DƯỢC LÍ Goodman & Gilman's The Pharmacological Basis of Therapeutics 12th, 2010

the time the patent is filed. During this period, the
patent owner may bring suit to prevent others from marketing
the product, giving the manufacturer of the
brand-name version exclusive rights to market and sell
the drug. When the patent expires, equivalent products
can come on the market, where they are sold much
more cheaply than the original drug, and without the
huge development costs borne by the original patent
holder. The marketer of the so-called generic product
must demonstrate “therapeutic equivalence” of the new
product: it must contain equal amounts of the same
active chemical ingredient and achieve equal concentrations
in blood when administered by the same routes.
Note, however, that the long time course of drug
development, usually more than 10 years (Figure 1–1),
dramatically reduces the time during which patent protection
functions as intended. Although The Drug Price
Competition and Patent Term Restoration Act of 1984
(the “Hatch-Waxman Act”) permits a patent holder to
apply for extension of a patent term to compensate for
delays in marketing due to FDA approval processes,
patents can be extended only for half the time period
consumed by the regulatory approval process, for a
maximum of 14 years. The average new drug brought
to market now enjoys only ~10-12 years of patent protection.
Some argue that patent protection for drugs
should be shortened, based on the hope that earlier
generic competition will lower healthcare costs. The
counter-argument is that new drugs would have to bear
higher prices to provide adequate compensation to
companies during a shorter period of protected time. If
that is true, lengthening patent protection would actually
permit lower prices. Recall that patent protection is
worth little if a superior competitive product is invented
and brought to market at any time in the patent cycle.
Drug Promotion
In an ideal world, physicians would learn all they need
to know about drugs from the medical literature, and
good drugs would thereby sell themselves; we are a
long way from the ideal. Instead we have print advertising
and visits from salespeople directed at physicians,
and extensive so-called “direct-to-consumer”
advertising aimed at the public (in print, on the radio,
and especially on television). There are roughly
100,000 pharmaceutical sales representatives in the
U.S. who target ~10 times that number of physicians.
It has been noted that college cheerleading squads are
attractive sources for recruitment of this sales force.
The amount spent on promotion of drugs approximates
or perhaps even exceeds that spent on research and
development. Pharmaceutical companies have been
especially vulnerable to criticism for some of their
marketing practices.
Promotional materials used by pharmaceutical companies
cannot deviate from information contained in the package insert. In
addition, there must be an acceptable balance between presentation of
therapeutic claims for a product and discussion of unwanted effects.
Nevertheless, direct-to-consumer advertising of drugs remains controversial
and is permitted only in the U.S. and New Zealand. Physicians
frequently succumb with misgivings to patients’ advertising-driven
requests for specific medications. The counter-argument is that
patients are educated by such marketing efforts and in many cases
will then seek medical care, especially for conditions that they may
have been denying (e.g., depression) (Donohue et al., 2007).
The major criticism of drug marketing involves some of the
unsavory approaches used to influence physician behavior. Gifts of
value (e.g., sports tickets) are now forbidden, but dinners where
drug-prescribing information is presented are widespread. Large
numbers of physicians are paid as “consultants” to make presentations
in such settings. It has been noted that the pharmaceutical companies’
sales representatives frequently deliver more pizza and free
drug samples than information to a doctor’s office. These practices
have now been brought squarely into the public view, and acceptance
of any gift, no matter how small, from a drug company by a physician,
is now forbidden at many academic medical centers and by law
in several states (e.g., Vermont and Minnesota).
The board of directors of the Pharmaceutical Research and
Manufacturers of America (PhRMA) has recently adopted an
enhanced code on relationships with U.S. healthcare professionals.
This code prohibits the distribution of non-educational items, prohibits
company sales representatives from providing restaurant meals
to healthcare professionals, and requires companies to ensure that
their representatives are trained about laws and regulations that govern
interactions with healthcare professionals.
Exploitation or “Medical Imperialism”
There is concern about the degree to which U.S. and
European patent protection laws have restricted access
to potentially life-saving drugs in developing countries.
Because development of new drugs is so expensive, private-sector
investment in pharmaceutical innovation
naturally has focused on products that will have lucrative
markets in wealthy countries such as the U.S.,
which combines patent protection with a free-market
economy. However, to lower costs, companies increasingly
test their experimental drugs outside the U.S. and
the E.U., in countries such as China, India, Russia, and
Mexico, where there is less regulation and easier access
to large numbers of patients. If the drug is successful
in obtaining marketing approval, consumers in these
countries often cannot afford the drugs they helped to
develop. Some ethicists have argued that this practice
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CHAPTER 1
DRUG INVENTION AND THE PHARMACEUTICAL INDUSTRY