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JAMA Network Open May 2021Chiral switching, a strategy in which drug manufacturers develop a single-enantiomer formulation of a drug to be substituted for a racemic formulation, allows...
IMPORTANCE
Chiral switching, a strategy in which drug manufacturers develop a single-enantiomer formulation of a drug to be substituted for a racemic formulation, allows manufacturers to maintain market exclusivity for drugs losing patent protection, even without demonstrating superior efficacy or safety.
OBJECTIVE
To identify and characterize all randomized clinical trials (RCTs) directly comparing a Food and Drug Administration (FDA)-approved single-enantiomer drug against a previously approved racemic drug for 1 or more efficacy or safety end points.
EVIDENCE REVIEW
Drugs were identified using the Drugs@FDA database. Randomized clinical trials were identified using Ovid MEDLINE (1949 to October 22, 2019), Ovid Embase (1974 to October 22, 2019), Web of Science Core Collection (all years), ClinicalTrials.gov, and Cochrane Central Registry of Controlled Trials (CENTRAL, Wiley, Issue 8 of 12, October 22, 2019). Trials were characterized as favoring the single-enantiomer or racemic drugs based on whether the primary efficacy, secondary efficacy, and safety end points achieved each study's defined significance level (eg, P < .05). Trials were characterized as favoring neither drug if no statistically significant differences were reported for any end point or if both drugs were found to be superior for 1 or more separate end points.
FINDINGS
Fifteen FDA-approved single-enantiomer drugs were identified with racemic precursors approved in the US or Europe. For 3 single-enantiomer racemic drug pairs, no RCTs directly comparing the drugs were identified. For the remaining 12 pairs, 185 RCTs comparing efficacy or safety of the drug pairs were identified, 124 (67.0%) of which studied 1 pair (levobupivacaine/bupivacaine). There were 179 RCTs directly comparing drug pairs using efficacy end points, of which 23 (12.8%) favored the single enantiomer based on primary efficacy end point results. There were 124 RCTs directly comparing drug pairs using safety end points, of which 17 (13.7%) favored the single-enantiomer drug. For 9 of the 15 single-enantiomer drugs (60.0%), no RCTs were identified providing evidence of improved efficacy, based on primary end point results, or safety as compared with their racemic precursors.
CONCLUSIONS AND RELEVANCE
The results of this systematic review suggest that most newly marketed FDA-approved single-enantiomer drugs are infrequently directly compared with their racemic precursors, and when compared, they are uncommonly found to provide improved efficacy or safety, despite their greater costs.
Topics: Drug Approval; Drug Compounding; Drug Prescriptions; Drugs, Generic; Humans; Medicare; Randomized Controlled Trials as Topic; Stereoisomerism; United States
PubMed: 33956134
DOI: 10.1001/jamanetworkopen.2021.5731 -
BMJ (Clinical Research Ed.) Feb 2020To conduct a systematic review and meta-analysis of the effects of rosiglitazone treatment on cardiovascular risk and mortality using multiple data sources and varying... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
To conduct a systematic review and meta-analysis of the effects of rosiglitazone treatment on cardiovascular risk and mortality using multiple data sources and varying analytical approaches with three aims in mind: to clarify uncertainties about the cardiovascular risk of rosiglitazone; to determine whether different analytical approaches are likely to alter the conclusions of adverse event meta-analyses; and to inform efforts to promote clinical trial transparency and data sharing.
DESIGN
Systematic review and meta-analysis of randomized controlled trials.
DATA SOURCES
GlaxoSmithKline's (GSK's) ClinicalStudyDataRequest.com for individual patient level data (IPD) and GSK's Study Register platforms, MEDLINE, PubMed, Embase, Web of Science, Cochrane Central Registry of Controlled Trials, Scopus, and ClinicalTrials.gov from inception to January 2019 for summary level data.
ELIGIBILITY CRITERIA FOR SELECTING STUDIES
Randomized, controlled, phase II-IV clinical trials that compared rosiglitazone with any control for at least 24 weeks in adults.
DATA EXTRACTION AND SYNTHESIS
For analyses of trials for which IPD were available, a composite outcome of acute myocardial infarction, heart failure, cardiovascular related death, and non-cardiovascular related death was examined. These four events were examined independently as secondary analyses. For analyses including trials for which IPD were not available, myocardial infarction and cardiovascular related death were examined, which were determined from summary level data. Multiple meta-analyses were conducted that accounted for trials with zero events in one or both arms with two different continuity corrections (0.5 constant and treatment arm) to calculate odds ratios and risk ratios with 95% confidence intervals.
RESULTS
33 eligible trials were identified from ClinicalStudyDataRequest.com for which IPD were available (21 156 patients). Additionally, 103 trials for which IPD were not available were included in the meta-analyses for myocardial infarction (23 683 patients), and 103 trials for which IPD were not available contributed to the meta-analyses for cardiovascular related death (22 772 patients). Among 29 trials for which IPD were available and that were included in previous meta-analyses using GSK's summary level data, more myocardial infarction events were identified by using IPD instead of summary level data for 26 trials, and fewer cardiovascular related deaths for five trials. When analyses were limited to trials for which IPD were available, and a constant continuity correction of 0.5 and a random effects model were used to account for trials with zero events in only one arm, patients treated with rosiglitazone had a 33% increased risk of a composite event compared with controls (odds ratio 1.33, 95% confidence interval 1.09 to 1.61; rosiglitazone population: 274 events among 11 837 patients; control population: 219 events among 9319 patients). The odds ratios for myocardial infarction, heart failure, cardiovascular related death, and non-cardiovascular related death were 1.17 (0.92 to 1.51), 1.54 (1.14 to 2.09), 1.15 (0.55 to 2.41), and 1.18 (0.60 to 2.30), respectively. For analyses including trials for which IPD were not available, odds ratios for myocardial infarction and cardiovascular related death were attenuated (1.09, 0.88 to 1.35, and 1.12, 0.72 to 1.74, respectively). Results were broadly consistent when analyses were repeated using trials with zero events across both arms and either of the two continuity corrections was used.
CONCLUSIONS
The results suggest that rosiglitazone is associated with an increased cardiovascular risk, especially for heart failure events. Although increased risk of myocardial infarction was observed across analyses, the strength of the evidence varied and effect estimates were attenuated when summary level data were used in addition to IPD. Because more myocardial infarctions and fewer cardiovascular related deaths were reported in the IPD than in the summary level data, sharing IPD might be necessary when performing meta-analyses focused on safety.
SYSTEMATIC REVIEW REGISTRATION
OSF Home https://osf.io/4yvp2/.
Topics: Cardiovascular Diseases; Humans; Hypoglycemic Agents; Information Dissemination; Randomized Controlled Trials as Topic; Risk Factors; Rosiglitazone
PubMed: 32024657
DOI: 10.1136/bmj.l7078 -
Translational Psychiatry Jun 2024Treatment-resistant depression (TRD) affects approximately 2.8 million people in the U.S. with estimated annual healthcare costs of $43.8 billion. Deep brain stimulation...
Treatment-resistant depression (TRD) affects approximately 2.8 million people in the U.S. with estimated annual healthcare costs of $43.8 billion. Deep brain stimulation (DBS) is currently an investigational intervention for TRD. We used a decision-analytic model to compare cost-effectiveness of DBS to treatment-as-usual (TAU) for TRD. Because this therapy is not FDA approved or in common use, our goal was to establish an effectiveness threshold that trials would need to demonstrate for this therapy to be cost-effective. Remission and complication rates were determined from review of relevant studies. We used published utility scores to reflect quality of life after treatment. Medicare reimbursement rates and health economics data were used to approximate costs. We performed Monte Carlo (MC) simulations and probabilistic sensitivity analyses to estimate incremental cost-effectiveness ratios (ICER; USD/quality-adjusted life year [QALY]) at a 5-year time horizon. Cost-effectiveness was defined using willingness-to-pay (WTP) thresholds of $100,000/QALY and $50,000/QALY for moderate and definitive cost-effectiveness, respectively. We included 274 patients across 16 studies from 2009-2021 who underwent DBS for TRD and had ≥12 months follow-up in our model inputs. From a healthcare sector perspective, DBS using non-rechargeable devices (DBS-pc) would require 55% and 85% remission, while DBS using rechargeable devices (DBS-rc) would require 11% and 19% remission for moderate and definitive cost-effectiveness, respectively. From a societal perspective, DBS-pc would require 35% and 46% remission, while DBS-rc would require 8% and 10% remission for moderate and definitive cost-effectiveness, respectively. DBS-pc will unlikely be cost-effective at any time horizon without transformative improvements in battery longevity. If remission rates ≥8-19% are achieved, DBS-rc will likely be more cost-effective than TAU for TRD, with further increasing cost-effectiveness beyond 5 years.
Topics: Humans; Deep Brain Stimulation; Cost-Benefit Analysis; Depressive Disorder, Treatment-Resistant; Quality-Adjusted Life Years; Male; Female; United States; Middle Aged; Quality of Life; Health Care Costs; Monte Carlo Method
PubMed: 38849334
DOI: 10.1038/s41398-024-02951-7 -
Journal of Clinical and Translational... 2024The Centers for Medicare & Medicaid Services have mandated that hospitals implement measures to screen social determinants of health (SDoH). We sought to report on... (Review)
Review
The Centers for Medicare & Medicaid Services have mandated that hospitals implement measures to screen social determinants of health (SDoH). We sought to report on available SDoH screening tools. PubMed, Scopus, Web of Science, as well as the grey literature were searched (1980 to November 2023). The included studies were US-based, written in English, and examined a screening tool to assess SDoH. Thirty studies were included in the analytic cohort. The number of questions in any given SDoH assessment tool varied considerably and ranged from 5 to 50 (mean: 16.6). A total of 19 SDoH domains were examined. Housing ( = 23, 92%) and safety/violence ( = 21, 84%) were the domains assessed most frequently. Food/nutrition ( = 17, 68%), income/financial ( = 16, 64%), transportation ( = 15, 60%), family/social support ( = 14, 56%), utilities ( = 13, 52%), and education/literacy ( = 13, 52%) were also commonly included domains in most screening tools. Eighteen studies proposed specific interventions to address SDoH. SDoH screening tools are critical to identify various social needs and vulnerabilities to help develop interventions to address patient needs. Moreover, there is marked heterogeneity of SDoH screening tools, as well as the significant variability in the SDoH domains assessed by currently available screening tools.
PubMed: 38655456
DOI: 10.1017/cts.2024.506 -
Journal of General Internal Medicine Oct 2019Changing Medicaid fees is a common approach for states to address budget fluctuations, and many currently set Medicaid physician fees at levels lower than Medicare and...
BACKGROUND
Changing Medicaid fees is a common approach for states to address budget fluctuations, and many currently set Medicaid physician fees at levels lower than Medicare and private insurers. The Affordable Care Act included a temporary Medicaid fee bump for primary care providers (PCPs) in 2013-2014 that recently led to both an increase and then subsequent decrease in PCP fees in many states.
OBJECTIVE
To conduct a systematic literature review on the effects of changing Medicaid fees on provider participation and enrollees' access to care and service use.
METHODS
We searched PubMed/Medline and JSTOR and identified 18 studies that assessed the longitudinal impact of provider fee changes in Medicaid on the outcomes of interest. We summarized information on study design, methods, and findings.
RESULTS
Seven studies examined the impact of fee changes on provider participation in Medicaid. Of these, three studies found that fee increases were associated with positive effects on providers' likelihood of accepting Medicaid patients or on their Medicaid caseloads. Five studies that examined the impact of fee changes on Medicaid enrollees' access to care found a positive association with one or more access measure, such as having a usual source of care or appointment availability. Lastly, eight of 14 studies that examined service use found positive associations between fee changes and at least one measure of use, such as changes in the probability of enrollees having any visit, the number of visits, and shifts in the site of care toward office-based care; others largely did not find significant associations.
CONCLUSIONS
There is mixed evidence on the impact of changing Medicaid fees on provider participation and enrollees' service use; however, increasing fees appears to have more consistent positive effects on access to care. Whether these improvements in access translate into better health outcomes or downstream cost savings are critical questions.
Topics: Fees and Charges; Health Services Accessibility; Humans; Medicaid; Patient Protection and Affordable Care Act; United States
PubMed: 31388912
DOI: 10.1007/s11606-019-05160-x -
ELife Sep 2023COVID-19 has strained population breast mammography screening programs that aim to diagnose and treat breast cancers earlier. As the pandemic has affected countries...
COVID-19 has strained population breast mammography screening programs that aim to diagnose and treat breast cancers earlier. As the pandemic has affected countries differently, we aimed to quantify changes in breast screening volume and uptake during the first year of COVID-19 . We systematically searched Medline, the World Health Organization (WHO) COVID-19 database, and governmental databases. Studies covering January 2020 to March 2022 were included. We extracted and analyzed data regarding study methodology, screening volume, and uptake. To assess for risk of bias, we used the Joanna Briggs Institute (JBI) Critical Appraisal Tool. Twenty-six cross-sectional descriptive studies (focusing on 13 countries/nations) were included out of 935 independent records. Reductions in screening volume and uptake rates were observed among eight countries. Changes in screening participation volume in five nations with national population-based screening ranged from -13 to -31%. Among two countries with limited population-based programs, the decline ranged from -61 to -41%. Within the USA, population participation volumes varied ranging from +18 to -39%, with suggestion of differences by insurance status (HMO, Medicare, and low-income programs). Almost all studies had high risk of bias due to insufficient statistical analysis and confounding factors. The extent of COVID-19-induced reduction in breast screening participation volume differed by region and data suggested potential differences by healthcare setting (e.g., national health insurance vs. private healthcare). Recovery efforts should monitor access to screening and early diagnosis to determine whether prevention services need strengthening to increase the coverage of disadvantaged groups and reduce disparities.
Topics: Aged; Female; Humans; Breast Neoplasms; COVID-19; Cross-Sectional Studies; Early Detection of Cancer; Medicare; United States
PubMed: 37698273
DOI: 10.7554/eLife.85680 -
Journal of Managed Care & Specialty... Jan 2024The use of potentially inappropriate medications (PIMs) is prevalent, costly, and harmful for older adults. These medications are to be avoided among older adults...
BACKGROUND
The use of potentially inappropriate medications (PIMs) is prevalent, costly, and harmful for older adults. These medications are to be avoided among older adults because they generally have (1) a high risk of adverse events in this population and/or (2) limited evidence of benefits in the presence of safer or more effective alternatives. Medication therapy management (MTM) programs can help address PIM use; however, there has not been a synthesis of studies examining the impact of MTM programs on PIM use.
OBJECTIVE
To review published literature evaluating the impact of MTM on PIM use in older adults.
METHODS
A systematic literature review was conducted in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analyses guidelines using MEDLINE (PubMed) studies were included if they (1) had a Medicare population, (2) were based in the United States, (3) examined an MTM program (ie, used the term "medication therapy management"), (4) focused on the impact of MTM programs on PIM use as the primary outcome, (5) had a randomized controlled trial or an observational study design, and (6) were available in English.
RESULTS
Of 221 articles identified, 31 full-text articles were assessed, and 7 met all inclusion and exclusion criteria. The studies took place in various settings, ranging from single-site tertiary medical centers to multisite outpatient clinics, community pharmacies, and nationwide telehealth MTM providers. Patient populations were majority female sex (ranging from 61% to 71%) and majority White (ranging from 81% to 94%), with a mean age of 73 to 78 years. In 5 of the 7 studies, MTM reduced the use of PIMs; however, 3 did not adjust for confounding or apply a comparator group. Measurement of MTM impacts on PIM use varied across studies. Patient-level and plan-level studies mostly assessed shorter-term PIM usage reduction (4 months or less), whereas studies performed at the provider and institutional level assessed PIM usage reduction trends across consecutive measurement years.
CONCLUSIONS
Based on the current limited evidence, MTM programs in older adults appear to have a positive impact on reducing PIM use. However, evidence was limited by study design, the lack of consistency in outcome measures, and a short follow-up period. Future work should adjust for confounding, apply comparator groups, include longer-term outcomes, and develop a core set of measures that can be consistently applied across studies.
Topics: Aged; Female; Humans; Medicare; Medication Therapy Management; Observational Studies as Topic; Pharmacies; Potentially Inappropriate Medication List; Randomized Controlled Trials as Topic; Research Design; United States
PubMed: 38153866
DOI: 10.18553/jmcp.2024.30.1.03 -
Blood Advances Nov 2023Social determinants of health (SDHs) have been reported as relevant factors responsible for health inequity. We sought to assess clinical data from observational studies...
Social determinants of health (SDHs) have been reported as relevant factors responsible for health inequity. We sought to assess clinical data from observational studies conducted in the United States evaluating the impact of SDHs on the outcomes of patients with hematologic malignancies. Thus, we performed a systematic review in 6 databases on 1 September 2021, in which paired reviewers independently screened studies and included data from 41 studies. We assessed the risk of bias using the Joanna Briggs Institute appraisal tools and analyzed the data using a descriptive synthesis. The most common SDH domains explored were health care access and quality (54.3%) and economic stability (25.6%); others investigated were education (19%) and social and community context (7.8%). We identified strong evidence of 5 variables significantly affecting survival: lack of health insurance coverage or having Medicare or Medicaid insurance, receiving cancer treatment at a nonacademic facility, low household income, low education level, and being unmarried. In contrast, the reports on the effect of distance traveled to the treatment center are contradictory. Other SDHs examined were facility volume, provider expertise, poverty, and employment rates. We identified a lack of data in the literature in terms of transportation, debt, higher education, diet, social integration, environmental factors, or stress. Our results underscore the complex nature of social, financial, and health care barriers as intercorrelated variables. Therefore, the management of hematologic malignancies needs concerted efforts to incorporate SDHs into clinical care, research, and public health policies, identifying and addressing the barriers at a patient-based level to enhance outcome equity (PROSPERO CRD42022346854).
Topics: Humans; Hematologic Neoplasms; Poverty; Social Determinants of Health; Health Status Disparities; Survival Rate
PubMed: 37639318
DOI: 10.1182/bloodadvances.2023010690 -
Medical Care Research and Review : MCRR Dec 2020An essential element in the pursuit of value-based health care is provider payment reform. This article aims to identify and analyze payment initiatives comprising a...
An essential element in the pursuit of value-based health care is provider payment reform. This article aims to identify and analyze payment initiatives comprising a specific manifestation of value-based payment reform that can be expected to contribute to value in a broad sense: (a) global base payments combined with (b) explicit quality incentives. We conducted a systematic review of the literature, consulting four scientific bibliographic databases, reference lists, the Internet, and experts. We included and compared 18 initiatives described in 111 articles/documents on key design features and impact on value. The initiatives are heterogeneous regarding the operationalization of the two payment components and associated design features. Main commonalities between initiatives are a strong emphasis on primary care, the use of "virtual" spending targets, and the application of risk adjustment and other risk-mitigating measures. Evaluated initiatives generally show promising results in terms of lower spending growth with equal or improved quality.
Topics: Aged; Delivery of Health Care; Humans; Medicare; Motivation; United States
PubMed: 31216945
DOI: 10.1177/1077558719856775 -
BMC Musculoskeletal Disorders Feb 2022Osteoarthritis (OA) is a chronic condition. Physiotherapy is known to be beneficial for people with OA. Patient adherence to physiotherapy exercise is essential for the...
INTRODUCTION
Osteoarthritis (OA) is a chronic condition. Physiotherapy is known to be beneficial for people with OA. Patient adherence to physiotherapy exercise is essential for the effective management of OA.
OBJECTIVES
To determine different methods used to enhance physiotherapy exercise adherence for a period of more than 12 months among patients with OA and to report the most effective methods to enhance exercise adherence among people with lower limb OA.
DESIGN
Systematic review.
METHODS
PubMed, Pedro, Web of Science, and EMBASE databases were searched for randomized controlled trials, cohort studies, case-control studies, and cross-sectional studies published in the English language from 2000 to 2020. The literature search was done on 27 August 2020. Two researchers independently conducted the screening, eligibility assessment, data extraction, methodology quality assessment using the PEDro scale, and risk of bias assessment using RoB2. A narrative synthesis of key outcomes is presented, percentage of adherence rate; Preferred Reporting Items for Systematic Review was used to report the review. Meta-analysis was not performed due to heterogeneity of studies. The study protocol was registered in Prospero (Prospero ID: CRD42020205653).
RESULTS
The primary search strategy identified 5839 potentially relevant articles, of which 5157 remained after discarding duplicates. After screening based on title and abstract, 40 papers were potentially eligible for inclusion. Five of these papers met all predefined eligibility criteria. Introducing methods to enhance exercise adherence has caused a significant increase in exercise adherence for less than 6 or 12 months. There were no significant differences in adherence for more than 12 months with different methods. The results indicate that booster-sessions (89.69%) and telephone-linked communication (86%) had higher percentages for exercise adherence. Secondary outcomes such as pain, stiffness and function show positive outcomes with increasing exercise adherence. However, there were no significant differences on these secondary outcomes.
CONCLUSION
The booster sessions and telephone-linked communication appear to enhance exercise adherence for more than 12 months among patients with OA. However, the number of high-quality studies is inadequate to confirm our findings. Therefore, more studies with higher methodological quality are needed to determine the best strategies to enhance long-term exercise adherence among people with OA.
Topics: Cross-Sectional Studies; Exercise; Humans; Lower Extremity; Osteoarthritis; Physical Therapy Modalities
PubMed: 35164714
DOI: 10.1186/s12891-022-05050-0