Shannon Kelly

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

Systematic review and network meta-analysis comparing antithrombotic agents for the prevention of stroke and major bleeding in patients with atrial fibrillation

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 centers average time in therapeutic range, a patients 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.

Triptans in the acute treatment of migraine: A systematic review and network meta-analysis.

Objective To examine the comparative efficacy and safety of antithrombotic treatments (apixaban, dabigatran, edoxaban, rivaroxaban and vitamin K antagonists (VKA) at a standard adjusted dose (target international normalised ratio 2.0–3.0), acetylsalicylic acid (ASA), ASA and clopidogrel) for non-valvular atrial fibrillation and among subpopulations. Design Systematic review and network meta-analysis. Data sources A systematic literature search strategy was designed and carried out using MEDLINE, EMBASE, the Cochrane Register of Controlled Trials and the grey literature including the websites of regulatory agencies and health technology assessment organisations for trials published in English from 1988 to January 2014. Eligibility criteria for selecting studies Randomised controlled trials were selected for inclusion if they were published in English, included at least one antithrombotic treatment and involved patients with non-valvular atrial fibrillation eligible to receive anticoagulant therapy. Results For stroke or systemic embolism, dabigatran 150 mg and apixaban twice daily were associated with reductions relative to standard adjusted dose VKA, whereas low-dose ASA and the combination of clopidogrel plus low-dose ASA were associated with increases. Absolute risk reductions ranged from 6 fewer events per 1000 patients treated for dabigatran 150 mg twice daily to 15 more events for clopidogrel plus ASA. For major bleeding, edoxaban 30 mg daily, apixaban, edoxaban 60 mg daily and dabigatran 110 mg twice daily were associated with reductions compared to standard adjusted dose VKA. Absolute risk reductions with these agents ranged from 18 fewer per 1000 patients treated each year for edoxaban 30 mg daily to 24 more for medium dose ASA. Conclusions Compared with standard adjusted dose VKA, new oral anticoagulants were associated with modest reductions in the absolute risk of stroke and major bleeding. People on antiplatelet drugs experienced more strokes compared with anticoagulant drugs without any reduction in bleeding risk. To fully elucidate the comparative benefits and harms of antithrombotic agents across the various subpopulations, rigorously conducted comparative studies or network meta-regression analyses of patient-level data are required. Systematic review registration number PROSPERO registry—CRD42012002721.

Quality of conduct and reporting in rapid reviews: an exploration of compliance with PRISMA and AMSTAR guidelines.

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.

DEFINING RAPID REVIEWS: A MODIFIED DELPHI CONSENSUS APPROACH.

BackgroundRapid reviews are an accelerated evidence synthesis approach intended to meet the timely needs of decision-makers in healthcare settings. Quality of conduct and reporting has been described in the rapid review literature; however, no formal assessment has been carried out using available instruments. The objective of this study was to explore compliance with conduct and reporting guidelines in rapid reviews published or posted online during 2013 and 2014.MethodsWe performed a comprehensive literature search for rapid reviews using multiple bibliographic databases (e.g. PubMed, MEDLINE, EMBASE, the Cochrane Library) through December 31, 2014. Grey literature was searched thoroughly, and health technology assessment agencies were surveyed to identify additional rapid review products. Candidate reviews were assessed for inclusion using pre-specified eligibility criteria. Detailed data was collected from the included reviews on study and reporting characteristics and variables significant to rapid reviews (e.g. nomenclature, definition). We evaluated the quality of conduct and reporting of included rapid reviews using the A Measurement Tool to Assess Systematic Reviews (AMSTAR) and Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklists. Compliance with each checklist item was examined, and the sum of adequately reported items was used to describe overall compliance. Rapid reviews were stratified to explore differences in compliance related to publication status. The association between compliance and time to completion or length of publication was explored through univariate regression.ResultsSixty-six rapid reviews were included. There were heterogeneous nomenclature, research questions and approaches to rapid reviews. Compliance with AMSTAR and PRISMA checklists was poor. Published rapid reviews were compliant with individual PRISMA items more often than unpublished reviews, but no difference was seen in AMSTAR item compliance overall. There was evidence of an association between length of publication and time to completion and the number of adequately reported PRISMA or AMSTAR items.ConclusionsTransparency and inadequate reporting are significant limitations of rapid reviews. Scientific editors, authors and producing agencies should ensure that the reporting of conduct and findings is accurate and complete. Further research may be warranted to explore reporting and conduct guidelines specific to rapid reviews and how these guidelines may be applied across the spectrum of rapid review approaches.

Testosterone therapy in hypogonadal men: a systematic review and network meta-analysis

OBJECTIVES Rapid reviews are characterized as an accelerated evidence synthesis approach with no universally accepted methodology or definition. This modified Delphi consensus study aimed to develop a comprehensive set of defining characteristics for rapid reviews that may be used as a functional definition. METHODS Expert panelists with knowledge in rapid reviews and evidence synthesis were identified. In the first round, panelists were asked to answer a seventeen-item survey addressing a variety of rapid review topics. Results led to the development of statements describing the characteristics of rapid reviews that were circulated to experts for agreement in a second survey round and further revised in a third round. Consensus was reached if ≥70 percent of experts agreed and there was stability in free-text comments. RESULTS A panel of sixty-six experts participated. Consensus was reached on ten of eleven statements describing the characteristics of rapid reviews. According to the panel, rapid reviews aim to meet the requirements and timelines of a decision maker and should be conducted in less time than a systematic review. They use a variety of approaches to accelerate the evidence synthesis process, tailor the methods conventionally used to carry out systematic reviews, and use the most rigorous methods that the delivery time frame will allow. CONCLUSIONS This study achieved consensus on ten statements describing the defining characteristics of rapid reviews based on the opinion of a panel of knowledgeable experts. Areas of disagreement were also highlighted. Findings emphasize the role of the decision maker and stress the importance of transparent reporting.

Allergen immunotherapy for the treatment of allergic rhinitis and/or asthma: an umbrella review

Objective To assess the relative effects of individual testosterone products among hypogonadal men. Design Systematic review and network meta-analysis. Methods We searched MEDLINE, Embase, Cochrane CENTRAL, and grey literature (25 May 2017) for randomised-controlled trials (RCTs) and non-randomised studies (NRS) that involved hypogonadal men given testosterone replacement therapy (TRT) for ≥3 months. Comparators were placebo, another TRT, or the same product at a different dose. Outcomes were quality of life, depression, libido, erectile function, activities of daily living and testosterone levels, as well as cardiovascular death, myocardial infarction, stroke, prostate cancer, heart disease, diabetes, serious adverse events, withdrawals due to adverse events and erythrocytosis. RCT data were pooled via meta-analysis and network meta-analysis. Risk of bias was assessed using Cochrane’s risk of bias tool (RCTs) andScottish Intercollegiate Guidelines Network (SIGN)50 (NRS). Results Eighty-seven RCTs and 51 NRS were included. Most were at high or unclear risk of bias, with short treatment duration and follow-up. When compared as a class against placebo, TRT improved quality of life (standardised mean difference (SMD) −0.26, 95% CI −0.41 to –0.11), libido (SMD 0.33, 95% CI 0.16 to 0.50), depression (SMD −0.23, 95% CI −0.44 to –0.01) and erectile function (SMD 0.25, 95% CI 0.10 to 0.41). Most individual TRTs were significantly better than placebo at improving libido (6/10). Only one TRT was better than placebo at improving quality of life, and no individual TRTs improved depression or erectile function. There was no increased risk of adverse events, with the exception of withdrawals due to adverse events with the use of some TRTs. Conclusion Despite a class effect of improving quality of life, depression, erectile function and libido, major improvements were not observed with the use of any individual product. We observed no statistically significant increase in the risk of adverse events; however, longer-term high-quality trials are needed to fully assess the risk of harm. PROSPERO registration number CRD42014009963.

Expediting evidence synthesis for healthcare decision-making: exploring attitudes and perceptions towards rapid reviews using Q methodology

BACKGROUND Allergic rhinitis and asthma are important public health concerns, yet there is no consensus about the benefits and harms of allergen-specific immunotherapy to treat these conditions. We performed an umbrella review of systematic reviews summarizing the current evidence for the benefits and harms of subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT). METHODS We searched MEDLINE, Embase, the Cochrane Library and the grey literature from Jan. 1, 2010 to Nov. 20, 2016 for systematic reviews of randomized controlled trials or prospectively controlled studies involving children or adults with allergic rhinitis or asthma. Outcomes were summarized narratively (benefits: total combined symptom-medication score, symptom score, medication score, disease-specific quality of life, adherence; harms: anaphylaxis, death, local and systemic reactions). RESULTS Twenty-three systematic reviews were included. SCIT and SLIT were more effective than placebo for most outcomes. SCIT was better than SLIT at improving medication and symptom scores, with no differences in quality of life; however, data were limited for this comparison. Anaphylaxis and death were infrequently reported. Few reviews assessed benefits or harms among children. INTERPRETATION Allergen immunotherapy appears to be effective among patients with allergic rhinitis and asthma. The safety of allergen immunotherapy is not conclusively established, although death and anaphylaxis appear to be rare. PROSPERO no.: CRD42015024590.

Optimal duration of dual antiplatelet therapy following percutaneous coronary intervention: protocol for an umbrella review.

Background Rapid reviews expedite the knowledge synthesis process with the goal of providing timely information to healthcare decision-makers who want to use evidence-informed policy and practice approaches. A range of opinions and viewpoints on rapid reviews is thought to exist; however, no research to date has formally captured these views. This paper aims to explore evidence producer and knowledge user attitudes and perceptions towards rapid reviews. Methods A Q methodology study was conducted to identify central viewpoints about rapid reviews based on a broad topic discourse. Participants rank-ordered 50 text statements and explained their Q-sort in free-text comments. Individual Q-sorts were analysed using Q-Assessor (statistical method: factor analysis with varimax rotation). Factors, or salient viewpoints on rapid reviews, were identified, interpreted and described. Results Analysis of the 11 individual Q sorts identified three prominent viewpoints: Factor A cautions against the use of study design labels to make judgements. Factor B maintains that rapid reviews should be the exception and not the rule. Factor C focuses on the practical needs of the end-user over the review process. Conclusion Results show that there are opposing viewpoints on rapid reviews, yet some unity exists. The three factors described offer insight into how and why various stakeholders act as they do and what issues may need to be resolved before increase uptake of the evidence from rapid reviews can be realized in healthcare decision-making environments.

Safety, Effectiveness, and Cost-Effectiveness of New Oral Anticoagulants Compared with Warfarin in Preventing Stroke and Other Cardiovascular Events in Patients with Atrial Fibrillation

Introduction Although dual antiplatelet therapy (DAPT) is routinely given to patients after percutaneous coronary intervention (PCI) with stenting, the optimal duration is unknown. Recent evidence indicates there may be benefits in extending the duration beyond 12 months but such decisions may increase the risk of bleeding. Our objective is to provide a comprehensive overview of the literature for clinicians and policymakers via an umbrella review assessing the optimal duration of DAPT. Methods and analysis We will perform a comprehensive search of the published and grey literature for systematic reviews involving randomised controlled trials (RCTs) assessing the optimal duration of DAPT following PCI with stenting. The intervention of interest is extended DAPT (beyond 12 months) compared with short-term DAPT (6–12 months). Studies will be selected for inclusion by two reviewers, and the quality will be assessed. The primary outcomes of interest are all-cause mortality and cardiovascular mortality. Secondary outcomes will be bleeding (major, minor and gastrointestinal), urgent target vessel revascularisation, major adverse cardiovascular events, myocardial infarction, stroke and stent thrombosis. Outcomes will be assessed while on DAPT and after withdrawal of DAPT. Data will be summarised with respect to the number of included RCTs, number of participants, effect estimates and heterogeneity. Data will be reported separately based on patient demographics, procedural parameters (eg, stent types, lesion complexity and concurrent disease) and clinical presentation (eg, acute coronary syndromes, infarct type). Ethics and dissemination Our umbrella review aims to provide a comprehensive overview of the benefits and harms associated with extending DAPT beyond 12 months following PCI with stenting. The results of this review will inform clinical and policy decisions regarding the optimal treatment duration and reimbursement of DAPT following PCI with stenting. Results will be disseminated through a peer-reviewed publication and conference presentations. Ethics approval is not required for this study. Trial registration number CRD42016047735.