Frequency and costs of pulmonary exacerbations in patients with cystic fibrosis in the United States.

BACKGROUND: Information is limited regarding the cost of pulmonary exacerbations (PEx) among patients with cystic fibrosis in the United States. METHODS: To examine PEx costs, medical chart data were linked to insurance claims for patients aged ≥6 years who had commercial coverage from a large US health insurer affiliated with Optum during 2008-2013. A PEx was categorized as an episode requiring newly started (1) oral antibiotics (PEx-O) or (2) intravenous (IV) antibiotics and/or inpatient stay (PEx-IV). RESULTS: Among 241 patients, 88.0% had ≥1 PEx (2.9/year) of any type, and 48.1% had ≥1 PEx-IV. Prior PEx-IV was the strongest risk factor for subsequent PEx-IV. The mean cost per episode was $12,784 for PEx of any type and $36,319 for PEx-IV. Patients with worse lung function were more likely to experience a PEx and incurred higher annual PEx-related costs. LIMITATIONS: This was an observational study using a convenience sample of patients with commercial coverage from a large US health insurer whose medical charts were available for abstraction. Results of the study may not be generalizable to individuals with Medicaid coverage and other types of insurance, or to the uninsured. CONCLUSIONS: Most patients experience ≥1 PEx annually, and nearly half require IV antibiotics and/or inpatient stay at considerable cost.

Cystic fibrosis in young children: A review of disease manifestation, progression, and response to early treatment.

BACKGROUND: Studies have described illness associated with cystic fibrosis (CF) early in life, but there is no comprehensive accounting of the prevalence and ages of disease manifestation and progression described in individual studies. METHODS: We searched for peer-reviewed English-language studies of the health of children ≤6years old with CF (published 1990-2014). Structural abnormalities and dysfunction of the digestive and respiratory systems were summarized across relevant studies by system and age group. RESULTS: Primary studies (125 total) from 22 countries described abnormalities, dysfunction, and disease progression in infancy and early childhood. Improved health was consistently observed in association with diagnosis via newborn screening compared with cohorts diagnosed later by symptomatic presentation. CONCLUSIONS: The peer-reviewed literature is remarkably consistent: CF-associated growth impairment and airway abnormalities are reported at birth, and disease progression is reported in infancy and throughout childhood. Earlier access to routine CF management is associated with improved subsequent health status.

Matching-adjusted indirect comparisons: a new tool for timely comparative effectiveness research.

OBJECTIVE: In the absence of head-to-head randomized trials, indirect comparisons of treatments across separate trials can be performed. However, these analyses may be biased by cross-trial differences in patient populations, sensitivity to modeling assumptions, and differences in the definitions of outcome measures. The objective of this study was to demonstrate how incorporating individual patient data (IPD) from trials of one treatment into indirect comparisons can address several limitations that arise in analyses based only on aggregate data. METHODS: Matching-adjusted indirect comparisons (MAICs) use IPD from trials of one treatment to match baseline summary statistics reported from trials of another treatment. After matching, by using an approach similar to propensity score weighting, treatment outcomes are compared across balanced trial populations. This method is illustrated by reviewing published MAICs in different therapeutic areas. A novel analysis in attention deficit/hyperactivity disorder further demonstrates the applicability of the method. The strengths and limitations of MAICs are discussed in comparison to those of indirect comparisons that use only published aggregate data. RESULTS: Example applications were selected to illustrate how indirect comparisons based only on aggregate data can be limited by cross-trial differences in patient populations, differences in the definitions of outcome measures, and sensitivity to modeling assumptions. The use of IPD and MAIC is shown to address these limitations in the selected examples by reducing or removing the observed cross-trial differences. An important assumption of MAIC, as in any comparison of nonrandomized treatment groups, is that there are no unobserved cross-trial differences that could confound the comparison of outcomes. CONCLUSIONS: Indirect treatment comparisons can be limited by cross-trial differences. By combining IPD with published aggregate data, MAIC can reduce observed cross-trial differences and provide decision makers with timely comparative evidence.

Treatment patterns, adherence, and persistence in ADHD: a Canadian perspective.

OBJECTIVE: To understand attention-deficit/hyperactivity disorder (ADHD) treatment patterns and estimate adherence and persistence in Quebec, Canada. DESIGN: This cross-sectional, retrospective prescription claims analysis used a random sample of 15 838 patients with ADHD from a Quebec database (Régie de l'assurance maladie du Québec [RAMQ]) to assess treatment patterns, adherence (1-year medication possession ratio in new users), and persistence (proportion persistent at 3, 6, and 12 months after index prescription). RESULTS: The mean patient age was 14 years; 72.6% were male. During the 5-year study period (2004-2009), 416 646 ADHD prescriptions were filled. Short-acting (SA) medications declined from 72.8% to 26.4% of all claims, while stimulant and nonstimulant long-acting (LA) medications increased from 27.2% to 73.6%. Approximately half of the patients used both SA and LA medications (either concomitantly or subsequently), and the others used only SA (30%) or LA (19%) drugs. Among patients using both, switching from SA to LA was the most frequent (27.9%) treatment pattern. More patients on LA methylphenidates (6.4%) compared with LA amphetamines (1.9%; P < 0.01) required augmentation with an SA drug. Fewer patients on SA stimulants (39.4%) were ≥ 80% adherent compared with LA stimulants (63%; P < 0.001) and LA nonstimulants (60.2%; P < 0.001). More patients on LA stimulants (81.1%) were persistent at 12 months compared with LA nonstimulants (61.7%; P < 0.001) and SA stimulants (59.6%; P < 0.001). Similar trends were observed at all time points measured. CONCLUSIONS: Switching from SA to LA medications and treatment augmentation are common in ADHD management, with implications for patient care and health care resource use. This analysis found poor adherence in ADHD treatment, although adherence and persistence were improved with LA stimulant formulations.

Comparative effectiveness research using matching-adjusted indirect comparison: an application to treatment with guanfacine extended release or atomoxetine in children with attention-deficit/hyperactivity disorder and comorbid oppositional defiant disorder.

OBJECTIVES: To illustrate a matching-adjusted indirect comparison by comparing the efficacy of guanfacine extended release (GXR) and atomoxetine (ATX) in reducing oppositional symptoms in children with attention-deficit/hyperactivity disorder and comorbid oppositional defiant disorder. METHODS: Individual patient data were used from a GXR trial; only published summary data were used from ATX trials. In a matching-adjusted indirect comparison, individual patients from the GXR trial were weighted such that their mean baseline characteristics matched those published for ATX trials. Placebo-arm outcomes were then compared to further assess balance between the matched populations. Changes in the Conners' Parent Rating Scale-Revised Short Form Oppositional Subscale from baseline to endpoint among GXR-treated and ATX-treated patients were then compared. RESULTS: Before matching, the GXR (n = 143) and ATX (n = 98) trial populations had significant differences in baseline characteristics and placebo-arm outcomes. After matching, baseline characteristics were well balanced across trials, and placebo-arm outcomes became nearly identical. Comparing active treatment arms across the matched populations, GXR was associated with a significantly greater reduction in mean Conners' Parent Rating Scale-Revised Short form oppositional subscale compared with ATX {-5.0 [95% confidence interval (CI): -6.6 to -3.4] vs. -2.4 [CI: -3.7 to -1.1], p = 0.01, effect size = 0.58}. CONCLUSIONS: In the absence of head-to-head randomized trials, matching-adjusted indirect comparisons can provide timely and reliable comparative evidence for decision makers and can be applied even when very few trials are available for the treatments of interest.

Moderators and mediators of symptoms and quality of life outcomes in an open-label study of adults treated for attention-deficit/hyperactivity disorder.

OBJECTIVE: The Quality of Life, Effectiveness, Safety, and Tolerability (QU.E.S.T.) study was designed to evaluate effectiveness of long-acting amphetamines in adults with attention-deficit/hyperactivity disorder (ADHD) in community practice settings. This article reports moderators and mediators of symptoms and quality of life outcomes. METHOD: This was an open-label study of 725 adults with DSM-IV-diagnosed ADHD, treated with mixed amphetamine salts extended release and followed for up to 8 months. Multiple regressions were used to determine if patient moderators impact response in ADHD symptoms and how ADHD symptoms and medication satisfaction mediate quality of life. The study was conducted from December 2003 to December 2004. RESULTS: Amphetamine treatment of ADHD resulted in a robust and enduring symptom response. Patient characteristics such as age, female gender, severity of illness, and treatment-naive status moderate improved symptom outcome. Symptom change and satisfaction with medication independently mediate change in mental but not physical quality of life outcomes. There is no time lag between changes in symptoms and improved quality of life. Attention is a stronger mediator of ADHD-specific quality of life outcomes than disruptive behavior. CONCLUSIONS: If symptoms and quality of life improve simultaneously, improvement in quality of life can be understood as more than just a downstream, secondary effect of symptom remission. Satisfaction with medication is a direct measure of the complex interplay of symptom change, tolerability, and patient perception of treatment that predicts self-report of quality of life benefits. Although the disruptive symptoms of ADHD are more obvious, adults self-report that attention has greater impact.

ADHD-hyperactive/impulsive subtype in adults.

This is the first study to evaluate ADHD-hyperactive/impulsive subtype in a large clinical sample of adults with ADHD. The Quality of Life, Effectiveness, Safety and Tolerability (QuEST) study included 725 adults who received clinician diagnoses of any ADHD subtype. Cross-sectional baseline data from 691 patients diagnosed with the hyperactive/impulsive (HI), inattentive (IA) and combined subtypes were used to compare the groups on the clinician administered ADHD-RS, clinical features and health-related quality of life. A consistent pattern of differences was found between the ADHD-I and combined subtypes, with the combined subtype being more likely to be diagnosed in childhood, more severe symptom severity and lower HRQL. Twenty-three patients out of the total sample of 691 patients (3%) received a clinician diagnosis of ADHD-hyperactive/impulsive subtype. Review of the ratings on the ADHD-RS-IV demonstrated, however, that this group had ratings of inattention comparable to the inattentive group. There were no significant differences found between the ADHD-HI and the other subtypes in symptom severity, functioning or quality of life. The hyperactive/impulsive subtype group identified by clinicians in this study was not significantly different from the rest of the sample. By contrast, significant differences were found between the inattentive and combined types. This suggests that in adults, hyperactivity declines and inattention remains significant, making the hyperactive/impulsive subtype as defined by childhood criteria a very rare condition and raising questions as to the validity of the HI subtype in adults.