Resource for evidence on vaccine safety and efficacy

Article: Scientific Evidence and the EU Court (link)

In a 2012 report on vaccine safety, the committee used four “categories of causation” when evaluating whether a vaccine causes an “adverse effect.”

1. Evidence convincingly supports a causal relationship
2. Evidence favors acceptance of a causal relationship
3. Evidence is inadequate to accept or reject a causal relationship
4. Evidence favors rejection of a causal relationship

But the 2012 report says the committee doesn’t use the category “establishes or convincingly supports no causal relationship” because it’s “virtually impossible to prove the absence of a relationship with the same certainty that is possible in establishing the presence of one.”

Why? Because “studies may not rule out the possibility that the reaction is caused by vaccine in a subset of individuals,” the committee says.

Alberto Ascherio, a professor of epidemiology at Harvard who has studied whether the hepatitis B vaccine causes MS, elaborated on this point.

Scientists can study “counterfactuals” in populations, but not individuals, he told us over the phone. That is, they can’t examine what would have happened if an individual person hadn’t received a vaccine, compared to if they had. But scientists can look at the rate of vaccination in a population of people who have a disease and compare it to the rate in a population of people who don’t.


Information on SV40 and the polio vaccine

2006 review of literature (link)

All 4 epidemiologic studies discussed in this review concluded, as had earlier studies,1 that the increased incidence of the cancers did not occur in those who had the highest risk of SV40 exposure from contaminated vaccine. As emphasized in the IOM report,1 these data by themselves do not disprove the role of SV40 in human cancer because the exposure to SV40 by the vaccine is not known at the level of the individual, but they do allow the more limited interpretation that the increased incidence of cancers was unrelated to the contaminated vaccine.

It is very likely that SV40 infections are not prevalent in human communities and are not linked to any human cancer. However, in order to maintain public confidence in vaccines, legitimate questions related to vaccine safety must be answered as fully as possible. The collective experience of the field suggests that future studies should incorporate the following features: (i ) blinded design; (ii ) tests of suspect cancer tissues as well as negative tissues; (iii ) employment of several primer pairs targeting different regions of the SV40 genome; (iv ) quantitative PCR; (v ) blinded panels for estimating sensitivity and specificity of the PCR essays; (vi ) tests for SV40 transcripts and for SV40 T antigen; and (vii ) tests of the sera of cancer cases and controls (donors of tissues tested for SV40 DNA sequences) for antibodies to SV40 VLPs and SV40 T antigen. It would be helpful if the IOM would revisit this issue to provide an updated report and to recommend what more needs to be done to resolve this controversy.
 

2007 review of recent studies (link)

Simian virus 40 (SV40) is a monkey virus that was administered to human populations by contaminated vaccines which were produced in SV40 naturally infected monkey cells.

Recent molecular biology and epidemiological studies suggest that SV40 may be contagiously transmitted in humans by horizontal infection, independently from the earlier administration of SV40-contaminated vaccines.

SV40 footprints in humans have been found associated at high prevalence with specific tumor types such as brain and bone tumors, mesotheliomas and lymphomas and with kidney diseases, and at lower prevalence in blood samples from healthy donors.

Contrasting reports appeared in the literature on the circulation of SV40 in humans by contagious transmission and its association, as a possible etiologic cofactor, with specific human tumors. As a consequence of the conflicting results, a considerable debate has developed in the scientific community. In the present review we consider the main results obtained by different groups investigating SV40 sequences in human tumors and in blood specimens, the putative role of SV40 in the onset/progression of specific human tumors, and comment on the hypotheses arising from these data.
 

2001 study following up on vaccine recipients after 35 years (link)

Early poliovirus vaccines, both inactivated and live attenuated, were inadvertently contaminated with simian virus 40 (SV40), a monkey virus known to be oncogenic for newborn hamsters. Although large epidemiologic studies have not identified an elevated cancer risk in persons who received SV40-contaminated vaccines, fragments of SV40 DNA have recently been identified in certain human tumours. We report the follow-up of a cohort of 1073 persons, unique because they received SV40-contaminated poliovirus vaccines as newborns in 1961–63. A previous report of the status of these subjects as of 1977–79 identified 15 deaths, none due to cancer. The present study utilized the National Death Index to identify deaths in the cohort for the years 1979–96. Expected deaths were calculated from Cleveland area sex-, age-, race- and year-specific mortality rates. Increased mortality from all causes was not found. 4 deaths from cancer were found compared to 3.16 expected (P= 0.77). However, 2 deaths from testicular cancer occurred, compared to 0.05 expected (P= 0.002), which may be a chance finding due to multiple comparisons. There were 2 deaths due to leukaemia, a non-significant finding, and no deaths due to tumours of the types putatively associated with SV40. Although these results are, for the most part, consistent with other negative epidemiologic investigations of risks from SV40-contaminated vaccines, further study of testicular cancer may be warranted, and it will be important to continue monitoring this cohort which is now reaching middle-age.


1. Safety and efficacy testing – what are the requirements?

U.S.-based vaccines.gov site on safety (link)

This is a basic info page, written for the public, on the process through which vaccines are tested before being released. Here is a sample:

Before a vaccine is ever recommended for use, it’s tested in labs. This process can take several years. FDA uses the information from these tests to decide whether to test the vaccine with people.

During a clinical trial, a vaccine is tested on people who volunteer to get vaccinated. Clinical trials start with 20 to 100 volunteers, but eventually include thousands of volunteers. These tests take several years and answer important questions like:

  • Is the vaccine safe?
  • What dose (amount) works best?
  • How does the immune system react to it?

Throughout the process, FDA works closely with the company producing the vaccine to evaluate the vaccine’s safety and effectiveness. All safety concerns must be addressed before FDA licenses a vaccine.
 

History of Vaccines page (link)

This one goes into detail on the various stages of testing. Here is a sample:

Successful Phase II candidate vaccines move on to larger trials, involving thousands to tens of thousands of people. These Phase III tests are randomized and double blind and involve the experimental vaccine being tested against a placebo (the placebo may be a saline solution, a vaccine for another disease, or some other substance).

One Phase III goal is to assess vaccine safety in a large group of people. Certain rare side effects might not surface in the smaller groups of subjects tested in earlier phases. For example, suppose that an adverse event related to a candidate vaccine might occur in 1 of every 10,000 people. To detect a significant difference for a low-frequency event, the trial would have to include 60,000 subjects, half of them in the control, or no vaccine, group (Plotkin SA et al. Vaccines, 5th ed. Philadelphia: Saunders, 2008).

Vaccine efficacy is tested as well. These factors might include 1) Does the candidate vaccine prevent disease? 2) Does it prevent infection with the pathogen? 3) Does it lead to production of antibodies or other types of immune responses related to the pathogen?
 

University of Oxford page on U.K. protocols (link)

These are some of the stages a vaccine will have gone through before use:

  • Literature review: looking at what has been done before.
  • Theoretical development or innovation: coming up with a new idea, or a variation on an existing idea.
  • Laboratory testing and development. This involves ‘in vitro’ testing using individual cells and ‘in vivo’ testing, often using mice. The vaccine has to pass rigorous safety tests at this stage, and demonstrate that it works in animals.
  • Phase I study – an initial trial involving a small group of adult participants (up to 100 people). This is carried out to make sure that the vaccine does not have major safety concerns in humans, and also to work out the most effective dose.
  • Phase II study – a trial in a larger group of participants (several hundred people). Phase II trials check that the vaccine works consistently, and look at whether it generates an immune response. Researchers also start looking for potential side effects.
  • Phase III study – a trial in a much larger group of people (usually several thousand). Phase III trials gather statistically significant data on the vaccine’s safety and efficacy (how well it works). This means looking at whether the vaccine generates a level of immunity that would prevent disease, and provides evidence that the vaccine can actually reduce the number of cases. It also gives a better chance of identifying rarer side effects not seen in the phase II study.
  • Licensing – expert review of all trial data by the UK government (through the Medicines and Healthcare products Regulatory Agency – MHRA) or European regulator (European Medicines Agency – EMA). At this stage the regulators check that the trials show that the product meets the necessary efficacy and safety levels. They also make sure that, for most people, the product’s advantages far outweigh the disadvantages.
  • Phase IV studies – post-marketing surveillance to monitor the effects of the vaccine after it has been used in the population. These may be requested by a regulatory body, or carried out by the pharmaceutical industry.

2. An example of a safety-tested vaccine

Safety and Immunogenicity of Different Schedules of Takeda’s Tetravalent Dengue Vaccine Candidate (TDV) in Healthy Participants

Abstract via The Lancet

An unmet clinical need remains for an effective tetravalent dengue vaccine suitable for all age groups, regardless of serostatus. We assessed the immunogenicity and safety of three different dose schedules of a tetravalent dengue vaccine (TAK-003) over a 48-month period in children living in dengue-endemic countries.

Link to full study including data table
 

3. What is Vaccine Court? What do we know about it? This is a federal court. If vaccines are safe, we should know from verdicts in Vaccine Court.

Wiki page on National Vaccine Injury Compensation Program (link)

The Office of Special Masters of the U.S. Court of Federal Claims, popularly known as “vaccine court”, administers a no-fault system for litigating vaccine injury claims. These claims against vaccine manufacturers cannot normally be filed in state or federal civil courts, but instead must be heard in the U.S. Court of Federal Claims, sitting without a jury.

The National Vaccine Injury Compensation Program (VICP or NVICP) was established by the 1986 National Childhood Vaccine Injury Act (NCVIA), passed by the United States Congress in response to a threat to the vaccine supply due to a 1980s scare over the DPT vaccine. Despite the belief of most public health officials that claims of side effects were unfounded, large jury awards had been given to some plaintiffs, most DPT vaccine makers had ceased production, and officials feared the loss of herd immunity.
 

Reproduced 1991 Forbes article giving details on why it was set up (link)

Time and again, one sees how an avalanche of lawsuits can be loosed by a tiny hiccup of error in scientific research. In 1985, for example, lawyers won a spectacular $5.1 million verdict against Ortho Pharmaceutical Corp., largely on the strength of a single study that had very tentatively suggested that spermicides might cause birth defects. Not quite two years after the verdict, however, the several authors of that study spoke out again. One acknowledged that their work “was not corroborated by subsequent studies,” and that their “study’s definition of exposure to spermicide near the time of conception was grossly inaccurate.” Another conceded: “I believe our article should never have been published. In our present litigious environment, the reservations and qualifications written into a published report are often ignored, and the article is used as ‘proof’ of a causal relationship.”

The legal disaster of the pertussis (whooping cough) vaccine unfolded in much the same way. The vaccine, first licensed in 1949, has virtually ended whooping cough as a dread disease (265,000 cases, with 7,500 deaths, recorded in 1934). But in 1981 a major British study suggested that the vaccine’s use might be causing one case of brain damage for every 310,000 immunizations. Extrapolated to the U.S., that would be about 50 cases a year. American lawyers responded with an avalanche of litigation, blaming the vaccine for epilepsy, mental retardation and various forms of brain damage.

In response, one major supplier of pertussis vaccine, Wyeth Laboratories, abandoned the market. More solid scientific evidence slowly accumulated. Then, in March 1990 the Journal of the American Medical Association reviewed three recent studies covering a total of 230,000 children and 713,000 immunizations. Conclusion: No evidence of serious neurological complications or deaths from the vaccine. “It is time for the myth of pertussis vaccine encephalopathy to end,” declared the journal. “We need to end this national nonsense.”
 

Documents referring to ‘vaccine court’ cases

Some lists of cases brought for vaccine injury compensation under the VICP.

“The National Childhood Vaccine Injury Act of 1986 as amended*, created the National Vaccine Injury Compensation Program (VICP), a no-fault alternative to the traditional tort system. It provides compensation to people found to be injured by certain vaccines. Even in cases in which such a finding is not made, petitioners may receive compensation through a settlement.

The VICP was established after lawsuits against vaccine manufacturers and healthcare providers threatened to cause vaccine shortages and reduce vaccination rates. The Program began accepting petitions (also called claims) in 1988.”

Here are ‘Injury Tables’ describing petitions brought for compensation between 2015-17. Doesn’t say how many cases or how they were adjudicated.

This is a comprehensive list updated monthly (from 1989 to date) that includes: Petitions Filed; Adjudications Compensated and Dismissed; Awards Paid by Type and Amount; Claims by Vaccine; Adjudications by Vaccine.
 

Article on VICP with some case details, from 2017 (link)

Durant’s injury, her legal practice, and the petitions filed at the vaccine court offer a window into the real risks of vaccination. Those risks can be as severe as extremely rare, dramatic deaths from anaphylaxis—an overwhelming allergic reaction—or as quotidian as shoulder injuries like Durant’s. And although petitions to the court do include the kind of bogus injuries that frighten parents, the most common, and prominent, of those has not been warmly received: Not once has the court compensated a petitioner claiming that a vaccine caused autism.

Durant, who says she makes her living by winning compensation for genuine vaccine injuries, emphasizes the point. “Vaccines keep us healthy. They eradicate disease. If I had children, I would get them vaccinated.”

The vaccine court’s data show that bona fide vaccine injuries are rare. For every million vaccine doses eligible for compensation that were distributed in the decade beginning in 2006, the court compensated one injury victim. Depending on the gravity of the disease in question, receiving a vaccine is orders of magnitude less dangerous than staying unvaccinated. The tetanus vaccine that Durant received causes a life-threatening allergic reaction in at most 0.0006% of people who get the shot. The U.S. case fatality rate from tetanus, by contrast, is 13.2%.

 
Clarifying Some Misconceptions About Vaccines

  • Vaccines do not cause autism.
  • Infant immune systems are easily capable of handling vaccinations, and bundling several vaccinations together has been proven to be safe.
  • Vaccine-given immunity is safer than naturally acquired immunity, since the symptoms of the disease are avoided.
  • Vaccines do not contain harmful levels of toxins. While some chemicals present in vaccines can poison you at high enough levels, those chemicals are present at far below the level where they become dangerous. Every substance can be lethal at a high enough dose (see LD-50). Water, salt, cyanide, etc. What matters is how much of it enters your body (compared to your weight).
  • Vaccines, not better hygiene, are the cause of reduced disease.
  • Vaccines are FAR safer than avoiding them and risking the diseases they prevent.
  • Vaccines in use today cannot give you the disease they’re meant to prevent.
  • Vaccines are still necessary to prevent the spread of disease even though the infection rates are already low.
  • More info (we will add additional scientific sources to support each of these points)

 

How the 1957 Flu Pandemic Was Stopped Early in Its Path (link)

Making a vaccine for a new flu strain is very different from making a vaccine for something completely new like COVID-19, the novel coronavirus that emerged in 2019. Doctors and scientists first developed viable flu vaccines in the 1940s, so they were not starting from scratch when they went to work on the 1957 flu vaccine. Still, Hilleman bypassed regulatory agencies in his efforts to push the vaccine forward because he worried those agencies would slow the process down.

When the new flu strain hit the United States in September, just as Hilleman had predicted it would, the country was ready with a vaccine. The virus, dubbed the “Asian flu,” killed an estimated 70,000 to 116,000 Americans and one to four million people worldwide, but experts suggest it would have killed many more if not for the vaccine. Around the time Hilleman was born, the “Spanish flu” of 1918 to 1919 killed an estimated 675,000 Americans and 50 million people worldwide.

“That’s the tricky thing about public health,” says Alexandra Lord, chair of the division of medicine and science at the Smithsonian National Museum of American History in Washington, D.C.

“When things go really, really well, it’s very hard to say, ‘this many lives were saved,’ because we don’t know what would’ve happened without it,” she says. “And so while it’s impossible for us to say how many lives exactly were saved, I think it’s just good to say that he dramatically turned a pandemic around.”