Sunday, March 7, 2010

Obedience = Protection

The following article is a critique of this paper:
Glanz, JM, et al. Parental Refusal of Pertussis Vaccination Is Associated With an Increased Risk of Pertussis Infection in Children. PEDIATRICS Vol. 123 No. 6 June 2009, pp. 1446-1451

So this guy named Glanz (and his buddies) looked into the database of an HMO and found 156 lab confirmed pediatric cases of pertussis, which also had clear vaccination records, in a 10 year period. Then he randomly picked 595 kids who didn't get pertussis diagnoses, matching the same age and gender of the lab confirmed pertussis kids, to serve as comparison cases.

Out of the 156 pertussis cases, he found 18 of these kids (11%) had parents who refused the pertussis vaccine. The rest, 138 of the kids (89%) had parents who accepted vaccines--their children either got the vaccine or had medical exemptions to miss one or more doses.

Now get this. What he studied wasn't whether or not the kids were vaccinated. There were unvaccinated kids in both the acceptor group and the refusal group! What Glanz was really after was whether parents were accepting or refusing of physician vaccination recommendations. Were they obedient or not? Did they believe in vaccines or not?

Here is my problem. Did the authors really think Bordetella pertussis cares WHY a kid is vaccinated or unvaccinated? Why draw a relationship between parental beliefs and a disease, regardless of vaccination status? They might as well have studied parental religion and pertussis, or parental belief in astrology and pertussis.

See, if it were me, and I were interested in the effects of vaccination on the risk of pertussis, I would group the kids by the number of shots they had, period. Fully vaccinated in one group, partially in the second group, and unvaccinated in the third. I would assume the bacteria do not care WHY kids were unvaccinated or partially vaccinated, forget whether the parents had a bad attitude or not, and focus on the kids' actual biology.

Let's go back to the 595 comparison cases for a moment. They found that while a full 11% of lab confirmed pertussis cases were vaccine refusers, only half a percent (0.5%) of the 595 kids without pertussis diagnoses were vaccine refusers.

So the Glanz guy says, "Hey, look! Most of the vaccine refusers we found are in the group who got pertussis! Kids with rebel, vaccine-refusing parents are 23 times more likely to get pertussis than kids with nice, obedient parents who either vaccinated or didn't vaccinate as they were told to by their doctors."

Breaking medical news! A parent's vaccine acceptance and compliance appears to extend magic protection over a child, regardless of actual immunity. Glanz has discovered a bacterial Passover.

(Eye rolling.) Nuff said, right?

Actually, I got more.

Glanz starts with a group of pertussis kids to find out whether their parents were vaccine acceptors or refusers. Fair enough. But when it came to conclusion time, he reverses the relationship and uses vaccine refusal to predict the risk of pertussis.

Uh uh. You don't do that. At best, it is sloppy. At worst, it is disingenuous. Either way, the reversal is unscientific and makes the conclusion invalid.

If he wanted to use vaccine refusal to predict the risk of pertussis, he should have started with finding all the vaccine refusers in the HMO database. Next, he can look for how many lab confirmed pertussis cases are amongst all the vaccine refusers vs. the randomly picked vaccine accepting controls. Then he can calculate the chances that given a refuser, he would also find lab confirmed pertussis in their charts.

Had he used this method, he might have found very different results. Why?

Not all refusers are exposed to pertussis, for one. What if all the pertussis cases occurred in one school, and that school happened to be in a neo-hippie community with an exceptionally high number of vaccine refusers? What if he took all the comparison cases with no diagnosed pertussis from different schools where pertussis was not going around and happened to have very few refusers.

(He could have matched the control group on age, gender, AND school attended. But he didn't. You would think exposure would be an important variable to control for, but this is the same guy who thinks bacteria care about doctor's notes. So…eye rolling again.)

Now if he had started with all the refusers, you could follow all of them, exposed or not. Match controls on age, gender, and school, and you can have a better idea if refusers truly have a higher risk than acceptors of having lab-confirmed pertussis. At least the conclusion wouldn't be completely incongruent with the study design.

As it stands, the only thing you can possibly conclude from this study is that given a child with lab confirmed pertussis, you are more likely to find that his parents were vaccine refusers than if you were given a child with no diagnosed pertussis (but possibly with asymptomatic pertussis).

First, note that this increased likeliness exists ONLY when compared to a child with no diagnosed pertussis. If you are just looking at the pertussis kids alone, remember that 89% were vaccine acceptors and only 11% were vaccine refusers. That means, given a child with lab confirmed pertussis, you are eight times more likely to find vaccine accepting parents than vaccine refusing parents.

Second, note that I keep saying "lab confirmed pertussis," and not just, "pertussis" like Glanz liked to say. Glanz himself identified three groups of pertussis infections: 1) "frequent asymptomatic infections" where people have pertussis, but show no symptoms; 2) symptomatic infection with no lab confirmation, and 3) symptomatic infection with lab confirmation. Now out of all three, he studied only the third type. Yet in his conclusion, he predicted the risk of pertussis infections in general. Science is supposed to be precise to avoid misleading people. It may sound like nitpicking, but imprecision and overgeneralization is very bad science.

Once you focus on lab confirmed pertussis, and not all pertussis infections, it becomes obvious that diagnostic bias could very well explain the difference between the group with lab confirmed pertussis and the group without diagnosed pertussis. It could be that physicians are more likely to order lab testing for children of vaccine refusers than children of vaccine acceptors. Indeed, Glanz acknowledged this bias.

But get this. He says this bias is roughly cancelled out by another bias: that vaccine refusers are less likely to attend clinics to begin with. He estimates that diagnostic bias is about threefold (3X), and clinic attendance bias was twofold (2x), so the biases cancel each other out and are "negligible." That is to say, doctors are 3 times more likely to order labwork on refusers than acceptors, but refusers are 2 times less likely than acceptors to see that doctor to begin with. So it's all okay.

How did he get this threefold vs twofold estimate? He did a little side analysis of very young children with vague symptoms, counting how many refusers vs acceptors went to a respiratory clinic, and how many refusers vs. acceptors got lab testing orders at the clinic.

Say what?

Very young children with vague symptoms do not represent the initial group, which had mostly older children and were unlikely to have only vague symptoms. It could be that in very young children with vague symptoms, the biases are 3X vs. 2X, but in older children with marked symptoms, the biases could be 5x vs. same, or same vs. 5x, which doesn't cancel out at all. Maybe refusers are more likely to skip clinics for vague symptoms, but if the symptoms are severe, they are just as likely as accepts to go. Maybe doctors are more likely to order labs for refusers for vague symptoms, but when the symptoms are severe, doctors are equally likely to order labs for both groups. We don't know. Again, he is generalizing without the data to support it. Bad, bad science. Since this side analysis of his doesn't represent the core sample of his study, it really is completely useless.

So we're back to the problem of diagnostic bias. It is just one of many possible factors that could explain why if given a child with lab confirmed pertussis, you are likely to find a vaccine refusing parent than given a child without lab confirmed pertussis. You could have doctors who like to order more labwork for refusers, you have happen to have more refuser kids at a school with a pertussis outbreak, you could have refuser kids more likely to exhibit stronger symptoms of pertussis than acceptor kids (who are either vaccinated or have other medical problems for medical exemptions), you could have refusers who are more likely to attend clinics because of stronger symptoms, and so on.

One thing is certain. What you cannot conclude is what Glanz concluded: "Our study found a strong association between parental vaccine refusal and the risk of pertussis infection in children." The study design does not support this conclusion. The methodology doesn't support this conclusion. The data doesn't support this conclusion. It's a case of find one thing, and generalize improperly to make it look like another. It's another case of pseudo-scientific sleight of hand. You got a waste basket for junk science? Crumple this one up and throw it in.

No comments:

Post a Comment