What is the diagnostic test performance of high-sensitivity (hs) cardiac troponin T (cTnT) and high-sensitivity cardiac troponin I (cTnI) assays compared with each other as well as with conventional cTnT and sensitive cTnI assays in patients with suspected acute coronary syndrom (ACS) symptoms in the emergency department (ED)?
What is the clinical effectiveness of hs-cTnT and hs-cTnI assays compared with each other as well as with conventional cTnT and sensitive cTnI assays in patients with suspected ACS symptoms in the emergency department (ED)?
What is the cost-effectiveness of hs-cTnT and hs-cTnI assays compared with each other as well as with conventional cTnT and and sensitive cTnI assays in patients with suspected ACS symptoms in the emergency department (ED)?
What is the budget impact associated with the adoption of hs-cTnT and hs-cTnI assays compared with each other as well as with conventional cTnT and sensitive cTnI assays in patients with suspected ACS symptoms in the emergency department (ED)?
An information specialist using a peer-reviewed search strategy, will perform the literature search. Searching the following bibliographic databases will identify published literature: MEDLINE (1946-present) with in-process records & daily updates via Ovid; EMBASE (1980-2012 current week); The Cochrane Library (2012, current issue) and HEED via Wiley; and PubMed (for non-Medline records). The search strategy will comprise both controlled vocabulary, such as the National Library of Medicine’s MeSH (Medical Subject Headings), and keywords. The main search concepts will be high-sensitivity cardiac troponin assay and medical emergency circumstances and acute myocardial infarction, cardiac ischemia, chest pain, or acute coronary syndrome.
Methodological filters will be applied to limit retrieval to health technology assessments, systematic reviews, meta-analyses, randomized controlled trials, non-randomized controlled clinical trials, comparative studies, and economic evaluations. Where possible, retrieval will be limited to the human population. The search will also be limited to English documents (with the exception of French Canadian technology assessments which are not translated). Regular alerts will be established to update the search until the end of the project.
We will identify grey literature (literature that is not commercially published) by searching relevant sections of the Grey Matters checklist (http://cadth.ca/resources/grey-matters). Google and other Internet search engines will be used to search for additional web-based materials. These searches will be supplemented by reviewing the bibliographies of key papers and through contacts with appropriate experts and industry.
Types of study to be included
Randomized controlled trials (RCTs) and non-randomized studies will be included. Qualitative or non-comparative studies will be excluded. Preliminary results in abstract form will also be excluded
Condition or domain being studied
Diagnostic cardiac tests in the emergency department.
Patients presenting to an emergency department (ED) with chest pain or other symptoms suggestive of ACS.
High-sensitivity cardiac troponin T (hs-cTnT) assay.
High-sensitivity troponin I (hs-cTnI) assay.
Conventional cardiac troponin T (cTnT) assay.
Sensitive cardiac troponin I (cTnI) assay.
Diagnostic test performance (sensitivity, specificity, negative predictive value, positive predictive value, area under the receiver operator curve).
Cost: Incremental cose-effectiveness ratio, cost per quality adjusted life year.
Quality of life, adverse events, ED time until diagnosis or detection of abnormal concentration.
Data extraction, (selection and coding)
Two reviewers will independently screen the titles and abstracts for relevance using a predefined checklist. Any discrepancies between reviewers will be discussed until consensus is reached. Full texts of any relevant titles/abstracts will be retrieved, and will be assessed by two independent reviewers for inclusion, using a checklist , incorporating explicit pre-determined criteria. These will be checked for agreement, and any disagreement between reviewers will be discussed until consensus is reached. The study selection process will be presented in a Preferred Reporting Items for Systematic Reviews and Meta- Analyses (PRISMA) flowchart.
One reviewer will perform data extraction for each article, using a pre-drafted data extraction form . A second reviewer will check the abstracted data for accuracy. Two reviewers will pilot data extraction forms a priori. A calibration exercise using a small number of studies will be undertaken to ensure consistency between the reviewers.
Risk of bias (quality) assessment
Two reviewers will independently evaluate the quality of the included diagnostic studies using the Revised Tool for the Quality Assessment of Diagnostic Accuracy Studies (QUADAS2). QUADAS2 is a tool that evaluates the risk of bias in selection of patients, index test, reference standard, and flow and timing of the study. The tool also includes concerns about the applicability of tests and signalling questions to help identify potential biases.
The methodological quality of the RCTs and comparative non-randomized studies will be assessed using a modified version of the Downs and Black instrument. The assessment instrument, which has been modified to include the source of funding for studies, has a total score ranging from 0 to 28, with higher scores indicating a higher-quality study.
The methodological quality of cost-effectiveness studies will be assessed using the guidelines for appraisal of economic studies by Drummond et al. Any disagreements will be resolved through discussion until consensus is reached.
The results of quality assessments will be used to summarize strengths and limitations of the included studies.
Strategy for data synthesis
The population, interventions and outcome measures will define comparability of the studies. When two or more comparable studies with quantitative outcomes are identified, pooled estimates of the outcome measures will be performed through meta-analysis. When the studies are not comparable in terms of population, interventions, or outcome measures, or if there is variation in the reporting of clinical outcomes, a formal meta-analysis will not be performed. Instead, the individual studies will be described and synthesized using a narrative approach.
Direct and indirect comparisons will be used to analyze the data depending on the availability of the evidence obtained in the data abstraction process. The outcomes to be estimated will be reported as the estimate and the 95% confidence interval (CI) (direct comparison) or 95% credibility interval (CrI) of the posterior distribution (indirect comparison). Based on the scoping of the literature, direct evidence on the relative performance between the two high sensitivity assays is absent and indirect methods to derive the comparative effectiveness are required.
Analysis of subgroups or subsets
Contact details for further information
600-865 Carling Avenue
Organisational affiliation of the review
Canadian Agency for Drugs and Technologies in Health
Anticipated or actual start date
14 May 2012
Anticipated completion date
29 November 2012
This review was led by the Canadian Agency for Drugs and Technologies in Health (CADTH), an independent, not-for-profit agency funded by Canadian federal, provincial, and territorial governments.
Formal screening of search results against eligibility criteria
Risk of bias (quality) assessment
PROSPERO This information has been provided by the named contact for this review. CRD has accepted this information in good faith and registered the review in PROSPERO. CRD bears no responsibility or liability for the content of this registration record, any associated files or external websites.