Disease outbreaks like the swine flu epidemic present an unparalleled opportunity — and to us, as doctors, an imperative — to gain knowledge to better protect the public. The spreading H1N1 influenza, now found in 40 countries and confirmed in some 10,000 patients, provides the chance to learn more about the drugs we are counting on using against it.
In the United States, the Strategic National Stockpile contains two drugs for influenza — oseltamivir, known by the trade name Tamiflu, and zanamivir, called Relenza. The Centers for Disease Control and Prevention’s Web site recommends that these drugs be given to selected patients who have the flu and be considered for other people in the patients’ households who are at risk of serious complications if they become infected. But there remain unanswered questions about how well the drugs work.
One of these is how soon the drugs must be used to keep flu from spreading. One clinical trial conducted by the maker of Tamiflu looked at what happened when people in the household of a flu patient were given the drug within two days of the patient’s symptoms. Only 1 percent of them caught the flu. This was a significant amount of protection; when people in other flu households were given a placebo, 12 percent got the flu.
But it’s unusual for healthy people to go to the doctor in the first two days of feeling symptoms of a cold or flu. Now that doctors’ offices are crowded with flu patients, it may be especially difficult to obtain quick medical attention. So we must wonder, if a flu patient doesn’t see a doctor in the first 48 hours, can the drugs still prevent illness in other members of the household? Would they be less effective as time goes by? These questions could be asked of both Tamiflu and Relenza.
The present epidemic provides an opportunity to investigate. Clinical trials could easily be set up to include patients who show up for medical attention 72 or 96 or more hours after their symptoms appear. The results could be used to plot a curve of risk over time to guide patients and doctors in the use of anti-influenza drugs. Knowing how much households stand to benefit from treating a patient who has had the flu for more than two days would also help public health officials plan for the most efficient use of our flu drug stockpiles.
Another important question is how well the drugs can work to save lives. In clinical trials conducted by the manufacturer, Tamiflu was shown to shorten the time in which influenza patients have symptoms like fever, headache, cough, muscle ache and fatigue. Patients who received the drug felt ill for 1.3 fewer days than those who received a placebo did. But it would be good to know more about what both Tamiflu and Relenza can do for patients with the new H1N1 flu, for which we have as yet no vaccine. As the cases increase, it becomes easier to assess whether the drugs reduce complications like post-influenza pneumonia, hospitalizations and fatalities.
Data from real-time clinical trials could enable us to not only provide better care for flu patients and their families but also better manage resources. And, armed with new data to meet this emergency, we could be better prepared for the next one.
Andrea Meyerhoff and Paul Lietman. They are on the faculty at Johns Hopkins University School of Medicine.