The
marketing application submitted by the manufacturer for a medicine
includes data on the pharmaceutical quality of the medicine, and
on efficacy and safety.
The
firm requesting a marketing authorisation carefully selects these
data. Obviously, the firm wants to show this product in its best
light. Very often, the clinical trials have been designed merely
to show that the medicine is just as effective as the existing treatments,
as the current regulation does not demand that a new medicine be
superior to available options.
The
pressure on experts from regulators is very important considering
the financial stakes. The experts who examine the data should therefore
have critical appraisal skills in order to detect possible biases
the firm could have introduced, and to come to an independent decision.
Theoretically, they should be able to examine data not provided
by the company, or at least data available in the scientific literature,
in the agencies of other countries, in independent evaluation organisations
and pharmacovigilance bodies.
The
recent celecoxib (CELEBREX°) affair is a case in point. In order
to present this product as having fewer serious effects on the gastrointestinal
system than its competitors and to obtain a corresponding modification
of the marketing authorisation, the company managed to publish in
a well-known journal (JAMA) a paper overstating the results of a
trial. A rigorous investigation of all trial results carried out
by the American Drug Agency (FDA) showed that the version published
had distorted the trial protocol, misconstrued the results by focusing
on the most favourable period of the trial and omitting the final
results. Eventually the modification to the marketing authorisation
was not granted but this decision took time and expertise.
Such
in-depth literature search and comparative appraisal of all data
is far from being achieved in the present time limit of 210 days
allowed for the decision to grant marketing authorisation. Experts
actually have at best two months within this time limit, and the
agencies do not usually provide them with any other data than what
has been selected by manufacturers.
Once
evaluation of data has been carried out, the experts hand in their
reports, which form the basis of the opinion given by the Committee
responsible for recommending the use of the medicine. Limitations
to usage, contraindications for some categories of patients (the
elderly, people with liver, kidney or heart problems) are some of
the difficult issues this Committee has to deal with. They show
that time and thoroughness are vital elements in the decision making
process, above all with this scarcity of data.
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