Opportunities and Barriers to the Development and Use of Open Source Health Economic Models: A Survey.

OBJECTIVES: Health economic (HE) models are routinely used to support health policy and resource allocation decisions but are often considered "black boxes" that may be prone to error and bias. Open source models (OSMs) have been advocated to increase the transparency, credibility, and reuse of HE models. Previous studies have demonstrated interest in OSMs among the health economics and outcomes research community, but the number of OSMs remains low. METHODS: We conducted an online survey of ISPOR (the leading professional society for health economics and outcomes research) members' perspectives on the usefulness of OSMs and barriers to their development and implementation. RESULTS: Respondents (N = 230) included academics (27%), pharmaceutical (or related) industry representatives (23%), health research or consulting representatives (21%), governmental or nonprofit agency representatives (10%), and others (19%). Respondents were generally not familiar with barriers to the development and adoption of OSMs. Most agreed that OSMs would improve transparency (92%), efficiency (76%), and HE model reuse (86%) and promote confidence in using HE models (75%). The use of OSMs by health technology assessment authorities was considered a very important indicator of the usefulness of OSMs by 49% of respondents. Three-quarters of respondents perceived legal concerns and the ability to transfer data as important barriers to the development and use of OSMs. CONCLUSIONS: Respondents believe that OSMs could increase the transparency, efficiency, and credibility of HE models, but that several barriers hamper their widespread adoption. Our results suggest that fundamental changes may be needed across the health economics and outcomes research community if OSMs are to become widely adopted.

Budget Impact of Next-Generation Sequencing for Molecular Assessment of Advanced Non-Small Cell Lung Cancer.

BACKGROUND: Genetic testing for nonsquamous advanced non-small cell lung cancer (aNSCLC) is recommended to guide first-line therapy. Activating mutations can be identified via single-gene testing or next-generation sequencing (NGS). OBJECTIVES: To evaluate the budget impact of NGS instead of single-gene testing for tissue-based molecular assessment of aNSCLC from the US health care payer perspective. METHODS: An annual cohort of newly diagnosed patients with nonsquamous aNSCLC in a hypothetical 1-million-member health care plan was evaluated using a Markov model over 5 years. Epidemiology and testing rates (EGFR, ALK, ROS1, BRAF, MET, HER2, and RET) were from the literature. Treatments were determined by available genetic information. Safety, progression, and survival with targeted therapy or chemotherapy were from randomized clinical trials. Single-gene testing and first-line and maintenance treatment costs were from RED BOOK and Medicare fee schedules; NGS testing, adverse event, and progression costs to payers were from the literature. RESULTS: Three hundred sixteen testing-eligible patients with aNSCLC were expected annually, of whom 179 undergo genetic testing. Of 57 patients expected to have activating mutations, single-gene testing identified 35, whereas NGS identified 54. NGS, instead of single-gene testing, decreased expected testing procedure-related costs to the health plan payer by $24,651. First-line and maintenance treatment costs increased by $842,205, offset by a $385,000 decrease in second-line treatment and palliative care costs. Over 5 years, total budget impact was $432,554 ($0.0072 per member per month). CONCLUSIONS: NGS is expected to identify more patients with activating mutations, thereby better enabling selection for targeted therapy and clinical trial enrollment. The budget impact to US payers is expected to be minimally cost-additive.

Comparison between Surgical and Endovascular Hemodialysis Arteriovenous Fistula Interventions and Associated Costs.

PURPOSE: To compare: (i) rate of arteriovenous fistula (AVF) interventions in both incident and prevalent end-stage kidney disease patients; (ii) their associated costs; and (iii) intervention-free survival between patients with surgical hemodialysis arteriovenous fistula (SAVF) versus those with an endovascularly created fistula (endoAVF). MATERIALS AND METHODS: Data from the United States Renal Data System (USRDS) were abstracted to determine the rate of AVF interventions performed in the first year and associated costs (based on Medicare payment rates) for SAVFs created from 2011 to 2013 in the incident and prevalent patient cohorts. Comparative data for endoAVF were obtained from the Novel Endovascular Access Trial (NEAT). Event rates, intervention-free survival, and costs were compared between endoAVF and SAVF cohorts after 1:1 propensity score (PS) matching. RESULTS: In the matched incident patients, the event rate was 0.74 per patient-year (PY) for endoAVF versus 7.22/PY for SAVF (P < .0001), with a difference in expenditures of $16,494. Similarly, in matched prevalent patients the event rate was 0.46/PY for endoAVF vs 4.10/PY for SAVF (P < .0001), resulting in a cost difference of $13,389. Time-to-event analysis showed that at 1 year, 70% of endoAVF patients experienced freedom from intervention versus only 18% of SAVF patients for incident patients; these numbers were 62% and 18% for endoAVF and SAVF prevalent patients, respectively (P < .0001 for both). CONCLUSIONS: Both incident and prevalent patients with endoAVF required fewer interventions and had lower costs within the first year compared with matched patients with SAVF.

Impact of Definitive Drug-Drug Interaction Testing on Medication Management and Patient Care.

BACKGROUND AND OBJECTIVE: Aegis Sciences Corporation developed a test (InterACT Rx™) that objectively and definitively identifies substances known to interact with drug-drug interaction-prone medications commonly prescribed in the treatment of chronic pain and behavioral health disorders. The objective of this study was to assess the severity of identified drug-drug interactions, the reduction in the frequency and severity of identified drug-drug interactions, and the impact of the test on healthcare utilization. METHODS: Patients with chronic pain, behavioral health disorders, or both who had one or more drug-drug interaction tests and one or more drug-drug interactions identified in the study period were included. Drug-drug interaction test results described the number and severity of interactions and detected substances involved in drug-drug interactions. Patients' electronic medical records were obtained to analyze outpatient visits and prescription medications. The cost of outpatient visits was based on the Medicare Physician Fee Schedule. Outcomes were compared between the pre- and post-study index periods to determine the impact of the drug-drug interaction test on patient care. RESULTS: A total of 262 patients were included. The majority of drug-drug interactions detected (77.9%) at index were of moderate severity. The number of monthly all-cause and pain-related outpatient visits was reduced in the post-index period compared with the pre-index period (0.74-0.54 and 0.69-0.49, respectively). Associated costs were reduced from US$64.92 to US$51.20, and from US$62.42 to US$47.62, (p < 0.0001 for both) for all-cause and pain-related outpatient visits, respectively. Follow-up drug-drug interaction testing for 43 patients revealed that previously reported drug-drug interactions at the index test were no longer identified in the subsequent test for 39.5% of patients. CONCLUSIONS: Employing a definitive test to detect substances whose interactions may cause adverse drug events can enhance a provider's insights, drive clinical decision making, and improve patient outcomes.

Cost impact of monitoring exhaled nitric oxide in asthma management.

BACKGROUND: Asthma guidelines recommend periodic assessment of impairment and risk factors to prevent exacerbations, which can lead to hospitalization and increased health care utilization and cost. According to recent meta-analysis data, fractional exhaled nitric oxide (FeNO) monitoring is associated with a 40-50% reduction in the risk of exacerbations. OBJECTIVE: Cost modeling of these data indicates the potential for significant cost savings with FeNO use. Therefore, we attempted to verify this potential for cost savings within a real-world data base of Medicare beneficiaries. METHODS: This retrospective observational study investigated asthma-related claims from a Medicare data base. Beneficiaries were included who had 2 years of records after an asthma-related inpatient hospitalization (IP) or emergency department (ED) claim. A case-crossover analysis was completed of asthma-related IP or ED events before and after FeNO use during the 2-year study period. RESULTS: Of the 5911 asthma beneficiaries who met the inclusion criteria within the data base, 101 had an FeNO test during the 2-year study period. During the period before FeNO use, 98 of 101 (97%) beneficiaries had an asthma-related IP or ED event compared with 46 of 101 (46%) during the FeNO period. Asthma-related IP or ED claims and charges per beneficiary per day during the period before FeNO were 0.004 and $16.21 compared with 0.002 and $6.46 during the FeNO period (p = 0.0433 and p = 0.0133, respectively). CONCLUSION: FeNO monitoring in beneficiaries with a history of exacerbations was associated with a substantial reduction in asthma-related IP and ED claims and charges. These data supported cost modeling estimates and demonstrated that FeNO use in asthma management was associated with significant cost savings.

Association of Inadequately Controlled Disease and Disease Severity With Patient-Reported Disease Burden in Adults With Atopic Dermatitis.

Importance: Real-world data are limited on the patient-reported burden of adult atopic dermatitis (AD). Objective: To characterize the patient-reported burden of AD with regard to impact of disease severity and inadequate control in adults from clinical settings. Design, Setting, and Participants: In this cross-sectional study using data from 6 academic medical centers in the United States collected by a self-administered internet-based questionnaire, 1519 adult patients with AD were stratified by AD severity as mild or moderate/severe using the Patient-Oriented Scoring Atopic Dermatitis (PO-SCORAD). Patients with moderate/severe disease using systemic immunomodulators/phototherapy were further stratified as having adequate or inadequate disease control. Strata were compared for all outcomes. Main Outcomes and Measures: Outcomes included validated measures and stand-alone questions assessing itch (pruritus numerical rating scale; PO-SCORAD itch visual analog scale), pain (numerical rating scale), sleep (PO-SCORAD sleep visual analog scale; sleep interference with function), anxiety and depression (Hospital Anxiety and Depression Scale), and health-related quality of life (Dermatology Life Quality Index). Results: Among the 1519 adult patients with AD, relative to mild AD (n = 689, 64% women; mean [SD] age, 46.5 [18.0] years), patients with moderate/severe AD (n = 830, 66.8% women; mean [SD] age, 45.1 [16.9] years) reported more severe itching and pain, greater adverse effects on sleep, higher prevalence of anxiety and depression (417 [50.2%] vs 188 [27.3%]), and greater health-related quality-of-life impairment. The 103 patients with moderate/severe AD with inadequate disease control despite treatment with systemic immunomodulators or phototherapy (55.7%) reported higher burdens of itch and sleeping symptoms vs patients with controlled disease including more days per week with itchy skin (5.7 vs 2.7) and higher proportions with itch duration greater than half a day (190 [22.8%] vs 20 [2.9%]). Sleep symptoms included trouble sleeping (3.9 vs 1.1 on the PO-SCORAD VAS), longer sleep latency (38.8 vs 21.6 minutes), more frequent sleep disturbances (2.6 vs 0.4 nights in past week), and greater need for over-the-counter sleep medications (324 [39%] vs 145 [21%]). Conclusions and Relevance: Inadequate disease control was common among patients with moderate/severe AD, and was associated with a higher patient-reported burden than patients with controlled disease. Regardless of disease control, the burden of moderate/severe AD was higher than mild AD, suggesting a need for more effective therapies for moderate/severe disease.

Assessment of the relationship between diabetes treatment intensification and quality measure performance using electronic medical records.

AIMS: Assess the relationship between timely treatment intensification and hemoglobin A1C (HbA1C) control quality-of-care performance measures, i.e., HbA1C levels, among patients with uncontrolled type 2 diabetes. MATERIALS AND METHODS: Electronic medical records and diabetes registry data from a large, accountable care organization (ACO) were used to isolate a sample of adult patients with type 2 diabetes who received at least one oral antidiabetes agent and had at least one HbA1C level measurement ≥8.0% (64 mmol/mol; i.e., uncontrolled diabetes) between 7/1/2011 and 6/30/2015. Treatment intensification status was evaluated for each patient during a 120-day treatment intensification window following the index HbA1c measure. Two-level hierarchical generalized linear models, with patients aggregated at the physician level, were used to assess the association between treatment intensification and achieving HbA1C quality performance measures. RESULTS: 547 patients met study selection criteria and 480 patients had at least one HbA1C test after the treatment intensification window and were used for the statistical analyses. About 40% of patients who had uncontrolled diabetes received treatment intensification during the 120-day window. Greater index HbA1C, greater patient body mass index, and fewer unique pre-index oral antidiabetes agents were significantly associated with greater likelihood of receiving timely treatment intensification. The odds of receiving treatment intensification were about 1.8 times higher (P = 0.0027) among patients with poor index HbA1C control (HbA1c level >9.0% [75 mmol/mol]) compared to other patients (index HbA1c 8.0% - 9.0%). Hispanic patients (compared to White patients) were significantly more likely to exhibit poor control after treatment intensification (odds ratio [OR] 2.91, P = 0.0304), underscoring the difficulty of controlling diabetes in this vulnerable group. In contrast, being male and being treated primarily by an internist (compared to primary treatment by a family medicine specialist) were both significantly associated with achieving superior control (HbA1c level <8.0%) after treatment intensification (OR 0.53 [P = 0.0165]; OR 0.41 [P = 0.0275], respectively). CONCLUSIONS: Timely treatment intensification was significantly associated with greater likelihood of patients achieving superior HbA1C control (<8.0%) and better HbA1C control quality performance for the practice. Even in an ACO with resources dedicated to diabetes control, it is incumbent upon clinicians to readily identify and open dialogues with patients who may benefit from closely supervised, individualized attention.

Patient-Reported Outcomes From the United States Clinical Trial for a Hybrid Cochlear Implant.

OBJECTIVE: To assess patient-reported outcomes (PROs) in individuals with significant residual low-frequency hearing and severe-to-profound high-frequency sensorineural hearing loss (SNHL) who received the hybrid cochlear implant (CI). STUDY DESIGN: Prospective, multicenter, nonrandomized, single-arm repeated measures, single-subject design. SETTING: Tertiary centers, ambulatory care. PATIENTS: Fifty adults with severe-to-profound high-frequency SNHL and residual low-frequency hearing with aided word recognition scores between 10 and 60% in the ear to be implanted, and in the contralateral ear greater than or equal to implant ear less than or equal to 80%. INTERVENTION: Therapeutic; hybrid CI. MAIN OUTCOME MEASURES: Speech, spatial and qualities of hearing scale (SSQ), device use questionnaire (DUQ), University of Washington Clinical Assessment of Music Perception (UW-CAMP) assessed preoperatively and after 6 and 12 (SSQ and DUQ only) months of hybrid CI use. RESULTS: Significant improvements in mean SSQ ratings were demonstrated at 6 and 12 months postactivation overall and for domains related to speech hearing, spatial hearing, and sound quality. Significant improvement was also found for overall satisfaction on the DUQ and across a number of specific listening situations in addition to aspects related to social engagement. UW-CAMP pitch discrimination and melody and timbre recognition abilities were not compromised postoperatively, allowing hybrid subjects to maintain superior music perception abilities than typically observed with standard CIs. CONCLUSIONS: Patients who received the hybrid CI demonstrated significant PRO benefits on the SSQ and the DUQ after 6 and 12 months of CI use. In addition, given the opportunity to maintain useful low-frequency acoustic hearing, patients retained music listening abilities, as assessed by the UW-CAMP.

Assessing the Impact of Medication Adherence on Long-Term Cardiovascular Outcomes.

BACKGROUND: Although guideline-recommended therapies reduce major adverse cardiovascular events (MACE) in patients after myocardial infarction (MI) or those with atherosclerotic disease (ATH), adherence is poor. OBJECTIVES: The goal of this study was to determine the association between medication adherence levels and long-term MACE in these patients. METHODS: We queried the claims database of a large health insurer for patients hospitalized for MI or with ATH. The primary outcome measure was a composite of all-cause death, MI, stroke, or coronary revascularization. Using proportion of days covered for statins and angiotensin-converting enzyme inhibitors, patients were stratified as fully adherent (≥80%), partially adherent (≥40% to ≤79%), or nonadherent (<40%). Per-patient annual direct medical (ADM) costs were estimated by using unit costs from 2 national files. RESULTS: Data were analyzed for 4,015 post-MI patients and 12,976 patients with ATH. In the post-MI cohort, the fully adherent group had a significantly lower rate of MACE than the nonadherent (18.9% vs. 26.3%; hazard ratio [HR]: 0.73; p = 0.0004) and partially adherent (18.9% vs. 24.7%; HR: 0.81; p = 0.02) groups at 2 years. The fully adherent group had reduced per-patient ADM costs for MI hospitalizations of $369 and $440 compared with the partially adherent and nonadherent groups, respectively. In the ATH cohort, the fully adherent group had a significantly lower rate of MACE than the nonadherent (8.42% vs. 17.17%; HR: 0.56; p < 0.0001) and the partially adherent (8.42% vs. 12.18%; HR: 0.76; p < 0.0001) groups at 2 years. The fully adherent group had reduced per-patient ADM costs for MI hospitalizations of $371 and $907 compared with the partially adherent and nonadherent groups. CONCLUSIONS: Full adherence to guideline-recommended therapies was associated with a lower rate of MACE and cost savings, with a threshold effect at >80% adherence in the post-MI population; at least a 40% level of long-term adherence needs to be maintained to continue to accrue benefit. Novel approaches to improve adherence may significantly reduce cardiovascular events.

A brief review of recent Charcot-Marie-Tooth research and priorities.

This brief review of current research progress on Charcot-Marie-Tooth (CMT) disease is a summary of discussions initiated at the Hereditary Neuropathy Foundation (HNF) scientific advisory board meeting on November 7, 2014. It covers recent published and unpublished in vitro and in vivo research. We discuss recent promising preclinical work for CMT1A, the development of new biomarkers, the characterization of different animal models, and the analysis of the frequency of gene mutations in patients with CMT. We also describe how progress in related fields may benefit CMT therapeutic development, including the potential of gene therapy and stem cell research. We also discuss the potential to assess and improve the quality of life of CMT patients. This summary of CMT research identifies some of the gaps which may have an impact on upcoming clinical trials. We provide some priorities for CMT research and areas which HNF can support. The goal of this review is to inform the scientific community about ongoing research and to avoid unnecessary overlap, while also highlighting areas ripe for further investigation. The general collaborative approach we have taken may be useful for other rare neurological diseases.

The role of globalization in drug development and access to orphan drugs: orphan drug legislation in the US/EU and in Latin America.

Compared to a decade ago, nearly three times as many drugs for rare diseases are slated for development. This article addresses the market access issues associated with orphan drug status in Europe and the United States in contrast to the legislation in five Latin American (LA) countries that have made strides in this regard--Mexico, Brazil, Colombia, Chile and Argentina. Based on the success of orphan drug legislation in the EU and US, LA countries should strive to adopt similar strategies with regard to rare diseases and drug development. With the implementation of new targeted regulations, reimbursement strategies, and drug approvals, accessibility to treatment will be improved for people afflicted with rare diseases in these developing countries.

A Retrospective Patient Chart Review and Survey in Patients with Cryopyrin-associated Periodic Syndromes Treated with Anakinra.

Background: Cryopyrin-associated periodic syndromes (CAPS) is a group of rare autoinflammatory diseases. Little is known about the burden of disease, patients' views on treatment, and adverse events (AEs) with current therapy. Objectives: The main study objective was to quantify the patients' burden of disease in terms of flares and resource use and to characterize patient symptomatology and tolerability of treatment with anakinra. A secondary objective included comparing chart review and patient recall of symptoms and AEs. Methods: A retrospective medical chart review and concurrent online patient survey was conducted in four European countries. Data 12 months prior to initiation of/during anakinra treatment were entered into web-based case report forms by study groups. Results: Forty-two patients received/were receiving anakinra as primary treatment for at least 12 months. Patients experienced a 79.5% reduction in flares after commencing anakinra treatment. During the past 12 months on anakinra, four of five (80%) patients who recalled experiencing flares reported cancelling social activities and staying home as the most common courses of action. Most common AEs were injection site pain upon treatment initiation and weight gain. According to patient recall, 12 of 21 patients (57.1%) discontinued anakinra to enter another clinical trial; of the 12, eight (38%) specifically discontinued anakinra only for that reason, and four patients cited entering a clinical trial as one of many reasons for discontinuing anakinra. Conclusions: To our knowledge, this is the most comprehensive survey of patient experience with CAPS. Although improved, CAPS treatment remains suboptimal and a significant burden is placed upon patients, caregivers, and the healthcare system. With new agents available, it will be important to compare outcomes in patients using all therapeutic options.

A retrospective randomized study of asthma control in the US: results of the CHARIOT study.

BACKGROUND: The third version of the National Asthma Education and Prevention Program (NAEPP) Expert Panel Report (EPR-3): Guidelines on the Diagnosis and Management of Asthma emphasizes the need to use asthma control rather than patient severity to base adjustments to treatment and ultimately improve patient outcomes. The objectives of the current study were to assess control of patients with moderate-to-severe asthma, examine the natural history of the disease, practice patterns and resource utilization in specialty community practices according to recently reviewed NAEPP guidelines. RESEARCH DESIGN AND METHODS: This analysis represents a retrospective, multicenter, randomized study of 1009 patient charts in sixty United States allergy and pulmonary medicine community practices. The proportion of patients with controlled and uncontrolled asthma over 12 months, prevalence and characteristics of atopy, past asthma history, pulmonary function, medications and treatment patterns, patient and clinical practice characteristics were analyzed. MAIN OUTCOME MEASURES: The primary outcome of interest was asthma control. RESULTS: A total of 365 male and 644 female patients with moderate-to-severe persistent asthma (mean 43.2 +/- 17.1 years) were enrolled. 81.9% of patients were uncontrolled according to recent NAEPP guidelines. Importantly, a greater percentage of patients with moderate asthma vs. severe persistent asthma were uncontrolled (p < 0.0114). Atopy was detected in 92% of patients. Patients with early onset of asthma were associated with control (p < 0.0433). Atopic symptoms, such as allergic rhinitis (p < 0.0130) and rhinosinusitis (p < 0.0476), were associated with uncontrolled asthma. Uncontrolled patients were also associated with more medications (a mean of 4.05 +/- 1.87 medications) than were controlled patients (a mean of 3.40 +/- 1.37 medications (p < 0.0001), although the temporal relationship of this association was not recorded. Limitations may have included patient and/or study site selection bias and difficulty in the process of operationalizing the definitions of control and disease severity. Since the current study only examined patients from specialty practices, the results may not be generalizable to the overall asthma population. CONCLUSIONS: Greater than 80% of asthma patients from specialty practices were uncontrolled with regard to asthma symptoms. Atopic symptoms, such as allergic rhinitis and rhinosinusitis, in addition to a greater number of medications, were associated with uncontrolled asthma. Moreover, patients designated as having asthma of moderate severity were associated with being uncontrolled more than were those with severe asthma (p < 0.0114), which suggests that the former population may not have received adequate assessment of impairment or risk, with subsequent changes in treatment for control of symptoms.