It sounds like the punch line of a bad joke, but it wasn't. And the confusion experienced by that patient more than a century ago hasn't changed much.

Many people still don't fully understand the seemingly simple label instructions on their prescription medication, according to a new study of low-income patients by Dr. Wolf, assistant professor of medicine at Northwestern University's Feinberg School of Medicine. The study was published November 29 online in Annals of Internal Medicine. Dr. Wolf presented a position piece on how to improve those labels November 29 at the American College of Physicians Foundation conference in Washington.

Dr. Wolf found that nearly half of the patients in the study misinterpreted at least one or more of the five prescription labels they were shown. Patients with low literacy made the most mistakes and frequently were unable to grasp four of five label instructions. But even people with a high school education and higher had problems.

“We came at this from a health literacy perspective, but we found it was a problem with many people in general,” said Dr. Wolf, director of Northwestern's new Health Literacy and Learning Program, which aims to improve patients' ability to understand and act on health information. “It was surprising how prevalent mistakes were regardless of an individual's literacy level. Just being able to read the label doesn't mean you'll be able to interpret it.”

Dr. Wolf believes the main culprit is awkward wording. “Why are we not phrasing things properly on bottles?” he asked.

Recent studies have shown that many patients don't take their medicine properly at home. Dr. Wolf's research with co-lead author Terry C. Davis, PhD, professor at Louisiana State University, is the first to show why the errors occur. Ruth M. Parker, MD, professor at Emory University, was senior author on the study.

Their research follows Dr. Wolf's widely publicized June 2006 study, which found that patients with low literacy skills had trouble understanding prescription drug warning labels.

Addressing medication error is a high priority in the health care system. In July the Institute of Medicine reported 1.5 million patients are injured each year by medication errors, of which more than one-third occur at home.

The potential for patient mistakes rises as Americans' countertops fill with ever more bottles of prescription medicines. The average adult took six or seven medicines a year in 2002 compared with four or five medicines a decade ago. Not only do more opportunities for mistakes exist, but Dr. Wolf's study also showed that the more medications a patient takes, the more likely he or she also will misunderstand the labels.

The most common mistake made by patients in the study was misinterpreting dosage instructions (a tablespoon versus a teaspoon), followed by misunderstanding the dose frequency.

“Just being able to read the label doesn't mean you'll be able to interpret it. Patients reading at a sixth-grade level or below could read it back. But if you ask them what it means to take two tablets twice daily, only one-third of the patients with limited literacy skills got that correct,” Dr. Wolf said.

“What is twice daily?” he asked in what sounded like an opening to a George Carlin comedy routine. “Do you take two at 8 a.m. or two at noon?”

“The most common misinterpretation was to take two pills a day. It's not that they couldn't figure out two plus two equals four. Rather, it's the way the instructions were written. It's awkward wording,” Dr. Wolf said, noting the wording is chosen by the individual pharmacist filling the prescription.

The more numbers included in the dosage, the more likely patients in the study got it wrong. The hardest label to understand: Take 1 teaspoon 3 times a day for 7 days. “It's possible people read this quickly because they perceive it as simple. They get the numbers flipped. They confuse and misread them,” Dr. Wolf said.

The gap between reading and actually understanding the dose means that the current “teach back” technique, in which patients are asked to repeat the instructions to a health care provider, may be inadequate to prevent patient mistakes.

The 395 patients participating in the study ranged from 18 through mid-70s and were from primary care clinics serving indigent populations in Chicago; Shreveport, Louisiana.; and Jackson, Michigan. Dr. Wolf said the study purposely focused on low-income patients because they are disproportionately affected by poor health. A patient was shown each commonly used medicine individually and asked how he or she would take it.

In his Northwestern office, Dr. Wolf pulled out giant plastic bags filled with the offending prescription bottles. Family members, friends, and colleagues send him their used bottles, which he stockpiles at home. “My wife hates that,” he admitted with a smile. He also has a flourishing collection of pharmacy bags stapled with patient education material.

Another study led by Dr. Wolf published in September in Patient Education and Counseling showed those FDA-approved education materials aren't useful to patients, especially those with low literacy skills. “There's too much information on them,” Dr. Wolf complained.

Dr. Wolf proposes a complete redesign and standardization of the text and format of prescription medication labels. The challenge is how to best use the limited “real estate” of the plastic cylinders to clearly instruct patients. He is working with study authors Drs. Parker and Davis as part of an American College of Physicians Foundation initiative to design a better label for prescription bottles. They expect to unveil the new label soon.

He also has a grant from Target Corp. to redesign the warning icons and usage instructions on its medication bottles. “There are 120 possible warnings and instruction stickers. Little evidence exists for a lot of these warnings. There is no process to say what warnings should be on the label and which should not,” he said.

Dr. Wolf's research is funded by a career development award through the Centers for Disease Control and Prevention.