Hypothesis testing and presentation of the outcome -- either positive or negative -- is a fundamental part of the scientific process. Accordingly, we have published studies that both do,1 and do not2 support a role for measles virus in chronic intestinal inflammation: this is called integrity. The latest of these studies was strongly positive,3 and was accepted by the MRC Review in February, 1998. By contrast, Brent Taylor and colleagues (June 12, p 2026)4 have ignored the rules. They are inappropriately didactic in their conclusions, despite the weakness of their method and the contradictions in their data. A case-series analysis is unlikely to identify a relation between exposure and disease, in which the onset is insidious and in which, very often, there is diagnostic delay.
Taylor et al tested the hypothesis that there should be no temporal clustering of first parental concerns with measles, mumps, and rubella (MMR) vaccination. They identified a statistically significant excess risk by 6 months after MMR, which they dismiss, post hoc, as indicating parental recall bias. Had this been the case it should have been seen in both of their vaccine groups -- those receiving MMR and those receiving any measles-containing vaccine. The excess risk was seen only in the MMR group; this is a fundamental flaw.
In 1998 the expected numbers of newly diagnosed autistic children in California should have been 105-263 cases, according to DSM-IV; the actual figure was 1685 new cases. The temporal trend in north-west London is almost identical, although the rise is delayed by about 10 years. The two countries use the same diagnostic criteria. The sequential trends are consistent with the timing of introduction of MMR to both regions.
However, it pales into insignificance compared with their failure to declare the fact of an MMR catch-up campaign that was initiated in 1988 with the introduction of this vaccine. This campaign was targeted at children, whatever their age, who presumably had not received either monovalent mumps or rubella vaccine whatever their exposure status. As such it was a novel and, in terms of safety, untested policy. On the basis of Taylor and colleagues' inclusion criteria, and taking account of the catch-up campaign, then those first birth cohorts who actually received MMR (circa 1986) were precisely those in whom a doubling of the numbers of cases of autism were seen. Thereafter these numbers continue to increase strikingly. Omission of this essential fact -- the catch-up campaign -- requires explanation lest it be misconstrued.
Can the dramatic increase in autism be ascribed to change in diagnostic practice? Data from the recent California report from the Office of Developmental Services belie this contention. The figure juxtaposes the data from California with those from north-west London. Identical temporal trends are shown, with the rise in autism from a steady baseline value, coinciding with the introduction of MMR vaccine as the single strategy in both countries that use the same diagnostic criteria for autism.
These data expose the danger of not only setting out to prove, rather than to test, hypotheses but also presenting the data whether they are supportive or not. The full story has yet to unfold. In a timely BMJ newspeice,5 Begg who is described as a leading virologist, calls for MMR research to be terminated on the basis of Taylor and co-workers' report and a non-peer-reviewed so-called analysis in Current Problems of Pharmacovigilance. Clearly there are some things that may end-up being terminated as a consequence of these events: research into the possible link between MMR, autism, and bowel disease is not one of them.
Andrew J Wakefield
Departments of Medicine and Histopathology, Royal Free and University College Medical School, Hampstead, London NW3 2PF, UK
1 Lewin J, Dhillon AP, Sim R, Mazure G, Pounder RE, Wakefield AJ. Persistent measles virus infection of the intestine: confirmation by immunogold electron microscopy. Gut 1995; 36: 564-69.
2 Chadwick N, Bruce IJ, Schepelman S, Pounder RE, Wakefield AJ. Measles virus RNA is not detected in inflammatory bowel disease using hybrid capture and reverse transcription followed by polymerase chain reaction. J Med Virol 1998; 70: 305-11.
3 Montgomery SM, Morris DL, Pounder RE, et al. Paramyxovirus infections in childhood and subsequent inflammatory bowel disease. Gastroenterology 1999; 116: 796-803.
4 Taylor B, Miller E, Farringdon CP, et al. MMR vaccine and autism: no epidemiological evidence for a causal association. Lancet 1999; 353: 2026-29.
5 Bower H. New research demolishes link between MMR vaccine and autism. BMJ 1999; 318: 1643.
Lancet Volume 354, Number 9182 11 September 1999
Official Vaccine Policy Flawed
Roger Schlafly, PhD
The use of vaccines to prevent and eradicate diseases like smallpox is one of the great successes of modern medicine. But recent developments supply grounds for skepticism about new vaccine initiatives. The corrupting influences are money and politics.
In the past ten years, vaccines have become very profitable for drug companies. At one time, the DTP (Diphtheria, Tetanus, Pertussis) vaccine sold for 10 cents per dose, and the drug manufacturers were dropping out of the market because of low profits and liability problems.(1) But in 1986, Congress sheltered the drug companies from liability. Those injured by vaccines can make claims against a special government fund. There is also a lot more money in the vaccine business. New vaccines are usually patented, and can sell for hundreds of dollars. Aggressive new vaccine requirements have made the market even more lucrative.
The vaccine market is also a perfect target for socialistic do-gooders, because nobody questions a plan to prevent children from getting crippling diseases. Many in the Clinton administration and elsewhere believe that the federal government should manage the health care industry, and that all Americans should carry national ID cards that link them to a national medical database. Portions of this plan were passed by Congress in the 1996 Health Insurance Portability and Accountability Act (also known as Kassebaum-Kennedy) which mandated a national ID number for tracking personal medical histories. The pilot project for this Orwellian scheme is the Immunization Registry at the Centers for Disease Control (CDC).(2) The Clinton administration is currently lobbying to repeal state privacy laws so that government officials will have unfettered access to private medical records. The plan is to do this first under the guise of removing obstacles to childhood immunization, and then to extend the database to other types of medical records later.
The United States immunization policy is largely dictated by the CDC. It appoints members of the Advisory Committee on Immunization Practices (ACIP), which then makes a schedule of vaccine recommendations and publishes it in the CDC Morbidity and Mortality Weekly Report. The members are often nominated by the drug companies and have substantial financial ties to the drug companies. Portions of the ACIP meetings are open to the public, but portions are also secret. Members are forbidden to publicly discuss what happens during closed portions of the meetings. The precise scientific, medical, and political bases for the vaccine recommendations are never revealed.
Thus the drug companies and the CDC have strong incentives to expand immunization programs. Physicians have a duty to critically examine whether this expansion is good for the health of their patients. It is not necessarily true that all vaccines are good for all people.
One of the current ACIP recommendations is that all newborn babies be given the hepatitis B vaccine within 24 hours of birth. This is not a conservative recommendation. Such a vaccination might be justified in cases where the mothers test positive for hepatitis B, but the babies are at extremely low risk otherwise. The biggest risk of hepatitis B to the babies occurs many years later when they grow up and then as adolescents become sexually active.(3)
Is the hepatitis B vaccine safe? It is hard to say based on the available evidence. There is epidemiological evidence that suggests it is quite safe, but there are also reports that it causes autoimmune and neurological disorders, and there have been no controlled tests which looked at such effects. The vaccine authorities do not like to do long-term tests of vaccine side-effects for fear that merely doing a test would provide ammunition to vaccine skeptics. France recently suspended hepatitis B vaccinations of schoolchildren because of fears that the vaccine causes multiple sclerosis and other diseases.(4) In spite of this concern, all American newborns are being vaccinated.
Another ACIP recommendation is the oral polio vaccine. The World Health Organization has declared polio eradicated from the western hemisphere. The last case of polio "in the wild" was in Peru in 1991. Yet, the live oral polio vaccine is still given, and some people still get polio from the vaccine.
Last year, the ACIP recommended the rotavirus vaccine. Rotavirus causes diarrhea in babies, but is not particularly common, severe, or contagious. The ACIP made the recommendation without even knowing the price of the vaccine (i.e., what the drug manufacturer was going to charge), so it is obvious that a cost/benefit analysis of the vaccine was not done.(5)
The CDC immunization policy is disgraceful from a scientific, medical, or public policy point of view. It is a scientific disgrace because vaccines only get short-term or epidemiological tests, and not controlled tests for long-term side effects. We do not know, for example, whether the radical increase in vaccinations during the last 20 years has any relation to the observed increase in incidence of asthma over the last 20 years.(6)
The immunization policy is a medical disgrace because physicians have been pressured to abandon their ethical principles of privacy and informed consent and freedom of choice for their patients. How many pediatricians tell their patients that they are more likely to get polio if they choose to get the vaccine? If they did, usage of the oral polio vaccine would plummet.
The immunization policy is a public policy disgrace because it is a secretive process conducted by biased and unaccountable parties. Ideally, the ACIP should:
1. Use an open process. All data, meetings, considerations, etc. should be open to the public, and rationales for all decisions should be documented.
2. Have a more representative membership. While vaccine researchers on the drug manufacturer payroll might be the most knowledgeable, most of the ACIP decisions concern public policy rather than biochemistry. Munitions experts develop plans for bombing Iraq, but they are not the ones who make the final decision of whether or not to bomb.
3. Publish the complete rationale for vaccine recommendations. There is no excuse for using proprietary and unrefereed company data or confidential political directives to make public policy.
4. Separate science and medicine from policy analysis in the vaccine recommendations.
5. Make a scientific analysis of the risks and benefits of particular vaccines.
Now you may think that the arguments for vaccinations are so compelling that all of this is unnecessary. But consider these arguments for vaccine policies.
1. The vaccine must be mandatory for all Americans in order to make it cost-effective for the drug manufacturer.
2. A discriminatory policy might be more effective, but it would not be politically viable. (For example, we could just give the rubella vaccine to girls, since the only significant risk is to pregnancies in later life. Other diseases affect certain ethnic groups disproportionately.)
3. The disease is no worse than a mild cold, but a vaccine might have a favorable cost/benefit analysis if it is based on saving the mother from taking a day off work.
4. The disease has been eradicated from this country, but we continue to vaccinate in order to set a good example for third world countries.
5. The vaccine is useless now, but it has been a tremendously positive thing in the past and we like to maintain the tradition.
6. The disease is risky for promiscuous and IV drug-abusing teenagers, but parents will not reliably predict such behavior so we give the vaccine to everyone at birth.
7. A live virus vaccine is preferred over a safer killed virus vaccine because the live virus vaccine has the secondary effect of exposing unvaccinated children to the virus.
8. The vaccine is more likely to cause harm than good on an individual basis but might still be good for society at-large because of the "herd immunity" effect.
9. The HIV vaccine is ineffective, but we need to flag the national vaccine registry entries of the people who are at risk for HIV so we can monitor other diseases that they might be spreading.
10. The vaccine is only medically justified for a particular ethnic group that is susceptible to the disease, but it is better to vaccinate everyone so that the group is not stigmatized.
11. The risk of getting the disease and dying is 1 in 300,000, and the risk of getting brain damage from the vaccine is 1 in 100,000. It is better to have three brain-damaged babies than one dead baby.
12. Vaccines make a very powerful argument for socialized medicine. Even hard-core libertarians usually admit that it is good to have government-sponsored vaccinations. A broader and centrally-managed vaccine program that goes unchallenged will set an example for government management of other medical operations.
All of these arguments are controversial. Most of them have been used to justify vaccines. Physicians who are being asked to recommend and administer vaccines need to know whether some of these arguments are part of the CDC's rationale. Unfortunately, we do not know. And we are unlikely to find out, because the CDC would consider revealing these reasons to be counterproductive.
Meanwhile, the practicing physician is caught in the middle. He is responsible for informing the patient of the risks and benefits, but his information from the CDC and the drug manufacturers is incomplete, at best. He has an ethical responsibility to give his patients an informed choice, but government authorities will use computer databases to monitor his compliance with official recommendations and seek to pressure him if his vaccination rates are low.
The average physician does not have the time and know-how to evaluate all of the evidence and arguments. The drug companies cannot be trusted because they are sheltered from liability. Besides, not even the drug companies claim their vaccines are good for everyone. Physicians need the CDC to fund experiments, collect data, and do analysis. What it does, though, falls quite a bit short of what is needed.
The vaccine analysis should clearly state the risk model. That is, it should say what risks are being estimated, what assumptions underlie the measurement of those risks, and what data contributes to the measurement. Only with such a risk model can someone draw any conclusions about risk to a particular individual.
The analysis should also separate science and medicine from policy analysis. Policy analysis, according to standard textbooks(7) and even the ACIP charter, should:
1. Verify, define, and detail the problem.
2. Establish evaluation criteria.
3. Identify alternative policies.
4. Evaluate alternative policies.
5.Display and distinguish among alternative policies.
But the ACIP never carries out these steps. Vaccine researchers and government bureaucrats are setting policies which are more political than scientific, and they are never required to reveal the bases for their decisions.
The ACIP does state its purpose, but it is not the purpose you might expect. The stated purpose of the ACIP is to increase the use of vaccines, not to promote health. According to its charter: "The overall goals of the ACIP are to provide advice which will assist the Department and the Nation in reducing the incidence of vaccine preventable diseases and to increase the safe usage of vaccines and related biological products, including active and passive immunoprophylaxis."(8) Thus nearly all of the controversial arguments listed above are consistent with the goals of the ACIP.
Finally, there should be a cost/benefit analysis of the vaccine. The vaccine should be good for society as a whole, in some sense which has clearly stated assumptions and quantitative conclusions. The costs and benefits may vary from one patient to the next, so the cost/benefit analysis should also give individuals a way to apply it to their own situations. As with any other medical procedure, a drug which is favorable to some people is apt to be unfavorable to others.
Ideally, the drug manufacturers would also supply these analyses and stand behind their products. But in today's market, the companies only need to do enough studies to get FDA approval, and publish a list of all the adverse reactions reported in the studies. Most people would not take the vaccines if they only read the drug company literature. The companies rely on the CDC and individual physicians to vouch for the vaccines in a way that the companies themselves will not do.
The CDC is not likely to move to an open and honest vaccine policy any time soon. There is too much money and politics favoring a dictatorial vaccine policy. The currently high vaccination rates (90 percent or so) would be very difficult to achieve based on reason and persuasion alone, and would be impossible if the public realized how weak the case is for some of the vaccines. The current policies of misinformation and intimidation are much more effective, and in the eyes of CDC do-gooders, anything which purportedly benefits children and promotes government medical programs is a good thing.
1. Plotkin SA, Mortimer EA. (eds.) Vaccines, Philadelphia, W. B. Saunders, 1994. This collection of articles has a wealth of medical information about vaccines.
2. See details at www.cdc.gov/nip/registry.
3. "The effect of routine infant vaccination on acute disease incidence may not be apparent for 20-30 years because currently most infections occur among young adults." Morbidity and Mortality Weekly Report, Vol. 44, No. 30, Aug. 4, 1995.
4. "In a sudden reversal of health policy, France has decided to suspend Hepatitis B vaccinations in secondary schools because of fears that the vaccine causes neurological disorders." New York Times, Oct. 3, 1998.
5. ACIP meeting minutes, Feb. 1998. Available from CDC.
6. The Economist 1998;344(8044):95(3). It suggested possible correlations between vaccines and other diseases such as asthma.
7. Patton CV, Sawicki DS. Basic Methods of Policy Analysis, Prentice Hall, 1993.
8. ACIP Policies and Procedures, July 1998. Available from the CDC or from Some other supporting evidence on immunization policy is also there.
Dr. Schlafly is summa cum laude B.S.E. from Princeton, has a PhD in mathematics from the University of California at Berkeley, and has held teaching positions at the University of Chicago and the University of California at Santa Cruz .