Influence of Treatment Intensification on A1c in Patients with Suboptimally Controlled Type 2 Diabetes After 2 Oral Antidiabetic Agents.

BACKGROUND: In the United States, more than 50% of patients with type 2 diabetes mellitus (T2DM) have hemoglobin A1c (A1c) levels that fail to achieve the recommended target of < 7.0%. Of these, 30%-45% have an A1c > 9.0%, the threshold for poorly controlled T2DM per National Committee for Quality Assurance (NCQA) measures. Treatment inertia is a known challenge. However, recent treatment intensification patterns and outcomes after treatment fails 2 classes of oral antidiabetic agents (OADs) are not well understood. OBJECTIVE: To characterize treatment intensification patterns and glycemic control outcomes in patients with A1c ≥ 7.0% on 2 OADs. METHODS: A retrospective cohort study was conducted in patients with T2DM from a regional health plan claims dataset augmented with A1c results between January 1, 2010, and March 31, 2017. Patients were identified with an A1c ≥ 7.0% (baseline), while on 2 OADs, and whose treatment was intensified with basal/biphasic insulin (insulin), glucagon-like peptide-1 receptor antagonist (GLP-1RA), or a third OAD within 365 days after the baseline A1c ≥ 7.0%. Patients had at least 1 A1c value 60-365 days (follow-up period) after treatment intensification. The proportion of patients with an A1c < 7.0% and < 9.0% at follow-up were identified by therapeutic intensification strategy. Odds ratios for achieving A1c < 7.0% and < 9.0% were calculated. RESULTS: 1,226 patients were included in the analysis, and 33.5% of the patients had a baseline A1c ≥ 9.0%. 24% of patients received insulin; 16% received GLP-1RA; and 60% received a third OAD for the treatment intensification. Overall, 26.0% achieved A1c < 7.0% and 76.1% of patients achieved < 9.0%, with a median follow-up of 119 days. The proportion of patients intensified with insulin who had an A1c ≥ 9.0% at follow-up was 34.6% versus 53.2% at baseline (P < 0.01). The corresponding percentages for those intensified with a GLP-1RA and OAD were 21.6% versus 27.1% (P = 0.24) and 20.1% versus 27.3% (P < 0.01). After controlling for baseline characteristics, the odds ratio (95% CI) of achieving A1c < 7.0% and < 9.0% was 2.05 (1.45-2.90) for GLP-1RA and 0.92 (0.61-1.40) for OAD. The association between goal attainment and GLP-1RA versus OAD intensification was influenced by the time to the A1c follow-up and baseline A1c. CONCLUSIONS: Treatment intensification was associated with improved glycemic control in patients after therapy failed 2 OADs. Patients with higher A1c at baseline were likely to initiate insulin, which was associated with a greater drop in A1c. GLP-1RA was associated with a higher likelihood of achieving NCQA-suggested glycemic control compared with a third OAD. However, the association varied by the follow-up period. These findings are important to health plans seeking to improve patient outcomes as reflected in high performance on NCQA diabetes quality measures by promoting effective and timely treatment intensification. DISCLOSURES: Research funding was provided by Sanofi to the Pharmacotherapy Outcomes Research Center at the University of Utah and SelectHealth to conduct this study. Thomas, Sterling, and Johnstone are employees and stock/shareholders of Sanofi. Kim, Unni, McAdam-Marx, and Brixner are employees of the Department of Pharmacotherapy at the University of Utah. Brixner also has served as an advisory board member and presenter for Sanofi. McAdam-Marx also reports grants to the Department of Pharmacotherapy, University of Utah, from AstraZeneca and Janssen, outside of the submitted work. Olsen is employed by SelectHealth. Part of the results of this study was presented at the Academy of Managed Care & Specialty Pharmacy Annual Meeting 2018 in Boston, MA, during April 23-26, 2018.

Achieve control: a pragmatic clinical trial of insulin glargine 300 U/mL versus other basal insulins in insulin-naïve patients with type 2 diabetes.

OBJECTIVE: This study aims to compare the effectiveness of insulin glargine 300 U/mL (Gla-300) with its accompanying patient support program with that of other basal insulin and available patient support programs in patients with type 2 diabetes (T2D) in a real-world setting in terms of achieving HEDIS (Healthcare Effectiveness Data and Information Set) individualized glycemic targets without documented symptomatic hypoglycemia. METHODS: Achieve Control is a US-based, multicenter, randomized, open-label, active-controlled, parallel group pragmatic Phase IV trial in insulin-naïve patients with T2D uncontrolled on ≥2 oral antidiabetes drugs (OAD) and/or glucagon-like peptide-1 receptor antagonists (GLP-1 RA). Inclusion criteria include a diagnosis of T2D, age ≥18 years, and glycated hemoglobin (HbA1c) between 8.0% and 11.0%. Patients will be assigned to either the Gla-300 or other basal insulin group. The primary end point is the proportion of patients achieving HEDIS HbA1c targets (<8.0% [64 mmol/mol] in patients with comorbidities or aged ≥65 years; <7.0% [58 mmol/mol] in all other patients) without occurrence of symptomatic hypoglycemia (blood glucose ≤70 mg/dL) from baseline to 6 months. Secondary end points include rates of documented symptomatic nocturnal hypoglycemia and severe hypoglycemia; change from baseline in HbA1c, fasting glucose, and body weight; treatment persistence; patient-reported outcomes; and healthcare resource utilization. Planned enrollment is 3270 patients across approximately 400 clinical sites. CONCLUSION: Pragmatic clinical trials offer the potential to assess comparative effectiveness in broadly based patient populations receiving care (with or without a corresponding educational support program) in real-world clinical settings. The results of Achieve Control should elucidate the benefits of management of T2D with Gla-300 versus other basal insulins in terms of patient outcomes, experiences, and perceptions, and its impact on healthcare resource utilization and cost. CLINICAL TRIAL REGISTRATION: www.clinicaltrials.gov identifier is NCT02451137.

Breast-feeding and cognitive development: a meta-analysis

Although the results of many clinical studies suggest that breast-fed children score higher on tests of cognitive function than do formula-fed children, some investigators have suggested that these differences are related to confounding covariables such as socioeconomic status or maternal education...

A practice-based research network focused on comparative effectiveness research in type 2 diabetes management.

PURPOSE: To establish a real-world research platform focused on comparative effectiveness research and health care decision making in diabetes care in order to obtain a detailed understanding of individualized patient management in primary care. METHODS: Diabetes FORWARD (Foundation of Real-World Assessment and Research in Diabetes) is a North American research platform being organized to conduct longitudinal, noninterventional investigations of an anticipated 10,000 patients with type 2 diabetes mellitus (T2DM). Recruitment will be stratified to reflect typical (primarily primary care) clinical T2DM populations. Streamlined data collection relying on electronic medical records (retrospective) and periodic surveys (prospective) will reduce the burden of study participation and, therefore, enhance enrollment by busy primary care and endocrinology practices. Physician data will include baseline demographic and practice information. Patient data will include demographics, T2DM characteristics and treatment, resource utilization information, and patient-reported outcomes. Responses can be tracked within the observation window in near-real time, allowing immediate, noninterventional reaction at the point of nonresponse. EXPECTED OUTCOMES: Diabetes FORWARD is expected to provide important real-world data describing how actual clinical T2DM management differs across sites, settings, and clinicians, and its impact on glycemic control, treatment adherence and persistence, and clinical outcomes. These data will also help to identify the effect of diabetes management on the onset and progression of retinopathy, neuropathy, nephropathy, and cardiovascular disease at 6-month intervals. CONCLUSION: To our knowledge, Diabetes FORWARD is the first diabetes-focused, practice-based research network in the United States and Canada. The current study will provide robust data that should reflect typical management of T2DM in clinical practice in North America.

Dosing patterns for duloxetine and predictors of high-dose prescriptions in patients with major depressive disorder: analysis from a United States third-party payer perspective.

BACKGROUND: Major depressive disorder (MDD) is a common illness that affects ∼7% of adults in the United States each year. Duloxetine is a dual reuptake inhibitor of serotonin and norepinephrine that has demonstrated efficacy and tolerability in the treatment of MDD. OBJECTIVE: The purpose of our study was to examine dosing patterns and pretreatment predictors of high-dose duloxetine therapy for patients with MDD in the usual clinical setting. METHODS: Data were from 6132 commercially insured patients with MDD initiated on duloxetine during 2005 and 2006. Patients had no duloxetine use in the previous 6 months and had continuous enrollment in a health plan for the 12 months immediately preceding and following initiation. Dosing patterns and predictors of high-dose therapy with duloxetine were examined. RESULTS: Initial doses of duloxetine were <60 mg/d, 60 mg/d, 90 mg/d, and ≥120 mg/d for 32.4%, 60.9%, 3.1%, and 3.5% of patients, respectively. Maximum daily doses were <60 mg, 60 mg, 90 mg, and ≥120 mg for 16.3%, 59.3%, 11.0%, and 13.3% of patients, respectively. Patients treated with >60 mg/d for at least 2 months were older, were more likely to have been treated by a psychiatrist, had greater comorbidity, and had used more health care resources and psychotropic and pain medications in the previous year. The following factors were independently associated with doses of >60 mg/d: older age (odds ratio [OR] = 1.33-1.46); comorbid neuropathic pain (OR = 1.88); fibromyalgia (OR = 1.36); dysthymic disorder (OR = 1.24); prior injury/poisoning (OR = 1.19); physician specialty (psychiatrist, OR = 1.55); and prior use of psychostimulants (OR = 1.26), benzodiazepines (OR = 1.19), venlafaxine (OR = 1.35), or atypical antipsychotics (OR = 1.35). CONCLUSIONS: Most of the commercially insured patients in this dataset were initiated and maintained on a duloxetine dose of 60 mg/d. Although the data are limited in their generalizability, the characteristics associated with higher dose therapy describe a complex group of patients who may require more intensive drug treatment and monitoring.

Real-world practice patterns, health-care utilization, and costs in patients with low back pain: the long road to guideline-concordant care.

BACKGROUND CONTEXT: Treatment guidelines suggest that most acute low back pain (LBP) episodes substantially improve within a few weeks and that immediate use of imaging and aggressive therapies should be avoided. PURPOSE: Assess the actual practice patterns of imaging, noninvasive therapy, medication use, and surgery in patients with LBP, and compare their costs to those of matched controls without LBP. STUDY DESIGN: A retrospective analysis of claims data from 40 self-insured employers in the United States. PATIENT SAMPLE: The study sample included 211,551 patients, aged 18 to 64 years, with one LBP diagnosis or more (per Healthcare Effectiveness Data and Information Set specification) during 2004 to 2006, identified from a claims database. Patients had continuous eligibility for 12 months or more after their index LBP diagnosis (study period), for 6 months or more before their index diagnosis (baseline period), and no other LBP diagnosis during the baseline period. Patients with LBP were matched to a random cohort of patients without LBP by age, gender, employment status, and index year. OUTCOMES MEASURES: Physiological measures (eg, imaging and diagnostic tests), functional measures (eg, pharmacologic and nonpharmacologic treatment for LBP, health-care resource use), and direct (medical and prescription drug) and indirect (disability and medically related absenteeism) costs were assessed within the year after the LBP diagnosis. METHODS: Univariate analyses described treatment patterns and compared baseline characteristics and study period costs. RESULTS: Patients with LBP had significantly higher rates of baseline comorbidities and resource use compared with controls. Of patients with LBP, 41.6% had imaging mean (median) [standard deviation] 34.3 (0) [78.6] days after the LBP diagnosis. Most patients with LBP (69.4%) used medications starting 51.9 (8) [86.2] days after the diagnosis. Opioids were commonly prescribed early (41.6% of patients; after 82.8 (25) [105.9] days). Of patients with LBP, 2.05% had surgery during the study period. Patients with LBP were likely to have chiropractic treatment first, followed by pharmacotherapy with muscle relaxants and nonsteroidal anti-inflammatory drugs. Except for less surgery, these findings also held for patients with only nonspecific LBP. Patients with LBP had higher mean direct costs compared with controls ($7,211 vs. $2,382, respectively; p<.0001), with surgery patients having mean direct costs of $33,931. CONCLUSIONS: Contrary to clinical guidelines, many patients with LBP start incurring significant resource use and associated expenses soon after the index diagnosis. Achieving guideline-concordant care will require substantial changes in LBP practice patterns.

Antipsychotic medication use patterns and associated costs of care for individuals with schizophrenia.

BACKGROUND: Schizophrenia is a costly and complicated disorder to treat. A variety of schizophrenia treatment guidelines have been developed to provide valuable expert advice to practicing psychiatrists on various treatment options that are presumed to result in the best outcomes. However, examination of antipsychotic medication use patterns has suggested that current prescribing practices do not mirror recommended treatment guidelines and may have adverse economic consequences. AIM OF THE STUDY: This study seeks to describe antipsychotic medication treatment patterns and estimate the total costs of care associated with treatment patterns for individuals diagnosed with schizophrenia in usual care settings. METHODS: Use of outpatient antipsychotic medications and other health services during 1997 was obtained for 2,082 individuals with a diagnosis of schizophrenia in the IMS Health LifeLink employer claims database. We describe outpatient antipsychotic treatment patterns, estimated the costs of schizophrenia care by treatment pattern, and compared costs by treatment pattern using regression models. RESULTS: During 1997, 26% (n=536) of individuals diagnosed with schizophrenia received no antipsychotic medication in the outpatient setting, while 52% (n=1,088) were treated with only one antipsychotic (Monotherapy). For individuals who received more than one antipsychotic medication during 1997 (n=458), 13% (n=262) switched antipsychotic medications (Switch), 7% (n=154) augmented their original antipsychotic therapy with an additional antipsychotic (Augment), and 2% (n=42) of individuals were on more than one antipsychotic therapy at the start of the year. After adjusting for covariates, Switch and Augment patterns were associated with significant increases in total costs (an increase of 4,706 dollars (p<0.0001) and 4,244 dollars (p=0.0002), respectively) relative to Monotherapy. DISCUSSION: These results indicate that a substantial proportion of individuals with a diagnosis of schizophrenia were not treated with or had low exposure to antipsychotic therapy. Individuals treated with antipsychotic monotherapy experienced nearly half the annual costs as individuals who were treated with antipsychotic polytherapy or who switched antipsychotic medications. These observations should be interpreted in the context of the study limitations. IMPLICATIONS FOR HEALTH CARE PROVISION AND USE: This analysis indicates that there may be considerable room for improvement in the treatment for individuals diagnosed with schizophrenia. IMPLICATIONS FOR HEALTH POLICIES: Though schizophrenia affects a very small portion of the population, the individual and societal burden associated with the disorder is quite high. This paper suggests that antipsychotic monotherapy and continuous therapy, commonly recommended by published treatment guidelines, may be associated with economic savings. IMPLICATIONS FOR FURTHER RESEARCH: Future research should evaluate the impact of newer antipsychotic medications on patterns of care and economic outcomes. More information is also needed on which individual patient characteristics are likely to predict success or failure on specific treatments. Finally, more detailed information on the reasons or rationale for switching or augmenting original pharmacotherapy would be valuable in improving medication management in these complex and often difficult to treat patients.

The Schizophrenia Care and Assessment Program Health Questionnaire (SCAP-HQ): an instrument to assess outcomes of schizophrenia care.

Advances in treatment technologies and development of evidence-based standards of care demand better methods for routine assessment of outcomes for schizophrenia in systems of care. This article describes the development and psychometrics of a new instrument to assess outcomes of routine care for persons with schizophrenia in service systems. Candidate items for the Schizophrenia Care and Assessment Program Health Questionnaire (SCAP-HQ) were drawn from existing measures. Domains covered include disease outcomes (symptoms, subjective medication effects, substance abuse), functional status, health status, quality of life, and public safety. A sample of 1,584 patients with schizophrenia or schizoaffective disorder who were recruited into a large prospective, naturalistic study on the course of treatment for schizophrenia completed the SCAP-HQ at baseline and 1 year later (n = 434), providing data for factor analysis, assessment of internal consistency, convergent validity, and responsiveness to change. A subsample of 121 patients completed a test-retest protocol. Fifteen scales were derived by factor analysis from 55 outcome items on the SCAP-HQ. These factors covered psychiatric symptoms, life satisfaction, instrumental activities of daily living, health-related disability, subjective medication side effects, vitality, legal problems, social relations, mental health-related disability, suicidality, drug and alcohol use, daily activities, victimization, violence, and employment. For most scales, standard psychometric parameters, including internal consistency and test-retest reliability, convergent validity, and responsiveness to change, were acceptable for application to large sample evaluations of care systems. This new measure represents an advance in the development of outcome measures for schizophrenia for use in large-scale studies of routine care.