With the current measles outbreaks in the US having, only a third of the way through 2019, surpassed the total number of cases seen in any year since measles was declared eradicated in 2000, thanks largely to pockets of unvaccinated children, you’d think that the antivaccine movement would be on the defensive. To some extent, it is, but as the number of measles cases climbs past 700 just since the beginning of the year, antivaxers are getting, if anything, more aggressive. They’re promoting legislation to make opting out of vaccine mandates easier, while trying to intimidate physicians, nurses, and advocates who speak out. Some of the antivaccine rhetoric is even getting disturbingly violent. In addition, the propaganda and conspiracy theories continue to flow in order to undermine public trust in the vaccination program. Enter ICAN (Informed Consent Action Network), an antivaccine group formed by Del Bigtree, producer of the antivaccine propaganda film disguised as a documentary, VAXXED.
I’ve been getting a number of inquiries on social media regarding a claim by ICAN that’s been making the rounds in the antivaccine underground and being thrown at science advocates as if to “prove” that the measles-mumps-rubella (MMR) vaccine wasn’t adequately tested before being approved by the Food and Drug Administration (FDA). Amazingly, this was an antivaccine claim that I hadn’t heard before; so I decided to investigate. First, let’s look at ICAN’s press release from last week, “MMR Vaccine Licensing Called Into Question Following ICAN’s Latest FOIA Exposure of FDA Coverup“:
In another significant legal win for vaccine risk awareness non-profit Informed Consent Action Network (ICAN), a new Freedom of Information Act disclosure from the Federal Food and Drug Administration (FDA) has revealed that the MMR vaccine was licensed based on clinical trials which in total had less than 1,000 participants and far more adverse reactions than previously acknowledged.
It’s alarming that an appeal was required to get this information, but it’s more alarming that every time ICAN prevails in obtaining a FOIA disclosure from the FDA, CDC or HHS, we learn about another serious shortcoming in their duties to assure Americans’ health and health care,” says Del Bigtree, ICAN founder and host of the weekly fact-based medical news show “The HighWire.”
“Vaccine risk awareness nonprofit”? More like vaccine risk massive exaggeration nonprofit or vaccine risk liar nonprofit. If there’s one thing we know about Del Bigtree (not to mention all groups who misuse the term “informed consent”) in their names, it’s that they massively inflate the risk of vaccination and attribute to vaccines complications, conditions, and diseases not caused by vaccines, such as autism, autoimmune disease, sudden infant death syndrome (SIDS), diabetes, and all manner of chronic health conditions, while massively underestimating the actual benefits of vaccination. That’s why I frequently refer to the antivaccine version of “informed consent” as misinformed consent. The idea is that, if you don’t know anything but what groups like ICAN tell you about vaccines, you’d be insane to vaccinate your child because the message these groups peddle about vaccines is that they don’t work very well and are dangerous—oh, and the diseases they protect against (e.g., measles) aren’t that bad, hence the “misinformed consent.” In the case of ICAN, just look at Bigtree’s video, in which he talks about eradicating “man-made diseases”; i.e., all the horrible things that, according to him, vaccines cause:
But what if ICAN is correct? It’s possible, albeit unlikely. Let’s look at Bigtree’s claims first, as enumerated in the press release. First, ICAN apparently got some documents using the Freedom of Information Act (FOIA) concerning the licensing of the MMR vaccine:
- There were eight clinical trials that in total had less than 1,000 individuals, out of which only 342 children received the MMR vaccine
- The safety review period only tracked ‘adverse events’ for 42 days after injection
- More than half or a significant percent of all participants in each of the eight trials developed gastrointestinal symptoms and upper respiratory infections
- All adverse events were generically described as ‘other viruses’ and not considered in safety profile of licensure
- The control group received other vaccines for either rubella or measles and rubella, and none of the controls received a placebo (an inert substance such as a saline injection)
As is the case of many antivaccine claims, what’s left unsaid is far more important than what is said. Let’s just say that the characterization above leaves out a lot of important information. I’ll dismiss the last charge right now, because it’s a common antivaccine trope that betrays a complete lack of understanding of clinical trial ethics. Here’s a hint: there already exists an effective treatment or vaccine for a condition or disease, it is unethical to do a placebo-controlled trial because that would require leaving the control group untreated or unprotected. The only ethical way to test such new therapeutics or vaccines is against the existing standard of care; that way no subject in the trial is intentionally left untreated or unprotected. I know that Bigtree knows this because science advocates have been telling him this ever since he emerged as the darling of the antivaccine movement; so here he’s clearly being intentionally deceptive, knowing that his audience won’t question his claim and will eat it up. He does a lot more of the same in this Highwire video from a month ago:
It’s a long video
So what’s the real story.
Things left unsaid
The press release leaves out a lot, as will become apparent if you look at the actual documents received by ICAN as a result of its FOIA request. The very first page is an approval letter dated September 15, 1978. If you know anything about the MMR vaccine, this should raise a red flag. The original MMR vaccine was approved in 1971. So this isn’t about the trials used to license the original MMR vaccine. So what is it about? Well, read the letter:
This is to inform you that the amendments to your product license applications to include the use of RA27/3 strain rubella virus grown in human diploid cells have been accepted for manufacture of the following products:
Rubella Virus Vaccine, Live
Measles Mumps, and Rubella Virus Vaccine, Live
Measles and Rubella Virus Vaccine, Live
What we’re talking about here is the second iteration of the MMR vaccine. As explained on Vaxopedia:
As most folks know, the original MMR vaccine, which combined the separate measles, mumps, and rubella shots, was licensed way back in 1971.
It included the original rubella vaccine, which was made with a duck embryo derivative of HPV-77 that was attenuated by passing it 77 times in monkey kidney cells.
Before the new conspiracy theories start, no, not that HPV.
It stands for High Passage Virus.
And while the vaccine worked, it didn’t work as well and caused more side effects than a RA27/3 rubella vaccine that was already approved in Europe:
“Over the next decade, accumulating evidence led to changes in the United States. First, the duck embryo and dog kidney vaccine strains caused significant joint reactions [24–27]. Second, reinfection on exposure to wild rubella virus was demonstrated frequently with all strains except the RA 27/3 vaccine [28–30]. Third, the good safety record of the RA 27/3 vaccine in Europe, the majority opinion of scientists, led the US Food and Drug Administration to license RA 27/3. Important pressure for this decision came from Dorothy Horstmann at Yale, who was convinced by her comparative studies of rubella vaccines , and by Maurice Hilleman at Merck, who sought a better rubella strain for measles-mumps-rubella (MMR) vaccine.”
Stanley Plotkin on The History of Rubella and Rubella Vaccination Leading to Elimination
So that’s it, they just changed out the rubella component for one that was safer and worked better.
So basically, a minor change was made in the MMR vaccine, substituting a different strain of rubella virus to use one that had already been approved for use in Europe with a subsequent good safety record. Not only that, but scientists went a step further and did a controlled cohort study comparing the new MMR vaccine to folks who didn’t receive any vaccine at the time of the study. This is, of course, a perfectly acceptable methodology when the primary outcomes measured are not subjective, like antibody responses. It is also not unreasonable only to follow patients a relatively short period of time after vaccination when what is being tested is a relatively minor change to the formulation of an existing vaccine with an excellent safety record. As noted in Vaxopedia, the studies leading to the licensure of MMR II followed much, much larger randomized controlled studies of the individual measles, mumps, and rubella vaccines. Basically, the measles vaccine was safe in 1968 when it was approved, as was the mumps vaccine in 1967 and the rubella vaccine in 1969. So was the MMR vaccine when it was approved in 1971, as was MMR II when it was approved in 1978.
In fairness, in his Highwire video (above), Del Bigtree does note that the clinical trials he is ranting about were for MMR II, not the original MMR; the press release, however, makes no mention of that or even the year. In addition, Bigtree also misrepresents the reasons why the changes in MMR were made to produce MMR II as being because Stanley Plotkin wanted to switch to a strain of rubella that could be grown in one of the cell lines derived from a human fetus, rather than because of concerns about joint reactions due to the strain of rubella virus being used in the originally approved MMR formulation. Amusingly, he confidently asserts that this would be the first MMR using a rubella strain grown on “aborted fetal DNA”, a howler of a scientific misstatement. (Del, I’d love to see someone try to grow a virus on fetal DNA. It currently takes cultured mammalian cells to grow a virus like rubella in sufficient quantities for a vaccine, you scientific ignoramus!) Naturally, he prefaces this with a rant about how children are being quarantined because their parents have not accepted this “ritual” of injecting “toxic products” multiple times in their life, they’re not allowed to go to school or synagogue (at approximately the 42 minute mark). Hilariously, he also glowingly cites Andrew Wakefield’s now retracted 1998 Lancet paper that started the whole MMR-autism conspiracy theory, in particular the claimed association between MMR vaccination and GI complaints. This little gem will become relevant in the next section.
As for “not being adequately studied” or not being studied for a long enough time, Bigtree is full of poop emoji there, too. Arguably, MMR II is the most studied vaccine in history. Unfortunately, a lot of the more recent studies of the vaccine came about because of Bigtree’s partner in crime with respect to making VAXXED, Andrew Wakefield, and his bad science suggesting that MMR can cause autism, but nonetheless MMR has been massively studied—and continues to be massively studied—for safety. There’s even been a double-blind, placebo-controlled crossover study of adverse reaction to MMR vaccination in twins! OK, the placebo wasn’t saline, but rather the same product including neomycin and phenol-red indicator but without the viral antigens, but, unlike what antivaxers try to claim, that is a perfectly acceptable placebo for a trial like this. Arguably it’s better than a saline placebo because it allows identification of whether any adverse effects observed were truly due to the vaccine antigens, particularly when you remember that MMR doesn’t contain aluminum adjuvants or mercury-containing thimerosal preservative, two of the biggest bogeymen in the antivaccine universe. But, hey, if antivaxers want saline controls, I’ll give them saline controls. Yes, there are randomized, double blind clinical trials of MMR II using saline as the placebo control. Granted, it wasn’t tested that way before FDA approval, but that’s because it didn’t need to be given that MMR II was a minor modification to the original MMR and the rubella strain being substituted already had an excellent safety record in Europe.
So, we’ve taken care of important things left unsaid by ICAN that show that, contrary to what ICAN claims, MMR II was tested adequately and since has been tested in double-blind, saline placebo controlled trials. Del is either ignorant or lying when he claims that the MMR was “never tested” in a double-blind saline placebo-controlled trial. But what about the claim of lots of adverse reactions that the FDA is “covering up”? As with ICAN’s other claims, there’s less there than meets the eye.
How to deceive with numbers the Del Bigtree way
The ICAN press release mentions that more “than half or a significant percent of all participants in each of the eight trials developed gastrointestinal symptoms and upper respiratory infections” and “adverse events were generically described as ‘other viruses’ and not considered in safety profile of licensure.” That sounds damning, doesn’t it? Not so much if you look closer. Fortunately for me, Magdalen Wind-Mozley wrote a long Facebook post that delves into this question and helped me enormously in perusing the tables that Bigtree so confidently discusses in an alarmist nature as he tries to imply strongly that all these symptoms were evidence that MMR really was causing autism in these children:
I’ll quote liberally where appropriate for those of you who don’t have FB accounts. The studies that Bigtree zeros in on are trials #442 and #443 (pages 9-43). Basically, the money discussion by Wind-Mozely comes after she describes how vaccine trials use a study diary, where every day parents would take their child’s temperature and grade a list of symptoms, commenting if they so desired:
Del instead wants you to think of “GI issues”; because we all know GI issues are associated with…autism.
He also wants you to believe that some children suffered for these symptoms for the whole period of the trial. Which is I think (being perhaps overly generous to Del) because he’s misunderstand the summary table.
You can see the sheet image attached, it records data for each day. In the summary table there are time periods, days: 0-4, 5-12, 13-18, 19-28 and 29-42.
So a child might be sick on day 3, have a tummy ache on day 20 and diarrhea on day 33; and be counted 3 times.
Also in the summary table is a column which tells you how many individuals were affected over the full 42 days.
In the case of GI issues this number is 43/102 children.
Del makes huge play of this number!
Mentioning autism, and claiming he “couldn’t make it up”.
As a comparison, she decided to ask members of a mothers’ forum of which she is a member how many of the mothers’ children had GI symptoms in the last 42 days, noting a couple of caveats. First, none of them were in vaccine trials, and, second, they weren’t filling out symptom diaries every day. If you’re in a trial and filling out a symptom diary every day, you’re definitely likely to be more vigilant looking for even minor symptoms than you would be otherwise. She also chose parents of children under 4 because 84% of the children in the trials were under 4. She also quite sensibly noted the limitations of her approach, which wasn’t scientific (obviously) and not systematic. Still, I think it’s worth noting:
I asked the question “Has your LO had an upset tummy over the course of 42 days? and captured the data at 200 responses.
I qualified the “upset tummy” by citing the symptoms from the study sheet:
“So including, BUT NOT RESTRICTED TO:
And what do we find? Out of 200 votes we have:
Those currently with a baby/small child reporting yes: 76
Those currently with a baby/small child reporting no: 83
Which gives us 48% with “GI issues”, compared with Del’s supposedly terrifying bombshell of 42% (43/102)
Those who are recalling a child who has now grown up:
Reporting yes: 13
Reporting no: 28
Which gives us 32% with “GI issues”.
Her conclusion: Minor GI issues in very young children are very, very common, or, as she put it in the comments: “Tl:dr (too long:didn’t read) version: little children vomit and have explosive poos. Nothing to do with vaccines…”
I know what you’re thinking: But, Dave, dude, this is just an unscientific survey on a mothers’ discussion group! Is there scientific literature that can help us? The topic is a complex one because, again, GI complaints are very common, so common that a lot of times parents don’t even take their children to the doctor for them, making it difficult to study this empirically. We know that the prevalence of recurrent abdominal pain in children can range from 11% to 45%. A 2016 systematic review of functional GI disorders in infants and toddlers found that infant regurgitation and functional constipation can be as high as 25.9% and 31%, respectively, although the authors noted that “included studies were of moderate to poor data quality with respect to absence of confidential interval for prevalence rate and inadequate sampling methods” and concluded that the “scarcity and heterogeneity of FGID data call for the necessity of well-designed epidemiological research in different levels of pediatric practice and refinement of diagnostic.” Another systematic review, this time from 2017, found that functional gastrointestinal disorder (FGID) “prevalence rates for student samples ranged from 9.9% to 29% to as high as 87% in clinical samples. Cyclic vomiting, irritable bowel syndrome and functional constipation were the most researched conditions, with a prevalence ranging from 0.2% to 6.2%, 0% to 45.1% and 0.5% to 86.9%, respectively.” The bottom line is that GI symptoms are very common in children, and, because data regarding their prevalence is relatively poor quality, their prevalence likely underestimated. Basically, 40% of parents with children in a vaccine trial noting GI symptoms during 42 days sounds alarming, but isn’t. GI complaints are very common in young children, as any pediatrician will tell you. Most are self-limiting and not severe.
I can’t help but mention here that in the double-blind placebo controlled twin study of MMR, “respiratory symptoms, nausea, and vomiting were observed more frequently in the placebo-injected group than in the MMR vaccinated group.” Unfortunately, this is not directly comparable to study #443 ranted about by Bigtree, because the questionnaire in this study did not include a daily diary and the only GI symptoms asked about were nausea and vomiting. The bottom line is that MMR is not associated with a markedly increased risk of significant GI symptoms nor, by Bigtree’s implied association, autism.
MMR is very safe, and Del Bigtree is deceiving by omission again
In response to the current outbreaks, the FDA issued a statement two weeks ago:
The MMR vaccine has been approved in the United States for nearly 50 years to prevent measles, mumps and rubella (also known as German Measles). As a result of its use, measles and rubella were completely eradicated in the United States, and mumps cases decreased by 99%. Large well-designed studies have confirmed the safety and effectiveness of the MMR vaccine and have demonstrated that administration of the vaccine is not associated with the development of autism. However we’re seeing an increasing number of outbreaks of measles in communities across the country, including those in New York, New Jersey, Washington, California, and Michigan.
We do not take lightly our responsibility to ensure the safety and effectiveness of vaccines, and work diligently to assess safety and effectiveness of all licensed vaccines for their intended uses. The MMR vaccine is very effective at protecting people against measles, mumps, and rubella. It also prevents complications caused by these diseases. And we have nearly 50 years of experience and evidence supporting that fact. In fact, according to the CDC, two doses of the MMR vaccine beginning at 12 months of age (the recommended dosing schedule) are 97% effective against measles, 88% effective against mumps, and 97% effective for rubella.
Like many medical products, the MMR vaccine has known potential side effects that are generally mild and short-lived, such as rash and fever. If parents have concerns about these side effects, we recommend that they speak with their health care providers about the benefits and risks of vaccines, along with the potential consequences of not vaccinating against diseases.
Bigtree’s “blockbuster” revelation is neither a revelation nor a blockbuster, except perhaps for being a blockbuster of cluelessness, deception, or both. Whether Bigtree’s deception by omission regarding the approval of MMR II by the FDA is unintentional and due to scientific ignorance or intentional and due to mendacity, I don’t know. I tend to think the former because Bigtree has demonstrated his scientific misunderstanding and cluelessness more times than I can recall, but maybe he’s smarter than that and it’s the latter. I don’t know and it doesn’t matter. Either way, Bigtree is, as usual, wrong as wrong can be. MMR II is incredibly safe, very effective, and does not cause autism. His fear mongering based on misinformation does nothing other than make the current measles outbreaks more difficult to bring under control by frightening parents about the MMR vaccine.