Initial safety trials on volunteers are carried out within fairly limited criteria. In the first instance, when assessing the safety of a vaccine, the adverse reactions researchers are looking for are, of course, going to be those similar to the symptoms of the disease being vaccinated against, there is a certain blinkered approach to the possibility of other adverse effects. For example when assessing the safety of a measles vaccine, researchers are more inclined to be looking for symptoms of measles with its known complications rather than the possibility of other symptoms.
Once the vaccine is in the population there are then acknowledged difficulties in assessing the incidence of adverse events by the relevant health authorities, this is mainly due to the reliance on ‘voluntary’ reports of adverse events sent in to the health authorities by doctors. It is interesting to note that in countries where reporting is compulsory such as in France the number of adverse events are higher than in countries like the UK where reporting is voluntary.
However the under-reporting of drug side-effects is a world-wide phenomenon, in 2006 the Drug research unit at Southampton University published a survey of reporting incidence in the international journal of toxicology and drug experience. (Drug safety 2006;29(5):385-96.)
In total, 37 studies using a wide variety of surveillance methods were identified from 12 countries. These generated 43 numerical estimates of under-reporting. The median under-reporting rate across the 37 studies was 94%. (L.Hazell & S.A Shakir.)
A massive 94% of side-effects are consistently not reported around the world and the research team found that many of these are severe reactions to drugs.
The withdrawal of the Urabe strain of mumps virus used in MMR vaccine illustrates quite clearly the phenomena of under-reporting with regard to adverse effects. The Urabe strain used in the mumps component of the MMR vaccine was implicated in some cases of meningitis because the vaccine virus particles were isolated from the cerebrospinal fluid of affected children. Canada stopped using the vaccine in 1989. In the UK however, where alternative strains of mumps vaccine were not so readily available, the health authority wanted to study the situation before considering the withdrawal of the vaccine whilst they had nothing to replace it, therefore various studies were conducted to assess the risk.
Studies based on voluntary reports gave reassuringly low estimates, 1 case of meningitis per 143,000 (notification by doctors) to 1 case in 250,000 (voluntary reports by paediatricians). So although there were cases of mumps meningitis being caused by the vaccine they were, according to the health authority, acceptably low. But when greater efforts were made to identify cases, for instance by cross-linking laboratory and hospital reports to vaccination records, the risk rose to between 1 in 4,000 (notification by doctors) and 1 in 21,000 (voluntary reports by paediatricians). These studies were reported by the UK Parliamentary office of science and technology and suggested significant under-reporting of vaccine-associated meningitis, which led to the withdrawal of the vaccine in 1992.
For many years MMR was therefore causing mumps meningitis in children and was essentially going unnoticed; its incidence was being under reported by a factor of 30. Thirty times more cases were found, using different methods of assessing the numbers of cases, and it took the withdrawal of the vaccine from another country before we noticed the problem in the UK. The main method used to assess the numbers of adverse events from vaccines, was through the use of voluntary reports made by doctors to the health authorities, essentially, doctors have to make the connection between a symptom and the vaccine and secondly admit to the connection between the health problem and the vaccine and finally to report it, all of which lead to significant under-reporting of that particular vaccine problem.
Perhaps researchers can be forgiven for not noticing and therefore not reporting the adverse effects of vaccines on individuals, especially if those effects appear to be unrelated to the illnesses being vaccinated against. The previous example of meningitis, is not a classical symptom of mumps and therefore not likely to be associated with the use of the mumps vaccine. Another example of this being, Lupus erythematosus, an autoimmune disease of the connective tissue, which has now been found to be associated with the Hepatitis B vaccine. Lupus is a self-destructive inflammatory condition with the formation of scar tissue often affecting the skin, heart, lungs and brain, whereas hepatitis is a condition affecting the liver.
However the USA National Academy of Sciences report into the side effects of vaccines published in September 1993 demonstrates that even when the adverse effects of the vaccine look similar to the symptoms of the vaccine illness, they are still being overlooked by the medical community.
The above 1993 report was written by an expert panel convened by the Academy’s Institute of Medicine and was headed by Richard Johnston, a Yale University Paediatrician who stated that the “biggest surprise” was the evidence showing that tetanus and oral polio vaccine caused Guillain-Barré syndrome. However Guillain-Barré syndrome involves symptoms of paralysis and could in fact easily be mistaken for polio.
Which in itself, bears testimony to the negligence of the researchers into the safety of the vaccine and the surveillance system set up to monitor the adverse effects of vaccines. Polio and tetanus, although different illnesses, are both characterised by symptoms of paralysis, Guillain-Barré also involves symptoms of paralysis, when vaccines are introduced into the population, at the very least, researchers would be looking at the incidence of symptoms that are similar to the symptoms of the illness being vaccinated against. Polio vaccine and tetanus vaccines were introduced, they were creating syndromes of paralysis (Guillain-Barré syndrome) and 30 – 40 years after the widespread introduction of these vaccines, in 1993 evidence of them causing paralysis was a “big surprise”.
This of course is evidence of an extremely poor monitoring system and, as reported in New Scientist 25 September 1993, Joanne Hatem, who heads the USA Health Research Council in her comments of the above report states: “The subtext of the report is that the FDA and CDC (the agencies involved in monitoring disease and drug reactions) have done a dismal job in following up and analysing reported reactions”. So, not only are the reporting systems deficient but the analysis and follow up of those reported cases are also inadequate.