Glaucoma treatment adherence difficult to measure, improve

Taking the right number of drops in the right way at the right time is more difficult in practice than it might appear to physicians.

Issue: June 2012

Patient adherence to glaucoma medical therapy is a well-known problem, and currently there are no reliable ways of assessing and improving adherence, a clinician said.

“Adherence is the extent to which patients continuously and consistently self-administer medications exactly as prescribed. They should take the correct number of drops in the correct way at the correct time of day. In practice, it is less easy than it looks,” Mark B. Sherwood, MD, said at a meeting.

There are four main components to adherence, he explained. The first is acceptance. Patients have to accept that they have a disease that must be treated. Only if this acceptance is achieved can patients enter into the second component, the compliance stage, which is the ability to self-administer medications in the correct dose at the correct time.

The third component is persistence, which is the length of time in which patients continue to take medications as prescribed.

Finally, the last component is execution, which is the ability to deliver the medication correctly so that it reaches the intended target.

“We have some loss due to discontinuation and some further loss because of the difficulty in getting the drop into the eye. In the course of time, quite a number of patients end up not taking their medicine on a regular basis,” Dr. Sherwood said.

Dr. Sherwood noted that much of the inspiration for his talk was based on multiple studies by Alan L. Robin, MD, an OSN U.S. Edition Glaucoma Board Member.

Factors

There are many factors that influence adherence, Dr. Sherwood said. There are medication-related factors, such as adverse reactions, cost, complexity of the regimen and changes to the regimen over the course of the disease. There are patient-related factors, ranging from difficulty in administering the drops to motivation, denial, forgetfulness and other issues.

“Generally speaking, the more educated the patient, the better the adherence, but not in every case,” Dr. Sherwood said.

There are also situational and environmental issues, related to common life events that compete for the patient’s attention, such as traveling and other changes in daily routine.

Measuring adherence

Measuring adherence is a complex task. There are different metrics, but all methods have a wide margin of error and, when combined, often show contradictory results, Dr. Sherwood said.

“We can measure dosing to find out whether patients are putting in too many or too few drops in a 24-hour period,” he said. “We can look at coverage to find out if there are periods of the day when there is no action of the pharmaceuticals. We can look at intra-dose intervals and the percentage of drops taken over the course of the month. All these are valid parameters, but how do we assess them?”

On one hand, there are subjective methods, such as asking patients or giving them questionnaires to answer. Objective methods, on the other hand, range from taking notes of the number of times that patients refill their drugs to the use of electronic dispensers or electronic chips in the bottle caps. Bottle cap chips, however, are no longer used because of sanitary issues.

A study by Okeke and colleagues used electronic dispensers and patient questionnaires or verbal declarations in a cohort of 196 subjects to measure 3 months of adherence. Results showed a wide discrepancy between reality and what patients said or even perceived of their own adherence.

“While patients self-reported a 95% adherence, objective methods showed that only 55% of them were taking more than 75% of the prescribed dose of medications. In other words, 45% of the patients were not taking three-quarters of their drops or more,” Dr. Sherwood said.

Also, physicians overestimated patients’ adherence, according to the same study. They estimated a 77% adherence, with a poor correlation with individual cases.

In addition, the Age-Related Eye Disease Study highlighted problems with adherence to the regimen in the field of macular degeneration. In that study, 72% of patients at risk were taking the proper dose. After the study, the number decreased to 45%.

“And these people knew very well that taking their supplements reduced the risk of progressive degeneration and vision loss,” Dr. Sherwood said.

Improving adherence

According to Dr. Sherwood, interventions with multiple means such as information, reminders, dosing aids, and close and frequent monitoring by the physician have an impact in the long term on adherence rates, but the result is not proportional to the effort.

Gray and colleagues reviewed all the literature regarding interventions for improving adherence to ocular hypotensive drugs up to January 2009. The authors found eight trials, either randomized control trials or quasi-randomized control trials, and discovered that all of them had a small sample size with missing data and a short-term follow-up. Meta-analysis was limited to two studies.

“Three out of five drug comparison studies showed benefit from reducing drop frequency,” Dr. Sherwood said. “One study that compared complicated with least complicated regimens showed no difference in adherence between the two regimens. A small study of 13 patients found a reminder device beneficial. Only one of two studies involving education and individualized care showed benefits.”

Another study by Okeke and colleagues used an electronic dosing aid and subsequently randomized 66 patients who took less than 75% of prostaglandin drops over a period of 3 months into two groups.

In the intervention group, patients watched an educational video, had a review of barriers to take drops with a coordinator and received regular phone call reminders and audible and visual reminders activated on the dosing aid.

In the control group, patients were told to take drops as prescribed.

Baseline compliance rate was less than 50%.

Adherence in the intervention group improved from 54% to 73%, while adherence in the control group had a lesser improvement from 46% to 51%.

“There was some improvement in the intervention group, but not dramatic. These results are emblematic of how complex the problem is and how difficult the challenge of finding effective solutions to it is. In addition, we have no clue on how to assess whether the drugs really get in the eye when patents self-administer them, and there are consequently no studies on this issue,” Dr. Sherwood said. – by Michela Cimberle

References:

Gray TA, Orton LC, Henson D, Harper R, Waterman H. Interventions for improving adherence to ocular hypotensive therapy. Cochrane Database Sys Rev. 2009;15(2):CD006132.
Okeke CO, Quigley HA, Jampel HD, et al. Adherence with topical glaucoma medication monitored electronically the Travatan Dosing Aid study. Ophthalmology. 2009;116(2):191-199.
Okeke CO, Quigley HA, Jampel HD, et al. Interventions to improve poor adherence with once daily glaucoma medications in electronically monitored patients. Ophthalmology. 2009;116(12):2286-2293.
Sleath B, Robin AL, Covert D, Byrd JE, Tudor G, Svarstad B. Patient-reported behavior and problems in using glaucoma medications. Ophthalmology. 2006;113(3):431-436.

For more information:

Mark B. Sherwood, MD, can be reached at University of Florida, Department of Ophthalmology, 1600 SW Archer Road, Box 100284, Gainesville, FL 32610, U.S.A.; +1-352-273-8708; email: sherwood@ufl.edu.
Disclosure: Dr. Sherwood has no relevant financial disclosures.