POCT/ Point of Care Tests: D-Dimer and Troponin

Duration: April 2019 - October 2019
Suggested by: Representatives of federal states
Language: English, EUnetHTA REA

Publication: LBI-HTA Project report No. 124: https://eprints.aihta.at/1224/
 

Background:
Point-of-care tests (POCTs) are diagnostic tests that are performed near patients rather than in central laboratories. POCTs provide rapid feedback of test results potentially enabling faster decisions about patient management. Both sampling and data analysis are performed at the same site, reducing transport and processing delays [1, 2]. In recent decades, there has been a steady increase in both the availability and use of POCTs. The trend was associated with both hopes (regarding benefits over laboratory testing) and concerns (regarding the overall benefit, potential over-diagnosis, and reliability) of such tests [1, 3].

In recent years, two biomarkers have, among others, been used as POC diagnostics: determination of D-dimers in patients with symptoms of deep vein thrombosis (DVT) or pulmonary embolism (PE) [4] and troponin, which can be used in patients with suspected coronary heart disease or myocardial infarction [5].

However, POCTs may only be useful if they bring about a positive change in patient management. For reasons of cost-effectiveness, for example, it would not make sense to use them only as "add-ons" without a real change in the diagnostic or therapeutic pathway. Therefore, it is essential to identify the diagnostic context for acute coronary syndrome and DVT/PE and thus the potential benefits of using these POCTs. The context is influenced by various factors such as referral behaviour, reimbursement aspects, organizational aspects, etc.

Project objectives:
The policy question is whether hospital stays, admissions or further tests can be avoided by using the two POC diagnostics (D-dimer and troponin). While many studies on POCTs deal with the analytical performance (diagnostic accuracy) of these tests, studies on the impact on clinical (triage) decisions and on patient-relevant endpoints are much rarer [6, 7]. This project has the following objectives:

1. Summarise knowledge from evidence-based (S3) guidelines on how the two POC diagnostics (D-dimer and troponin) are to be used in clinical practice. In order to identify context factors, country-specific recommendations for Austria (S1 and S2 level) on general diagnostics of DVT/PE and acute coronary syndromes will also be collected.
2. Evidence primarily from systematic reviews and, where necessary, individual clinical studies will be systematically synthesized in order to evaluate whether the two POC diagnostics (D-dimer and troponin) have sufficient diagnostic accuracy and influence patient management.
3. A further aim is to investigate the question of how D-dimer and Tn-POCT are used in the Austrian health care system in order to assess implementation and realisation options. Particular attention will be given to specific settings (emergency medicine in the hospital setting, specialist community medicine and general practice).

Accordingly, the following research questions will be answered:

1. How do evidence-based guidelines recommend D-dimer-POCT and Tn-POCT be used (position in the diagnostic path, threshold values in different patient populations, settings)?
2. What are the clinical benefits of D-dimer POCT in the management of symptomatic patients (adults)?
3. What are the clinical benefits of Tn-POCT in the management of symptomatic patients (adults)?
4. Can a theoretical benefit of POCT (D-dimer and Tn) be realized in the Austrian context?

Methods:
A guideline synopsis (Part I) will be prepared to answer RQ 1:

• Systematic search for relevant evidence-based guidelines in guideline databases ("Guideline International Network (GIN), Trip Database) as well as hand-searching selected websites of international institutions producing guidelines (e.g. National Institute for Health and Care Excellence)
• Selection of guidelines by two independent researchers
• Quality assessment using AGREE (Appraisal of Guidelines for Research & Evaluation) performed by one researcher and checked by another
• Extraction of recommendations for the application of POCTs according to the status of the test in diagnostic pathways, threshold values and significance of test results in different patient populations (emergency, general medicine)

To answer RQ 2+3, two separate systematic reviews (Part II) on the patient-relevant benefits of POC diagnostics will be carried out.

• Two separate systematic literature searches in the following databases will be conducted to identify existing systematic reviews on diagnostic accuracy and impact on patient management:
  • Cochrane (CENTRAL)
  • Centre for Research and Dissemination (CRD)
  • Embase
  • Ovid MEDLINE
• If no SRs can be identified, or available SRs require updating, primary studies will be searched in the databases listed above.
• Study selection, data extraction, assessment of the risk of bias (QUADAS-2 or AMSTAR) as well as evidence synthesis will be conducted by two groups (one for each POCT) consisting of two independent researchers:
  • Screening and selection of literature in EndNote
  • Assessment of the Risk of Bias (RoB) using adequate tools/checklists
  • Data will be extracted by one researcher and checked by another
  • Assessment of the strength of the evidence using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) method
  • Qualitative evidence synthesis

To support RQ 4 (Austrian context), interviews will be conducted with representatives of emergency medicine, general medicine and/or specialist medicine (cardiology,...). The Main Association of Austrian Social Security Institutions will provide reimbursement data on the use of tests in primary care and by community-based specialists.

Inclusion criteria (PICO) for Tn-POCT

Inclusion criteria (PICO) for D-dimer-POCT

Timeplan / Milestones:

References:

1.         Larsson, A., R. Greig-Pylypczuk, and A. Huisman, The state of point-of-care testing: a European perspective. Ups J Med Sci, 2015. 120(1): p. 1-10.

2.         Zehnder, J. Clinical use of coagulation tests. 2019  20.04.2019]; Available from: https://www.uptodate.com/contents/clinical-use-of-coagulation-tests?source=history_widget.

3.         St John, A. and C.P. Price, Existing and Emerging Technologies for Point-of-Care Testing. The Clinical biochemist. Reviews, 2014. 35(3): p. 155-167.

4.         Lee-Lewandrowski, E. and K. Lewandrowski, Perspectives on cost and outcomes for point-of-care testing. Clin Lab Med, 2009. 29(3): p. 479-89.

5.         Tomonaga, Y., et al., Diagnostic accuracy of point-of-care testing for acute coronary syndromes, heart failure and thromboembolic events in primary care: a cluster-randomised controlled trial. BMC family practice, 2011. 12: p. 12-12.

6.         Pecoraro, V., L. Germagnoli, and G. Banfi, Point-of-care testing: where is the evidence? A systematic survey. Clin Chem Lab Med, 2014. Mar;52(3): p. 313-24.

7.         Pecoraro, V., et al., A systematic evaluation of immunoassay point-of-care testing to define impact on patients' outcomes. Ann Clin Biochem, 2017 Jul;5(4): p. 420-431.

8.         Collinson, P., et al., Randomised Assessment of Treatment using Panel Assay of Cardiac markers--Contemporary Biomarker Evaluation (RATPAC CBE). Health Technol Assess, 2013. 17(15): p. 1-122.

9.         Geersing, G., et al., Excluding venous thromboembolism using point of care D-dimer tests in outpatients: a diagnostic meta-analysis. BMJ, 2009 Aug 14(339): p. b2990.

10.       Canadian Agency for Drugs and Technologies in Health (CADTH), Point-Of-Care D-Dimer Testing: A Review of Diagnostic Accuracy, Clinical Utility, and Safety, in Rapid Response: Summary with Critical Appraisal, CADTH, Editor 2017.