The Association of American Physicians and Surgeons, Inc.
Re: Requirements for pneumococcal and chicken pox vaccines in children
before Judge Beverly Heydinger Office of Administrative Hearings
February 28, 2003
Jane M. Orient, M.D., F.A.C.P.
Interest of the Association
The Association of American Physicians and Surgeons was founded in 1943 to preserve the traditional patient-physician relationship based on the Oath of Hippocrates. We believe that physicians should prescribe for their patients based on their own knowledge and judgment for the benefit of each individual patient. We represent thousands of physicians in all specialties nationwide. We are supported only by dues, and have no income from business interests, foundations, or government.
Summary of the AAPS Position on Vaccine Requirements
AAPS believes that vaccines are often very valuable but that, like other medical interventions, there are both risks and benefits. We believe that patients have the right to refuse treatment, even when recommended by their physician. Some will argue that a clear, present, and serious public health danger could override that right. However, that argument does not pertain to rare, nonepidemic conditions such as invasive pneumococcal disease (IPD) or to conditions that are generally mild, such as chickenpox.
Vaccine requirements might be justified only with convincing evidence that the intervention does more good than harm. There is no such evidence for mass immunization, particularly for Prevnar and Varivax. Requiring use in children is actually a societal experiment -- a poorly designed, uncontrolled experiment unlikely to yield satisfactory data for prudent future policy determinations. It is a well-established principle of international law, as in the Nuremberg Protocol, that human experimentation requires informed consent. The right to claim an exemption is very different from affirmative, fully informed consent. The requirement implies that the State has adequate knowledge to be certain that the intervention is beneficial in the vast majority of cases.
The State has the burden of proof. AAPS will argue that this burden has not been met, and that the requirements are arbitrary and unreasonable.
The Case for Prevnar
I have personally recommended and administered pneumococcal vaccine to patients at special risk for invasive pneumococcal disease (IPD), such as those who have undergone splenectomy. More may choose to vaccinate at the present time because of the increasing antibiotic resistance of the pneumococcus.
The largest benefit demonstrated for Prevnar was the prevention of about 39 cases of invasive pneumococcal disease in a study population of about 19,000 children, compared with a control population who received a meningococcal conjugate vaccine, or about 0.2% (1). There was no evidence of an increased risk of invasive disease caused by serotypes not contained in the vaccine, but follow-up was for a relatively short period of time. The trial started in October, 1995, cases were collected until April, 1999, and results were accepted for publication in December, 1999. Local and systemic reactions were rated as "relatively mild" for both vaccines, and no serious adverse events were attributed to the vaccine, although such events did occur. There was no placebo control, so the only possible conclusion on adverse effects was a comparison between the adverse reactions of conjugated pneumococcal vaccine and conjugated meningococcal vaccine.
1. What is the long-term effect of Prevnar and Varivax, or multiple vaccines, on overall health?
2. How will the pneumococcal vaccine change the distribution of serotypes of colonizing bacteria?
3. How will vaccines affect children who, unlike the study subjects, are not in optimal health?
4. Will serious effects adverse effects become manifest when larger populations are vaccinated?
5. How will chickenpox vaccination in childhood affect the incidence of the disease in older populations or in the next generation?
6. How good are mechanisms for detecting vaccine adverse events?
1. Overall Health Effects
Vaccination rates may be used as a proxy for health, but this is a process measurement, not an outcome. The incidence of childhood diseases is a pertinent outcomes measure, but it is not the only important one. There is evidence that the burden of chronic illness in children has increased substantially, despite reductions in vaccine-preventable acute illness episodes. Asthma, diabetes, autism, other neurodevelopment disorders, and atopic skin disease are the most prominent examples. The increases are unexplained. Although it may be said that there is "no hard scientific evidence" that vaccines had a causative role -- despite scattered studies showing a correlation -- there are also no well-designed studies of sufficient statistical power to rule out such causation. Vaccine safety studies are generally too short to investigate any such delayed effects.
Adverse events following vaccination are generally not attributed to the vaccine unless causation is "biologically plausible." It is important to remember, however, that our notions of biologic plausibility have been dramatically revised in other contexts, such as the role of Helicobacter pylori in the causation of peptic ulcer disease.
2. Pneumococcal Serotypes
Although the study by Black et al. was reassuring about the lack of a shift to serotypes not included in Prevnar in causing invasive pneumococcal disease, this remains a serious concern. Antibiotic resistance, after all, did not develop in a few years either.
Outside the United States, studies have shown that coverage by Prevnar may be poor. In Germany, only 10.5% to 78.3% of the serotypes causing meningitis in children age 6 months and older were included in Prevnar (2). Data from the United Kingdom indicate that the "epidemiology of IPD is heterogeneous and requires continued surveillance" (3). In Canada, significant natural variation was found in the proportion of isolates matching 7-valent vaccines from year to year and among centers (4).
3. Safety in the General Population
For ethical reasons, studies performed on human subjects must carefully exclude patients with possible contraindications. Such a careful screening process is not necessarily done on children being rushed through the process of receiving required, presumably safe vaccines. All too often, children may even be vaccinated while they are ill, as a matter of convenience for parents and physicians.
4. Uncommon and Delayed Adverse Effects
It is not uncommon for drugs and other medical products to be withdrawn from the market upon the appearance of serious adverse effects that were not apparent in clinical trials. Feasible studies are simply too small to detect them. This is the reason that many physicians prefer not to prescribe any new drug until it has been in use for a considerable length of time. The period of post-marketing surveillance is, in effect, a prolonged experiment.
A regulatory rule of thumb is that the threshold for regulatory action is a serious risk of 1 in 10,000 for voluntary risks (such as occupational risks) and 1 in 100,000 for involuntary risks (as from consumer products or environmental effects). A study with 19,000 experimental subjects is quite likely to miss a risk as low as 1 in 10,000, even for a biologically plausible, short-term effect that the study is equipped to detect.
Thus, children are often required to have vaccines posing a risk higher than that to which industrial workers may lawfully be exposed in the course of their employment.
While it is true that children are expected to derive an offsetting benefit from the vaccine, the population expected to derive much of the benefit (the elderly, the immunocompromised) does not necessarily include the individuals who must bear the risk, which may rarely include death or lifelong, devastating neurologic disability.
5. Long-Range Effects on Vaccine-Targeted Diseases
An unintended consequence of widespread antibiotic use, even in benign, self-limited illnesses, has resulted in increasing problems with virulent, antibiotic-resistant pathogens. Could vaccines against certain pathogens simply change the balance of nature so that different pathogens emerge to cause disease that may be even less susceptible to our treatments? It is simply too soon to answer that question.
Black et al. state that "knowledge of the protection afforded by [pneumococcal] vaccine may have a profound effect on the management of infants who present to physicians with fever and no localized signs of illness. It is likely that clinical laboratory diagnostic procedures, hospitalizations and presumptive antibiotic use in the vaccinated children will be significantly reduced" (1). Other say that "the number of children with fever coming to physicians' offices, however, is unlikely to change…. Until more experience is available…, the febrile child without focus of infection should be managed without consideration of immunization with PCV7 [Prevnar]." (5) Indeed, depriving children of antibiotic therapy because of dependence on the vaccine could conceivably result in fatal treatment delays.
Patients who are especially vulnerable to serious consequences, even death, from generally mild diseases such as chickenpox, include infants and the elderly, or even young adults. This is the rationale for "chickenpox parties." The presentation of the disease may be atypical and thus not easily recognized. It is too early to say whether waning, vaccine-induced immunity will result in this consequence. Additionally, the effect on newborns will not be detectable for at least 20 years. Newborns cannot be immunized and depend on antibodies transmitted to them by their mothers. This borrowed immunity may be far less robust from mothers whose only exposure to the disease-causing organisms was in vaccines.
6. The System for Monitoring Vaccine Side Effects
The rapid recall of rotavirus vaccine after reports of intussusception is often cited as proof that the system works. However, concerns about this problem were raised on the basis of prelicensure studies and denied until reports started coming in to the Vaccine Adverse Effects Reporting System. See extracts from documents obtained through a Freedom of Information Act request. AAPS pointed out a likely systematic flaw in prelicensure studies: comparing the total incidence of possible adverse effects in study and control populations, instead of considering proximity to the immunization. This delays the recognition of an increased incidence of an effect that is otherwise rare by taking a longer time and a greater number of cases to reach statistical significance.
Many parents raised concerns about mercury-containing preservatives in vaccines. Manufacturers, official agencies, and vaccine advocates such as the American Academy of Pediatrics continue to deny the possibility that serious disability may be traced to this component, even while supporting its removal from vaccines manufactured in the future. (It is present in existing stocks that are still being marketed.) Persuasive evidence is now being presented, on the basis of VAERS reports, of a strong correlation between the total dose of mercury received from childhood vaccines and the incidence of neurodevelopment disorders and cardiac arrest. (See preprint of paper by Geier and Geier.)
Potential conflicts of interest are pervasive in committees making "recommendations" about vaccine requirements. This takes many forms: consulting fees, honoraria, grant support, journal advertising revenues, and educational grants. Such support may even be required to achieve recognition as a vaccine "expert."
Parents cannot have confidence in a process that depends so heavily on a small number of selected "experts" who derive their expertise from association with the regulated industry. The only way to assure integrity is to make safety data accessible to analysis by truly independent scientists. Such data may now be unobtainable. Even a Freedom of Information Act request has not been successful in acquiring prelicensure safety data supporting the use of hepatitis b vaccine in newborns. No special expertise in vaccines is required to critique such data: the principles of probability and statistics are the same, whether the subject of the analysis pertains to geologic exploration, stock-market performance, or medical interventions. Unbiased peer review is probably possible only if the reviewers are blinded to authors and the actual intervention, which might be identified as "Group A" or simply "experimental group."
Careful after-market surveillance is a critical part of assuring the safety of medical interventions. However, the mere fact of having such surveillance is an admission that new drugs and vaccines are in a sense experimental: an admission that raises serious ethical questions about any requirements to accept the product. The requirements also vastly complicate efforts to address the unanswered questions detailed above. Without an unvaccinated control group, how can a vaccine ever be implicated?
Vast data bases are being accumulated about vaccines. Unfortunately, the purpose seems to be to enforce (or very strongly encourage) compliance rather than to monitor the consequences.
Parents should be offered vaccines for their children, with full disclosure and without the pressure of a "requirement." Overall population health measures must be monitored.
Epilogue: Lessons from Smallpox Vaccination
Though the success of vaccination in freeing the world of smallpox is frequently cited, it is now becoming apparent that this is a mixed blessing. Virtually the entire population of the world is now vulnerable to this highly contagious, frequently lethal scourge, while there is mounting evidence that it has been weaponized.
The willingness of those who advocate requirements for childhood vaccines to accept the risk of vaccination for themselves is now being tested. Only about 4,200 medical professionals have been vaccinated, and the plans to vaccinate 500,000 workers are now stalled. We have very good data about adverse reaction rates to the vaccine, from 1 in 1 million deaths to 17.7 to 223 in 1 million cases of generalized vaccinia. The rates of adverse reactions might well be higher today, a testimony to the diminished overall health of our population. Nonetheless, they are still probably less than the serious consequences of widely mandated childhood vaccines.
(1) Black S, Shinefield H, Fireman B, et al. Efficacy, safety and immunogenicity of heptavalent pneumococcal conjugate vaccine in children. Pediatr Infect Dis J 2000;19:187-195.
(2) Von Kries R, Hermann M, Hachmeister A, et al. Prediction of the potential benefit of different pneumococcal conjugate vaccines on invasive pneumococcal disease in German children. Pediatr Infect Dis J 2002;21(11):1017-1023.
(3) Sleeman K, Knox K, Miller GR. Invasive pneumococcal disease in England and Wales: vaccination implications. J Infect Dis 2001;183:239-246.
(4) Scheifele D, Halperin S, Pelletier L, et al. Invasive pneumococcal infections in Canadian children, 1991-1998: implications for new vaccination strategies. Canadian Paediatric Society/Laboratory Centre for Disease Control Immunization Monitoring Program, Active (IMPACT). Clin Infect Dis 2000;31(1):58-64.
(5) Klein JO. Management of the febrile child without a focus of infection in the era of universal pneumococcal immunization. Pediatr Infect Dis J 2002;21(6):584-588; discussion, 613-614.