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Threshold Analysis as an Alternative to GRADE for Assessing Confidence in Guideline Recommendations Based on Network Meta-analyses.

ABSTRACT: Guideline development requires the synthesis of evidence on several treatments of interest, typically by using network meta-analysis (NMA). Because treatment effects may be estimated imprecisely or be based on evidence lacking internal or external validity, guideline developers must assess the robustness of recommendations made on the basis of the NMA to potential limitations in the evidence. Such limitations arise because the observed estimates differ from the true effects of interest, for example, because of study biases, sampling variation, or issues of relevance. The widely used GRADE (Grading of Recommendations Assessment, Development and Evaluation) framework aims to assess the quality of evidence supporting a recommendation by using a structured series of qualitative judgments. This article argues that GRADE approaches proposed for NMA are insufficient for the purposes of guideline development, because the influence of the evidence on the final recommendation is not taken into account. It outlines threshold analysis as an alternative approach, demonstrating the method with 2 examples of clinical guidelines from the National Institute for Health and Care Excellence (NICE) in the United Kingdom. Threshold analysis quantifies precisely how much the evidence could change (for any reason, such as potential biases, or simply sampling variation) before the recommendation changes, and what the revised recommendation would be. If it is judged that the evidence could not plausibly change by more than this amount, then the recommendation is considered robust; otherwise, it is sensitive to plausible changes in the evidence. In this manner, threshold analysis directly informs decision makers and guideline developers of the robustness of treatment recommendations.

SUBMITTER: Phillippo DM

PROVIDER: S-EPMC6739230 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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Threshold Analysis as an Alternative to GRADE for Assessing Confidence in Guideline Recommendations Based on Network Meta-analyses.

Phillippo David M DM Dias Sofia S Welton Nicky J NJ Caldwell Deborah M DM Taske Nichole N Ades A E AE

Annals of internal medicine 20190326 8

Guideline development requires the synthesis of evidence on several treatments of interest, typically by using network meta-analysis (NMA). Because treatment effects may be estimated imprecisely or be based on evidence lacking internal or external validity, guideline developers must assess the robustness of recommendations made on the basis of the NMA to potential limitations in the evidence. Such limitations arise because the observed estimates differ from the true effects of interest, for exam ...[more]

PMID: 30909295

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Project description:BACKGROUND:Network meta-analysis (NMA) has rapidly grown in use during the past decade for the comparison of healthcare interventions. While its general use in the comparison of conventional medicines has been studied previously, to our awareness, its use to assess complementary and alternative medicines (CAM) has not been studied. A scoping review of the literature was performed to identify systematic reviews incorporating NMAs involving one or more CAM interventions. METHODS:An information specialist executed a multi-database search (e.g., MEDLINE, Embase, Cochrane), and two reviewers performed study selection and data collection. Information on publication characteristics, diseases studied, interventions compared, reporting transparency, outcomes assessed, and other parameters were extracted from each review. RESULTS:A total of 89 SR/NMAs were included. The largest number of NMAs was conducted in China (39.3%), followed by the United Kingdom (12.4%) and the United States (9.0%). Reviews were published between 2010 and 2018, with the majority published between 2015 and 2018. More than 90 different CAM therapies appeared at least once, and the median number per NMA was 2 (IQR 1-4); 20.2% of reviews consisted of only CAM therapies. Dietary supplements (51.1%) and vitamins and minerals (42.2%) were the most commonly studied therapies, followed by electrical stimulation (31.1%), herbal medicines (24.4%), and acupuncture and related treatments (22.2%). A diverse set of conditions was identified, the most common being various forms of cancer (11.1%), osteoarthritis of the hip/knee (7.8%), and depression (5.9%). Most reviews adequately addressed a majority of the PRISMA NMA extension items; however, there were limitations in indication of an existing review protocol, exploration of network geometry, and exploration of risk of bias across studies, such as publication bias. CONCLUSION:The use of NMA to assess the effectiveness of CAM interventions is growing rapidly. Efforts to identify priority topics for future CAM-related NMAs and to enhance methods for CAM comparisons with conventional medicine are needed. SYSTEMATIC REVIEW REGISTRATION: https://ruor.uottawa.ca/handle/10393/35658.

Project description:BackgroundIdentifying persistence and extinction thresholds in species-habitat relationships is a major focal point of ecological research and conservation. However, one major concern regarding the incorporation of threshold analyses in conservation is the lack of knowledge on the generality and transferability of results across species and regions. We present a multi-region, multi-species approach of modeling threshold responses, which we use to investigate whether threshold effects are similar across species and regions.Methodology/principal findingsWe modeled local persistence and extinction dynamics of 25 forest-associated breeding birds based on detection/non-detection data, which were derived from repeated breeding bird atlases for the state of Vermont. We did not find threshold responses to be particularly well-supported, with 9 species supporting extinction thresholds and 5 supporting persistence thresholds. This contrasts with a previous study based on breeding bird atlas data from adjacent New York State, which showed that most species support persistence and extinction threshold models (15 and 22 of 25 study species respectively). In addition, species that supported a threshold model in both states had associated average threshold estimates of 61.41% (SE?=?6.11, persistence) and 66.45% (SE?=?9.15, extinction) in New York, compared to 51.08% (SE?=?10.60, persistence) and 73.67% (SE?=?5.70, extinction) in Vermont. Across species, thresholds were found at 19.45-87.96% forest cover for persistence and 50.82-91.02% for extinction dynamics.Conclusions/significanceThrough an approach that allows for broad-scale comparisons of threshold responses, we show that species vary in their threshold responses with regard to habitat amount, and that differences between even nearby regions can be pronounced. We present both ecological and methodological factors that may contribute to the different model results, but propose that regardless of the reasons behind these differences, our results merit a warning that threshold values cannot simply be transferred across regions or interpreted as clear-cut targets for ecosystem management and conservation.

Project description:Bisphosphonates have been found to be effective in preventing fragility fractures. However, their comparative effectiveness in populations at risk has yet to be defined. In light of recent clinical trials, we aimed to compare four bisphosphonates (alendronate, ibandronate, risedronate, and zoledronate) and to identify which are the most effective for the prevention of fragility fractures. This is an update of a systematic review previously published as part of a NICE HTA report. We conducted a systematic review and network meta-analysis, updating the estimates regarding the comparative effectiveness of the aforementioned bisphosphonates. Studies identified from published and unpublished sources between 2014 and 2021 were added to the studies identified in the previous review. Screening, data extraction and risk of bias assessment were independently undertaken by two reviewers. Outcomes were fractures, femoral neck bone mineral density (BMD), mortality, and adverse events. We identified 25 additional trials, resulting in a total population of 47,007 participants. All treatments had beneficial effects on fractures versus placebo with zoledronate being the most effective treatment in preventing vertebral fractures (hazard ratio [HR] 0.38; 95% credibility interval [CrI], 0.28-0.49). Zoledronate (HR 0.71; 95% CrI, 0.61-0.81) and risedronate (HR 0.70; 95% CrI, 0.53-0.84) were found to be the most effective treatments in preventing nonvertebral fractures. All treatments were associated with increases in femoral neck BMD versus placebo with zoledronate being the most effective treatment mean difference (MD 4.02; 95% CrI, 3.2-4.84). There was a paucity of data regarding hip and wrist fractures. Depending on its cost-effectiveness, zoledronate could be considered a first-line option for people at increased risk of fragility fractures. © 2022 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Dataset Information

Threshold Analysis as an Alternative to GRADE for Assessing Confidence in Guideline Recommendations Based on Network Meta-analyses.

Publications

Threshold Analysis as an Alternative to GRADE for Assessing Confidence in Guideline Recommendations Based on Network Meta-analyses.

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