks, distancing, ventilation and cycles of lockdowns as surges flare up. Deaths from COVID-19 infection, along with economic and mental health effects from the shutdowns, have been devastating. The need for an ultimate solution -- safe and effective vaccines -- has been paramount.
On November 9, 2020 (just 8 months after the pandemic announcement), the press release for the first effective COVID-19 vaccine from Pfizer/BioNTech was issued, followed by positive announcements regarding the safety and efficacy of five other vaccines from Moderna, University of Oxford/AztraZeneca, Novavax, Johnson and Johnson and Sputnik V. The Moderna and Pfizer vaccines have earned emergency use authorization through the FDA in the United States and are being distributed. We -- after many long months -- are seeing control of the devastating COVID-19 pandemic glimmering into sight.
To be clear, these vaccine candidates for COVID-19, both authorized and not yet authorized, are highly effective and safe. In fact, across all trials and sites, all six vaccines were 100% effective in preventing hospitalizations and death from COVID-19.
All Vaccines' Phase 3 Clinical Data
Complete protection against hospitalization and death from COVID-19 exhibited by all vaccines with phase 3 clinical trial data.
This astounding level of protection from SARS-CoV-2 from all vaccine candidates across multiple regions is likely due to robust T cell response from vaccination and will "defang" the virus from the concerns that led to COVID-19 restrictions initially: the ability of the virus to cause severe illness. This is a time of hope and optimism. After the devastating third surge of COVID-19 infections and deaths over the winter, we finally have an opportunity to stem the crisis – if only people readily accept the vaccines.
Amidst these incredible scientific advancements, however, public health officials and politicians have been pushing downright discouraging messaging. The ubiquitous talk of ongoing masks and distancing restrictions without any clear end in sight threatens to dampen uptake of the vaccines. It's imperative that we break down each concern and see if we can revitalize our public health messaging accordingly.
The first concern: we currently do not know if the vaccines block asymptomatic infection as well as symptomatic disease, since none of the phase 3 vaccine trials were set up to answer this question. However, there is biological plausibility that the antibodies and T-cell responses blocking symptomatic disease will also block asymptomatic infection in the nasal passages. IgG immunoglobulins (generated and measured by the vaccine trials) enter the nasal mucosa and systemic vaccinations generate IgA antibodies at mucosal surfaces. Monoclonal antibodies given to outpatients with COVID-19 hasten viral clearance from the airways.
Although it is prudent for those who are vaccinated to wear masks around the unvaccinated in case a slight risk of transmission remains, two fully vaccinated people can comfortably abandon masking around each other.
Moreover, data from the AztraZeneca trial (including in the phase 3 trial final results manuscript), where weekly self-swabbing was done by participants, and data from the Moderna trial, where a nasal swab was performed prior to the second dose, both showed risk reductions in asymptomatic infection with even a single dose. Finally, real-world data from a large Pfizer-based vaccine campaign in Israel shows a 50% reduction in infections (asymptomatic or symptomatic) after just the first dose.
Therefore, the likelihood of these vaccines blocking asymptomatic carriage, as well as symptomatic disease, is high. Although it is prudent for those who are vaccinated to wear masks around the unvaccinated in case a slight risk of transmission remains, two fully vaccinated people can comfortably abandon masking around each other. Moreover, as the percentage of vaccinated people increases, it will be increasingly untenable to impose restrictions on this group. Once herd immunity is reached, these restrictions can and should be abandoned altogether.
The second concern translating to "doom and gloom" messaging lately is around the identification of troubling new variants due to enhanced surveillance via viral sequencing. Four major variants circulating at this point (with others described in the past) are the B.1.1.7 variant ("UK variant"), B.1.351 ("South Africa variant), P.1. ("Brazil variant"), and the L452R variant identified in California. Although the UK variant is likely to be more transmissible, as is the South Africa variant, we have no reason to believe that masks, distancing and ventilation are ineffective against these variants.
Moreover, neutralizing antibody titers with the Pfizer and Moderna vaccines do not seem to be significantly reduced against the variants. Finally, although the Novavax 2-dose and Johnson and Johnson (J&J) 1-dose vaccines had lower rates of efficacy against moderate COVID-19 disease in South Africa, their efficacy against severe disease was impressively high. In fact J&J's vaccine still prevented 100% of hospitalizations and death from COVID-19. When combining both hospitalizations/deaths and severe symptoms managed at home, the J&J 1-dose vaccine was 85% protective across all three sites of the trial: the U.S., Latin America (including Brazil), and South Africa.
In South Africa, nearly all cases of COVID-19 (95%) were due to infection with the B.1.351 SARS-CoV-2 variant. Finally, since herd immunity does not rely on maximal immune responses among all individuals in a society, the Moderna/Pfizer/J&J vaccines are all likely to achieve that goal against variants. And thankfully, all of these vaccines can be easily modified to boost specifically against a new variant if needed (indeed, Moderna and Pfizer are already working on boosters against the prominent variants).
The third concern of some public health officials is that people will abandon all restrictions once vaccinated unless overly cautious messages are drilled into them. Indeed, the false idea that if you "give people an inch, they will take a mile" has been misinforming our messaging about mitigation since the beginning of the pandemic. For example, the very phrase "stay at home" with all of its non-applicability for essential workers and single individuals is stigmatizing and unrealistic for many. Instead, the message should have focused on how people can additively reduce their risks under different circumstances.
The public will be more inclined to trust health officials if those officials communicate with nuanced messages backed up by evidence, rather than with broad brushstrokes that shame. Therefore, we should be saying that "vaccinated people can be together with other vaccinated individuals without restrictions but must protect the unvaccinated with masks and distancing." And we can say "unvaccinated individuals should adhere to all current restrictions until vaccinated" without fear of misunderstandings. Indeed, this kind of layered advice has been communicated to people living with HIV and those without HIV for a long time (if you have HIV but partner does not, take these precautions; if both have HIV, you can do this, etc.).
Our heady progress in vaccine development, along with the incredible efficacy results of all of them, is unprecedented. However, we are at risk of undermining such progress if people balk at the vaccine because they don't believe it will make enough of a difference. One of the most critical messages we can deliver right now is that these vaccines will eventually free us from the restrictions of this pandemic. Let's use tiered messaging and clear communication to boost vaccine optimism and uptake, and get us to the goal of close human contact once again.
Breakthrough therapies are breaking patients' banks. Key changes could improve access, experts say.
CSL Behring’s new gene therapy for hemophilia, Hemgenix, costs $3.5 million for one treatment, but helps the body create substances that allow blood to clot. It appears to be a cure, eliminating the need for other treatments for many years at least.
Likewise, Novartis’s Kymriah mobilizes the body’s immune system to fight B-cell lymphoma, but at a cost $475,000. For patients who respond, it seems to offer years of life without the cancer progressing.
These single-treatment therapies are at the forefront of a new, bold era of medicine. Unfortunately, they also come with new, bold prices that leave insurers and patients wondering whether they can afford treatment and, if they can, whether the high costs are worthwhile.
“Most pharmaceutical leaders are there to improve and save people’s lives,” says Jeremy Levin, chairman and CEO of Ovid Therapeutics, and immediate past chairman of the Biotechnology Innovation Organization. If the therapeutics they develop are too expensive for payers to authorize, patients aren’t helped.
“The right to receive care and the right of pharmaceuticals developers to profit should never be at odds,” Levin stresses. And yet, sometimes they are.
Leigh Turner, executive director of the bioethics program, University of California, Irvine, notes this same tension between drug developers that are “seeking to maximize profits by charging as much as the market will bear for cell and gene therapy products and other medical interventions, and payers trying to control costs while also attempting to provide access to medical products with promising safety and efficacy profiles.”
Why Payers Balk
Health insurers can become skittish around extremely high prices, yet these therapies often accompany significant overall savings. For perspective, the estimated annual treatment cost for hemophilia exceeds $300,000. With Hemgenix, payers would break even after about 12 years.
But, in 12 years, will the patient still have that insurer? Therein lies the rub. U.S. payers, are used to a “pay-as-you-go” model, in which the lifetime costs of therapies typically are shared by multiple payers over many years, as patients change jobs. Single treatment therapeutics eliminate that cost-sharing ability.
"As long as formularies are based on profits to middlemen…Americans’ healthcare costs will continue to skyrocket,” says Patricia Goldsmith, the CEO of CancerCare.
“There is a phenomenally complex, bureaucratic reimbursement system that has grown, layer upon layer, during several decades,” Levin says. As medicine has innovated, payment systems haven’t kept up.
Therefore, biopharma companies begin working with insurance companies and their pharmacy benefit managers (PBMs), which act on an insurer’s behalf to decide which drugs to cover and by how much, early in the drug approval process. Their goal is to make sophisticated new drugs available while still earning a return on their investment.
New Payment Models
Pay-for-performance is one increasingly popular strategy, Turner says. “These models typically link payments to evidence generation and clinically significant outcomes.”
A biotech company called bluebird bio, for example, offers value-based pricing for Zynteglo, a $2.8 million possible cure for the rare blood disorder known as beta thalassaemia. It generally eliminates patients’ need for blood transfusions. The company is so sure it works that it will refund 80 percent of the cost of the therapy if patients need blood transfusions related to that condition within five years of being treated with Zynteglo.
In his February 2023 State of the Union speech, President Biden proposed three pilot programs to reduce drug costs. One of them, the Cell and Gene Therapy Access Model calls on the federal Centers for Medicare & Medicaid Services to establish outcomes-based agreements with manufacturers for certain cell and gene therapies.
A mortgage-style payment system is another, albeit rare, approach. Amortized payments spread the cost of treatments over decades, and let people change employers without losing their healthcare benefits.
Only about 14 percent of all drugs that enter clinical trials are approved by the FDA. Pharma companies, therefore, have an exigent need to earn a profit.
The new payment models that are being discussed aren’t solutions to high prices, says Bill Kramer, senior advisor for health policy at Purchaser Business Group on Health (PBGH), a nonprofit that seeks to lower health care costs. He points out that innovative pricing models, although well-intended, may distract from the real problem of high prices. They are attempts to “soften the blow. The best thing would be to charge a reasonable price to begin with,” he says.
Instead, he proposes making better use of research on cost and clinical effectiveness. The Institute for Clinical and Economic Review (ICER) conducts such research in the U.S., determining whether the benefits of specific drugs justify their proposed prices. ICER is an independent non-profit research institute. Its reports typically assess the degrees of improvement new therapies offer and suggest prices that would reflect that. “Publicizing that data is very important,” Kramer says. “Their results aren’t used to the extent they could and should be.” Pharmaceutical companies tend to price their therapies higher than ICER’s recommendations.
Drug Development Costs Soar
Drug developers have long pointed to the onerous costs of drug development as a reason for high prices.
A 2020 study found the average cost to bring a drug to market exceeded $1.1 billion, while other studies have estimated overall costs as high as $2.6 billion. The development timeframe is about 10 years. That’s because modern therapeutics target precise mechanisms to create better outcomes, but also have high failure rates. Only about 14 percent of all drugs that enter clinical trials are approved by the FDA. Pharma companies, therefore, have an exigent need to earn a profit.
Skewed Incentives Increase Costs
Pricing isn’t solely at the discretion of pharma companies, though. “What patients end up paying has much more to do with their PBMs than the actual price of the drug,” Patricia Goldsmith, CEO, CancerCare, says. Transparency is vital.
PBMs control patients’ access to therapies at three levels, through price negotiations, pricing tiers and pharmacy management.
When negotiating with drug manufacturers, Goldsmith says, “PBMs exchange a preferred spot on a formulary (the insurer’s or healthcare provider’s list of acceptable drugs) for cash-base rebates.” Unfortunately, 25 percent of the time, those rebates are not passed to insurers, according to the PBGH report.
Then, PBMs use pricing tiers to steer patients and physicians to certain drugs. For example, Kramer says, “Sometimes PBMs put a high-cost brand name drug in a preferred tier and a lower-cost competitor in a less preferred, higher-cost tier.” As the PBGH report elaborates, “(PBMs) are incentivized to include the highest-priced drugs…since both manufacturing rebates, as well as the administrative fees they charge…are calculated as a percentage of the drug’s price.
Finally, by steering patients to certain pharmacies, PBMs coordinate patients’ access to treatments, control patients’ out-of-pocket costs and receive management fees from the pharmacies.
Therefore, Goldsmith says, “As long as formularies are based on profits to middlemen…Americans’ healthcare costs will continue to skyrocket.”
Transparency into drug pricing will help curb costs, as will new payment strategies. What will make the most impact, however, may well be the development of a new reimbursement system designed to handle dramatic, breakthrough drugs. As Kramer says, “We need a better system to identify drugs that offer dramatic improvements in clinical care.”
Each afternoon, kids walk through my neighborhood, on their way back home from school, and almost all of them are walking alone, staring down at their phones. It's a troubling site. This daily parade of the zombie children just can’t bode well for the future.
That’s one reason I felt like Gaia Bernstein’s new book was talking directly to me. A law professor at Seton Hall, Gaia makes a strong argument that people are so addicted to tech at this point, we need some big, system level changes to social media platforms and other addictive technologies, instead of just blaming the individual and expecting them to fix these issues.
Gaia’s book is called Unwired: Gaining Control Over Addictive Technologies. It’s fascinating and I had a chance to talk with her about it for today’s podcast. At its heart, our conversation is really about how and whether we can maintain control over our thoughts and actions, even when some powerful forces are pushing in the other direction.
Listen on Apple | Listen on Spotify | Listen on Stitcher | Listen on Amazon | Listen on Google
We discuss the idea that, in certain situations, maybe it's not reasonable to expect that we’ll be able to enjoy personal freedom and autonomy. We also talk about how to be a good parent when it sometimes seems like our kids prefer to be raised by their iPads; so-called educational video games that actually don’t have anything to do with education; the root causes of tech addictions for people of all ages; and what kinds of changes we should be supporting.
Gaia is Seton’s Hall’s Technology, Privacy and Policy Professor of Law, as well as Co-Director of the Institute for Privacy Protection, and Co-Director of the Gibbons Institute of Law Science and Technology. She’s the founding director of the Institute for Privacy Protection. She created and spearheaded the Institute’s nationally recognized Outreach Program, which educated parents and students about technology overuse and privacy.
Professor Bernstein's scholarship has been published in leading law reviews including the law reviews of Vanderbilt, Boston College, Boston University, and U.C. Davis. Her work has been selected to the Stanford-Yale Junior Faculty Forum and received extensive media coverage. Gaia joined Seton Hall's faculty in 2004. Before that, she was a fellow at the Engelberg Center of Innovation Law & Policy and at the Information Law Institute of the New York University School of Law. She holds a J.S.D. from the New York University School of Law, an LL.M. from Harvard Law School, and a J.D. from Boston University.
Gaia’s work on this topic is groundbreaking I hope you’ll listen to the conversation and then consider pre-ordering her new book. It comes out on March 28.