The American Journal of Managed Care July 2009
Adherence to Osteoporosis Medications After Patient and Physician Brief Education: Post Hoc Analysis of a Randomized Controlled Trial
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.
Objective: To examine whether adherence to osteoporosis medications can be improved by educational interventions targeted at primary care physicians (PCPs) and patients.
Study Design: 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.
Methods: 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.
Results: 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 (P = .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.
Conclusion: The educational intervention did not significantly improve medication compliance or persistence with osteoporosis drugs.
(Am J Manag Care. 2009;15(7):417-424)
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.
Successful medication adherence interventions for other chronic diseases such as hypertension and asthma have been multifactorial and focused on the patient.5 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.10 Another populationbased study11 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.12 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.12
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.13
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”).14-16 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.17
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.18-21 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.7,21 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.3 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.22 Analyses were performed using SAS version 8.02 (SAS Institute, Cary, NC).