It's not surprising that patients don't always take their medications exactly as prescribed. But most doctors might be astonished at the actual degree of nonadherence and the extent to which some patients might go to disguise it.

A study recently reported that one-third of volunteers who were assigned regular use of an inhaled bronchodilator in a clinical trial dumped the contents shortly before clinic follow-up visits in an effort to conceal their failure to take the medicine properly. The study was published in the August issue of the journal Chest.

Patient adherence to treatment and doctors' ability to monitor that compliance is at the heart of chronic disease management. There are always some patients who will admit to not taking treatment as prescribed. However, the study raises questions about how often patients deliberately mislead doctors in clinical trials -- and clinical practice -- and the ability of physicians to detect that deception.

Indeed, the patients who deceive physicians often are the individuals one might least suspect.

The study findings have wide-ranging implications. "If 30 percent of patients are not using their medications at all or hardly using them, you could misinterpret data on the efficacy of a drug or overestimate the dose required to provide a desired effect," said study co-author Donald P. Tashkin, M.D., professor of pulmonary medicine at the University of California, Los Angeles.

Adherence is already a major issue in patient care, particularly for individuals treated for mental illnesses, HIV and chronic conditions, such as diabetes. The issue is expected to gain in importance as the population ages.

"We will see more people live to reach old age, and we will see more morbidity requiring treatment, and consequently the need for more complex medical regimens that will have to be followed," said Eleanor Schron, R.N., a clinical trials researcher at the National Heart, Lung and Blood Institute (NHLBI) at the National Institutes of Health.

Not Wanting to Disappoint:

Subjects in the Chest report were a subset of participants in the 5,000-patient Lung Health Study, a five-year clinical trial to evaluate the effect of intensive smoking-cessation counseling and regular use of an inhaled bronchodilator on the progression of chronic obstructive pulmonary disease. All of the research subjects were smokers between 35 and 60 who had mild to moderate airway obstruction.

Participants knew their canisters would be weighed at each clinic visit and that a microelectronic device had been attached to the inhalers. But most were not told the device would record the exact date and time of each use. "We found about 30 percent of the participants over the course of the first year had, on at least one occasion and often on multiple occasions, completely eliminated the contents by actualizing the inhaler as many as 100 times successively, not knowing we would be able to detect this," Tashkin said. It's widely believed that in real-world clinical practice about 50 percent of patients with chronic conditions such as hypertension, asthma and diabetes fail to adhere to treatment regimens.

Noncompliance among subjects in clinical trials is believed to be much lower because of volunteers' willingness to participate in research. However, recent studies using objective measures, such as pill counting or weighing canisters, have found that nonadherence is more widespread in clinical trials than previously thought.

"You can prescribe all the pills in the world, but it still comes down to patient behavior," said study co-author Cynthia S. Rand, Ph.D., associate professor of medicine in the division of pulmonary and critical care medicine at Johns Hopkins School of Medicine.

Why would a volunteer purposely fail to follow directions? Ironically, patients who engage in dumping behavior are otherwise ideal research subjects. They tend to get along well with staff. They can be relied upon to complete questionnaires and show up for follow-up clinic visits. "They are very nice people who don't want to disappoint you," said Rand, a health psychologist. On paper, they appear to be "super compliers", when, in actuality, they are the least compliant. "This source of error in clinical-trial data may be one of the reasons that we often have postmarketing dosing adjustments," Rand said.

Compliance depends on many factors, including the study population, type of intervention, the duration of treatment, the complexity of the treatment, real or perceived side effects and life circumstances.

Some level of nonadherence in a clinical trial "can be considered a good thing because there's always some level of noncompliance in real-world clinical practice," said John Yates, M.D., executive director of clinical research for Merck Research Laboratories. "To the extent that it occurs in trials, it reflects real life."

Researchers anticipate some noncompliance and build it into the study, said Schron, who conducts clinical trials in cardiovascular disease for NHLBI's division of epidemiology and clinical applications.

The study co-authors suggest the use of electronic monitoring whenever feasible. "Our data suggest that dumping behavior meant to deceive study personnel cannot be predicted or detected readily based on data generally available in clinical trials, unless electronic monitors are used to gather data on actual medication use patterns," they wrote.

However, state-of-the-art monitoring devices are probably not feasible for office practice because of the cost and technical skill required to use them. Instead, doctors will need to do a better job educating patients "about why a drug is taken in a certain way and why we need to know exactly what people are taking so we can determine if a drug works or not," said Adrian Dobs, M.D., associate professor of medicine at Johns Hopkins University School of Medicine and director of the clinical trials units.

Yates said the single most effective tool physicians can employ is honest dialogue with patients about their ability to follow the prescribed therapy.

"If you can make something easier, more convenient, more straightforward and easier to understand, patients will improve their level of compliance," he said.