Twenty-four centuries ago, Hippocrates counseled physicians to "keep aware of the fact that patients often lie when they state that they have taken certain medicines."
In today's medical parlance, that time-honored warning would come under the heading of "noncompliance" -- patients not taking their medicine as prescribed, whether through forgetfulness, refusal, misunderstanding or simple error.
"Noncompliance," says Dr. R. Brian Haynes, associate professor of medicine at McMaster University in Canada, "is simply one of the prices to be paid for free will."
It's a high price. The Food and Drug Administration estimates that between 30 and 50 percent of patients deviate far enough from their prescribed drug treatment to hinder its effectiveness or jeopardize their health. More than 1.5 billion prescriptions, about half of them refills, were dispensed by retail pharmacies last year. That means at least 225 million instances of danger due to noncompliance.
A patient who suddenly stops taking medicine to control high blood pressure can suffer a stroke. A child with chronic asthma who forgets to take a mid-day dose of pills may suddenly have trouble breathing and require emergency care.
Noncompliance can be measured in several ways -- blood tests, pill counts, patient interviews, public surveys -- none of which is totally reliable. But the outlines of the problem have been suggested in numerous studies:
* One in five patients failed to fill their initial prescription, reported a survey last year of more than 1,000 patients 45 and older by the American Association of Retired Persons.
* Nearly half the households surveyed by CBS-TV reported borrowing prescription medicines from friends or using previously prescribed drugs for a similar illness.
* More than half of the patients in a University of Rochester survey did not understand the instructions given for taking their medication.
* More than 10 percent of admissions to a large teaching hospital were due at least partly to failure to follow a medication schedule.
* About 94 percent of persons with high blood pressure comply with their drug therapy for a year, one study showed, but the figure dropped to 65 percent after two years and 34 percent after three.
Other studies show compliance rates as low as 55 percent for tuberculosis patients, 48 percent for insulin-dependent diabetics, 46 percent for patients with asthma and 42 percent for patients prescribed eyedrops for glaucoma, Dr. Craig Burrell, vice president of the drug company Sandoz Inc., told a recent National Pharmaceutical Council symposium here.
"These findings may reflect badly on patients," Burrell said, "but they may also be an indictment of those prescribing the medication."
Some take issue with the term "compliance" itself.
"It puts all the blame on the patient," said Louis A. Morris, chief of the FDA's education, research and labeling branch. He suggests "adherence" as a more neutral term.
Dr. C. Everett Koop, U.S. surgeon general, puts much of the blame on "the attitude we ourselves have in medicine -- an attitude which is reflected in drug marketing and dispensing."
Doctors, Koop told the pharmaceutical symposium, tend to view taking a pill or a capsule as "the patient's most significant activity, around which all other activities of the day will revolve.
"But that isn't the way people live and organize their lives," said Koop, who urged doctors to "put medicine into the context of a full day of work and shopping and going to school and visiting friends, whatever."
That's a challenge, because noncompliance is really a cluster of problems. Not showing up for a doctor's appointment is a form of noncompliance. So is not taking a pill, taking too many pills, straying from a diet, not buckling a safety belt. It can be harmless (missing a daily vitamin) or life-threatening (missing an insulin injection or confusing the dose of a potent cardiac drug).
Noncompliance has spawned new devices equipped with buzzers, beepers, flashing lights, digital readouts or other features to measure exact doses and remind patients when to take their medicines. The U.S. Patent and Trademark Office has issued 160 patents for pill dispensers, with countless others pending approval.
But a problem as common as people ignoring other people's good advice (one expert traces noncompliance back to the Garden of Eden) resists easy solution.
"I haven't seen any magic bullets," FDA's Morris said.
The first step, he said, is better communication between doctor and patient. But for elderly patients who take complex regimens of 10 or 20 drugs over a long period of time, a combination of reminders, written information and discipline may be needed.
"I wish I could say, 'Give everybody injections and forget the pills,' " Morris said. "But it's not that simple." Name That Drug
Here are some questions you should ask your doctor, nurse or druggist whenever you are given a prescription, advises the National Council on Patient Information and Education:
* What is the name of the drug, and what is it supposed to do?
* How and when do I take it -- and for how long?
* What foods, drinks, other medicines or activities should I avoid while taking this drug?
* Are there any side effects, and what do I do if they occur?
* Is there any written information available about the drug?