Understanding authorized generics-A review of the published clinical data.

WHAT IS KNOWN AND OBJECTIVES: Despite the large body of evidence demonstrating equivalent efficacy and safety for branded drugs and their generic counterparts, some patients and providers have the perception that generics may be less safe and effective than branded agents. Authorized generics (AGs) are a category of generic drugs defined by the United States Food and Drug Administration (FDA) as being the same as the brand-name drug without the brand's name on the label and which may have minor differences, such as tablet or capsule markings for identification. Studies in which AGs are considered along with other generics may increase our understanding of factors that may influence perceptions about generics and shed light on areas where education may be impactful. The objectives of this paper are to provide information about AGs, review studies in which they have been evaluated and explore the role that AGs may fill in the individualized treatment of patients. METHODS: A literature review was conducted on 30 September 2019 with follow-up search on 4 March 2020. The search was focussed on published papers and meeting abstracts that provided information on AGs with respect to medical and health outcomes of therapy as well as switching in individuals receiving branded, AG, or other generic agents. Information about patients' perceptions of generic medications and adherence to therapy was also included. Additional information, including relevant government sources, such as the FDA website and the Federal Trade Commission Report, was included as appropriate. RESULTS: The literature specific to AGs is limited, but available data clearly highlight the importance of patient perception of generics as well as medication appearance as factors that may affect adherence and potentially more frequent switchbacks to branded agents from generics or AGs. WHAT IS NEW AND CONCLUSION: To our knowledge, this is the first narrative review to provide a summary of the published evidence about AGs with respect to clinical and health outcomes and switching. There is a need for more research and education regarding the use of AGs in clinical practice if they are to become more recognized as a potential treatment choice for patients. Generic medications play an important role in the healthcare system, and AGs may be able to provide an option to meet the specific needs of individual patients.

Patient and caregiver opinions about an FDA-developed generic drug educational handout: A pilot cross-sectional survey.

OBJECTIVE: To examine patient and caregiver opinions and "receptivity" regarding generic drug educational material in terms of content, format and design, delivery channel, and level of satisfaction. METHODS: Interviewer-administered surveys were conducted with patients and caregivers who were clients of a regional medication management program or pharmacy services clinic to gather perceptions about generic drugs and input on a generic drug educational handout developed by the U.S. Food and Drug Administration (FDA). Survey questions were developed by the investigators and pretested before use. Data were analyzed using descriptive statistics, and responses to open-ended questions were assessed using qualitative content analysis. Survey psychometrics were examined using exploratory factor analysis (EFA). RESULTS: Of the 100 survey participants, most (93%) had positive perceptions about generic drug safety and effectiveness after reading the handout. Most participants were satisfied or very satisfied with the handout's content (87%) as well as format and design (92%). However, more than 20% of participants were still unsure about the benefits and risks of generic drugs compared with those of brand drugs, and more than 15% were still unsure about which benefits and risks mattered most to them. The participants' preferred source for the handout was a pharmacy (49%) or doctor's office (27%). In an EFA of the survey instrument, 2 factors emerged related to the educational handout's content: (1) generic drug information, a 7-item factor (Cronbach alpha = 0.882); and (2) personal relevance, a 3-item factor (Cronbach alpha = 0.692). CONCLUSION: The findings indicate an overall positive "receptiveness" toward generic drug informational materials from patients and caregivers, which highlights the feasibility and importance of educational outreach programs about generic drugs targeted toward this population. Future studies may focus on more diverse populations and tailor materials to the needs of specific patient and caregiver subgroups and health literacy levels.

An Examination of Prescribing Responsibilities between Psychiatrists and Primary Care Providers.

Patients with comorbid mental health and chronic conditions often receive care from both psychiatrists and primary care physicians (PCPs). The introduction of multiple providers into the care process introduces opportunities for disruptions in care continuity. The purpose of this study was to explore psychiatrists' and PCPs' comfort prescribing, along with their comfort having other physician specialties prescribe medications for cardiometabolic, psychiatric, and neurological/behavioral conditions. This cross-sectional study utilized an online, validated, pilot-tested, anonymous survey to examine prescribing practices of psychiatrists and PCPs. Eligible participants included physicians with medical degrees, U.S. prescribing authority, and active patient care for ≥2 days/week. Outcomes of interest were physicians' self-comfort and cross-specialty comfort (other specialists prescribing mutual patients' medications) prescribing cardiometabolic, psychiatric, and neurological/behavioral medications. Comfort prescribing was measured using 7-point Likert scales. Discrepancies in comfort were analyzed using student's, one-sample, and paired t-tests. Multiple linear regressions examined associations between physician practice characteristics and physicians' comfort-level prescribing cardiometabolic and psychiatric medication categories. Among 50 psychiatrists and 50 PCPs, psychiatrists reported significantly lower self-comfort prescribing cardiometabolic medications (mean ± SD = 2.99 ± 1.63 vs. 6.77 ± 0.39, p < 0.001), but significantly higher self-comfort prescribing psychiatric medications (mean ± SD = 6.79 ± 0.41 vs. 6.00 ± 0.88, p < 0.001) and neurological/behavioral medications (mean ± SD = 6.48 ± 0.74 vs. 5.56 ± 1.68, p < 0.001) than PCPs. After adjusting for covariates, physician specialty was strongly associated with self-comfort prescribing cardiometabolic and psychiatric medication categories (both p < 0.001). Differences between self-comfort and cross-specialty comfort were identified. Because comfort prescribing medications differed by physician type, incorporating psychiatrists through collaborative methods with PCPs could potentially ensure comfort among physicians when initiating medications.

National trends in prescription proton pump inhibitor use and expenditure in the United States in 2002-2017.

OBJECTIVES: In the United States, proton pump inhibitors (PPIs) are one of the most commonly prescribed classes of drugs, but contemporary data on national-level utilization patterns for PPI use are limited. This study examined the trends in prescription PPI use and expenditures, overall and by patient subgroups, and identified predictors of PPI use. METHODS: Prescription PPI use was identified from the 2002-2017 Medical Expenditure Panel Survey data using the brand and generic names. Trends in PPI use were examined overall and by patients' sociodemographic characteristics and disease status. Trends in brand and generic PPI users and total and average PPI expenditures were also examined. A multivariable model was used to identify patient factors associated with PPI use. RESULTS: The overall proportion of PPI users increased from 5.70% in 2002-2003 to 6.73% in 2016-2017 (P value = 0.011). Increased trends in PPI use were observed among U.S. adults aged 65 years and older, both males and females, non-Hispanic whites, non-Hispanic blacks, Hispanics, Asians, in all 4 geographic regions, with public health insurance, and those who were obese (all P value < 0.05). Whereas PPI use increased significantly, the average PPI expenditure per patient decreased significantly. Multivariable results found that participants who were aged 25 years or older, were female, were non-Hispanic whites, resided in the Northeast, had higher incomes, had public or private health insurance, were obese, were married had a higher likelihood of using PPIs. CONCLUSION: Increased PPI use was observed among most of the patient subgroups. Understanding the utilization patterns of PPIs could help practitioners identify potential treatment disparities and monitor the safety of PPI use.

Comparison of 3 risk factor-based screening tools for the identification of prediabetes.

OBJECTIVE: To compare risk factor-based screening tools for identifying prediabetes. METHODS: Participants in an employer-based wellness program were tested for glycosylated hemoglobin (A1C) at a regularly scheduled appointment, and prediabetes risk factor information was collected. The likelihood of having prediabetes and the need for laboratory testing were determined based on 3 risk factor-based screening tools: the Prediabetes Screening Test (PST), Prediabetes Risk Test (PRT), and 2016 American Diabetes Association guidelines (ADA2016). The results from the screening tools were compared with those of the A1C test. The predictive ability of the PST, PRT, and ADA2016 were compared using logistic regression. Results were validated with data from a secondary population. RESULTS: Of the 3 risk factor-based tools examined, the PRT demonstrated the best combination of sensitivity and specificity for identifying prediabetes. From July 2016 to March 2017, 740 beneficiaries of an employer-sponsored wellness program had their A1C tested and provided risk factor information. The population prevalence of prediabetes was 9.3%. Analysis of a second independent population with a prediabetes prevalence of more than 50% of confirmed PRT's superiority despite differences in the calculated sensitivity and specificity for each population. CONCLUSION: Because PRT predicts prediabetes better than PST or ADA2016, it should be used preferentially.

Description of a pharmacist-led diabetes prevention service within an employer-based wellness program.

OBJECTIVES: To describe a pharmacist-led diabetes prevention service piloted within an employer-based wellness program. PRACTICE DESCRIPTION: A pharmacist-led ambulatory care clinic within a school of pharmacy that provides wellness services to university employees. PRACTICE INNOVATION: Implementation of a diabetes prevention service using opportunistic A1C screening within a biometric screening program. Patients with a prediabetes-level A1C from July 2016 to March 2019 were invited to participate in the National Diabetes Prevention Program (NDPP). EVALUATION: Comparison of baseline characteristics of participants with normal and elevated A1C. Evaluation of participation in the NDPP and changes in clinical values at the subsequent biometric screening appointment for individuals with a prediabetes-level AlC. RESULTS: A1C testing of 740 individuals identified 69 participants (9.3%) with a prediabetes-level A1C and 7 (1.0%) with a diabetes-level A1C. Compared with those with a normal A1C (< 5.7%), participants with an elevated A1C were more likely to be older, nonwhite, obese, and physically inactive, to have a sibling with diabetes, higher random blood sugar (RBS), lower high-density lipoprotein (HDL), and more likely to have hypertension. Twelve patients participated in the NDPP, although most attended only 1 session. Attenders had a significantly lower baseline weight and body mass index (BMI). There were no significant differences in the changes in A1C, BMI, weight, RBS, or HDL between attenders and nonattenders approximately 1 year later. CONCLUSION: This pilot demonstrated that opportunistic A1C testing could be incorporated into an ambulatory care clinic within a pharmacist-led employer-based wellness program. Uptake and retention of the NDPP were poor. Barriers to NDPP participation need to be investigated and addressed to improve service impact.

Trends in botanical dietary supplement use among US adults by cancer status: The National Health and Nutrition Examination Survey, 1999 to 2014.

BACKGROUND: Patients with cancer may use botanical dietary supplements (BDS) in an attempt to manage the side effects of chemotherapy, yet evidence about BDS use among patients with cancer is limited. The authors examined trends in BDS use among US adults according to cancer status and patient characteristics. METHODS: A serial, cross-sectional study was conducted using data from the National Health and Nutrition Examination Survey from 1999 through 2014 (n = 43,644). Self-reported cancer diagnosis history and any BDS use in the preceding 30 days were determined. The prevalence of BDS use was calculated in each cycle for respondents with and without cancer, both overall and by patient characteristics. Simple linear regression models were applied to test for trends in BDS use at a 2-sided P value < .05. Multiple logistic regression models were performed to identify the patient factors associated with BDS use. The results were weighted to represent national estimates. RESULTS: The prevalence of BDS use was greater among participants who had cancer compared with participants who did not have cancer, but trends remained stable during 1999 through 2014 for both groups. Trends in BDS use declined in patients with cancer who were older (Ptrend = .047), had a low annual family income (Ptrend = .028), and had a lower education level (Ptrend = .004). Among the respondents without cancer, trends in BDS use declined in those who were middle-aged (Ptrend = .025), non-Hispanic whites (Ptrend = .025), those with a lower education level (Ptrend = .011), and those who were not receiving prescription medication (Ptrend = .036). Patient age, sex, race/ethnicity, income, education, and health conditions were associated with BDS use. CONCLUSIONS: The overall use of BDS remained stable during 1999 through 2014 for US adults with and without cancer, but it varied by individual characteristics. Cancer 2018;124:1207-15. © 2017 American Cancer Society.

Dipeptidyl Peptidase-4 Inhibitor-Associated Risk of Bleeding: An Evaluation of Reported Adverse Events.

BACKGROUND: Dipeptidyl peptidase-4 (DPP-4) inhibitors improve glycemic control, and sitagliptin has been associated with a reduction in cardiovascular events. In vivo data suggest reduced platelet activation, and aggregation may play a role, and therefore, increased bleeding risk is possible. OBJECTIVE: Comparatively assess bleeding risks associated with DPP-4 inhibitors against standard treatment. METHODS: Exploratory analyses of adverse event reports (AERs) from the US Food and Drug Administration Adverse Event Reporting System (FAERS) database (2004-2012 periods) were conducted. DPP-4 inhibitor-related bleeding was assessed with metformin as negative control, and aspirin, clopidogrel, and prasugrel illustrated positive comparators. Reporting odds ratios (RORs) and 95% CIs were calculated as a measure of disproportionality of reporting, and RORs were compared across drugs with the Breslow-Day statistics. RESULTS: From 2004 to 2012, 36 298, 4288, and 1202 AERs were found for sitagliptin, saxagliptin, and linagliptin, respectively, with 863, 102, and 14 bleeding complications. The relative reporting rate was not elevated with any DPP-4 inhibitor (sitagliptin: ROR = 0.71, 95% CI = 0.67-0.76; saxagliptin: ROR = 0.72, 95% CI = 0.59-0.87; linagliptin: ROR = 0.35, 95% CI = 0.20-0.59) or with metformin (ROR = 0.77; 95% CI = 0.75-0.78). Sitagliptin showed relatively higher reporting as compared with linagliptin ( P = 0.006) but not with saxagliptin ( P = 0.98). As positive references, antiplatelet drugs demonstrated relatively higher reporting compared with metformin (aspirin: ROR = 1.50, 95% CI = 1.48-1.51; clopidogrel: ROR = 2.28, 95% CI = 2.23-2.33; prasugrel: ROR = 5.09, 95% CI = 4.57-5.67). CONCLUSION: DPP-4 inhibitors were not associated with an undue increase in bleeding AERs in the FAERS database.

Disclosure of industry payments to prescribers: industry payments might be a factor impacting generic drug prescribing.

PURPOSE: Pharmaceutical companies paid at least $3.91bn to prescribers in 2013, yet evidence indicating whether industry payments shift prescribing away from generics is limited. This study examined the association between amount of industry payments to prescribers and generic drug prescribing rates among Medicare Part D prescribers. METHODS: A cross-sectional analysis was conducted among 770 095 Medicare Part D prescribers after linking the 2013 national Open Payments data with 2013 Medicare Provider Utilization and Payment data. The exposure variable was the categorized amount of total industry payments to prescribers (i.e., meals, travel, research, and ownership). The outcome was prescriber's annual generic drug prescribing rate. Multivariable generalized linear regression models were used to examine the association between the amount of industry payments and prescriber's annual generic drug prescribing rates, controlling for prescriber's demographic and practice characteristics. RESULTS: In this sample, over one-third (38.0%) of Medicare Part D prescribers received industry payments in 2013. The mean annual generic drug prescribing rate was highest among prescribers receiving no payments and lowest among those receiving more than $500 of industry payments (77.5% vs. 71.3%, respectively; p < 0.001). The receipt of industry payments was independently associated with prescribers' generic drug prescribing rate; higher payments corresponded with lower generic drug prescribing rates. Other prescriber characteristics associated with higher annual generic drug prescribing rate included male sex, non-northeast region, specialty, and patient volume. CONCLUSIONS: Receipt of industry payments was associated with a decreased rate of generic drug prescribing. How this affects patient care and total medical costs warrants further study. Copyright © 2017 John Wiley & Sons, Ltd.

Cardiotoxicity in targeted therapy for breast cancer: A study of the FDA adverse event reporting system (FAERS).

Purpose Cancer chemotherapy-induced cardiotoxicity is concerning. Certain anthracyclines and targeted therapies are known to have potential for cardiotoxicity, but existing trial evidence is inadequate to understand real-world patterns of cardiotoxicity with newer targeted therapies and their common combinations with older agents. This study evaluated chemotherapy-related cardiotoxicity reports for targeted therapies and their combinations in breast cancer patients. Methods The US Food and Drug Administration Adverse Event Reporting System (FAERS) database from January 2004 through September 2012 was used to summarize characteristics of reported cardiotoxicity events and their health outcomes. Disproportionality analyses with reporting odds ratios (ROR) and 95% confidence intervals (95% CI) were conducted to detect event signals using a case/non-case method for each targeted therapy and combination. Results A total of 59,739 cases of cardiotoxicity reports were identified; 937 cases identified targeted therapy as the suspect drug. Trastuzumab had the highest number of reports followed by bevacizumab and lapatinib. Proportions of reports of death and disability outcomes for each targeted therapy were approximately 20-25% of the total reports of serious events. Trastuzumab had the highest ROR as a single agent (ROR = 5.74; 95% CI = 5.29-6.23) or combination use of cyclophosphamide (ROR = 16.83; 95% CI = 13.32-21.26) or doxorubicin (ROR = 17.84; 95% CI = 13.77-23.11). Relatively low cardiotoxicity reporting rates were found with lapatinib, regardless of use with combination therapy. Conclusions Analysis of FAERS data identified signals for adverse cardiotoxicity events with targeted therapies and their combinations. Practitioners should consider factors that may increase the likelihood of cardiotoxicity when assessing treatment. Findings support continued surveillance, risk factor identification, and comparative studies.

Association of authorized generic marketing with prescription drug spending on antidepressants from 2000 to 2011.

OBJECTIVES: Prior research suggests that authorized generic drugs increase competition and decrease prices, but little empirical evidence supports this conclusion. This study evaluated the impact of authorized generic marketing on brand and generic prices. DESIGN: Longitudinal analysis of the household component of the Medical Expenditure Panel Survey. SETTING: Interview panels over 12 years, with a new panel each year. For each panel, 5 rounds of household interviews were conducted over 30 months. PATIENTS OR PARTICIPANTS: Nationally representative sample of the U.S. civilian noninstitutionalized population, focusing on people using 1 of 5 antidepressant drugs that became generically available between 2000 to 2011. INTERVENTION: Drugs and dose/formulations with versus without an authorized generic drug marketed. MAIN OUTCOME MEASURES: Multiple linear regression models with lagged variables evaluated the effect of an authorized generic on average inflation-adjusted brand and generic price, adjusting for payment sources, generic entry time, competitor price, and year. RESULTS: During 2000-2011, annual brand antidepressant utilization decreased from 51.47 to 7.52 million prescriptions, and generic antidepressant utilization increased from 0 to 88.83 million prescriptions. Over time, payment per prescription for brand prescriptions increased 25% overall, and generic payments decreased 70% for all payer types. With unadjusted data, after generic entry the average brand price decreased $0.59 per year with and $3.62 per year without an authorized generic in the market. Average generic prices decreased $10.30 per year with and $8.47 per year without an authorized generic in the market. In multiple regression models with lagged variables adjusted for heteroscedasticity, payer source, time since generic entry, competitor price, and year, authorized generics significantly reduced average payment for generic (-$3.03) and brand (-$60.64) prescriptions, and over time this price change slowly diminished. CONCLUSION: Availability of an authorized generic was associated with reduced average generic and brand price in the antidepressant market, supporting prior evidences.

Pilot Study to Test the Effectiveness of Different Financial Incentives to Improve Medication Adherence.

BACKGROUND: Medication nonadherence affects health care costs, morbidity, and mortality. Concepts from behavioral economics can guide the development of interventions to improve medication adherence. OBJECTIVE: To measure the relative effectiveness of 2 behavioral economic-based incentive structures to improve medication adherence. METHODS: This randomized controlled trial compared adherence among participants taking antihypertensive or antihyperlipidemic medications randomized to usual care (UC), guaranteed pay-out (GPO) incentives, or lottery incentives. Daily adherence was measured over a 90-day period using electronic caps (Medication Event Monitoring System [MEMS]). The GPO group received $30 up-front in a virtual account, with $0.50 deducted for each missed dose. Lottery group participants were eligible for a weekly $50 drawing, but only if they had taken their medication as prescribed all week. An electronic survey assessed self-reported adherence. Statistical analysis included descriptive statistics, paired t tests, ANOVA, and Pearson's correlations. RESULTS: In all, 36 participants were randomized (UC, n = 11; GPO, n = 14; lottery, n = 11). Mean percentage (±SD) of days adherent during the incentive period was highest in the lottery group (96% ± 5%), followed by the GPO group (94% ± 9%) and the UC group (94% ± 9%). There were no statistically significant differences among groups (P > 0.05). MEMS-measured adherence was not significantly correlated with a patient's self-reported adherence (P > 0.05) at baseline but was correlated at 90-day follow-up (P < 0.001). CONCLUSIONS: Although no statistically significant differences in adherence were demonstrated in this small sample of highly adherent participants, larger studies in a more diverse population or with other medications might show otherwise.

Antidepressant Medication Use and Its Association With Cardiovascular Disease and All-Cause Mortality in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) Study.

BACKGROUND: Mixed evidence suggests that second-generation antidepressants may increase the risk of cardiovascular and cerebrovascular events. OBJECTIVE: To assess whether antidepressant use is associated with acute coronary heart disease (CHD), stroke, cardiovascular disease (CVD) death, and all-cause mortality. METHODS: Secondary analyses of the Reasons for Geographic and Racial Differences in Stroke (REGARDS) longitudinal cohort study were conducted. Use of selective serotonin reuptake inhibitors, serotonin and norepinephrine reuptake inhibitors, bupropion, nefazodone, and trazodone was measured during the baseline (2003-2007) in-home visit. Outcomes of CHD, stroke, CVD death, and all-cause mortality were assessed every 6 months and adjudicated by medical record review. Cox proportional hazards time-to-event analysis followed patients until their first event on or before December 31, 2011, iteratively adjusting for covariates. RESULTS: Among 29 616 participants, 3458 (11.7%) used an antidepressant of interest. Intermediate models adjusting for everything but physical and mental health found an increased risk of acute CHD (hazard ratio [HR] = 1.21; 95% CI = 1.04-1.41), stroke (HR = 1.28; 95% CI = 1.02-1.60), CVD death (HR = 1.29; 95% CI = 1.09-1.53), and all-cause mortality (HR = 1.27; 95% CI = 1.15-1.41) for antidepressant users. Risk estimates trended in this direction for all outcomes in the fully adjusted model but only remained statistically associated with increased risk of all-cause mortality (HR = 1.12; 95% CI = 1.01-1.24). This risk was attenuated in sensitivity analyses censoring follow-up time at 2 years (HR = 1.37; 95% CI = 1.11-1.68). CONCLUSIONS: In fully adjusted models, antidepressant use was associated with a small increase in all-cause mortality.

Prescriber continuity and medication adherence for complex patients.

BACKGROUND: Medication adherence is a critical aspect of managing cardiometabolic conditions, including diabetes, hypertension, dyslipidemia, and heart failure. Patients who have multiple cardiometabolic conditions and multiple prescribers may be at increased risk for nonadherence. OBJECTIVE: The purpose of this study was to examine the relationship between number of prescribers, number of conditions, and refill adherence to oral medications to treat cardiometabolic conditions. METHODS: In this retrospective cohort study, 7933 veterans were identified with 1 to 4 cardiometabolic conditions. Refill adherence to oral medications for diabetes, hypertension, and dyslipidemia was measured using an administrative claims-based continuous multiple-interval gap (CMG) that estimates the percentage of days a patient did not possess medication. We dichotomized refill adherence for each condition as a CMG ≤20% for each year of analysis. Condition-specific logistic regression models estimated the relationship between refill adherence and number of cardiometabolic conditions and number of prescribers, controlling for demographic characteristics, other comorbidities, and a count of cardiometabolic drug classes used. RESULTS: Compared with patients with 1 prescriber, antihypertensive refill adherence was lower in patients seeing ≥4 prescribers (odds ratio [OR] = 0.69; 95% CI = 0.59-0.80), but the number of cardiometabolic conditions was not a significant predictor. Antidyslipidemia refill adherence was lower in patients seeing 3 prescribers (OR = 0.80; 95% CI = 0.70-0.92) or ≥4 prescribers (OR = 0.77; 95% CI = 0.64-0.91). Conversely, antidyslipidemia refill adherence improved with the number of cardiometabolic conditions, but differences were only statistically significant for ≥3 conditions (OR = 1.31; 95% CI = 1.09-1.57). In multivariate regression models, the number of conditions and number of prescribers were not significant predictors of refill adherence in the group of patients with diabetes. CONCLUSIONS: Effective management of care and medication regimens for complex patients remains an unresolved challenge, but these results suggest that medication refill adherence might be improved by minimizing the number of prescribers involved in a patient's care, at least for hypertension and dyslipidemia.

The intersection of patient complexity, prescriber continuity and acute care utilization.

BACKGROUND: Care continuity is considered a critical characteristic of high-performing health systems. Few studies have examined the continuity of medication management of complex patients, who often have multiple providers and complex medication regimens. PURPOSE: The purpose of this study was to characterize patient factors associated with having more prescribers and the association between number of prescribers and acute care utilization. DESIGN AND SUBJECTS: A retrospective cohort study was conducted of 7,933 Veterans with one to four cardiometabolic conditions (diabetes, hypertension, hyperlipidemia or congestive heart failure) and prescribed medications for these conditions in 2008. MAIN MEASURES: The association between number of cardiometabolic conditions and prescribers was modeled using Poisson regression. The number of cardiometabolic conditions and number of prescribers were modeled to predict probability of inpatient admission, probability of emergency room (ER) visits, and number of ER visits among ER users. Demographic characteristics, number of cardiometabolic medications and comorbidities were included as covariates in all models. KEY RESULTS: Patients had more prescribers if they had more cardiometabolic conditions (p < 0.001). The adjusted odds of an ER visit increased with the number of prescribers (two prescribers, Odds Ratio (OR) = 1.16; three prescribers, OR = 1.21; 4+ prescribers, OR = 1.39), but not with the number of conditions. Among ER users, the number of ER visits was neither associated with the number of prescribers nor the number of conditions. The adjusted odds of an inpatient admission increased with the number of prescribers (two prescribers, OR = 1.27; three prescribers, OR = 1.30; 4+ prescribers, OR = 1.34), but not with the number of conditions. CONCLUSIONS: Having more prescribers was associated with greater healthcare utilization for complex patients, despite adjustment for the number of conditions and medications. The number of prescribers may be an appropriate target for reducing acute care utilization by complex patients.

Developing an expert panel process to refine health outcome definitions in observational data.

OBJECTIVES: Drug safety surveillance using observational data requires valid adverse event, or health outcome of interest (HOI) measurement. The objectives of this study were to develop a method to review HOI definitions in claims databases using (1) web-based digital tools to present de-identified patient data, (2) a systematic expert panel review process, and (3) a data collection process enabling analysis of concepts-of-interest that influence panelists' determination of HOI. METHODS: De-identified patient data were presented via an interactive web-based dashboard to enable case review and determine if specific HOIs were present or absent. Criteria for determining HOIs and their severity were provided to each panelist. Using a modified Delphi method, six panelist pairs independently reviewed approximately 200 cases across each of three HOIs (acute liver injury, acute kidney injury, and acute myocardial infarction) such that panelist pairs independently reviewed the same cases. Panelists completed an assessment within the dashboard for each case that included their assessment of the presence or absence of the HOI, HOI severity (if present), and data contributing to their decision. Discrepancies within panelist pairs were resolved during a consensus process. RESULTS: Dashboard development was iterative, focusing on data presentation and recording panelists' assessments. Panelists reported quickly learning how to use the dashboard. The assessment module was used consistently. The dashboard was reliable, enabling an efficient review process for panelists. Modifications were made to the dashboard and review process when necessary to facilitate case review. Our methods should be applied to other health outcomes of interest to further refine the dashboard and case review process. CONCLUSION: The expert review process was effective and was supported by the web-based dashboard. Our methods for case review and classification can be applied to future methods for case identification in observational data sources.

Real-world utilization patterns and outcomes of colesevelam hcl in the ge electronic medical record.

BACKGROUND: In randomized controlled trials (RCTs), colesevelam HCI, added to other anti-diabetic therapy, reduced hemoglobin A1C by approximately 0.3% to 0.4% over 16- to 26-weeks compared with an increase of approximately 0.1% to 0.2% for placebo, for a placebo-adjusted treatment effect of approximately 0.5%. Evidence on real-world effectiveness is unknown. This retrospective cohort study examined A1C changes following colesevelam HCL initiation in patients with diabetes, regardless of concomitant anti-diabetic medication use. METHODS: 2000-2011 GE Centricity electronic medical records data were used to identify patients with type 2 diabetes mellitus (T2DM) aged 18 or older initiating colesevelam HCL. The sample was further restricted to uncontrolled patients with database activity ≥ 395 days before and after colesevelam HCL initiation, A1C > 7% during 90 days prior to starting colesevelam HCL, without prior use of bile acid sequestrants, and with at least one A1C result between 42 to 210 days after initiation. Three overlapping time intervals were created for A1C measurement, including 16-weeks, 26-weeks, and 52-weeks following therapy initiation. The last observed A1C lab measurement during each interval was used to define change from baseline. Mean change in A1C was examined using paired t-tests. Sensitivity analyses considered only patients who remained on colesevelam HCL through each respective measurement period, as well as the effect of concomitant diabetes medications. RESULTS: Of 1,709,393 patients in the GE database with T2DM, 1,747 met inclusion criteria. The cohort was 58% female, 38% age ≥ 65, and the majority was white. For the 16-week endpoint (N = 1,385), A1C dropped from a mean of 8.22% to 7.75% (mean change -0.47%; P < 0.0001). For the 26- and 52-week endpoints (N = 1,747), A1C dropped from a mean of 8.25% to 7.81% (mean change -0.44%; P < 0.0001) and 8.25% to 7.79% (mean change -0.46%; P < 0.0001), respectively. Sensitivity analyses showed that A1C reductions were of similar direction and magnitude for patients who remained on treatment, and for the subgroups of patients stratified by receipt of concomitant T2DM treatments. CONCLUSIONS: The 0.44% to 0.47% A1C reduction observed in this study was similar to the reduction observed in RCTs, supporting the real-world effectiveness of colesevelam HCL in reducing A1C.

Investigating differences in treatment effect estimates between propensity score matching and weighting: a demonstration using STAR*D trial data.

PURPOSE: The choice of propensity score (PS) implementation influences treatment effect estimates not only because different methods estimate different quantities, but also because different estimators respond in different ways to phenomena such as treatment effect heterogeneity and limited availability of potential matches. Using effectiveness data, we describe lessons learned from sensitivity analyses with matched and weighted estimates. METHODS: With subsample data (N = 1292) from Sequenced Treatment Alternatives to Relieve Depression, a 2001-2004 effectiveness trial of depression treatments, we implemented PS matching and weighting to estimate the treatment effect in the treated and conducted multiple sensitivity analyses. RESULTS: Matching and weighting both balanced covariates but yielded different samples and treatment effect estimates (matched RR 1.00, 95% CI: 0.75-1.34; weighted RR 1.28, 95% CI: 0.97-1.69). In sensitivity analyses, as increasing numbers of observations at both ends of the PS distribution were excluded from the weighted analysis, weighted estimates approached the matched estimate (weighted RR 1.04, 95% CI 0.77-1.39 after excluding all observations below the 5th percentile of the treated and above the 95th percentile of the untreated). Treatment appeared to have benefits only in the highest and lowest PS strata. CONCLUSIONS: Matched and weighted estimates differed due to incomplete matching, sensitivity of weighted estimates to extreme observations, and possibly treatment effect heterogeneity. PS analysis requires identifying the population and treatment effect of interest, selecting an appropriate implementation method, and conducting and reporting sensitivity analyses. Weighted estimation especially should include sensitivity analyses relating to influential observations, such as those treated contrary to prediction.

Performance of Medometer visual tool for measuring medication adherence and comparison with other measures.

OBJECTIVES: To measure adherence in older adults with the use of a novel visual scale screening tool and to compare this adherence measurement with other adherence measures. DESIGN: Noncontrolled prospective intervention trial. SETTING: Geriatric psychiatry clinic in North Carolina between February 2008 and July 2009. PARTICIPANTS: 27 geriatric psychiatry clinic patients were identified as meeting eligibility criteria, and 26 of these participants completed the baseline and 3- and 6-month visits. INTERVENTION: Pharmacist-provided medication management program. MAIN OUTCOME MEASURES: A novel visual scale, the Medometer, assessed patient adherence to individual medications and aggregate medication regimen. The Medometer was compared with pharmacist subjective adherence assessment and the four-item Morisky scale. RESULTS: Aggregate regimen adherence based on the Morisky scale was 44%, 50%, and 38% at baseline, 3 months, and 6 months, respectively. Similarly it was 48%, 50%, and 46%, respectively, for the aggregate Medometer measurement. Measured individually by drug, average adherence at baseline, 3 months, and 6 months was 44%, 50%, and 35%, respectively, with the Medometer and 74%, 65%, and 50%, respectively, for the pharmacist's subjective assessment. Less stringent definitions for categorizing adherence identified a higher proportion of patients as adherent, with similar trends across measures. Individual medication and aggregate regimen adherence estimates provided face validity for the Medometer, with moderate agreement with other measures. CONCLUSION: The Medometer is a visual scale that can assess individual medication and overall medication regimen adherence. It performed well in this pilot study, but additional research is needed to assess the reliability and validity of this tool in larger, diverse populations and to test the effectiveness of this tool in guiding pharmacists' efforts to improve medication outcomes.

Treating depression after initial treatment failure: directly comparing switch and augmenting strategies in STAR*D.

OBJECTIVE: Augmenting and switching antidepressant medications are the 2 most common next-step strategies for depressed patients failing initial medication treatment. These approaches have not been directly compared; thus, our objectives are to compare outcomes for medication augmentation versus switching for patients with major depressive disorder in the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) clinical trial. METHODS: We conducted a retrospective analysis of participants aged 18 to 75 years with DSM-IV nonpsychotic depression who failed to remit with initial treatment in the STAR*D clinical trial (N = 1292). We compared depressive symptom remission, response, and quality of life among participants in each study arm using propensity score matching to minimize selection bias. RESULTS: The propensity-score-matched augment (N = 269) and switch (N = 269) groups were well balanced on measured characteristics. Neither the likelihood of remission (risk ratio, 1.14; 95% confidence level, 0.82-1.58) or response (risk ratio, 1.14; 95% confidence level, 0.82-1.58), nor the time to remission (log-rank test, P = 0.946) or response (log-rank test, P = 0.243) differed by treatment strategy. Similarly, quality of life did not differ. Post hoc analyses suggested that augmentation improved outcomes for patients tolerating 12 or more weeks of initial treatment and those with partial initial treatment response. CONCLUSIONS: For patients receiving and tolerating aggressive initial antidepressant trials, there is no clear preference for next-step augmentation versus switching. Findings tentatively suggest that those who complete an initial treatment of 12 weeks or more and have a partial response with residual mild depressive severity may benefit more from augmentation relative to switching.