Hard to Swallow
The $800 Million Pill: The Truth Behind the Cost of New
Drugs. Merrill Goozner. vi + 297 pp. University of California
Press, 2004. $24.95.
The title chosen for Merrill Goozner's The $800 Million
Pill was outdated before the book was even released. The dollar
amount cited is the average cost of developing a single new drug,
according to a Tufts University study published late in 2001. But in
late 2003, the consulting firm Bain and Company put the cost at a
staggering $1.7 billion. This figure included some
marketing costs not counted in the Tufts study.
The high—and rising—cost of prescription drugs has been
on the minds of many people, from angry protesters in front of drug
companies' headquarters to American senior citizens traveling to
Canada or Mexico to buy cheaper medicines. The U.S. Congress has
responded by authorizing a prescription drug benefit for Medicare.
Pharmaceutical companies are viewed by many as greedy entities
(their average profit margin is considerably higher than that of
chemical companies in general) that are set on enriching themselves
at the expense of the public.
Goozner attempts to get to the root of this issue by investigating
the discovery and development of numerous drugs now on the market.
His conclusion, to simplify a bit, is that because many drugs are
discovered by government scientists, or government-funded
scientists, and some drugs are even put through clinical trials by
government laboratories, pharmaceutical companies do little more
than manufacture and sell the drug. Thus, he reasons, they are
charging the public unjustifiably high prices for their products,
because much of the arduous spadework in bringing a drug to market
is done by academic and government researchers at taxpayer cost.
This assertion is a gross oversimplification. Certainly, many
promising drug candidates are discovered by, say, academic
scientists funded by the National Institutes of Health or other
government agencies. Often, however, a synthetic pathway to the new
molecule may not exist, or it may require such exotic reagents,
solvents or conditions that industrial manufacture of the drug would
be impossible. Or the synthesis may turn out to be extremely
low-yielding, necessitating development of a completely new set of
reactions for making the molecule. For example, a Novartis team
recently came up with a hybrid synthesis of two previously published
methods for making an anti-tumor agent. The new synthesis took 39
steps and 20 months to devise!
And the development process does not end with a new synthetic
protocol. The synthesis has to be scaled up to commercial
quantities, and the drug has to be formulated—that is,
converted to a form that can be taken by the patient. Should it be
given in the salt or neutral form? Which crystal polymorph of the
drug is the most appropriate for delivery? How stable is the drug in
air at room temperature?
This type of grindingly difficult work, which won’t get you
published in Science or Nature, is the
"D" in R&D. Development scientists often toil in
obscurity for years, while their academic counterparts receive
accolades and public praise for their discovery efforts. I
know—I spent three years working as a development scientist
for a biotechnology-related firm. Goozner shows scant appreciation
for these aspects of drug development and breezily glosses over the
process between the discovery of an interesting new molecule and the
manufacture of a viable medicine. According to a recent (March 22,
2004) report in Chemical and Engineering News, these costs
can amount to hundreds of millions of dollars for a single drug.
Even if all of the above development hurdles are overcome, a company
may find that a drug candidate it has bet millions on fails in
critical patient trials. This is a huge risk that the company has to
assume—only one molecule in thousands ever receives FDA
approval. Furthermore, patent protection on new drugs lasts only for
a limited time. The portion of this "period of
exclusivity" during which a pharmaceutical company is actually
earning revenues from the drug is getting shorter. The patent
protection clock starts ticking once the drug is discovered, but the
company can't make money until it undergoes preclinical development,
passes all stages of clinical trials, and is approved by the FDA and
finally marketed. This process can easily take a dozen years or
more, leaving only a few years during which the drug can be sold
without generic competition. There are also marketing costs involved
in selling a drug, and these can be substantial, to say nothing of
legal expenses. By Goozner's own estimates, "the total
marketing budgets among drug industry firms may have exceeded $40
billion." Goozner largely ignores these costs associated with
drug development. In the final analysis, these companies are not
charities; they are under constant pressure not only to recoup the
billions they spend but also to make a profit.
This is not to say that pharmaceutical companies are above
criticism. Some of Goozner's complaints about them are quite
justified. Succumbing to pressure to report outsize profits each
year, they have focused on the blockbuster-drug business model,
which emphasizes the creation of new drugs that will generate
several hundreds of millions of dollars in sales each year. And they
deserve the castigation they receive here for developing scads of
"me too" drugs—simple modifications of existing
medications that have marginally greater efficacy than the original
(although some of these variants—for example, those for the
treatment of allergy or depression—may be important). The
myriads who suffer and die from tropical diseases such as malaria,
tuberculosis and leishmaniasis, most of whom are desperately poor,
hardly register on the radar of "big pharma," because
therapies for their ailments would not generate much in drug sales.
After all, do we really need another Viagra when millions die each
year from drug-resistant tuberculosis?
Unfortunately, The $800 Million Pill is heavy-handed and
repetitious. For example, the "compassionate use" policy
of giving experimental drugs to desperately ill patients is defined
and elaborated on more than once, and Margaret Fischl's AIDS
research is described twice. The central (flawed) thesis—that
the government invented the drug, so citizens should get it
cheaply—is repeated over and over.
The book is further vitiated by errors in the science, especially in
the abysmally poor summary of chirality (the "handedness"
of certain molecules), which Goozner describes as arising from
"carbon atoms arrang[ing] themselves in six-sided rings.”
He also refers to “the amino acid sequence of a gene."
And he writes that x-ray crystallography was developed with
"federal research dollars," implying that it was a U.S.
invention, whereas it was actually developed in Great Britain by
William Henry Bragg and Lawrence Bragg.
The issues in drug development are complex. They are incompletely
addressed by Goozner's one-sided analysis, which overlooks important
aspects of drug development.—Tim Royappa, Chemistry,
University of West Florida