James C. McAllister III, MS, FASHP
Mr. McAllister is a health-systems consultant based in Chapel Hill, North Carolina.
In January 2009, the FDA issued
Good Reprint Practices for the
Distribution of Medical Journal
Articles and Medical or Scientific
Reference Publications on Unapproved
New Uses of Approved Drugs
and Approved or Cleared Medical
Devices (FDA.2008.D.0053). The 1997
statute and the implementing regulations
for the industry promoting unapproved
uses ceased to be effective
in September 2006, so new guidelines
were issued. After first review,
I thought the new recommendations
were significantly less stringent and
had opened doors for abuse by the
industry. A more careful review, however,
revealed "nonbinding recommendations"
that could maintain the
status quo if we hold the manufacturers
accountable for compliance.
The use of drugs for unapproved
indications has been an issue that has
frequently been discussed and sometimes
caused great angst in hospitals
and health systems. The predominant
conundrum has been genuine interest
in achieving optimal drug therapy
outcomes while ensuring safety and
minimizing cost.
The issue is complicated, if not created,
by the drug approval process
itself. Pharmaceutical manufacturers
usually race to drug approval to maximize
patent protection as well as generate
revenue. To achieve FDA approval
as rapidly as possible, the company
usually seeks approved indications for
use with data that are as robust and
least controversial as possible. Thus,
although there may be indications that
look promising, study data to support
this use may be incomplete or questionable
at some level. Manufacturers then
must decide whether to seek approval
for limited indications to bring the
product to market as soon as possible
or delay overall approval to expand the
number of approved indications.
Following the initial approval of
the new drug, the manufacturer must
then decide whether the investment
required in conducting additional trials
to achieve approval for new indications
will result in an acceptable financial
return. As you might imagine, a myriad
of factors, including the availability of
competitive products and duration of
patent protection, and the availability
of resources that could be available
for other drugs under development are
considered, but the dominant factor
will always be net profit.
Prior to approval, clinical trials generate
a great deal of interest among
research physicians who give presentations
and publish papers, the results of
which generate interest in using a drug,
including uses outside those indications
that are eventually approved by
the FDA. Clinical trials using the drug
often continue following FDA approval
and sometimes result in reliable data
supporting other indications. Some
other "trial" results also may be published
but without the scientific rigor
commonly used in studies submitted in
the approval process.
Individual prescribers are not bound
by the FDA-approved indications and
thus prescribe new drugs for unapproved
indications based on their professional
judgment. Pharmacy and
Therapeutic Committees have struggled
to ensure that such uses are substantiated
by as much reliable data as
possible and to minimize the influence
of manufacturers' representatives and
any promotional material that were
not substantiated by well-controlled
clinical trials.
The 1997 FDA Modernization Act
began the establishment of conditions
under which manufacturers could
distribute materials discussing unapproved
indications. In 2000, following an
Appeals Court decision, the FDA published
a notice clarifying a "safe harbor"
for manufacturers regarding distributing
materials about a drug's unapproved
uses. As a result, companies halted their
sales force from discussing unapproved
uses at all and frequently created a
cadre of providers—often pharmacists
and dubbed "medical science liaisons"
whose compensation was not tied to
sales and who were allowed to discuss
unapproved uses with providers. From
my perspective, this strategy had positive
results in terms of limiting inappropriate
influence of manufacturers on
prescribers who might consider inappropriate
uses.
Limiting inappropriate influence of
manufacturers over unapproved uses
will require vigilance on our part. We
must become familiar with the new
recommendations and report excesses
to the FDA. I think we are up to it.
What do you think?
Inside the Issue
