I
enjoyed the article "Premarket Approval or
Premarket Notification: An Update" by Jonathan
S. Kahan (October 1984). and I found it to be
accurate and well written. Since I was formerly
a medical officer for FDA, I would offer some
suggestions to assist companies in preparing and presenting the clinical
aspects of a premarket approval (PMA) application.
Probably most important is learning to write a
protocol. This document is critical and can make
or break a study. The protocol should clearly
state the motivation for the study with a
reasonable literature review and should discuss
the objectives (i.e., purpose, methods of
measurement, length of time, and number of
patients required). The study design should
include how patients will be recruited, which
patients will be accepted, and which patients
will be specifically excluded. FDA requirements
on informed consent, institutional review
boards, etc., should always be conscientiously
followed.
Choosing the proper clinical trial is also
important; for this, comparability is the key.
The ideal clinical trial would be large,
multicentered, double-blind, and randomized; but
such studies are expensive and difficult to
achieve. Therefore, you may need to consider an
alternative.
One option is to use nonrandomized concurrent
controls, in which two groups of patients, not
selected on a random basis, are studied with
different treatments or tests. A disadvantage is
that since patients are not randomly selected,
there is always the question of selection bias.
For example, were the sickest patients given
conventional care and the healthier patients
given the new therapy?
Randomized control trials are those that are
recommended. Here, there is a comparative study
in which the treatment and control groups are
assigned randomly to eliminate selection bias.
The three main advantages of such a study are
the elimination of bias in patient selection,
the tendency for balance of the baseline or
prognostic factors (i.e., the severity of the
illness), and the determination of a valid test
of significance.
Another option is to use an uncontrolled study.
Although it is rare that these studies are
satisfactory, they may be useful in collecting
safety data when large numbers of patients are
required to determine a safety issue.
Since PMAs are reviewed by both FDA and an
outside panel of experts, knowing how to prepare
for the presentation can prove equally
beneficial. Effective presentations require
skill, experience, and effort; clear conclusions
should be achieved from a thorough analysis of
the subject.
1.
First and foremost, know the submission
requirements and submit all documents.
2.
Inquire about providing additional copies of
your report so that a reviewer does not have to
be waiting for a copy.
3.
Know your audience. The interests, backgrounds,
and expertise of those participating in the
review should affect your presentation.
4.
Explain why this new technology is important --
e.g., does it save lives, time, or money? Does
it improve the quality of life?
5.
Define your goals. Be clear and specific about
your conclusions. The sponsor should be
absolutely clear and certain about what is to be
achieved, i.e., the labeling goals.
6.
Know your visual aids and be prepared to
continue your presentation in the event of a
mechanical failure.
7.
Be mindful of the allotted time. Begin by
stating your objective and conclude by
summarizing the achievement you expect.
