Clinical Outcomes in Measurement-based Treatment (Comet): a trial of depression monitoring and feedback to primary care physicians.

BACKGROUND: Despite the availability of effective treatments for depression, many patients under the care of primary care physicians do not achieve remission. Clinical Outcomes in Measurement-based Treatment (COMET) was designed to assess whether communicating patient-reported depression symptom severity to primary care physicians affects patient outcomes at 6 months. METHODS: Nine hundred fifteen patients (intervention: n = 503; control: n = 412) diagnosed with major depressive disorder were enrolled in a prospective trial in which physician practice sites were assigned to either the intervention or control study arm. Only patients who were prescribed an antidepressant by their physician were eligible, but medication type was independent of the study protocol. Intervention-arm physicians received monthly updates on their patients' depression severity, which was determined with the nine-item Patient Health Questionnaire (PHQ-9) administered during telephone interviews. Remission was defined as a PHQ-9 score <5 at 6 months; response was defined as a score reduction ≥50%. RESULTS: Among patients with baseline PHQ-9 score ≥5, 45.0% achieved remission (46.7% intervention versus 42.8% control) and 63.9% responded (67.0% intervention versus 59.7% control) at 6 months. After adjusting for baseline demographic and clinical variables, odds of remission (odds ratio [OR], 1.59 [95% CI, 1.07-2.37]) or response (OR, 2.02 [95% CI, 1.36-3.02]) were significantly greater for the intervention group than for control patients. CONCLUSIONS: This study demonstrated that regular patient symptom monitoring with feedback to physicians improved outcomes of depression treatment in the primary care setting. Determining reasons for the high observed nonremission rates requires further investigation.

Patient-reported outcomes of dual bronchodilator fixed-dose combination versus bronchodilator monotherapy in individuals with COPD.

Background: This study compared real-world patient-reported outcomes (PROs) measured by the Clinical COPD Questionnaire (CCQ), the London Chest Activities of Daily Living (LCADL) scale, and the Work Productivity and Activity Impairment (WPAI) questionnaire between individuals with COPD initiating LAMA/LABA fixed-dose combination (FDC) dual therapy versus either long-acting muscarinic antagonist (LAMA) or long-acting beta2-agonist (LABA) monotherapy. Methods: Individuals with COPD aged ≥40 years initiating a LAMA/LABA FDC dual therapy or a LAMA or LABA monotherapy (index date = first prescription date) between January 1, 2016 and December 31, 2016 were identified from a large US administrative claims database. Individuals were excluded if they were prescribed an inhaled corticosteroid (ICS) or ICS/LABA two months prior to the index date or were diagnosed with cystic fibrosis, idiopathic pulmonary fibrosis, or asthma. The cohorts were propensity score matched (PSM) 1:1 for COPD severity using baseline measures. Each participant completed a survey. Results: Surveys were completed by 399 participants in the dual therapy cohort, and 718 participants in the monotherapy cohort. Following PSM, 379 participants remained in each cohort for analysis (monotherapy: 369 LAMA and 10 LABA). The dual therapy cohort reported fewer COPD-related symptoms (CCQ symptom score 2.75 vs 2.97, respectively, P=0.023), and, fewer limitations in leisure activities (LCADL leisure score 4.78 vs 5.17, respectively, P=0.021) versus the monotherapy cohort. No significant differences were found in the WPAI. A greater percentage of participants in the dual therapy cohort stayed on index therapy (63.1%) when compared with the monotherapy cohort (30.3%, P<0.0001). Conclusions: Only 30% of the participants prescribed monotherapy, usually with a LAMA, remained on index therapy alone at the time of survey administration. In the dual therapy cohort, 63% of the participants remained on the index medication and had fewer COPD-related symptoms and fewer limitations in leisure activities compared with participants in the monotherapy cohort.

A Retrospective Claims Analysis of Dual Bronchodilator Fixed-Dose Combination Versus Bronchodilator Monotherapy in Patients with Chronic Obstructive Pulmonary Disease.

INTRODUCTION: Patients with chronic obstructive pulmonary disease (COPD) increasingly receive combination bronchodilator therapies. Real world evidence for the benefits of combination therapy compared to monotherapy is lacking. METHODS: COPD patients aged ≥ 40 years initiating monotherapy (MT) with either a long-acting muscarinic antagonist (LAMA) or long-acting beta2-agonist (LABA) or dual therapy (DT) with a LAMA/LABA fixed dose combination (FDC) between January 1, 2016 and December 31, 2016 were identified from a large U.S. administrative claims database. Patients diagnosed with cystic fibrosis, idiopathic pulmonary fibrosis, or asthma were excluded. Cohorts were propensity score matched 1:1 using baseline measures (e.g., exacerbations, hospitalizations) as proxies for COPD severity to create balanced cohorts. RESULTS: Following propensity score matching (PSM), 1286 patients remained in each cohort for analysis. Patients were followed for approximately 1 year. Patients in the DT versus MT cohort had lower rates of exacerbations leading to hospitalization (incidence rate ratio 0.7886; p=0.019), lower mean COPD-related pharmacy costs per patient per month (PPPM) ($300 versus $379, respectively; p<0.001) and total costs PPPM ($990 versus $1203, respectively; p=0.003). This occurred despite lower mean COPD-related pharmacy fills PPPM in the DT versus MT cohorts (1.41 versus 1.51, respectively; p=0.038). Patients in the DT cohort had lower rates of switching (p<0.001) and augmentation (p<0.001), and higher rates of non-persistence (p<0.001) versus the MT cohort. Rates of discontinuation were similar. CONCLUSIONS: Patients in the DT cohort had lower rates of exacerbations leading to hospitalization, lower COPD-related pharmacy and total costs PPPM, and lower rates of switching and augmentation compared to patients in the MT cohort.

Methodological challenges in assessing the impact of comorbidities on costs in Alzheimer's disease clinical trials.

BACKGROUND: Alzheimer's disease (AD) is associated with considerable costs and has a significant impact on health and social care systems. OBJECTIVE: This study assessed whether baseline comorbidities present in 2,594 patients with AD participating in two semagacestat randomized placebo-controlled trials (RCTs) would significantly impact overall costs. METHODS: Resource utilization was captured using the Resource Utilization in Dementia Scale-Lite. Comorbidities and concomitant medications were tabulated via patient and caregiver reports. Only baseline data were analyzed. Direct and indirect costs per month were calculated per patient. The relationship between cost and explanatory variables was explored in a regression model. RESULTS: The baseline monthly cost of care in this RCT population was £1,147 ± 2,483, with informal care costs accounting for 75% of costs. Gender, age, and functional status were significant predictors of costs (p ≤ 0.0001). The cost ratio was not impacted when the number of comorbidities was added to the model (cost ratio = 0.95; 95% CI 0.91-0.99) or when combined with the number of concomitant medications (cost ratio = 0.97; 95% CI 0.95-1.00). Inconsistent findings related to the impact of individual comorbidities on costs were noted in sensitivity analyses. CONCLUSIONS: The number of comorbidities, alone or when combined with concomitant medications, did not impact baseline costs of care, perhaps because RCTs often enroll less severely ill and more medically stable patients. However, higher costs were consistently associated with greater functional impairment similar to non-RCT databases. Supplemental sources (e.g., claims databases) are likely needed to better estimate the effects of disease and treatment on costs of illness captured in RCTs for AD.

Association Between Cognitive Function and Health Care Costs 3 Months and 6 Months After Initiating Antidepressant Medication for Depressive Disorders.

BACKGROUND: Major depressive disorder is one of the most common and disabling mental health disorders and is associated with substantial costs in terms of direct health care utilization and workplace productivity. Cognitive dysfunction, which alone substantially increases health care costs, is commonly associated with major depressive disorder. However, the health care costs of cognitive dysfunction in the context of depressive disorder are unknown. Recovery from mood symptoms is not always associated with resolution of cognitive dysfunction. Thus, cognitive dysfunction may contribute to health care burden even with successful antidepressant therapy.  OBJECTIVE: To compare health care utilization and costs for patients with a depressive disorder with and without cognitive dysfunction, at 3 and 6 months after initiation of antidepressant medication.  METHODS: This was an observational study, combining a cross-sectional patient survey, administered during a telephone interview, with health care claims data from a large, geographically diverse U.S. health plan. Included patients had at least 1 pharmacy claim for an antidepressant medication between August 1 and September 30, 2012, and no claim for any antidepressant during the 6 months prior to the index date. In addition to other criteria assessed in the claims data, patients confirmed a diagnosis of depression or major depressive disorder and the absence of any exclusionary neurological diagnoses possibly associated with cognitive impairment. Eligible patients were administered validated cognitive function assessments of verbal episodic memory (Hopkins Verbal Learning Test-Revised, Delayed and Total); attention (Digit Span Forward Maximum Sequence Length); working memory (Digit Span Backward Maximum Sequence Length); and executive function (D-KEFS-Letter Fluency Test). Based on comparison of scores with normative data, patients were assigned to cognitive dysfunction or cognitive normal cohorts. All-cause (all diagnoses) and depressive disorder-related health care utilization and costs (all from a payer perspective) were assessed 6 months prior (baseline) to antidepressant initiation and 3 months and 6 months after (follow-up) initiation of antidepressant medication. Health care utilization and costs included ambulatory (office and hospital outpatient), emergency room, inpatient hospital, pharmacy, other medical (e.g., laboratory and diagnostics), and total (all categories combined). All-cause and depressive disorder-related total costs during the 3- and 6-month follow-up periods were modeled with generalized linear modeling with gamma distribution and log link, while adjusting for potential confounders (age, race, gender, education, employment, and comorbidities). RESULTS: Of the 13,537 patients who were mailed an invitation, 824 (6%) were eligible and agreed to participate. Of these, 563 patients provided informed consent, completed the interview, maintained eligibility, and were included in the 3-month calculations. Among these, 255 (45%) were classified as having cognitive dysfunction. Mean patient age was 41.3 (± 12.5) years; 80% were female. Most patients were white and employed. More patients in the cognitive normal cohort were white (P less than 0.001) and employed full time (P = 0.029), had higher education attainment (P less than 0.001), and had fewer comorbidities (P = 0.007) than those in the cognitive dysfunction cohort. Over the first 3 months, patients with cognitive dysfunction had higher adjusted all-cause costs ($3,309 vs. $2,157, P = 0.002) and higher adjusted depressive disorder-related costs ($718 vs. $406, P less than 0.001) than patients without cognitive dysfunction. At 6 months, data from 4 patients were removed from the analysis because of exclusionary diagnoses. Over 6 months, patients with cognitive dysfunction had higher adjusted all-cause costs ($4,793) than patients without cognitive dysfunction ($3,683, P = 0.034). Over 6 months, depressive disorder-related costs did not significantly differ between patients with ($771) and without cognitive dysfunction ($594, P = 0.071). The main drivers of all-cause costs were office visits, outpatient hospital visits, and inpatient costs, and the main driver of depressive disorder-related costs was inpatient costs. CONCLUSIONS: Cognitive dysfunction was associated with higher adjusted all-cause and depressive disorder-related costs 3 months after initiation of an antidepressant medication. This difference persisted for all-cause costs through 6 months. Identification and treatment of cognitive dysfunction in patients with depressive disorder might reduce health care costs.

A simple rule to identify patients with chronic obstructive pulmonary disease who may need treatment reevaluation.

BACKGROUND: A simple rule based on short-acting inhaled ß2-agonist (SABA) use could identify patients with chronic obstructive pulmonary disease (COPD) at increased risk of exacerbations and signal the need for maintenance therapy change, similar to asthma "Rules of Two(®)". METHODS: Associations between SABA use, COPD exacerbations, and health care costs over 1 year were examined retrospectively using de-identified patient data from the Optum Research Database (ORD; N = 56,581) and the Impact National Benchmark Database (IMPACT™; N = 9423). Nebulized and metered-dose inhaler (MDI) SABA doses were normalized to 2.5 mg and 90 mcg albuterol equivalents, respectively. RESULTS: The GOLD initiative establishes ≥2 exacerbations/year as indicative of increased risk in COPD. We identified a correlation (p < 0.0001) between 1.5 SABA doses/day and this frequency of exacerbations. In ORD, patients using ≥1.5 versus <1.5 SABA doses/day experienced significantly more exacerbations: 1.92 (95% confidence interval [CI], 1.89-1.96) versus 1.36 (95% CI, 1.34-1.38) per patient year (PPY). Above-threshold use was associated with higher average annual COPD-related costs (2010 $US): $21,868 (standard deviation [SD], $53,910) versus $11,686 (SD, $32,707) for nebulized SABA only, $9216 (SD, $30,710) versus $7334 (SD, $24,853) for MDI SABA only, and $15,806 (SD, $35,260) versus $11,233 (SD, $27,006) for both nebulized and MDI SABA. IMPACT™ validated these findings. CONCLUSION: Patients with COPD using ≥1.5 SABA doses/day were at increased risk of exacerbations. Our results suggest a "Rule of 3-2": SABA use ≥3 times in 2 days should be considered a clinical marker for needing treatment reevaluation.

Depression monitoring and patient behavior in the Clinical Outcomes in MEasurement-Based Treatment (COMET) trial.

OBJECTIVE: In this secondary analysis of results of the Clinical Outcomes in MEasurement-Based Treatment (COMET) trial, patient behaviors that might account for the differences observed in clinical outcomes were examined. METHODS: Patients (N=914) diagnosed as having major depressive disorder participated in telephone interviews either monthly for six months (intervention) or at three and six months (usual care) asking about antidepressant medication-taking, use of psychotherapy or counseling, and participation in depression support groups. Physicians (N=83) in the intervention arm received monthly feedback regarding their patients' depression severity. RESULTS: A total of 664 (73%) patients completed the month 6 interview. The adjusted odds of current antidepressant use at six months were 85% greater (p=.01) for patients in the intervention (N=380) versus usual care (N=284) arms, according to multivariate regression analyses. CONCLUSIONS: More frequent measurement of depression symptoms was associated with greater medication persistence, which in turn may have mediated clinical improvements.

Effect of communicating depression severity on physician prescribing patterns: findings from the Clinical Outcomes in MEasurement-based Treatment (COMET) trial.

OBJECTIVE: In this secondary analysis from the Clinical Outcomes in MEasurement-based Treatment trial (COMET), we evaluated whether providing primary care physicians with patient-reported feedback regarding depression severity affected pharmacological treatment patterns. METHOD: Intervention-arm physicians received their patients' 9-item Patient Health Questionnaire scores monthly. Odds of having no change in antidepressant treatment during the 6-month study period were calculated. Relationships between depression symptom status (partial or nonresponse) at month 3 and treatment changes in months 3 through 6 were assessed. RESULTS: Among 503 intervention and 412 usual care (UC) patients with major depressive disorder, most received antidepressant monotherapy at baseline (79.4% UC vs. 88.4% intervention; P=.047). Few switched their baseline antidepressant (17.4%), increased their dose (12.4%) or augmented with a second medication (2%). Odds of having no change in antidepressant therapy did not differ significantly between study arms (odds ratio 1.21; 95% confidence interval 0.78-1.88; P=.392). Few month 3 partial or nonresponders had a regimen change over the following 3 months; the study arms did not differ significantly (partial responders: 4.1% UC vs. 7.7% intervention; P=.429; nonresponders: 14.6% UC vs. 15.9% intervention; P=.888). CONCLUSIONS: Among depressed patients treated in primary care, little active management was observed. The lack of treatment modification for the majority of partial and nonresponders was notable.