Tammy Clifford

THE EFFECT OF ENGLISH-LANGUAGE RESTRICTION ON SYSTEMATIC REVIEW-BASED META-ANALYSES: A SYSTEMATIC REVIEW OF EMPIRICAL STUDIES

OBJECTIVES The English language is generally perceived to be the universal language of science. However, the exclusive reliance on English-language studies may not represent all of the evidence. Excluding languages other than English (LOE) may introduce a language bias and lead to erroneous conclusions. STUDY DESIGN AND SETTING We conducted a comprehensive literature search using bibliographic databases and grey literature sources. Studies were eligible for inclusion if they measured the effect of excluding randomized controlled trials (RCTs) reported in LOE from systematic review-based meta-analyses (SR/MA) for one or more outcomes. RESULTS None of the included studies found major differences between summary treatment effects in English-language restricted meta-analyses and LOE-inclusive meta-analyses. Findings differed about the methodological and reporting quality of trials reported in LOE. The precision of pooled estimates improved with the inclusion of LOE trials. CONCLUSIONS Overall, we found no evidence of a systematic bias from the use of language restrictions in systematic review-based meta-analyses in conventional medicine. Further research is needed to determine the impact of language restriction on systematic reviews in particular fields of medicine.

Efficacy and safety outcomes of oral anticoagulants and antiplatelet drugs in the secondary prevention of venous thromboembolism: systematic review and network meta-analysis

Objective To summarise and compare the efficacy and safety of various oral anticoagulants (dabigatran, rivaroxaban, apixaban, and vitamin K antagonists) and antiplatelet agents (acetylsalicylic acid) for the secondary prevention of venous thromboembolism. Design Systematic review and network meta-analysis. Data sources Literature search using Medline (1950 to present), Embase (1980 to present), and the Cochrane Register of Controlled Trials using the OVID interface. Publications from potentially relevant journals were also searched by hand. Review methods Randomised controlled trials of patients receiving anticoagulants, antiplatelet drugs, or placebo or observation for secondary prevention of venous thromboembolism. Selected outcomes were rates of recurrent venous thromboembolism and major bleeding. Two reviewers independently extracted data onto standardised forms. Results 12 articles met our inclusion criteria, with 11 999 patients evaluated for efficacy and 12 167 for safety. All treatments reduced the risk of recurrent venous thromboembolism. Compared with placebo or observation, vitamin K antagonists at a standard adjusted dose (target international normalised ratio 2.0-3.0) showed the highest risk difference (odds ratio 0.07; 95% credible interval 0.03 to 0.15) and acetylsalicylic acid showed the lowest risk difference (0.65; 0.39 to 1.03). Risk of major bleeding was higher with a standard adjusted dose of vitamin K antagonists (5.24; 1.78 to 18.25) than with placebo or observation. Fatal recurrent venous thromboembolism and fatal bleeding were rare. Detailed subgroup and individual patient level data were not available. Conclusions All oral anticoagulants and antiplatelet agents investigated in this analysis were associated with a reduced recurrence of venous thromboembolism compared with placebo or observation, although acetylsalicylic acid was associated with the lowest risk reduction. Vitamin K antagonists given at a standard adjusted dose was associated with the greatest risk reduction in recurrent venous thromboembolism, but also the greatest risk of major bleeding.

Funding source, trial outcome and reporting quality: are they related? Results of a pilot study

BackgroundThere has been increasing concern regarding the potential effects of the commercialization of research.MethodsIn order to examine the relationships between funding source, trial outcome and reporting quality, recent issues of five peer-reviewed, high impact factor, general medical journals were hand-searched to identify a sample of 100 randomized controlled trials (20 trials/journal). Relevant data, including funding source (industry/not-for-profit/mixed/not reported) and statistical significance of primary outcome (favouring new treatment/favouring conventional treatment/neutral/unclear), were abstracted. Quality scores were assigned using the Jadad scale and the adequacy of allocation concealment.ResultsSixty-six percent of trials received some industry funding. Trial outcome was not associated with funding source (p= .461). There was a preponderance of favourable statistical conclusions among published trials with 67% reporting results that favored a new treatment whereas 6% favoured the conventional treatment. Quality scores were not associated with funding source or trial outcome.ConclusionsIt is not known whether the absence of significant associations between funding source, trial outcome and reporting quality reflects a true absence of an association or is an artefact of inadequate statistical power, reliance on voluntary disclosure of funding information, a focus on trials recently published in the top medical journals, or some combination thereof. Continued and expanded monitoring of potential conflicts is recommended, particularly in light of new guidelines for disclosure that have been endorsed by the ICMJE.

A Microsoft-Excel-based tool for running and critically appraising network meta-analyses—an overview and application of NetMetaXL

BackgroundThe use of network meta-analysis has increased dramatically in recent years. WinBUGS, a freely available Bayesian software package, has been the most widely used software package to conduct network meta-analyses. However, the learning curve for WinBUGS can be daunting, especially for new users. Furthermore, critical appraisal of network meta-analyses conducted in WinBUGS can be challenging given its limited data manipulation capabilities and the fact that generation of graphical output from network meta-analyses often relies on different software packages than the analyses themselves.MethodsWe developed a freely available Microsoft-Excel-based tool called NetMetaXL, programmed in Visual Basic for Applications, which provides an interface for conducting a Bayesian network meta-analysis using WinBUGS from within Microsoft Excel. . This tool allows the user to easily prepare and enter data, set model assumptions, and run the network meta-analysis, with results being automatically displayed in an Excel spreadsheet. It also contains macros that use NetMetaXL’s interface to generate evidence network diagrams, forest plots, league tables of pairwise comparisons, probability plots (rankograms), and inconsistency plots within Microsoft Excel. All figures generated are publication quality, thereby increasing the efficiency of knowledge transfer and manuscript preparation.ResultsWe demonstrate the application of NetMetaXL using data from a network meta-analysis published previously which compares combined resynchronization and implantable defibrillator therapy in left ventricular dysfunction. We replicate results from the previous publication while demonstrating result summaries generated by the software.ConclusionsUse of the freely available NetMetaXL successfully demonstrated its ability to make running network meta-analyses more accessible to novice WinBUGS users by allowing analyses to be conducted entirely within Microsoft Excel. NetMetaXL also allows for more efficient and transparent critical appraisal of network meta-analyses, enhanced standardization of reporting, and integration with health economic evaluations which are frequently Excel-based.

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

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.

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.

RAPID REVIEW: AN EMERGING APPROACH TO EVIDENCE SYNTHESIS IN HEALTH TECHNOLOGY ASSESSMENT

BACKGROUND Increasingly, healthcare decision makers demand quality evidence in a short timeframe to support urgent and emergent decisions related to procurement, clinical practice, and policy. Health technology assessment (HTA) producers are responding by developing innovative approaches to evidence synthesis that can be executed more quickly than traditional systematic review. These approaches, and the broader implications they bring to bear on health decision making and policy development, however, are generally neither well-understood nor well-described. This study intends to contribute to an emerging literature around methodological approaches to rapid review in HTA by outlining those developed and implemented by the Canadian Agency for Drugs and Technologies in Health (CADTH). METHODS Since 2005, CADTH has developed and implemented a rapid review approach that synthesizes evidence to support informed healthcare decisions and policy. Rapid Response reports are tailored to the identified needs of Canadian health decision makers, representing a range of options with regard to depth, breadth, and time-to-delivery. RESULTS Preliminary observations indicate that CADTHs approach to rapid evidence review is generally well-received by Canadian health decision makers; real-world case studies provide pragmatic examples of how health decision makers have used Rapid Response reports to support evidence-informed health decisions across Canada. CONCLUSIONS Rapid review is becoming an increasingly important approach to evidence synthesis, both within and external to the field of HTA. Transparent reporting of the methods used to develop rapid review products will be critical to the assessment of their relevance, utility and effects in a range of contexts.

Factors Influencing Full Breastfeeding in a Southwestern Ontario Community: Assessments at 1 Week and at 6 Months Postpartum

Factors associated with full breastfeeding (FBF) at 1 week and at 6 months postpartum were examined in a cohort of 856 mother-infant dyads. Questionnaires were mailed at 4 time points over the first 6 months postpartum. At 1 week, 68% of infants were FBF; at 6 months, 23% were FBF. Factors significantly associated with FBF at 1 week were hospital of delivery, residing with a smoker, maternal shiftwork during pregnancy, and having no prior breast-feeding experience. Cox proportional hazards regression analysis showed that residing with a smoker, having consumed caffeine during pregnancy, reporting elevated maternal trait anxiety at 1 week postpartum, having been employed full-time outside the home prior to delivery, and having received anesthesia/analgesia during labor/delivery were associated with earlier cessation of FBF, whereas not having previous breastfeeding experience predicted its continuation. Although most mothers are breastfeeding early on, a number of factors adversely affect its successful continuation.

Complementary and Alternative Medicine Use by Pediatric Specialty Outpatients

OBJECTIVE: Complementary and alternative medicine (CAM) use is high among children and youth with chronic illnesses. The objective of this study was to assess the prevalence and patterns of CAM use in 10 subspecialty clinics in Canada and to compare CAM use between 2 geographically diverse locations. METHODS: This survey was carried out at 1 Children’s Hospital in western Canada (Edmonton) and 1 Children’s Hospital in central Canada (Ottawa). Questionnaires were completed by parents in either French or English. RESULTS: Although demographic characteristics of the 2 populations were similar, CAM use at the western hospital was 71% (n = 704) compared with 42% (n = 222) at the central hospital (P < .0001). Most respondents agreed or strongly agreed that they feel comfortable discussing CAM in their clinic. The most common CAM products currently used were multivitamins/minerals, herbal products, and homeopathic remedies. The most common CAM practices currently used were massage, chiropractic, relaxation, and aromatherapy. Eighty adverse effects were reported, and 55 (68.8%) of these were self-assessed as minor. CONCLUSIONS: Results of this study indicate that CAM use is high among pediatric specialty clinic outpatients and is much greater in the western than in the central hospital. Most respondents felt that their CAM use was helpful with few or no harms associated. Many patients, using CAM alongside their conventional medicines, are still not discussing their CAM use with their physicians and are increasing the likelihood for potential interactions and preventable harms.

Case studies that illustrate disinvestment and resource allocation decision-making processes in health care: a systematic review.

OBJECTIVE Technological change accounts for approximately 25 percent of health expenditure growth. To date, limited research has been published on case studies of disinvestment and resource allocation decision making in clinical practice. Our research objective is to systematically review and catalogue the application of frameworks and tools for disinvestment and resource allocation decision making in health care. METHODS An electronic literature search was executed for studies on disinvestment, obsolete and ineffective technologies, and priority healthcare setting, published from January 1990 until January 2012. Databases searched were MEDLINE, MEDLINE In-Process and Other Non-Indexed Citations, Embase, The Cochrane Library, PubMed, and HEED. RESULTS Fourteen case studies on the application of frameworks and tools for disinvestment and resource allocation decisions were included. Most studies described the application of program budgeting and marginal analysis (PBMA), and two reports used health technology assessment (HTA) methods for coverage decisions in a national fee-for-service structure. Numerous healthcare technologies and services were covered across the studies. We describe the multiple criteria considered for decision making, and the strengths and limitations of these frameworks and tools are highlighted. CONCLUSIONS Disinvestment and resource allocation decisions require evidence to ensure their transparency and objectivity. PBMA was used to assess resource allocation of health services and technologies in a fixed budget jurisdiction, while HTA reviews focused on specific technologies, principally in fee-for-service structures. Future research can review the data requirements and explore opportunities to increase the quantity of available evidence for disinvestment and resource allocation decisions.