10-point-agenda for higher standards in vaccine licensing

vaccination
vaccines should fulfill a minium standard

DAGIA (Doctors Active for Global Immunization Awareness) In our opinion the current licensing practice does not meet the criteria which would support the evidence based use of vaccines. Still, there is no genuine discussion in professional circles on minimum standards for licensing. DAGIA as an independent organization is aiming at initiating a debate among experts with regard to that. If you are a medical doctor who considers these ten postulates reasonable you can document this by signing a list. Supporting these demands by as many signatures as possible we aim at laying emphasis on this topic in health care politics. This list is now online.
 

Definition of Expectations

Vaccine manufacturers as well as health authorities in charge cannot guarantee efficacy and safety for the individual.

However, they do promise a statistical health benefit for a defined number of vaccinated individuals as opposed to the unvaccinated.

Prior to the evaluation of a vaccine expectations pertaining to its quality need to be defined. These expectations, of course, must be defined from the point of view of those who are likely to benefit from the vaccination and also taking the risk of potential side effects, i.e. the vaccinated individuals or their parents and carers.

Necessity

The necessity of a vaccination expected to reduce the risk of contagion and the outbreak of a disease arises from the realistic risk of contracting the disease on the one hand and from the lack of alternatives in terms of treatment and prevention on the other.

Significant Health Benefits

In actual fact vaccinated individuals ought to demonstrate a significant health benefit compared to the unvaccinated.

Therefore, symptoms expected to be prevented by the vaccine have to be looked at and in addition all clinical parameters indicative of potential side-effects as well.

Risk Assessment of Vaccinations

In order to assess the risk-benefit ratio the risk of contracting a disease and the clinical efficacy of a vaccine need to be determined and also the statistical probability of side-effects.

Our concrete demands for licensing studies are as follows:

1. Randomized Placebo-controlled Multi-blinded Comparative Studies

In order to evaluate the health advantage of vaccinated individuals as against the unvaccinated both groups need to be compared in a clinical trial with open outcome and the exclusion of all potential variables that could lead to a distortion of results. Randomized placebo-controlled double-blinded studies are considered the gold standard of evidence based medicine.

In future however we may expect triple-blinded studies to become standard in order to prevent a distortion of the outcome in the process of analyzing the data.

2. Mandatory Entry into a Public Clinical Study Register

The scandal surrounding the influenza drug TAMIFLU where the manufacturer withheld study data clearly shows that a study is only fit to be included in the licensing process if entered into a public study register well ahead of time before launching it. Non-disclosure of crucial clinical trials and study data can lead to a significant bias in presenting the facts.

3. The Use of a True Placebo

A placebo is a dummy medication that has no active ingredient and no side-effects, for example a normal saline solution. Dummy placebos which contain ingredients of the vaccine do not meet the criteria of a placebo as defined above. Hence, data obtained in a clinical trial using a dummy placebo merely are of academic nature. A study comparing a vaccine to a different vaccine instead of a true placebo is equally useless. The requirement of using true placebos can not be taken for granted as shown by the licensing of the HPV vaccines GARDASIL and CERVARIX or the Rotavirus vaccines ROTARIX and ROTATEC (all licensed since 2006).

4. Adequate Sample Size and Study Duration

The objective of arriving at a relevant evaluation of health benefits in the vaccinated group can only be achieved by defining a minimum number of test subjects required for every group and by setting a minimum length of time for the study. Taking this into account rare, severe side-effects will be recorded which is crucial for balancing the calculated risks of a vaccine and the risks of the disease itself. A low incidence of a disease (preventable by vaccination) calls for a large sample size in order to determine comparable morbidity rates. In light of latest scientific data with regards to long term effects of aluminium adjuvants the duration of a clinical trial should be one year at least, preferably three years.

5.Transparency of Study Design and Data

The design of a study is a major determinant of its predicative power. Design and anonymized data need to be publicly accessible. Any alterations in the design of the study while it is ongoing are to be documented meticulously. The same holds true for the methods used in compiling the test subjects and accounting for those who quit the study and those having been excluded especially in cases of death.

6. Unrestricted Recording of Clinical End Points

During the entire duration of the trial all of the clinically relevant occurrences are to be recorded not just selected symptoms or pure laboratory data such as antibody titers.

7. Certified Confidential Person

Experience has shown that doctors conducting clinical trials tend to play down potential side effects in the presence of the test subjects. For this reason the trial participants must have access to a confidential person at all times who does not belong to the study.

8. Independence from Manufacturers

Clinical trials sponsored by drug manufacturers are biased as has been proved. There is a simple explanation for that: In cases of an unfavorable outcome of a vaccine study the research institutes and their staff will be less likely getting commissioned again in the future. It must be ensured that planning and conducting of clinical studies for licensing will be put in the hands of financially independent institutions.

9. Realistic Projection of the Epidemiology within the Population

The clinical licensing trials of the Rotavirus vaccines ultimately made it clear that disease outbreaks as recorded in a study did not necessarily reflect the actual epidemiology within the population due to the chosen diagnostic methods. A cross-check is mandatory with a third group of test subjects receiving neither an active agent nor a placebo. The strategy of recording data should include retrospective and prospective elements.

10. Longterm Surveillance of the Test Subjects

Following the licensing of a vaccine long term health implications in the test subjects need to be monitored in the setting of a longitudinal study.

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