Jeff J. Guo

A Process for Measuring the Quality of Cancer Care: The Quality Oncology Practice Initiative

PURPOSE The Quality Oncology Practice Initiative (QOPI) is a practice-based system of quality self-assessment sponsored by the participants and the American Society of Clinical Oncology (ASCO). The process of quality evaluation, development of the pilot questionnaire, and preliminary results are reported. METHODS Physicians from seven oncology groups developed medical record abstraction measures based on practice guidelines and consensus-supported indicators of quality care. Each practice completed two rounds of records review and received practice and aggregate results. Mean frequencies of responses for each indicator were compared among practices. RESULTS Participants universally, if informally, find QOPI helpful, and results show statistically significant variation among practices for several indicators, including assessing pain in patients close to death, documentation of informed consent for chemotherapy, and concordance with granulocytic and erythroid growth factor administration guidelines. Measures with universally high concordance include the use of serotonin antagonist antiemetics according to the ASCO guideline; the presence of a pathology report in the record; the use of chemotherapy flow sheets; and adherence to standard chemotherapy recommendations for patients with certain stages of breast, colon, and rectal cancer. Concordance with quality indicators significantly changed between survey rounds for several measures. CONCLUSION Pilot results indicate that the QOPI process provides a rapid and objective measurement of practice quality that allows comparisons among practices and over time. It also provides a mechanism for measuring concordance with published guidelines. Most importantly, it provides a tool for practice self-examination that can promote excellence in cancer care.

A Review of Quantitative Risk–Benefit Methodologies for Assessing Drug Safety and Efficacy—Report of the ISPOR Risk–Benefit Management Working Group

OBJECTIVE Although regulatory authorities evaluate the risks and benefits of any new drug therapy during the new drug-approval process, quantitative risk-benefit assessment (RBA) is not typically performed, nor is it presented in a consistent and integrated framework when it is used. Our purpose is to identify and describe published quantitative RBA methods for pharmaceuticals. METHODS Using MEDLINE and other Internet-based search engines, a systematic literature review was performed to identify quantitative methodologies for RBA. These distinct RBA approaches were summarized to highlight the implications of their differences for the pharmaceutical industry and regulatory agencies. RESULTS Theoretical models, parameters, and key features were reviewed and compared for the 12 quantitative RBA methods identified in the literature, including the Quantitative Framework for Risk and Benefit Assessment, benefit-less-risk analysis, the quality-adjusted time without symptoms and toxicity, number needed to treat (NNT), and number needed to harm and their relative-value-adjusted versions, minimum clinical efficacy, incremental net health benefit, the risk-benefit plane (RBP), the probabilistic simulation method, multicriteria decision analysis (MCDA), the risk-benefit contour (RBC), and the stated preference method (SPM). Whereas some approaches (e.g., NNT) rely on subjective weighting schemes or nonstatistical assessments, other methods (e.g., RBP, MCDA, RBC, and SPM) assess joint distributions of benefit and risk. CONCLUSIONS Several quantitative RBA methods are available that could be used to help lessen concern over subjective drug assessments and to help guide authorities toward more objective and transparent decision-making. When evaluating a new drug therapy, we recommend the use of multiple RBA approaches across different therapeutic indications and treatment populations in order to bound the risk-benefit profile.

Treatment Effects of Antidepressants in Patients with Post-Stroke Depression: A Meta-Analysis

Background: Appropriate treatment of post-stroke depression (PSD) is critically important, considering the negative impact of PSD. Data regarding the treatment efficacy of antidepressants in patients with PSD are conflicting, and the time-dependent effects of antidepressant treatment in this population are unknown. Objective: To systematically assess treatment effects of antidepressants in patients with PSD, incorporating data from recent studies. Methods: A meta-analysis of randomized placebo-controlled trials (RCTs) of antidepressants in patients with PSD was conducted, using published studies from 1984 to 2006. Outcome measures of antidepressant treatment included response rate, depression rating scale scores, recovery of neurologic impairments, and improvements in activities of daily living (ADLs) after stroke. The effect size was presented as rate difference (RD) and weighted mean difference for dichotomous outcomes and continuous outcomes, respectively. Pooled effect sizes were calculated by both fixed-effects and random-effects models. Results: A total of 1320 patients who met inclusion criteria were identified from 16 RCTs. The pooled response rates in the active and placebo groups were 65.18% (234/359) and 44.37% (138/311), respectively. The pooled RD was 0.23 (95% CI 0.03 to 0.43), indicating a significantly higher response rate in the active group compared with the placebo group. From baseline to endpoint, patients in the active group had significantly greater improvement in depressive symptoms compared with patients in the placebo group. Longer duration of treatment was positively correlated with the degree of improvement in depressive symptoms (Spearmans correlation, [ρ] = -0.93, p = 0.001). No consistent evidence was found for positive antidepressant effects on the recovery of neurologic impairments and improvements in ADLs. Conclusions: The results of this meta-analysis suggest that use of antidepressants among patients with a diagnosis of PSD is associated with improvement in depressive symptoms. Longer durations of antidepressant treatment may be associated with greater reductions in depressive symptoms.

Risk of Cerebrovascular Events Associated with Antidepressant Use in Patients with Depression: A Population-Based, Nested Case-Control Study:

Background: Given the widespread use of antidepressants and the negative consequence of cerebrovascular events (CVEs), an evaluation of the risk of CVEs associated with antidepressants is warranted. Objective: To examine the association between the use of an antidepressant and risk of CVEs among patients diagnosed with depression. Methods: A case-control study was performed using a managed care medical claims database from 1998 through 2002. A total of 1086 cases with CVEs were identified and matched with 6515 controls by age, sex, and the year ol the index date of depression Case patients were categorized by stroke type: hemorrhagic stroke, ischemic stroke, and other CVEs. Diagnoses of depression, CVEs, and other medical comorbidities were identified based on International Classification of Diseases, Ninth Revision, codes. Patients were defined as current users (antidepressant ended ≤30 days before CVE). recent users (31–60 days before CVE), past users {61–90 days before CVE), and remote/nonusers (≥91 days before CVE or nonuse). Cox proportional hazards regression analysis was conducted to estimate the risk of CVEs associated with antidepressant use. Results: A 24% increased risk of a CVE was noted in patients with current exposure to selective serotonin-reuptake inhibitors (SSRIs; adjusted hazard ratio [HR) 1.24; 95% CI 1.07 to 1.44), 34% increased risk for current exposure to tricyclic antidepressants (HR 1.34; 95% CI 1.10 to 1.62), and 43% increased risk for current exposure toother antidepressants (HR 1.43; 95% CI 1.21 to 1.69). The risk of ischemic stroke in current SSRI users was significantly higher (HR 1.55; 95% CI 1.00 to 2.39) compared with remote/nonusers. Conclusions: Current users of antidepressants may be at increased risk of a CVE. Clinicians should consider the relationship of antidepressants with the occurrence of CVEs when determining the risk-benefit profile of pharmacologic treatment in patients with depression, particularly those with existing risk factors for a CVE.

Antidepressant prophylaxis for poststroke depression: a meta-analysis.

Given the high incidence of poststroke depression, its serious sequelae, and inherent problems with diagnosis, prophylactic use of antidepressants may be a viable management strategy in patients experiencing stroke. The purpose of this study was to assess the prophylactic effects of antidepressants in nondepressed patients with stroke. A meta-analysis of randomized placebo-controlled trials evaluating the prophylactic effects of antidepressants in nondepressed patients with stroke was conducted. Literature searches in MEDLINE, PubMed, CINAHL, PsycINFO, EMBASE, Cochrane library, and CNKI from 1950 to August 2006 were used to identify the relevant studies. Outcome measures included the occurrence rate of newly developed poststroke depression cases and severity of depressive symptoms as indicated by mean depression rating scale scores. The effect size was presented as rate difference or weighted mean difference. From 10 randomized clinical trials, a total of 703 nondepressed patients after stroke were identified. The pooled occurrence rate of newly developed poststroke depression cases in the intervention and control groups were 12.54 (41/327) and 29.17% (91/312), respectively (pooled rate difference=−0.17, 95% confidence interval: −0.26 to −0.08). Prophylactic effects of antidepressants were not related to duration of use {coefficient of Pearsons correlation [&ggr;]=0.57, P=0.11}. In conclusion, antidepressant prophylaxis is associated with a significant reduction in the occurrence rate of newly developed poststroke depression, suggesting antidepressants may be considered along with other vascular preventive strategies in the management of stroke patients.

Utilization, price, and spending trends for antidepressants in the US Medicaid Program

BACKGROUND Antidepressants are often used in the treatment of major depressive disorder and other mental illnesses, and constitute one of the most widely prescribed and costly medication classes in the US Medicaid Program. However, antidepressant utilization and price patterns within this market have not yet been adequately characterized. OBJECTIVES This study was undertaken to analyze antidepressant drug utilization and price trends and to quantify market-share competition in Medicaid. METHODS Quarterly utilization and payment data were retrieved from the national Medicaid pharmacy claims files provided by the Centers for Medicare & Medicaid Services. Quarterly per-prescription prices were estimated by dividing the payment amounts by the number of prescriptions. Descriptive time series analysis was conducted to assess the trends of utilization, expenditures, market shares, and prices from January 1991 through December 2005, for 3 major antidepressant subclasses--Selective Serotonin Reuptake Inhibitors (SSRIs), Tricyclic Antidepressants, and Other Antidepressants--as well as for individual agents within these subclasses. Using exponential smoothing models, 3-year market-share forecasts were produced. RESULTS From 1991 to 2005, the total number of antidepressant prescriptions rose 380% from 6.82 million to 32.72 million. Total expenditures on antidepressants increased from

Type 2 Diabetes Mellitus in Youth Exposed to Antipsychotics: A Systematic Review and Meta-analysis

159 million in 1991 to

Access and Utilization Patterns of School-Based Health Centers at Urban and Rural Elementary and Middle Schools

2.26 billion in 2004, then decreased to

Risk of diabetes mellitus associated with atypical antipsychotic use among Medicaid patients with bipolar disorder: a nested case-control study.

1.99 billion in 2005, following the entry of lower-priced generic fluoxetine in 2001 and generic paroxetine in 2003. The payment market share for the SSRIs increased from 40% in 1991 to 82% in 1997, then decreased to 64% in 2005. It is projected to be 64% (95% confidence interval [CI]: 51-77%) in 2008 quarter 4. CONCLUSIONS Increases in antidepressant drug expenditures were primarily because of rising utilization; however, there was also some increase in average price per prescription for many of the antidepressants studied. Switching to generic drugs may offer significant cost-saving potential.

Impact of school-based health centers on students with mental health problems.

IMPORTANCE Antipsychotics are used increasingly in youth for nonpsychotic and off-label indications, but cardiometabolic adverse effects and (especially) type 2 diabetes mellitus (T2DM) risk have raised additional concern. OBJECTIVE To assess T2DM risk associated with antipsychotic treatment in youth. DATA SOURCES Systematic literature search of PubMed and PsycINFO without language restrictions from database inception until May 4, 2015. Data analyses were performed in July 2015, and additional analyses were added in November 2015. STUDY SELECTION Longitudinal studies reporting on T2DM incidence in youth 2 to 24 years old exposed to antipsychotics for at least 3 months. DATA EXTRACTION AND SYNTHESIS Two independent investigators extracted study-level data for a random-effects meta-analysis and meta-regression of T2DM risk. MAIN OUTCOMES AND MEASURES The coprimary outcomes were study-defined T2DM, expressed as cumulative T2DM risk or as T2DM incidence rate per patient-years. Secondary outcomes included the comparison of the coprimary outcomes in antipsychotic-treated youth with psychiatric controls not receiving antipsychotics or with healthy controls. RESULTS Thirteen studies were included in the meta-analysis, including 185,105 youth exposed to antipsychotics and 310,438 patient-years. The mean (SD) age of patients was 14.1 (2.1) years, and 59.5% were male. The mean (SD) follow-up was 1.7 (2.3) years. Among them, 7 studies included psychiatric controls (1,342,121 patients and 2,071,135 patient-years), and 8 studies included healthy controls (298,803 patients and 463,084 patient-years). Antipsychotic-exposed youth had a cumulative T2DM risk of 5.72 (95% CI, 3.45-9.48; P < .001) per 1000 patients. The incidence rate was 3.09 (95% CI, 2.35-3.82; P < .001) cases per 1000 patient-years. Compared with healthy controls, cumulative T2DM risk (odds ratio [OR], 2.58; 95% CI, 1.56-4.24; P < .0001) and incidence rate ratio (IRR) (IRR, 3.02; 95% CI, 1.71-5.35; P < .0001) were significantly greater in antipsychotic-exposed youth. Similarly, compared with psychiatric controls, antipsychotic-exposed youth had significantly higher cumulative T2DM risk (OR, 2.09; 95% CI, 1.50-52.90; P < .0001) and IRR (IRR, 1.79; 95% CI, 1.31-2.44; P < .0001). In multivariable meta-regression analyses of 10 studies, greater cumulative T2DM risk was associated with longer follow-up (P < .001), olanzapine prescription (P < .001), and male sex (P = .002) (r(2) = 1.00, P < .001). Greater T2DM incidence was associated with second-generation antipsychotic prescription (P ≤ .050) and less autism spectrum disorder diagnosis (P = .048) (r(2) = 0.21, P = .044). CONCLUSIONS AND RELEVANCE Although T2DM seems rare in antipsychotic-exposed youth, cumulative risk and exposure-adjusted incidences and IRRs were significantly higher than in healthy controls and psychiatric controls. Olanzapine treatment and antipsychotic exposure time were the main modifiable risk factors for T2DM development in antipsychotic-exposed youth. Antipsychotics should be used judiciously and for the shortest necessary duration, and their efficacy and safety should be monitored proactively.