This article about the August 2020 ACIP COVID-19 vaccines meeting was written by Dorit Rubinstein Reiss, Professor of Law at the University of California Hastings College of the Law (San Francisco, CA), who is a frequent contributor to this and many other blogs, providing in-depth, and intellectually stimulating, articles about vaccines, medical issues, social policy, and the law.
Professor Reiss writes extensively in law journals about the social and legal policies of vaccination. Additionally, Reiss is also a member of the Parent Advisory Board of Voices for Vaccines, a parent-led organization that supports and advocates for on-time vaccination and the reduction of vaccine-preventable disease.
On August 26, 2020, the Advisory Committee on Immunization Practices (ACIP) held an emergency meeting to discuss COVID-19 vaccines. This was an emergency meeting, as opposed to one of its three annual scheduled meetings, but it was not “emergency” in the sense of being unplanned – it was announced long in advance, and the announcement was repeated during the June and July emergency meetings.
The ACIP COVID-19 vaccines meeting consisted of four to five hours of presentations from the COVID-19 vaccines workgroup, convened in April, and one hour of public comments that included multiple pro-vaccine speakers and four anti-vaccine individuals.
The main takeaway most people would have from the meetings are, I expect, the same as mine – that COVID-19 vaccines safety is taken extremely seriously by the workgroup and the committee, that there is still a lot of uncertainty about which of the vaccine in the pipeline will be effective, and that there are thorny, hard questions in deciding how to allocate the first vaccine doses.
This will be a very short overview of the meeting. The next meeting is on September 22, and I encourage and urge people to listen and learn from it. The presentation slides for the previous meetings can be found here.
ACIP COVID-19 vaccines meeting – introduction
The meeting opened with an introduction by Dr. Beth Bell, the chair of the ACIP Covid-19 vaccines workgroup, and a professor of Global Health in the University of Washington. Dr. Bell explained that there are currently over 200 COVID-19 vaccines in development, and 4 large clinical trials ongoing. The ACIP COVID-19 vaccine workgroup meets weekly, to oversee the data on these vaccines and discuss other issues.
Dr. Bell’s presentation was followed by two presentations by industry representatives: Dr. Jacqueline Miller, who spoke to Moderna’s vaccine candidate’s trials and Dr. Nicholas Kitchin who talked of the trial data for Pfizer’s candidate.
Moderna’s coronavirus vaccine candidate is mRNA-1273. Dr. Miller described the vaccine – an mRNA sequence for the coronavirus spike protein, and how it’s assembled inside the body. This vaccine will be given on a two-dose schedule, 28 days apart. The vaccine requires cold storage – it needs to be shipped and stored at -33º (-28ºF).
There is preclinical data described by Dr. Miller as “strong neutralizing antibodies in mice, aged mice, and non-human primates. Robust protection, no indication of enhanced respiratory disease after viral challenge even when sub-protective doses of mRNA-1273 used.”
Human clinical studies started in March with a phase one trial that included three age groups – 18-55, 56-70, and over 71. Three doses were studied initially – 250, 100, and 25 mcg. Since there were high levels of fever in the young group for the 250 mcg dose – no lasting harm, but seizures – they stopped using that dose, and continued with the 25 and 100 mcg doses. Phase II trials started in May, phase III, funded by the government, started July 27, still recruiting, and aims for 30,000 participants.
The main interesting point of the studies is that all three phases will include at least one year follow up. They ended up selecting the 100 mcg dose for the larger trials – it induced better titers of antibodies against COVID-19 than 25 mcg and was also well-tolerated, with very little moderate or more reactions, most of them injection site pain, fever, and that’s not uncommon.
There were no serious reactions reported.
The immune data at this point is based on titers, not infection rates, but those were promising – the data shows neutralizing antibodies titers – titers equivalent to the higher dose you find in people that recovered from a COVID-19 infection – across all age groups, including those over 71.
This is promising because often vaccines work less well in the elderly. Of course, you need to be careful, because the interaction between having antibodies and being immune can be complex, but it’s promising, and a reason to continue trials.
Generally, the conclusion was:
…the data is encouraging, but limited and in a fairly homogenous population. Also need to study pediatric subjects, pregnant women, immunocompromised patients.
In response to questions, Dr. Miller also clarified that there was “no indication of enhanced respiratory disease and no inflammation in lungs.”
So it’s a good start.
I have a more limited summary of the second vaccine presentation, since it coincided with kid care (the east coast/west coast time issue didn’t help). Pfizer’s trials will also go on for a long time – they’re scheduled for 24 months. One person out of the trial was hospitalized but was fine, and the results were promising enough for the company to move to a larger phase 1 trial with 195 subjects in two groups – 18-55 and 65-85. The company looked at two vaccines, and chose one – BMT162b2 – as the candidate to move on because it had “better reactogenicity profile in younger and older adults, stronger T-cell responses, earlier clearance in challenged monkeys.”
The company also considered the safety profile “acceptable”. So this, too, has promising early results but is at an early stage, and we still don’t know if it will be effective or safe.
Also, this vaccine, too, needs cold storage – at a colder temperature, below -57º (70ºF) That’s a concern because it means distribution and storage needs to be done right, and it may be a challenge to some clinics. If this vaccine shows promise in clinical trials there will be practical issues to solve.
ACIP COVID-19 vaccines meeting – safety
Dr. Tom Shimabukuro Covid-19 Vaccine Safety Monitoring
This presentation is worth your time watching in full when the video is available. Here are the slides, which are also worth looking at:
What this presentation showed is that in addition to the large trials before licensing, Covid-19 vaccines will be subject to extremely extensive safety monitoring. This will draw on a combination of the existing and extensive safety monitoring mechanisms and new approaches. A lot of effort is already going into planning for and preparing safety monitoring, showing how seriously people take safety.
Existing safety monitoring will include:
- VAERS – the passive reporting monitoring system.
- Three active monitoring systems for adults: CMS (Medicare and Medicaid Services data), VSD, and Veterans Affairs data.
- VSD for children, and two FDA systems that cover them – BEST and PRISM.
- Department of Defense (DOD) surveillance.
- Indian Health Service monitoring.
- Case reviews in multiple ways.
New programs will look more specifically at healthcare workers – assumed by all to be among the first groups to get the vaccines – and will include active questioning.
Basically, a lot of effort is already going into safety, and aggressive oversight is planned.
ACIP COVID-19 vaccines meeting – epidemiology
The next presentation looked was from Dr. Nancy McClung who discussed the epidemiology of individuals who might be at increased risk from the COVID-19.
Basically, the USA is not doing well. Cases are increasing. The numbers are going down, but the daily level is still high.
As of August 23, there were 176,223 deaths from COVID-19 reported to CDC. Dr. McClung presented the mortality trends – it peaked in April, declined in June, then goes up again, and is stable at about 1000 deaths per day. To be clear, 1000 COVID-19 deaths a day is not a good place to be.
Who is at special risk? Adults 65 and older and people of any age with certain underlying medical conditions are at increased risk of severe illness, hospitalization, and death from Covid-19. The presentation went in detail into this, but I’m worried that this post is already getting too long. The full presentation can be found here. It is painful.
ACIP COVID-19 vaccines meeting – allocation of supply
Dr. Rachel Slayton examined the modeling of allocation strategies for the initial coronavirus vaccine supply. She presented two strategies for the initial allocation of the first doses of vaccine supply. It addressed both general allocations, prioritized by occupation and risk factors (age and additional conditions), and allocation in nursing homes.
Generally speaking, she suggested that allocating by profession will have a 3-4% reduction in both infection and deaths. Allocating by age will not decrease infections as much, but will reduce deaths by 8.6%.
For nursing homes, it found that giving the vaccines to staff would decrease infections and deaths more than vaccinating residents (though vaccinating residents would also reduce both).
This is an unfairly truncated version of a long, thoughtful presentation available here.
ACIP COVID-19 vaccines meeting – workgroup interpretation
Dr. Sara Oliver provided an overview of the entire day. It can be found here.
Her main points were:
- There are multiple vaccines in trials.
- Trials are actively recruiting.
- There are different types of vaccines in the works: viral vector, mRNA, sub-unit, inactivated.
Workgroup interpretation of clinical trial data showed:
- Moderna vaccine – reactogenicity higher after the second vaccination, no serious adverse events (SAE).
- Pfizer/biotech – local and systemic symptoms.
Both have plans for stage III trials. Both have extremely low-temperature supply chain requirements.
The workgroup thought phase I data shows neutralizing antibodies at 7 days that are more than convalescent plasma, which supports going to phase III clinical trials. Low-temperature supply chain issues may have an impact.
The workgroup emphasized the need for diverse study participants and for sufficient time after dose 2 to evaluate safety signals, report on the maternal and fetal outcomes, assess the effect on shedding and transmission among the symptomatic and asymptomatic groups. It reminded companies to consider trials in other populations, like children and pregnant women.
The presentation went over the epidemiology and models on allocation discussed above, too.
ACIP COVID-19 vaccines meeting – next steps
Dr Kathleen Dooling made the last presentation which described the focus of the workgroup. Its goals are to assure that we have a safe and effective vaccine. That the vaccine reduces transmission, morbidity, and mortality of COVID-19 and reducing disturbance from the pandemic.
The presentation reviewed who is at high risk from COVID-19, what are the implementation challenges for the vaccine, and so forth. It ended with the next steps:
The main thing I will say about the public comment during the ACIP COVID-19 vaccines meeting is that portions of it fit the purposes of public comment – addressing what the agency – in this case, the advisory committee – does, giving it input, and letting citizens feel heard. For example, addressing the allocation of vaccines – something discussed during that very meeting.
Dr. Montoya-Barthelemy argued for giving vaccine priority to those incarcerated and those in other congregate care – places where there have been COVID-19 clusters.
Lindsey Clark from the Alliance of Aging Research encouraged ACIP to have more geriatric experts on the committee since part of their work is recommending vaccines for the elderly – another comment directly offering useful advice.
Deborah Wexler from the Immunization Action Coalition reminded members that flu season is coming, and together with Covid-19, can be harmful – and thanked ACIP for emphasizing that need and discussing how to increase uptake.
Nisa Shaffi from the National Consumers League reminded the committee how important it is that Covid-19 trials be inclusive of all demographics – also directly related to the day’s discussions. Less directly advising the committee, but related to vaccine uptake, Shoshanna Fishbein from Families Fighting Flu encouraged more use of stories in vaccine advocacy.
One fun comment was from a Mr. Erwin, from the Fraternal Order of Real Bearded Santas, who called for harnessing the power of Santas to fight diseases.
On the other hand, the anti-vaccine commenters (apparently, there’s a YouTube channel that collects their comments) seemed unaware of the day’s discussion.
For example, anti-vaccine activist Del Bigtree, ignoring the detailed presentations and discussion of the vaccines’ safety and studies, argued that there are no safety controls in place and warned – almost threatened – the committee members that approving the vaccine would lead to disaster and it will be their fault (ignoring, by the way, the harms of the disease).
Similarly, an anti-vaccine nurse- Mariah Gahry – claimed that COVID-19 mortality is small – ignoring the discussions that mentioned the 170,000 and more dead – and the risks of the vaccines “huge” – when the vaccines have not yet undergone clinical trials, and large parts of the day was devoted to discussing how to make sure they’re safe and do not have more than small risks.
The final speaker – an anti-vaccine activist named Lee Ducat, who expressly asked to go last – also did not provide any useful advice or addressed the actual discussions. She claimed that recent lawsuits showed the CDC provided vaccines to children that were not placebo tested.
There are no such lawsuits to my knowledge, and many vaccines were placebo tested (see here under phase III trials, here, and here), so the claim is not credible. She alleged that without inert placebo testing no one can claim the risks of a vaccine are less than the risks of the infection – something that is generally untrue since there are other kinds of studies.
Indeed, decades of studies and extensive monitoring show that vaccines’ risks are very small, and benefits large.
As for COVID-19, the presentations of the day highlighted both the risks of the disease and the mechanisms in place to ensure the vaccines will be safe. The speaker continued in this vein, clearly not even trying to offer on-point suggestions.
These anti-vaccine comments reinforce a point I made in the past. Public participation has important goals. It can improve agency decision making and provide participation benefits to citizens. But when it’s used for anti-vaccine posturing – to create theater, videos that can be used as propaganda, without a goal to address the policy-making or participation benefits – it is misused.
ACIP needs input. But there is no need to get that input in ways that allow anti-vaccine activists to use the process as theater or propaganda. It is legal – and under the circumstances appropriate – to limit participation to written comments to prevent such misuse.
It would be a shame to lose oral commenting, but the misuse makes its harms – allowing anti-vaccine activists to create short propaganda videos, of no value to the committee, that they can then present as “testimony to the CDC” – outweigh any benefit that would not be captured by allowing written comments.