May 25 2010

Vaccines – Too Few, Too Late

The anti-vaccine movement is nothing if not savvy about marketing their nonsense – at least in the last decade. One of their successful slogans has been “too many, too soon” – implying that children are receiving too many vaccines while they are still too young to deal with them. The result, anti-vaccinationists argue, is potential neurological toxicity or “overwhelming” the immune system.

The slogan also serves double duty, allowing anti-vaccinationists to argue that they are not “anti-vaccine” just “pro-safe vaccine.” This is just more marketing savvy, however – a deliberate deception, as many of the people who make this claim also state that they would never vaccinate. (Orac has pointed this out many times in great insolent detail.)

But there are some parents who have bought into this notion and have reduced and/or delayed the number of vaccines their children receive in the hopes that they can strike a better balance of risk vs benefit than the experts have struck. And there are fringe doctors, like Dr. Jay Gordon, who promotes his own evidence-free alternate vaccine schedule, playing into the “too many, too soon” meme.

We can argue along theoretical grounds that the vaccine schedule is safe, without making much of a psychological impact.  Paul Offit has pointed out that the environment presents a far greater daily challenge to young immune systems than a few vaccines do. Further the modern vaccine schedule contains fewer antigens (immune provoking substances) than at any time in the last 100 years (because of the elimination of the smallpox vaccine and improvements made to the pertussis vaccine).

We can also point out the safety data for the recommended vaccine schedule and the utter lack of any evidence to support the claim that Dr. Gordon’s or any other alternate schedule is safer. But fear and anecdote are easier spread than reassurance through dry data.

It is always nice, therefore, to have evidence directly comparing the standard schedule vs a delayed and reduced schedule – and now we have that data. A study published just yesterday online in Pediatrics compares neurological outcomes at age 7 and 10 in 1047 children based upon their vaccine schedule. They used publicly available data from a prior study – the VaccineSafety Datalink study of thimerosal exposure which tracked 42 neuropsychological outcomes.

The authors conclude:

Receipt of all recommended childhood vaccines on time in the first year of life in 1993–1997 had no negative impact on neuropsychological outcomes at 7 to 10 years of age, compared with delayed receipt or nonreceipt of >=1 dose during infancy. In fact, children who received each dose of each vaccine on time performed better on 2 of the 42 outcomes tested after adjustment for multiple familial and socioeconomic factors. Those with delayed receipt or nonreceipt of >=1 infant dose did not perform better on any measure.

There were actually 12 outcomes out of 42 that were superior for the on-time group than the delayed group, but only 2 of these held up after multivariable analysis. What this means is that if you take each outcome by itself there was statistical significance for 12, but because you are looking at 42 different variables that is 42 chances to reach statistical significance, and so we would expect a few to be positive by randomness alone. You can compensate for this with multivariable analysis, and after adjusting for multiple comparisons 2 outcomes remained significant in favor of the on-time group.

This could represent just noise in the data, or it could reflect the fact that parents who comply with the vaccine schedule may provide a more nurturing or healthy environment for their children in other ways. It could also reflect a decreased disease burden in vaccinated children.

In any case – the data strongly argues against any benefit from delaying or reducing vaccine. Meanwhile, delaying or skipping vaccines does come with an increased risk of contracting potential serious childhood diseases, like pertussis.

The usual caveats apply – this study is observational and not experimental. The vaccine schedule was chosen by the parents and not randomized or blinded. A randomized trial at this point, however, has serious ethical concerns and for that reason will likely never be done. Parents who believe in vaccines would probably not allow their children to potentially be randomized to a reduced or absent vaccine schedule, and parents fearful of vaccines may not want their children randomized to a full vaccine schedule. So don’t hold your breath for such a study.

Regardless, this is still a solid study and while not definitive is further evidence and reassurance for the safety of the vaccine schedule and the lack of any safety advantage (in fact a potential disadvantage) to alternate vaccine schedules.

Critics are likely to point out that the cohort of patients studied in this trial were born between 1993 and 1997 and the vaccine schedule has increased since then. However, in order to get long term follow up (like the 10 year follow up in this study) you have to look at the vaccine schedule from at least 10 years ago. Also, the schedule today actually has fewer antigens and almost no thimerosal. Further if there were any safety advantage to delaying or reducing the vaccine schedule this study should still have been able to detect it.

We’ll see how Dr. Gordon and other advocates of an alternate vaccine schedule respond to this new evidence. A science-based practitioner should alter what they do as new evidence comes in. But Gordon and the anti-vaccinationists have demonstrated adequately that they are not evidence-based, and prefer to rely more on their instincts.

On a side note – the British doctor, Andrew Wakefield, whose discredited MMR study was largely responsible for spreading fears about vaccines and autism, was recently “struck off” the list of medical doctors in the UK. This essentially means he has lost his license to practice. Although now he is already on to his next career here in the US as a martyr for the anti-vaccine movement, and this latest dishonor will only enhance that career.


Reference: Michael J. Smith and Charles R. Woods. On-time Vaccine Receipt in the First Year Does Not Adversely Affect Neuropsychological Outcomes. Pediatrics. published online May 24, 2010; DOI: 10.1542/peds.2009-2489



A letter has been published on the Pediatrics website concerning this study. The author, Lawrence Rosen, points out that the numbers in the results section do not add up. He writes:

If all of the subjects are added as listed, a total of 1037 (not 1047) is obtained. Furthermore, the percentages are incorrect as listed. The final group (311) is in fact 30% of the incorrect total, not 20% as listed.

He is correct, but I think he is using what is essentially a copy edit error to try to discredit publicly available data. The numbers in the tables do add up to 1047 – so one of the numbers copied to the results section was written wrong. The “20%” error is also just a copy mistake and does not affect the data at all. It should be corrected to “30%.”

Dr. Rosen also points out:

Of greater concern to me, personally, is the Financial Disclosure listings. It is very difficult in this day and age to review the authors’ conclusions without considering their considerable potential biases given where their funding comes from. I believe every known vaccine manufacturer is listed on the payroll.

This is the “Conflict of Interest” gambit now common in the anti-vaccine crowd.  Here is the full COI from the paper:

Drs Smith and Woods are or have been unfunded subinvestigators for cross-coverage purposes on vaccine clinical trials for which their colleagues receive funding from Wyeth, Sanofi Pasteur, GSK, MedImmune, and Novartis; and Dr Woods has received honoraria for speaking engagements from Merck, Sanofi Pasteur, Pfizer, and MedImmune and has received research funding from Wyeth and Sanofi Pasteur.

The first part is hardly a conflict – they worked with other researchers without getting paid. Dr. Smith has no other conflicts. Dr. Woods has received some speaking fees and has received research funding from two companies, Wyeth and Sanofi Pasteur.

In other words – they are academic researchers. This does not mean that they are “on the payroll” of pharmaceutical companies, and the COI disclosure says nothing about this study being funded by any company. This is the kind of study that academics can do without external funding, just as part of their academic activities.

But Dr. Rosen is using connections that are ultimately trivial and not relevant to this study as a way to cast doubt on the findings. This is surely to be the strategy of the anti-vaccine movement as a whole, as they have done in the past.

Of course, we need to be vigilant about real conflicts of interest in medical research. But what Dr. Rosen is doing is a COI witch hunt designed to dismiss inconvenient data.

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