Saira A. Jan, MS, PharmD

To examine whether adherence to osteoporosis medications can be improved by educational interventions targeted at primary care physicians (PCPs) and patients.

Post hoc analysis of data collected as part of a prospective randomized controlled trial to improve initiation of osteoporosis management such as bone mineral density testing or osteoporosis drug initiation.

The trial was conducted among patients at risk for osteoporosis enrolled in Horizon Blue Cross Blue Shield of New Jersey. For a 3-month period, randomly selected PCPs and their patients received education about osteoporosis diagnosis and treatment. The PCPs received face-to-face education by trained pharmacists, while patients received letters and automated telephone calls. The control group received no education. We assessed medication adherence during 10 months following the start of the intervention using the

medication possession ratio (MPR), the ratio of available medication to the total number of days studied.

These analyses included 1867 patients (972 randomized to the intervention group and 875 to the control group) and their 436 PCPs. During 10 months following the intervention, the median MPRs were 74% (interquartile range [IQR], 19%-93%) for the intervention group and 73% (IQR, 0%-93%) for the control group (

 = .18). The median times until medication discontinuation after the intervention were 85 days (IQR, 58-174 days) for the intervention group and 79 days (IQR, 31-158 days) for the control group.

The educational intervention did not significantly improve medication compliance or persistence with osteoporosis drugs.

Medication adherence for osteoporosis is poor, and there are few proven effective interventions.

In a post hoc analysis of a randomized controlled trial of brief education, medication adherence was no better in the intervention group compared with the control group.

Interventions focused on initiation of chronic disease management may not enhance medication adherence.

Adherence interventions should focus on patients, not physicians.

Improving patient adherence with osteoporosis medications is an important challenge. Higher levels of adherence may be associated with reduced fracture rates

 demonstrate suboptimal adherence among patients in the community. Oft-cited barriers to achieving adequate adherence include insufficient patient education, specific patient health beliefs, complex medication regimens, polypharmacy, poor provider-patient relations, patient forgetfulness, and medication costs.

 Strategies targeting these barriers, as well as patient monitoring systems and feedback based on clinical markers, have been proposed to improve medication adherence for osteoporosis treatments.

Successful medication adherence interventions for other chronic diseases such as hypertension and asthma have been multifactorial and focused on the patient.

 A small randomized trial attempted to enhance adherence to raloxifene hydrochloride among 75 women with osteopenia; a nurse-run patient monitoring program with clinic appointments every 12 weeks improved adherence to raloxifene at 1 year.

 of patients with osteoporosis who sustained distal forearm fractures showed that timely provision of educational brochures, primary care provider appointments, and bone mineral density testing appointments improved adherence over 6 months of follow-up. However, many of the most adherent patients had the best bone mineral density.

While medication adherence may be primarily a patient behavior, it is unclear whether physician-directed interventions can influence this behavior. To our knowledge, no prior intervention for osteoporosis medication adherence has focused on the physician. In this study, we performed a post hoc analysis of data from a randomized controlled trial for improving osteoporosis management to determine whether a brief physician-oriented intervention improved compliance or persistence with osteoporosis medications.

These analyses are based on a cluster randomized controlled trial conducted in Horizon Blue Cross Blue Shield of New Jersey (HBCBSNJ) that has been described in detail elsewhere.

 Briefly, we randomly assigned primary care physicians (PCPs) and their patients at risk for osteoporosis (defined herein) to receive a multifaceted intervention or usual care. Randomization was clustered so that all patients of a particular physician were assigned to the same arm, either intervention or usual care. Patients were randomized with their PCP to reduce any contamination within a given physician’s practice. The trial was aimed at improving the management of osteoporosis among at-risk patients, including initiation of bone mineral density testing and pharmacotherapy for osteoporosis. The brief intervention proved effective for the primary outcome: initiation of osteoporosis management was enhanced by 45% (95% confidence interval [CI], 9%-93%) in the intervention group compared with the control group.

While initiation of testing and treatment are the necessary first steps for osteoporosis management, we pursued the present analyses to determine whether this intervention also enhanced adherence with medications used for osteoporosis. We examined 2 aspects of adherence, compliance and persistence. These analyses are post hoc and should be considered in light of all the known limitations of such analyses.

We ascertained baseline patient and physician characteristics during the period from July 1, 2002, through August 31, 2004. The intervention occurred during a 3-month interval between September 1, 2004, and December 1, 2004. Adherence was assessed by prescription filling data from September 1, 2004, through June 24, 2005. All aspects of the study were approved by the Partners Healthcare Institutional Review Board.

Eligible participants for the parent trial were insured by HBCBSNJ and were at risk for osteoporosis. At-risk status was defined as the following: (1) women 65 years or older, (2) men or women 45 years or older with a prior fragility fracture (including hip, wrist, humerus, or spine), or (3) men or women 45 years or older who took oral glucocorticoids for at least 90 days during the baseline period.

All subjects who filled at least 1 prescription during the baseline or follow-up period for a medication used for osteoporosis were included. Osteoporosis medications were alendronate sodium, calcitonin, estrogen, raloxifene hydrochloride, risedronate sodium, and teriparatide (there was no use of ibandronate sodium in the study population). Estrogen therapy was included, although we cannot determine the indication for use in the study database. Subjects were further classified into the following 3 groups: new users of osteoporosis medications during the intervention period, current users at the time the intervention started, and past users based on prescription filling during the baseline period. New users had never filled a prescription for an osteoporosis medication during the baseline period. Current users filled at least 1 prescription for an osteoporosis medication during the baseline period and filled at least 1 prescription in the 90 days before the start of the study period. Ninety days represents the longest prescription duration allowed. This definition intended to capture those patients who were filling prescriptions for osteoporosis medications on a somewhat regular basis immediately before the intervention. Past users filled at least 1 prescription for an osteoporosis medication during the baseline period but did not fill in the 90 days before the start of the study period. We assumed that these patients used osteoporosis medications in the past but stopped before the intervention.

The intervention consisted of education about osteoporosis diagnosis and appropriate treatment. This information was delivered to physicians in a single one-on-one educational encounter during a 3-month intervention period. Physician education was accomplished with a visit from a pharmacist-educator. These pharmacists had participated in a 1-day training session and several follow-up teleconferences about osteoporosis and the principles of one-on-one physician education (“academic detailing”).

 They learned specific teaching techniques and included the continuing medical education curriculum during their visits with the physicians. At the visits, they provided the physicians with the following educational material: a list of the physician’s patients who were deemed at risk for osteoporosis; written summaries of osteoporosis epidemiology, diagnosis, and treatment; an algorithm for diagnosis and treatment of osteoporosis that was laminated as a card to fit in a coat pocket; a guide to osteoporosis pharmacotherapy; “tear sheets” resembling prescription pads with check boxes for fall prevention, calcium and vitamin D use, bone mineral density testing, and treatment; and patient pamphlets on fall prevention (available from the author on request). Finally, the study paid for physicians to apply for continuing medical education credit on completion of a postvisit test.

In addition to the physician-directed education, patients in the intervention group received an introductory letter outlining the importance of osteoporosis, its diagnosis, and appropriate treatment. This letter was followed by an automated telephone call inviting them to undergo bone mineral density testing. This call used interactive voice response technology that has been used for other screening tests but which was ineffective in that trial.

This study measured medication compliance as the primary end point and persistence as a secondary end point. Compliance was expressed as the medication possession ratio (MPR), defined as number of days for which medication is available divided by number of days in the follow-up period.

 A patient who consistently fills prescriptions and has medication available for each day is 100% adherent. For new and past users (who did not have osteoporosis medications available in the 90 days before the intervention), the follow-up period started on the date of the first filled prescription for an osteoporosis medication on or after September 1, 2004 (the first day of the study period). For current users, the follow-up period started on September 1, 2004, with “rollover” of available osteoporosis medications from previously filled prescriptions. The end of follow-up occurred at the first of the following: death, loss of HBCBSNJ eligibility, or the end of the study period.

As a secondary end point, we examined persistence. Persistence measures complement the MPR in that they provide insight into a patient’s medication use over time.

 Persistence was expressed as days until discontinuation, where discontinuation was defined as at least 30 days without any medication available. Prior analyses found that 30 days without any medication available strongly correlated with permanent discontinuation.

 For new, current, and past users, the followup period started on the date of the first filled prescription for osteoporosis medications on or after September 1, 2004. As already defined, the end of follow-up occurred at the first of the following: death, loss of HBCBSNJ eligibility, or the end of the study period.

Two different patients could have the same MPR but different persistence values. For example, a patient who has medication available for the first 150 days of a 300-day study period has an MPR of 50%. Likewise, a patient who takes osteoporosis medications every other day for all 300 days also has an MPR of 50%. The first patient was persistent for 150 days, whereas the second patient was persistent for 300 days.

We used insurance claims as our source of outcomes and baseline patient data. Patient baseline data included demographics, comorbidities associated with increased risk of osteoporosis and fractures, health-seeking behaviors such as immunizations and cancer screening, and types of preintervention osteoporosis medications. We also collected data regarding filling of prescriptions for osteoporosis medications, including types of medication, dates filled, and amount of medication dispensed. This source of data does not contain indications for medication use; thus, some of the estrogen therapy was likely used for nonosteoporosis indications.

We compared the characteristics of patients randomized to intervention versus control groups. The outcome analyses considered new users of osteoporosis medications separately from current or past users. All analyses used an intent-to-treat approach, including physicians and patients in whom the educational interventions were not successfully completed. The median MPR and days until discontinuation were calculated and compared for intervention and control groups. We modeled MPRs using Poisson distribution regression analysis adjusting for the correlation with generalized estimating equations. Time until discontinuation or persistence was modeled with Cox proportional hazards regression analysis using sandwich estimators to adjust for the clustering within physician practice. For both adjusted models, we included all variables using the inverse probability treatment weighting method.

 Analyses were performed using SAS version 8.02 (SAS Institute, Cary, NC).

A total of 1867 patients and 436 PCPs were randomized and included in this study. There were 126 new osteoporosis medication users, 1157 current users, and 584 past users. Demographic characteristics, medical history, risk factors for osteoporosis, and health behavior were not notably different between the intervention and control groups (

). Most patients were between 65 and 74 years old, and almost all were female. Few patients had documented osteoporosis by diagnosis codes during the baseline period, and approximately 1 in 10 had sustained a fracture. Baseline osteoporosis treatments included all of the major categories, with bisphosphonates predominating (

Across all patients studied, new and prevalent users, the median MPRs were 74% (interquartile range [IQR], 19%-93%) for the intervention group and 73% (IQR, 0%-93%) for the control group (

 = .18). The median times until first refill after the intervention were 57 days (IQR, 22-298 days) for the intervention group and 61 days (IQR, 23-298 days) for the control group (

Among new users, the unadjusted median MPR was 88.6% for the intervention group compared with 76.4% for the control group (

). After adjusting for baseline characteristics listed in Table 1, there was no difference in MPRs (relative risk [RR], 1.05; 95% CI, 0.89-1.23). Before adjustment, persistence (measured as the median days until discontinuation) was 85 days for the intervention group compared with 79 days for the control group (

). The intervention group exhibited a trend toward higher number of days until discontinuation; however, this increase was not statistically significant in the adjusted model (RR, 0.85; 95% CI, 0.48-1.49).

As with new users, the median MPR and median persistence were similar between current users in the intervention and control groups. The median MPRs were 87.6% for the intervention group and 88.8% for the control group (

 = .60) (Table 3). The median persistence durations were 227 days for the intervention group and 229 days for the control group (

 = .31) (Table 4). Among current users, only 0.84% in the intervention group and 0.53% in the control group did not fill any osteoporosis medication prescriptions during the study period. Adjusted analyses showed no difference in the MPR or persistence.

Past users in both groups did not frequently begin to fill prescriptions for osteoporosis medications again during the study follow-up. The median MPR for the intervention group was 0.0 (IQR, 0.0-36.0), while the median for the control group was also 0.0 but with a much narrower IQR of 0.0 to 10.4 (Table 3). The adjusted analysis showed an increase in the MPR for the intervention group (RR, 1.35; 95% CI, 1.00-1.81). The median times until medication discontinuation (for those who filled ≥1 prescription) were 130 days for the intervention group and 104 days for the control group (

= .21). The adjusted analysis suggested a trend toward a reduced risk of discontinuation among the intervention group (RR, 0.81; 95% CI, 0.56-1.18). Among past users, 62.7% of the intervention group and 73.7% of the control group never filled osteoporosis medication prescriptions during the study period.

A randomized brief educational intervention targeting initiation of testing and treatment for osteoporosis did not improve compliance or persistence with osteoporosis medications over a 10-month follow-up period. There was a suggestion for some improvement among patients who had used osteoporosis medications in the past, but there was no demonstrable improvement among current or new users of these medications. The intervention was successful at improving the frequency of initiating of bone mineral density testing and osteoporosis medication prescription.

 Our ability to observe a difference in compliance or persistence may have been affected by our 10-month follow-up and a high rate of baseline adherence in the control group. In general, an MPR of 80% or higher is regarded as adequate. Furthermore, results of some studies

 suggest that an MPR of 80% or higher is associated with reduced rates of fracture.

The analyses we present are secondary analyses of a trial designed to improve initiation of osteoporosis management. We pursued these post hoc analyses because the intervention produced a positive effect on initiation of medication use, suggesting that there might have been benefits to adherence. However, the intervention (focused more on PCPs than on patients) did not produce substantial gains in medication adherence. This implies that medication adherence is a specific behavior that likely requires potent interventions designed specifically for adherence.

Several limitations of this intervention need mention. Our source of data for this study was a large healthcare utilization database that does not contain information on the reasons for prescribing a given medication. Some of the estrogen therapy users were likely using this treatment for other indications. We followed up patients for 10 months to determine their compliance. This limits our ability to detect clinical outcomes such as fractures. The compliance level of the control arm was high, limiting our ability to detect an incremental effect due to the intervention. Finally, our intervention was brief; a more sustained intervention might have been more effective at enhancing adherence.

Strengths of this study include its randomized nature and the use of a typical community population versus a clinical trial population, where volunteers may be different from usual patients. Much of the literature on medication adherence is based on observational findings

 rather than randomized findings and suggests that adherent patients have improved outcomes such as reduced fractures.

 It is critical to recognize that adherence is not a random behavior; adherent patients may have improved outcomes for many reasons, only one of them being consuming more osteoporosis medication. In fact, randomized trials in other areas have found that adherent patients receiving placebo often fare better than nonadherent patients in the intervention arm.

Our negative results, using a brief intervention focused on physicians, suggest that adherence interventions for osteoporosis might be more effective when focused on patients. A recent successful intervention for other chronic medications targeted patients with education and the use of medication blister packs.

 Prior interventions to improve osteoporosis medication adherence have examined the effects of simpler regimens, patient monitoring, and education. Several studies

 demonstrate that oral bisphosphonates dosed weekly versus daily may improve adherence. An observational study

 of 2741 postmenopausal American women starting bisphosphonate therapy showed a significantly higher mean MPR for weekly dosing (69.2%) compared with 57.6% for daily dosing. Over 365 days, the median persistence was significantly increased for weekly dosing versus daily dosing (269 vs 134 days). Another observational study

 involving 2124 postmenopausal Dutch women starting bisphosphonate therapy also demonstrated better persistence at the end of 1 year for weekly versus daily dosing. Despite these encouraging results, all study authors pointed out that, even for the patients taking bisphosphonates dosed weekly, adherence and persistence were suboptimal. Although it is possible that a less frequently dosed bisphosphonate might further improve adherence,

 the literature suggests that enhancing medication adherence is much more complicated than implementing less frequent dosing.

 conducted a randomized controlled trial using a monitoring intervention. In that study, 75 postmenopausal women with osteopenia were newly prescribed raloxifene and assigned to nurse monitoring or usual care (no monitoring). Those patients who were randomized to the monitoring group attended 3 appointments (spaced 12 weeks apart) with nursing staff, during which they were asked 6 questions related to well-being, problems with medication, and adverse events. No information about osteoporosis per se was offered, unless patients happened to ask about it. Monitored patients demonstrated a statistically significant increase in rates of adherence: 65% were adherent (defined as taking >75% of prescribed raloxifene tablets) at 1 year compared with 42% in the nonmonitored group. These study findings suggest that a patient-directed program of ongoing intensive counseling improves adherence.

 suggests that patient education is an important strategy for improving adherence. Additional studies

 of patients with chronic diseases such as rheumatoid arthritis and asthma show that face-to-face counseling from healthcare providers can improve adherence. Other than our study, there are few studies investigating the effect of education on adherence with osteoporosis medications. Cuddihy and colleagues

 describe a prospective nonrandomized population-based study involving women with osteoporosis having recent distal forearm fractures. Soon after the fracture, patients were provided educational pamphlets, a PCP appointment, and a bone mineral density testing appointment. For 38 women advised to begin therapy for osteoporosis, the intervention improved self-reported medication adherence at 6 months (36% were adherent compared with 9% in a historical cohort). Nielsen and colleagues

 describe preliminary results from a prospective randomized study of 280 patients with osteoporosis undergoing an educational intervention consisting of “school” comprising 16 days of classes over 4 weeks. Self-reported persistence with pharmacotherapy was higher in the school group compared with the control group. However, the high persistence rates (93%-99%) for the 61 patients who reached 24 months of follow-up suggest that this extraordinarily motivated study population may not be representative of the wider community.

The brief intervention we tested that targeted PCPs to improve their initiation of management of osteoporosis did not enhance medication adherence, primarily a patient behavior. We have since conducted several focus groups with patients that suggest the following: it is critical to convince patients of the importance of treating a largely asymptomatic condition at the outset of treatment; most patients would rather not take medications chronically, and thus any adverse experience or concern is often enough to interfere with adherence; and persistent use of treatments requires reminder systems that are often idiosyncratic to a given patient. These observations and recent review articles

 have helped us to design new adherence interventions for osteoporosis that we anticipate will be more effective than what we describe herein. We will not realize the full potential of our new treatments for osteoporosis without better adherence.

Division of Pharmacoepidemiology (AD-HS, MRS, JMP, DHS) and Division of Rheumatology (DHS), Brigham and Women’s Hospital, Boston, MA; Division of Endocrinology (AD-HS), Columbia Presbyterian Hospital, New York, NY; Horizon Blue Cross Blue Shield (SAJ, MP, CT, LB), Newark, NJ; and Outcomes Research Group (Y-TC, TWW), Merck & Co, Inc, West Point, PA. Ms Truppo is now with Care Management International, Hoboken, NJ. Ms Breiner is now with NYC Department of Health, New York, NY.

Portions of this educational trial were supported by Merck & Co, Inc. Dr Solomon’s work on osteoporosis is also supported by the Arthritis Foundation and the National Institutes of Health (National Institute of Arthritis and Musculoskeletal and Skin Diseases [NIAMS] K24 AR055989 and NIAMS P60 AR 047782).

 Drs Chen and Weiss are full-time employees of Merck & Co, Inc, the funder of this study, and report owning stock in that company. Dr Solomon reports receiving research grants pending from Novartis and Amgen. The other authors (AD-HS, MRS, JMP, SAJ, MP, CT) report no relationship or financial interest with any entity that would pose a conflict of interest with the subject matter of this article.

 Concept and design (AD-HS, SAJ, MP, Y-TC, TWW, DHS); acquisition of data (JMP, CT, TWW, DHS); analysis and interpretation of data (AD-HS, MRS, Y-TC, TWW, DHS); drafting of the manuscript (AD-HS, DHS); critical revision of the manuscript for important intellectual content (JMP, SAJ, MP, Y-TC); statistical analysis (MRS); provision of study materials or patients (CT); obtaining funding (MP, Y-TC); and administrative, technical, or logistic support (JMP, CT).

 Daniel H. Solomon, MD, MPH, Division of Pharmacoepidemiology, Brigham and Women’s Hospital, 75 Francis St, Boston, MA 02115. E-mail: dhsolomon@partners.org.

1. Caro JJ, Ishak KJ, Huybrechts KF, Raggio G, Naujoks C.

 The impact of compliance with osteoporosis therapy on fracture rates in actual practice. 

2. McCombs JS, Thiebaud P, McLaughlin-Miley C, Shi J. 

Compliance with drug therapies for the treatment and prevention of osteoporosis. 

Compliance with osteoporosis medications. 

 Improving compliance and persistence with bisphosphonate therapy for osteoporosis. 

 Interventions to enhance patient adherence to medication prescriptions: scientific review [published correction appears in 

 Persistence with bisphosphonate treatment for osteoporosis: finding the root of the problem. 

 Approaches to patient education: emphasizing the long-term value of compliance and persistence. 

Articles

Post hoc analysis of a randomized controlled trial found that a 1-session educational intervention targeted at patients and primary care physicians did not improve osteoporosis medication adherence.


Adherence to Osteoporosis Medications After Patient and Physician Brief Education: Post Hoc Analysis of a Randomized Controlled Trial

 To propose standardized methods for measuring concurrent adherence to multiple related medications and to apply these definitions to a cohort of patients with diabetes mellitus.

Retrospective cohort study of 7567 subjects with diabetes prescribed 2 or more classes of oral hypoglycemic agents in 2005.

For each medication class, adherence for each patient was estimated using prescription-based and interval-based measures of proportion of days covered (PDC) from cohort entry until December 31, 2006. Concurrent adherence was calculated by applying these 2 measures in the following 3 ways: (1) the mean of each patient’s average PDC, (2) the proportion of days during which patients had at least 1 of their medications available to them, and (3) the proportion of patients with a PDC of at least 80% for all medication classes. Because patients taking multiple related medications have distinct patterns of use, the analysis was repeated after classifying patients into mutually exclusive groups.

Concurrent medication adherence ranged from 35% to 95% depending on the definition applied. Interval-based measures provide lower estimates than prescription-based techniques. Definitions that require the use of at least 1 drug class categorize virtually all patients as adherent. Requiring patients to have a PDC of at least 80% for each of their drugs results in only 30% to 40% of patients being defined as adherent. The variability in adherence is greatest for patients whose treatment regimen changed the most during follow-up.

The variability in adherence estimates derived from different definitions may substantially impact qualitative conclusions about concurrent adherence to related medications. Because the measures we propose have different underlying assumptions, the choice of technique should depend on why adherence is being evaluated.

Variability in adherence estimates derived from different definitions of concurrent adherence

to related medications may lead to very different qualitative conclusions about adherence in a

Therefore, it is important to establish how concurrent adherence to multiple related medications should be calculated.

This study found that concurrent medication adherence varied widely depending on the definitions applied because of the assumptions on which they are based.

The choice of adherence measurement technique should depend on the reason why adherence is being measured.

dherence (also called compliance) to prescribed medications is a key dimension of healthcare quality. Nonadherence is associated with poor health outcomes

 and threatens the gains in quality that have been made by appropriate pharmacotherapy over the past several decades.

 Efforts to accurately measure and improve adherence have received increasing attention from patients, physicians, payers, and other healthcare stakeholders. Moreover, the National Committee for Quality Assurance has recently included adherence among the measures by which it evaluates the quality of care provided by healthcare plans.

Adherence may be assessed in various ways, including surveying patients, directly observing medication taking, measuring drug or metabolite blood levels, and using electronic medication monitors.

 Pharmacy refill claims, which are highly correlated with these measures,

 provide an objective way to measure adherence for large populations of patients. Such data are frequently used by health services researchers and pharmacy benefit plan managers to calculate adherence by estimating the amount of medication available to a patient over a given interval.

These measures were developed and have been most widely used to evaluate adherence to individual medications or medication classes. For example, Benner et al

 assessed statin adherence by measuring the proportion of days covered (PDC) for patients newly prescribed 1 of these agents. However, it is common for patients with chronic conditions (such as hypertension, coronary artery disease, or congestive heart failure) to switch between classes of medications or to receive multiple medications to treat a single disease. Such behavior is clinically sensible and formalized in practice guidelines but is inadequately captured by measuring adherence for a single agent or medication class.

Studies that have measured concurrent adherence to multiple medication classes have used various techniques,

 and unlike adherence to single medications or single medication classes,

 there are no published definitions or guidelines about how to structure these measurements. Understanding the variability in adherence estimates obtained from different measures will assist in selecting appropriate definitions. In this article, we propose standardized methods for measuring concurrent adherence, apply them to a cohort of patients with diabetes mellitus receiving treatment with oral hypoglycemic agents, and compare their performances.

We assembled a cohort of patients who received pharmacy

 benefits through Horizon Blue Cross Blue Shield of New Jersey and who were prescribed an oral hypoglycemic agent between January 1, 2005, and December 31, 2005. We considered only those patients who had 1 or more inpatient or outpatient claims with a diagnosis of diabetes (

International Classification of Diseases, Ninth Revision, Clinical Modification

 code 250.x) and were prescribed 2 or more classes of oral hypoglycemic medications during this period. While all oral hypoglycemics may be considered members of 1 therapeutic class, we defined classes on a mechanistic basis (ie, sulfonylurea, metformin hydrochloride, glitazones, acarbose, and meglitinides), as many patients take agents belonging to these different classes concurrently. Furthermore, this strategy allows for the generalization of our methods to patients using noninterchangeable medication classes (eg, statins, angiotensin-converting enzyme inhibitors, antiplatelets, and 

We excluded patients who lost eligibility or did not fill any prescriptions or use any medical services in 2006. We defined an index date for each oral hypoglycemic class prescribed to each patient as the first prescription date for any member of the class during the accrual period.

We combined filled prescription data for patients in our cohort with complete paid claims data and eligibility files to create a relational database consisting of data for all filled prescriptions, procedures, inpatient and outpatient physician encounters, hospitalizations, and deaths for the patients in our cohort. Prescription information in the claims data included drug name, dosage, date dispensed, quantity dispensed, and days supplied. All traceable person-specific identifying factors were transformed into anonymous coded study numbers. The institutional review board of Brigham and Women’s Hospital approved the study.

To measure adherence, we first created a supply diary for each patient-day by stringing together consecutive fills of each medication class being studied based on dispensing dates and reported days’ supply. All drugs dispensed within a therapeutic class (eg, glyburide and glipizide in the sulfonylurea class) were considered interchangeable. When a dispensing occurred before the previous dispensing should have run out, utilization of the new medication was assumed to begin the day after the end of the old dispensing. If a patient accumulated more than 180 days’ supply on a given day, the accumulated supply was truncated at 180 days.

We estimated adherence by calculating the PDC for each drug class prescribed to each patient from the index date to the end of our assessment period (December 31, 2006) using 2 different methods that differ in how the denominator of the adherence measure is calculated (

). We defined prescription-based adherence based on medication possession for all drugs within a class during the time between 2 prescriptions; that is, the number of days of medication supplied between the first and last prescriptions in a given period (numerator) was divided by the number of days between these 2 prescriptions plus the accumulated days supplied from the last prescription (denominator). In contrast, we defined interval-based adherence based on medication possession during the interval from the index date to December 31, 2006. In this way, the number of days of medication supplied throughout the period (numerator) was divided by the number of days in it (denominator).

Adherence to Multiple Medications Concurrently

We estimated simultaneous adherence to multiple medication classes for each patient by using the prescription-based adherence estimated for each class in 3 distinct ways (

 First, we calculated an average of the prescription-based PDC for each patient and then generated a group mean of these averages for the entire cohort. For example, for patients taking 2 classes of oral hypoglycemics, the PDC for each was calculated and then averaged, and this average was used to calculate the mean group PDC. Second, we calculated the number of days during which patients had at least 1 of their prescribed medications available to them beginning from the date they filled their first prescription for any oral hypoglycemic (ie, their earliest index date) until their latest prescription date for any of the medications they were using. For example, for a patient being treated with metformin and glyburide, the numerator of the adherence measure was the number of days during which he or she had either metformin or glyburide available. Third, we estimated the proportion of patients who had a prescription-based PDC of at least 80% for each medication they were using. For example, for patients treated with glyburide and metformin, each patient was considered adherent if his or her prescription-based PDC for each was at least 80%.

This study compares the performance of several definitions of concurrent adherence to related medications.

Author | Saira A. Jan, MS, PharmD

Articles

New content coming soon, please check back later.