Treatment persistence in attention deficit/hyperactivity disorder: a retrospective analysis of patients initiated on lisdexamfetamine vs other medications

Abstract

Objective:

To compare treatment persistence in attention-deficit/hyperactivity disorder (ADHD) of patients initiated on lisdexamfetamine (LDX) vs other ADHD medications.

Methods:

A large US administrative claims database was used to select ADHD patients who initiated an ADHD medication (index treatment) during/after 2007. Patients were classified, based on age and previous treatment status, as treatment-naïve or previously treated children and adolescents (6–17 years) and treatment-naïve or previously treated adults (18 years and older). Furthermore, patients were classified into seven mutually exclusive treatment groups, based on their index treatment: LDX, atomoxetine (ATX), osmotic-release methylphenidate hydrochloride long-acting (OROS MPH), other methylphenidate/dexmethylphenidate short-acting (MPH SA) and long-acting (MPH LA), and amphetamine/dextroamphetamine short acting (AMPH SA) and long-acting (AMPH LA). Treatment persistence, analyzed through discontinuation (interruption of the index treatment for ≥30 consecutive days), was compared between treatment groups using multivariate Cox proportional hazards. Patients were followed until first treatment discontinuation or up to 12 months after the initiation of the index treatment, whichever occurred first.

Results:

Among children and adolescents, LDX patients had a significantly lower discontinuation rate compared to other treatment groups (range hazard ratios [HRs]; 1.04–2.26; all p?<?0.05), except when compared to treatment-naïve patients on ATX and OROS MPH, where no statistically significant differences were found and where LDX had a higher risk of discontinuation, respectively. Among adults, LDX patients had a significantly lower discontinuation rate compared to patients in other treatment groups (range HR; 1.14–1.86; all p?<?0.05), except for the comparison with AMPH LA patients, where differences were not statistically significant.

Limitations:

This study did not control for ADHD severity.

Conclusion:

LDX-treated patients were associated with higher persistence compared to patients initiated on other ADHD medications, except for the comparisons with OROS MPH and ATX treated patients in treatment-naïve children and adolescents and AMPH LA-treated patients in adults.     

Examining the heterogeneity of treatment patterns in attention deficit hyperactivity disorder among children and adolescents in the Texas Medicaid population: modeling suboptimal treatment response

Objectives: To examine suboptimal responses (SR) in attention deficit hyperactivity disorder (ADHD) among pediatric patients in the Texas Medicaid program receiving osmotic-release oral system methylphenidate (OROS-MPH) or lisdexamfetamine (LDX) and apply an SR prediction model to identify patients most likely to experience an SR to either OROS-MPH or LDX therapies.

Methods: A retrospective cohort study was conducted using Texas Medicaid claims data of ADHD children and adolescents (6–17?years of age) initiating OROS-MPH or LDX. Primary SR endpoints were drug discontinuation, switching, and augmentation 12-months post-ADHD drug initiation. Logistic regression models were developed to predict SR to OROS-MPH and LDX in 1:1 matched groups of children and adolescent cohorts.

Results: A total of 3,633 children and 1,611 adolescents were matched for each cohort. SR was observed among more children (76.4% vs 72.3%; p?p?=?0.002) initiating OROS-MPH compared to LDX. Patient sub-groups with the highest predicted risk of OROS-MPH SR experienced significantly lower observed SR rates (p?Conclusions: This study demonstrated how a personalized medicine approach using administrative claims data can be used to identify sub-groups of child and adolescent ADHD patients with different risks for suboptimal response with OROS-MPH or LDX in a Medicaid population.     

Identifying patient subgroups who benefit most from a treatment: using administrative claims data to uncover treatment heterogeneity

Abstract

Objectives:

To illustrate how claims data can be used to (1) develop outcome scores that predict response to a traditional treatment and (2) estimate the economic impact of individualized assignment to a newer treatment based on the outcome score. An example application is based on two treatments for attention deficit hyperactivity disorder (ADHD): osmotic-release oral system methylphenidate (OROS-MPH) and lisdexamfetamine dimesylate (LDX).

Methods:

Adolescents with ADHD initiating OROS-MPH (n?=?6320) or LDX (n?=?6394) were selected from the MarketScan claims database. A model was developed for predicting risk of switching/augmentation with OROS-MPH using multiple baseline characteristics. The model was applied to an independent sample to stratify patients by their predicted risk and, within each stratum, risk of switching/augmentation and ADHD-related total costs were compared between OROS-MPH and LDX patients using inverse probability of treatment weighting.

Results:

The prediction model resulted in substantial stratification, showing risk of switching/augmentation with OROS-MPH ranging from 11.3–42.1%. In the two strata where OROS-MPH had highest risk of switching/augmentation, LDX had significantly lower risk of switching/augmentation than OROS-MPH (by 7.0–8.2%) and lower ADHD-related annual total costs (by $264–$625 per patient).

Limitations:

The current study has used the risk of switching/augmentation as a proxy measure for treatment efficacy to establish the prediction model. Future research using a clinical measure for ADHD symptoms is warranted to verify the findings.

Conclusions:

Combining multiple patient characteristics into a predicted score for treatment outcomes with a traditional treatment can help identify subgroups of patients who benefit most from a new treatment. In this analysis, ADHD patients with a high predicted score for switching/augmentation with OROS-MPH had a lower rate of switching/augmentation with LDX. Assigning OROS-MPH and LDX treatments based on the predicted scores that are heterogeneous in a patient population may help improve clinical outcomes and the cost-effectiveness of care.     

A cost analysis of the management of attention-deficit/hyperactivity disorder (ADHD) in children in the UK

SUMMARY

A decision analysis was performed to model the effects and health economic differences of current UK management approaches to attention-deficit/hyperactivity disorder (ADHD) in children aged between 6 and 16 years. The approaches modelled were: medication using a standard immediate-release methylphenidate (MPH-IR) (once, twice or three times daily); medication using CONCERTA®XL (OROS®* methylphenidate; MPH), a long-acting once-daily formulation of methylphenidate; or behavioural therapy (BEH). Starting treatment with BEH alone resulted in the highest annual cost (UK£2,147), while the costs of starting treatment with MPH-IR alone (£1,332), or OROS®* MPH alone (£1,362) were comparable. Treatment switches to behavioural treatment or combined treatment (medication and behavioural) due to treatment failure occurred in 11.8% of OROS®* MPH and 24.2% of MPH-IR patients. Probabilistic sensitivity analyses showed that the results were sensitive towards treatment success and the proportion of patients with comorbidities, although conclusions were not altered. UK treatment costs over 1 year appear comparable regardless of whether patients were treated first with OROS®* MPH or MPH-IR. Treating patients first with BEH and then adding stimulant medication if needed resulted in higher overall annual treatment costs.

CONCERTA® XL and OROS® are trademarks of ALZA Corporation, USA.     

Compliance and persistence with Alzheimer’s disease treatment: a retrospective analysis of multiregional hospital databases in Thailand

Aims: Due to the lack of studies evaluating compliance or persistence with Alzheimer’s Disease (AD) treatment outside High-Income Countries (HICs), this study aimed to assess compliance, persistence, and factors associated with non-compliance and non-persistence by utilizing existing “real-world” information from multiregional hospital databases in Thailand.

Materials and methods: Study subjects were retrospectively identified from databases of five hospitals located in different regions across Thailand. AD patients aged ≥60 years who were newly-prescribed with donepezil, galantamine, rivastigmine, or memantine between 2013 and 2017 were eligible for analysis. The Medication Possession Ratio (MPR) was used as a proxy for compliance, while the Kaplan–Meier survival analysis was employed to estimate persistence. Logistic and Cox regressions were used to assess determinants of non-compliance and non-persistence, adjusted for age and gender.

Results: Among 698 eligible patients, mean (SD) MPR was 0.83 (0.25), with 70.3% of the patients compliant to the treatment (having MPR?≥?0.80). Half of the patients discontinued their treatment (having a treatment gap >30 days) within 177 days with a 1-year persistence probability of 21.1%. The patients treated in the university-affiliated hospital were more likely to be both non-compliant (OR?=?1.71; 95% CI?=?1.21–2.42) and non-persistent (HR?=?1.33; 95% CI?=?1.12–1.58). In addition, non-compliance was higher for those prescribed with single AD treatment (OR?=?2.52; 95% CI?=?1.35–4.69), while non-persistence was higher for those unable to reimburse for AD treatment (HR?=?1.34; 95% CI?=?1.11–1.62).

Limitations: By using retrospective databases, a difficulty in validating whether the medications are actually taken after being refilled may over-estimate the levels of compliance and persistence. Meanwhile, possible random coding errors may under-estimate the strength of association findings.

Conclusions: This study reveals the situation of compliance and persistence on AD treatment for the first time outside HICs. The determinants of non-compliance and non-persistence underline key areas for improvement.     

Medication adherence and persistence in the treatment of rheumatoid arthritis with adalimumab and etanercept. Six years of analysis

Objective:

The aim of this study was to evaluate medication adherence and persistence of patients treated with Etanercept and Adalimumab for Rheumatoid Arthritis, also giving economic evaluations on therapy costs for Received Daily Dose (RDD).

Materials and methods:

This retrospective study took into account 6 years from January 1, 2007 to December 31, 2012. Medication adherence was quantified utilizing the ratio between RDD and Prescribed Daily Dose (PDD). Persistence has been reckoned taking into account the actual days of therapy comparing posology with supplied dose. The persistence has been graphed according to Kaplan-Meier method. The cost per RDD was reckoned starting from the expense incurred by Pescara General Hospital.

Results:

Medication adherence gave results in values between 0.88–0.97 for Etanercept and 0.83–0.90 for Adalimumab. The value of persistence was 100% for Etanercept and 90% for Adalimumab for the first year, and 70% for Etanercept and 80% for Adalimumab for the second year. In the 3rd year the persistence for Etanercept was 50% while for Adalimumab it was 60%. In the fourth year the persistence for Etanercept was 21% while for Adalimumab it was 27%. The statistical analysis was conducted using the Log rank test. The average cost per RDD was €32.97 for Etanercept and for Adalimumab it was €32.00 as an average of 6 years.

Conclusion:

The medication adherence was good for both Etanercept and Adalimumab. The rate of persistence decreased strictly in the fourth year of treatment. This data suggests the need for continuous monitoring of patients in treatment with TNF blockers.     

Anxiety disorders,major depressive disorder and the dynamic relationship between these conditions: treatment patterns and cost analysis

Abstract

Objective: To determine the treatment pattern and impact on healthcare costs of anxiety disorders and major depressive disorder (MDD), and influence of their concomitance and subsequence.

Methods: A retrospective cohort study was conducted using a US reimbursement claims database. Adult patients with an incident diagnosis of anxiety or MDD (index date) were included. Their sociodemographic data, diagnoses, healthcare resource use and associated costs were collected over the 6 months preceding and 12 months following index date.

Results: A total of 599,624 patients were identified and included. Patients with phobia or post-traumatic stress disorder had the highest 12-month costs ($8,442 and $8,383, respectively). Patients with social anxiety disorder had the lowest costs ($3,772); generalized anxiety disorder ($6,472) incurred costs similar to MDD ($7,170). Costs were substantially increased with emergence of anxiety during follow-up in MDD patients ($10,031) or emergence of MDD in anxiety patients ($9,387). This was not observed in patients with both anxiety and MDD at index date ($6,148).

Conclusion: This study confirms the high burden of costs of anxiety, which were within the same range as MDD. Interestingly, the emergence of anxiety or MDD in the year following a first diagnosis of MDD or anxiety, respectively, increased costs substantially. Major limitations were short follow-up and lack of absenteeism costs.     

Hybrid input-output analysis of wastewater treatment and environmental impacts: A case study for the Tokyo Metropolis

This paper proposes a new hybrid input-output model designed to analyze both the generation and treatment of wastewater. This model, named wastewater treatment input-output model (WWIO), can be regarded as an extension of the waste input-output model (WIO) (Nakamura, S. and Kondo, Y., 2002. Input-output analysis of waste management. Journal of Industry Ecology, 6(1): 39-63.). As an application, I compiled the Tokyo Metropolitan WWIO table for 2000, which comprises 482 economic sectors, 11 wastewater treatment sectors, 12 types of wastewater-related waste and 6 types of environmental load. The model was applied to different scenarios to compare alternative wastewater treatment systems. The results indicate that replacing the simple treatment with the high-class treatment improves the quality of treated water while increasing CO₂-equivalent emissions. Meanwhile, when the dewatered sludge is incinerated instead of landfilling, both CO₂-equivalent emissions and landfill volume decrease.     

Economic impact of switching from metoprolol to nebivolol for hypertension treatment: a retrospective database analysis

Objective:

To estimate the real-world economic impact of switching hypertensive patients from metoprolol, a commonly prescribed, generic, non-vasodilatory β₁-blocker, to nebivolol, a branded-protected vasodilatory β₁-blocker.

Methods:

Retrospective analysis with a pre–post study design was conducted using the MarketScan database (2007–2011). Hypertensive patients continuously treated with metoprolol for ≥6 months (pre-period) and then switched to nebivolol for ≥6 months (post-period) were identified. The index date for switching was defined as the first nebivolol dispensing date. Data were collected for the two 6-month periods pre- and post-switching. Monthly healthcare resource utilization and healthcare costs pre- and post-switching were calculated and compared using Wilcoxon test and paired t-test. Medical costs at different years were inflated to the 2011 dollar.

Results:

In total, 2259 patients (mean age: 60 years; male: 52%; cardiovascular [CV] disease: 37%) met the selection criteria. Switching to nebivolol was associated with statistically significant reductions in the number of all-cause hospitalization (?33%; p?p?p?p?p?Conclusions:

This real-world study suggests that switching from metoprolol to nebivolol is associated with an increase in medication costs and significant reductions in hospitalizations and outpatient visits upon switching, resulting in an overall neutral effect on healthcare costs. These results may be interpreted with caution due to lack of a comparator group and confounding control caused by design and limitations inherent in insurance claims data.     

Use of opioid substitution therapies in the treatment of opioid use disorder: results of a UK cost-effectiveness modelling study

Aims: This study investigated the cost-effectiveness of buprenorphine maintenance treatment (BMT) and methadone maintenance treatment (MMT) vs no opioid substitution therapy (OST) for the treatment of opioid use disorder, from the UK National Health Service (NHS)/personal social services (PSS) and societal perspectives over 1 year.

Methods: Cost-effectiveness of OST vs no OST was evaluated by first replicating and then expanding an existing UK health technology assessment model. The expanded model included the impact of OST on infection rates of human immunodeficiency virus (HIV) and hepatitis C virus (HCV) infection.

Results: Versus no OST, incremental cost-effectiveness ratios (ICERs) for BMT and MMT were £13,923 and £14,206 per quality-adjusted life year (QALY), respectively, from a NHS/PSS perspective. When total costs (NHS/PSS and societal) are considered, there are substantial savings associated with adopting OST; these savings are in excess of £14,032 for BMT vs no OST and £17,174 for MMT vs no OST over 1 year. This is primarily driven by a reduction in victim costs. OST treatment also impacted other aspects of criminality and healthcare resource use.

Limitations: The model’s 1-year timeframe means long-term costs and benefits, and the influence of changes over time are not captured.

Conclusions: OST can be considered cost-effective vs no OST from the UK NHS/PSS perspective, with a cost per QALY well below the UK’s willingness-to-pay threshold. There were only small differences between BMT and MMT. The availability of two or more cost-effective options is beneficial to retaining patients in OST programs. From a societal perspective, OST is estimated to save over £14,032 and £17,174 per year for BMT and MMT vs no OST, respectively, due to savings in victim costs. Further work is required to fully quantify the clinical and health economic impacts of different OST formulations and their societal impact over the long-term.     

Comparing olanzapine and ziprasidone in the treatment of schizophrenia: a case study in modeling

SUMMARY

When a new drug is introduced to the market, the availability of head-to-head data for comparisons of annual cost and health outcomes with other drugs already on the market is usually insufficient. When only limited head-to-head data are available, one alternative is to perform preliminary modeling using data from the best available studies. In this paper, we synthesise data from the most comparable available studies to create a model to compare the annual costs and health outcomes when initiating treatment for schizophrenia with one of two antipsychotic drugs: olanzapine, which was launched in the United States (US) market in September 1996, and ziprasidone, which was approved by the US Food and Drug Administration (FDA) in February 2001. Annual treatment costs were determined by response and relapse rates as well as acquisition costs. The results indicate similar annual treatment costs (US$48,676 for olanzapine; US$48,873 for ziprasidone), despite the lower drug acquisition cost for ziprasidone. Annual health outcomes differed between the olanzapine and ziprasidone groups with 23.5% and 25.2% relapsed, 36.7 and 37.4 hospital days, and 60.0 and 60.1 EPS days in the olanzapine and ziprasidone groups respectively. A head-to-head naturalistic trial is needed to validate the results of this modeling exercise.     

Patients’ preferences for the treatment of anxiety and depressive disorders: a systematic review of discrete choice experiments

Abstract

Introduction: Matching available mental health services to patients’ preferences, as well as is possible, may increase patient satisfaction and help increase adherence to certain treatments. This study systematically reviewed discrete-choice experiments (DCEs) on patients’ preferences for treatment of depressive and anxiety disorders and assessed the relative importance of outcome, process and cost attributes to improve the current and future treatment situations.

Methods: A systematic literature review using PubMed, EMBASE and PsychInfo was conducted to retrieve all relevant DCEs published up to 15 April 2019, eliciting patient preferences for treatment of depressive and anxiety disorders. Data were extracted using an extraction sheet, and attributes were classified into outcome, process and cost attributes. The relative importance of each attribute category was then assessed, and studies were evaluated according to their reporting quality, using validated checklists.

Results: A total of 11 studies were identified for qualitative analysis. All studies received an aggregate score of 4 on the five-point PREFS checklist (Purpose, Respondents, Explanation, Findings and Significance). Most attributes were outcome related (52%), followed by process (42%) and cost (6%) attributes. Comparing the attribute categories and summing up the relative importance weights for each category within the studies, process attributes were ranked as most important, followed by cost and outcome attributes.

Conclusions: In this systematic review, heterogeneous results were observed regarding the inclusion and framing of different attributes across studies. Overall, patients considered process and cost attributes to be more important than outcome attributes. Outcomes and process are important for patients, and thus clinicians should be particularly aware of this and take patients’ preferences into account, although the attribute importance may depend on chosen attributes and related levels.     

Peginterferon beta-1a versus other self-injectable disease-modifying therapies in the treatment of relapsing-remitting multiple sclerosis in Scotland: a cost-effectiveness analysis

Aims: Peginterferon beta-1a 125?mcg administered subcutaneously every 2 weeks, a new disease-modifying therapy (DMT) for relapsing-remitting multiple sclerosis (RRMS), was approved in January 2015 by the Scottish Medicines Consortium. This study assesses long-term clinical and economic outcomes of peginterferon beta-1a compared with other self-injectable DMTs (interferon beta-1a [22?mcg, 30?mcg, and 44?mcg], interferon beta-1b, and glatiramer acetate 20?mg) in the treatment of RRMS, from the National Health Service and Personal Social Services perspective in Scotland.

Methods: A previously published, validated Markov cohort model was adapted for this analysis. The model estimates changes in patient disability, occurrence of relapses, and other adverse events, and translates them into quality-adjusted life years and costs. Natural history data came from the ADVANCE trial of peginterferon beta-1a, the London Ontario (Canada) database, and a large population-based MS survey in the UK. The comparative efficacy of each DMT vs placebo was obtained from a network meta-analysis. Costs (2015 British Pounds) were obtained from public databases and literature. Clinical and economic outcomes were projected over 30 years and discounted at 3.5% per year.

Results: Over 30 years, peginterferon beta-1a was dominant compared with interferon beta-1a (22, 30, and 44?mcg), and interferon beta-1b, and cost-effective compared with glatiramer acetate 20?mg. Results were most sensitive to variations in each DMT’s efficacy and acquisition costs. Deterministic and probabilistic sensitivity analyses confirmed the robustness of the results.

Limitations: The impact of improved adherence with peginterferon beta-1a on clinical and economic outcomes and the impact of subsequent DMTs after treatment discontinuation were not considered. Oral and infused DMTs were not included as comparators.

Conclusion Long-term treatment with peginterferon beta-1a improves clinical outcomes, while its cost profile makes it either dominant or cost-effective compared with other self-injectable DMTs for the treatment of RRMS in Scotland.     

Real-world dosing and drug costs with everolimus or axitinib as second targeted therapies for advanced renal cell carcinoma: a retrospective chart review in the US

Objective:

To describe dosing patterns and to compare the drug costs per month spent in progression-free survival (PFS) among patients with advanced renal cell carcinoma (aRCC) treated with everolimus or axitinib following a first tyrosine kinase inhibitor (TKI).

Methods:

A medical record retrospective review was conducted among medical oncologists and hematologists/oncologists in the US. Patient eligibility criteria included: (1) age ≥18 years; (2) discontinuation of first TKI (sunitinib, sorafenib, or pazopanib) for medical reasons; (3) initiation of axitinib or everolimus as a second targeted therapy during February 2012–January 2013. Real-world dosing patterns were summarized. Dose-specific drug costs (as of October 2014) were based on wholesale acquisition costs from RED BOOK Online. PFS was compared between everolimus and axitinib using a multivariable Cox proportion hazards model. Everolimus and axitinib drug costs per month of PFS were compared using multivariable gamma regression models.

Results:

A total of 325 patients received everolimus and 127 patients received axitinib as second targeted therapy. Higher proportions of patients treated with axitinib vs everolimus started on a higher than label-recommended starting dose (14% vs 2%) or experienced dose escalation (11% vs 1%) on second targeted therapy. The PFS did not differ significantly between patients receiving everolimus or axitinib (adjusted hazard ratio (HR)?=?1.16; 95% confidence interval [CI]?=?0.73–1.82). After baseline characteristics adjustment, axitinib was associated with 17% ($1830) higher drug costs per month of PFS compared to everolimus ($12,467 vs $10,637; p?<?0.001).

Limitations:

Retrospective observational study design and only drug acquisition costs considered in drug costs estimates.

Conclusions:

Patients with aRCC receiving axitinib as second targeted therapy were more likely to initiate at a higher than label-recommended dose and were more likely to dose escalate than patients receiving everolimus. With similar observed durations of PFS, drug costs were significantly higher—by 17% per month of PFS—with axitinib than with everolimus.     

Clinical comorbidities,treatment patterns,and direct medical costs of patients with osteoarthritis in usual care: a retrospective claims database analysis

Abstract

Objective:

Comorbidities and resource utilization among patients with osteoarthritis (OA) in clinical practice have been infrequently characterized. The purpose of this study was to examine comorbidities, pain-related pharmacotherapy, and direct medical costs of patients with OA in clinical practice.

Method:

This retrospective cohort analysis used medical and pharmacy claims data from the LifeLink? Database. OA patients (ICD-9-CM codes 715.XX) were matched (age, gender, and region) with individuals without OA. Comorbidities, pain-related pharmacotherapy, and direct medical costs (pharmacy, outpatient, inpatient, total) were examined for the calendar year 2008.

Results:

The sample consisted of 112,951 OA patients and 112,951 controls (mean age: 56.9 [SD?=?9.5] years; 62% female). Relative to controls, OA patients were significantly more likely (p?<?0.0001) to have comorbidities, including musculoskeletal (84.3 vs. 37.1%) and neuropathic pain (22.0 vs. 6.1%) conditions, depression (12.4 vs. 6.4%), anxiety (6.6 vs. 3.5%), and sleep disorders (11.9 vs. 4.2%). OA patients were significantly more likely (p?<?0.0001) to receive pain-related medications, including opioids (40.7 vs. 17.1%), NSAIDs (37.1 vs. 11.5%), tramadol (9.8 vs. 1.8%), and adjunctive medications for treating depression, anxiety, and insomnia. Mean [SD] total direct medical costs were more than two times higher among OA patients ($12,905 [$21,884] vs. $5099 [$13,855]; p?<?0.001) and median costs were more than three times higher ($6188 vs. $1879; p?<?0.0001). Study limitations include potential errors in coding and recording; overestimation of the comorbidity burden; inability to link condition of interest, OA, with prescribed medications; and possible underestimation of the true costs of OA, because indirect costs were not considered and the direct costs were from a third party payer (commercial insurance) perspective.

Conclusion:

The patient burden of OA was characterized by a high prevalence of comorbidities. The payer burden was also substantial, with significantly greater use of pain-related and adjunctive medications, and higher direct medical costs.