Incorporating adherence into health economic modelling of osteoporosis (original) (raw)
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The Journal of Clinical Endocrinology & Metabolism, 2011
Context: Adherence to osteoporosis treatment is low. Although new therapies and behavioral interventions may improve medication adherence, questions are likely to arise regarding their cost-effectiveness. Objective: Our objectives were to develop and validate a model to simulate the clinical outcomes and costs arising from various osteoporosis medication adherence patterns among women initiating bisphosphonate treatment and to estimate the cost-effectiveness of a hypothetical intervention to improve medication adherence. Design: We constructed a computer simulation using estimates of fracture rates, bisphosphonate treatment effects, costs, and utilities for health states drawn from the published literature. Probabilities of transitioning on and off treatment were estimated from administrative claims data. Setting and Patients: Patients were women initiating bisphosphonate therapy from the general community. Intervention: We evaluated a hypothetical behavioral intervention to improve medication adherence. Main Outcome Measures: Changes in 10-yr fracture rates and incremental cost-effectiveness ratios were evaluated. Results: A hypothetical intervention with a one-time cost of 250andreducingbisphosphonatediscontinuationby30250 and reducing bisphosphonate discontinuation by 30% had an incremental cost-effectiveness ratio (ICER) of 250andreducingbisphosphonatediscontinuationby3029,571 per qualityadjusted life year in 65-yr-old women initiating bisphosphonates. Although the ICER depended on patient age, intervention effectiveness, and intervention cost, the ICERs were less than $50,000 per quality-adjusted life year for the majority of intervention cost and effectiveness scenarios evaluated. Results were sensitive to bisphosphonate cost and effectiveness and assumptions about the rate at which intervention and treatment effects decline over time. Conclusions: Our results suggests that behavioral interventions to improve osteoporosis medication adherence will likely have favorable ICERs if their efficacy can be sustained.
Potential Clinical and Economic Impact of Nonadherence with Osteoporosis Medications
Calcified Tissue International, 2010
This study aims to estimate the potential clinical and economic implications of therapeutic adherence to bisphosphonate therapy. A validated Markov microsimulation model was used to estimate the impact of varying adherence to bisphosphonate therapy on outcomes (the number of fractures and the quality-adjusted life-years [QALYs]), health-care costs, and the cost-effectiveness of therapy compared with no treatment. Adherence was divided into persistence and compliance, and multiple scenarios were considered for both concepts. Analyses were performed for women aged 65 years with a bone mineral density T-score of -2.5. Health outcomes and the cost-effectiveness of therapy improved significantly with increasing compliance and/or persistence. In the case of real-world persistence and with a medical possession ratio (MPR; i.e., the number of doses taken divided by the number of doses prescribed) of 100%, the QALY gain and the number of fractures prevented represented only 48 and 42% of the values estimated assuming full persistence, respectively. These proportions fell to 27 and 23% with an MPR value of 80%. The costs per QALY gained, for branded bisphosphonates (and generic alendronate), were estimated at €19,069 (€4,871), €32,278 (€11,985), and €64,052 (€30,181) for MPR values of 100, 80, and 60%, respectively, assuming real-world persistence. These values were €16,997 (€2,215), €24,401 (€6,179), and €51,750 (€20,569), respectively, assuming full persistence. In conclusion, poor compliance and failure to persist with osteoporosis medications results not only in deteriorating health outcomes, but also in a decreased cost-effectiveness of drug therapy. Adherence therefore remains an important challenge for health-care professionals treating osteoporosis.
Value in Health, 2012
Medication nonadherence is common for osteoporosis, but its consequences have not been well described. This study aimed to quantify the clinical and economic impacts of poor adherence and to evaluate the potential cost-effectiveness of improving patient adherence by using hypothetical behavioral interventions. Methods: A previously validated Markov microsimulation model was adapted to the Irish setting to estimate lifetime costs and outcomes (fractures and quality-adjusted life-year [QALY]) for three adherence scenarios: no treatment, real-world adherence, and full adherence over 3 years. The real-world scenario employed adherence and persistence data from the Irish Health Services Executive-Primary Care Reimbursement Services pharmacy claims database. We also investigated the cost-effectiveness of hypothetical behavioral interventions to improve medication adherence (according to their cost and effect on adherence). Results: The number of fractures prevented and the QALY gain obtained at real-world adherence levels represented only 57% and 56% of those expected with full adherence, respectively. The costs per QALY gained of real-world adherence and of full adherence compared with no treatment were estimated at €11,834 and €6,341, respectively. An intervention to improve adherence by 25% would result in an incremental cost-effectiveness ratio of €11,511 per QALY and €54,182 per QALY, compared with real-world adherence, if the intervention cost an additional €50 and €100 per year, respectively. Discussion: Poor adherence with osteoporosis medications results in around a 50% reduction in the potential benefits observed in clinical trials and a doubling of the cost per QALY gained from these medications. Depending on their costs and outcomes, programs to improve adherence have the potential to be an efficient use of resources.
Value in health : the journal of the International Society for Pharmacoeconomics and Outcomes Research
To estimate the impact of medication adherence on the cost-effectiveness of mass-screening by bone densitometry followed by alendronate therapy for women diagnosed with osteoporosis. A validated Markov microsimulation model with a Belgian health-care payer perspective and a lifetime horizon was used to assess the cost per quality-adjusted life year (QALY) gained of the screening/treatment strategy compared with no intervention. Real-world adherence to alendronate therapy and full adherence over 5 years were both investigated. The real-world adherence scenario employed adherence data from published observational studies, and medication adherence was divided into persistence, compliance, and primary adherence. Uncertainty was investigated using one-way and probabilistic sensitivity analyses. At 65 years of age, the costs per QALY gained because of the screening/treatment strategy versus no intervention are euro32,008 and euro16,918 in the real-world adherence and full adherence scenar...
Compliance with osteoporosis drug therapy and risk of fracture
Osteoporosis International, 2007
Introduction Patient compliance with osteoporosis drug therapy is often poor in clinical practice and may be associated with higher risk of fracture. Methods A nested case-control study was undertaken using a US health insurance claims database. The source population included all women aged ≥45 years who began drug therapy for osteoporosis. Cases consisted of those who experienced an osteoporosis-related fracture; they were matched to controls without osteoporosis-related fracture. Compliance with osteoporosis drug treatment was assessed in terms of the number of therapy-days received and medication possession ratio (MPR). Conditional logistic regression was employed to examine the relationship between compliance and fracture risk. Results A total of 453 women with osteoporosis-related fracture were identified and matched to 2,160 controls. Fracture risk was significantly lower for patients with >180 days of therapy [181–360 days: odds ratio (OR) = 0.70, 95% CI = 0.49–0.99; >360 days: OR = 0.65, 95% CI = 0.43–0.99) versus those with ≤30 days. Risk was also lower for patients with MPR ≥90% (OR = 0.70, 95% CI = 0.52–0.93) versus those with MPR trend Conclusion Among women initiating drug therapy for osteoporosis, better compliance is associated with reduced risk of fracture.
Clinical therapeutics, 2008
Background: Nonadherence to treatment is an important determinant of long-term outcomes in women with osteoporosis. Objectives: This study was conducted to investigate the association between adherence and osteoporotic fracture risk and to identify optimal thresholds for good compliance and persistence. A secondary objective was to perform a preliminary evaluation of the cost consequences of adherence. Method: This was a retrospective case-control analysis. Data were derived from the Thales prescription database, which contains information on >1.6 million patients in the primary health care setting in France. Cases were women aged ::::50 years who had an osteoporosis-related fracture in 2006. For each case, 5 matched controls were randomly selected. Both compliance and persistence aspects of treatment adherence were examined. Compliance was estimated based on the medication possession ratio (MPR). Persistence was calculated as the time from the initial filling of a prescription for osteoporosis medication until its discontinuation. Results: The mean (SD) MPR was lower in cases compared with controls (58.8% [34.7%] vs 72.1 % [28.8%], respectively; P < 0.001). Cases were more likely than controls to discontinue osteoporosis treatment (50.0% vs 25.3%; P < 0.001), yielding a significantly lower proportion of patients who were still persistent at 1 year (34.1 % vs 40.9%; P < 0.001). MPR was the best predictor of fracture risk, with an area under the receiver-operating-characteristic curve that was higher than that for persistence (0.59 vs 0.55). The optimal MPR threshold for predicting fracture risk was ::::68.0%. Compared with less-compliant 2410 women, women who achieved this threshold had a 51 % reduction in fracture risk. The difference in annual drug expenditure between women achieving this threshold and those who did not was approximately €300. The optimal threshold for persistence with therapy was at least 6 months. Attaining this threshold was associated with a 28% reduction in fracture risk compared with less-persistent women. Conclusions: In this study, better treatment adherence was associated with a greater reduction in fracture risk. Compliance appeared to predict fracture risk better than did persistence.
Determinants of Oral Medication Compliance in Osteoporosis: The Role of Medication Beliefs
Chapter 6 Conclusions 129 References 141 reduce fracture risk are indicated in those with osteoporosis by bone density criteria, with a prevalent radiographic vertebral fracture, or a recent clinical fracture. Most prescriptions for fracture prevention therapy are medications in the bisphosphonate family. The two most commonly prescribed medications, alendronate and risedronate, are taken once weekly, and a less commonly used bisphosphonate, ibandronate, is taken once monthly. Hormone replacement therapy (HRT) is now used much less frequently for the primary purpose of fracture prevention, since the Women's Health Initiative study in 2002 documented increased risk of myocardial infarction, stroke, breast cancer, and thromboembolic disease associated with its use.(22) Raloxifene is a daily selective estrogen receptor modulator that is also FDA-approved for fracture prevention, but also is not generally used as a first line agent for fracture prevention because of its lack of efficacy with respect to preventing non-spine fractures.(16, 23) As is true with many other chronic diseases such as hypertension(24, 25) and hyperlipidemia,(26, 27) a substantial proportion of those prescribed medication to prevent osteoporosis stop medication prematurely, take it less frequently than prescribed, or take it inappropriately in some other manner. Assessing compliance and persistence with fracture prevention medication using pharmacy claims databases Recently, Kothawala and colleagues have performed a meta-analysis of observational studies that have assessed medication persistence and compliance to oral medication to prevent osteoporotic fracture.(28) The pooled persistence rate from the six studies that assessed persistence using pharmacy claims through 1 year from the index prescription was 50%. Thirteen studies assessed persistence by self-report, and among these the pooled estimated rate of persistence through 1 year of therapy was 80%. This meta-analysis included, however, studies of compliance with hormone replacement therapy and cyclical etidronate, an older bisphosphonate taken daily only for a two week period every 3 months that is no longer used for fracture prevention therapy. A systematic review limited to 14 studies of compliance and persistence with oral bisphosphonate therapy assessed with large pharmacy claims databases estimated that persistence 1 year after an index prescription for a daily alendronate or risedronate ranged from 26% to 56%, and after an index prescription for a weekly 7 and 54% of those prescribed alendronate, respectively, answered "no" to all items of the Morisky-Green scale, considered to be indicative of good compliance. The mean treatment duration was 324 days for raloxifene, and 291 days for alendronate. Participants prescribed raloxifene estimated that they remembered to take a mean 94% of all prescribed tablets, and those prescribed alendronate estimated that they took 90% of all prescribed tablets. A second set of investigators in Spain identified patients from 126 general practices who were being prescribed raloxifene, and randomized the 126 practices to either hand out a leaflet to study participants with additional information regarding raloxifene or to simply follow their usual practice.(52) Compliance was assessed by self-report with the Morisky-Green scale, with high compliance defined as all 4 items of the scale being answered "no". High self-reported compliance was no different between the two groups, being 47.5% and 52.5%, respectively, in the intervention and no intervention groups after 12 months of followup. Quality of life assessed by self-report with the visual analog scale part of the EQ-5D was negatively associated with self-reported compliance in both groups. Carnvale and colleagues surveyed over 2,000 Italian patients who suffered a hip fracture a mean 543 days before the survey date. Twenty one percent of those treated with a fracture prevention medication at the time of or immediately after the fracture self-reported stopping that medication by the time of the survey date. Performance of bone densitometry, younger age, and female sex were associated with fracture prevention medication persistence.(53) Five studies have used surveys to assess both self-reported compliance to and persistence with osteoporosis medication, and reasons for discontinuation. Tosteson and colleagues conducted telephone surveys with 956 women prescribed medication to prevent osteoporotic fracture a mean 7 months after their first prescription. Twenty six percent, 19%, and 19%, respectively, of those prescribed hormone replacement therapy (HRT), raloxifene, or alendronate had discontinued therapy.(54) Among those discontinuing HRT, raloxifene, or alendronate, respectively, 59%, 42% and 49% reported very bothersome side effects. With all three medications, persistence with medication was more likely among those with an accurate recollection of their bone density test results. Similarly, among 275 consecutive post-menopausal women prescribed risedronate (another oral bisphosphonate) 42 of 48 patients who by selfreport discontinued the medication cited one or more side effects as the reason for 8 discontinuation.(55) Two other studies, however, have suggested that side effects account for a lower percentage of premature discontinuation of osteoporosis medications. Of 310 post-menopausal women prescribed medication to prevent osteoporotic fracture following a bone density test, Pickney and colleagues reported that 150 self-reported discontinuation of the medication, and of those less than half cited side effects as the main reason.(56) Twenty six percent (26%) cited cost as the main reason for discontinuation. Side effects were also cited by a smaller proportion of patients as the main reason for discontinuation of osteoporosis medication prescribed to 9,851 post-menopausal women by several osteoporosis specialty centers across Italy.(57) Self-reported discontinuation rates over a mean follow-up time of 14 months (range 11-18 months) varied from just 6.9% for weekly alendronate to 23% for hormone replacement therapy, to 28.7% for intramuscular clodronate (administered once every 1-2 weeks). Persistence was positively associated with prior vertebral fractures, early menopause, and having had a bone density test showing low bone mass. Self-reported reasons for discontinuation were side effects in 24%, lack of motivation in 21%, safety concerns in 13%, and cost in 10%. Uniquely among these studies, Cline and colleagues assessed the association of self-reported use of hormone replacement therapy or oral bisphosphonate medication within the month prior to the survey date with latent variables postulated to be associated with medication use by the Health Belief Model, specifically perceived susceptibility to osteoporosis, perceived severity (health consequences) of osteoporosis, perceived effectiveness of medications to treat osteoporosis, and perceived barriers to use of medications to treat osteoporosis.(58) Notably, the target condition was framed as "osteoporosis" and not specifically as osteoporotic fractures. This study also assessed type of health insurance coverage and "cues to action" (events or health history that indicate risk of osteoporosis or related fractures) such as having had a diagnosis of osteoporosis or osteopenia, family history of fracture, and a personal history of fracture. Having had a bone density test and having Medicare HMO health care coverage were both strongly associated with self-reported recent use of an anti-resorptive agent. Perceived susceptibility to osteoporosis, perceived effectiveness of drug therapy, and perceived lack of barriers to medication use were all modestly associated with self-reported recent use of anti-resorptive drug therapy. 10 Consequences of non-compliance with fracture prevention medications Several studies now have documented that among those at high risk of fracture, suboptimal compliance with prescribed fracture prevention medication is associated with a higher risk of fracture, (34, 59-65) and higher net health care utilization and costs.(60, 62, 64) The precise nature of the association between noncompliance and fracture risk, however, remains unclear. Siris and colleagues, however, could find no fracture reduction benefit for those with an MPR less than 50%, and then an exponentially greater fracture reduction benefit as MPR increased from 50% to 100%.(63) A major difficulty with these studies based entirely on administrative pharmacy and health care claims, however, is that is not clear that those with low compliance are in fact as comparable risk of fracture as those with higher compliance. The study of Rabenda and colleagues from Belgium is helpful in that pharmacologic fracture prevention therapy in Belgium is restricted to those with osteoporosis by bone density criteria (femoral neck T-score ≤-2.5) and/or vertebral fractures, ensuring that all of those studied are indeed at high risk of fracture. In this study, there was a linear 33% reduction in hip fracture incidence as compliance improved from an MPR of 0% to 100%.(65) Patient-Provider Relationship Quality Medication Concerns Med Use Self-Efficacy Perceived Medication Cost Burden 109 Results: The patient-provider relationship quality was modestly but significantly associated with self-reported non-persistence, such that with all other predictors and covariates at their mean value, a one standard deviation increase in the patientprovider relationship quality would reduce the probability of non-persistence from 34.2% to 28.5%. Half of this effect appears to be mediated by perceived need for fracture prevention medication, with lesser proportions mediated by medication concerns, and medication use self-efficacy. Conclusion: Providers who have a better relationship with their patients at high risk of fracture may be better able to influence those patients' perceived need for...