Group members: David Friedman, Lou Cantor, Steve Obstbaum, John Walt

The committee reviewed the literature on compliance interventions and determined that there are several major reasons that patients fail to cooperate with medical therapy for glaucoma. These are:

1. Knowledge: Patients do not understand the disease, the possibility of going blind, the need for lifelong therapy and the role that medicines play.
2. Complexity: Patients may forget to take their drops or they may be unable to structure their time to include time for putting in drops. For example, putting in drops at bedtime may lead to missed doses due to falling asleep.
3. Capacity: Patients are unable to put drops in the eyes due to physical limitations or to limited mental capacities.
4. Denial: Patients do not want to have a disease and therefore stop taking medicines to treat the disease.
5. Access/Financial: Patients cannot afford medications. Also, patients may have difficulty getting their medicines from the pharmacy if they are isolated.

6. Drug-Related: Pain, discomfort, redness, side effects, bottle construction. 

A recent review of interventions aimed at increasing compliance looked at several chronic disease states, including hypertension, hypercholesterolemia and asthma. The authors report the following regarding each of the major obstacles to cooperation with therapy:

1. Knowledge: Just handing out literature and speaking to patients does not seem to improve compliance outcomes. More complex interventions are required.
2. Complexity: Simplifying the regimen appears to lead to better outcomes, as does a multi-pronged approach to help patients remember to take medicines. Such approaches include increased counseling and follow-up phone calls.
   1. HTN: Simplifying dosing regimens shown to increase pills taken with QD versus BID metoprolol, increased pills and better cholesterol with BID niacin versus QID.
   2. HTN: Phone system to counsel patients for HTN showed benefit including better BP control.
   3. Asthma: Complex intervention with one-on-one support, groups, calls… showed improvement in asthma compliance. A less complex approach with written materials and self-guided treatment failed to show a benefit.
   4. Asthma: Another nursing-guided intervention provided benefit with increased peak flow, fewer rescue meds… at six months.
   5. DM: used automated self-assessment phone calls that triggered nursing response and had lower HgbA1c levels.
   6. AIDS: Individual counseling increased adherence, reduced viral loads.
   7. Rheumatoid arthritis: Group therapy failed.

3. Capacity: Approaches to help forgetful patients have not been highly successful.
   Blister pack with days on it not helpful for HTN;
   Previous eye research indicated possible benefit of a reminder on the cap, but the reminder cap was removed from the market because many found it confusing;
   Companies are currently actively sending reminder letters from pharmacies (to patients) when the patients fail to refill a prescription; Little is published on the effectiveness of this approach.

4. Denial: Little data on how to influence this, but a better review might reveal something.

The last two major reasons for non-cooperation with therapy (financial and access issues and drug-related issues) have not been addressed and are unlikely to be within the scope of this project.

Regarding such proposed intervention studies, two sample versions were proposed:

1. Intervention Program A

   1. Waiting room survey of patient knowledge about glaucoma;

   2. Physician discussion of misunderstandings based on the survey responses;

   3. Video/DVD of proper drop instillation;

   4. Review with technician drop schedule;

   5. Three-month supply provided to patient of whatever medicines are prescribed;

   6. Patient called at one week and one month by technician to administer brief, structured interview to ask about drop taking issues and to answer questions;

   7. Interview and bottle weight at 8 to 12 weeks;

   8. Controls get the free bottles and nothing else;

2. Intervention Program B

   1. Waiting room survey of patient knowledge about glaucoma

   2. Physician discussion of misunderstandings based on the survey responses.

   3. Video/DVD of proper drop instillation

   4. Review with technician drop schedule

   5. Alarm (simple stick on or something) on medicines goes off at times that are agreed upon to remind patients

   6. Black tip on dropper bottle if available.

   7. Controls get usual care.

It was suggested that similar research carried out in two different countries, i.e. by two Glaucoma Societies, would have value in comparing the effects that were culturally different. Studies within a country in groups that receive care under different socio-economic models could evaluate the effect of financial motivators.

For studies in developing countries, simpler designs are appropriate. For example, among a series of newly identified glaucoma patients, medication is prescribed. This could be either by giving it free on a regular basis or by prescribing it within the country's health care system as it is. Then, at regular intervals, the patients are contacted and/or examined to determine if the medication is being used at all.

Literature Studies in Ophthalmic and Glaucoma Cooperation

1. Studies that used patient interview or focus groups

• Spaeth GL. Visual loss in a glaucoma clinic. I. Sociological considerations.
  Invest Ophthalmol 1970; 9: 73-82.
  
  Verbal reports suggest that 31% of patients admit to failing to use medication properly. Risk factors included being 'unaware of the nature of their disease'. No association of poor cooperation and age, sex, race, income, education level, fear of blindness, self-sufficiency. Those with better vision reported poorer cooperation than those with severe vision loss.
  
• Bloch S, Rosenthal AR, Friedman L, Caldarolla P. Patient compliance in glaucoma.
  Br J Ophthalmol 1977; 61: 531-534.
  
  Forty patients interviewed and felt non-cooperative with therapy. Risk factors for poor cooperation were: males, no other medical disorder than glaucoma, side effects from drops, and lack of knowledge that it could blind them.
  
• MacKean JM, Elkington AR. Compliance with treatment of patients with chronic open-angle glaucoma.
  Br J Ophthalmol 1983; 67: 46-49.
  
  Interviews indicated 42% admitted to missing at least some eyedrops for glaucoma. Those claiming better drop-taking were those who knew the name 'glaucoma' for their disease, those who knew it could cause vision loss. More admitted non-cooperation with tid and qid regimens than bid (knowledge, easier regimen).
  
• Bour T, Blanchard F, Segal A. Observance thérapeutique et vécu du glaucoma primitif à angle ouvert.
  J Fr Ophthalmol 1993; 16: 380-391.
  
  Thirty-two percent admit to at least some non-cooperation with eyedrop taking. Causes reported for poor cooperation were: forgetfulness, time constraints, poor doctor-patient relationship, and lack of knowledge about the disease.
  
• Rocheblave A. La coopération des maladies proteurs d'un glaucoma chronique primitif à angle ouvert.
  J Fr Ophthalmol 1983; 6: 837-841.
  
  Questionnaire matched to visit keeping (not eyedrop taking). Cooperation better with higher socio-economic status, family member to help remember, and those prescribed eyedrops.
  
• Patel SC, Spaeth GL. Compliance in patients prescribed eyedrops for glaucoma.
  Ophthalmic Surgery 1995; 26: 233-236.
  
  We studied the rate of failure to use eyedrops as prescribed for glaucoma and some of the factors possibly associated with that noncompliance by interviewing 100 patients being followed in a setting emphasizing correct usage. Fifty-nine reported they had not used their eyedrops precisely as prescribed. Factors significantly influencing compliance included daily dose frequency, forgetfulness, inconvenience, and unaffordability. Gender and race were marginally significant factors, with men and blacks reporting somewhat higher rates of missed doses than women and whites. Side effects and age were not significant causes of noncompliance.
  
• Konstas AG, Maskaleris G, Gratsonidis S, Sardelli C. Compliance and viewpoint of glaucoma patients in Greece.
  Eye 2000; 14: 752-756.
  
  PURPOSE: To document the prevalence of non-compliance and to investigate patients' perceptions concerning glaucoma in a Greek cohort. METHODS: We investigated 100 consecutive patients referred to our glaucoma clinic and already treated for chronic glaucoma. Compliance and patients' insight were ascertained by two independent observers by means of a predetermined questionnaire. All patients were subsequently assessed for their ability to instill their eyedrops accurately. RESULTS: Fifty one per cent of our patients were not aware of the nature of glaucoma, but 80% were afraid it might lead to blindness. Clinically significant non-compliance (more than two doses missed per week) was established in 44% of our patients. Men and those using eyedrops more than four times a day were more likely to default. Non-compliant patients exhibited higher mean intraocular pressure (22.9 vs 18.5 mmHg; p > 0.001) and worse visual field loss (10.8 vs 7.0 dB; p = 0.008) compared with compliant patients. Involuntary non-compliance was also common in our group, with only 53% instilling their eye drops accurately. CONCLUSION: Non-compliance is a significant limiting factor in glaucoma therapy in Greece.
  
• Stack RR, McKellar MJ. Black eye drop bottle tips improve compliance.
  Clin Experiment Ophthalmol 2004; 32: 39-41.
  
  AIM: To determine if dark coloured tips on eye drop bottles facilitate ocular therapy. METHODS: Eye drop bottles were modified by placing sterile black tape around the bottle tip. Patients on regular timolol therapy were asked to use bottles with the modified tip for one month. They then completed a questionnaire comparing the black tips with the standard tips on the bottle they normally use. RESULTS: Eighty-eight per cent of patients found the black tipped bottles easier to use than bottles with the standard tip. Sixty-eight percent of patients had fewer occasions on which they needed to instill a second drop and 30% of patients touched their eyelid less when using the modified bottle tips. CONCLUSION: Black coloured bottle tips aid ocular therapy. They are easier to use, result in less contact with the eye on instillation and patients note a reduction in need for a second or additional drop. This is likely to improve compliance and reduce contamination. A change in manufacturing practise should be encouraged.
  
• Taylor SA, Galbraith SM, Mills RP. Causes of non-compliance with drug regimens in glaucoma patients: a qualitative study.
  J Ocular Pharmacol Therap 2002; 18: 401-409.
  
  The purpose of this study was to gain insights into why patients are not compliant with their glaucoma medications. Patients were recruited from lists provided by two ophthalmologists. Each patient had seen a minimum of two ophthalmologists for their glaucoma, and was taking at least two topical medications for glaucoma. Qualitative methodology was utilized, including two focus groups and eleven in-depth interviews in patients' homes. The results showed that forgetfulness was the number one reported reason for non-compliance. Patients did not claim to be non-compliant specifically because of side effects, but they did complain about them. Communication between physicians and patients is a key factor in compliance for glaucoma patients. Specifically, patients would like their physicians to teach them how to instill their eye drops, tell them about new/alternate medications and procedures as they become available, and offer new ways to make their regimen easier. Patients often do not tell their physician if they experience a side effect unless it is intolerable to them, yet they do realize the seriousness of glaucoma, and the consequences of not following their doctor's orders. Finally, while cost was not a reported deterrence to compliance, some patients would prefer less expensive alternatives.
  
• Deokule S, Sadiq S, Shah S. Chronic open angle glaucoma: patient awareness of the nature of the disease, topical medication, compliance and the prevalence of systemic symptoms.
  Ophthalmic Physiol Opt 2004; 24: 9-15.
  
  PURPOSE: To study the awareness of the nature of the disease, compliance with treatment, and prevalence of systemic symptoms in a group of patients with chronic open angle glaucoma (COAG). METHOD: A structured questionnaire was designed and given to 260 consecutive COAG patients attending a general ophthalmology clinic. Questions related to the increased risk of COAG amongst family members, screening of family members, nature of field defects, variation in IOP, topical treatment and availability of a free eye test for a COAG patient in the UK were asked. Compliance and systemic symptoms were also assessed. RESULTS: Forty-one percent (107 of 260) of patients in the study group were aware of the increased risk of COAG in family members and 45.5% (118 of 260) of patient's family members had undergone screening for COAG. Seventy-three per cent (191 of 260) of the patients were aware of their own and their family members' entitlement to a free eye test. Seventy-seven percent of patients claimed full compliance. Thirty percent of patients were noted to have systemic symptoms. CONCLUSIONS: The awareness of the nature of COAG in this population was low and incidence of perceived drug related systemic symptoms very high. Both of these may contribute to poor compliance.
  
• Day DG, Sharpe ED, Atkinson MJ, Stewart JA, Stewart WC. The clinical validity of the treatment satisfaction survey for intraocular pressure in ocular hypertensive and glaucoma patients.
  Eye 2005, Jun 3 (Epub ahead of print)
  
  PURPOSE: To provide initial validation of the Treatment Satisfaction Survey-Intraocular Pressure (TSS-IOP) quality-of-life survey that analyses specific issues related to side effects, patient satisfaction, and compliance. METHODS: A prospective, observational cohort of 250 consecutive patients with primary open-angle glaucoma or ocular hypertension was administered the TSS-IOP survey. RESULTS: Factors that correlated with patient satisfaction included perceived effectiveness of the medicine (F = 7.47, P < 0.001), ocular irritation (F = 6.06, P < 0.001), conjunctival hyperaemia (F = 4.40, P < 0.001), ease of use (F = 8.52, P < 0.001), and convenience of use (F = 6.90, P < 0.001). Patient compliance, acceptance of their illness, and knowledge of glaucoma were also related to perceived effectiveness of the medicine (P < 0.001), ease of use (P < 0.05) and convenience (P < 0.001). Physician ratings of patient pressure control, side effects, and instillation problems also were significantly correlated to patient satisfaction (R = 0.13-0.26, P = 0.05-0.001). The physician ratings of patient compliance, however, were not significantly related to any dimension of patient satisfaction (P > 0.05). Among monotherapy prostaglandin treatments, latanoprost demonstrated statistically greater satisfaction than bimatoprost or travoprost regarding conjunctival hyperaemia (P < 0.05) and eye irritation (P < 0.01). CONCLUSIONS: This study provides initial evidence that patient satisfaction may be related to compliance, perceived effectiveness of treatment, adverse side effects, ease and convenience of use, acceptance of illness, and knowledge of glaucoma.
  
• Stewart WC, Konstas AG, Pfeiffer N. Patient and ophthalmologist attitudes concerning compliance and dosing in glaucoma treatment.
  J Ocul Pharmacol Ther 2004; 20: 461-469.
  
  AIM: The aim of this study was to identify research avenues that might improve patient compliance with glaucoma therapy. METHODS: Five hundred patients and physicians were interviewed by telephone in five European countries, and the results were compiled and evaluated by two independent physicians. RESULTS: Most physicians believed that pressure reduction is useful (UK (96%), France (94%), Spain (80%), Italy (72%), and Germany (70%), p < 0.0001). The majority of physicians believed that noncompliance exists in 0%-25% of patients, whereas 34% of patients admitted to noncompliance. Physicians believed patients would prefer once-daily dosing (92%) and that it would help compliance, whereas 60% of patients preferred once-daily dosing, and 20% of patients believed it would help compliance. Physicians (94%) believed that noncompliance could lead to visual loss and, while this information concerned most physicians, this was less likely in Germany (52%) (p < 0.0001). Most patients received information concerning dosing of their medicines (79%), and, accordingly, waited an average of ten minutes between doses; but only half of the patients had been told to wait at least five minutes between instilling preparations. Approximately two of three patients knew that missing medicines could cause visual loss. CONCLUSIONS: Once-daily dosing to increase patient satisfaction and/or dosing convenience and providing patient education are potential clinical techniques that could be further evaluated as a means to increase compliance.
  
• Balkrishnan R, Bond JB, Byerly WG, Camacho FT, Anderson RT. Medication-related predictors of health-related quality of life in glaucoma patients enrolled in a medicare health maintenance organization.
  Am J Geriatr Pharmacother 2003; 1: 75-81.
  
  BACKGROUND: Glaucoma is an important public health concern in the United States, particularly among older adults (aged ≥ 65 years). Pharmacologic therapy for glaucoma consists mainly of topical eye drops containing beta-blockers or prostaglandin analogs. OBJECTIVE: The goal of this study was to assess the associations between factors of topical medication use (self reported medication compliance, belief in benefit of medication use, usage difficulty, usage assistance, and complexity of medication regimen) and health-related quality of life (HRQOL) in a cross-sectional population of older patients with glaucoma. METHODS: A self-administered, 48-question survey soliciting information on medication-taking behaviors, treatment-related factors, and HRQOL was mailed to members of a Medicare health maintenance organization who were aged ≥ 65 years and had primary open-angle glaucoma. Two mailings were conducted four months apart; the second was sent to members whose responses to the first mailing had not yet been received. The 12-Item Short-Form Health Survey (SF-12) and the 25-Item National Eye Institute Visual Function Questionnaire (VFQ-25) were used to assess HRQOL. Other questions addressed perceptions of eye drop use in these patients. Multiple regression techniques were used to analyze associations between medication-related factors and HRQOL in this population. RESULTS: The questionnaire was mailed to 589 patients; 375 responded (218 in the first mailing and 157 in the second mailing). A total of 358 responses were complete and analyzable (effective response rate, 62%). After controlling for the effects of other confounders, we found that self reported difficulty in using eye drops was strongly associated with decreased HRQOL (11.5% in VFQ-25 total score and 8.4% in SF-12 mental health score, P < 0.05). Other medication-related factors that were examined were not significantly associated with changes in HRQOL. CONCLUSION: Based on our findings, patients aged ≥ 65 years with glaucoma were likely to have significant comorbidity, which affected both visual and general health and well-being perception. Additionally, a significant proportion of these patients reported difficulty with use of topical medication, which was independently associated with a significant decrease in HRQOL. Care of older patients with glaucoma should incorporate strategies to minimize the difficulty associated with medication use.
  
  HQ Note: it would seem that self-reported cooperation with therapy was not associated with HRQOL.

2. Studies with medication monitoring devices

• Norell SE, Granstrom PA. Self-medication with pilocarpine among outpatients in a glaucoma clinic.
  Br J Ophthalmol 1980; 64: 137-141.
  
  A recording medication monitor and fluorescein technique were used to study self-medication by 82 patients with primary open-angle glaucoma for whom pilocarpine eye drops three times a day had been prescribed. Of these patients 34 (41%) missed six or more doses during a 20-day period, and for 35 (43%) an eight-hour dose interval was exceeded at least 20% of the time. Consequences may include lack of effectiveness in preventing visual loss and unnecessary prescription of more potent, and more toxic, drugs.
  
• Norell SE. Monitoring compliance with pilocarpine therapy. Am J Ophthalmol 1981; 92: 727-731.
  
  Work with compliance monitor showing a correlation of increasing number of missed doses with increasing time since last visit to doctor.
  
• Granstrom P-A, Norell S. Visual ability and drug regimen: relation to compliance with glaucoma therapy.
  Acta Ophthalmol 1983; 61: 206-219.
  
  Cooperation with pilocarpine therapy judged by monitor not related to reported side effects nor visual acuity (but visual field was not included in analysis). Cooperation was poorer among those who agreed with the statement that "eyedrops were very unpleasant".
  
• Granstrom P-A. Glaucoma patients not compliant with their drug therapy: clinical and behavioural aspects.
  Br J Ophthalmol 1982; 66: 464-470.
  
  Small patient group in which education of patient seemed to improve monitored cooperation with pilocarpine eyedrop taking.
  
• Kass MA, Meltzer DW, Gordon M. A miniature compliance monitor for eyedrop medication. Arch Ophthalmol 1984; 102: 1550-1554.
  Kass MA, Gordon M, Meltzer DW. Can ophthalmologists correctly identify patients defaulting from pilocarpine therapy?
  Am J Ophthalmol 1986a; 101: 524-530.
  
  Outcomes were compared to actual drop-taking: not related to measured intraocular pressure (r = -0.02, p = .64), nor physician prediction (r = 0.2, p = 0.0001), daily log of drops taken (r = 0.24, p = 0.08), weight of pilocarpine utilized from bottle (r = 0.18, p = 0.0007), and patient report (r = 0.2, p = 0.0003). Even combination of best three measures explained only 15% of the variation in drop-taking.
  
• Kass MA, Meltzer DW, Gordon M, Cooper D, Goldberg J. Compliance with topical pilocarpine treatment.
  Am J Ophthalmol 1986b; 101: 515-523.
  
  Patients administered 76% of pilocarpine doses while reporting that they took 97%. Twenty-five percent of the patients had at least one day per month with no administrations of drug, 30% compressed them during daytime hours, and cooperation was significantly higher in the 24-hour period preceding the doctor visit.
  
• Kass MA, Gordon M, Mobley RE, Meltzer DW, Goldberg JJ. Compliance with topical timolol treatment.
  Am J Ophthalmol 1987; 103: 188-193.
  
  Patients administered 82.7% of doses prescribed (range 20% to 100%)
  
• Chang JS Jr, Lee DA, Petursson G, Spaeth G, Zimmerman TJ, Hoskins HD, Mills R, Brown R, Kass M, Lue J. The effect of a glaucoma medication reminder cap on patient compliance and intraocular pressure.
  J Ocul Pharmacol 1991; 7: 117-124.
  
  A multi-site, open-labeled clinical trial was conducted to evaluate the ease of use and acceptance of a newly developed medication cap with a memory aid (C Cap Compliance Cap, Allergan, Inc.) and its effect on patient compliance and intraocular pressure. One-hundred-twenty-two patients with glaucoma or ocular hypertension received their prescribed eye drops in bottles with the compliance cap. Overall, 83% of the patients found the compliance cap very easy to use. By the end of the study, significantly more patients (67%) claimed 100% compliance than prior to using the compliance cap (41%). An overall drop in intraocular pressure of 0.8 mmHg was seen. However, in a subset of patients who reported an increase in compliance, mean intraocular pressure decreased from baseline by 1.7 mmHg. The results of this study suggest that the compliance cap helps patients with glaucoma or ocular hypertension remember to take their medication as prescribed.
  
• Sclar DA, Skaer TL, Chin A, Okamoto MP, Nakahiro RK, Gill MA. Effectiveness of the C Cap in promoting prescription refill compliance among patients with glaucoma.
  Clin Ther 1991; 13: 396-400.
  
  In an attempt to increase patient compliance with a dosing regimen, prescriptions for topical solutions of glaucoma medication were refilled using the C Cap, a memory aid designed to help patients to remember to instill the medication as prescribed. A comparison of the number of prescription refills requested by 121 patients with glaucoma showed that patients who received the C Cap requested significantly more refills in the six months after receiving the C Cap than before and requested significantly more refills than did patients who did not receive the C Cap.
  
• Laster SF, Martin JL, Fleming JB. The effect of a medication alarm device on patient compliance with topical pilocarpine.
  J Am Optom Assoc 1996; 67: 654-658.
  
  BACKGROUND: This study was performed to investigate the use of an electronic medication alarm device (Prescript TimeCap) to enhance compliance in glaucoma patients taking pilocarpine. METHODS: Thirteen subjects were selected who had been diagnosed with open-angle glaucoma and were receiving one drop of pilocarpine solution four times a day in both eyes. For each subject, the study was divided into two 30-day phases, one with the medication alarm device and the other without. Thus, each subject served as his or her own control. Compliance was measured based on the amount of pilocarpine used and by patient questionnaire. In addition, the subjects completed a post-study questionnaire regarding the ease of use of the TimeCap and whether it helped them remember to take their medication. RESULTS: When subjects used the TimeCap, they administered an average of 2.867 g (P < 0.0001) more pilocarpine over the 30 days than during the period without it. Subjects also estimated a significant difference in compliance level, 95.8 percent with the alarm device versus 83.1 percent without it (p < 0.01). All subjects reported no difficulty using the TimeCap, and all reported that it helped them remember to take their medication. CONCLUSIONS: These results are highly suggestive that the TimeCap is an effective compliance aid for glaucoma patients on pilocarpine.

3. Risk factors identified for cooperation

• Bigger JF. A comparison of patient compliance in treated vs untreated ocular hypertension.
  Trans Amer Acad Ophthalmol Otol 1976; 81: 277-283.
  
  Kosoko O, Quigley HA, Vitale S, Enger C, Kerrigan LA, Tielsch JM. Risk factors for non-compliance with glaucoma follow-up visits.
  Ophthalmology 1998; 105: 2105-2111.
  
  Both studies show patients are more likely to return for visits if medication is prescribed.

4. Large database studies

• Gurwitz JH, Glynn RJ, Monane M, Everitt DE, Gilden D, Smith N, Avron J. Treatment of glaucoma: adherence by the elderly.
  Am J Public Health 1993; 83: 711-716.
  
  OBJECTIVES: The purpose of this study was to determine the extent of nonadherence to treatment for glaucoma among elderly patients. METHODS: This was a retrospective cohort study of 2440 patients older than age 65 who were enrolled in the New Jersey Medicaid Program and who were newly initiated on a topical agent for the treatment of glaucoma. Two patient-specific measures of nonadherence were employed: (1) no filled prescription for any glaucoma medication over a 12-month period after the initiation of therapy and (2) number of days without therapy for glaucoma during this 12-month period. RESULTS. By the first measure, 569 patients (23%) were found to be nonadherent. The mean number of days without therapy during the study year was 112. Factors associated with nonadherence included the use of glaucoma medication requiring more than 2 administrations per day and the presence of multiple other medications in the patient's drug regimen. Patients started on multiple glaucoma medication were more adherent than those started on a single agent. Age and sex were not found to be predictors of nonadherence. CONCLUSIONS: Substantial nonadherence was found to be common in this population. More attention to the issue of nonadherence could result in important benefits in the preservation of sight.
  
• Gurwitz, JH, Yeomans SM, Glynn RJ, Lewis BE, Levin R, Avorn J. Patient noncompliance in the managed care setting. The case of medical therapy for glaucoma.
  Medical Care 1998; 36: 357-369.
  
  OBJECTIVES: The authors identify demographic and clinical characteristics associated with noncompliance in patients beginning medical therapy for the treatment of glaucoma in a managed care setting. METHODS: The authors describe a retrospective cohort study in a group-model health maintenance organization in Massachusetts. Patients were members of the health maintenance organization who were newly initiated on topical drug therapy to treat open-angle glaucoma during the period January 1, 1987 through December 31, 1990, who met eligibility requirements, and who had evidence of health services utilization for a 12-month follow-up period. For all study subjects, we determined the number of days without available therapy for glaucoma during the 12-month period. Study subjects who did not fill prescriptions adequate to provide medication to cover at least 80% of days during the study period were considered noncompliant. Logistic regression analysis was used to assess demographic and clinical factors independently associated with noncompliance among patients initiated on medical therapy for the treatment of glaucoma. RESULTS: Of 616 subjects who met inclusion criteria, 152 (24.7%; 95% confidence interval, 21.3%-28.1%) met the study definition for noncompliance. These patients had an average number of days without therapy during the 12-month study period of 103.9 ± 70.0 days compared with 6.8 ± 19.5 days for those categorized as compliant. Of a variety of selected demographic and clinical characteristics, having fewer visits with an ophthalmologist during the study period (< 2) was most strongly related to noncompliance (odds ratio 2.99; 95% confidence interval 2.03, 4.40). There were no differences in average intraocular pressure between the compliant and noncompliant groups during the study period. CONCLUSIONS: Noncompliance with prescribed medical therapy for glaucoma was found to be common in a managed care setting characterized by essentially unrestricted access to health care and medications. It remains difficult to identify noncompliant patients based on demographic and clinical characteristics. The use of automated prescription data to identify noncompliant patients is feasible in large managed health care insurance programs where such data are collected routinely for administrative purposes.
  
  Editor's note: By standard of filling enough to cover 80% or more of days, 25% non-compliant. Big database, $2 copay, older pop. Only 2% stopped altogether (much better than 1993 Gurwitz).
  
• Dasgupta S, Oates V, Bookhart BK, Vaziri B, Schwartz GF, Mozaffari E. Population-based persistency rates for topical glaucoma medications measured with pharmacy claims data.
  Am J Manag Care 2002; 8: S255-S261.
  Spooner JJ, Bullano MF, Ikeda LI, et al. Rates of discontinuation and change of glaucoma therapy in a managed care setting.
  Am J Manag Care 2002; 8: S262-S270.
  Shaya FT, Mullins CD, Wong W, Cho J. Discontinuation rates of topical glaucoma medications in a managed care population.
  Am J Manag Care 2002; 8: S271-S277.
  
  This series of articles in a supplement used the same methodology as in Reardon et al., though in apparently different managed care pharmacy linked databases. Its major analysis compared prostaglandin to other medications, reporting that persistency and discontinuation rates were better with prostaglandin.
  
• Reardon G, Schwartz GF, Mozaffari E. Patient persistency with topical ocular hypotensive therapy in a managed care population.
  Am J Ophthalmol 2004; 137(Suppl): S3-S12.
  
  Large Protocare database study of persistency in 28,741 persons treated with glaucoma drops, but majority with no documentation of type of glaucoma (diagnosis code not required for inclusion). Persistency defined as refilling within 90 days after index prescription without lapse or as a switch to prescription of another medication. 50% never filled the second prescription, and by one year, fewer than 30% were persistent with any drug. Persistence was significantly better with prostaglandin than other agents. Rate of continuing to take statin drug orally for cholesterol was similar to that for eyedrops.
  
• Schwartz GF, Reardon G, Mozaffari E. Persistency with latanoprost or timolol in primary open-angle glaucoma suspects.
  Am J Ophthalmol 2004; 137: S13-S16.
  
  Subset of data from Reardon et al., showing persistency better with prostaglandin than beta blocker eyedrop in glaucoma suspects (by billing code).
  
• Platt R, Reardon G, Mozaffari E. Observed time between prescription refills for newer ocular hypotensive agents: the effect of bottle size.
  Am J Ophthalmol 2004; 137: S17-S23.
  
  Same database as Reardon et al., showing that refill rate does not follow bottle size, and unexpectedly, the refill rate for larger bottles is more often than predicted from the stated volume.
  
• Zhou Z, Althin R, Sforzolini BS, Dhawan R. Persistency and treatment failure in newly diagnosed open angle glaucoma patients in the United Kingdom.
  Br J Ophthalmol. 2004; 88: 1391-1394.
  
  AIM: To determine utilisation patterns and calculate treatment failure and discontinuation rates in patients with open angle glaucoma treated in the United Kingdom with any of six groups of intraocular pressure (IOP) lowering agents. METHODS: The UK General Practice Research Database was used to identify newly diagnosed (after 1 January 1997) open angle glaucoma patients who were naive to therapy with any of six index drug groups: carbonic anhydrase inhibitors, latanoprost, miotics, sympathomimetics, timolol, and other (non-timolol) beta blockers. Analyses included drug treatment data for one year following diagnosis. Outcomes were (1) time to therapy failure, defined as either change in index drug (replacement or addition of therapy) or patient referral for surgery, and (2) time to therapy discontinuation, defined as either therapy failure or no refill of the index drug in a period twice that covered by the first prescription fill. Cox proportional hazard regression and Kaplan-Meier and life table methods were used to compare groups. RESULTS: Among the 2001 eligible patients, a beta blocker other than timolol was the most widely prescribed (42%), followed by timolol (32%), carbonic anhydrase inhibitors (10%), and latanoprost (7%). Compared to latanoprost, those treated with any alternative agent were significantly more likely to fail (p ≤ 0.005 for each comparison) and to discontinue (p ≤ 0.05 for each comparison) therapy. Failure rates ranged from 13% (latanoprost) to 45% (sympathomimetics), and discontinuation rates ranged from 30% (latanoprost) to 63% (miotics). CONCLUSION: Latanoprost treated patients demonstrated lower rates of therapy failure and therapy discontinuation compared with patients treated with other widely used IOP lowering medications, including beta blockers.
  
• Day DG, Schacknow PN, Sharpe ED, Ellyn JC, Kulze JC 3rd, Threlkeld AB, Jones ED, Brown RH, Jenkins JN, Stewart WC A persistency and economic analysis of latanoprost, bimatoprost, or beta-blockers in patients with open-angle glaucoma or ocular hypertension.
  J Ocul Pharmacol Ther 2004; 20: 383-392.
  
  PURPOSE: The aim of this study was to evaluate differences in the persistency and treatment costs for latanoprost, bimatoprost, or beta-blockers in open-angle glaucoma or ocular hypertensive patients. METHODS: This study was a retrospective, multicenter, parallel, active-controlled comparison of patients who were prescribed with ocular hypotensive monotherapy between September 1996 and August 2002. RESULTS: 1,182 patients were included. The Kaplan Meier life table analysis showed that latanoprost was continued longest among the groups for the first year of therapy (p = 0.02). A significant difference existed between groups in the final intraocular pressure for latanoprost (17.3 ± 3.9, N = 357), for bimatoprost (18.0 ± 3.6, N = 146), and for the beta-blockers (17.9 ± 3.7, N = 335) (p = < 0.0001). The average number of visits was statistically higher for beta-blockers (3.3), compared to latanoprost (2.9) and bimatoprost (3.1) (p = 0.01). Further, the mean number of medicine changes was greater for bimatoprost (0.45) and beta-blockers (0.47) than for latanoprost (0.27) (p=0.0008). The cost of visits and medications was lowest for beta-blockers ($119.3 ± $78.9) and highest for bimatoprost ($163.8 ± $51.2) (p < 0.0001). CONCLUSIONS: Patients were more persistent with latanoprost and demonstrated lower intraocular pressure, fewer visits, and fewer medicine changes when compared to bimatoprost or beta-blocker therapy. In contrast, the beta-blocker group provided lower overall cost.
  
• Robin AL, Covert D. Does adjunctive glaucoma therapy affect adherence to the initial primary therapy?
  Ophthalmology 2005; 112: 863-868.
  
  OBJECTIVE: To examine the effect of adding complexity to a glaucoma medical treatment regimen - specifically, what would occur to the refill rate (and, by inference, to adherence) when a second medication was added to a currently used once-daily drug. DESIGN: Open-label retrospective review of patient records. PARTICIPANTS: Patients of a large national health care provider who had received a prescription for latanoprost between July 1, 2001 and June 30, 2002. There were 1784 patients who had a second medication added and 3146 patients who remained on monotherapy. METHODS: For each patient, the mean number of days between refills was calculated for both the period before and that subsequent to the addition of the second medication, and an interperiod difference in refill interval between the two periods was calculated. Probability comparisons were performed using paired t tests (continuous) and Wilcoxon signed rank tests (categorical). RESULTS: The mean age of the population using second-line therapy was 68.3 ± 14.5 years (range, 4-97), and 56% were female. In this population of 1784 patients who used two different ocular-hypotensive medications, mean refill intervals for latanoprost were 40.6 ± 21.8 days before the addition of a second drug and 47.4 ± 24.4 days after the addition of a second drug, with a mean increase of 6.7 ± 25.6 days. For 22.9% (409/1784) of patients, the interval was increased by > 2 weeks (P < 0.0001). The mean refill interval was longer than that for the 3146 patients who continued on latanoprost monotherapy, which was 41 ± 24 days. CONCLUSIONS: This statistically and clinically significant increase in refill intervals may affect intraocular pressure control. We suggest that, when adding a second drug, physicians need to consider the possible impact on the patient's adherence to the first drug.
  
• Friedman DS, Nordstrom BL, Mozaffari E, Quigley HA. Glaucoma management among individuals enrolled in a single comprehensive insurance plan Ophthalmology 2005; 112: 1500-1504.
  
  OBJECTIVE: To determine the management patterns for glaucoma and suspect glaucoma in a nationally representative sample of newly treated persons. DESIGN: Retrospective cohort study of persons enrolled in a large managed care organization. PARTICIPANTS: One thousand seven hundred twelve diagnosed suspects and 3623 diagnosed glaucoma patients. METHODS: Linked pharmacy and patient care data were used to examine the glaucoma management and treatment patterns in this cohort of persons insured by a single managed care organization. Rates of monitoring and treatment were calculated for the 3 study groups. MAIN OUTCOME MEASURES: Probability of monitoring (return visits, visual fields [VFs], and optic nerve head imaging or photography) and treatment (argon laser trabeculoplasty [ALT] and surgery) for newly treated persons with suspect and glaucoma diagnoses. RESULTS: After a median follow-up of 440 days, 83% of treated diagnosed suspects had had a billed follow-up office visit to either an optometrist or an ophthalmologist at any time during follow-up, 46% had had at least one billed VF, and 13% had had some form of optic nerve head imaging. Rates were slightly higher for those with diagnosed glaucoma (P > 0.05). Surgery and ALT were performed rarely in this treated population (1%-6% at two years). CONCLUSIONS: This study suggests that a large proportion of individuals felt to require treatment for glaucoma or suspect glaucoma are falling out of care and are being monitored at rates lower than expected from recommendations of published guidelines. More research is needed to confirm these findings and to determine the reasons for loss to follow-up and low monitoring rates.
  
• Friedman DS, Nordstrom BL, Mozaffari E, Quigley HA. Women may be undertreated for adult-onset open-angle glaucoma.
  Ophthalmology 2005; 112: 1494-1499.
  
  OBJECTIVE: To determine the predictors of treatment for glaucoma and suspect glaucoma in a nationally representative sample of diagnosed persons. DESIGN: Retrospective cohort study of persons enrolled in a large managed care organization. PARTICIPANTS: Thirty-five thousand seven hundred fifty-four diagnosed suspects, 5265 diagnosed glaucoma persons, and 2633 individuals coded as having cupping of the optic disc. METHODS: Linked pharmacy and patient care information were used to examine the predictors of initiating glaucoma treatment in this cohort of persons insured by a single managed care organization. Predictors entered into logistic regression models included diagnostic group (suspect vs. diagnosed), age group, gender, region of the country, provider type at the initial visit (optometrist or ophthalmologist), diagnosis index date divided into two periods (1995-1998 and 1999-2001), and health plan enrollment duration after the initial diagnosis. MAIN OUTCOME MEASURES: Occurrence of and factors associated with treatment for glaucoma (argon laser trabeculoplasty [ALT], surgery, or topical ocular hypotensives). RESULTS: A logistic regression model adjusting for glaucoma status, age, region, clinician seen at initial visit, and index date found that women were less likely to undergo treatment (topical ocular hypotensives, ALT, or surgery) than men (odds ratio, 0.76; 95% confidence interval, 0.71-0.80). Factors other than gender that were associated with greater likelihood of treatment were glaucoma diagnosis, older age, region, and longer follow-up. CONCLUSIONS: We have documented wide variation in treatment among individuals diagnosed as having glaucoma or as glaucoma suspects. Women were 24% less likely to be treated than men, and younger individuals were far less likely to be treated than older ones. Furthermore, treatment varied by region of the country. Understanding the sources of these variations will help in determining how to arrive at better management strategies for individuals with glaucoma and suspect glaucoma.
  
• Nordstrom BL, Friedman DS, Mozaffari E, Quigley HA, Walker AM. Persistence and adherence with topical glaucoma therapy
  Am J Ophthalmol 2005; 140: 598-606.
  
  PURPOSE: The present study describes the patterns and predictors of treatment persistence and adherence among patients who are diagnosed with glaucoma or as glaucoma suspects (based on claims codes). DESIGN: A retrospective cohort study using health insurance claims data. METHODS: Newly treated individuals with diagnosed glaucoma (n = 3623) and suspect glaucoma (n = 1677) were obtained from healthcare claims data in the Ingenix Research Database. For each of these two diagnostic groups, we calculated the duration of continuous treatment with the initially prescribed medication (persistence) and the prevalence of use of the initial medication at various time points (adherence). Four drug classes were included: beta-blockers, alpha-agonists, carbonic anhydrase inhibitors, and prostaglandin analogs. RESULTS: Nearly one half of the individuals who had filled a glaucoma prescription discontinued all topical ocular hypotensive therapy within six months, and just 37% of these individuals recently had refilled their initial medication at three years after the first dispensing. Prostaglandins were associated with better persistence than any other drug class, which was indicated by hazard ratios for discontinuation of prostaglandins compared with beta-blockers of 0.40 (95% confidence interval, 0.35-0.44) for diagnosed patients and 0.44 (95% confidence interval, 0.37-0.52) for patients with suspect glaucoma. Prostaglandins showed a similar advantage in adherence. Furthermore, patients with diagnosed glaucoma were more likely to adhere to therapy than patients with suspect glaucoma (relative risk = 1.11; 95% confidence interval, 1.05-1.18). CONCLUSION: Persistence and adherence were substantially better with prostaglandins than with other drug classes, and patients with diagnosed open-angle glaucoma were more likely to adhere to treatment than suspected glaucoma.

5. Reviews

• Ashburn FS, Goldberg I, Kass MA. Compliance with ocular therapy.
  Surv Ophthalmol 1980; 24; 237-248.
  Zimmerman TJ, Zalta AH. Facilitating patient compliance in glaucoma therapy.
  Surv Ophthalmol 1983; 28: S252-S257.
  Kass MA, Meltzer DW, Gordon MO. The compliance factor.
  In: Drance SM, Neufeld AH (eds), Glaucoma: Applied Pharmacology in Medical Treatment. Grune & Stratton, Inc. Orlando, 1984.
  Mansukani SS. Improving adherence to drug-treatment regimens for glaucoma.
  Manag Care 2002; 11: S49-S53.
  Olthoff CM, Schouten JS, van de Borne BW, Webers CA. Noncompliance with ocular hypotensive treatment in patients with glaucoma or ocular hypertension an evidence-based review.
  Ophthalmology 2005; 112: 953-961.
  
  OBJECTIVE: To summarize the available scientific evidence to support clinical decisions on how to deal with noncompliance in glaucoma patients. CLINICAL RELEVANCE: Insufficient reduction of intraocular pressure and progression of visual field (VF) loss in glaucoma patients due to noncompliance with topical treatment may result in unnecessary therapy, with additional risks and costs. METHODS/LITERATURE REVIEWED: We conducted a literature search in the databases MEDLINE, EMBASE, CINAHL, PsychInfo, and Cochrane and reference lists. Thirty-four articles describing 29 original quantitative studies, in English, German, French, or Dutch, were included. Studies on noncompliance in drug trials were excluded. Two investigators independently selected the articles and abstracted their content, before negotiating their inclusion or exclusion. RESULTS: The proportions of patients who deviate from their prescribed medication regimen ranged from 5% to 80%. The impact of noncompliance on clinical outcome has not yet been established. There are no determinants sensitive and specific enough to identify potential noncompliers accurately. Patient knowledge and dose frequency can be used as starting points to improve compliance. A combination of patient education and prevention of forgetting doses seems to be successful in enhancing patient compliance. CONCLUSION: Noncompliance with hypotensive treatment is common among glaucoma patients. However, there is no strong evidence supporting a relation between noncompliance and progression of VF loss. Only a few guidelines for clinicians can be derived from the currently available literature. Future research should be guided by clinically relevant questions.
  
• Schwartz GF. Compliance and persistency in glaucoma follow-up treatment. Curr
  Opin Ophthalmol 2005; 16: 114-121.
  
  PURPOSE OF REVIEW: To summarize research published between 1980 and October 2004 regarding compliance (the extent to which patients' behaviors correspond with providers' recommendations) and persistency (total time on therapy) in patients diagnosed with open-angle glaucoma or ocular hypertension; to suggest approaches ophthalmologists might consider to improve compliance and persistency; and to identify areas warranting future research. RECENT FINDINGS: Medication compliance, the focus of most compliance-related research, has been measured using a variety of methods including patient self-reports, the medication possession ratio, and electronic monitoring. Noncompliance rates of at least 25% commonly have been reported. The primary obstacles to medication compliance appear to be situational/environmental (i.e., being away from home or a change in routine) or related to the medication regimen (i.e., side effects or complexity). Persistency with ocular hypotensive therapies has been found to be poor. Retrospective cohort studies using survival analyses have reported that fewer than 25% of patients are persistent over 12 months. SUMMARY: Accurately assessing patient compliance and persistency is important to optimizing patient care. Physicians may mistake either medication noncompliance or lack of persistency with poor efficacy. Such errors would likely increase health care costs if they result in unnecessary changes to a patient's therapeutic regimen or in surgery.

6. Selected Systemic Medication Cooperation Studies (non-glaucoma)

Many prescriptions are ordered, but not picked up at the pharmacy - at least not immediately

• Farmer KC, Gumbhir AK. Unclaimed prescriptions: an overlooked opportunity.
  Am Pharm 1992; 32: 55-59.
  
  Unclaimed prescriptions are an overlooked component of medication noncompliance. Of 21 pharmacies surveyed for prescriptions unclaimed for 30 days or more, pharmacies averaged 21.4 prescriptions each (450 total), with the mean age of 45.6 days. More than 50% of unclaimed prescriptions were new phoned-in prescriptions. Anti-infective agents were the largest class of unclaimed medications, followed by analgesics and respiratory agents. Pharmacists can use unclaimed prescriptions as a basis for increasing their patient-oriented services.
  
• Kirking MH, Kirking DM. Evaluation of unclaimed prescriptions in an ambulatory care pharmacy.
  Hosp Pharm 1993; 28: 90-91.
  
  Unclaimed prescriptions, that is, those filled but not obtained by the patient, may influence patient care and pharmacy operations. The authors' objectives were to (1) describe characteristics of unclaimed prescriptions and the patients for whom these prescriptions were written, and (2) compare and contrast characteristics of prescriptions never dispensed with those that were eventually dispensed. During the 8-week study, 180 patients with 224 unclaimed prescriptions were identified at the University of Michigan Hospital's Ambulatory Care Pharmacy. The most frequent categories of unclaimed prescriptions were skin/mucous membrane, central nervous system, and anti-infective medications. In 25.9% of cases of unclaimed prescriptions, they were telephoned in by a healthcare professional as new prescriptions. Overall, 64.3% were new, rather than refill, prescriptions. Approximately two thirds of the unclaimed prescriptions were eventually dispensed. Of the characteristics evaluated for differences between unclaimed prescriptions eventually dispensed and those never dispensed, only new versus refill prescriptions and class of medication were significantly different. Most unclaimed prescriptions were eventually dispensed after a delay. However, the types of medications involved suggest that these delays from initially unclaimed prescriptions could have resulted in problems.
  

Non-adherence with medication regimens is as high as 49-75% in older populations

• Maronde RF, Chan LS, Larsen FJ, Strandberg LR, Laventurier MF, Sullivan SR. Underutilization of antihypertensive drugs and associated hospitalization.
  Med Care 1989; 27: 1159-1166.
  
  The association of underutilization of drugs prescribed for the treatment of hypertension and acute-care hospital readmissions was evaluated. The data base consisted of computerized hospitalization records and computerized out-patient pharmacy records, checked by chart audit for validity. The number of days' supply of antihypertensive agents was estimated by dividing the quantity of drugs dispensed by the daily dose indicated by the prescription instructions. All patients had been admitted to an acute-care hospital during a six-month period with the diagnosis of hypertension. Following discharge from the hospital, drug utilization and readmission status were determined for a minimum of one year. The drug compliance of a group of patients who were readmitted to the hospital was compared with the patients who were not readmitted. The readmitted group had a significantly higher ratio of days when they were without any antihypertensive agents relative to the length of time in the study. There were no statistically significant differences in demographic features or blood-pressure levels between the patient groups. These findings indicate that underutilization of antihypertensive drugs may be associated with hospitalization, which could be prevented if patients had complied with their medication schedules.
  
• Cramer JA. Effect of partial compliance on cardiovascular medication effectiveness.
  Heart 2002; 88: 203-206.
  
  Review indicating general principles and other references.
  
• Loghman-Adham M. Medication noncompliance in patients with chronic disease: issues in dialysis and renal transplantation.
  Am J Manag Care 2003; 9: 155-171.
  
  For many chronic conditions, poor patient compliance with prescribed medications and other aspects of medical treatment can adversely affect the treatment outcome. Compliance with long-term treatment for chronic asymptomatic conditions such as hypertension is on the order of 50%. Although drugs with a longer therapeutic half-life may ease the burden of repeated daily dosing, the efficacy of any self-administered medication depends to a large extent on patient compliance. This article addresses the compliance issues in patients undergoing renal replacement therapy and in those with a successful renal transplant. A focused discussion of compliance in dialysis and renal transplant patients is followed by a general review of the literature on patient compliance. Many factors associated with poor compliance in this patient population are identified via a review of the recent literature. The difficulties in monitoring medication compliance and the methods used are discussed. Among factors associated with poor compliance, the following have been identified in several studies: frequent dosing, patient's perception of treatment benefits, poor patient-physician communication, lack of motivation, poor socioeconomic background, lack of family and social support, and younger age. Many strategies have been suggested to improve medication compliance, most without scientific validation. Strategies to improve compliance in dialysis and transplant patients are similar to those described for other chronic conditions and include simplifying the treatment regimen, establishing a partnership with the patient, and increasing awareness through education and feedback.
  
• Balkrishnan R, Carroll CL, Caamacho FT & Feldman SR. Electronic monitoring of medication adherence in skin disease: results of a pilot study.
  J Am Acad Dermatol 2003; 49: 651-654.
  
• Claxton AJ, Cramer J, Pierce C. A systematic review of the associations between dose regimens and medication compliance.
  Clin Ther 2001; 23:1296-1310.
  Hamilton GA. Measuring adherence in a hypertension clinical trial.
  Eur J Cardiovasc Nurs 2003: 2: 219-228.
  Hinkin CH, Castellon SA, Durvasula RS, Hardy DJ, Lam MN, Mason KI, Thrasher D, Goetz MB, Stefaniak, M. Medication adherence among HIV+ adults: effects of cognitive dysfunction and regimen complexity.
  Neurology 2002; 59: 1944-1950.
  
• Knobel H, Alonso J, Casado JL, Collazos J, Gonzalez J, Ruiz I, Kindelan JM, Carmona A, Juega J, Ocampo A. Validation of a simplified medication adherence questionnaire in a large cohort of HIV-infected patients: the GEEMA Study.
  AIDS 2002; 16: 605-613.
  
• McNabb JJ, Nicolau DP, Stoner JA, Ross J. Patterns of adherence to antiretroviral medications: the value of electronic monitoring.
  AIDS 2003; 17: 1763-1767.
  
• O'Brien G, Lazebruk R. Telephone call reminders and attendance in an adolescent clinic.
  Pediatrics 1998; 101: 1-7.
  
• Peterson AM, Takiya L, Finley R. Meta-analysis of trials of interventions to improve medication adherence.
  Am J Health Syst Pharm 2003; 7: 657-665.
  
• Wagner GJ. Predictors of antiretroviral adherence as measured by self-report, electonic monitoring, and medication diaries.
  AIDS Patient Care STDS 2002; 26: 599-608.
• Winland-Brown JE, Valiante J. Effectiveness of different medication management approaches on elders; medication adherence.
  Outcomes Mange Nurs Pract 2000; 4: 172-174.