We found that a multifaceted program for enhancing glaucoma eyedrop usage improved the adherence rate from 54% to 73% (p < 0.001) in persons whose baseline drop-taking was less than 75%. The intervention was administered completely by study staff, and did not include physician input with the patient. The intervention was designed to maximize the chance that the adherence with medication use would improve. Our findings suggest that using several approaches at once likely did increase the probability that the interventions changed eyedrop use. While the strategy used in this trial clearly was effective, we cannot determine which aspects of the intervention were most valuable and which individual elements can pragmatically be implemented in clinical practice. We did not record the actual time required for the video and structured interview or determine costs for implementation of the intervention. However, our demonstration that adherence can be improved should stimulate further research into the individual components of our intervention.
While better adherence should produce lower IOP in general, improvement in adherence was not matched by lower IOP levels as measured in the clinic. This was not surprising, since we had only 3 IOP measurements, one at each study visit—compared to daily values for adherence. In addition, our phase one data14
showed that poorly adherent patients increase drop taking during the two weeks prior to the office visit. Hence, IOP taken during the office visit was an inadequate surrogate for estimating adherence. These findings are not unique to ophthalmology. Studies of interventions in patients with hypertension and asthma also have found improved adherence, but not necessarily improved clinical measurements at the time of office visits.10,11
We found previously that physicians have used the IOP level as an important measure of poor adherence.9
A patient who is failing to achieve the IOP target needs either a change in medication or an improvement in adherence. But, the current findings clearly showed that many non-adherent patients had satisfactory IOP at routine visits. Thus, better tools are needed to distinguish poor adherence from poor efficacy in patients not at target in order to avoid overmedication (or over-prescription with continued poor adherence to multiple drugs).
It is likely that educational efforts to improve patient drop taking played an important role in improving patient adherence in the intervention arm. These included instruction on proper administration of eye drops, correct dosing schedules, minimization of waste of medication, and a clear discussion that vision can be lost if the medications are not used properly. Further research on the most effective methods to communicate with patients, through better physician communication, educational programs administered by office staff, video presentations, or combinations of these, is needed.
We showed that the effect of education and reminder systems could be sustained for at least 3 months. Norell12
found a significant decrease in adherence with pilocarpine drops over the interval between visits when the education effort occurred only in the office. Laster's use of a device alarm showed a more continuous effect over the interval in between office visits.13
With the availability of cell phones and internet communication, there are several potential avenues that deserve exploration to improve adherence using continuous reminder systems. 16,17,18
Past studies have shown that the cost of medication and access to care are significant barriers to adherence.19,20
Our study eliminated both of these obstacles by providing free medication and by assuring minimal loss to follow-up among persons already able to access care. The authors speculate that adherence would be even lower among patients for whom these barriers remain in place.
Among our patients, there were 3 factors associated with greater improvement in adherence in univariate analysis: intervention, bilateral use of medicine, and attendance at the Wilmer Eye Institute Glaucoma service. Among these 3 factors, the multivariate analysis showed that only the intervention remained significantly associated with improved adherence, while institution and bilateral use of medicine were no longer significant and ethnicity and extremely low baseline adherence became significant. There may be substantial correlation among these variables. For example, nearly all our Scheie Institute patients were African-derived, while the majority of Wilmer patients were White. Patients from Wilmer had taken drops longer than those at Scheie. Other factors that may play a role in associations between ethnicity and adherence include patient-physician interaction,21
perceived personal dissimilarity of the patient with the doctor,22
and having had experiences with discrimination23
may also contribute to a patient's decreased intent to adhere. Further research is needed to understand more clearly what factors led African-American patients to have both lower baseline adherence14
and lower improvement in adherence with intervention. It is possible that interventions for adherence must be tailored to the beliefs and situation of major ethnic groups.
A baseline adherence rate < 50% was associated with improved adherence. It is possible that this finding is in part due to regression to the mean. However, we previously found an association between less knowledge about glaucoma treatment and low adherence(Friedman DS. Risk factors for poor adherence with eyedrops in electronically monitored glaucoma patients. Poster presented at American Glaucoma Society, March 2008, Washington, D.C.) This has been demonstrated in Korean hypertension patients whose adherence was higher in those more informed about the disease.24
It is logical that our educational efforts about the disease in the intervention eliminated some of the lack of adherence due to this factor.
Our study had some limitations. Though we used a standard randomization process, the intervention group had somewhat more veteran eyedrop takers. This could have increased the magnitude of the intervention effect, since our univariate analysis showed lower adherence among less experienced drop takers. The adherence rate of the controls rose slightly, which was most likely due to regression to the mean. This effect was small in comparison to the treatment effect in the intervention group, but if we assume the intervention group would have had a similar rise, the treatment effect is likely smaller than measured. We informed patients that they were being monitored, and provided drugs at no cost. It is likely that the adherence of patients who are not in a study under these conditions would be lower at baseline, and perhaps might exhibit a different intervention effect.
We used an electronic device to measure adherence as the primary outcome variable. Electronic monitoring of drug-taking behavior is the most accurate method for identifying nonadherence.14,25,26
Research with the DA has limitations, however, as shown by patients in this study who took their drops without placing the bottle in the devices, which in fact lowered the measured adherence rate in the intervention group, but not significantly. When excluding those who took drops without the DA, the measured adherence improved slightly in the control group, but still the difference in magnitude of improved adherence between the intervention and control groups remained large. In addition, the findings here were limited to the use of one prostaglandin analogue, since only its bottle fits in the device.
In conclusion, adherence with glaucoma drop usage improved over a 3-month period with an intervention strategy consisting of education and reminder systems. Additionally, improvement was immediate and sustained over 3 months. There was greater improvement in adherence among those with the lowest baseline adherence and among White patients. IOP was a poor surrogate for monitoring adherence, probably due to increased adherence just before the visit. Further research is needed to determine which components of this intervention were most effective.