POCT/ Point-of-Care Tests: D-Dimer and Troponin - Update 2024

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Research area: High tech medicine

Project leaders: Claudia Wild

Project team: Judit Erdös, Claudia Wild

                          Mirjana Huic (first author, HTA/EBM Center, Croatia)
Duration: 02/2024 – 07/2024
Language: English (with German Summary)
Publication: HTA Project Report No. 124, 1. Update 2024: https://eprints.aihta.at/1524/

 

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. 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.

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) and troponin, which can be used in patients with suspected coronary heart disease or myocardial infarction.

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 Tn and DVT/PE and thus the potential benefits of using these POCTs.

Project objectives: The policy question is whether emergency care referrals, hospital admissons 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. This project aims at answering the following

Research questions:

  • RQ 1: What are the clinical benefits of D-dimer POCT in the management of symptomatic patients (adults)?
  • RQ 2: What are the clinical benefits of Tn-POCT in the management of symptomatic patients (adults)?

Methods: To answer RQ 1+2, two separate systematic reviews on the patient-relevant benefits of POC diagnostics will be carried out.

Inclusion criteria (PICO) for (high-sensitivity) cardiac Tn-POCT

 Population

Adult patients >=18 years with signs and or symptoms such as chest pain or breathlessness that are potentially indicative of acute coronary syndrome (ACS) and acute myocardial infarction,

presenting in primary care (general practice, internal medicine or pulmonology in private practice) and has not been ruled out.

Specific high-risk groups of patients will be excluded. Emergency care will be excluded.

MeSH-terms: acute coronary syndrome, myocardial infarction, unstable angina pectoris, cardiac troponin.

ICD-10: I20-I24

 Intervention

Point of care tests (POCT) high-sensitivity cardiac troponin POC products that are available on the market such as:

  • PATHFAST (LSI Medicine Corporation, Tokyo, Japan);
  • TriageTrue (QuidelOrtho, San Diego, United States);
  • Atellica VTLi (Siemens Healthineers, Erlangen, Germany)

with the intention to rule-out the acute disease.

 Comparison

All comparators will be included.

For the impact of POCT on patient management, usual care (incl. central laboratory methods) will be used. In the diagnostic performance testing, reference standard tests are likely to include angiography and laboratory testing (as opposed to the near-patient testing devices).

 Outcomes

Effectiveness/clinical utility in patient-management:

  • Hospital referral rate;
  • Hospital admissions for chest pain;
  • Morbidity and mortality, including fatal and nonfatal acute myocardial infarction;
  • Length of stay;
  • Health related QoL;
  • Patient satisfaction;
  • Staff satisfaction (e.g., user-friendliness)

Safety: AEs, SAEs

Diagnostic accuracy :

  • sensitivity, and negative predictive value for Acute Coronary Syndrome (ACS) and major adverse cardiac events (MACE)

*MACE is defined as a combined endpoint of ACS, percutaneous coronary intervention, coronary artery bypass grafting, coronary angiography revealing procedurally correctable stenosis managed conservatively and all-cause mortality

 Study design

An iterative step-wise approach will be conducted:

  • At the first stage, systematic reviews and meta-analyses as well as HTA-reports and evidence-based guidelines (Level of Evidence/LoE and Grade of Recommendation/GoR) will be searched.
  • In a second stage, primary studies (controlled trials ? 10 participants) may be included in order to update the results of available systematic reviews or expand the scope of available systematic reviews.
  • Inclusion period: June 1, 2019 – March 1, 2024

 

Inclusion criteria (PICO) for D-dimer POCT

Population

Adult patients ?18 years with low pre-test probability of deep venous thrombosis (DVT) or pulmonary embolism (PE) with symptoms such as leg swelling, chest pain or trouble breathing that are potentially indicative of DVT or PE,

presenting in primary care (general practice, internal medicine or pulmonology in private practice) and has not been ruled out.

Specific high-risk groups of patients (e.g. those with a previous VTE or those with cancer) will be excluded. Emergency care will be excluded.

MeSH-terms: Pulmonary Embolism, venous thrombosis, thromboembolism, “fibrin fibrinogen degradation products”

Pulmonary embolism ICD 10: 0882, I269, I260; Deep vein thrombosis ICD 10: I801, I828, I829, O223, I822, I820, I802, I81, O082, I823, O871; Thrombophlebitis ICD 10: I809, I821, I808, I803.

Intervention

Quantitative D-dimer POCTs included the following products:

  • Exdia TRF Plus (Precision Biosensor Inc.)
  • AFIAS-1® (Boditech Med Inc)
  • Standard F200® (SD Biosensor)
  • LumiraDx™ (LumiraDx Ltd.)
  • Hipro AFS/1® (Hipro Biotechnology)
  • and additional two: Nano-checker 710 and iChroma-II (from 2020 study)

with the intention to rule-out the presence of venous thromboembolism often in conjunction with use of a clinical prediction rule (e.g., such as Wells or Geneva).

Comparison

All comparators will be included.

For the impact of POCT on patient management, usual care (incl. central laboratory methods) will be used.

In the diagnostic performance testing, reference standard tests are likely to include computerized tomography pulmonary angiography (CTPA), ultrasound, venography/ angiography and laboratory testing (as opposed to the near-patient testing devices).

Outcomes

Effectiveness/clinical utility in patient-management:

  • Hospital referral rate;
  • Hospital admissions for chest pain;
  • Morbidity and mortality (all-cause and VTE related mortality);
  • Length of stay;
  • Health related QoL;
  • Patient satisfaction;
  • Staff satisfaction (e.g., user-friendliness)

Safety: AEs, SAEs

Diagnostic accuracy

  • sensitivity, and negative predictive value

Study design

An iterative step-wise approach will be conducted:

  • At the first stage, systematic reviews, and meta-analyses as well as HTA-reports and evidence-based guidelines (Level of Evidence/LoE and Grade of Recommendation/GoR) will be searched.
  • In a second stage, primary studies (controlled trials ? 10 participants) may be included in order to update the results of available systematic reviews or expand the scope of available systematic reviews.
  • Inclusion period: June 1, 2019 – March 1, 2024

Systematic literature search in 4 databases and 1 clinical trial registry:

  • INAHTA Database
  • Cochrane Library
  • Medline via Ovid
  • Embase
  • ClinicalTrials.gov.

Search limited to studies published in German or English since June 2019 to March 2024.

Literature Selection: Abstract and full text literature selection is conducted by 2 reviewers (MH, CW). First reviewer screens all abstracts, the second reviewer only the excluded studies The literature selection process will be presented via a PRISMA diagram.

  • If no SRs can be identified, or available SRs require updating, primary studies will be searched in the databases listed above.

Data extraction: The following data will be extracted: study details (author, country, setting, number of patients, length of follow-up), patient characteristics, intervention characteristics, outcomes (as defined in the PICO table above). Data will be extracted by the first reviewer (MH) and checked by the second reviewer (JE).

Data synthesis: The outcomes will be reported as qualitative evidence synthesis.

Risk of bias and strength of evidence: Risk of bias assessment will be conducted by two researchers (MH, JE) using the according Risk of Bias Tool (https://www.latitudes-network.org/)

Time schedule/ milestones:

 Period

Task

February to March 2024

Systematic literature search, abstract screening, full text screening and study selection, PRISMA diagram

April to May 2024

Critical appraisal (risk of bias assessment), data extraction

June 2024

1st Draft for internal review, Revision and external review

July 2024

Completion of final report
   

References:

Goetz, G. and Schmidt, L. and Erdos, J. and Ciutan, M. and Florescu, S. and Sasu, C. and Scintee, S. G. (2019): POCT/ Point of Care Tests: D-Dimer and Troponin. HTA-Projektbericht 124. https://eprints.aihta.at/1224/