Posted March 30, 2004
Patent Law Changes May Help in Race Against
|Ramanan Laxminarayan: “We
have to make people more aware of the cost they are imposing on
the rest of society.”
The rapidly increasing resistance of bacteria to antibiotics, one
of the 20th century’s wonder drugs, is happening because neither
users nor makers have incentives to care about the problem, according
to Ramanan Laxminarayan, a natural resources economist with Resources
for the Future, a Washington, D.C.-based think tank on environmental
policy. Laxminarayan spoke on “Drug Resistance: Economics and
Regulation” at the Law School March 24.
Broadening patents on antibiotic drugs to cover whole classes of drugs
rather than particular compounds may give pharmaceutical companies
sufficient reason to care about the growing threat of superbugs, bacteria
that now defy formerly effective drugs, said Laxminarayan, who also
teaches at the Johns Hopkins University School of Advanced International
Antibiotics are now taken for granted, although there are still elderly
people who can recall the days when infections commonly caused death.
Penicillin, the first known antibiotic, was discovered serendipitously
in 1928 by Scottish scientist Alexander Fleming but not available for
widespread use until World War II. Fleming predicted future bacterial
resistance, but for a time scientists believed that the drugs could
allow the eradication of infection. It soon became clear that Darwin’s
principle of natural selection was working and superbugs were evolving
that would be invulnerable to known antibiotics.
“A small, persistent percent of the bacterial population is
naturally resistant,” and selection pressure “straight
out of Darwin’s playbook” means the resistant ones survive
and multiply, he said. Control thus gets successively weaker over time.
In 1987 only .02 percent of bacteria were penicillin–resistant.
By 2002, 16.5 percent were. Staphylococcus resistance is now at 40
percent. Resistance to Vancomycin, the most powerful of the antibiotics
and so prescribed only as a last resort, had reached 12 percent by
1994, he said.
Selection pressure is exerted because human patients do not comply
with usage instructions (failure to complete a course of treatment
means some of the more resistant bacteria survive and reproduce); through
long-term antibiotic treatment of nursing home patients; and through
the prophylactic use of antibiotics in poultry and cattle feed, where
lowered rates of infection also produce weight gains.
“The speed of global travel is spreading resistance too,” Laxminarayan
said. He cited the 40-year global spread of malaria’s resistance
to chloroquinine as an example.
Resistance increases mortality from infection and raises the cost
of developing new drugs. To combat the growth of resistant germs, “everybody
has to move to the new drug even if they are not infected with a resistant
strain.” Thus costs amplify.
“No one has an incentive to care about resistance because the
costs are externalized. Physicians and pharmaceutical companies don’t
really care either,” said Laxminarayan. “We have to make
people more aware of the cost they are imposing on the rest of society.”
All antibiotics are derived from the same 15 or 16 compounds. With
the average cost of developing a new drug now at $500 million, the
strongest incentive for manufacturers is to make drugs that people
continue to take to treat chronic conditions. But in the case of antibiotics, “you
depress the market by entering it,” Laxminarayan explained.
There are two avenues for dealing with the resistance issue, he said:
getting better compliance about usage and finding new drugs. Greater
compliance might be possible through raising prices and regulatory
burdens, but better compliance also reduces the incentive to find new
drugs. Higher co-pays raise social equity issues. One study showed
that patients with drug insurance get 85 percent more antibiotics than
patients who must pay part of the cost of the drug themselves.
In 2000 there were 16 new antibiotics in trials and three pending
approval from the FDA. One drug is in a new class, but the rest are
the result of “tinkering around with existing molecules,” Laxminarayan
said. Antibiotic research is an “extraordinary small” share
of drug research. In 2000, $26.4 billion was spent on drug research
and of that, only 14 percent was toward new anti-infectives. Within
that category, most money is directed toward finding drugs effective
Because few new antibiotics have been discovered, newer ones tend
to be held in reserve for use against resistant germs. But it would
be better if they were used as “workhorses,” Laxminarayan
said. “More diversity of antibiotics reduces the likelihood of
general resistance. If the drugs have different mechanisms for working,
the chance of developing resistance is extraordinarily low.
“This is a game where we could try to co-evolve with the pathogens,
but the pathogens reproduce generations rapidly—faster than this
lecture takes. So this is not a good strategy.
“We need to give the pharmaceutical industry incentives to
develop narrow-spectrum antibiotics.” Patent law changes that
allowed drug makers to hold monopoly rights over broader chemical groups
could be one approach, Laxminarayan said. Three years ago the Food
and Drug Administration asked Bayer to stop selling a drug used to
treat salmonella for similar reasons, but the company refused because
it had competitors who would keep producing the drug.
During discussion, U.Va. professor of pediatrics Dr.
Tom Massaro, formerly a Health Sciences Center administrator,
said that “any resistant infection in a patient adds $30,000
to $50,000 to the cost of his or her care.” He proposed that
Medicare rules be changed to give hospitals incentives to lower resistance
rates. He also cited nursing homes as key incubators of resistant
Laxminarayan suggested that other strategies to consider would be
to subsidize the cost of antibiotics, to develop vaccines for diseases,
to extend the term of patents, and to speed up the drug-approval process.
He said the FDA is considering product labels, but “They don’t
really work. They’re like billboards that ask you to carpool.”
Laxminarayan’s talk was sponsored by the Sadie Lewis Webb Program
in Law and Biomedicine and hosted by associate professor Anup
• Reported by M. Marshall