Article

How Quickly Do Physicians Adopt New Drugs? The Case of Second-Generation Antipsychotics

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Abstract

Objective The authors examined physician adoption of second-generation antipsychotic medications and identified physician-level factors associated with early adoption. Methods The authors estimated Cox proportional-hazards models of time to adoption of nine second-generation antipsychotics by 30,369 physicians who prescribed antipsychotics between 1996 and 2008, when the drugs were first introduced, and analyzed the total number of agents prescribed during that time. The models were adjusted for physicians’ specialty, demographic characteristics, education and training, practice setting, and prescribing volume. Data were from IMS Xponent, which captures over 70% of all prescriptions filled in the United States, and the American Medical Association Physician Masterfile. Results On average, physicians waited two or more years before prescribing new second-generation antipsychotics, but there was substantial heterogeneity across products in time to adoption. General practitioners were much slower than psychiatrists to adopt second-generation antipsychotics (hazard ratios (HRs) range .10−.35), and solo practitioners were slower than group practitioners to adopt most products (HR range .77−.89). Physicians with the highest antipsychotic-prescribing volume adopted second-generation antipsychotics much faster than physicians with the lowest volume (HR range .15−.39). Psychiatrists tended to prescribe a broader set of antipsychotics (median=6) than general practitioners and neurologists (median=2) and pediatricians (median=1). Conclusions As policy makers search for ways to control rapid health spending growth, understanding the factors that influence physician adoption of new medications will be crucial in the efforts to maximize the value of care received by individuals with mental disorders as well as to improve medication safety.

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... The 35 eligible studies were all conducted in developed countries-mostly in North America (17 studies) [1,6,7,[12][13][14][15]19,[26][27][28][29][30]33,35,38,39] and North-Western Europe (11 studies) [5,11,18,[20][21][22][23]32,34,40,41]-14 studies were conducted in the US [7,[12][13][14][15]19,[26][27][28][29][30]33,38,39], four in Denmark [20][21][22]40], three each in Canada [1,6,35] and Spain [16,24,25], two each in the Netherlands [11,23] and Taiwan [36,37], and one each in Australia [17], Finland [32], Germany [41], Ireland [18], Sweden [5], and the UK [34], while one study [31] covered ten developed countries-Belgium, Canada, France, Germany, Italy, Japan, the Netherlands, Spain, the UK, and the US. The sample populations varied greatly, in both unit of observation and size. ...
... The 35 eligible studies were all conducted in developed countries-mostly in North America (17 studies) [1,6,7,[12][13][14][15]19,[26][27][28][29][30]33,35,38,39] and North-Western Europe (11 studies) [5,11,18,[20][21][22][23]32,34,40,41]-14 studies were conducted in the US [7,[12][13][14][15]19,[26][27][28][29][30]33,38,39], four in Denmark [20][21][22]40], three each in Canada [1,6,35] and Spain [16,24,25], two each in the Netherlands [11,23] and Taiwan [36,37], and one each in Australia [17], Finland [32], Germany [41], Ireland [18], Sweden [5], and the UK [34], while one study [31] covered ten developed countries-Belgium, Canada, France, Germany, Italy, Japan, the Netherlands, Spain, the UK, and the US. The sample populations varied greatly, in both unit of observation and size. ...
... In one study [31], the unit of observation was the country-in five others [5,16,20,21,37], the healthcare provider, ranging from 32 healthcare centres [16] to 191 practices [20,21], with a mean of 146 and one study not disclosing the number [37]. However, doctors were the unit of observation for 29 [1,6,7,11-15, 17-19,22-30,32-36,38-41] of the 35 eligible studies-nine studies observed general practitioners (GPs) [7,11,15,17,18,22,23,34,40], three specialists (SPs) [14,25,36], and 17 both [1,6,12,13,19,24,[26][27][28][29][30]32,33,35,38,39,41]. The sample populations ranged from 68 [22] to 74,075 doctors [39], with a median of 770. ...
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Background The successful diffusion of new drugs is crucial for both pharmaceutical companies and patients—and of wider stakeholder concern, including for the funding of healthcare provision. Micro-level characteristics (the socio-demographic and professional characteristics of medical professionals), meso-level characteristics (the prescribing characteristics of doctors, the marketing efforts of pharmaceutical companies, interpersonal communication among doctors, drug attributes, and the characteristics of patients), and macro-level characteristics (government policies) all influence the diffusion of new drugs. This systematic literature review examines the micro- and meso-level characteristics of early prescribers of newly introduced drugs. Understanding the characteristics of early adopters may help to speed up the diffusion process, promote cost-efficient prescribing habits, forecast utilisation, and develop targeted intervention strategies. Methods The PubMed and Scopus electronic databases were chosen for their extensive coverage of the pertinent literature and used to identify 205 potentially relevant studies by means of a four-layered search string. The 35 studies deemed eligible were then synthetized carefully and critically, to extract variables relevant to this review. Results Early adoption of new drugs is not a personal trait, independent of drug type, but early adopters share both micro- and meso-level characteristics. At prescriber level, doctors’ interest in particular therapeutic areas, participation in clinical trials, and volume of prescribing—either in total or within the therapeutic class of the new drug—increase the likelihood of early adoption. The marketing efforts of pharmaceutical companies and doctors’ professional and social interactions leading to prescribing contagion are very powerful predictors of new drug uptake. At patient level, doctors with younger patients, patients with higher socioeconomic statuses and/or patients with poorer health statuses are more inclined to prescribe new drugs early. In contrast, the socio-demographic characteristics of prescribers and many practice-related factors play little role in the adoption process. Conclusions The most powerful predictors of new drug uptake include the doctors’ strong scientific commitment, high prescribing volume in total or in within the therapeutic class of the new drug, high exposure to marketing, and intense communication with colleagues.
... A recent Danish study [13] compared physicians when initiating antidepressant treatment and found that practitioners in psychiatry tended to initiate newer antidepressants more than GPs. In this line, Huskamp and colleagues [14] demonstrated that on GPs tended to be slower in adopting newer antipsychotics when compared to psychiatrists. Moreover, psychiatrists tended to prescribe a wider range of antipsychotics, whereas GPs tended to stick to a more limited selection of products [14]. ...
... In this line, Huskamp and colleagues [14] demonstrated that on GPs tended to be slower in adopting newer antipsychotics when compared to psychiatrists. Moreover, psychiatrists tended to prescribe a wider range of antipsychotics, whereas GPs tended to stick to a more limited selection of products [14]. Finally, a significant increase in antipsychotics sales in several countries in the last two decades has been demonstrated repeatedly. ...
... Although no significant differences in this trend could be found, GPs seemed to have a slight delay in adapting the SGAs: In 2012, 33.5% of the all AP prescriptions were FGAs in the GP---population, whereas this was the case for only 19% in psychiatrists/neurologists. This corroborates the findings of Huskamp and colleagues [14], who also found GPs to be slower than psychiatrists in adopting SGAs. It was also demonstrated that the age of the prescriber, irrespective of his/her specialty. ...
Article
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In recent decades, a substantial increase in prescriptions of antipsychotics has been reported in several countries. This increase in antipsychotic sales has been attributed to the success of second-generation antipsychotics. This national register-based study investigated the evolution of outpatient antipsychotic sales in Belgium between 1997 and 2012. The impact of the specialization of the prescriber and the demographic characteristics of both prescribing doctors and patients were examined. The study used data obtained from the Belgian National Institute for Health and Disability Insurance and IMS Health Belgium. Over this 15-year period, antipsychotic sales increased by 122% in Belgium. This growth was mainly explained by a 3-fold increase in antipsychotic prescriptions by psychiatrists and neurologists. Overall, only 29.5% of prescriptions for antipsychotics were for psychotic disorders and only 26.2% of prescriptions for antipsychotics were for mood disorders, suggesting a large amount of off-label use. A significant shift toward second-generation agents was found in prescriptions by both psychiatrists and general practitioners, although there may have been a small delay in moving toward second-generation agents in the latter group. This increase in second-generation antipsychotic prescribing was mainly due to the steep rise in sales of quetiapine, followed by olanzapine and risperidone. The shift toward the newer products was also mainly seen in younger prescribers. The results of this study suggest that there has been an increase in adequate management of patients in need of antipsychotic treatment. Nevertheless, very few of the patients received continued treatment throughout the year, which implies that few outpatients with schizophrenia are receiving adequate treatment.
... Studies in other medication classes point to widespread variation in physician prescribing of new drugs based on specialty, practice setting, age, sex, and training. [12][13][14][15][16][17] We used an all-payer dataset on the prescribing behavior of all physicians in Pennsylvania who regularly prescribed oral anticoagulants in the 12 months prior to dabigatran's introduction to examine adoption patterns at the physician-level. We measured time to first prescription of dabigatran, a frequently-used adoption measure. ...
... Xponent™ directly captures >70% of all US prescriptions filled in retail pharmacies and utilizes a patented proprietary projection method to represent 100% of prescriptions filled in these outlets. 9,15,[20][21][22] We obtained monthly physician-level data on all oral anticoagulant prescriptions dispensed in Pennsylvania between October 1, 2009 and December 31, 2011. Xponent™ contains limited patient-level information relevant to the prescriptions including the source of payment (Medicare, Medicaid fee-for-service (FFS), commercial insurance, cash or uninsured), and patient age, with no patient identifiers. ...
... Studies of physician adoption typically measure the time to first prescription, dividing physicians into 'rapid' or 'slow' adopters. 15,[24][25][26][27][28][29] However, the decision to adopt a new drug is multifaceted. A physician needs to decide whether to adopt a new drug, the speed with which he/she will do so, and the volume of prescribing he/she will do for the new drug. ...
Article
Background: Variation in physician adoption of new medications is poorly understood. Traditional approaches (eg, measuring time to first prescription) may mask substantial heterogeneity in technology adoption. Objective: Apply group-based trajectory models to examine the physician adoption of dabigratran, a novel anticoagulant. Methods: A retrospective cohort study using prescribing data from IMS Xponent™ on all Pennsylvania physicians regularly prescribing anticoagulants (n=3911) and data on their characteristics from the American Medical Association Masterfile. We examined time to first dabigatran prescription and group-based trajectory models to identify adoption trajectories in the first 15 months. Factors associated with rapid adoption were examined using multivariate logistic regressions. Outcomes: Trajectories of monthly share of oral anticoagulant prescriptions for dabigatran. Results: We identified 5 distinct adoption trajectories: 3.7% rapidly and extensively adopted dabigatran (adopting in ≤3 mo with 45% of prescriptions) and 13.4% were rapid and moderate adopters (≤3 mo with 20% share). Two groups accounting for 21.6% and 16.1% of physicians, respectively, were slower to adopt (6-10 mo post-introduction) and dabigatran accounted for <10% share. Nearly half (45.2%) of anticoagulant prescribers did not adopt dabigatran. Cardiologists were much more likely than primary care physicians to rapidly adopt [odds ratio (OR)=12.2; 95% confidence interval (CI), 9.27-16.1] as were younger prescribers (age 36-45 y: OR=1.49, 95% CI, 1.13-1.95; age 46-55: OR=1.34, 95% CI, 1.07-1.69 vs. >55 y). Conclusions: Trajectories of physician adoption of dabigatran were highly variable with significant differences across specialties. Heterogeneity in physician adoption has potential implications for the cost and effectiveness of treatment.
... In a pharmaceutical sector, high-priced new drugs are continuously granted marketing authorization and have replaced old and inexpensive drugs [7][8][9]. However, adoption of new drugs among health care institutions is uneven [10][11][12][13][14][15]. Not surprisingly, the speed of adoption of new drugs and frequencies of substitutions leads to changes in health care expenditures as well as patient outcomes. ...
... Furthermore, we found that most health care institutions (64%) have not prescribed NOACs even after the coverage extended with the need of a letter of opinion, indicating that health care institutions were conservative in adopting new drugs. Being conservative in adopting NOACs could be explained by a variety of factors, such as an intentionally cautious approach to adopting new drugs to ensure patient safety or a lack of awareness of a drug's introduction [11]. More specifically, physicians have incomplete information on the safety and effectiveness of new drugs [23,24], and initial clinical trials are often too small to detect rare adverse reactions or demonstrate comparative effectiveness [31]. ...
... Our observations were consistent with the previous literature presenting that physicians were conservative in prescribing new drugs and that physician specialty was the most consistent predictors of adopting new drugs [10,11,13,23,32,33]. For instance, Anderson et al. ...
Article
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Background: The speed of adoption of new drugs and frequencies of substitutions leads to changes in health care expenditures as well as patient outcomes. In this study, we aim to understand the speed of adoption of new drugs and their prescription volume in health care institutions and evaluate the impact of policy options to manage pharmaceutical expenditure. Methods: We conducted a retrospective cohort study of health care institutions prescribing NOACs, including Apixaban, Dabigatran, and Rivaroxaban, to address the speed of adoption and their substitution from October 1, 2010, through December 31, 2015, using the National Health Insurance Service-National Sample Cohort. Two threshold time points, including the extension of reimbursement with the need for the letter of opinion and the withdrawal of the letter of opinion, were noted in this study. Then, we applied a survival analysis to elucidate factors that affected the speed of adoption of NOACs, and interrupted time series analysis to estimate the effect of amendments in reimbursement coverage in prescription volume. Results: Among 934 health care institutions in a study population, 334 institutions (36%) had prescribed NOACs at least one time during the study period, indicating that health care institutions were conservative in adopting new drugs. However, the speed of adoption was related to the characteristics of health care institution. We also found that prescriptions of NOACs before the withdrawal of the need for the letter of opinion were marginal, and the prescription volume of NOACs was significantly increased after the withdrawal of a letter of opinion. Conclusions: Health care institutions were conservative in adopting new drugs, and the speed of adoption is not closely related to an increased prescription volume in the short run. Thus, policies that are centered on managing pharmaceutical expenditure should be devised with considering the impact of introducing new drugs in the long run. A letter of opinion, which was devised to manage prescriptions of NOACs, was effective in managing pharmaceutical expenditures in health care institutions, particularly for tertiary institutions. Conversely, the withdrawal of the need for the letter of opinion should be implemented with caution.
... Regional differences in brand name drug prescribing are likely tied to regional differences in the speed with which physicians adopt new drugs. Studies have evidenced tremendous physician-level variation in adoption speed in several drug categories [6][7][8][9][10]; however, the association between region-level differences of physician adoption of newly introduced brand name drugs and prescription drug spending is still poorly understood. ...
... Third, we obtained physician-level prescribing data from QuintilesIMS Xponent™ which directly captures > 70% of all US prescriptions filled in retail pharmacies, including all payers (Medicare, Medicaid fee-for-service, commercial insurance, cash, and uninsured). Xponent™ utilizes a patented proprietary projection method to represent 100% of prescriptions filled in these outlets and has been widely used by researchers to examine medication use patterns [9,[16][17][18][19][20]. Our Xponent™ data includes all physician prescribers practicing in PA during January 2007-December 2011. ...
... In order to capture both speed and extent of physician adoption of sitagliptin we then constructed two measures: 1) mean time (in months) to first sitagliptin prescription across all physicians in a county using 2007-2011 data, and 2) percent of physicians within a county prescribing sitagliptin at least once in 2007. For the first measure, we chose to allow a five year period for the study physicians to adopt sitagliptin, this is based on prior literature, which has found that the rate of physicians adopting a newly introduced drug plateaus between three and five years post-market introduction [9,24]. Additionally, the latter measure was weighted by each physician's total anti-diabetic prescription volume to give higher weight to physicians with high patient volumes: P AD prescribing volumephysician AD prescribing volumecounty Ã#physicians prescribed sitagliptin in 12 months #of physicians in county : ...
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Background: In the United States, there is well-documented regional variation in prescription drug spending. However, the specific role of physician adoption of brand name drugs on the variation in patient-level prescription drug spending is still being investigated across a multitude of drug classes. Our study aims to add to the literature by determining the association between physician adoption of a first-in-class anti-diabetic (AD) drug, sitagliptin, and AD drug spending in the Medicare and Medicaid populations in Pennsylvania. Methods: We obtained physician-level data from QuintilesIMS Xponent™ database for Pennsylvania and constructed county-level measures of time to adoption and share of physicians adopting sitagliptin in its first year post-introduction. We additionally measured total AD drug spending for all Medicare fee-for-service and Part D enrollees (N = 125,264) and all Medicaid (N = 50,836) enrollees with type II diabetes in Pennsylvania for 2011. Finite mixture model regression, adjusting for patient socio-demographic/clinical characteristics, was used to examine the association between physician adoption of sitagliptin and AD drug spending. Results: Physician adoption of sitagliptin varied from 44 to 99% across the state's 67 counties. Average per capita AD spending was $1340 (SD $1764) in Medicare and $1291 (SD $1881) in Medicaid. A 10% increase in the share of physicians adopting sitagliptin in a county was associated with a 3.5% (95% CI: 2.0-4.9) and 5.3% (95% CI: 0.3-10.3) increase in drug spending for the Medicare and Medicaid populations, respectively. Conclusions: In a medication market with many choices, county-level adoption of sitagliptin was positively associated with AD spending in Medicare and Medicaid, two programs with different approaches to formulary management.
... Medium to high quality studies suggested younger [33,48,53,62] or older [27,42], male [23,42,48,85], graduating from a top-20 medical [23,62] or foreign medical school [48] prescribers were earlier adopters. Other medium to high quality studies reported that age [29,42,48], gender [29,62], prescribers' length of practice [35,85], graduating from a top-20 medical school [48,62] did not influence prescribing decisions. ...
... Medium to high quality studies suggested younger [33,48,53,62] or older [27,42], male [23,42,48,85], graduating from a top-20 medical [23,62] or foreign medical school [48] prescribers were earlier adopters. Other medium to high quality studies reported that age [29,42,48], gender [29,62], prescribers' length of practice [35,85], graduating from a top-20 medical school [48,62] did not influence prescribing decisions. ...
... Medium to high quality studies suggested younger [33,48,53,62] or older [27,42], male [23,42,48,85], graduating from a top-20 medical [23,62] or foreign medical school [48] prescribers were earlier adopters. Other medium to high quality studies reported that age [29,42,48], gender [29,62], prescribers' length of practice [35,85], graduating from a top-20 medical school [48,62] did not influence prescribing decisions. ...
Article
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Background Implementation and uptake of novel and cost-effective medicines can improve patient health outcomes and healthcare efficiency. However, the uptake of new medicines into practice faces a wide range of obstacles. Earlier reviews provided insights into determinants for new medicine uptake (such as medicine, prescriber, patient, organization, and external environment factors). However, the methodological approaches used had limitations (e.g., single author, narrative review, narrow search, no quality assessment of reviewed evidence). This systematic review aims to identify barriers and facilitators affecting the uptake of new medicines into clinical practice and identify areas for future research. Method A systematic search of literature was undertaken within seven databases: Medline, EMBASE, Web of Science, CINAHL, Cochrane Library, SCOPUS, and PsychINFO. Included in the review were qualitative, quantitative, and mixed-methods studies focused on adult participants (18 years and older) requiring or taking new medicine(s) for any condition, in the context of healthcare organizations and which identified factors affecting the uptake of new medicines. The methodological quality was assessed using QATSDD tool. A narrative synthesis of reported factors was conducted using framework analysis and a conceptual framework was utilised to group them. Results A total of 66 studies were included. Most studies (n = 62) were quantitative and used secondary data (n = 46) from various databases, e.g., insurance databases. The identified factors had a varied impact on the uptake of the different studied new medicines. Differently from earlier reviews, patient factors (patient education, engagement with treatment, therapy preferences), cost of new medicine, reimbursement and formulary conditions, and guidelines were suggested to influence the uptake. Also, the review highlighted that health economics, wider organizational factors, and underlying behaviours of adopters were not or under explored. Conclusion This systematic review has identified a broad range of factors affecting the uptake of new medicines within healthcare organizations, which were grouped into patient, prescriber, medicine, organizational, and external environment factors. This systematic review also identifies additional factors affecting new medicine use not reported in earlier reviews, which included patient influence and education level, cost of new medicines, formulary and reimbursement restrictions, and guidelines. Registration PROSPERO database (CRD42018108536).
... Therefore, we constructed three measures: 1) any prescription of the newly approved medication in the final year of the study period (2011), 2) proportion of new medication among the medication class, and 3) time to first adoption of the newly approved medication. Time to first adoptiondefined as the time from FDA approval to first prescription of the new drugprovides a measure of speed of adoption, while the other two measures identify the extent of provider adoption over time [19]. In order to assess NP and PA prescribing trends in general, we also measured the share of prescribing within the drug classes of interest accounted for by NPs and PAs compared to PCPs over time. ...
... Given an older, more complex patient panel, PCPs may be more likely to prescribe from a broader prescription armamentarium, including newly approved drugs. In addition, some evidence points to provider sex as an important factor in health technology adoption; male providers tend to adopt new treatment more rapidly on average [19]. Our findings support this notion, given that the vast majority of NPs and PAs were female compared to one-third of PCPs. ...
Article
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Background: Medications to treat and prevent chronic disease have substantially reduced morbidity and mortality; however, their diffusion has been uneven. Little is known about prescribing of chronic disease medications by nurse practitioners (NPs) and physician assistants (PAs), despite their increasingly important role as primary care providers. Thus, we sought to conduct an exploratory analysis to examine prescribing of new chronic disease medications by NPs and PAs compared to primary care physicians (PCPs). Methods: We obtained prescribing data from IMS Health's Xponent™ on all NPs, PAs, and PCPs in Pennsylvania regularly prescribing anticoagulants, antihypertensives, oral hypoglycemics, and/or HMG-Co-A reductase inhibitors pre- and post-introduction of five new drugs in these classes that varied in novelty (i.e., dabigatran, aliskiren, sitagliptin or saxagliptin, and pitavastatin). We constructed three measures of prescriber adoption during the 15-month post-FDA approval period: 1) any prescription of the medication, 2) proportion of prescriptions in the class for the medication, and 3) time to adoption (first prescription) of the medication. Results: From 2007 to 2011, the proportion of antihypertensive prescriptions prescribed by NPs and PAs approximately doubled from 2.0 to 4.2 % and 2.2 to 4.9 %, respectively. Similar trends were found for anticoagulants, oral hypoglycemics, and HMG-Co-A reductase inhibitors. By 2011, more PCPs had prescribed each of the newly approved medications than NPs and PAs (e.g., 44.3 % vs. 18.5 % vs. 20 % for dabigatran among PCPs, NPs, and PAs). Across all medication classes, the newly approved drugs accounted for a larger share of prescriptions in the class for PCPs followed by PAs, followed by NPs (e.g., dabigatran: 4.9 % vs. 3.2 % vs. 2.8 %, respectively). Mean time-to-adoption for the newly approved medications was shorter for PCPs compared to NPs and PAs (e.g., dabigatran, 7.3 vs. 8.2 vs. 8.5 months; P all medications <0.001). Conclusions: PCPs were more likely to prescribe each of the newly approved medications per each measure of drug adoption, regardless of drug novelty. Differences in the rate and speed of drug adoption between PCPs, NPs, and PAs may have important implications for care and overall costs at the population level as NPs and PAs continue taking on a larger role in prescribing.
... [15][16][17][18] The diffusion of innovation theory postulates that an S-shaped curve characterizes the adoption of a new technology or scientific advance, with initial uptake by a small number of early adopters followed by rapid dissemination of knowledge and utilization by the remainder of a population. [19][20][21][22] The process can occur quite quickly, as in the case of protease inhibitors for use in HIV. 17 An analysis of sildenafil prescriptions in the 24 weeks following its availability in an HMO plan showed that 85% of the prescriptions were placed within the first 12 weeks of availability, primarily by PCPs. 23 Our findings that overall OAC prescriptions did not differ by PCP gating status may suggest completion of the rapid dissemination and uptake phase for most AF treatments. ...
Article
Background Cost‐effectiveness or value of cardiovascular therapies may be undermined by unwarranted cost variation, particularly for heterogeneous procedures such as catheter ablation for atrial fibrillation (AF). We sought to characterize cost variation of AF ablation in the U.S. health care system and the relationship between cost and outcomes. Methods and results We performed a retrospective cohort study using data from the MarketScan® commercial claims and Medicare supplemental databases including patients who received an AF ablation from 2007 through 2011. We aggregated encounter cost, reflecting total payments received for the encounter, to the facility level to calculate median facility cost. We classified procedures as outpatient or inpatient and assessed for association between cost and 30‐day and one‐year outcomes. The analysis cohort included 9,415 AF ablations (59±11 years; 28% female; 52% outpatient) occurring at 327 facilities, with large cost variation across facilities (median: $25,100; 25th percentile: $18,900, 75th percentile: $35,600, 95th percentile: $57,800). Among outpatient procedures, there was reduced health care utilization in higher cost quintiles with reductions in rehospitalization at 30‐days (Quintile 1: 16.1%, Quintile 5: 8.8%, p < 0.001) and one‐year (Quintile 1: 34.8%, Quintile 5: 25.6%, p < 0.001), which remained significant in multivariate analysis. Conclusions Although median costs of AF ablation are below amounts used in prior cost‐effectiveness studies that demonstrated good value, large facility variation in cost suggests opportunities for cost reduction. However, for outpatient encounters, association of cost to modestly improved outcomes suggests cost containment strategies could have variable effects. This article is protected by copyright. All rights reserved
... To examine if regions where beneficiaries were more likely to be seen by an endocrinologist had higher rates of IM use, we created a beneficiary-level dichotomous variable indicating receipt of any antidiabetic prescription from an endocrinologist. [19][20][21] ...
Article
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When incretin mimetic (IM) medications were introduced in 2005, their effectiveness compared with other less-expensive second-line diabetes therapies was unknown, especially for older adults. Physicians likely had some uncertainty about the role of IMs in the diabetes treatment armamentarium. Regional variation in uptake of IMs may be a marker of such uncertainty. To investigate the extent of regional variation in the use of IMs among beneficiaries and estimate the cost implications for Medicare. This was a cross-sectional analysis of 2009-2010 claims data from a nationally representative sample of 238 499 Medicare Part D beneficiaries aged ≥65 years, who were continuously enrolled in fee-for-service Medicare and Part D and filled ≥1 antidiabetic prescription. Beneficiaries were assigned to 1 of 306 hospital-referral regions (HRRs) using ZIP codes. The main outcome was adjusted proportion of antidiabetic users in an HRR receiving an IM. Overall, 29 933 beneficiaries (12.6%) filled an IM prescription, including 26 939 (11.3%) for sitagliptin or saxagliptin and 3718 (1.6%) for exenatide or liraglutide. The adjusted proportion of beneficiaries using IMs varied more than 3-fold across HRRs, from 5th and 95th percentiles of 5.2% to 17.0%. Compared with non-IM users, IM users faced a 155% higher annual Part D plan ($1067 vs $418) and 144% higher patient ($369 vs $151) costs for antidiabetic prescriptions. Among older Part D beneficiaries using antidiabetic drugs, substantial regional variation exists in the use of IMs, not accounted for by sociodemographics and health status. IM use was associated with substantially greater costs for Part D plans and beneficiaries. © The Author(s) 2014.
... In addition, in those disorders where there is some evidence for use of a short-acting alpha agonist (e.g., autism), it is anticipated that further studies of the use of long-acting formulations will follow. The sustained predominance of short-acting forms over the course of the study period is consistent with prior research that found slow and inconsistent adoption of new psychotropic medications (Huskamp, et al. 2013), and could also indicate a preference for focusing on symptoms confined to particular times of day (e.g., before bedtime). ...
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The purpose of this study was to describe rates and patterns of long- and short-acting alpha agonist use for behavioral problems in a primary care population following Food and Drug Administration (FDA) approval of the long-acting alpha agonists guanfacine and clonidine. Children and adolescents 4-18 years of age, who received an alpha agonist prescription between 2009 and 2011, were identified from a sample of 45 United States primary care practices in two electronic health record-based research networks. Alpha agonist receipt was identified using National Drug Codes and medication names. The proportion of subjects receiving long- and short-acting prescriptions in each year was calculated and examined with respect to reported mental health diagnoses, and whether indications for use were on-label, had evidence from clinical trials, or had no trial evidence. In a cohort of 282,875 subjects, 27,671 (10%) received any psychotropic medication and only 4,227 subjects (1.5%) received at least one prescription for an alpha agonist, most commonly a short-acting formulation (83%). Only 20% of alpha agonist use was on-label (use of long-acting formulations for attention-deficit/hyperactivity disorder [ADHD]). Most subjects (68%) received alpha agonists for indications with evidence of efficacy from clinical trials but no FDA approval, primarily short-acting formulations for ADHD and autism; 12% received alpha agonists for diagnoses lacking randomized clinical trial evidence in children, including sleep disorders and anxiety, or for which there was no documented mental health diagnosis. Rates of long-acting alpha agonist use increased more than 20-fold from 0.2% to 4%, whereas rates of short-acting alpha agonist use grew only slightly between 2009 and 2011 from 10.6% to 11.3%. Alpha agonist use was uncommon in this population, and most subjects received short-acting forms for conditions that were off-label, but with clinical trial evidence. The safety and efficacy of use for conditions, including sleep disorders and anxiety, lacking evidence from randomized trials, warrant further investigation.
... This has at least two important clinical impacts: (i) it facilitates "patient-centered care" in which patients play a key role in decision making and the evaluation of their own health outcomes; and (ii) it offers a principled means for matching patient preferences to an optimal treatment based on potentially complex outcome profiles. While many clinical and intervention scientists already seek to implement patientcentered care and to personalize treatment decisions based on patient preferences, it is recognized that the rapid introduction of new therapies and a high-degree of patient preference heterogeneity makes this a difficult task to perform using expert judgement alone (Smoller and Nierenberg, 1999;Basu and Meltzer, 2007;Frank and Zeckhauser, 2007;Hodgkin et al., 2012;Huskamp et al., 2013). The proposed methodology can be viewed as a tool for clinical decision support in the context of patient-centered care. ...
Article
Precision medicine seeks to provide treatment only if, when, to whom, and at the dose it is needed. Thus, precision medicine is a vehicle by which healthcare can be made both more effective and efficient. Individualized treatment rules operationalize precision medicine as a map from current patient information to a recommended treatment. An optimal individualized treatment rule is defined as maximizing the mean of a pre-specified scalar outcome. However, in settings with multiple outcomes, choosing a scalar composite outcome by which to define optimality is difficult. Furthermore, when there is heterogeneity across patient preferences for these outcomes, it may not be possible to construct a single composite outcome that leads to high-quality treatment recommendations for all patients. We simultaneously estimate the optimal individualized treatment rule for all composite outcomes representable as a convex combination of the (suitably transformed) outcomes. For each patient, we use a preference elicitation questionnaire and item response theory to derive the posterior distribution over preferences for these composite outcomes and subsequently derive an estimator of an optimal individualized treatment rule tailored to patient preferences. We prove that as the number of subjects and items on the questionnaire diverge, our estimator is consistent for an oracle optimal individualized treatment rule wherein each patient's preference is known a priori. We illustrate the proposed method using data from a clinical trial on antipsychotic medications for schizophrenia.
... The most abundant data are for FGA, while studies on SGA are sparse, even in the last decade during which SGAs have essentially replaced FGAs in clinical practice (7,(23)(24)(25). The largest study on the association between SGA and breast cancer is a case-control study including only 96 SGA-exposed breast cancer cases, reporting no excess risk of SGA compared with FGA (26). ...
Article
Aims: Some antipsychotics increases prolactin levels, which might increase the risk of breast cancer. Existing evidence is conflicting and based on sparse data, especially for the increasingly used second-generation antipsychotics. We conducted a nationwide case-control study of the association between antipsychotic use and incident breast cancer. Methods: From the Danish Cancer Registry, we identified women with a first-time diagnosis of breast cancer 2000-2015 (n=60,360). For each case, we age-matched 10 female population controls. Using conditional logistic regression, we calculated odds ratios (ORs) for breast cancer associated with use of antipsychotics. We stratified antipsychotics by first and- second generation status and by ability to induce elevation of prolactin. Results: 4,951 cases (8.1%) and 47,643 controls (7.1%) had ever used antipsychotics. Long-term use (≥10,000 mg olanzapine equivalents) was associated with breast cancer, with an adjusted OR of 1.18 (95%CI, 1.06, 1.32). A weak dose-response pattern was seen, with ORs increasing to 1.27 (95% CI 1.01, 1.59) for ≥50,000mg olanzapine equivalents. Associations were similar for first- and second-generation antipsychotics (ORs 1.17 vs 1.11), but also for non-prolactin inducing antipsychotics (OR 1.17). Stratifying by estrogen receptor status, positive associations were seen for estrogen receptor positive cancers (long-term use: OR 1.29; 95% CI 1.13, 1.47) while no associations were observed for estrogen receptor negative cancers. Conclusions: Overall, our results do not suggest a clinically important association between antipsychotic use and risk of breast cancer. The importance of drug-induced prolactin elevation is unclear but may lead slightly increased risk of estrogen receptor positive breast cancer.
... Moreover, significant variations among cantons' healthcare costs have been observed [4], which raises the question of fair access to new products. Thus, researchers and policy makers are interested in finding ways to control factors that influence physician's adoption of new medications (see, e.g., this paper on mental disorders drugs [5]). ...
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Background: Drug markets are very complex and, while many new drugs are registered each year, little is known about what drives the prescription of these new drugs. This study attempts to lift the veil from this important subject by analyzing simultaneously the impact of several variables on the prescription of novelty. Methods: Data provided by four Swiss sickness funds were analyzed. These data included information about more than 470,000 insured, notably their drug intake. Outcome variable that captured novelty was the age of the drug prescribed. The overall variance in novelty was partitioned across five levels (substitutable drug market, patient, physician, region, and prescription) and the influence of several variables measured at each of these levels was assessed using a non-hierarchical multilevel model estimated by Bayesian Markov Chain Monte Carlo methods. Results: More than 92% of the variation in novelty was explained at the substitutable drug market-level and at the prescription-level. Newer drugs were prescribed in markets that were costlier, less concentrated, included more insured, provided more drugs and included more active substances. Over-the-counter drugs were on average 12.5 years older while generic drugs were more than 15 years older than non-generics. Regional disparities in terms of age of prescribed drugs could reach 2.8 years. Conclusions: Regulation of the demand has low impact, with little variation explained at the patient-level and physician-level. In contrary, the market structure (e.g. end of patent with generic apparition, concurrence among producers) had a strong contribution to the variation of drugs ages.
... [15][16][17][18] The diffusion of innovation theory postulates that an S-shaped curve characterizes the adoption of a new technology or scientific advance, with initial uptake by a small number of early adopters followed by rapid dissemination of knowledge and utilization by the remainder of a population. [19][20][21][22] The process can occur quite quickly, as in the case of protease inhibitors for use in HIV. 17 An analysis of sildenafil prescriptions in the 24 weeks following its availability in an HMO plan showed that 85% of the prescriptions were placed within the first 12 weeks of availability, primarily by PCPs. 23 Our findings that overall OAC prescriptions did not differ by PCP gating status may suggest completion of the rapid dissemination and uptake phase for most AF treatments. ...
Article
Background Atrial fibrillation (AF) is treated by many types of physician specialists, including primary care physicians (PCPs). Health plans have different policies for how patients encounter these providers, and these may affect selection of AF treatment strategy. Hypothesis We hypothesized that healthcare plans with PCP‐gatekeeping to specialist access may be associated with different pharmacologic treatments for AF. Methods We performed a retrospective cohort study using a commercial pharmaceutical claims database. We utilized logistic regression models to compare odds of prescription of oral anticoagulant (OAC), non‐vitamin K‐dependent oral anticoagulant (NOAC), rate control, and rhythm control medications used to treat AF between patients with PCP‐gated healthcare plans (e.g. HMO, EPO, POS) and patients with non‐PCP‐gated healthcare plans (e.g. PPO, CHDP, HDHP, Comprehensive) between 2007 and 2012. We also calculated median time to receipt of therapy within 90 days of index AF diagnosis. Results We found similar odds of OAC prescription at 90 days following new AF diagnosis in patients with PCP‐gated plans compared to those with non‐PCP‐gated plans (OR: OAC 1.01, p=0.84; warfarin 1.05, p=0.08). Relative odds were similar for rate control (1.17, p<0.01) and rhythm control agents (0.93, p=0.03). However, PCP‐gated plan patients had slightly lower likelihood of being prescribed NOACs (0.82, p=0.001) than non‐gated plan patients. Elapsed time until receipt of medication was similar between PCP‐gated and non‐gated groups across drug classes. Conclusions Pharmaceutical claims data do not suggest that PCP‐gatekeeping by healthcare plans is a structural barrier to AF therapy, although it was associated with lower use of NOACs.
... Data are needed on factors at the system, clinician, and patient level that influence use of WMM to supplement behavioral weight-loss treatment. Experience with uptake of other medications indicates that the reasons for adoption often do not involve national CFU or even site-level written policies but may be influenced by informal local policies and opinion climates (40)(41)(42)(43)(44)(45). These, in turn, may reflect clinicians' relative valuations of WMM safety, efficacy, and workflow impact. ...
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Objective Weight‐management medications (WMM) are recommended for the treatment of obesity. This study examined characteristics associated with initial receipt of WMM among eligible veterans in the first year following enrollment in the Veterans Health Administration (VHA) MOVE! behavioral weight‐management program. Methods We conducted a retrospective cohort study of VHA patients with obesity or overweight and obesity‐related comorbidities who enrolled in MOVE! from October 2013 to September 2016 (N = 153,939). Multivariable logistic regression models estimated predictors of having a filled prescription for WMM and for orlistat. Results A total of 1.1% of these veterans received WMM. The most common WMM included orlistat (70.4%), phentermine/topiramate (11.2%), and bupropion/naltrexone (9.7%). Female sex, higher BMI, obstructive sleep apnea, osteoarthritis, depression, lower back pain, and alcohol abuse were associated with greater odds of use of WMM, whereas age over 65 years, Hispanic ethnicity, and required co‐payments were associated with lower odds. Among patients receiving WMM, older age, black race, female sex, higher BMI, cardiovascular disease, lower back pain, and congestive heart failure were associated with use of orlistat versus any other WMM. Conclusions Of patients engaged in MOVE! in the VHA, 1.1% received WMM. WMM are underutilized among veterans. Additional research is needed to understand barriers to incorporating WMM into comprehensive obesity treatment plans.
... These two drugs, classified as first-generation antipsychotics (FGAs), are used less frequently now than in the past, although they are known to be effective and safe for the treatment of schizophrenia. 15 Haloperidol may produce significant extrapyramidal side effects (EPS) which were often associated with its high doses. 16 However, PET studies have suggested that its low doses are preferable. ...
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Background: Implementation and uptake of novel and cost-effective medicines can improve patient health outcomes and healthcare efficiency. However, the uptake of new medicines into practice faces a wide range of obstacles Earlier reviews provided insight into determinants for new medicine uptake (such as medicine, prescriber, patient, organization, and external environment factors), but the methodological approaches used had limitations (e.g., single author, narrative review, narrow search, no quality assessment of reviewed evidence).This systematic review aims to identify barriers and facilitators affecting the uptake of new medicines into clinical practice and identify areas for future research. Method: A systematic search was undertaken within seven databases. Eligible qualitative, quantitative, and mixed-methods studies focused on adult participants (18 years and older) requiring or taking new medicine(s) for any condition, in the context of healthcare organizations and identified factors affecting the uptake of new medicines. The methodological quality was assessed using QASTDD tool. A narrative synthesis of reported factors was conducted using framework analysis and conceptual framework was utilised to group them. Results: A total of 66 studies were included. Most studies (n=62) were quantitative and used secondary data (n=46) from various databases, e.g., insurance databases. The identified factors had a varied impact on the uptake of the different studied new medicines. Differently from earlier reviews, patient factors (patient education, engagement with treatment, therapy preferences), cost of new medicine, reimbursement and formulary conditions, and guidelines were suggested to influence the uptake. Also, the review highlighted that health economics, wider organizational factors, and underlying behaviours of adopters were not or under explored. Conclusion: This systematic review identifies additional factors affecting new medicine use not reported in earlier reviews, which included patient influence and education level, cost of new medicines, formulary and reimbursement restrictions, and guidelines. Further research employing determinant frameworks or implementation theories is needed to gain a better understanding of factors, especially patient, prescriber, and organizational, affecting the uptake of new medicines into clinical practice. Registration: PROSPERO database (CRD42018108536)
Article
Academic medical centers (AMCs) have increasingly adopted conflict of interest policies governing physician-industry relationships; it is unclear how policies impact prescribing. To determine whether 9 American Association of Medical Colleges (AAMC)-recommended policies influence psychiatrists' antipsychotic prescribing and compare prescribing between academic and nonacademic psychiatrists. We measured number of prescriptions for 10 heavily promoted and 9 newly introduced/reformulated antipsychotics between 2008 and 2011 among 2464 academic psychiatrists at 101 AMCs and 11,201 nonacademic psychiatrists. We measured AMC compliance with 9 AAMC recommendations. Difference-in-difference analyses compared changes in antipsychotic prescribing between 2008 and 2011 among psychiatrists in AMCs compliant with ≥7/9 recommendations, those whose institutions had lesser compliance, and nonacademic psychiatrists. Ten centers were AAMC compliant in 2008, 30 attained compliance by 2011, and 61 were never compliant. Share of prescriptions for heavily promoted antipsychotics was stable and comparable between academic and nonacademic psychiatrists (63.0%-65.8% in 2008 and 62.7%-64.4% in 2011). Psychiatrists in AAMC-compliant centers were slightly less likely to prescribe these antipsychotics compared with those in never-compliant centers (relative odds ratio, 0.95; 95% CI, 0.94-0.97; P<0.0001). Share of prescriptions for new/reformulated antipsychotics grew from 5.3% in 2008 to 11.1% in 2011. Psychiatrists in AAMC-compliant centers actually increased prescribing of new/reformulated antipsychotics relative to those in never-compliant centers (relative odds ratio, 1.39; 95% CI, 1.35-1.44; P<0.0001), a relative increase of 1.1% in probability. Psychiatrists exposed to strict conflict of interest policies prescribed heavily promoted antipsychotics at rates similar to academic psychiatrists and nonacademic psychiatrists exposed to less strict or no policies.
Article
Antipsychotics are prescribed frequently to treat a wide range of psychiatric and non-psychiatric indications. Over the last few years there has been a marked increase in the use of antipsychotics. However, specific prescribing patterns seem to be determined mainly by regional and national differences. In this study we compare developments in the sales of antipsychotics in the three Belgian regions (Flanders, Wallonia and Brussels) between 2004 and 2012. For our study we used data supplied by Pharmanet regarding the sales of their antipsychotics in Belgium. Pharmanet forms part of the National Institute for Health and Disability Insurance (RIZIV), which is the organisation responsible for collecting information about the prescription behaviour of Belgian doctors. Between 2004 and 2012 the sales of antipsychotics in Belgium increased by 57 %. Nevertheless, the low percentage of prescriptions for long-term use (6.6-8.7 % of the antipsychotics prescribed for a treatment period of six months or longer) suggests that several important groups of patients were being undertreated. Relative to the size of the population of Belgium as a whole, more antipsychotics were sold in Wallonia and Brussels than in Flanders, a trend that remained relatively stable over time, namely over the period 2004 and 2012. The preference for second-generation antipsychotics was more pronounced in Flanders and the shift to second-generation antipsychotics occurred faster in Flanders than in Wallonia and Brussels. In Belgium there seems a clear need for a more unified and rational policy with regards to the prescribing and use of psychotropic drugs.
Article
Objectives: Limited information is available regarding provider- and patient panel-level factors associated with primary care provider (PCP) adoption/prescribing of medication for opioid use disorder (MOUD). Methods: We assessed a retrospective cohort from 2015 to 2018 within the Pennsylvania Medicaid Program. Participants included PCPs who were Medicaid providers, with no history of MOUD provision, and who treated ≥10 Medicaid enrollees annually. We assessed initial MOUD adoption, defined as an index buprenorphine/buprenorphine-naloxone or oral/extended release naltrexone fill and sustained prescribing, defined as ≥1 MOUD prescription(s) for 3 consecutive quarters from the PCP. Independent variables included provider- and patient panel-level characteristics. Results: We identified 113 rural and 782 urban PCPs who engaged in initial adoption and 36 rural and 288 urban PCPs who engaged in sustained prescribing. Rural/urban PCPs who issued increasingly larger numbers of antidepressant and antipsychotic medication prescriptions had greater odds of initial adoption and sustained prescribing (P < 0.05) compared to those that did not prescribe these medications. Further, each additional patient out of 100 with opioid use disorder diagnosed before MOUD adoption increased the adjusted odds for initial adoption 2% to 4% (95% confidence interval [CI] = 1.01-1.08) and sustained prescribing by 4% to 7% (95% CI = 1.01-1.08). New Medicaid providers in rural areas were 2.52 (95% CI = 1.04-6.11) and in urban areas were 2.66 (95% CI = 1.94, 3.64) more likely to engage in initial MOUD adoption compared to established PCPs. Conclusions: MOUD prescribing adoption was concentrated among PCPs prescribing mental health medications, caring for those with OUD, and new Medicaid providers. These results should be leveraged to test/implement interventions targeting MOUD adoption among PCPs.
Article
Physician adoption of new technologies is a key issue for population health and the sustainability of the healthcare system. This paper explores gender differences in general practitioners’ (GPs) adoption of new oral anticoagulants. We combine detailed individual data on physician and practice style characteristics from the Medicine in Australia: Balancing Employment and Life (MABEL) panel survey of Australian physicians with administrative prescribing data from the Australian Pharmaceutical Benefits Scheme (PBS) and the Medicare Benefits Schedule (MBS) for the period 1 January 2012 and 31 December 2015. After adjusting for various factors proposed in the literature as drivers of this gender gap, in addition to risk preferences and personality traits, we find a large statistical gender difference in the speed of adoption with men being faster than women in uptake. However, conditional on having prescribed for the first time, female and male GPs differ only slightly in the intensity of use of these new drugs. The relatively large gender difference that remains in the speed of adoption could be due to gender-based differences in access to information and networks in medicine, and women’s greater caution as the result of differences in practice styles.
Article
New prescription medications are a primary driver of spending growth in the United States. For patients with severe mental illnesses, second generation antipsychotic (SGA) medications feature prominently. However, many SGAs are costly, particularly before generic entry, and some may increase the risk of diabetes. Because physicians play a prominent role in new prescription adoption, understanding their prescribing behaviors is policy‐relevant. Several features of prescription data, such as different antipsychotic choice sets over time, variable physician prescription volumes, and correlation among drug choices within physicians, complicate inferences. We propose a multivariate Bayesian hierarchical model with piecewise random effects to characterize the diffusion of new antipsychotic drugs. This model captures the complex prescriber‐specific relationships among the different diffusion processes and takes advantage of the Bayesian paradigm to quantify uncertainty for all parameters straightforwardly. To evaluate the prescribing patterns for each physician, we propose various indices to identify early new SGA adopters. A sample of nearly 17,000 U.S. physicians whose antipsychotic drug prescribing information was collected between January 1, 1997 and December 31, 2007 illustrates the methods. Determinants of high prescription rates and adoption speeds of new SGAs included physician sex, age, hospital affiliation, physician specialty, and office location. Large within‐ and between‐provider variations in prescribing patterns of new SGAs were identified. Early adopters for one drug were not early adopters for another drug. This article is protected by copyright. All rights reserved
Article
Objectives The number of antipsychotic prescriptions are increasing rapidly worldwide, a trend which is mainly driven by the steep rise in second-generation antipsychotic (SGA) prescriptions. However, the success of SGA, compared with the older first-generation antipsychotics (FGAs), cannot be explained by evidence. Several studies concluded on equal efficacy of FGA and SGA on positive, negative and cognitive symptoms of schizophrenia. Next to that, the influence of the pharmaceutical industry on prescription behaviour has drawn considerable interest. Therefore, the relationship between antipsychotic prescription patterns and exposure to information directly provided by pharmaceutical companies was studied. Methods A cross-sectional online survey, addressing psychiatrists, general practitioners (GPs) and trainees in Flanders, was carried out. Respondents were questioned about their prescription behaviour, opinion about efficacy of SGA versus FGA and the nature and frequency of their contact with the pharmaceutical industry. Using Spearman's rank correlations and χ² tests, the relationship between different variables and group differences were examined. Results Psychiatrists, GPs and trainees in Flanders clearly favour olanzapine and risperidone, followed by quetiapine and aripiprazole above all other agents. This behaviour is supported by the conviction that SGAs have superior efficacy and a more benign side effect profile, compared with FGA. Frequent contact with drug representatives is correlated with a preference of SGA over FGA. 41% of the respondents acknowledge to be influenced by the pharmaceutical industry, which is more than that previously reported.
Article
BackgroundA recent large database analysis raised concerns of potential acute kidney injury (AKI) risk associated with antipsychotics. However, whether individual atypical and typical antipsychotics are associated with differential AKI risks has not been investigated. Objective The current study compared the risks of AKI and known causes of AKI associated with a broad range of atypical and typical antipsychotics. Method This retrospective cohort analysis used January 2007–June 2013 US nationwide Humana claims data to define episodes of antipsychotic drug therapy for patients with schizophrenia and bipolar disorder. Study drugs were aripiprazole, fluphenazine, haloperidol, olanzapine, quetiapine, risperidone, and ziprasidone. Study outcomes were hospitalizations with AKI, and known causes of AKI, i.e., hypotension, acute urinary retention, neuroleptic malignant syndrome/rhabdomyolysis, and pneumonia. AKI was the primary outcome of the study. Cox regressions using haloperidol as the baseline comparator were used to estimate the impact of alternative antipsychotics on the risks of study adverse events following the initiation of treatment. The Cox models controlled for treatment history, comorbidities, and concomitant drug use in the prior 6 months. They also controlled for patient demographics and dose of current treatment. ResultsThe overall incidence of AKI was 25.0 per 1000 person-years. According to our multivariate regression results, the risk of AKI was significantly increased in patients taking olanzapine [hazard ratio (HR) 1.344, 95% confidence interval (CI) 1.057–1.708], quetiapine (HR 1.350, 95% CI 1.082–1.685), and ziprasidone (HR 1.338, 95% CI 1.035–1.729) relative to haloperidol. Aripiprazole (HR 1.152, 95% CI 0.908–1.462) and risperidone (HR 1.147, 95% CI 0.923–1.426) had insignificantly higher risks of AKI compared with haloperidol, whereas fluphenazine (HR 0.729, 95% CI 0.483–1.102) had an insignificantly lower risk of AKI. When compared between drug classes, atypical antipsychotics had a significantly higher risk of AKI (HR 1.313, 95% CI 1.083–1.591) than typical antipsychotics. Conclusions Antipsychotics are associated with differential AKI risks, with several atypical antipsychotics having higher risks than haloperidol. However, the overall incidence of AKI was moderate, and AKI risk should only raise concern for clinicians with elderly patients or patients who are vulnerable to kidney disease.
Article
Background: Regional variation in US Medicare prescription drug spending is driven by higher prescribing of costly brand-name drugs in some regions. This variation likely arises from differences in the speed of diffusion of newly-approved medications. Second-generation antipsychotics were widely adopted for treatment of severe mental illness and for several off-label uses. Rapid diffusion of new psychiatric drugs likely increases drug spending but its relationship to non-drug spending is unclear. The impact of antipsychotic diffusion on drug and medical spending is of great interest to public payers like Medicare, which finance a majority of mental health spending in the US. Aims: We examine the association between physician adoption of new antipsychotics and antipsychotic spending and non-drug medical spending among disabled and elderly Medicare enrollees. Methods: We linked physician-level data on antipsychotic prescribing from an all-payer dataset (IMS Health's XponentTM) to patient-level data from Medicare. Our physician sample included 16,932 US. psychiatrists and primary care providers with > 10 antipsychotic prescriptions per year from 1997-2011. We constructed a measure of physician adoption of 3 antipsychotics introduced during this period (quetiapine, ziprasidone and aripiprazole) by estimating a shared frailty model of the time to first prescription for each drug. We then assigned physicians to one of 306 U.S. hospital referral regions (HRRs) and measured the average propensity to adopt per region. Using 2010 data for a random sample of 1.6 million Medicare beneficiaries, we identified 138,680 antipsychotic users. A generalized linear model with gamma distribution and log link was used to estimate the effect of region-level adoption propensity on beneficiary-level antipsychotic spending and non-drug medical spending adjusting for patient demographic and socioeconomic characteristics, health status, eligibility category, and whether the antipsychotic was for an on- vs. off-label use. Results: In our sample, mean patient age was 62 years, 42% were male, and 86% had low-income. Half of antipsychotic users in Medicare had an on-label indication. The weighted average propensity to adopt the three new antipsychotics varied four-fold across HRRs. For every one standard deviation increase in the propensity to adopt there was a 5% increase in antipsychotic spending after adjusting for covariates (adjusted ratio of spending 1.05, 95% CI 1.01-1.08, p = 0.005). Physician propensity to adopt new antipsychotics was not associated with non-drug medical spending (adjusted ratio 0.96, 95% CI 0.91-1.01, p < 0.117). Discussion: These findings suggest wide regional variation in physicians' propensity to adopt new antipsychotic medications. While physician adoption of new antipsychotics was positively associated with antipsychotic expenditures, it was not associated with non-drug spending. Our analysis is limited to Medicare and may not generalize to other payers. Also, claims data do not allow for the measurement of health outcomes, which would be important to evaluate when calculating the value of rapid vs. slow technology adoption.
Article
Background The use of equipment powered by electricity in the operating room increased the risk of fires in the presence of flammable agents such as ether and cyclopropane. Chloroform was associated with cardiac arrhythmias and liver damage. The introduction of halothane in the late 1950s was heralded as a solution to many problems facing the specialty. We explore whether the manufacturer promptly reported halothane's adverse effects to regulatory agencies and practitioners. Sources We consulted documents submitted by Ayerst Laboratories to federal authorities, through the freedom of information act (FOIA), promotional advertisements, package inserts, published articles, and textbooks. Results Two major complications associated with the use of halothane, cardiac arrhythmias and the risk of hepatotoxicity, were disclosed by the manufacturer when the drug was first introduced to the United States (US) market. Reports appeared timely and complete; there was no apparent attempt to conceal or otherwise downplay these risks. Conclusion The process of drug discovery and approval for clinical use has always been a lengthy, complex and extremely expensive undertaking, with only a small minority of compounds receiving approval. The risk of adverse effects or drug interaction directly impacts commercial viability. In the case of halothane, the manufacturer disclosed major side effects and the drug enjoyed decades of popularity until it was replaced by agents with a better drug profile.
Article
Over the last year, in response to public outcry, the US Congress has taken a special interest in—and held several hearings on—prescription drug prices. While this is a welcome move, these debates largely ignore prudent discussions surrounding exorbitant health expenses associated with approved novel cancer drugs. In this commentary, we argue that significant financial burden associated with these promising therapies is a reminder of how increasing utilization of these medications—without regard to unbiased distribution—specifically breeds unintended consequences, such as racial and ethnic health inequities. Additionally, we elucidate how variations in access to novel cancer treatments may even exacerbate current health inequities. Our editorial also highlights how inequitable dissemination of novel cancer drugs takes place along racial and socio-economic lines and how this leads to financial toxicities and other adverse consequences. We introduce a novel and an innovative research framework for investigators that can be used in research projects that aim to understand the dissemination of novel therapies.
Article
Background: Little is known about physicians' approaches to adopting new cardiovascular drugs and how adoption varies between drugs of differing novelty. Methods: Using data on dispensed prescriptions from IMS Health's Xponent™ database, we created a cohort of all primary care physicians (PCPs) and cardiologists in Pennsylvania who regularly prescribed anticoagulants, antihypertensives and statins from 2007 to 2011. We examined prescribing of three new cardiovascular drugs of differing novelty: dabigatran, aliskiren and pitavastatin. Outcomes were rapid adoption of each new drug, defined by early and sustained monthly prescribing detected by group-based trajectory models, by physicians within the first 15 months of marketplace introduction. Results: 5953 physicians regularly prescribed each drug class. The majority of physicians (63.8%) adopted zero new drugs in the first 15 months, 35.0% rapidly adopted one or two, and 1.2% rapidly adopted all three. Physicians were more likely to rapidly adopt the most novel drug, dabigatran (27.3%), than aliskiren (10.5%) or pitavastatin (8.0%). Physician specialty and sex were the most consistent predictors of adoption. Compared to PCPs, cardiologists were more likely to rapidly adopt dabigatran (Adjusted Odds Ratio 8.90, 95% confidence interval 7.42-10.67; P<0.001) aliskerin (2.05, CI 1.56-2.69; P<0.001) and pitavastatin (3.44, CI 2.60-4.57; P<0.001). Female physicians were less likely to adopt dabigatran (0.71, CI 0.59-0.85; P <0.001) and aliskiren (0.64, CI 0.49-0.83; P <0.001). Conclusions: Physicians vary in their prescribing of recently-introduced cardiovascular drugs. Though most physicians did not rapidly adopt any new cardiovascular drugs, drug novelty and cardiology training were associated with greater adoption.
Article
Objectives: This study aimed to assess physician comfort, knowledge, and implementation barriers regarding the use of intranasal fentanyl (INF) for pain management in patients with long-bone fractures in a pediatric emergency department (ED) with an INF pain pathway. Methods: A retrospective chart review was conducted of patients, 3 to 21 years old, in our ED with an International Classification of Diseases-9th Revision code for a long-bone fracture from September 1, 2013, to August 31, 2015. Patients were divided into 4 groups: (1) received INF on the pathway appropriately; (2) "missed opportunities" to receive INF, defined as either INF was ordered and then subsequently canceled (for pain ratings, ≥6/10), or INF was ordered, cancelled, and intravenous (IV) morphine given, or INF was not ordered and a peripheral IV line was placed to give IV morphine as first-line medication; (3) peripheral IV established upon ED arrival; (4) no pain medication required. Additionally, a survey regarding practice habits for pain management was completed to evaluate physician barriers to utilization of the pathway. Results: A total of 1374 patients met the inclusion criteria. Missed opportunities were identified 41% of the time. Neither younger patient age nor more years of physician experience in the ED were associated with increased rates of missed opportunities. The survey (95% response rate) revealed greater comfort with and preference for IV morphine over INF. Conclusions: The high rate of missed opportunities, despite the implementation of an INF pain pathway, indicates the need for further exploration of the barriers to utilization of the INF pain pathway.
Article
Background Benzodiazepines, opioids, proton-pump inhibitors (PPIs), and antibiotics are frequently prescribed inappropriately by primary care physicians (PCPs), without sufficient consideration of alternative options or adverse effects. We hypothesized that distinct groups of PCPs could be identified based on their propensity to prescribe these medications.Objective To identify PCP groups based on their propensity to prescribe benzodiazepines, opioids, PPIs, and antibiotics, and patient and PCP characteristics associated with identified prescribing patterns.DesignRetrospective cohort study using VA data and latent class regression analyses to identify prescribing patterns among PCPs and examine the association of patient and PCP characteristics with class membership.ParticipantsA total of 2524 full-time PCPs and their patient panels (n = 2,939,636 patients), from January 1, 2017, to December 31, 2018.Main MeasuresWe categorized PCPs based on prescribing volume quartiles for the four drug classes, based on total days’ supply dispensed of each medication by the PCP to their patients (expressed as days’ supply per 1000 panel patient-days). We used latent class analysis to group PCPs based on prescribing and used multinomial logistic regression to examine patient and PCP characteristics associated with latent class membership.Key ResultsPCPs were categorized into four groups (latent classes): low intensity (23% of cohort), medium-intensity overall/high-intensity PPI (36%), medium-intensity overall/high-intensity opioid (20%), and high intensity (21%). PCPs in the high-intensity group were predominantly in the highest quartile of prescribers for all four drugs (68% in the highest quartile for benzodiazepine, 86% opioids, 64% PPIs, 62% antibiotics). High-intensity PCPs (vs. low intensity) were substantially less likely to be female (OR: 0.30, 95% CI: 0.21–0.42) or practice in the northeast versus other census regions (OR: 0.10, 95% CI: 0.06–0.17).ConclusionsVA PCPs can be classified into four clearly differentiated groups based on their prescribing of benzodiazepines, opioids, PPIs, and antibiotics, suggesting an underlying typology of prescribing. High-intensity PCPs were more likely to be male.
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Physicians prescribing drugs for patients with schizophrenia and related conditions are remarkably concentrated in their choice among antipsychotic drugs. In 2007 the single antipsychotic drug prescribed by a physician accounted for 66% of all antipsychotic prescriptions written by that physician. Which particular branded antipsychotic was the prescriber's "favorite" varied widely across physicians, i.e. physician prescribing concentration patterns are diverse. Building on Frank and Zeckhauser's [2007] characterization of physician treatments varying from "custom made" to "ready-to-wear", we construct a model of physician learning that generates a number of hypotheses. Using 2007 annual antipsychotic prescribing behavior on 17,652 physicians from IMS Health, we evaluate these predictions empirically. While physician prescribing behavior is generally quite concentrated, prescribers having greater volumes, those with training in psychiatry, male prescribers, and those not approaching retirement age tend to have less concentrated prescribing patterns.Institutional subscribers to the NBER working paper series, and residents of developing countries may download this paper without additional charge at www.nber.org.
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Policy discussions concerning pharmaceutical promotion often assume that small promotional items are unlikely to influence prescribing behavior. Our experiment measures whether exposure to these items results in more favorable attitudes toward marketed products and whether policies that restrict pharmaceutical marketing mitigate this effect. This is a randomized controlled experiment of 352 third- and fourth-year medical students at two US medical schools with differing policies toward pharmaceutical marketing. Participants assigned to treatment were exposed to small branded promotional items for Lipitor (atorvastatin) without knowledge that the exposure was part of the study. We measured differences in implicit (ie, unconscious) attitudes toward Lipitor and Zocor (simvastatin) in exposed and control groups with the Implicit Association Test (IAT). Self-reported attitudes were also measured, and a follow-up survey was administered measuring attitudes toward marketing. Fourth-year students at the University of Miami Miller School of Medicine exposed to Lipitor promotional items had more favorable implicit attitudes about that brand-name drug compared to the control group (IAT effect: 0.66 vs 0.47; P = .05), while the effect was reversed at the University of Pennsylvania School of Medicine (IAT effect: 0.22 vs 0.52; P = .002) where restrictive policies are in place limiting pharmaceutical marketing (interaction effect: P = .003). No significant effect was observed among third-year students. On a "skepticism" scale, University of Miami students held more favorable attitudes toward pharmaceutical marketing compared to University of Pennsylvania students (0.55 vs 0.42; P < .001) but the results were similar to those of a previously published national study (0.42 vs 0.43; P = .53). Subtle exposure to small pharmaceutical promotional items influences implicit attitudes toward marketed products among medical students. We observed a reversal of this effect in the setting of restrictive policies and more negative school-level attitudes toward marketing.
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Hardly a week goes by without a front-page newspaper article on rising health care costs and the uninsured. In this article, I focus mainly on costs, arguing that the issue has been somewhat misconceived: while the level of medical care spending in the U.S. is a cause for concern, the welfare losses associated with rises in that level of spending may not be as large as the public rhetoric can make them seem. In fact, cost containment may not be as urgent as is widely supposed, and some proposed "cost containment" policies may result in welfare losses for the insured and even increase the number of uninsured
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The influence of patient and physician variables on antipsychotic drug choice for patients with schizophrenia was assessed. Interviews with 100 psychiatrists on drug choice for 200 patients suffering from schizophrenia were conducted. Data were analyzed by using multiple logistic regression. Older physicians were up to five times more likely to prescribe first-generation antipsychotics. Patient variables did not influence treatment decisions significantly. There is an urgent need for more research on clinical decision making and quality management.
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Schizophrenia is associated with several chronic physical illnesses and a shorter life expectancy, compared with life expectancy in the general population. One approach to improving the health of patients with schizophrenia is to improve the monitoring of physical health that occurs in psychiatric settings. The authors discuss a consensus panel's recommendations for improving the physical health monitoring of patients with schizophrenia who are treated in outpatient settings. A consensus meeting including psychiatric and other medical experts assembled on October 17-18, 2002, to evaluate the existing literature and to develop recommendations for physical health monitoring of patients with schizophrenia. Conference participants reviewed the literature in the following areas: 1) weight gain and obesity; 2) diabetes; 3) hyperlipidemia; 4) prolongation of the QT interval on the ECG; 5) prolactin elevation and related sexual side effects; 6) extrapyramidal side effects, akathisia, and tardive dyskinesia; 7) cataracts; and 8) myocarditis. Experts for each topic area formulated monitoring recommendations that were discussed by all of the participants until a consensus was reached. Consensus recommendations included regular monitoring of body mass index, plasma glucose level, lipid profiles, and signs of prolactin elevation or sexual dysfunction. Information from monitoring should guide the selection of antipsychotic agents. Specific recommendations were made for cardiac monitoring of patients who receive medications associated with QT interval prolongation, including thioridazine, mesoridazine, and ziprasidone, and for monitoring for signs of myocarditis in patients treated with clozapine. Patients who receive both first- and second-generation antipsychotic medications should be examined for extrapyramidal symptoms and tardive dyskinesia. Patients with schizophrenia should receive regular visual examinations. The conference participants recommended that mental health care providers perform physical health monitoring that typically occurs in primary care settings for their patients who do not receive physical health monitoring in those settings. This change in usual practice is recommended on the basis of the conference participants' belief that this additional monitoring will result in the earlier detection of common, serious risk factors that could, without detection and intervention, contribute to impaired health of patients with schizophrenia.
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This article summarizes an extensive literature review addressing the question, How can we spread and sustain innovations in health service delivery and organization? It considers both content (defining and measuring the diffusion of innovation in organizations) and process (reviewing the literature in a systematic and reproducible way). This article discusses (1) a parsimonious and evidence-based model for considering the diffusion of innovations in health service organizations, (2) clear knowledge gaps where further research should be focused, and (3) a robust and transferable methodology for systematically reviewing health service policy and management. Both the model and the method should be tested more widely in a range of contexts.
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Increasing numbers of reports concerning diabetes, ketoacidosis, hyperglycaemia and lipid dysregulation in patients treated with second-generation (or atypical) antipsychotics have raised concerns about a possible association between these metabolic effects and treatment with these medications. This comprehensive literature review considers the evidence for and against an association between glucose or lipid dysregulation and eight separate second-generation antipsychotics currently available in the US and/or Europe, specifically clozapine, olanzapine, risperi-done, quetiapine, zotepine, amisulpride, ziprasidone and aripiprazole. This review also includes an assessment of the potential contributory role of treatment-induced weight gain in conferring risk for hyperglycaemia and dyslipidaemia during treatment with different antipsychotic medications.
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Second-generation (atypical) antipsychotics (SGAs) are more expensive than first-generation (typical) antipsychotics (FGAs) but are perceived to be more effective, with fewer adverse effects, and preferable to patients. Most evidence comes from short-term efficacy trials of symptoms. To test the hypothesis that in people with schizophrenia requiring a change in treatment, SGAs other than clozapine are associated with improved quality of life across 1 year compared with FGAs. A noncommercially funded, pragmatic, multisite, randomized controlled trial of antipsychotic drug classes, with blind assessments at 12, 26, and 56 weeks using intention-to-treat analysis. Fourteen community psychiatric services in the English National Health Service. Two hundred twenty-seven people aged 18 to 65 years with DSM-IV schizophrenia and related disorders assessed for medication review because of inadequate response or adverse effects. Randomized prescription of either FGAs or SGAs (other than clozapine), with the choice of individual drug made by the managing psychiatrist. Quality of Life Scale scores, symptoms, adverse effects, participant satisfaction, and costs of care. The primary hypothesis of significant improvement in Quality of Life Scale scores during the year after commencement of SGAs vs FGAs was excluded. Participants in the FGA arm showed a trend toward greater improvements in Quality of Life Scale and symptom scores. Participants reported no clear preference for either drug group; costs were similar. In people with schizophrenia whose medication is changed for clinical reasons, there is no disadvantage across 1 year in terms of quality of life, symptoms, or associated costs of care in using FGAs rather than nonclozapine SGAs. Neither inadequate power nor patterns of drug discontinuation accounted for the result.
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APA's Practice Guideline for the Treatment of Patients With Schizophrenia, Second Edition, was published in April 2004 (1). This watch highlights key research studies published since that date. The studies were identified by a MEDLINE literature search for meta-analyses and randomized, con-trolled trials published between 2002 and 2008, using the same key words used for the literature search performed for the 2004 guideline. With regard to pharmacotherapy, there have been sev-eral important randomized trials of antipsychotics. For chronic schizophrenia, trials include the National Insti-tute of Mental Health (NIMH) Clinical Antipsychotic Trial for Intervention Effectiveness (CATIE) and the United Kingdom–funded Cost Utility of the Latest Antipsychotics in Schizophrenia (CUtLASS). For first-episode schizophrenia, there are two industry-funded trials, the European First Episode Schizophrenia Trial (EUFEST)—funded by AstraZeneca, Pfizer, and Sanofi-Aventis—and the Comparison of Atypicals for First Epi-sode Schizophrenia (CAFE)—funded by AstraZeneca. For early-onset schizophrenia, there is one trial, the NIMH-funded Treatment of Early-Onset Schizophrenia Spectrum Disorders (TEOSS). These trials point to a re-consideration of treatment with the antipsychotics per-phenazine and molindone and by extension other first-generation antipsychotics, with the possible exception of haloperidol, for which some trials have shown greater rates of extrapyramidal side effects or less favorable clinical re-sponse (2). In addition, a recent population-based cohort study (3) that encompassed 11 years of follow-up showed decreased rates of mortality with perphenazine as compared with other first-and second-generation antipsychotic agents; only clozapine use was associated with lower rates of overall mortality. For the period April 2008 to August 2009, Dr. Dixon reports attending a consultation meeting for Janssen and receiving a grant from Bristol-Meyers-Squibb for investigator-initiated research, Dr. Perkins reports receiving research funding from Janssen (ended Janu-ary 2009) and reports receiving income for consulting for Dainippon (data safety monitoring board on lurasidone studies) and for serving on speakers bureaus for Eli Lilly, and Dr. Calmes reports no competing interests. The Executive Committee on Practice Guidelines reviewed this watch and found no evidence of influence from these relationships. The American Psychiatric Association's (APA's) practice guidelines are developed by expert work groups using an explicit meth-odology that includes rigorous review of available evidence, broad peer review of iterative drafts, and formal approval by the APA Assembly and Board of Trustees. APA practice guidelines are intended to assist psychiatrists in clinical decision making. They are not intended to be a standard of care. The ultimate judgment regarding a particular clinical procedure or treatment plan must be made by the psychiatrist in light of the clinical data presented by the patient and the diagnostic and treatment options available. Guideline watches summarize significant developments in practice since publication of an APA practice guideline. Watches may be authored and reviewed by experts associated with the original guideline development effort and are approved for publication by APA's Executive Committee on Practice Guidelines. Thus, watches represent opinion of the authors and approval of the Executive Committee but not policy of the APA. This guideline watch was published in September 2009.
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This review summarises the preclinical and clinical pharmacology of antipsychotics that are on the verge of introduction into clinical practice by juxtaposition of these data with the information that is already available for clozapine and risperidone. The pharmacology of clozapine is characterised by low affinity for and occupancy of dopamine D2 receptors. Furthermore. the locus of action of clozapine may lie at a number of other sites, possibly D4 or serotonin 5-HT2 receptors. Risperidone is characterised by a high D2 receptor affinity and occupancy and a particularly high 5-HT2 receptor occupancy. Some investigators postulate that the action of these drugs at 5-HT2 receptors is responsible for their efficacy against the negative symptoms of schizophrenia and the low incidence of extrapyramidal adverse effects associated with their use. The effects of olanzapine on receptor systems lie between those of classical antipsychotics and clozapine. The behavioural profile of the drug is atypical. and clinical response is associated with low D2 receptor occupancy. Quetiapine (lCI-204636: Seroquel: is also behaviourally an atypical antipsychotic. Its receptor binding profile is one of broad spectrum and low affinity. but rank potencies are the same as those of clozapine. Sertindole and ziprasidone seem to be high affinity D2 and 5-HT2 receptor antagonists, and share many of the properties of risperidone. Much of the clinical infonnation on olanzapine, quetiapine, sertindole and ziprasidone is not in the public domain, but early indications are that all these drugs are useful and well tolerated. While the clinical infonnation may not discriminate one from another, their introduction will make the need to resort to classical anti psychotics less justifiable in a wider range of clinical circumstances.
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The SGAs are of great benefit to a wide variety of people with psychiatric disorders. As with all drugs, SGAs are associated with undesirable side effects. One constellation of adverse effects is an increased risk for obesity, diabetes, and dyslipidemia. The etiology of the increased risk for metabolic abnormalities is uncertain, but their prevalence seems correlated to an increase in body weight often seen in patients taking an SGA. Direct drug effects on β-cell function and insulin action could also be involved, since there is insufficient information to rule out this possibility. In the general population, being overweight or obese also carries a much higher risk of diabetes and dyslipidemia. These three adverse conditions are closely linked, and their prevalence appears to differ depending on the SGA used. Clozapine and olanzapine are associated with the greatest weight gain and highest occurrence of diabetes and dyslipidemia. Risperidone and quetiapine appear to have intermediate effects. Aripiprozole and ziprasidone are associated with little or no significant weight gain, diabetes, or dyslipidemia, although they have not been used as extensively as the other agents. The choice of SGA for a specific patient depends on many factors. The likelihood of developing severe metabolic disease should also be an important consideration. When prescribing an SGA, a commitment to baseline screening and follow-up monitoring is essential in order to mitigate the likelihood of developing CVD, diabetes, or other diabetes complications.
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The analysis of censored failure times is considered. It is assumed that on each individual are available values of one or more explanatory variables. The hazard function (age-specific failure rate) is taken to be a function of the explanatory variables and unknown regression coefficients multiplied by an arbitrary and unknown function of time. A conditional likelihood is obtained, leading to inferences about the unknown regression coefficients. Some generalizations are outlined. LIFEtables are one of the oldest statistical techniques and are extensively used by medical statisticians and by actuaries. Yet relatively little has been written about their more formal statistical theory. Kaplan and Meier (1958) gave a comprehensive review of earlier work and many new results. Chiang in a series of papers has, in particular, explored the connection with birth-death processes; see, for example, Chiang (1968). The present paper is largely concerned with the extension of the results of Kaplan and Meier to the comparison of life tables and more generally to the incorporation of regression-like arguments into life-table analysis. The arguments are asymptotic but are relevant to situations where the sampling fluctuations are large enough to be of practical importance. In other words, the applications are more likely to be in industrial reliability studies and in medical statistics than in actuarial science. The procedures proposed are, especially for the two-sample problem, closely related to procedures for combining contingency tables; see Mantel and Haenzel (1959), Mantel (1963) and, especially for the application to life tables, Mantel (1966). There is also a strong connection with a paper read recently to the Society by R. and J. Peto (1972). We consider a population of individuals; for each individual we observe either the time to "failure" or the time to ccloss" or censoring. That is, for the censored individuals we know only that the time to failure is greater than the censoring time. Denote by T a random variable representing failure time; it may be discrete or continuous. Let F(t) be the survivor function, %(t) = pr (T2 t)
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The abstract for this document is available on CSA Illumina.To view the Abstract, click the Abstract button above the document title.
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Cost-related underuse of medications is common among older adults, who seldom discuss medication costs with their physicians. Some older adults may use free drug samples or industry-sponsored patient assistance programs (PAP) in hopes of lowering out-of-pocket costs, although the long-term effect of these programs on drug spending is unclear. To examine older adults' use of industry-sponsored strategies to reduce out-of-pocket drug costs and the association between doctor-patient communication and use of these programs. Cross-sectional analysis of a 2006 nationally representative survey of Medicare beneficiaries. 14,322 community-dwelling Medicare beneficiaries age ≥65. We conducted bivariate and multivariate analyses of the association between receipt of free samples and participation in PAPs with sociodemographic characteristics, health status, access to care, drug coverage, medication cost burden, and doctor-patient communication. 51.4% of seniors reported receiving at least one free sample over the last 12 months and 29.2% reported receiving free samples more than once. In contrast, only 1.3% of seniors reported participating in an industry-sponsored PAP. Higher income respondents were more likely to report free sample receipt than low-income respondents (50.8% vs. 43.8%, p < 0.001) and less likely to report participating in a PAP (0.42% vs. 2.2%, p < 0.001). In multivariate analyses, those who reported talking to their doctor about the cost of their medications had more than twice the odds of receiving samples as those who did not (OR 2.17, 95% CI 1.95-2.42). In 2006, over half of seniors in Medicare received free samples, but only 1.3% reported receiving any medications from a patient assistance program. Doctor-patient communication is strongly associated with use of these programs, which has important implications for clinical care regardless of whether these programs are viewed as drivers of prescription costs or a remedy for them.
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For many disorders, patient heterogeneity requires physicians to customize their treatment to each patient's needs. We test for the existence of customization in physicians' prescribing for bipolar disorder, using data from a naturalistic clinical effectiveness trial of bipolar disorder treatment (STEP-BD), which did not constrain physician prescribing. Multinomial logit is used to model the physician's choice among five combinations of drug classes. We find that our observed measure of the patient's clinical status played only a limited role in the choice among drug class combinations, even for conditions such as mania that are expected to affect class choice. However, treatment of a patient with given characteristics differed widely depending on which physician was seen. The explanatory power of the model was low. There was variation within each physician's prescribing, but the results do not suggest a high degree of customization in physicians' prescribing, based on our measure of clinical status.
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Most previous studies of the incidence of tardive dyskinesia with atypical antipsychotics compared with conventional antipsychotics have not had tardive dyskinesia as their primary focus. The current study aimed to compare the incidence of tardive dyskinesia with atypical vs conventional antipsychotics using methods similar to those from a previous prospective cohort study at our site in the 1980s. Three hundred fifty-two initially tardive dyskinesia-free psychiatric outpatients (diagnosed at baseline using the Structured Clinical Interview for DSM-IV) were examined for a new diagnosis of tardive dyskinesia (using the Abnormal Involuntary Movement Scale and Glazer-Morgenstern criteria) every 6 months for up to 4 years at a community mental health center. At baseline, subjects were receiving conventional antipsychotics only (23%), atypicals only (64%), or both (14%). Only 26 subjects had never received conventional antipsychotics. Baseline evaluations were conducted from November 2000 through May 2003. Follow-ups were conducted through February 2005. Compared with subjects treated with conventional antipsychotics alone since the previous visit, the adjusted tardive dyskinesia incidence rate-ratio for subjects treated with atypical antipsychotics alone was 0.68 (95% CI, 0.29-1.64). The incidence and prevalence of tardive dyskinesia was similar to previous findings at this site in the 1980s. The incidence of tardive dyskinesia with recent exposure to atypical antipsychotics alone was more similar to that for conventional antipsychotics than in most previous studies. Despite high penetration of atypical antipsychotics into clinical practice, the incidence and prevalence of tardive dyskinesia appeared relatively unchanged since the 1980s. Clinicians should continue to monitor for tardive dyskinesia, and researchers should continue to pursue efforts to treat or prevent it.
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The purpose of this article is to discuss the principles of academic detailing, or educational outreach, in primary care and review the evidence of its effectiveness in, and potential for improving, mental health care. The general educational research literature on improving physician performance was reviewed along with studies that were designed to test academic detailing. Four rigorous studies have tested this approach specifically on mental health care. These studies are reviewed in detail. Measuring pre-intervention performance to target those with increased educational needs and identifying barriers to change are associated with substantially improved program effectiveness. To change strongly held beliefs or to overcome patient demands, person-to-person contact with credible experts who provide structured alternatives is necessary. Brief reinforcement visits increase success rates and targeting programs to physicians at greatest need improves the cost effectiveness of educational interventions. Academic detailing is one of the few educational interventions that has consistently demonstrated improved physician performance. Educational outreach methods to improve mental health practices in primary care are in need of much additional research. Improving the detection of mental disorders and underuse of mental health treatment may prove to be more difficult than reducing the overuse of unnecessary medications.
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The objective of this meta-analysis is to summarize the efficacy and tolerability of the new antipsychotics risperidone, olanzapine, sertindole and quetiapine in schizophrenia compared to placebo and conventional antipsychotics. The main results are: (1) All of the 4 new drugs are more effective than placebo, but the magnitude of the effect is only moderate [mean effect size, r, of all antipsychotics vs. placebo = 0.25, with a 95% confidence interval (CI) = 0.22-0.28, n = 2477]. (2) According to the studies published to date, sertindole and quetiapine are as effective as haloperidol, and risperidone and olanzapine are slightly more effective than haloperidol in the treatment of global schizophrenic symptomatology. (3) With respect to negative symptoms, all new antipsychotics are more effective than placebo. However, contrary to widespread opinion, so is the 'conventional' antipsychotic haloperidol. Risperidone and olanzapine are slightly superior, sertindole is as effective and--according to the only study fully published to date--quetiapine is even slightly less effective than haloperidol in this regard. (4) All new antipsychotics are associated with less frequent use of antiparkinson medication than haloperidol, with risperidone appearing to have a slightly less favourable EPS-profile than the other new antipsychotics. The methodological limitations of this review, the generalizability of the results and expectations from future research are discussed.
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I examine the importance of physicians in the process by which patients receive either trade-name or generic drugs. Using a dataset on physicians, their patients, and the multisource drugs prescribed, I find that almost all physicians prescribe both types of drugs to their patients, but some physicians are more likely to prescribe generic drugs while other physicians are more likely to prescribe trade-name drugs. Very little of the prescription decision can be explained by observable characteristics of individual patients, but all of the evidence indicates that physicians are indeed an important agent in determining whether patients receive either trade-name or generic drugs.
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There is a large variation in implementing research findings in clinical practice. We examined whether the concept of early or late adopters is universal for the diffusion of all new drugs, and whether it is associated with non-scientific factors in general practice. We identified all prescriptions for five new drugs from the population-based prescription database in North Jutland County, Denmark (490000 inhabitants) from 1993 to 1996, and calculated the period from release of the drugs to the issuing of the first prescription by each GP. Logistic regression was performed to predict early or late prescribing from physician characteristics, practice activity and the number of prescriptions, adjusted for age and sex. The distributions of the diffusion time of the drugs by 95 solo practitioners were asymmetrical, with a long upper tail representing the late prescribers. The shape and slope of the diffusion curve were highly drug dependent. There was poor agreement of the three adopter categories (early, intermediate and late prescribers) between the five drugs (kappa < 0.35), but being a late prescriber was the most consistent condition. Late prescribing of tramadol, compared with intermediate prescribing, was associated with female physicians (odds ratio (OR) 5.7; 95% CI 1.5-21.3), smaller list size (OR 0.1; 95% CI 0.0-0.8), a strong general restrictive attitude to pharmacotherapy (OR 0.07; 95% CI 0.01-0.68) and a tendency to lower diagnostic activity per patient (OR 0.4; 95% CI 0.1-1.9). The slope and shape of the diffusion curve are both dependent on physician and drug characteristics, but late prescribers share some common characteristics.
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Consensus panel recommendations regarding choice of an antipsychotic agent for schizophrenia differ markedly, but most consider second-generation antipsychotics (SGAs) as a homogeneous group. It has been suggested that SGAs seem falsely more efficacious than first-generation antipsychotics (FGAs) as a result of reduced efficacy due to use of a high-dose comparator, haloperidol. We performed (1) a meta-analysis of randomized efficacy trials comparing SGAs and FGAs, (2) comparisons between SGAs, (3) a dose-response analysis of FGAs and SGAs, and (4) an analysis of the effect on efficacy of an overly high dose of an FGA comparator. Literature search of clinical trials between January 1953 and May 2002 of patients with schizophrenia from electronic databases, reference lists, posters, the Food and Drug Administration, and other unpublished data. We included 124 randomized controlled trials with efficacy data on 10 SGAs vs FGAs and 18 studies of comparisons between SGAs. Two of us independently extracted the sample sizes, means, and standard deviation of the efficacy data. Using the Hedges-Olkin algorithm, the effect sizes of clozapine, amisulpride, risperidone, and olanzapine were 0.49, 0.29, 0.25, and 0.21 greater than those of FGAs, with P values of 2 x 10-8, 3 x 10-7, 2 x 10-12, and 3 x 10-9, respectively. The remaining 6 SGAs were not significantly different from FGAs, although zotepine was marginally different. No efficacy difference was detected among amisulpride, risperidone, and olanzapine. We found no evidence that the haloperidol dose (or all FGA comparators converted to haloperidol-equivalent doses) affected these results when we examined its effect by drug or in a 2-way analysis of variance model in which SGA effectiveness is entered as a second factor. Some SGAs are more efficacious than FGAs, and, therefore, SGAs are not a homogeneous group.
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Prior research has shown that prescription drug spending grew substantially during the decade of the 1990s. This analysis uses 1996 to 1998 State Medicaid Research File (SMRF) fee-for-service (FFS) data for 29 participating States to provide insight into the factors driving this growth. The analysis examines cost variation by census region, State, Medicaid basis of eligibility, and therapeutic use of drugs. In 1998, the highest expenditures were for central nervous system (CNS) drugs and for anti-psychotics compared to three other groups of CNS drugs (anti-anxiety agents, anti-depressants, and hypnotics). By eligibility group, expenditures were typically highest for disabled enrollees. There were major variations among SMRF States and their respective regions.
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Results of studies conducted 10-20 years ago show the prominence of commercial information sources in the adoption process of new drugs. Over the past decade, there has been a growing emphasis on practicing evidence-based medicine in drug prescribing. This raises the question whether professional information sources currently counterbalance the influence of commercial information sources in the adoption process. The aim of this study was to identify determinants influencing the adoption of a new drug class, the angiotensin II receptor blockers (ARBs), by general practitioners (GPs) in The Netherlands. A retrospective study was conducted to assess prevalent ARB prescribing for hypertensive patients using the Integrated Primary Care Information (IPCI) database. We conducted a survey among all GPs who participated in the IPCI project in 2003 to assess their exposure to commercial and professional information sources, perceived benefits and risks of ARBs, perceived influences of the professional network, and general characteristics. Multilevel logistic regression was applied to identify determinants of ARB adoption while adjusting for patient characteristics. Data were obtained from 70 GPs and 9470 treated hypertensive patients. A total of 1093 patients received ARBs (12%). GPs who reported frequent use of commercial information sources were more likely to prescribe ARBs routinely in preference to other antihypertensives, whereas GPs who used a prescribing decision support system and those who were involved in pharmacotherapy education were less likely to prescribe ARBs. Other factors that were associated with higher levels of ARB adoption included a more positive perception of ARBs regarding their effectiveness in lowering blood pressure, and working in single-handed practices or in rural areas. Aside from determinants related to the patient population, adoption of a new drug class among Dutch GPs is still determined more by their reliance on promotional information than by their use of professional information sources.
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To customize treatments to individual patients entails costs of coordination and cognition. Thus, providers sometimes choose treatments based on norms for broad classes of patients. We develop behavioral hypotheses explaining when and why doctors customize to the particular patient, and when instead they employ "ready-to-wear" treatments. Our empirical studies examining length of office visits and physician prescribing behavior find evidence of norm-following behavior. Some such behavior, from our studies and from the literature, proves sensible; but other behavior seems far from optimal.
Article
The metabolic syndrome (MS) is associated with increased risk for diabetes mellitus and coronary heart disease, and is highly prevalent among schizophrenia patients. Given concerns over antipsychotic metabolic effects, this analysis explored MS status and outcomes in phase 1 of the CATIE Schizophrenia Trial. The change in proportion of subjects with MS and individual criteria was compared between antipsychotic treatment groups, along with mean changes for individual criteria. Primary analyses examined subjects with fasting laboratory assessments at baseline and 3 months. Other analyses examined 3-month changes in MS status, waist circumference (WC), HDL cholesterol and blood pressure in all subjects, metabolic changes at the end of phase 1 participation (EOP), and repeated measures changes in HDL, blood pressure (BP) and WC over phase 1. At 3 months, there were no significant between-drug differences for the change in proportion of subjects meeting MS status or individual MS criteria in the smaller fasting cohort (n = 281) or for those meeting criteria for parameters not dependent on fasting status (BP, HDL, WC) among all subjects (n=660). Among all subjects whose MS status could be determined at 3 months (n=660), MS prevalence increased for olanzapine (from 34.8% to 43.9%), but decreased for ziprasidone (from 37.7% to 29.9%) (p=.001). Although effect sizes varied across subgroups, at 3 months olanzapine and quetiapine had the largest mean increase in waist circumference (0.7 in. for both) followed by risperidone (0.4 in.), compared to no change for ziprasidone (0.0 in.) and a decrease in waist circumference for perphenazine (-0.4 in.). Olanzapine also demonstrated significantly different changes in fasting triglycerides at 3 months (+21.5 mg/dl) compared to ziprasidone (-32.1 mg/dl). EOP exposure data was obtained, on average, nine months from baseline for all metabolic variables. Results from EOP and repeated measures analyses were consistent with those at 3 months for mean changes in WC and fasting triglycerides, but between group differences emerged for HDL and SBP. This large non-industry sponsored study confirms the differential metabolic effects between antipsychotics. Clinicians are advised to monitor all metabolic parameters, including WC, HDL and serum triglycerides, during antipsychotic treatment.
Article
The publicly funded Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) did not support superiority hypotheses for second-generation antipsychotic drugs in schizophrenia. Instead, the study supported the view that first- and second-generation antipsychotics have similar therapeutic properties and diverse adverse effect profiles. This emphasizes the importance of designing pharmacotherapy for the individual in order to optimize the benefit-to-risk profile. First- and second-generation antipsychotic drugs are extensively similar in mechanism of action, efficacy for psychosis, and lack of efficacy for avolition and impaired cognition. However, adverse effect profiles vary between drugs. The authors review the clinical implications of these data, with an emphasis on individualizing pharmacotherapy in an effort to reduce risk. Rather than selecting drugs on the basis of unfounded expectations of superior efficacy, clinicians can focus on selecting drugs and optimizing dosages to minimize adverse effects without sacrificing efficacy. Tardive dyskinesia may be a good reason to avoid a high dosage of first-generation antipsychotics, although the evidence for differential risk is less compelling for a modest dosage of low-affinity first-generation antipsychotics. Similarly, the metabolic effects of some second-generation antipsychotics can be decisive in considering risks. In either case, the clinician should detect earliest signs and take action while dyskinetic or metabolic effects are most reversible. Bottom line: the dichotomy between first- and second-generation antipsychotics was not supported by efficacy data (and now, is not supported effectiveness data). Only clozapine has documented superiority in treatment-resistant cases.
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American Association of Clinical Endocrinologists, et al: Consensus development conference on antipsychotic drugs and obesity and diabetes. Diabetes Care 27:596-601, 2004