Wednesday, November 6, 2013

"My Crystal Clear Stance on Vaccination" #2: Flawed Research--No Randomized, Controlled Trials on Vaccines Have Ever Been Done

The chiropractor seems to have some counter-factual beliefs about how vaccines are developed and tested, as well as not-very-nuanced ideas about clinical research.

FLAWED RESEARCH: The scientific mantra of vaccines is that they are safe and effective based on their research.  Their research is flawed and is a double standard from any other drug product studied.  The Gold Standard in research design is the double blinded, randomized controlled trial (RCT). 
This means that people are split into 2 groups randomly and participants are given either the real thing or the fake thing being tested.  Then progress is charted on who gets better, who gets worse, and the like.  In theory there should be no bias as to reporting because the researchers don’t know who is in the placebo or the real intervention group.
This is a very cursory, but essentially accurate description of RTCs.  A better description would be:

A quantitative study in which selected people are allocated at random (by chance alone) to receive one of several clinical interventions. One of these interventions is the standard of comparison or control. The control condition may be an inert substance ("placebo" or "sugar pill"), or no intervention at all. In a single-blind study, the study subjects do not know whether the are in the control condition or the experimental condition. In a double-blind study, neither the subjects nor the researchers know which participants are in which study conditions. Very careful study design and execution is required to avoid confounders --  a third variable that can make it appear (sometimes incorrectly) that the variable of interest is associated with an outcome, by affecting the measured outcome. Confounders lead to bias that distorts the magnitude of the relationship between two factors of interest.

The chiropractor is partially correct that RTCs are the "gold standard".  Here is a graphic of one version of "the hierarchy of evidence".

Back to the chiropractor's post:

How many vaccines have ever been studied in this manner?  ZERO!  The reason?
This is an inaccurate claim in several dimensions.

First, in 1954, Salk's polio vaccine was tested in an RTC

In all, over 1.3 million children participated in the trial. The trial was a randomized, double-blind test, meaning that children were randomly assigned to either the control group or the vaccine group. Neither the children (or their parents) nor health officials knew which children had received the vaccine and which had received the injected placebo fluid. (A smaller control group received no injection. Rather, officials observed them throughout the trial period for signs of polio infection.)

The outcome?  There were 609 cases of paralytic polio in the unvaccinated children, and only 71 cases of paralytic polio in the vaccinated children.

As to RTC vaccine safety studies, they are almost too many to count, as each new vaccine is tested in the process of development.  

The chiropractor seems blissfully unaware of the stages of vaccine development.  If the infographic below isn't clear enought for you, The History of Vaccines website has a useful overview, as does the HIV Vaccine Trials Network, if you don't like the infographic from the CDC


This is a common question from anti-vaccine true believers.  For example, here is a question posed by a naturopath, answered by Mark Crislip MD, an infectious disease specialist, at the Science Based Medicine post Nine Questions, Nine Answers

Show me one double-blind, placebo-controlled study that can prove the safety and effectiveness of vaccines? 
One trial? It took me 55 seconds to find  "Efficacy of 23-valent pneumococcal vaccine in preventing pneumonia and improving survival in nursing home residents: double blind, randomised and placebo controlled trial” and that included time to boot the browser and mis-spell the search terms.  ’Vaccine’, ‘efficacy’,  ’randomized’ and  ’placebo control trial’  results in 416 Pubmed references; add ‘safety’ to the search terms, you get 126 returns. 416 is easily more than one.  Of course, to find them you have to look.

However,  evidently the chiropractor is demanding an RTC in which some children are not vaccinated at all. He is not alone; this demand has been made often enough that it's known as The One Study To Rule Them All.

Allison Hagood writes (here and here)

Multiple studies in multiple countries using multiple research models and multiple research groups, with multiple funding sources, have found no link between vaccines and autism. They have also found no links between vaccines and a long list of other conditions, such as ADHD, asthma, diabetes and auto-immune disorders, that anti-vaccine propagandists attempt to link to vaccinations. 

What would it take to conduct "the One True Study" of all vaccines? An alternate universe. 

These studies have been dismissed by those anti-vaccine propagandists as having the wrong funding source, the wrong research design, the wrong focus, not separating out antigens from other vaccine ingredients, separating antigens from other vaccine ingredients inappropriately, not testing this or that, or some other reason that likely lacks validity.

Meanwhile, those in the anti-vaccine movement want ONE study. The One Study To Rule Them All. The One Study that tests every possible aspect of every vaccine and finds them all, together and separately, through this One Study, to be completely effective and completely safe for all children and not linked to any conditions. 

Back to the chiropractor's post:
The researchers will say they cannot perform an RCT because it would be unethical to NOT give a child a vaccine because if that child dies of something that could have been prevented, then they don’t want to be responsible.  
That's not quite right. In the United States, approval for research involving humans is governed by the Code of Federal Regulations, TITLE 45: PUBLIC WELFARE DEPARTMENT OF HEALTH AND HUMAN SERVICES PART 46 PROTECTION OF HUMAN SUBJECTS, which requires human subject studies to be authorized by Institutional Review Boards (IRBs).

There are three principals fundamental to determining if a research proposal is ethical.

  1. Respect for Persons: Subjects must give voluntary consent to participate in research; that subjects are adequately and thoroughly informed about the research and what is required, and that subjects' privacy and confidentiality are protected. 
  2. Beneficence: The risks of participating in a research project are justified by potential benefits to the individual or society;  the research design is such that those risks are minimized. 
  3. Justice: The risks and benefits are distributed equitably,  meaning that one subset of a population should not take on all the burden of risk and reap all of the rewards; risks and rewards should be applicable and available to all subsets of a community.

We can already see that a vaccinated vs. non-vaccinated trial in children would flunk all three principles. It's not necessary that an unvaccinated study subject dies; many of the vaccine-preventable diseases have high risk of other poor outcomes (think of the measles and encephalitis, for example.)

ToddW, who has been part of a number of IRBs, has written a useful series of blog posts on the topic of ethics in research:

Back to the chiropractor's post:
But if someone dies in their trials from taking their anti-depressants, it must be ok.
Wow, what a non-sequitur!  The risk of suicide in clinical trials of antidepressants has been studied.  At any rate, the chirpractor's comments again shows how naive he is about clinical trials for medical interventions.

Back to the chiropractor's post:
Hey drug companies, I will volunteer my child to be in the placebo group and compare him to the health and well being of those that have gotten all the recommended vaccines.  I’m sure I can gather a few hundred thousand more to be in the placebo group to create a large sample.
Again, some naiveté about clinical trials.  Let us recall the idea of "randomized".  Assigning a child to a known treatment arm violates the idea of randomization.  I wonder if the chiropractor would be willing to enroll his child in a true RTC study, in which his child might receive all vaccines?  

Back to the chiropractor's post:
Instead of research to see safety and effectiveness, they instead see if the person builds anti-bodies to the antigen (the foreign invader) that is in the vaccine.  If antibodies are built, then it’s ‘safe and effective,’ or so they lead us to believe. These studies are rarely, if ever done on kids younger than 4 years old.  How can you say it's safe or effective for a baby if it's never studied on a baby?

I don't know where the chiropractor gets the idea that the only research that's done in the process of vaccine development is assessing antibody response.  It's clearly not true.  Look at the Phase I, Phase II and Phase III trials for new proposed vaccines, for example. Also, the bit about "studies rarely done on kids younger than 4" is also clearly false, as a quick look through PubMed will reveal, here are just two out of hundreds: Danchin et al. and Kulkarni et al.

The chiropractor seems quite ill-informed, or ill-educated,  about the development of vaccines, and ongoing research into vaccine safety and efficacy.  I have been mulling over whether the chiropractor's statements can accurately be called a series of straw men. I don't think so, quite, because the I suspect that the chiropractor sincerely believes in the inaccurate statements he makes. In other words, if you have been taught falsehoods, and use those falsehoods to argue against a scientific reality, you aren't making a dishonest argument, but an ignorant one.


"My Crystal Clear Stance on Vaccinations" by Kurt Perkins DC, posted May 2012


Danchin M, Kirkwood CD, Lee KJ, Bishop RF, Watts E, Justice FA, Clifford V, Cowley D, Buttery JP, Bines JE. Phase I trial of RV3-BB rotavirus vaccine: a human neonatal rotavirus vaccine. Vaccine. 2013 May 28;31(23):2610-6. doi: 10.1016/j.vaccine.2013.04.008. Epub 2013 Apr 16.

History of Vaccines, Polio

Thomas Francis, Robert Korn, et al. "An Evaluation of the the 1954 Poliomyelitis Vaccine Trials." American Journal of Public Health 45 (1955), 50 page supplement with a 63 page appendix.

Kulkarni PS, Sapru A, Bavdekar A, Naik SS, Patwardhan M, Barde P, Pandit AN. Immunogenicity of two diphtheria-tetanus-whole cell pertussis-hepatitis B vaccines in infants: a comparative trial. Hum Vaccin. 2011 Sep;7(9):941-4. doi: 10.4161/hv.7.9.15994. Epub 2011 Sep 1.

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