A Targeted Review of Worldwide Indirect Treatment Comparison Guidelines and Best Practices.

OBJECTIVES: Controls and governance over the methodology and reporting of indirect treatment comparisons (ITCs) have been introduced to minimize bias and ensure scientific credibility and transparency in healthcare decision making. The objective of this study was to highlight ITC techniques that are key to conducting objective and analytically sound analyses and to ascertain circumstantial suitability of ITCs as a source of comparative evidence for healthcare interventions. METHODS: Ovid MEDLINE was searched from January 2010 through August 2023 to identify publicly available ITC-related documents (ie, guidelines and best practices) in the English language. This was supplemented with hand searches of websites of various international organizations, regulatory agencies, and reimbursement agencies of Europe, North America, and Asia-Pacific. The jurisdiction-specific ITC methodology and reporting recommendations were reviewed. RESULTS: Sixty-eight guidelines from 10 authorities worldwide were included for synthesis. Many of the included guidelines were updated within the last 5 years and commonly cited the absence of direct comparative studies as primary justification for using ITCs. Most jurisdictions favored population-adjusted or anchored ITC techniques opposed to naive comparisons. Recommendations on the reporting and presentation of these ITCs varied across authorities; however, there was some overlap among the key elements. CONCLUSIONS: Given the challenges of conducting head-to-head randomized controlled trials, comparative data from ITCs offer valuable insights into clinical-effectiveness. As such, multiple ITC guidelines have emerged worldwide. According to the most recent versions of the guidelines, the suitability and subsequent acceptability of the ITC technique used depends on the data sources, available evidence, and magnitude of benefit/uncertainty.

Building infrastructure for outcomes-based agreements in Canada: can administrative health data be used to support an outcomes-based agreement in oncology?

BACKGROUND: Outcomes-based agreements (OBAs) have the potential to provide more timely patient access to novel therapies, although they are not suitable for every new medication or reimbursement scenario. The authors of this paper studied how to operationalize an OBA in oncology by leveraging existing real-world data (RWD) infrastructure in the province of Alberta. OBJECTIVE: The main objectives were to (1) evaluate which health outcomes in oncology are suitable for OBAs and whether they can be tracked with existing infrastructure, and (2) determine how RWD in oncology can be used to implement an OBA and the expected timing for delivery. METHODS: Using the Oncology Outcomes (O2) Group infrastructure and Alberta administrative data, a review of five key oncology outcomes was performed to determine suitability to support an OBA. RESULTS: Overall survival and time-to-next-treatment were determined as potentially suitable oncology outcomes for OBAs; progression-free survival, patient-reported outcomes, and return to work were deemed inadequate for OBAs at the current time due to data limitations. CONCLUSIONS: Results indicate that it is feasible to leverage RWD to support OBAs in oncology in Alberta, with minimal additional data, resources, and infrastructure. The operational processes and steps to collect and analyze RWD for OBAs were identified, starting with performing an RWD feasibility study. The expected timeframe to fulfill the real-world evidence (RWE) requirements for an OBA is approximately 3 years for cancers with short trajectories.

CDK4/6 inhibitors in HR+/HER2- advanced/metastatic breast cancer: a systematic literature review of real-world evidence studies.

Background: This review aims to qualitatively summarize the published real-world evidence (RWE) for CDK4/6 inhibitors (CDK4/6i) approved for treating HR+, HER2-negative advanced/metastatic breast cancer (HR+/HER2- a/mBC). Materials & methods: A systematic literature review was conducted to identify RWE studies of CDK4/6i in HR+/HER2- a/mBC published from 2015 to 2019. Results: This review identified 114 studies, of which 85 were only presented at scientific conferences. Most RWE studies investigated palbociclib and demonstrated improved outcomes. There are limited long-term and comparative data between CDK4/6i and endocrine monotherapy, and within the CDK4/6i class. Conclusion: Available RWE suggests that CDK4/6i are associated with improved outcomes in HR+/HER2- a/mBC, although additional studies with longer follow-up periods are needed.

Incorporating adjustments for variability in control group response rates in network meta-analysis: a case study of biologics for rheumatoid arthritis.

BACKGROUND: The importance of adjusting for cross-study heterogeneity in control group response rates when conducting network meta-analyses (NMA) was demonstrated using a case study involving a comparison of biologics for the treatment of moderate-to-severe rheumatoid arthritis. METHODS: Bayesian NMAs were conducted for American College of Rheumatology (ACR) 50 treatment response based upon a set of randomized controlled trials (RCTs) identified by a recently completed systematic review of the literature. In addition to the performance of an unadjusted NMA, a model adjusting for cross-study heterogeneity of control group response rates using meta-regression was fit to the data. Model fit was evaluated, and findings from both analyses were compared with regard to clinical interpretations. RESULTS: ACR 50 response data from a total of 51 RCTs and 16,223 patients were analyzed. Inspection of cross-study variability in control group response rates identified considerable differences between studies. NMA incorporating adjustment for this variability was associated with an average change of 38.1% in the magnitude of the ORs between treatment comparisons, and over 64% of the odds ratio changed by 15% or more. Important changes in the clinical interpretations drawn from treatment comparisons were identified with this improved modeling approach. CONCLUSIONS: In comparing biologics for moderate to severe rheumatoid arthritis, failure to adjust for cross-trial differences in the control arm response rates in NMA can lead to biased estimates of comparative efficacy between treatments.

Acquisition of Multidrug-resistant Organisms in the Absence of Antimicrobials.

A nested case-control study among 137 nursing home residents who did not receive antimicrobials, of whom 44 acquired a multidrug-resistant organism, was performed. Risk factors for acquisition included gastrointestinal medications that affect the gut microbiome, number of visits from healthcare workers, pressure ulcers, and not residing in a dementia unit.

Prolonged operative duration is associated with complications: a systematic review and meta-analysis.

BACKGROUND: The aim of this study was to systematically synthesize the large volume of literature reporting on the association between operative duration and complications across various surgical specialties and procedure types. METHODS: An electronic search of PubMed, Cochrane Central Register of Controlled Trials, and Cochrane Database of Systematic Reviews from January 2005 to January 2015 was conducted. Sixty-six observational studies met the inclusion criteria. RESULTS: Pooled analyses showed that the likelihood of complications increased significantly with prolonged operative duration, approximately doubling with operative time thresholds exceeding 2 or more hours. Meta-analyses also demonstrated a 14% increase in the likelihood of complications for every 30 min of additional operating time. CONCLUSIONS: Prolonged operative time is associated with an increase in the risk of complications. Given the adverse consequences of complications, decreased operative times should be a universal goal for surgeons, hospitals, and policy-makers. Future study is recommended on the evaluation of interventions targeted to reducing operating time.

Performance of Harmonic devices in surgical oncology: an umbrella review of the evidence.

BACKGROUND: We performed an umbrella review of systematic reviews summarizing the evidence on the Harmonic scalpel (HS) compared with conventional techniques in surgical oncology (including lymph node dissection). METHODS: We searched MEDLINE, EMBASE, and the Cochrane Database of Systematic Reviews from inception to end of March of 2017 for meta-analyses or systematic reviews of randomized trials comparing HS to conventional techniques in surgical oncology. We assessed the quality of included systematic reviews with AMSTAR (A MeaSurement Tool to Assess systematic Reviews) and assessed the certainty in evidence for each pooled outcome using GRADE (Grading of Recommendations Assessment, Development, and Evaluation). RESULTS: We identified ten systematic reviews on breast cancer (n = 3), gastric cancers (n = 3), oral, head, and neck cancers (n = 1), and colon cancers (n = 3). Most reviews received a higher rating using AMSTAR. For operative time, systematic reviews reported a reduction of 25 to 29 min for HS compared with conventional methods across oncology types, with the exception of breast cancer where little differences were observed (very low to moderate quality of evidence (GRADE)). For blood loss and drainage volume, the majority of reviews reported statistically significant reductions with HS, and reductions ranged from 42 to 141 mL, and from 42 to 292 mL, respectively (very low to moderate quality of evidence). Hospitalization days were reported to decrease with use of HS by 0.2 to 3.2 days; however, reductions were only statistically significant for half of the included reviews (low to moderate quality of evidence). Regarding perioperative complications, two of six reviews reported a significantly reduced risk with HS use (breast cancer surgery) (moderate to high quality evidence)). CONCLUSION: Across surgical oncology types, the majority of included systematic reviews showed a statistically significant or numerical improvement in surgical outcomes with use of the HS compared with conventional methods. Well-designed randomized studies with large sample sizes will help to provide more precise estimates and reduce the risk of heterogeneity.

Systematic review and network meta-analysis comparing palbociclib with chemotherapy agents for the treatment of postmenopausal women with HR-positive and HER2-negative advanced/metastatic breast cancer.

PURPOSE: To compare palbociclib + letrozole and palbociclib + fulvestrant with chemotherapy agents in postmenopausal women with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) advanced/metastatic breast cancer (ABC/MBC) who had no prior systemic treatment for advanced disease (first line) or whose disease progressed after prior endocrine therapy or chemotherapy (second line). METHODS: A systematic search identified randomized controlled trials (RCTs) published from January 2000 to January 2016 that compared endocrine-based therapies, chemotherapy agents, and/or chemotherapy agents + biological therapies in the first- and second-line treatment of postmenopausal women with HR+/HER2- ABC/MBC. The main outcome of interest was progression-free survival (PFS)/time to progression (TTP). Bayesian network meta-analyses (NMAs) and pairwise meta-analyses were conducted. Heterogeneity and inconsistency were assessed. RESULTS: Sixty RCTs met eligibility criteria and were stratified by line of therapy. In the first line, palbociclib + letrozole showed statistically significant improvements in PFS/TTP versus capecitabine [intermittent: HR 0.28 (95% CrI 0.11-0.72)] and mitoxantrone [HR 0.28 (0.13-0.61)], and trended toward improvements versus paclitaxel [HR 0.59 (0.19-1.96)], docetaxel [HR 0.51 (0.14-2.03)] and other monotherapy or combination agents (HRs ranging from 0.24 to 0.99). In the second line, palbociclib + fulvestrant showed statistically significant improvements in PFS/TTP versus capecitabine [intermittent: HR 0.28 (0.13-0.65)], mitoxantrone [HR 0.26 (0.12-0.53)], and pegylated liposomal doxorubicin [HR 0.19 (0.07-0.50)], and trended toward improvements versus paclitaxel [HR 0.48 (0.16-1.44)], docetaxel [HR 0.71 (0.24-2.13)] and other monotherapy or combination agents (HRs ranging from 0.23-0.89). NMA findings aligned with direct evidence and were robust to sensitivity analyses. CONCLUSIONS: Palbociclib + letrozole and palbociclib + fulvestrant demonstrate trends in incremental efficacy compared with chemotherapy agents for the first- and second-line treatment of HR +/HER2- ABC/MBC.

Transient elastography for the diagnosis of liver fibrosis: a systematic review of economic evaluations.

BACKGROUND: Liver biopsy remains the gold standard for the diagnosis of liver fibrosis, but its use as a diagnostic tool is limited by its invasive nature and high cost. OBJECTIVE: The aim of this study was to systematically review the cost-effectiveness of transient elastography (TE) with and without controlled attenuation parameter (CAP) for the diagnosis of liver fibrosis or steatosis in patients with hepatitis B, hepatitis C, alcoholic liver disease and non-alcoholic fatty liver disease. METHODS: An economic literature search was performed. Eligibility criteria included systematic reviews, health technology assessments or economic evaluations of TE compared to liver biopsy and other non-invasive tests. After abstract screening, full-text reports of potentially relevant articles were assessed in duplicate. The methodological quality of the included studies was also appraised. RESULTS: The database search yielded 253 records; four cost-effectiveness and four cost-utility studies were included. The methodological quality of the included studies varies. High-quality cost-effectiveness studies not only suggested that TE is less costly but also less accurate than liver biopsy. The incremental cost-effectiveness ratio (ICER) of TE improves with a greater level of diagnostic accuracy and a higher degree of liver fibrosis. High-quality cost-utility studies indicated that TE is a cost-effective alternative to biopsy with ICER between $9000 and $14 000 per QALY for patients with hepatitis C. We did not find studies that assessed the cost-effectiveness of TE with CAP for the diagnosis of liver steatosis. CONCLUSIONS: Transient elastography is an economically attractive alternative to liver biopsy and other non-invasive diagnostic tests especially for patients with a higher degree of liver fibrosis.

Aripiprazole Lauroxil Compared with Paliperidone Palmitate in Patients with Schizophrenia: An Indirect Treatment Comparison.

BACKGROUND: Aripiprazole lauroxil (AL) is a long-acting injectable atypical antipsychotic recently approved for treatment of schizophrenia on the basis of a large-scale trial of two doses of AL versus placebo. There are no direct-comparison studies with paliperidone palmitate (PP; long-acting antipsychotic used most often in acute settings) for the acute psychotic episode. OBJECTIVES: To indirectly compare efficacy and safety of the pivotal AL study with all PP studies meeting indirect comparison criteria. METHODS: Systematic searches of MEDLINE, Embase, Cochrane CENTRAL, PsycINFO, ClinicalTrials.gov, International Clinical Trials Registry Platform, and gray literature were performed to identify randomized controlled trials of PP with similar designs to the AL trial. Bayesian network meta-analysis compared treatments with respect to symptom response and tolerability issues including weight gain, akathisia, parkinsonism, and likelihood of treatment-emergent adverse events. RESULTS: Three appropriate PP studies were identified for indirect comparison. Both doses of AL (441 mg and 882 mg monthly) were used and compared with two efficacious doses of PP (156 mg and 234 mg monthly). All four active-treatment conditions were associated with comparable reductions in acute symptoms (Positive and Negative Syndrome Scale) versus placebo and were of similar magnitude (range of mean difference -8.12 to -12.01, with overlapping 95% credible intervals). Between-group comparisons of active-treatment arms were associated with summary estimates of magnitude near 0. No clinically meaningful differences in selected safety or tolerability parameter incidence were found between active treatments. CONCLUSIONS: These results suggest that both AL and PP are effective for treatment of adults experiencing acute exacerbation of schizophrenia.

Risk of serious infection in biological treatment of patients with rheumatoid arthritis: a systematic review and meta-analysis.

BACKGROUND: Serious infections are a major concern for patients considering treatments for rheumatoid arthritis. Evidence is inconsistent as to whether biological drugs are associated with an increased risk of serious infection compared with traditional disease-modifying antirheumatic drugs (DMARDs). We did a systematic review and meta-analysis of serious infections in patients treated with biological drugs compared with those treated with traditional DMARDs. METHODS: We did a systematic literature search with Medline, Embase, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov from their inception to Feb 11, 2014. Search terms included "biologics", "rheumatoid arthritis" and their synonyms. Trials were eligible for inclusion if they included any of the approved biological drugs and reported serious infections. We assessed the risk of bias with the Cochrane Risk of Bias Tool. We did a Bayesian network meta-analysis of published trials using a binomial likelihood model to assess the risk of serious infections in patients with rheumatoid arthritis who were treated with biological drugs, compared with those treated with traditional DMARDs. The odds ratio (OR) of serious infection was the primary measure of treatment effect and calculated 95% credible intervals using Markov Chain Monte Carlo methods. FINDINGS: The systematic review identified 106 trials that reported serious infections and included patients with rheumatoid arthritis who received biological drugs. Compared with traditional DMARDs, standard-dose biological drugs (OR 1.31, 95% credible interval [CrI] 1.09-1.58) and high-dose biological drugs (1.90, 1.50-2.39) were associated with an increased risk of serious infections, although low-dose biological drugs (0.93, 0.65-1.33) were not. The risk was lower in patients who were methotrexate naive compared with traditional DMARD-experienced or anti-tumour necrosis factor biological drug-experienced patients. The absolute increase in the number of serious infections per 1000 patients treated each year ranged from six for standard-dose biological drugs to 55 for combination biological therapy, compared with traditional DMARDs. INTERPRETATION: Standard-dose and high-dose biological drugs (with or without traditional DMARDs) are associated with an increase in serious infections in rheumatoid arthritis compared with traditional DMARDs, although low-dose biological drugs are not. Clinicians should discuss the balance between benefit and harm with the individual patient before starting biological treatment for rheumatoid arthritis. FUNDING: Rheumatology Division at the University of Alabama at Birmingham.

Increasing Minimally Invasive Hysterectomy: A Canadian Academic Health Centre Experience.

OBJECTIVE: An institution wide strategic plan was established to improve minimally invasive surgery (MIS) across all surgical divisions at The Ottawa Hospital (TOH). The primary objective of this study is to determine the change in MIS hysterectomy rate between 2005 and 2012 at this centre. Secondary objectives include determining the impact on overall length of stay (LOS) in hospital, complications, return to hospital, operating room time, and cost. METHODS: We performed a retrospective analysis of all hysterectomies for benign disease performed at TOH between 2005 and 2012. Cases were excluded if they were related to pregnancy or classified as "partial hysterectomy." The outcomes and cost of the approaches were compared. RESULTS: A total of 4337 hysterectomy cases were reviewed. The MIS hysterectomy rate increased from 40.1% in 2005 to 74.2% in 2012. There was a decrease in mean LOS from 2.5 to 1.6 days. This translated to a saving of 1898 inpatient bed days. Compared with laparotomy, laparoscopic hysterectomy was associated with a reduced risk of transfusion and a reduced risk of ileus, and vaginal hysterectomy was associated with an increased risk of postoperative abscess. There was no difference in rates of returning to hospital or other complications between women undergoing abdominal hysterectomy and women undergoing MIS hysterectomy (which included both laparoscopic and vaginal approaches). The mean (SD) cost per approach was $7241 ($1985), $4532 ($1718), and $5637 ($1579) for abdominal hysterectomy, vaginal hysterectomy, and laparoscopic hysterectomy, respectively. CONCLUSION: The initiatives implemented at TOH in 2007 resulted in a significant increase in the MIS hysterectomy rate, a decrease in mean LOS, and substantial theoretical cost savings for the hospital.

The PRISMA extension statement for reporting of systematic reviews incorporating network meta-analyses of health care interventions: checklist and explanations.

The PRISMA statement is a reporting guideline designed to improve the completeness of reporting of systematic reviews and meta-analyses. Authors have used this guideline worldwide to prepare their reviews for publication. In the past, these reports typically compared 2 treatment alternatives. With the evolution of systematic reviews that compare multiple treatments, some of them only indirectly, authors face novel challenges for conducting and reporting their reviews. This extension of the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) statement was developed specifically to improve the reporting of systematic reviews incorporating network meta-analyses. A group of experts participated in a systematic review, Delphi survey, and face-to-face discussion and consensus meeting to establish new checklist items for this extension statement. Current PRISMA items were also clarified. A modified, 32-item PRISMA extension checklist was developed to address what the group considered to be immediately relevant to the reporting of network meta-analyses. This document presents the extension and provides examples of good reporting, as well as elaborations regarding the rationale for new checklist items and the modification of previously existing items from the PRISMA statement. It also highlights educational information related to key considerations in the practice of network meta-analysis. The target audience includes authors and readers of network meta-analyses, as well as journal editors and peer reviewers.

Direct costs of adult chronic rhinosinusitis by using 4 methods of estimation: Results of the US Medical Expenditure Panel Survey.

BACKGROUND: Chronic rhinosinusitis (CRS) is an inflammatory disease that affects 2% to 16% of the US population. Despite its increasing prevalence, there are currently limited data in the literature evaluating the economic burden of this disease. OBJECTIVE: This study aimed to determine the direct health care costs of CRS from the perspective of the US government. METHODS: A prevalence-based approach was used to estimate cost of illness for CRS from the 2011 Medical Expenditure Panel Survey database by using a 4-part model: (1) an estimated sum of all health care expenditures, (2) an attribution model for disease-specific estimation of expenditures, (3) an estimation based on a propensity score model, and (4) estimated disease-specific expenditure by using a linear regression-based approach. A disease prevalence of 3.5% was used. RESULTS: The mean CRS-specific annual expenditure was $5955 (95% CI, $5087-$6823) by using method 1 compared with $5560 (95% CI, $4689-$6431) by using method 2 and $5560 (95% CI, $4653-$6467) by using method 3. The annual expenditure, as estimated by using method 4, was $5589 (95% CI, $4986-$6192). Ambulatory expenses accounted for the largest proportion of expenditures, followed by prescription and in-hospital expenses. CONCLUSIONS: This study provided a range of estimates of the direct medical expenditures associated with CRS. We demonstrated that the economic burden attributable to this disease was an estimated $60.2 to $64.5 billion US dollars in 2011, with a wide variation in the total and incremental direct expenditures depending on the type of estimation model used and the prevalence assumed.

Triptans in the Acute Treatment of Migraine: A Systematic Review and Network Meta-Analysis.

BACKGROUND: Although triptans are widely used in the acute management of migraine, there is uncertainty around the comparative efficacy of triptans among each other and vs non-triptan migraine treatments. We conducted systematic reviews and network meta-analyses to compare the relative efficacy of triptans (alone or in combination with other drugs) for acute treatment of migraines compared with other triptan agents, non-steroidal anti-inflammatory drugs (NSAIDs), acetylsalicylic acid (ASA), acetaminophen, ergots, opioids, or anti-emetics. METHODS: The Cochrane Library, MEDLINE, and EMBASE were searched for randomized controlled trials that compared triptans (alone or in combination with other drugs) with placebo-controlled or active migraine treatments. Study selection, data extraction, and quality assessment were completed independently by multiple reviewers. Outcome data were combined and analyzed using a Bayesian network meta-analysis. For each outcome, odds ratios, relative risks, and absolute probability of response were calculated. RESULTS: A total of 133 randomized controlled trials met the inclusion criteria. Standard dose triptans relieved headaches within 2 hours in 42 to 76% of patients, and 2-hour sustained freedom from pain was achieved for 18 to 50% of patients. Standard dose triptans provided sustained headache relief at 24 hours in 29 to 50% of patients, and sustained freedom from pain in 18 to 33% of patients. Use of rescue medications ranged from 20 to 34%. For 2-hour headache relief, standard dose triptan achieved better outcomes (42 to 76% response) than ergots (38%); equal or better outcomes than NSAIDs, ASA, and acetaminophen (46 to 52%); and equal or slightly worse outcomes than combination therapy (62 to 80%). Among individual triptans, sumatriptan subcutaneous injection, rizatriptan ODT, zolmitriptan ODT, and eletriptan tablets were associated with the most favorable outcomes. INTERPRETATION/CONCLUSIONS: Triptans are effective for migraine relief. Standard dose triptans are associated with better outcomes than ergots, and most triptans are associated with equal or better outcomes compared with NSAIDs, ASA, and acetaminophen. Use of triptans in combination with ASA or acetaminophen, or using alternative modes of administration such as injectables, may be associated with slightly better outcomes than standard dose triptan tablets.

Network meta-analysis for comparing treatment effects of multiple interventions: an introduction.

Systematic reviews and meta-analyses of randomized trials have long been important synthesis tools for guiding evidence-based medicine. More recently, network meta-analyses, an extension of traditional meta-analyses enabling the comparison of multiple interventions, use new statistical methods to incorporate clinical evidence from both direct and indirect treatment comparisons in a network of treatments and associated trials. There is a need to provide education to ensure that core methodological considerations underlying network meta-analyses are well understood by readers and researchers to maximize their ability to appropriately interpret findings and appraise validity. Network meta-analyses are highly informative for assessing the comparative effects of multiple competing interventions in clinical practice and are a valuable tool for health technology assessment and comparative effectiveness research.

Clinical and safety outcomes associated with treatment of acute venous thromboembolism: a systematic review and meta-analysis.

IMPORTANCE: Many anticoagulant strategies are available for the treatment of acute venous thromboembolism, yet little guidance exists regarding which drug is most effective and safe. OBJECTIVE: To summarize and compare the efficacy and safety outcomes associated with 8 anticoagulation options (unfractionated heparin [UFH], low-molecular-weight heparin [LMWH], or fondaparinux in combination with vitamin K antagonists); LMWH with dabigatran or edoxaban; rivaroxaban; apixaban; and LMWH alone) for treatment of venous thromboembolism. DATA SOURCES: A systematic literature search was conducted using MEDLINE, EMBASE, and the evidence-based medicine reviews from inception through February 28, 2014. STUDY SELECTION: Eligible studies were randomized trials reporting rates of recurrent venous thromboembolism and major bleeding in patients with acute venous thromboembolism. Of the 1197 studies identified, 45 trials including 44,989 patients were included in the analyses. DATA EXTRACTION AND SYNTHESIS: Two reviewers independently extracted trial-level data including number of patients, duration of follow-up, and outcomes. The data were pooled using network meta-analysis. MAIN OUTCOMES AND MEASURES: The primary clinical and safety outcomes were recurrent venous thromboembolism and major bleeding, respectively. RESULTS: Compared with the LMWH-vitamin K antagonist combination, a treatment strategy using the UFH-vitamin K antagonist combination was associated with an increased risk of recurrent venous thromboembolism (hazard ratio [HR], 1.42; 95% credible interval [CrI], 1.15-1.79). The proportion of patients experiencing recurrent venous thromboembolism during 3 months of treatment were 1.84% (95% CrI, 1.33%-2.51%) for the UFH-vitamin K antagonist combination and 1.30% (95% CrI, 1.02%-1.62%) for the LMWH-vitamin K antagonist combination. Rivaroxaban (HR, 0.55; 95% CrI, 0.35-0.89) and apixaban (HR, 0.31; 95% CrI, 0.15-0.62) were associated with a lower risk of bleeding than was the LMWH-vitamin K antagonist combination, with a lower proportion of patients experiencing a major bleeding event during 3 months of anticoagulation: 0.49% (95% CrI, 0.29%-0.85%) for rivaroxaban, 0.28% (95% CrI, 0.14%-0.50%) for apixaban, and 0.89% (95% CrI, 0.66%-1.16%) for the LMWH-vitamin K antagonist combination. CONCLUSIONS AND RELEVANCE: Using meta-analytic pooling, there were no statistically significant differences for efficacy and safety associated with most treatment strategies used to treat acute venous thromboembolism compared with the LMWH-vitamin K antagonist combination. However, findings suggest that the UFH-vitamin K antagonist combination is associated with the least effective strategy and that rivaroxaban and apixaban may be associated with the lowest risk for bleeding.

Cost-effectiveness of new oral anticoagulants compared with warfarin in preventing stroke and other cardiovascular events in patients with atrial fibrillation.

OBJECTIVES: The primary objective was to assess the cost-effectiveness of new oral anticoagulants compared with warfarin in patients with nonvalvular atrial fibrillation. Secondary objectives related to assessing the cost-effectiveness of new oral anticoagulants stratified by center-specific time in therapeutic range, age, and CHADS2 score. METHODS: Cost-effectiveness was assessed by the incremental cost per quality-adjusted life-year (QALY) gained. Analysis used a Markov cohort model that followed patients from initiation of pharmacotherapy to death. Transition probabilities were obtained from a concurrent network meta-analysis. Utility values and costs were obtained from published data. Numerous deterministic sensitivity analyses and probabilistic analysis were conducted. RESULTS: The incremental cost per QALY gained for dabigatran 150 mg versus warfarin was $20,797. Apixaban produced equal QALYs at a higher cost. Dabigatran 110 mg and rivaroxaban were dominated by dabigatran 150 mg and apixaban. Results were sensitive to the drug costs of apixaban, the time horizon adopted, and the consequences from major and minor bleeds with dabigatran. Results varied by a center's average time in therapeutic range, a patient's CHADS2 score, and patient age, with either dabigatran 150 mg or apixaban being optimal. CONCLUSIONS: Results were highly sensitive to patient characteristics. Rivaroxaban and dabigatran 110 mg were unlikely to be cost-effective. For different characteristics, apixaban or dabigatran 150 mg were optimal. Thus, the choice between these two options may come down to the price of apixaban and further evidence on the impact of major and minor bleeds with dabigatran.

Electrode-Skin Impedance Model Parameter Estimation in the Frequency-Domain.

This paper presents a method for identifying parameter values for a double parallel resistor/constant-phase-element model of the electrode-skin interface for individual silver and silver/silver chloride electrodes. The impedance of each electrode was measured in five from 1 Hz-10 kHz. Phase features of these data were used to guide initial estimates for parameter values which were refined using a least squares algorithm. Resultant model impedances were compared with experimental data across a typical biosignal bandwidth (1 Hz-500 Hz). The method was effective in estimating component values in most datasets, and resulted in a mean relative RMS error of 7 % (σ = 8.3%) across the biosignal bandwidth.Clinical relevance- This work establishes a feature-based method for finding component parameter estimates for an electrode contact impedance model.