Pharmacoeconomic aspects of poor adherence: can better adherence reduce healthcare costs?

Abstract

Background:

Poor adherence to medical treatment is one of the main reasons why patients do not achieve the full benefits of their therapy. It also has a substantial financial weight in terms of money wasted for unused medication and increased healthcare costs including hospitalization due to clinical complications.

Objective:

To provide an overview and examples of the financial and economic consequences of poor adherence to treatment, techniques and devices for monitoring adherence and interventions for improvement of treatment adherence.

Results:

New electronic devices with monitoring features may help to objectively monitor patients’ adherence to a treatment regimen that can help a healthcare professional determine how to intervene to improve adherence and subsequent clinical outcome. Interventions that aim to enhance adherence may confer cost-effectiveness benefits in some indications and settings. The nature of the intervention(s) used depends on a range of factors, including patient preference, therapy area and cost of the intervention. However, there is a pressing need for rigorous trials, as current studies often have major flaws in the economic methodology, especially in terms of incremental analysis and sensitivity analysis.

Limitations:

This review has focused on a limited number of therapeutic areas as coverage of a more extensive range of diseases may be beyond the scope of such a summary. Nevertheless, the examples are representative of the challenges encountered in many other diseases.

Conclusions:

The clinical and economic consequences of non-adherence and interventions to improve compliance reflect the nature and severity of non-adherence, as well as the pathophysiology and severity of the disease. Interventions that aim to enhance adherence may confer cost-effectiveness benefits in some indications and settings, and good adherence can help payers and providers contain costs by extracting maximum value from their investment in therapies.     

Implications of Real-world Adherence on Cost-effectiveness Analysis in Multiple Sclerosis

Abstract

Objectives:

Adherence to medication is essential for optimal outcomes, especially for chronic diseases such as multiple sclerosis (MS). Studies in MS indicate that lower adherence is associated with an increased risk of relapse, hospitalization or emergency room (ER) visits, and higher medical costs. A previous investigation assessed the cost per relapse avoided for patients with MS receiving first-line disease modifying therapies (DMTs); however, the model assumed 100% adherence.

Methods:

Because real-world utilization patterns influence the actual effectiveness of medications, this analysis assessed the impact of real-world adherence from a US commercial payer perspective, using updated costs.

Results:

As was seen in the original study, in this revised model, fingolimod was associated with the lowest cost per relapse avoided ($90,566), followed by SC IFN β-1b (Extavia: $127,024), SC IFN β-1b (Betaseron: $137,492), SC IFN β-1a ($144,016), glatiramer acetate ($160,314), and IM IFN β-1a ($312,629). The model inputs that had the greatest impact on the results were adherence-adjusted relative relapse rate reduction (RRR) of fingolimod, the wholesale acquisition costs of fingolimod, and the average number of relapses in untreated patients with MS.

Limitations:

The estimates of DMT adherence are from a single claims database study of a large national pharmacy benefit manager that only measured adherence, not actual relapses, and the model does not incorporate manufacturer discounts and rebates, which are not publicly available.

Conclusion:

These results suggest that economic analyses of MS therapies should incorporate real-world adherence rates where available, rather than relying exclusively on trial-based efficacy estimates when considering the economic value of treatment alternatives, and that highly efficacious therapies with low adherence may yield real-world efficacy that is substantially lower than that observed in closely monitored clinical trials.     

Cost effectiveness of paliperidone palmitate versus risperidone long-acting injectable and olanzapine pamoate for the treatment of patients with schizophrenia in Sweden

Abstract

Objective:

To model the cost effectiveness of paliperidone palmitate (paliperidone long-acting injectable; PLAI), a new once-monthly long-acting antipsychotic therapy, compared with risperidone long-acting injectable (RLAI) and olanzapine pamoate (OLAI), in multi-episode patients (two or more relapses) with schizophrenia in Sweden.

Methods:

A Markov decision analytic model was developed to simulate the history of a cohort of multi-episode patients transitioning through different health states on a monthly basis over a 5-year time horizon from the perspective of the Swedish healthcare system. Therapeutic strategies consisted of starting treatment with RLAI (mean dose 37.5?mg every 2 weeks), PLAI (mean dose 75?mg equivalent (eq.) every month) or OLAI (150?mg every 2 weeks or 300?mg every 4 weeks). Probability of relapse, level of adherence, side-effects (extrapyramidal symptoms, tardive dyskinesia, weight gain and diabetes) and treatment discontinuation (switch) were derived from long-term observational data when feasible. Incremental cost-effectiveness outcomes, discounted at 3% annually, included cost per quality-adjusted life-year (QALY) and cost per relapse avoided (expressed in 2009 Swedish Krona SEK).

Results:

Relative to RLAI and OLAI, PLAI is economically dominant: more effective (additional QALYs, less relapses) and less costly treatment option over a 5-year time horizon. The results were robust when tested in sensitivity analysis.

Limitations:

The impact of once-monthly treatment on adherence levels is not yet known, and not all variables that could impact on real-world outcomes and costs were included in this model.

Conclusion:

PLAI was cost saving from a Swedish payer perspective compared with RLAI and OLAI in the long-term treatment of multi-episode (two or more relapses) schizophrenia patients.     

Mail-order pharmacy use and medication adherence among Medicare Part D beneficiaries with diabetes

Abstract

Objective:

To examine medication adherence among Medicare Part D beneficiaries initiating oral anti-diabetic medications and explore whether there is any association of using mail-order pharmacy (vs. retail pharmacy) with better adherence in this patient population.

Research design and methods:

Using administrative pharmacy claims data, we conducted a retrospective cohort study on Medicare Part D beneficiaries who newly initiated oral anti-diabetic treatment between July 1, 2008 and December 31, 2008. Mail-order pharmacy users were matched to retail pharmacy users via propensity scoring, controlling for patient demographic and clinical characteristics. Adherence with oral anti-diabetic medications during the benefit year of 2009 was assessed using the proportion of days covered (PDC). Comparison of medication adherence between the mail-order pharmacy group and retail pharmacy group was conducted in the propensity matched sample using the paired t-tests and McNemar’s tests.

Results:

A total of 22,546 patients who initiated oral anti-diabetic medications were identified. The average PDC was 0.60 and only 41.6% of the study population attained good adherence (defined as PDC?≥?0.8) with oral anti-diabetic medications during calendar year 2009. The matched sample included 1361 patients in each of the mail-order and retail pharmacy cohorts. Compared with the retail pharmacy group, mail-order pharmacy users demonstrated a significantly higher PDC (0.68 vs. 0.61; P?<?0.001) throughout the benefit year. More patients in the mail-order pharmacy group (49.7%) attained good adherence with their oral anti-diabetic medications compared to 42.8% in the retail pharmacy group (P?<?0.001).

Limitations:

The study was subject to limitations inherent in retrospective claims database analysis.

Conclusions:

Adherence with oral anti-diabetic medications among Medicare Part D beneficiaries is suboptimal. Patients using mail-order pharmacy had better adherence to oral anti-diabetic medications than those who used retail pharmacies. However, the causal relationship between mail-order pharmacy use and adherence should be further examined in a randomized study setting.     

Real-world treatment patterns and healthcare costs among biologic-naive patients initiating apremilast or biologics for the treatment of psoriasis

Objective: This study compared real-world treatment patterns and healthcare costs among biologic-naive psoriasis patients initiating apremilast or biologics.

Methods: A retrospective cohort study was conducted using the Optum Clinformatics? claims database. Patients with psoriasis were selected if they had initiated apremilast or biologics between January 1, 2014, and December 31, 2015; had 12?months of pre-index and post-index continuous enrollment in the database; and were biologic-naive. The index date was defined as the date of the first claim for apremilast or biologic, and occurred between January 1, 2014, and December 31, 2015. Treatment persistence was defined as continuous treatment without a?>?60-day gap in therapy (discontinuation) or a switch to a different psoriasis treatment during the 12-month post-index period. Adherence was defined as a medication possession ratio (MPR) of ≥ 80% while persistent on the index treatment. Persistence-based MPR was defined as the number of days with the medication on hand measured during the patients’ period of treatment persistence divided by the duration of the period of treatment persistence. Because patients were not randomized, apremilast patients were propensity score matched up to 1:2 to biologic patients to adjust for possible selection bias. Treatment persistence/adherence and all-cause healthcare costs were evaluated. Cost differences were determined using Wilcoxon rank-sum tests.

Results: In all, 343 biologic-naive patients initiating apremilast were matched to 680 biologic-naive patients initiating biologics. After matching, patient characteristics were similar between cohorts. Twelve-month treatment persistence was similar for biologic-naive patients initiating apremilast vs biologics (32.1% vs 33.2%; p?=?0.7079). While persistent on therapy up to 12?months, per-patient per-month (PPPM) total healthcare costs were significantly lower among biologic-naive cohorts initiating apremilast vs biologics ($2,214 vs $5,184; p?p?p?p?Limitations: Data were limited to individuals with United Healthcare commercial and Medicare Advantage insurance plans, and may not be generalizable to psoriasis patients with other insurance or without health insurance coverage.

Conclusion: Biologic-naive patients with similar patient characteristics receiving apremilast vs biologics had significantly lower PPPM costs, even when they switched to biologics during the 12-month post-index period. These results may be useful to payers and providers seeking to optimize psoriasis care while reducing healthcare costs.     

Comparison of utilization,cost, adherence,and hypoglycemia in patients with type 2 diabetes initiating rapid-acting insulin analog with prefilled pen versus vial/syringe

Abstract

Background:

Studies examining outcomes of different insulin delivery systems are limited. The objective of this study was to compare healthcare utilization, costs, adherence, and hypoglycemia rates in patients with type 2 diabetes mellitus (T2DM) initiating rapid-acting insulin analog (RAIA) using prefilled pen versus vial/syringe.

Methods:

A retrospective analysis was conducted using a US claims database (1/1/2007 to 12/31/2008). Inclusion criteria were: ≥18 years old, with T2DM, ≥12 months of continuous eligibility, and new to RAIA. Difference-in-difference analyses after propensity score matching were conducted to compare changes in outcomes from 6 months prior to and 6 months after initiating RAIA with a prefilled pen versus vial/syringe (Wilcoxon rank-sum test for costs and t-test for other outcomes). Categories of utilization and costs (2009 USD) included total and diabetes-related inpatient, outpatient, and emergency room. Adherence was measured by proportion of days covered (PDC). Hypoglycemia was identified using ICD-9-CM codes.

Results:

Baseline characteristics were similar between the prefilled pen (n?=?239) and vial/syringe (n?=?590) cohorts after matching. Adherence to RAIA was greater in the prefilled pen cohort than the vial/syringe cohort (PDC: 54.6 vs. 45.2%, p?<?0.001). While the increase in diabetes-related pharmacy costs from before to after initiating RAIA was greater in the prefilled pen cohort than the vial/syringe cohort (+$900 vs. +$607, p?<?0.001), the prefilled pen cohort was associated with greater reductions in the total diabetes-related costs (–$235 vs. +$61, p?=?0.006) and the utilization of oral anti-hyperglycemic agents (–1.3 vs. –0.7, p?=?0.016). There were no significant differences in other outcomes.

Limitations:

Claims databases do not provide optimal measures for adherence or T2DM severity, and only capture hypoglycemia events requiring clinical intervention.

Conclusion:

Initiating RAIA with a prefilled pen was associated with better adherence and greater reduction in total diabetes-related costs than a vial/syringe. There was no significant difference in total healthcare costs.     

Inflammatory bowel disease: healthcare costs for patients who are adherent or non-adherent with infliximab therapy

Objective:

Healthcare costs of inflammatory bowel disease are substantial. This study examined the effect of adherence versus non-adherence on healthcare costs in patients with inflammatory bowel disease.

Methods:

Adults who started infliximab treatment between 2006 and 2009 and had a diagnosis of inflammatory bowel disease were identified from MarketScan Databases. Medication adherence was defined as an infliximab medication possession ratio of 80% or greater in the first year. Mean treatment effects (adherence versus non-adherence) on costs in adherent patients were estimated with propensity-weighted generalized linear models.

Results:

A total of 1646 patients were identified. Significant variables in the model used to develop propensity weights were age, year of infliximab initiation, having Medicare coverage, presence of supplementary diagnoses, office as the place of service for infliximab initiation, prior aminosalicylate use, prior outpatient costs, number of prior outpatient visits, and number of prior colonoscopies. Mean total costs in adherent (n?=?674) and propensity-weighted non-adherent (n?=?972) patients were $41,713 versus $47,411 overall (p?p?p?p?p?p?=?0.460).

Limitations:

Costs associated with infliximab administration (infusions, adverse events) were captured in healthcare costs (inpatient, outpatient, and emergency room), not in infliximab costs. The influence of adherence on indirect costs (e.g., time lost from work) could not be determined. Reasons for non-adherence were not available in the database.

Conclusions:

In patients who were adherent to infliximab treatment (a medication possession ratio of 80% or greater in the first year), adherence versus non-adherence was associated with lower total healthcare costs, supporting the overall value of infliximab adherence in patients with inflammatory bowel disease.     

Continuous prophylaxis with recombinant factor IX Fc fusion protein and conventional recombinant factor IX products: comparisons of efficacy and weekly factor consumption

Background: Continuous prophylaxis for patients with hemophilia B requires frequent injections that are burdensome and that may lead to suboptimal adherence and outcomes. Hence, therapies requiring less-frequent injections are needed. In the absence of head-to-head comparisons, this study compared the first extended-half-life-recombinant factor IX (rFIX) product—recombinant factor IX Fc fusion protein (rFIXFc)—with conventional rFIX products based on annualized bleed rates (ABRs) and factor consumption reported in studies of continuous prophylaxis.

Methods: This study compared ABRs and weekly factor consumption rates in clinical studies of continuous prophylaxis treatment with rFIXFc and conventional rFIX products (identified by systematic literature review) in previously-treated adolescents and adults with moderate-to-severe hemophilia B. Meta-analysis was used to pool ABRs reported for conventional rFIX products for comparison. Comparisons of weekly factor consumption were based on the mean, reported or estimated from the mean dose per injection.

Results: Five conventional rFIX studies (injections 1 to >3 times/week) met the criteria for comparison with once-weekly rFIXFc reported by the B-LONG study. The pooled mean ABR for conventional rFIX was slightly higher than but comparable to rFIXFc (difference=0.71; p?=?0.210). Weekly factor consumption was significantly lower with rFIXFc than in conventional rFIX studies (difference in means?=?42.8–74.5?IU/kg/week [93–161%], p?Conclusion: Comparisons of clinical study results suggest weekly injections with rFIXFc result in similar bleeding rates and significantly lower weekly factor consumption compared with more-frequently-injected conventional rFIX products. The real-world effectiveness of rFIXFc may be higher based on results from a model of the impact of simulated differences in adherence.     

Adherence to iron chelation therapy and associated healthcare resource utilization and costs in Medicaid patients with sickle cell disease and thalassemia

Background:

Sub-optimal patient adherence to iron chelation therapy (ICT) may impact patient outcomes and increase cost of care. This study evaluated the economic burden of ICT non-adherence in patients with sickle cell disease (SCD) or thalassemia.

Methods:

Patients with SCD or thalassemia were identified from six state Medicaid programs (1997–2013). Adherence was estimated using the medication possession ratio (MPR) of ≥0.80. All-cause and disease-specific resource utilization per-patient-per-month (PPPM) was assessed and compared between adherent and non-adherent patients using adjusted incidence rate ratios (aIRR). All-cause and disease-specific healthcare costs were computed using mean cost PPPM. Regression models adjusting for baseline characteristics were used to compare adherent and non-adherent patients.

Results:

A total of 728 eligible patients treated with ICT in the SCD cohort, 461 (63%) adherent, and 218 in the thalassemia cohort, 137 (63%) adherent, were included in this study. In SCD patients, the adjusted rate of all-cause outpatient visits PPPM was higher in adherent patients vs non-adherent patients (aIRR [95% CI]: 1.05 [1.01–1.08], p?<?0.0001). Conversely, adherent patients incurred fewer all-cause inpatients visits (0.87 [0.81–0.94], p?<?0.001) and ER visits (0.86 [0.78–0.93], p?<?0.001). Similar trends were observed in SCD-related resource utilization rates and in thalassemia patients. Total all-cause costs were similar between adherent and non-adherent patients, but inpatient costs (adjusted cost difference?=??$1530 PPPM, p?=?0.0360) were lower in adherent patients.

Conclusion:

Patients adherent to ICT had less acute care need and lower inpatient costs than non-adherent patients, although they had more outpatient visits. Improved adherence may be linked to better disease monitoring and has the potential to avoid important downstream costs associated with acute care visits and reduce the financial burden on health programs and managed care plans treating SCD and thalassemia patients.