Improve CT participant adherence with these tips

There are three typical adherence problems

Clinical trial coordinators and investigators could prevent the problems posed by study variability in trial adherence by taking measures to improve participant adherence.

There are three typical problems with medication adherence, suggests John Urquhart, MD, DrHC, FRCPE, FAAAS, FISPE, FBMES, FRSE, chief scientist with AARDEX Ltd. of Union City, CA, and Zug, Switzerland.

They are as follows:

1. Patients never start the drug. "Sometimes patients who are prescribed a drug will never start taking it," Urquhart says. "That's called non-acceptance, and it can happen in clinical trials."

This is a variable that depends on incentives to patients, he says.

For instance, if people are recruited in the United States for a clinical trial that includes some doctor's check-ups, and the patients have no health insurance, then it's a big incentive to enroll simply for the check-ups, Urquhart says.

"Any trial participant can camouflage his/her nonadherence by discarding the trial medication and returning an empty container," he adds.

2. Execution can be a problem. Problems can occur in how well patients execute their drug-taking. More evening doses are missed than morning doses, and more weekend doses are missed than weekday doses, Urquhart says.

3. They quit early. Many patients have short persistence. There are many plausible reasons for quitting the medication early, but not much solid data on which reasons are most important, Urquhart says.

An example of these adherence problems was highlighted in a study of 4,800 hypertensive patients followed after being prescribed once-daily hypertension drugs of proven efficacy, he says.

"Fifty percent of the patients had quit within one year," he says. "The prescribed drugs had proven efficacy and no difference in recorded side effects from what was in the placebo group, so they were safe, effective, and convenient."

The first step in preventing adherence problems is to measure adherence, Urquhart says.

"It's okay for patients to miss an occasional single dose, but if they miss three or more in a row, then the drug action stops," Urquhart says.

The second step is to anticipate execution problems and take measures to prevent them. If clinical trial coordinators and investigators anticipate that participants will miss some doses, then they can give instructions up-front on how to handle it when they realize they've missed a dose.

For example, consider how women take low-dose, oral contraceptives, and the careful instructions they're given for how to handle missed doses, Urquhart says.

"There is labeling with instructions for what to do if you miss a pill," he explains. "It tells you that if you miss one pill you take the missed dose as soon as you recognize it, and continue on with daily pill-taking, but use back-up barrier methods for the next seven days."

If a woman misses two pills, then she must take one of the pills today and take the other missed one tomorrow with seven days of back-up barrier contraception, Urquhart adds.

"And if you missed more than two pills, you throw away the pill pack and institute back-up barrier contraception, waiting for the next period to come and a new cycle to begin," he says.

Another way to improve adherence is to use the research-proven measurement guided medication management, using the micro-electro-mechanical systems, which is an electronic device on pill bottles that collects data on how frequently and at what times the pill bottle is opened, Urquhart suggests.

"When you download data from the package, you receive in several minutes a series of graphs that show what the dosing history looks like," he says.

Clinical trial staff can show participants their graphs and explain what these mean. Where the graphs show times and dates when the participant missed the medication, the clinical trial coordinator can ask what he or she can do to help the participant change a pill-taking time or behavior to increase adherence.

For example, if the participant always bowls on Wednesday evenings and has a few drinks afterwards and then misses his bedtime dose, then the clinical trial coordinator can suggest a better time, perhaps before bowling, when the participant can take the medication, Urquhart says.

"Measurement and improvement are all part of the same package," he says.

It's a management task to bring the patient's actual dosing patterns closer to the prescribed dosing arrangement, Urquhart says.

"Think of adherence as an independent variable, and look at patterns," he says.

"When people take half as many pills as they're prescribed, and the drug is still working, they think they don't need as much," Urquhart adds.

And sometimes patients are right. One out of four recently-introduced drugs have had a 50 percent reduction in dose after marketing, he says.

This happens because the higher the price of the new drug, the more drive there is among patients to see if they can get away with using less of it, Urquhart says.

Another pattern is negligence. People often forget to take their medications because they haven't incorporated it into their daily routine, he says.

"So they need some kind of external help to show them how to take their medication correctly," Urquhart explains. "They don't need Freudian psychoanalysis, they need a few practical pointers on how to integrate the dosing regimen into their daily routine."