Imaginary tense conversation from not so long ago: Physician: “I have to have my Covid patient on X medication or take them off X medication because otherwise they might die!” Researcher: “But you don’t even have the data to know if X medication is a good choice. If you keep your patient in the research protocol, soon we’ll know enough to make good decisions for future patients.” Upshot: After six million cases and counting, the U.S. has produced little useful clinical data on Covid-19 treatments. I have a great deal of empathy for the doctors with almost no tools working 24/7 to save their patients’ lives. Nonetheless, we botched an important opportunity to learn, even though we came up with a fancy name for our research effort – Patient-Centered Outcomes Research Institute – and spent millions of dollars on it.
In contrast, the U.K. did the more rational thing: beginning in mid-March, they instituted a Covid-19 treatment research program called Recovery in every hospital in the country. It learned that hydroxychloroquine and a lopinavir-ritonavir drug combo do not work. It also learned that dexamethasone, an inexpensive steroid (anti-inflammatory), does help with very sick patients. The British shared their findings with the whole world. Thanks, Britain!
If we drill down into the details of why the U.S. flopped and the U.K. soared, there’s a lot to learn about ease of clinical trial enrollment, types of trials, bureaucratic approval, government leadership, and organized national effort. Most of all, there’s something to learn about money, power, and who has a health care delivery system less siloed from its public health system.
Then there’s the question of vaccines. There’s so much competition globally to release the first reasonably acceptable vaccine that the World Health Organization is finding that some nations choose “vaccine nationalism”, which we could also call “me-first-ism”, over global collaboration. Is it a surprise that the U.S. has pulled out of an ethically admirable “Covid vaccines for all” international collaboration? Alas, no.
Since we’re likely to be vaccine nationalists, let’s look at how that’s going. We know the White House would like a vaccine to be approved in October, if not yesterday. This is partly (largely?) for political reasons. There is also clear public health urgency. I personally don’t know anyone who isn’t hoping for an effective, safe vaccine to be available when we wake up tomorrow morning.
It’s very easy to think of vaccines as extremely effective, as many of them are. But the bar for success of the Covid-19 vaccine has been set pretty low. For the FDA to approve it, it needs to show only 50% efficacy. (Or, the FDA can give emergency approval to something even less effective.) That’s the efficacy level of the flu vaccine some years – and we know that millions of people don’t find getting it to be worth the effort. Public health experts fear that with a not so great vaccine, people will act like they’re more protected by it than they are. Then the infection rate will rise and faith in vaccines will sink.
Our federal vaccine development is called Operation Warp Speed. Vaccine trials are being rushed and the traditional three phases of clinical trials are sometimes being compressed so that phases two and three are being conducted simultaneously. This makes scientists nervous for very good reasons. If a mediocre – or worse, unsafe – vaccine is approved prematurely, it’s going to be a terrible thing for the American public. (If you have questions about Covid-19 vaccines, here’s a resource: https://www.chop.edu/centers-programs/vaccine-education-center/making-vaccines/prevent-covid)
Would Americans actually get a vaccine if one were FDA-approved and available? A recent STAT / Harris Poll revealed that if a Covid-19 vaccine were approved quickly, over 80% of Americans say they “would worry about how safe it is.” Nearly as many worry that the vaccine approval process is “driven more by politics than science”. People say they want to get the vaccine, but there’s fear out there, too.
Breaking news: The CDC has announced that we should get ready for mystery Covid-19 vaccines “A” and “B” to be ready in as little as a month. As the New York Times reported, “Many of the details listed for the two vaccines — including required storage temperature, the number of days needed between doses, and the type of medical center that can accommodate the product’s storage — match what Pfizer and Moderna have said about their products, which are based on so-called mRNA technology. Neither company responded to requests for comment.”
To put the warp speed issue in perspective, on May 18, 2020, Moderna announced some Phase I (first phase in human) testing results: 8 of 45 human subjects had produced “neutralizing antibodies” in response to its vaccine candidate. That doesn’t mean the vaccine was safe or effective, merely that there was hope for it. On July 27, Moderna had leapfrogged ahead to Phase III (final phase) testing. Note that the phases of vaccine development typically take 10-15 years. The FDA’s website states that Phase III vaccine testing is typically 1-4 years, and that there’s a Phase IV that often follows it.
Here's information on successful vaccine technologies and which FDA-approved vaccines make use of them:
· Live, attenuated vaccine: Measles, mumps, rubella (MMR), Varicella (chickenpox), Influenza (nasal spray), etc.
· Inactivated/killed vaccine: Polio, Hepatitis A, Rabies
· Toxoid (inactivated toxin) vaccine: Diphtheria, Tetanus
· Subunit/Conjugate vaccine: Influenza (injection), Hepatitis B, Pneumoccal (re pneumonia), Meningococcal (re meningitis), HPV
In contrast, the mRNA technology that the Moderna vaccine is based on hasn’t produced a single vaccine approved for the public, though researchers have been working on the technology for over 20 years. So count me a bit skeptical that this fall will be the technology’s breakthrough moment.
Stay tuned for future developments, as the next few months are sure to be interesting. Just over a week ago, Dr. Robert R. Redfield, Director of the CDC, sent a letter to all 50 state governors. It states that federal agencies are preparing “to implement large-scale distribution of Covid-19 vaccines in the fall of 2020.” The McKesson Corporation has been contracted to do the distribution. It’s a huge company, probably as well-equipped as any to undertake the assignment, but it has been accused of sloppiness that helped fuel the opioid epidemic. Redfield’s letter asks on behalf of the CDC that our governors “consider waiving requirements that would prevent these [vaccine distribution] facilities from becoming fully operational by November 1, 2020.” Two days before the election! Are you thinking what I’m thinking?
Fingers crossed for a vaccine with good efficacy and an excellent safety profile that is released when it’s adequately tested. I think more than one vaccine will be approved over time, and it might be that the tortoise (that takes longer to come to market) is a better bet than the hare. Personally, I will be studying the fine print before I let anyone stick that needle in my arm.