By Isadora B. Stehlin

Ads in the paper. Referrals from personal physicians. Lots of phone calls and months of waiting. These are the typical ways people find out about and participate in drug studies. But for Washington, D.C., psychiatrist Stephen Peterson, M.D., his participation in a drug study began with lunch.

On a spring day in 1994, Peterson joined two friends, allergists Martha White, M.D., and Michael Kaliner, M.D., for lunch at the Washington Hospital Center cafeteria. Peterson is the chairman of the Department of Psychiatry at the center, and White and Kaliner are with the center's Institute for Allergy and Asthma.

During the meal, Peterson started talking about his asthma and ended up being recruited for White's study of an asthma drug.

"She got real excited," says Peterson. "She said if I was taking [inhaled] steroids [for my asthma], I could be part of her study."

Peterson, 44, says that although the inhaled steroids he was taking at the time had his asthma under control, "I was happy to help out because I very much believe in the scientific method."

What Peterson agreed to participate in is commonly called a clinical trial--that is, an experiment done with people. These trials are performed at hospitals and research centers around the country. FDA reviews the data from clinical trials and other research in deciding whether to approve a new drug application.

The drug White and Kaliner are studying is Aerobid-M (flunisolide), manufactured by Forest Pharmaceuticals, Inc. An inhaled corticosteroid, Aerobid-M is used on a continuing basis to prevent asthma attacks. FDA approved the drug in 1984 for adults with asthma who require daily medication with corticosteroids. So why are the scientists running another study?

White explains that the approved dosage is two puffs, twice a day. "What the drug company wants to know is if someone can take four puffs just once a day and do just as well," she says. "They're hoping to be able to simplify the dosing regimen. Clearly if you can take a medication once a day instead of twice a day it's É easier on the patient [and therefore] will probably increase compliance."

"We try to encourage these kinds of studies," says Cathie Schumaker, a pharmacist and consumer safety officer in FDA's division of oncology and pulmonary drug products. "Anything that will help the drug be used more efficiently, encourage compliance, or make it available to a wider population means people will get better health care."

Even though a drug--like Aerobid-M--is already approved, if a study is being done to support a change in the approved labeling, the manufacturer must submit an amendment to its original investigational new drug application, explains Schumaker. Then, when the study is complete, a supplement to the original new drug application is required.

Peterson says his asthma is relatively mild compared to other people's. But it is serious enough to have kept him on several drugs over the past 11 years.

Although he didn't realize it at the time, his asthma began in 1983.

"I noticed when I was running, I was having a hard time finishing my run, especially during high pollen times," he explains. "A couple of times I found I was wheezing after running." But, he says, he didn't really understand what the problem was until, out of professional, not personal, curiosity, he went to a lecture about asthma.

After the lecture, "I talked to my colleague who's a pulmonologist and he offered to give me a pulmonary function test. The test was abnormal and that's how I found out I really had a problem with asthma."

Asthma is a lung disease that may be inherited or may develop as a severe allergic reaction to pollen, viruses, dust, cigarette smoke, and other "triggers" (but not everyone with allergies develops asthma and not every asthmatic has allergies). Chronic asthma occurs whenever sufferers are repeatedly exposed to a trigger. Another common form is exercise-induced asthma, which occurs only when a person exercises.

Peterson's asthma is both exercise-induced and chronic, triggered by pollen in the spring and summer, leaf mold in the fall, and dogs.

Once Peterson knew the cause and triggers of his asthma, he began preventive treatment. While he's tried many different treatment regimens, he's had the greatest success with inhaled corticosteroids used daily and occasional use of a bronchodilator about 15 minutes before running. Inhaled corticosteroids reduce inflammation of the airways, decrease mucus production and swelling, and may allow other asthma medicines to work more effectively. Bronchodilators work very quickly to dilate (open) the narrowed bronchial tubes, allowing oxygen to enter and carbon dioxide to exit the lungs more freely.

Peterson's history is typical of the people recruited to participate in this study. "We are looking for participants who are asthma success stories when on usual doses of inhaled corticosteroids," says White. The study began in early 1994 and should take a little over a year to complete. Between 250 to 300 patients across the country will have participated by the time it's over.

Peterson participated in the clinical trial four months. First, he had to read and sign a consent form, required by law, that informed him that the dosing regimen he would receive is experimental. It also explained the known possible side effects of the drug.

Corticosteroid inhalants can occasionally cause throat irritation and thrush (a fungal infection in the mouth). Gargling with warm water after using the inhaler helps avoid those problems. Prolonged use of very high doses may increase the risk of side effects such as high blood pressure, diabetes, osteoporosis, and suppression of bone growth in children.

Next, he underwent a complete physical exam. Then he, and everyone in the study, took the already approved dose of two puffs twice a day of Aerobid-M for a month.

At the end of the month, White tested Peterson's lung function with a methacholine challenge test. The test involves inhaling the drug Provocholine (methacholine chloride). In normal people this drug has no effect. In asthmatics, it causes bronchospasms and wheezing.

"It's a very good diagnostic test," says White, "and it's also used to determine just how severe the asthma is. The more severe the asthma, the lower the dose É that will cause tightness."

As soon as someone reacts to the drug, a bronchodilator is administered to bring the lungs back to normal.

Peterson says that the worst part of the methacholine test wasn't the wheezing but the preservative-like smell of the drug. "It reminded me of anatomy class [in medical school]."

Peterson then began the main part of the study. To prevent bias that can sometimes lead to overrated positive results, Peterson, like all the other trial participants, received four different canisters. He was told to take two puffs from each of two of the canisters in the morning and two puffs from each of the other two at night. That made eight puffs total, but, at the most, only four puffs were actually Aerobid-M. The other puffs were placebos containing inactive substances. Not only was Peterson "blind" to how much real medication he was receiving, the doctors also were purposely ignorant of Peterson's regimen. When both patients and researchers are unaware of the patient's drug regimen, the study is considered to be "double-blind."

In this study, the patients were divided into three groups: one group took four puffs of Aerobid-M once a day; a second group took two puffs of the drug in the morning and two puffs at night (the labeled dosing regimen); and a third group took only two puffs of Aerobid-M once a day. The purpose of the third group was to determine the effectiveness of a reduced dose.

"At first, most doctors put people on the recommended dose of an inhaled steroid to get their symptoms under good control," explains White. "Then [the doctors] start backing down on the dose to figure out how much is necessary to maintain them. But, as far as I know there haven't really been any studies on this practice. We've all been doing it in practice anyway. This study may give some validity to it and perhaps some guidelines."

This study had no placebo controls--people off corticosteroids completely. "We were all uncomfortable doing that because these were people who had already demonstrated the need to be on corticosteroids," says White.

Besides inhaling four puffs in the morning and four at night, "I also needed to test myself twice a day with a peak-flow meter," Peterson says.

A peak-flow meter helps asthmatics monitor their symptoms by measuring how fast air is blown out of the lungs.

During the trial, Peterson says, sometimes he felt better than when on other drugs and sometimes worse. At the end of the three months, White gave Peterson another methacholine challenge test.

"Overall, he did fine," says White, "but the test was blinded, so I don't know what dose [schedule] he was on."

"I learned a great deal about pulmonary function tests," Peterson says. "I also learned that [for the researchers] doing a scientific study like this is a lot of work."

Peterson says he would be glad to participate in another clinical trial, and, as if to allay any doubts about his sincerity, he still joins Kaliner and White for lunch several times a month.

Source: Food and Drug Administration (FDA)
"Drug Testing from a Patient's Perspective" appeared for the first time in the FDA Consumer Special Report on New Drug Development in the United States (January 1995).
Isadora B. Stehlin is a staff writer for FDA Consumer.