Can we just say that vaccines are safe, already? Can we just say that, of all the medical interventions ever conceived by the minds of humans, vaccines have almost certainly saved more lives and prevented more illness? Can we finally say that vaccines do not cause autism?
Of course not, unfortunately. I ask the same question about whether we can finally say that the earth isn’t 6,000 years old, but rather billions of years old, and there are still people out there who believe that evolution is a sham and the earth really is only 6,000 years old. Truly, the irrationality of humans is without bounds. So it is with vaccines, where, despite mountains of evidence testifying to their efficacy and safety and large studies failing to find even the whiff of a hint of a link between vaccines and autism that, for all intents and purposes, it is reasonable to conclude that there is no such link. None of this stops antivaccinationists from demonizing vaccines as a major cause of the “autism epidemic,” sudden infant death syndrome (SIDS), asthma, cancer, and just about every disease you can think of.
That’s why it always warms the cockles of my heart (if a Plexiglass box of blinky lights has a heart) to see yet another study trying to drive a stake in the heart of the vampire that is the myth that vaccines cause autism. In any rational world, the myth would have exploded into a pile of red goo and blood, like the vampires in True Blood when they’re staked, but, again, this is not a rational world. Still, it’s always worth reviewing more evidence that vaccines are safe, and yesterday there was a doozy of a summation of that evidence published in Pediatrics in the form of a massive review of the evidence regarding vaccine safety carried out by investigators from the RAND Corporation, UCLA, and Boston Children’s Hospital.
This study came about because the Agency for Healthcare Research and Quality (AHRQ) requested an evidence report on the safety of vaccines recommended for routine immunization of adults, children, and adolescents. in order to identify gaps in evidence. This review article therefore reviews the safety of vaccines recommended for routine use in children aged 6 years and younger and presents the results of a comprehensive and systematic review of scientific evidence, describes statistical associations between vaccines and adverse events (AEs), and reports on any risk factors identified. And, boy, was that review big:
As presented in Fig 1, 20,478 titles were identified through electronic literature searches; review of product inserts; review of Food and Drug Administration, Advisory Committee on Immunization Practices, and other Web sites; reference mining; and requests for Scientific Information Packets from drug manufacturers. Of those, 17 270 were excluded on review of abstract or title for reasons such as “not about a vaccine,” “vaccine not within the scope of this project” (formulations never available in the United States, recommended only for travel), or because they were animal studies. Upon full text review of the remaining 3208 articles, 392 were identified as relevant background/theoretical materials and set aside as potential references for the Introduction; 2749 other articles were excluded. The most common reason for exclusion was lack of suitable study design (1549): individual case reports, nonsystematic reviews, and studies using passive surveillance were excluded. Many publications (458) discussed vaccines on the recommended schedule but did not report or assess AEs. Eighty-eight studies on adults or adolescents were excluded for this article, as were 11 studies of children with preexisting conditions such as HIV, juvenile arthritis, or cancer, which left 67 studies. These studies are in addition to those included in the 2011 IOM consensus report Adverse Effects of Vaccines: Evidence and Causality, which were not abstracted.
The schema is illustrated below:
People often wonder why such a large collection of references is routinely winnowed down so much in these review articles, it’s because the initial search is designed to find as many articles as possible, and the subsequent culling is designed to get rid of irrelevant articles, articles thad don’t meet the predefined quality criteria, and the like. For instance, in this case, articles that dealt with vaccines that are no longer used would not be relevant to the specific question the investigators were interested in, namely the safety of the current vaccine schedule. I’m sure this will be something that antivaccinationists attack, saying that their children were “vaccine injured” even though the vaccine that “injured them” aren’t used anymore.
Another important aspect of such a study is to evaluate the quality of adverse events (AE) reporting. In this case, the authors used the McHarm scale, which is the name for the McMaster Quality Assessment Scale of Harms. It’s a scale that requires yes/no answers (or whether it’s unsure) to questions like:
- Were the harms PRE-DEFINED using standardized or precise definitions?
- Were SERIOUS events precisely defined?
- Were SEVERE events precisely defined?
- Were the number of DEATHS in each study group specified OR were the reason(s) for not specifying them given?
- Was the mode of harms collection specified as ACTIVE?
- Was the mode of harms collection specified as PASSIVE?
- Did the study specify WHO collected the harms?
- Did the study specify the TRAINING or BACKGROUND of who ascertained the harms?
- Did the study specify the TIMING and FREQUENCY of collection of the harms?
There are more questions, but you get the idea. Here’s a sample analysis for a series of studies used in a systematic review and meta-analysis of cognitive enhancers for patients with mild cognitive impairment.
Next, the authors basically listed their findings for each vaccine that is used. For example, for the DTaP (Diptheria-Tetanus-acellular Pertussis) vaccine, they found:
The IOM studied diphtheria toxoid, tetanus toxoid, and acellular pertussiscontaining vaccines alone and in combination in both children andadults. The IOM committee did not find evidence that “favors acceptance” of causal relationships for any conditions. They found the evidence “favors rejection” of a causal relationship between type 1 diabetes and vaccines containing diphtheria toxoid, tetanus toxoid, and acellular pertussis antigens. We found no additional studies in children published after the IOM search date; our review of their assessment supports their conclusions.
In other words, the authors found no good evidence suggesting that DTaP causes diabetes or any other condition.
And so it goes. For example, the Hib vaccine was associated with redness at the injection site and swelling, but not with hospitalizations, nor was it associated with fever or any other serious AEs. A summary of the findings by the authors includes:
- Support for the IOM results that the vaccine against hepatitis B is not associated with an long or short term AEs.
- Support for the IOM results that the MMR vaccine is associated with febrile seizures.
- Moderate evidence linking influenza vaccines with mild gastrointestinal events
- Support for an association between the trivalent influenza vaccine with febrile seizures.
- Moderate evidence of an association between the MMR vaccine and thrombocytopenic purpura; similar associations were found for the varicella and hepatitis A vaccines.
- Moderate evidence of an association between the varicella vaccine and thrombocytopenic purpura in children aged 11 to 17 years
- No evidence of an association between vaccines and leukemia or lymphoma.
- Support for the IOM results of no evidence of an association between MMR and autism; indeed, the authors characterized this as “strong evidence that the MMR vaccine is not associated with autism.”
- High level evidence for an association between the varicella vaccine and anaphylaxis
- High level evidence for an association between the varicella vaccine and disseminated varicella infection in the immunosuppressed
There are a bunch of others, mostly with moderate to weak evidence of associations with a few rare AEs and associations with more common but minor AEs. There’s no such thing as a highly effective medical intervention that never causes AEs, and vaccines are no different. However, although the authors found evidence for some serious AEs due to vaccine, the risks were very, very low. For instance:
Although 1 large US epidemiologic study found no association, a recent analysis of the US PRISM program found both RotaTeq and Rotarix associated with intussusception in the short term. Estimated rates were 1.1 to 1.5 cases per 100 000 doses of RotaTeq and 5.1 cases per 100 000 doses of Rotarix.
In other words, severe AEs from vaccines are extremely rare. There were few weaknesses in this study, and what weaknesses there were were minor. For instance, the authors intentionally did not use studies that mined the VAERS database for AEs because it’s a passive surveillance system and cannot be used to assess a statistical association. It was a wise decision, because of how hopelessly compromised the VAERS database has become due to litigation and lawyers urging people to report everything and anything, particularly autism, as AEs to vaccines, whether there is a convincing association or not.
Of course, none of this is anything new. We’ve known that, although minor AEs like redness at the injection site or febrile reactions are not uncommon, severe AEs from vaccines are very rare. Indeed, this study was conceived to build on a previous review by the Institute of Medicine, which I characterized a year and a half ago as “Quoth the Institute of Medicine: The current vaccine schedule is safe and effective. Quoth antivaccinationists: Gahhhh!” The reaction of antivaccinationists is about the same now. That’s how antivaccinationists always react to another brick in the wall supporting the safety and efficacy of vaccines, particularly when it’s a particularly large and strong brick. Weighing the benefits versus the risks of vaccines, the evidence comes down very much in favor of vaccines. As Carrie Byington, MD, a pediatrician at the University of Utah, Salt Lake City, puts it in an accompanying editorial, fortunately, the AEs identified by the authors are rare and expected to resolve quickly and completely in most cases. These have to be weighed against the incredible benefits of vaccination, which, as Dr. Byington puts it, “This [the risk of vaccination] contrasts starkly with the natural infections that vaccines are designed to prevent, which may reduce the quality of life through permanent morbidities, such as blindness, deafness, developmental delay, epilepsy, or paralysis and may also result in death. She also notes that these benefits aren’t just ancient history, either, as in the elimination of smallpox and the impending (we hope) elimination of polio, but continue today:
An evaluation of the US vaccine program from 1900 to 1998 demonstrated reduction or elimination of many infectious diseases that had resulted in substantial childhood morbidity and mortality, including smallpox, diphtheria, pertussis, tetanus, polio, measles, mumps, rubella, and Haemophilus influenzae type b (Hib). Newer vaccines, including those that target pneumococci, human papilloma virus, influenza, rotavirus, and varicella, are also reducing morbidity and mortality. Modeling of vaccine impact demonstrates that routine childhood immunizations in the 2009 US birth cohort would prevent ∼42 000 deaths and 20 million cases of disease and save $13.5 billion in direct health care costs and $68.8 billion in societal costs. The Vaccines for Children program, operating since 1994 to provide vaccines at no cost to low-income children, has eliminated racial and ethnic disparities in immunization coverage, ensuring that all US children have an opportunity to enjoy the benefits of vaccines.
Oddly enough, the response of the antivaccine movement has been largely muted. The best the antivaccine crank blog Age of Autism could come up with is a post by its “media editor” Anne Dachel, asking What does generally safe mean? It’s basically an attack on Mike Stobbe, an AP reporter, who is lambasted for his reporting on this story, calling him a “true believer,” ranting that he’s never called for the unicorn that is the “vaxed/unvaxed study” that antivaccinationists always call for, she then writes:
Mike Stobbe needs to understand that despite the years of his faithful reporting on vaccines, WE’RE NOT BUYING IT. There’s just too much autism out there that no one can responsibly explain and too many autistic kids who also have seizures. AND JUST TOO MANY PARENTS WHO SAY IT WAS THE VACCINES!
Confusing correlation with causation, thinking that the plural of “anecdote” is “data” supporting causation, it’s all there. It’s also all completely recycled. It’s as though Dachel isn’t even really trying anymore.
Meanwhile, someone whom I have never heard of before, Suzanne Posel, posts five reasons to question recent RAND Study. It’s nothing more than rehashed antivaccine talking points that I’ve refuted more times than I can remember on this blog, all delivered in a confusing fashion. After all, if you’re going to do a post with a title that is obvious link-bait (as most titles that advertise lists like “five reasons that…” are), you should number the reasons clearly. From what I could gather, one of the reasons is “[INSERT GENERIC ANTIVACCINE GARDASIL FEAR MONGERING HERE]” followed by SaneVax nonsense about HPV DNA in vaccines. It’s so dumb that I can’t believe SaneVax keeps repeating it as “microcompetition.” If Posel thinks SaneVax is a reliable source and knows vaccine science, she’s just revealed herself as clueless about vaccines.
Oh, wait. She cites Lucija Tomljenovic, who has been co-author on a number of execrable papers seeking to link vaccines with autoimmune diseases, premature ovarian failure, and, of course, death based on a truly incompetent analysis.
As I said, it’s as though antivaccine loons aren’t even trying anymore.
And vaccines are safe, no matter what the antivaccine loons say.