This article about the February 2020 ACIP 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.
I attended a large part of the February 2020 ACIP meeting (Advisory Committee of Immunization Practices) in Atlanta, GA. I had planned to stay throughout, but my airline changed my return flight and I had to leave before the end on the second day. I did, however, watch the first day and the first two parts of the second.
The coronavirus crisis changed some things. For example, there were multiple international groups visiting the CDC (there was also at least one group that was there for other reasons and sat on part of the meeting). And we had a presentation on the topic from Dr. Nancy Messonnier.
I will describe the meeting in the order it happened, though this is the very abbreviated version. As I said before, an ACIP meeting is a geek’s dream – there’s a lot of data provided and in-depth discussions of details. The committee has a heavy and important responsibility, and since it was targeted by anti-vaccine activists is carrying it out under tricky circumstances.
Ebola Vaccine Discussion
After the initial introductions, the February 2020 ACIP meeting opened with two lengthy sessions on the Ebola vaccine. The question before the committee was whether to recommend the existing recombinant live virus vaccine licensed on December 19, 2019, by the FDA (for adults only) for three populations at high occupational risk of exposure to it –
- Individuals responding to an outbreak of Ebolavirus disease (EVD).
- Individuals who work as laboratorians and support staff at biosafety level 4 facilities (BSL-4) that handle the replication-competent Ebolavirus.
- Healthcare personnel at Ebola designated treatment centers.
The workgroup is considering other populations at risk but was not ready to make a recommendation about them.
Dr. May Choi discussed Ebolavirus disease and the vaccine against it, reminding us of the previous Ebola outbreaks, including the two largest (and recent) outbreaks – 2014-2016 West Africa and the current and ongoing outbreak in the Democratic Republic of Congo (DRC).
She reminded us of the high rate of mortality of the disease. She also added another interesting point of information – the fact that most who survive the acute illness suffer some sequelae, which could be severe – even blindness.
Data shows that within one year of discharge, Ebola survivors have 5-fold greater mortality than the general population. Studies suggest it may be linked to renal disease from acute infection. Data also shows that Ebola virus persists in immune-privileged sites (testes, eyes, brain, placenta) and can lead to continued disease transmission.
In the United States, 11 individuals total were treated for EVD, all as a result of the 2014-2016 West Africa outbreak, 9 infected in West Africa, and out of those 11, 2 (18%) died. There was only one case that led to secondary transmission in the United States, and that was to healthcare workers, in 2014.
It was initially developed by the public health agency of Canada and New Link Genetics, and Merck holds current intellectual rights. It only covers the Zaire strain of Ebolavirus. It’s administered as a 1ml dose. The vaccine’s protective effect is likely a combination of innate and adaptive immunity. Immunity persists for at least 12 months.
The vaccine was tested in a two-part phase III cluster-randomized open-label ring vaccination trial, at a time when the EVD outbreak was waning. Clusters were randomized to immediate vaccination or delayed (21 days later). Vaccine efficacy was 100%, so randomization was discontinued and all subsequent clusters offered immediate vaccination.
The vaccine was used in the DRC outbreak – ring vaccination started 1 week after the outbreak was declared. Evolved over time. First, it was given to contacts and contacts of contacts, then added potential contacts – people in the same area.
At this point, the Ebola vaccine was administered to over 200,000 people. No public data, but appears “quite effective”, and Serious Adverse Events (SAE) reported were “rare”.
The workgroup looked at safety generally, safety in pregnancy, concerns about transmission of the vaccine virus (which cannot cause Ebolavirus disease but can cause other reactions, including arthritis).
The workgroup conducted a literature search. In total 1818 published records were identified, and one unpublished record. 1742 were excluded after examining the abstract, 77 full texts examined, and finally, 18 articles with data from 11 studies were included in the qualitative analysis, 9 in quantitative analysis.
The workgroup walked us through a very detailed discussion of the data. The main problem was that the quality of the data was not very good, and there was limited data on most points. But what was showed that the vaccine was very effective and that the vaccine could cause arthralgia, arthritis or joint pain, but that those were mostly short-lived, and mostly not severe.
On pregnancy outcomes, there was one study – the Legardy-Williams, 2020 non-randomized sub-study. They found that 14 out of 31 pregnant women who were immediately vaccinated experienced pregnancy loss versus 11 out of 33 unvaccinated pregnant women. The rate of loss was not significantly different between the groups.
Three other studies without comparison groups showed 3 adverse pregnancy outcomes in 20 women, but the lack of a comparison group makes conclusions hard to draw.
Although this was reassuring, the small number of cases makes the data statistically weak.
While there is no evidence of actual transmission of the vaccine virus to others, there is evidence that the vaccinated are positive for it and that it sheds in saliva and urine. But that data is limited, so it’s unclear.
On safety, there were 12 studies, which included 19,184 individuals who received the vaccine – three Serious Adverse Events were judged related or possibly related to it. The two vaccine-related ones were a febrile reaction and anaphylaxis, and both resolved without sequelae. The one possibly related, flu-like illness, also resolved without sequelae.
Because there was no control group here, the quality of this data was also considered low.
So the disease is dangerous, the vaccine highly effective, and the risks low according to the current data, but there is uncertainty there, because of the limits of that data. And this is where some anti-vaccine people likely feel that, given the limits of the safety data, there is no room to recommend the vaccine to anyone.
The problem is that such an approach misses the risks of not recommending it. Ebola is a dangerous disease – not giving the high-risk populations the vaccine means they may face it without available protection. There is never complete information – making decisions under conditions of uncertainty is an important part of this expert committee’s job, and the question is when is there enough information to go ahead and make recommendations.
In this case, the workgroup felt that there was enough information to recommend the vaccine to these limited, high-risk groups – because there were available efficacy data and safety data in an outbreak setting that included over 19,000 individuals.
There followed a detailed discussion, with many questions from the committee, on the specifics of the data, going through every aspect of it. One concern the committee had was that the initial recommendation was only for “healthy, non-pregnant, non-lactating adults” – the concern was that this phrasing makes the vaccine inaccessible to pregnant women or less healthy adults that may find themselves in these high-risk situations. After discussion, a consensus was reached to remove the language but include warnings against use in pregnancy in the notes.
The language that ended up being proposed for the vote, after the workgroup worked on it during the lunch break, was that:
…pre-exposure vaccination with the vaccine is recommended for adults 18 years of age or older in the United States population who are at potential risk of exposure to Ebola virus (species Zaire ebolavirus) and:
• Are responding to an outbreak of EVD.
• Work as healthcare personnel at federally-designated Ebola treatment centers in the United States.
• Work as laboratorians or other staff at biosafety-level 4 facilities in the United States.
The vote was delayed until after public comment. To remove suspense, I’ll say here that the committee unanimously voted in favor of the recommendations (and that none of the public comments actually addressed them).
Public comment at February 2019 ACIP Meeting
As in past meetings, 18 individuals, out of all of those who requested to do so, were selected by lottery to make comments. In this case, four people registered to comment did not show up, and the comments came from 12 anti-vaccine individuals and two pro-vaccine individuals.
The two pro-vaccine individuals, Karen Ernst from Voices for Vaccines and Deborah Wexler from the Immunization Action Coalition, provided examples of how vaccines improved their lives and thanked the committee for its thorough work at keeping our vaccine supply safe and protecting our population (there was more, but this post is already too long).
I discussed the problems with the anti-vaccine comments previously,
and they were not much better this time. As before, the anti-vaccine comments were not on the topics discussed in the meeting.
While it’s not required that they be on topic – public comments can address general themes related to the committee’s jurisdiction – completely ignoring the meeting’s topic is an indication that the comments are being used, in this case, for goals not compatible with the goals of public participation.
Several comments were not even related to the committee’s general work. The anti-vaccine comments were generally inaccurate (if not grossly incorrect), dripping with anger and with very few relevant comments.
But there were some differences.
First, it was even more blatant than in the past that most commenters were not seeking to make meaningful contributions – to provide comment the committee can use to improve its decision-making – but to create videos aimed at believers, at inside members of the anti-vaccine groups.
This became obvious when one member asked to have a tripod to video the comments after she could not find a seating place that would allow her the angle she preferred.
Second, the tone of more of the comments was openly threatening and aggressive, even if the threats were not reality-based. One example was a commenter who warned the committee to expect “Nuremberg Trials” – clearly trying to scare the committee members with an imagined death penalty.
The comparison, of course, reflected the speaker’s lack of knowledge of history, law, and science more than anything else. The Nuremberg trials were an international tribunal addressing a post-war international situation, and are not a judicial recourse for complaints about an alleged violation of domestic laws.
The speaker also did not point out actual violations of law, and his view that the scientific consensus that vaccines do not cause autism, or the fact that the flu vaccine is our best defense against influenza, is incorrect, is not actually a substitute for pointing out legal transgressions. However much he would like to believe it, the fact that the Committee does not accept his anti-vaccine views is not a crime.
And of course, the comparison between the actions of the committee that recommends vaccines to protect children from disease and the holocaust does not reflect a good grasp of reality, either (for a more detailed discussion of that comment, see this and this). But however baseless the threat, the aggressive intent behind it was unmistakable, and a natural question is what someone this extreme – or some of the other extreme members of the anti-vaccine movement – will do once they realize that the threat alone doesn’t work.
Other comments also had threatening undertones – like the anti-vaccine activist who said:
We are awake. We are watching. And not going away.
Or the anti-vaccine activist who accused the committee of “crimes against humanity” and said:
Your gig is up. The public is no longer deceived. Think long and hard about what you’re doing.
Or the very angry anti-vaccine activist that suggested an undefined “they” could sue the Committee for false advertising, suggesting some deep misconceptions about these laws.
More than before, the undertone of the comments was angry, spiteful, and threatening (maybe because the focus was, in fact, on a photo op, and threatening comments go over better with their anti-vaccine audience) – a trend other commenters have pointed out in online comments, too.
One commenter targeted Dr. Paul Offit, taking issue with a comment the speaker alleged he made during a dinner with her and other anti-vaccine activists. Such a personal attack based on such a comment was out of line – this is not an official scientific statement but a passing comment in a social interaction where parties expect to be able to be at their ease.
Dr. Offit’s comments about vaccines during a social dinner are not anyone’s official position statements – not even his – and using them this way is a misuse. The lesson for Dr. Offit is that at least some anti-vaccine activists meeting with him for dinner are not there seeking to converse in good faith, but are looking for real or imagined gotcha moments to attack him in public with. Under such circumstances, dining with them is inadvisable.
The comments were also, this time too, consistently inaccurate (Obviously, I won’t cover all the errors). Among other things, the commenters repeated inaccurate claims blaming vaccines for autism, SIDS, and other things they don’t cause.
The inaccurate claim that only 1% of adverse events are reported to the Vaccine Adverse Event Reporting System (VAERS) was repeated, as were comments overstating the number of vaccine doses on the schedule. The incorrect claim that 54% of children suffer from chronic conditions was also mentioned.
Similarly, a doctor who specializes, among other things, in promoting unscientific, dangerous treatments like chelation for children with autism – in other words, whose business model is built on convincing parents that vaccines cause their child’s autism, and who speaks in anti-vaccine forums elsewhere – misrepresented a report by the Institute of Medicine, claiming it said there was (this is my summary, not a transcript): “no study on vaccine schedule. No study comparing vaccinated and unvaccinated individuals.”
What the report actually concluded on this was:
…the IOM committee finds no evidence that the schedule is unsafe. …
Existing mechanisms to detect safety signals—including three major surveillance systems of FDA-approved products maintained by the CDC and a supplemental vaccine safety monitoring initiative by the FDA—provide further confidence that the current childhood immunization schedule is safe.
On the unvaccinated v. vaccinated study, the committee said:
The committee does not endorse conducting a new randomized controlled clinical trial that would compare the health out- comes of unvaccinated children with their fully immunized peers. Although this is the strongest study design type, ethical concerns prohibit this study, as unvaccinated individuals and communities intentionally would be left vulnerable to morbidity and mortality. …
A new observational study, a complex undertaking that also would require a considerable investment, would be less likely than a randomized controlled clinical trial to conclusively reveal differences in health outcomes between children who are fully immunized and unimmunized children. Fewer than 1 percent of Americans refuse all immunizations. Enrolling sufficient numbers of unvaccinated children and matching them with vaccinated children of the same age, gender, ethnicity, and geographic location—a necessary step to rule out chance findings—would be prohibitively difficult and time-consuming.
The IOM committee finds analysis using existing databases to be the most feasible approach to studying the safety of the childhood immunization schedule. It concludes that the Vaccine Safety Datalink (VSD), a collaborative effort between the CDC and nine managed care organizations that monitors potentially rare and serious side effects after vaccines are marketed, is the best available system for studying the U.S. immunization schedule.
VSD data represent more than 9 million children and adults—roughly 3 percent of the U.S. population—and include medical details, such as the diagnoses and procedures associated with outpatient, inpatient, and urgent care vis- its. For this reason, the committee concludes that the VSD is currently the best available system for studying the childhood immunization schedule.
In other words, the committee ended very far from the doctor’s “do the study” demand he tried to use the report to demand.
One notable difference from past years is that the number of anti-vaccine activists attending seemed very limited. In past years, there were many of them – this time I doubt there were even twenty.
I can say more, but I am already spending more time than I wanted on what was, in reality, a short and less meaningful portion of an intense two-day meeting. So I will stop here.
After the public comment portion of the February 2020 ACIP Meeting, Dr. Nancy Messonnier from CDC gave an update on the unfolding coronavirus pandemic followed by a lengthy question and answer session. I initially had a lengthy summary of it. But things are moving fast, and her comments are already more or less out of date – they were before there was evidence of community transmission, and her main guidance was about preparing for a response. Here is a more recent update.
What I will point out is that after Dr. Messonnier finished her update, Dr. William Schaffner, a well-known expert and science communicator, opened his questions on the topic by thanking Dr. Messonnier for her open, clear communication – and the room reacted with a standing ovation. Dr. Messonnier answered questions openly and with detail, and there were many – the committee and the other experts were deeply engaged.
The next major session of the February 2020 ACIP meeting examined data about influenza. There was no vote from that session. But it was an extremely data-heavy one.
It included an update on a quadrivalent adjuvanted vaccine phase III trial, comparing that vaccine’s safety to that of a Tdap vaccine – and concluding, after close examination, that the adjuvanted vaccine was extremely safe.
It included an update on the current influenza season. Basically, the current influenza season has an unusually high number of hospitalizations of children, coupled with 105 child deaths – and a vaccine that’s 45% effective overall and more effective in children across the board. We were reminded that the much less effective influenza vaccine of 2018-2019 averted 3,500 deaths, 58,000 hospitalizations and 4.4 million cases of influenza – even with limited use – so the much more effective vaccine this year can have much higher benefits – and when we are not giving it to our children, we are doing them a wrong. They deserve protection.
Finally, we saw the result of a randomized controlled trial with about 600 people examining the safety of a trivalent adjuvanted influenza vaccine and a high-dose trivalent influenza vaccine and examining their absolute safety, too.
The short version was that both these vaccines were found about equally safe, and very safe. Both vaccines had local reactions, but most were mild, and only three were severe. There were no serious adverse events (SAE) that were found related to vaccination, and no real difference between the proportion of SAE between the groups. The main systemic reactions were fever, myalgia, malaise, and a few more, and “no systemic reactions led to a medical visit.”
Not only were these results reassuring, but they were consistent with the pre-licensure data of both vaccines, making them stronger.
The group ended by setting its plan for research going forward, and it’s planning several systematic reviews.
And with that, the first day ended.
The second day of the February 2020 ACIP meeting opened with updates from several agencies that, although fascinating, I will cut out to keep this post less monstrous than it’s turning out.
In the last session of the February 2020 ACIP meeting I could attend, they addressed the rabies vaccine, and specifically, the known data on using the vaccine for PreP – Pre-Exposure Prophylaxis. The workgroup’s plan was to provide more data on PreP by June, and provide some data on Post-Exposure Prophylaxis (PEP), and in October vote on the PreP recommendation and present more data on PEP, then in February 2021 vote on a PEP recommendation.
The focus of the discussion was on giving rabies vaccines to high-risk populations before exposure, as a precaution. Apparently there are about 15,000 people in the United States who get that vaccine as a precaution each year.
There are two licensed vaccines – a human diploid cell vaccine (HDCV) (Imovax) and purified chick embryo cell vaccine (PCECV) (RabAvert), and both are given intramuscularly, or IM.
The workgroup presented the safety data –
- VAERS reports – 1666 reports following HDCV – 94.3% non-serious. Systemic reactions – headache, pyrexia, nausea. Consistent with pre-licensure studies.
- VAERS for PCECV – 739 reports, 92.8% non-serious. Systemic – headache, pyrexia, nausea.
They reviewed literature from trials – 25 trials. Their findings were consistent with before – no changes to the observed safety profile.
Purpose of PrEP – partial immunity, but individuals still need PEP after exposure. Won’t need rabies immune globulin not given, vaccine series shorter. It’s aimed at people who may have unrecognized or frequent exposure to rabies virus or delays in starting PEP.
The workgroup presented a systematic review on the vaccines, among other things, comparing the recommendations as given since 1965 – three doses, at 0, 7, and 21 days – to other schedules. The data suggested two doses may be as effective as three short-term but could use a booster at a year. The committee’s goal in the next step was to examine whether to move to a two-dose schedule and whether to add a booster dose later.
To my intense chagrin, I had to leave the February 2020 ACIP meeting at this point.
As I said, the airline changed my flight, and I had to leave to catch it. I was especially sad to miss the session on polio vaccines and the switch from the oral polio vaccine to inactivated polio vaccine (which is given by injection), featuring Mr. John Salamone, who was extremely active in arguing for the switch after his son, David, was paralyzed by OPV.
I hope that next time, I can stay for the entire meeting.