I recently commented on a post by Dr. Stacy Beller Stryer at Dr. Val’s new digs.  Today, Dr. Stryer responded.  Before I get started, I’d like to thank both of them for taking time out of their schedules to respond.  That said, I was somewhat dismayed by its failure to address the concerns I raised.

Dr. Stryer said:

Indian Cowboy comments that he is a member of the “current generation of medical students,” where evidence-based medicine is important. Does this mean that we old-timers (yes, I am an ancient 45 years old), don’t practice medicine based on results of quality studies and proof of what actually works?

I implied nothing of the sort, I was making a cultural reference to the fact that ‘evidence-based medicine’ has become a buzzword in recent years, which is plain to see by the way I described it: “It has been beaten through the current generation of medical students’ heads that this is the era of ‘evidence-based medicine’.”

If she took that as an implication that older doctors (and 45 isn’t particularly old) don’t practice intelligently, I apologize, but I think its easy to see that I meant no offense.

I also never implied that any doctor said there are no risks to vaccines. I know of no doctor who has ever made that statement. Few also question the existence of more serious side effects, though rare.

I also don’t question the role of vaccines in improving public health throughout the 20th century. In India, you still see polio myelitis victims, people with the lingering effects of pertussis, decades after their infection, and countless other vaccine-preventable illnesses. There is no question about their benefits.

Dr. Stryer further says:

Just as importantly, and an absolute necessity is discussing that the risk of becoming seriously ill or dying secondary to a vaccine is much lower than the risk of developing a serious illness or dying if a child becomes ill with one of the infections for which they could have been vaccinated.

This is a clear over-reach as I have emphatically and rigorously detailed in my previous post. The bottom line is that we don’t actually know what the risk is for many vaccines. If a patient with angina comes into my office and I want to start them on aspirin, and he or she asks me what the risks and benefits are, I can tell them fairly concretely what their risk of serious complications such as bleeding, GI upset, and even tinnitus are. I can back that up by telling them just how much they’ll reduce their risk of a heart attack. Now, on the other hand, if a parent wants to know how likely their child is to develop a serious neurologic or autoimmune reaction to gardasil or recombivax, this is a number I cannot quote them. I can tell them that these are relatively rare complications (I think both Dr. Stryer and I agree on this), but I can’t tell them how rare. But hepatitis B infection and cervical cancer are also relatively rare, particularly when one avoids risky lifestyle choices, and in the case of the latter, gets regular pap smears (which are still necessary even if one gets the HPV vaccine).

This is because unlike in trials involving medications, many vaccine trials do not actually monitor for adverse events for the entire course of the studies (which often do last years). This prevents them from reporting one-year incidence rates of serious diseases among the vaccinated versus non-vaccinated populations. More worrisome, the ‘placebo’ used in these trials was an aluminum adjuvant, which itself is immunologically active and has a much higher reported rate of side effects than a simple saline solution. Between inadequate length and failure to use a true placebo, it’s hard to defend the notion that pre-licensure safety studies are adequate.

Dr. Stryer says:

Back to Indian Cowboy – he also comments that we really don’t know much about vaccine safety because studies only last days or, at most, a couple of weeks. This is also far from the truth. Before a vaccine is licensed, the Federal Drug Administration (FDA) requires testing.

She says it’s far from the truth, yet if you look at Merck’s inserts on Recombivax, and Gardasil, it is plain to see that the safety arm of these pre-approval studies lasted between 5 and 14 days. As I have detailed ad nauseum in my previous post on this subject, this is an inadequate way to measure for severe adverse neurologic and autoimmune sequelae, given that this is not enough time to mount a full immune response to the vaccine and that it may take even longer for an autoimmune or neurologic side effect to appear. Again, I submit that these vaccines should be monitored for side effects and rates of serious disease for at least 6 months and more optimally one year in order to get a better idea of risk of serious adverse events. This would give us directly comparable figures to the general population: 1 year incidence in the vaccine study group versus 1 year incidence in the control population. And once again, I submit, given that an aluminum adjuvant ‘placebo’ results in high rates of side effects similar to the vaccine itself, one cannot consider it a placebo.

The efficacy arms of these studies can and do last for years, and involve measurement of antibody titers and rates of infections in vaccinated versus non-vaccinated individuals. But not the safety arms. There is no data on long-term side effects and rates of disease from pre-approval studies of these drugs.

With concerns regarding vaccine injury mounting throughout the 1980s to today, surely it wouldn’t have been too hard to gather this kind of data since these same patients were already being followed in the study for efficacy?

Now, admittedly, even if we followed the thousands of patients involved in these studies we might still miss more rare side effects such as Guillaine Barre Syndrome. Such is the rational behind the Vaccine Adverse Events Reporting System and Vaccine Safety Datalink.

Dr. Stryer did briefly discuss the problems with VAERS but failed to address the underlying problem of using VAERS incidence rates uncorrected in claims that rates of serious side effects are no higher than in the general population. An uncorrected VAERS figure can be 5-10 times lower than the actual figure. This study, which I’ve linked to before, provides a very clear illustration of this phenomenon. Reporting these uncorrected figures is disingenuous in the extreme, yet it is commonly done with no qualification of the inadequacy of reporting.

She also did not counter my review of pubmed which revealed that most retrospective case-control studies looked at single diseases rather than the whole spectrum of neurologic and autoimmune complications, which in case reports and series were revealed to have features of more well-known diseases but weren’t necessarily categorizable as rheumatoid arthritis or multiple sclerosis, which is to be expected. As an example, the potential association between Multiple Sclerosis and Hepatitis B Vaccination has been the subject of many retrospective studies. However, if one looks at case reports and VAERS data, MS is not as commonly reported as peripheral demyelination or seizures, and all of these are reported in higher than expected figures. A better approach would be to look at demyelination as a whole, or even better, neurologic disease as a whole. Neurologic and autoimmune disease remain the most feared and concerning among potential vaccine adverse events, and if a retrospective case-control study is going to be efficacious (which they are by nature less effective than a prospective RCT or cohort study), it needs to take a look at the sum total of these events.

At least with respect to Hepatitis B infection, neurologic sequelae are known and relatively common. Proposed mechanisms have been elucidated and have to do with cross-reaction between the Hepatitis B viral envelope and aspects of neuronal tissue. Furthermore, “challenge-rechallenge” evidence also exists regarding the vaccine and neurologic and autoimmune side effects. We also have histologic evidence of HBsAG immune complexes deposited in the Together, this represents the “gold-standard” of evidence that there is a potential causal relationship between the vaccine and severe side effects.

And as I wrote about more exhaustively in my earlier post, the aluminum adjuvant itself (present in both Gardasil and Recombivax, as well as the other vaccines in which concerns regarding autoimmune and neurologic side effects have been raised) may be implicated in potential side effects itself. This is readily revealed in the earlier-linked to Gardasil package insert. Again, a simple 15 minute review of the literature reveals that the aluminum adjuvant has serious concerns associated with it as well. It strongly affects the actions of our dendritic cells, macrophages, IgE-mediated allergic response, and Th2 T-Cells; and in some individuals these changes may last for long periods of time. And that, by causing an imbalance in Th2 versus Th1 immunity, as well as activating the inflammatory response, it may predispose individuals to the development of autoimmunity and inflammatory disorders. Animal models of neurologic and autoimmune disease due to parenteral administration of aluminum adjuvants in equivalent doses exist as well. Indeed, there is a continued search for newer adjuvants precisely because of the high rate of side effects associated with aluminum adjuvants.

Dr. Stryer goes on to say that:

I could continue, but the bottom line is that immunizations have been tested extensively for safety and continue to be monitored by reputable, quality organizations. There is an abundance of information available on safety for every vaccine.

Again, I’ve laid out the numerous problems with pre-licensure safety studies. I’ve highlighted the inefficacy of VAERS and VSD. And I’ve pointed to moderate to strong evidence for causality in the role of certain vaccines and vaccine adjuvants in the development of autoimmune and neurologic disease.

The Institute of Medicine concurs that, with respect to Hepatitis B vaccination, the evidence remains unclear regarding whether it causes or exacerbates neurologic disease as a whole. Concerns about what is unknown regarding long-term side effects have been voiced about Gardasil by leading gynecologists. And a lot of attention has been focuses on aluminum recently.

Perhaps most damningly, of the vaccine safety issues that the Institute of Medicine has investigated, they were unable to find enough evidence one way or another for 2/3 of the claims. If, as Dr. Stryer asserts, the state of vaccine safety pre-licensure trials and post-marketing monitoring was so effective, one would harldy predict this to be the case.

Dr. Stryer ends with an emotional entreaty:

I certainly hope that the one case of epiglottitis and pertussis that Indian Cowboy saw last year makes him realize not only how serious these infections can be in infants and children, but also that he only saw one case of each whereas, without immunizations, he would have seen many more and, most likely, a few deaths.

Yes, I realize that. I also realize that, rather than preventing a life-changing event, a vaccine changed my life forever 11 years ago when I developed painful demyelinating neuropathy. I live with the sequelae of it every day, as do thousands of others who developed similar reactions to the Hepatitis B and other vaccinations. I also know that many of us are not recorded in VAERS. And that there is good evidence for plausibility of a causal relationship between the two events ranging from theoretical to positive challenge-rechallenge evidence in humans. And that I had an infinitessimal risk of acquiring the infection itself due to my lifestyle. I also know that I’m seeing a similar pattern of reports of neurologic side effects being reported with Gardasil, and that the vaccine isn’t a replacement for regular pap smears and screening. I also know that aluminum is associated with significant neurotoxicity, inflammatory reactions, and autoimmunity, and that infants have a reduced ability to clear it from their system. I also know that we understand many of the biological mechanisms behind these adverse events associated with aluminum.

So let me say it one more time. We know that certain infections and thus their vaccinations may predispose individuals to the development of serious neurologic and autoimmune complications. We know that aluminum adjuvants may contribute to the problem or may even be the problem itself. We also have an understanding of why this is so in both cases. What we don’t know is how often it happens, who it happens to, and how much of this can be prevented by less toxic formulations (such as removing the aluminum adjuvant). Our efforts should go toward determining just how risky these vaccines are and how to make them less risky.

Even the IOM agress with me on that.