Association of out-of-pocket costs on adherence to common neurologic medications.

OBJECTIVE: To determine the association between out-of-pocket costs and medication adherence in 3 common neurologic diseases. METHODS: Utilizing privately insured claims from 2001 to 2016, we identified patients with incident neuropathy, dementia, or Parkinson disease (PD). We selected patients who were prescribed medications with similar efficacy and tolerability, but differential out-of-pocket costs (neuropathy with gabapentinoids or mixed serotonin/norepinephrine reuptake inhibitors [SNRIs], dementia with cholinesterase inhibitors, PD with dopamine agonists). Medication adherence was defined as the number of days supplied in the first 6 months. Instrumental variable analysis was used to estimate the association of out-of-pocket costs and other patient factors on medication adherence. RESULTS: We identified 52,249 patients with neuropathy on gabapentinoids, 5,246 patients with neuropathy on SNRIs, 19,820 patients with dementia on cholinesterase inhibitors, and 3,130 patients with PD on dopamine agonists. Increasing out-of-pocket costs by $50 was associated with significantly lower medication adherence for patients with neuropathy on gabapentinoids (adjusted incidence rate ratio [IRR] 0.91, 0.89-0.93) and dementia (adjusted IRR 0.88, 0.86-0.91). Increased out-of-pocket costs for patients with neuropathy on SNRIs (adjusted IRR 0.97, 0.88-1.08) and patients with PD (adjusted IRR 0.90, 0.81-1.00) were not significantly associated with medication adherence. Minority populations had lower adherence with gabapentinoids and cholinesterase inhibitors compared to white patients. CONCLUSIONS: Higher out-of-pocket costs were associated with lower medication adherence in 3 common neurologic conditions. When prescribing medications, physicians should consider these costs in order to increase adherence, especially as out-of-pocket costs continue to rise. Racial/ethnic disparities were also observed; therefore, minority populations should receive additional focus in future intervention efforts to improve adherence.

Drug Product Life-Cycle Management as Anticompetitive Behavior: The Case of Memantine.

A "product hop" involves the substitution of a new formulation of a prescription drug by a pharmaceutical manufacturer for an old version to forestall generic competition. In 2015, for example, Forest Laboratories, the brand-name drug manufacturer of memantine, an Alzheimer's disease treatment, introduced an extended-release version and tried to restrict patient access to the previous version. Product hops can lead to useful incremental innovation but can also have major public health implications by disrupting patients on stable treatment regimens and increasing costs for patients and payers. This commentary reviews alleged anticompetitive product hopping in the case of memantine, which involved proposed conduct that would have left Alzheimer's disease patients with no effective choice but to transition to memantine XR. Policy solutions that can limit anticompetitive product hops include raising the bar for obtaining patents on new drug product formulations and changing automatic generic substitution laws. DISCLOSURES: No outside funding supported this research. To support his work at PORTAL in the summer of 2015, Capati was the recipient of the University of New Hampshire School of Law Rudman Center Public Service Fellowship. Kesselheim's research was supported by Greenwall Faculty Scholars program, the Laura and John Arnold Foundation, and the Harvard Program in Therapeutic Science. In 2013, Kesselheim served as an expert on behalf of a class of individual plaintiffs against Warner Chilcott regarding potential antitrust violations Kesselheim was responsible for concept and design of this commentary. Capati took the lead in data collection and analysis, along with Kesselheim. Capati wrote the manuscript, which was revised by primarily by Kesselheim, along with Capati.

Memantine for treatment of moderate or severe Alzheimer's disease patients in urban China: clinical and economic outcomes from a health economic model.

OBJECTIVE: To estimate the clinical and economic benefits of memantine treatment initiated in moderate Alzheimer's disease (AD) in China, compared with initiation in severe AD only. METHODS: A Markov model with a 5-year time horizon simulated moderate patients' progression through health states. Two groups were compared: patients receiving memantine from the moderate stage (i.e., at model entry), continuing treatment when reaching the severe stage; patients initiating memantine only when they developed severe disease. RESULTS: After 5 years, fewer patients receiving memantine from the moderate stage were severe (49%), dependent (59%) or aggressive (47%) compared with moderate patients who initiated treatment from severe stage only (58, 67 and 55%, respectively). Total cost of care was lower for treatment from moderate stage (67 billion RMB) when compared with treatment from severe stage (73 billion RMB). CONCLUSIONS: In China, AD treatment with memantine from the moderate stage could result in substantial cost savings.

Consumption trends for specific drugs used to treat dementia in the region of Madrid (Spain) from 2002 to 2012.

INTRODUCTION: Analysing drug consumption in large population groups lets us observe consumption trends and compare them between different settings. OBJECTIVE: to analyse the time trends for consumption and costs of specific drugs used to treat dementia in the region of Madrid (Spain) and compare trends by sex and age cohort. METHODS: Descriptive study of cholinesterase inhibitors (N06DA) and memantine (N06DX01) dispensed in Madrid between 2002 and 2012 and covered by the Spain's national health system. Consumption was calculated by analysing changes in DDD (defined daily doses) to find total and yearly increases. The cost was estimated based on DDD price. To compare consumption rates by age and sex, we calculated DDD per 100 inhabitants/day. RESULTS: Between 2002 and 2012, consumption of drugs used to treat dementia increased sixfold. During this period, cholinesterase inhibitors accounted for 76.70% of the drugs consumed and memantine, 23.30%. The estimated cost rose by a by a factor of 5.7 over 11 years (or by a factor of 4 taking into account the use of generic drugs). In 2012, 2.42% of the patients aged 65 or over consumed cholinesterase inhibitors (women 2.82%, men 1.83%) and 0.90% consumed memantine (women 1.10%, men 0.61%). Consumption increased in age cohorts up to 86 to 90 (5.84% for cholinesterase inhibitors and 2.33% for memantine) and declined thereafter. CONCLUSIONS: Consumption of cholinesterase inhibitors and memantine gradually increased, but consumption in 2012 did not reach levels equivalent to dementia prevalence figures. Pharmaceutical expenditure restraint measures may temporarily slow the cost increase temporarily but if the same trend of consumption persists, costs will rise.

Cost-effectiveness of memantine in moderate and severe Alzheimer's disease in Norway.

BACKGROUND: The cost-effectiveness of memantine for the treatment of moderate and severe Alzheimer's disease has been assessed in several European countries. Objective of the study was to assess it in Norwegian settings. METHODS: This cost-utility analysis used a Markov modelling approach to simulate the evolution of patients until their need for full-time care (FTC) over a 5-year period. FTC was defined as a patient becoming either dependent or institutionalised. Transition probabilities were estimated using a newly developed predictive equation of time to FTC. Health resource use and utilities were obtained from the Scandinavian Study of Cost and Quality of Life in Alzheimer's Disease study, and mortality was obtained from the Oslo study. Memantine efficacy was based on a meta-analysis of six large trials. The model compared memantine with its alternative in this population, that is no pharmacological treatment or background therapy with acetylcholinesterase inhibitors. The model underwent extensive sensitivity analyses. RESULTS: In Norway, memantine was found to delay the need for FTC by 4.4 weeks compared with standard care and was associated with increased quality-adjusted life years. Memantine was the dominant strategy with cost savings of €3739 (30 041 NOK) per patient. The probability of being the dominant strategy was 98.8%. This result was confirmed across multiple sensitivity analyses. CONCLUSIONS: The model suggests that memantine prolongs time to FTC for no additional cost to the healthcare system and society. It can be regarded as a cost-effective choice in the management of moderate and severe Alzheimer's disease.

Treatment of Alzheimer disease.

Alzheimer disease is the most common form of dementia, affecting nearly one-half [corrected] of Americans older than 85 years. It is characterized by progressive memory loss and cognitive decline. Amyloid plaque accumulation, neurofibrillary tau tangles, and depletion of acetylcholine are among the pathologic manifestations of Alzheimer disease. Although there are no proven modalities for preventing Alzheimer disease, hypertension treatment, omega-3 fatty acid supplementation, physical activity, and cognitive engagement demonstrate modest potential. Acetylcholinesterase inhibitors are first-line medications for the treatment of Alzheimer disease, and are associated with mild improvements in cognitive function, behavior, and activities of daily living; however, the clinical relevance of these effects is unclear. The most common adverse effects of acetylcholinesterase inhibitors are nausea, vomiting, diarrhea, dizziness, confusion, and cardiac arrhythmias. Short-term use of the N-methyl-D-aspartate receptor antagonist memantine can modestly improve measures of cognition, behavior, and activities of daily living in patients with moderate to severe Alzheimer disease. Memantine can also be used in combination with acetylcholinesterase inhibitors. Memantine is generally well tolerated, but whether its benefits produce clinically meaningful improvement is controversial. Although N-methyl-D-aspartate receptor antagonists and acetylcholinesterase inhibitors can slow the progression of Alzheimer disease, no pharmacologic agents can reverse the progression. Atypical antipsychotics can improve some behavioral symptoms, but have been associated with increased mortality rates in older patients with dementia. There is conflicting evidence about the benefit of selegiline, testosterone, and ginkgo for the treatment of Alzheimer disease. There is no evidence supporting the beneficial effects of vitamin E, estrogen, or nonsteroidal anti-inflammatory drug therapy.

Cost-effectiveness analysis of a new 8% capsaicin patch compared to existing therapies for postherpetic neuralgia.

OBJECTIVE: The purpose of this study was to compare the cost effectiveness of a new 8% capsaicin patch, compared to the current treatments for postherpetic neuralgia (PHN), including tricyclic antidepressants (TCAs), topical lidocaine patches, duloxetine, gabapentin, and pregabalin. METHODS: A 1-year Markov model was constructed for PHN with monthly cycles, including dose titration and management of adverse events. The perspective of the analysis was from a payer perspective, managed-care organization. Clinical trials were used to determine the proportion of patients achieving at least a 30% improvement in PHN pain, the efficacy parameter. The outcome was cost per quality-adjusted life-year (QALY); second-order probabilistic sensitivity analyses were conducted. RESULTS: The effectiveness results indicated that 8% capsaicin patch and topical lidocaine patch were significantly more effective than the oral PHN products. TCAs were least costly and significantly less costly than duloxetine, pregabalin, topical lidocaine patch, 8% capsaicin patch, but not gabapentin. The incremental cost-effectiveness ratio for the 8% capsaicin patch overlapped with the topical lidocaine patch and was within the accepted threshold of cost per QALY gained compared to TCAs, duloxetine, gabapentin, and pregablin. The frequency of the 8% capsaicin patch retreatment assumption significantly impacts its cost-effectiveness results. There are several limitations to this analysis. Since no head-to-head studies were identified, this model used inputs from multiple clinical trials. Also, a last observation carried forward process was assumed to have continued for the duration of the model. Additionally, the trials with duloxetine may have over-predicted its efficacy in PHN. Although a 30% improvement in pain is often an endpoint in clinical trials, some patients may require greater or less improvement in pain to be considered a clinical success. CONCLUSIONS: The effectiveness results demonstrated that 8% capsaicin and topical lidocaine patches had significantly higher effectiveness rates than the oral agents used to treat PHN. In addition, this cost-effectiveness analysis found that the 8% capsaicin patch was similar to topical lidocaine patch and within an accepted cost per QALY gained threshold compared to the oral products.

Variability in the prescription of cholinesterase inhibitors and memantine.

BACKGROUND/AIM: To estimate the prevalence of Alzheimer's disease (AD) treatment in Aragon (Spain), analyzing differences according to age, gender and health area. METHODS: Retrospective study on AD treatment prevalence of cholinesterase inhibitors and memantine during 2005, using pharmaco-epidemiological data from prescription refunds transferred monthly from pharmacies to the Health Care Service. RESULTS: Differences between health areas were considerable, with adjusted prescription rates between 121.6 and 248.6/100,000 individuals. Treatment rates for women doubled those of men in each health area. Variability was greater among men than women. Drug prescription distribution was also different between health areas. CONCLUSION: Considerable variability in AD treatment has been detected. More consensus is needed to reduce variability in order to improve the quality of the pharmacotherapy for AD and assure equal treatment opportunities for every patient.

Cost-effectiveness analysis of a lidocaine 5% medicated plaster compared with gabapentin and pregabalin for treating postherpetic neuralgia: a german perspective.

OBJECTIVE: This study set out to assess the cost effectiveness of using a 5% lidocaine (lignocaine) medicated plaster for the treatment of postherpetic neuralgia (PHN) compared with gabapentin, pregabalin 300 mg/day or 600 mg/day in German primary care. The analysis took the perspective of the Statutory Health Insurance scheme (GKV). METHODS: A Markov model was used to calculate the costs (2007) and benefits of the lidocaine plaster, gabapentin 1800 mg/day and pregabalin 300 or 600 mg/day over a 6-month time horizon in elderly patients with PHN who experienced insufficient pain relief with standard analgesics and could not tolerate or had contraindications to tricyclic antidepressants. The model calculated the cost per quality-adjusted life-year (QALY) gained and the cost per additional month without symptoms or intolerable adverse effects. The majority of transition probabilities were obtained from randomized controlled trials identified from a systematic literature review. Further model inputs, including resource use, concomitant medication and long-term efficacy/adherence data, were obtained from a Delphi panel. Utility values were taken from a previous study and age adjusted. Cost data were obtained from official price tariffs. Mortality, indirect costs and costs associated with inpatient treatment were not considered in the present analysis due to the perspective and time horizon employed. RESULTS: Over the 6-month period modelled, the mean total therapy cost per patient treated with the lidocaine plaster was euro911, compared with euro728 for gabapentin, euro875 for pregabalin 300 mg/day and euro977 for pregabalin 600 mg/day. Treatment with the lidocaine plaster was related to greater numbers of QALYs and more months without symptoms or intolerable adverse effects (mean 0.300 QALYs and 4.06 months per patient) than with gabapentin (mean 0.247 QALYs and 2.72 months), pregabalin 300 mg/day (mean 0.253 QALYs and 3.02 months) or pregabalin 600 mg/day (mean 0.256 QALYs and 3.22 months). The lidocaine plaster cost euro3453/QALY gained and euro137 per additional month without adverse effects or symptoms relative to gabapentin and euro766/QALY and euro35 per month without adverse effects or symptoms relative to pregabalin 300 mg/day. The lidocaine plaster dominated pregabalin 600 mg/day, being less costly and more effective. Probabilistic sensitivity analysis indicated that there is a 99.36% chance that the lidocaine plaster is the most clinically effective treatment considered in the analysis and a 99.09% chance that the lidocaine plaster is the most cost-effective treatment of the four therapies considered in the analysis if the GKV is willing to pay at least euro20 000/QALY gained. Extensive deterministic sensitivity analyses demonstrated that the findings are robust. CONCLUSIONS: The 5% lidocaine-medicated plaster is a cost-effective treatment option for the management of PHN in Germany compared with gabapentin and both 300 and 600 mg/day of pregabalin.

[Use of specific drugs for Alzheimer's disease]. / Utilización de fármacos específicos para la enfermedad de Alzheimer.

OBJECTIVE: To evaluate the consumption evolution and financial impact of specific treatments for Alzheimer's disease (AD) in Aragon (Spain), analyzing consumption patterns and trends, and to estimate the proportion of AD patients treated with these drugs. METHODS: Descriptive study of outpatient utilization of cholinesterase inhibitors and memantine (1996-2004), obtained from the drug packages dispensed by community pharmacists through prescriptions charged to the National Health Service. According to the defined daily doses (DDD) and expenditure data available, data were expressed in DDD per 1,000 inhabitants per day (DHD), DDD per 1,000 inhabitants older than 64 (DHD65), first-last year increase (%), drug consumption pattern, annual cost per inhabitant and daily treatment cost (DTC). To estimate the proportion of treated patients we compared the DHD65 data with the estimated AD prevalence. RESULTS: Overall consumption of these drugs has increased from 0.026 DHD (1996) to 3.235 DHD (2004). Donepezil remains as the most prescribed, though it is proportionally decreasing as a result of the quick introduction of newer alternatives. Overall cost of the DHD dispensed in 2004 reached nearly 6 million euros. DTC decreased about 30% over the study period, but the total cost increased ninety-fold (sixty-fold when non-variable euros from 2004 were considered). According to our estimates, 34% of people with AD were receiving specific treatment. CONCLUSIONS: There is a significant increase in the consumption and economical burden of these drugs, whose cost-effectiveness has been questioned in some studies. More studies including specific patient data are needed in order to identify individual characteristics and evaluate treatment appropriateness.

Efficacy and safety of memantine in moderate-to-severe Alzheimer disease: the evidence to date.

Memantine, a moderate-affinity, uncompetitive N-methyl-D-aspartate receptor antagonist, is currently the only agent approved for moderately severe to severe Alzheimer disease (AD) in Europe and for moderate-to-severe Alzheimer disease in the United States. In clinical trials, memantine has consistently demonstrated a reduced rate of deterioration on global, cognitive, functional, and behavioral measures, across a range of outcome measures compared with usual care. Notably, improvements versus placebo were seen in individual activities of daily living and behavior, particularly agitation. Efficacy was demonstrated in patients with newly diagnosed Alzheimer disease, patients previously or currently receiving acetylcholinesterase inhibitors, and both institutionalized and community-dwelling Alzheimer disease patients. Memantine has a tolerability profile similar to placebo. This review presents the results of key clinical trials, and includes clinically relevant analyses, such as numbers-needed-to-treat and effect sizes. Increased dependency and institutionalization are significant cost drivers in Alzheimer disease. Memantine is able to reduce dependency, caregiver time required, and mean monthly caregiver and societal costs. Recent studies of the relationship between Alzheimer disease progression, caregiver burden, and healthcare costs emphasize the need for treatments such as memantine that can slow the rate of decline in Alzheimer disease.

Cost effectiveness of memantine in Alzheimer's disease: an analysis based on a probabilistic Markov model from a UK perspective.

BACKGROUND: Clinical trials with memantine, an uncompetitive moderate-affinity NMDA antagonist, have shown improved clinical outcomes, increased independence and a trend towards delayed institutionalisation in patients with moderately severe-to-severe Alzheimer's disease. In a randomised double-blind, placebo-controlled, 28-week study conducted in the US, reductions in resource utilisation and total healthcare costs were noted with memantine relative to placebo. While these findings suggest that, compared with placebo, memantine provides cost savings, further analyses may help to quantify potential economic gains over a longer treatment period. OBJECTIVE: To evaluate the cost effectiveness of memantine therapy compared with no pharmacological treatment in patients with moderately severe-to-severe Alzheimer's disease over a 2-year period. METHODS: A Markov model was constructed to simulate patient progression through a series of health states related to severity, dependency (determined by patient scores on the Alzheimer's Disease Cooperative Study-Activities of Daily Living [ADCS-ADL] inventory and residential status ('institutionalisation') with a time horizon of 2 years (each 6-month Markov cycle was repeated four times). Transition probabilities from one health state to another 6 months later were mainly derived from a 28-week, randomised, double-blind, placebo-controlled clinical trial. Inputs related to epidemiological and cost data were derived from a UK longitudinal epidemiological study, while data on quality-adjusted life-years (QALYs) were derived from a Danish longitudinal study. To ensure conservative estimates from the model, the base case analysis assumed drug effectiveness was limited to 12 months. Monte Carlo simulations were performed for each state parameter following definition of a priori distributions for the main variables of the model. Sensitivity analyses included worst case scenario in which memantine was effective for 6 months and one-way sensitivity analyses on key parameters. Finally, a subgroup analysis was performed to determine which patients were most likely to benefit from memantine. Informal care was not included in this model as the costs were considered from National Health Service and Personal Social Services perspective. RESULTS: The base case analysis found that, compared with no treatment, memantine was associated with lower costs and greater clinical effectiveness in terms of years of independence, years in the community and QALYs. Sensitivity analyses supported these findings. For each category of Alzheimer's disease patient examined, treatment with memantine was a cost-effective strategy. The greatest economic gain of memantine treatment was in independent patients with a Mini-Mental State Examination score of > or =10. CONCLUSION: This model suggests that memantine treatment is cost effective and provides cost savings compared with no pharmacological treatment. These benefits appear to result from prolonged patient independence and delayed institutionalisation for moderately severe and severe Alzheimer's disease patients on memantine compared with no pharmacological treatment.

Cost effectiveness of treatments for amyotrophic lateral sclerosis: a review of the literature.

Amyotrophic lateral sclerosis (ALS) is a difficult to diagnose, fatal, progressive degenerative disease with an average survival time of 2 to 5 years. Percutaneous endoscopic gastrotomy (PEG) and bi-level intermittent positive pressure (BIPAP) ventilation may be the major interventions leading to longer survival of patients with ALS. Riluzole has been shown to have modest effects on survival (as opposed to functional) gains and is currently the only drug approved for the treatment of ALS. There is conflicting evidence with regard to the ability of recombinant human insulin-like growth factor (rhIGF-I) to retard ALS progression. Mechanical ventilation (via a tracheostomy tube) is expensive, but is widely used in later stage patients with ALS in the US. A review of nine cost-effectiveness studies of riluzole and one of rhIGF-I found the following: drug costs and survival gains are the major drivers of cost effectiveness; survival gains are estimated from truncated databases with a high degree of uncertainty; more accurate stage-specific utility weights based on patients who agreed to treatment are needed; case incidence-based evaluations should be carried out; cost-effectiveness ratios are insensitive to discount rates; employment and caregiver issues or externalities have been widely ignored; threshold acceptance cost-effectiveness values are ill-defined and evaluations are not generalisable to other countries because of cost and treatment style differences. On account of the high degree of uncertainty pertaining to survival gains and the relatively high costs per life years or quality-adjusted life-years gained, and while acknowledging that not every therapy has to be cost effective (e.g. orphan drugs), it is still inconclusive as to whether or not riluzole or rhIGF-1 can be considered as cost-effective therapies for ALS.