developed world. The fundamentals are given in
theGuidance for Industry – Good Pharmacovigi-
lance Practices and Pharmacoepidemiologic
Assessments (http://www.fda.gov/cder/guidance/
index.htm). This document outlines the methods
of obtaining and assessing observational data
regarding drugs; it considers the methods of detect-
ing signals of adverse effects, assessing and inter-
preting these signals and planning effective PMS.
A second similar document is entitledGuidance
for Industry – E2E – Pharmacovigilance Planning.
This is available on the same web site and is, in
essence, concerned with the generation and review
of a formal plan for the conduct of a well thought
out PMS or pharmacovigilance program. The third
document in this series is entitledGuidance for
Industry – Development and Use of Risk Minimi-
zation Action Plans. This document, like those of
other regulatory authorities, has arisen from dis-
cussion over recent years and it accepts that there is
a risk, and plans to discuss the risk and minimize it.
Not to plan and conduct an effective pharmacov-
igilance and risk minimization program is clearly
negligent.
44.3 When the balloon goes up
The threat to the marketing authorization usually
develops very rapidly and often in response to an
event which grossly biases the data. Typically a
few worrying reports have been trickling in and
then one of the regulatory bodies makes an
announcement seeking additional data – and this
produces a flood. Doctors and other reporters
remember a case they could not make up their
minds about, but the announcement, however gen-
tle, makes up their minds for them and they report.
The trickle becomes a flood and the company is
put on notice that action of some sort is likely to
have to be taken. There is no sacred text that tells
the officers of a company what to do, but the
following steps should, experience suggests, be
considered:
- Organize a task force of appropriate in-house
experts and specialists supported by outside
consultants who have lived through the present-
ing kind of problem before. Support the task
force by obtaining the advice of two or three
national specialists whose expertise is directly
relevant to the problem. The task force should
be chaired by the Chief Executive Officer and
have the Research Director, Medical Director,
Legal Advisor, Head of Regulatory Affairs and
the Principals dealing with the product in ques-
tion on it. It should meet frequently, have an
organized agenda and record minutes.- Advise the regulatory authority who is on the
task force and who is its Technical Secretary and
contact point. This will reassure the regulatory
people with whom it is essential to establish
professionally trustworthy relationships. - If any information has leaked out (e.g. by
requests for additional data), prepare a sensible
and comprehensive press release. This should
emphasize that these problems cannot be pre-
vented as rare events but they can and are being
controlled. Have one Press Liaison Officer and
allow no other press contacts. Any evidence
of a ‘cover-up’ provides the press with a story
in its own right and this is best avoided by
openness. - In an organized way reexamine the molecular
structure of the drug and the known adverse
effects of related molecules. In the same way,
revisit the animal safety evaluation data and
the clinical trials data to make sure, in the light
of the new suspicion, that nothing has been
missed. - Get full but anonymized copies of the suspected
Adverse Drug Reaction Reports in the hands of
the regulatory authority. Eliminate duplicate
and triplicate reports (as these can swell the
numbers in an alarming way). Do everything
possible to ensure that the reports have been
followed up properly and the final diagnosis
established. Make sure that patients suffering
from inborn errors of metabolism are not being
included just because they are receiving the
drug in question. Look for clustering, for
44.3 WHEN THE BALLOON GOES UP 581