Saturday, December 22, 2007

Evidence Based Medicine

This item was emailed to this blog. -AR

The double edged sword of vaccines is that as we increase their use we will increase adverse events particularly as relates to autoimmune phenomena. Where is the simple science that assesses the rates of autoimmune disease as a function of number of vaccinations received?

For the protection of the children of this country and improved health outcomes without threatening herd immunity we have to do more checking of vaccine efficacy rather than assume we need 3 boosters in every child in some series of vaccines. Where is the safety data that ensures giving multiple vaccines at one clinic visit is as safe as separating them. Where is the safety data with a normal saline (NOT ADJUVANT) placebo control on the hepatitis B series?

Participants in such a study who got placebo after safety assessments were in for day of birth immunization would have plenty of time to get catch-up vaccination, I never got hepatitis B shots until college clearly such a disease that have a major behavioral component to transmission could be intensely scrutinized for safety in childhood; there is no medical literature, no documented evidence that indicates these safety assessments have been done.

Focused, smarter protocols with titer checks will easily accomplish this. Concerned parents and a growing number of concerned physicians can develop a congress of "the evidence based" schedule. In the end it will be more appropriate to make decisions on clinical evidence of need. Boosters are inappropriate in those who have documented immunity, titer levels are all I ever had to prove immunity to the diseases of childhood when I started medical school (my vaccine records were lost). Grassroots public awareness campaigns can get the word out that titer level documentation of immunity is actually more appropriate documentation of immunity than a written record of shots that could be forged anyway. Such social nightmares for both sides of the arguments of safety and need such as occurred in Maryland recently could easily be avoided with this simple information.

Nothing is 100% safe and I do think the risks of certain diseases at certain ages warrant vaccination with serial titers for follow up, why waste the shot though if you don't need it? If parents don't want to pursue that slightly more arduous course they can make the assumptions of safety similar to the CDC, but the atmosphere needs to change so that patient education leads to this consideration of this approach as a primary discussion point.

Teasing out the small percentage of vaccine-intolerant kids on the basis of biochemical screening is the goal that government research dollars should be driven towards-it is the HONORABLE thing to do, admitting that there are vulnerable patients who will have a discordantly high risk of injury due to a universal mandate is not easy, those with character will at least admit this goal should be pursued.

I see this same point being made in other areas of medicine with much less angst. Why is this goal ignored, is it conditioning? I have on many occasions turned a friendly colleague around in their thinking on this after getting through the conditioning of medical culture.

We can come together and improve the lives of children in both areas of safety and immunity by taking these simple steps. Even if hubris prevents it coming from the CDC, the culture of pediatrics, and academia; the grassroots efforts of many Great Americans can pull this idea together for the good of our nation's health.

Its hard to argue against this approach in a way that can be justified on truly medical grounds. Simple fact is we have no good evidence of what the rates of vaccine-related iatrogenesis are because there are no prospective controlled studies on this liability issue, the onus is
on the CDC to provide that evidence; is it 1/100, 1/1000, 1/10,000 or 1/1,000,000?

Even at a 1/1,000,000 rate of adverse contrast reactions ,radiologists are still going to be put to task for how they attempted to avoid an ill fated injection by patients, lawyers and health advocates. I am glad we are; we continually improve our safety, most often by the prodding of our colleagues outside of our specialty.

Many thanks again to the KOMU staff and the University of Missouri
School of Journalism,

You have provided a brave investigation that others with a greater
audience could never endeavor!

Edward F. Fogarty, M.D.
Chairman of Radiology
University of North Dakota School of Medicine
Father of a great kid who is slowly beginning to speak.


ANB said...

You propose your titer test prior to a booster shot to determine if the child already has antibodies. But here's what I don't get: since this is for a booster, you already have evidence if the child can tolerate the vaccine, right?

So why not go with the data you already have? Aren't you just searching for a disease to go with your cure, figuratively speaking?

FOGARTY said...

ANB: Many autoimmune phenomena require a first exposure as a sensitizer and subsequent exposures are the problem.


Anonymous said...

Ed, be a man and apply for an RO1 for it. Put your money where your mouth is. Be sure to post the reviewer comments, we could all use a bit of cheer.

Anonymous said...

Dr. Fogarty states:

"Even at a 1/1,000,000 rate of adverse contrast reactions ,radiologists are still going to be put to task for how they attempted to avoid an ill fated injection by patients, lawyers and health advocates."

It might be relevant to know that a June 2006 study of over 50,000 patients in the journal European Radiology found that the rate of adverse reactions for one of the safest intravenous contrast agent (iobitridol) was about 1% (0.96%) and the rate of severe adverse reactions was 0.044% (about one in 2,300). These results are similar to those found in other studies.

These rates are much higher than the "1/1,000,000" rate cited by Dr. Fogarty.

I think that this just shows how dangerous it is to rely on "gut feeling" when assessing risks.

I agree with Dr. Fogarty that it is important to study potential long-term adverse reactions to vaccines, but it is also important to use our limited research resources (not only money, but time, people and facilities) wisely.

To that end, I would liked to have seen the evidence Dr. Fogarty had to support his concern that vaccines cause autoimmune diseases.

After all, if we are to spend time, money, and facilities to research this possibility, shouldn't we be asking if there is a plausible reason to spend these resources there instead of somewhere else?

The reality is that it takes little effort - and no data - to say that something might cause a disease. The effort comes in showing whether that idea is correct or not.

And while we are spending our time, money and facilities researching that idea, other worthy research projects remain untouched.


BillinMidMO said...

Speaking of risk... Dr Fogarty, Chairman of Radiology, have you considered Prenatal Ultrasounds as an autism risk? Retrospectively, autistic kids are found in many cases to have failed the newborn hearing assessment. Hmmmm, could it be that ultrasound has rearranged something?
How may children have you caused to have autism...I wonder.
Lets immediately stop all ultrasonograghy until all the data are in. While we are at it , we need to immediately stop the use of all imaging. MRI, CT scans, X Ray... that sounds dangerous too!

FOGARTY said...

Another good point in the discussion here is how physicians actually grossly underestimate and misunderstand the risks of a know carcinogen-medical radiation.

Again, these are pervasive misunderstandings that should be troubling to all, I don't let my specialty off the hook for misunderstanding risks of radiation or other specialties who are the ordering physicians.

Same problem (physician understanding of risks) different venue:
From Medpage and based on NEJM paper by Brenner and Hall listed below:
[In a recent survey of radiologists and emergency room physicians, they said, "about 75% of the group significantly underestimated the radiation dose from a CT scan, and 53% of radiologists and 91% of emergency room physicians did not believe that CT scans increased the lifetime risk of cancer."]

Brenner DJ, Hall EJ, "Computed tomography -- an increasing source of radiation exposure" N Engl J Med 2007; 357: 2277-2284.

Not only is it a problem that 91% of ER docs don't think its at all related to cancer risk, even more than half the radiologists don't get it. So why should we trust that the average US pediatrician understands the risk of their greatest arm of therapeutics?

EFFIIIMD said...

Bill: In the susceptible population I would guess that sono and electromagnetic wave forms could be problems too so you have hit on some good points, prenatal screening would be practically impossible but maybe that can get done too after we hone in on the screening of these kiddos as neonates. CT would likely have some issues greater than the troubling issues with pediatric CT that have been getting studied for the last several years. So if I knew a kid was autistic-inclined I would avoid that and favor MRI (without contrast). Again, I never said stop vaccinating, I said vaccinate smarter just as I would ask my colleagues to order imaging tests more thoughtfully-just last week 2 pregnant gals got MRIs instead of CTs for headaches because I pushed for it after the ED doc ordered a head CT.

Jim: Contrast I was talking about was gadolinium. Prior to 2006 most radiologists in the country would say the risk of serious adverse events from IV injection would be less than 1 in 1,000,000 and that rate of risk may even still be true but we have identified an at risk population for NSF and that heavy metal medical product has quickly been black boxed. Tell me you thoughts on the abstract below as regards a potential similar susceptible population of humans and the potential risks of autoimmunity relating to vaccines containing thimerosal, and then ask yourself after reading the Simpsonwood transcripts why it shouldn't have been blackboxed too:

Toxicol Appl Pharmacol. 2005 Apr 15;204(2):109-21.
Immunosuppressive and autoimmune effects of thimerosal in mice.

Havarinasab S, Häggqvist B, Björn E, Pollard KM, Hultman P.

Department of Molecular and Clinical Medicine, Molecular and Immunological Pathology (AIR), Linköping University, SE-581 85 Linköping, Sweden.
The possible health effects of the organic mercury compound thimerosal (ethylmercurithiosalicylate), which is rapidly metabolized to ethylmercury (EtHg), have recently been much debated and the effect of this compound on the immune system is largely unknown. We therefore studied the effect of thimerosal by treating A.SW (H-2s) mice, susceptible to induction of autoimmunity by heavy metals, with 10 mg thimerosal/L drinking water (internal dose ca 590 microg Hg/kg body weight/day) for up to 30 days. The lymph node expression of IL-2 and IL-15 mRNA was increased after 2 days, and of IL-4 and IFN-gamma mRNA after 6 and 14 days. During the first 14 days treatment, the number of splenocytes, including T and B cells as well as Ig-secreting cells decreased. A strong immunostimulation superseded after 30 days treatment with increase in splenic weight, number of splenocytes including T and B cells and Ig-secreting cells, and Th2- as well as Th-1-dependent serum immunoglobulins. Antinucleolar antibodies (ANoA) targeting the 34-kDa nucleolar protein fibrillarin, and systemic immune-complex deposits developed. The H-2s strains SJL and B10.S also responded to thimerosal treatment with ANoA. The A.TL and B10.TL strain, sharing background genes with the A.SW and B10.S strain, respectively, but with a different H-2 haplotype (t1), did not develop ANoA, linking the susceptibility to H-2. Thimerosal-treated H-2s mice homozygous for the nu mutation (SJL-nu/nu), or lacking the T-cell co-stimulatory molecule CD28 (B10.S-CD28-/-), did not develop ANoA, which showed that the autoimmune response is T-cell dependent. Using H-2s strains with targeted mutations, we found that IFN-gamma and IL-6, but not IL-4, is important for induction of ANoA by thimerosal. The maximum added renal concentration of thimerosal (EtHg) and inorganic mercury occurred after 14 days treatment and was 81 microg Hg/g. EtHg made up 59% and inorganic mercury 41% of the renal mercury. In conclusion, the organic mercury compound thimerosal (EtHg) has initial immunosuppressive effects similar to those of MeHg. However, in contrast to MeHg, thimerosal treatment leads in genetically susceptible mice to a second phase with strong immunostimulation and autoimmunity, which is T-cell dependent, H-2 linked and may at least partly be due to the inorganic mercury derived from the metabolism of ethyl mercury.

PMID: 15808517 [PubMed - indexed for MEDLINE]