Government & Medicine

Antimicrobials aren't immune to public policy

To fight an advancing horde of infections, changes
are needed to make R&D more cost-effective

By Hugh W Coulthart

Alarm bells are ringing in infectious disease circles as ominous storm fronts gather and appear more and more likely to converge in a global whirlwind of contagion.

Dr Coleman Rotstein, of McMaster University's Division of Infectious Diseases, is one of an army of specialists across the country waging daily war with pathogens against which there are no effective antimicrobial agents. According to Dr Rotstein, the availability of antimicrobial agents is only one strategic element in a campaign broad enough to meet the challenges brought by infectious diseases. In his view, the campaign must become an urgent priority of the federal government's new public health policy initiatives and should encompass improved and continuous surveillance of the incidence and distribution of infectious diseases across the country.

OLD & NEW
The battle is underway on many fronts. Scientists are having to contend with re-emergent infections like tuberculosis, gonorrhea and syphilis, which are joining a wave of newer infections, including HIV, SARS, West Nile virus, and most recently, avian flu.

Another challenge is that microbial pathogens are becoming increasingly resistant to existing antimicrobial agents. One incident that caused particular concern among public health officials in Michigan and Pennsylvania in 2002 was the emergence of Staphylococcus aureus that was resistant to vancomycin, typically the drug of last resort for treating it and several other infections. Until recently, methicillin-resistant S aureus had appeared only in elderly or immune-compromised patients in hospital settings. It's now infecting the young and the healthy in the general population.

The battery of defensive resources available to physicians is not keeping pace with the growth of new and re-emergent infections. The Infectious Disease Society of America (IDSA) sums up the situation starkly: "The pharmaceutical pipeline of new antimicrobials, particularly antibacterial drugs, is drying up." According to the IDSA, in 2002 there was not one new antibacterial drug among the 89 medicines approved by the FDA. Since 1998, only nine new antibacterials have been approved and, of those, only two had novel active mechanisms.

RETURN ON INVESTMENT
The pharmaceutical industry's lack of interest in antimicrobial R&D is a matter of simple economics. Measured against the staggering costs of developing new antimicrobial agents, which the IDSA estimates at $900 million US, projected returns are unattractive. Quite apart from the cost of R&D, the nature of infectious diseases requires complex and lengthy clinical trials for any new antimicrobial agent. Once approved, they're prescribed for limited periods of seven to 14 days, compared to products for chronic diseases which may be prescribed for life. In addition, pharmacologists and microbiologists like to restrict the use of new agents, preferring to hold them in reserve as a last resort for when existing drugs fail. A wise strategy, perhaps, but one that further restricts market size. If you're going to invest almost $1 billion to develop a new product, you simply have to have a reasonable expectation of a healthy return before giving it the green light.

The Canadian Infectious Disease Society (CIDS), of which Dr Rotstein is president, and the IDSA, suggest that public policy needs to be adjusted to create incentives to stimulate R&D, and to mitigate -- if not eliminate -- disincentives. The CIDS also wants enhanced infection control practices in hospitals, doctors' offices and all public facilities. They believe that positive incentives are required to encourage new research, and approval processes must be adjusted to make it easier and less costly to get new antimicrobial agents out to the physicians on the front lines.

A critically important element in the campaign must be modification of the national immunization strategy as recommended by the October 2003 Report of the National Advisory Committee on SARS and Public Health. At present, public funding of immunization programs is unevenly distributed across the country, with the best coverage available to residents of Alberta. Four new vaccines are unfunded in most other provinces and territories. Without adequate federal funding, physicians across the country are not battling infectious diseases on a level playing field.