Screening (and Diagnosis) of 15 Respiratory Viruses Using NAAT

Transcription

1 Screening (and Diagnosis) of 15 Respiratory Viruses Using NAAT April 2013 DISCLAIMER: This document was originally drafted in French by the Institut national d'excellence en santé et en services sociaux (INESSS), and that version can be consulted at It was translated into English by the Canadian Agency for Drugs and Technologies in Health (CADTH) with INESSS s permission. INESSS assumes no responsibility with regard to the quality or accuracy of the translation. While CADTH has taken care in the translation of the document to ensure it accurately represents the content of the original document, CADTH does not make any guarantee to that effect. CADTH is not responsible for any errors or omissions or injury, loss, or damage arising from or relating to the use (or misuse) of any information, statements, or conclusions contained in or implied by the information in this document, the original document, or in any of the source documentation.

2 1 GENERAL INFORMATION 1.1 Submitting company, Institution or organization: CHUQ-CHUL 1.2 Application submitted: September 9, Notice issued: April 2, 2013 Note: This notice is based on the scientific and commercial information [submitted by the requestor(s) and on a complementary review of the literature] according to the data available at the time that this test was assessed by INESSS. 2 TECHNOLOGY, COMPANY, AND LICENCE(S) 2.1 Name of the Technology Seeplex RV15 OneStep ACE Detection from Seegene Inc. (called herein the OneStep PCR test ). 2.2 Brief Description of Technology A commercial kit for producing a polymerase chain reaction (PCR) that amplifies the nucleic acids of 15 viruses. 11 This qualitative test is performed using samples taken either by nasopharyngeal aspiration or swabbing or by bronchoalveolar lavage. It comprises three main steps: isolating the nucleic acids from the viruses, amplifying this material with primers based on DPO technology, 12 and detecting the various amplification products with either a computerized system or with agarose gel electrophoresis. This kit improves PCR reproducibility and ease of use because the reverse transcription (generating DNA from RNA) and DNA amplification steps take place in the same tube (hence the name OneStep ) [Seegene 2010]. 2.3 Company or Developer: Seegene Inc., Seoul, South Korea 2.4 Licence(s): Not applicable 2.5 Patent, if Applicable: Not applicable 11 The Seeplex RV15 OneStep ACE Detection kit can be used to detect the following respiratory viruses: influenza virus A (including subtypes H5N1 and H1N1), influenza virus B, human respiratory syncytial virus A, human respiratory syncytial virus B, human adenovirus (almost all type B, C and E and some type A and D), human metapneumovirus, human coronavirus 229E/NL63, human coronavirus OC43, human parainfluenza virus 1, human parainfluenza virus 2, human parainfluenza virus 3, human parainfluenza virus 4, human rhinovirus A/B/C, human enterovirus, and human bocavirus. 12 DPO TM: Dual Priming Oligonucleotide. This technology from Seegene Inc. maximizes PCR specificity and sensitivity. 1

3 2.6 Approval Status (Health Canada, FDA) - Canada (Health Canada): Licence No , first issued 10/08/2010; the kit can be used for in vitro diagnosis. - European Union: The kit has the CE mark under directive 98/79/EC; it can be used for in vitro diagnosis. - United States (FDA): this kit is not available in the United States. - Other countries: this kit should be used for research only. 2.7 Weighted Value: 265.0, according to the request. 3 CLINICAL INDICATIONS, PRACTICE SETTINGS, AND TESTING PROCEDURES 3.1 Targeted Patients This application targets immunosuppressed patients with pneumonia and no identified germ, and patients in intensive-care units with pneumonia and no identified germ. 3.2 Targeted Diseases Acute viral infections of the respiratory tract are the main cause of hospitalization of children in industrialized countries. The viruses most often responsible for these infections in children and adults are influenza viruses A, B and C; parainfluenza viruses 1, 2, and 3; respiratory syncytial virus; adenoviruses; and rhinoviruses [Mahony et al. 2011]. Examples of the infections that these viruses can cause include flu, pneumonia, laryngotracheobronchitis (croup), pharyngitis, rhinitis, and bronchiolitis. 3.3 Number of Patients to Be Tested According to the application, 140 tests per year for RUIS Université Laval [Laval University Integrated Health Network], which can be increased if CHUQ [Quebec City University Hospital Centre] is designated to test for other regions. 3.4 Medical Specialists Involved (and Other Professionals, If Any) According to the requestor, the OneStep PCR can be prescribed by pediatricians, hematologists, geriatricians, respirologists, etc., but they must have the approval of the microbiologist/infectious disease specialist on duty. 3.5 Testing Procedure The OneStep PCR is used to analyze samples taken either by nasopharyngeal aspiration or swabbing or by bronchoalveolar lavage from symptomatic patients in hospital settings. ESwab swabs (from the company Copan in Italy) can be used for this purpose. The samples must be transported as quickly as possible, and at low temperature (2 C to 8 C). They can be stored at 4 C for up to 72 hours. If they must be stored longer, the temperature should set to 70 C. Repeated thawing and freezing of the samples degrades the nucleic acids and can therefore reduce the sensitivity of the test [Seegene 2010]. According to the application, this test would be performed in winter and spring, two to five times per week, on demand. 2

4 4 TECHNOLOGY BACKGROUND 4.1 Nature of the Diagnostic Technology Unique. For information: the submitted test seeks to replace the 25-virus PCR INFINITI RVP Plus test from AutoGenomics, which is used even though it is not listed in the Index (information provided by the requestor). 4.2 Brief Description of the Current Technological Context According to the requestor, viral culture in cells, in combination with the detection of antigens by immunofluorescence, is used first. The OneStep PCR can be used with the approval of the microbiologist/infectious disease specialist on duty if: 1) tests for influenza virus A and B are negative, or 2) test for respiratory syncytial virus is negative in a young child, or 3) no germ was identified in an immunosuppressed patient or one with severe pneumonia. Another multiplex NAAT for 12 respiratory viruses is already listed in the Index (code 41339, weighted value 61.0). 4.3 Brief Description of the Advantages Cited for the New Technology The detection of viral nucleic acids was shown to be the most sensitive diagnostic approach [Mahony et al. 2011]. 13 Also, in a single test, a multiplex PCR can detect the important viral pathogens and determine, among several viruses with similar clinical manifestations, which one or ones a patient is infected with. Drugs can then be prescribed in a targeted way (for example, neuraminidase inhibitors to treat influenza viruses). As stated in the application, the OneStep PCR is faster than viral culturing and can detect some of the most recently discovered respiratory viruses, such as influenza A H1N1 (2009), bocavirus (2005), and metapneumovirus (2001) [Seegene 2010]. Unlike some other PCR tests, it can discriminate between enteroviruses and rhinoviruses. Lastly, according to the requestor, the OneStep PCR requires fewer steps by laboratory workers than the Luminex xtag RVP Fast PCR and so may present a lower risk of contamination and false-positive results. 4.4 Cost of the Technology and the Options According to the information submitted by the requestor, the total cost is $CAN 265 (including $230 per patient-result for the reagents and materials, plus 5% taxes on the reagents). According to information submitted by the requestor (on the basis of an unpublished study conducted in the requestor s laboratory), the cost per test is $68 plus labour and other incidentals. No published economic assessment was found. 13 Thus, the idea that viral culture and immunofluorescence represent the gold standard is now being questioned, and a new paradigm, with molecular testing as the gold standard, is emerging [Mahony et al. 2011]. 3

5 5 EVIDENCE 5.1 Clinical Relevance (Utility and Validity) and Analytical Validity Other Tests Replaced No information is available Diagnostic or Prognostic Value No information is available Therapeutic Value No information is available. 5.2 Clinical Validity Component Presence Absence Not Applicable Sensitivity Specificity Positive predictive value (PPV) Negative predictive value (NPV) Likelihood ratio (LR) ROC curve Accuracy According to the requestor, the sensitivity 14 of the OneStep PCR is greater than or equal to that of the INFINITI RVP Plus PCR (AutoGenomics) and the xtag RVP Fast PCR (Luminex), except for in relation to bocaviruses, for which this last test is the most sensitive. The OneStep PCR is the most sensitive for coronavirus 229E/NL63, influenza A, parainfluenza 3 and 4, and respiratory syncytial virus A/B. 5.3 Analytical (Technical) Validity Component Presence Absence Not Applicable Repeatability Reproducibility Analytical sensitivity Analytical specificity Matrix effect Concordance Correlation Other, according to type of test 14 The specificity described refers to the number of specimens detected per target. 4

6 5.4 Recommendations for Listing in Other Jurisdictions No information is available. Bottom line: the utility of the Seegene Seeplex RV15 OneStep ACE Detection biomedical test is uncertain because of the absence of data on this subject. First of all, the three articles submitted with the application were not specifically on this PCR. Second, the literature search we conducted did not identify any studies on this PCR. This test should be re-assessed if data are published specifically on the Seegene Seeplex RV15 OneStep ACE Detection kit. 6 ANTICIPATED OUTCOMES OF INTRODUCING THIS TEST 6.1 Impact on Human and Material Resources According to the aforementioned study conducted by the requestor, the OneStep PCR is the fastest in regard to handling time (one hour). The time required for the first result to be obtained five hours is the same for this PCR as for the xtag RVP Fast PCR. With the OneStep PCR, the software is easy to use, and the results are easy to interpret. According to the requestor, the OneStep PCR is simple and can be used by staff with minimal qualifications. 6.2 Economic Impact of Including This Test in the Health and Social Services System The cost of molecular biology testing is offset by its more optimal use of labour compared with conventional methods (such as cell culture) and by the savings generated when a sensitive, specific result allows additional testing and hospitalization to be avoided [Gharabaghi et al. 2011]. In addition, testing for several viruses at once can provide greater savings, in particular on technical labour [Mahony et al. 2011]. 6.3 Main Organizational, Ethical, Social, Legal, and Political Issues According to the requestor, the small number of steps in the OneStep PCR protocol helps to lower the risk of contamination, leading to fewer false-positive results than the xtag RVP Fast test. 5

7 7 INESSS NOTICE IN BRIEF Screening (and diagnosis) of 15 Respiratory Viruses Using NAAT Status of the diagnostic technology X Established Innovative Experimental (for research only) Replacement for technology:, which is becoming obsolete. INESSS recommendation X Test already in the Index: Code Use only one code for multiplex testing of respiratory viruses by NAAT. Include in the Index Do not include in the Index Reassess INESSS decision regarding any required work Draw connection with listing of drugs, if it is a companion test. X Produce an optimal use manual about indications, commercial kits and in-house tests, the number of viruses, the professional who prescribes the test, etc. Produce indicators, if close monitoring is required. X Change the description for Code to read Detection of a panel of respiratory viruses by multiplex NAAT (minimum number of viruses to be determined by the Advisory Committee) and recalculate the weighted value, which should be unique and not vary according to which commercial kit is used. 6

8 REFERENCES Gharabaghi F, Hawan A, Drews SJ, Richardson SE. Evaluation of multiple commercial molecular and conventional diagnostic assays for the detection of respiratory viruses in children. Clinical Microbiology and Infection 2011;17(12): Mahony JB, Petrich A, Smieja M. Molecular diagnosis of respiratory virus infections. Critical Reviews in Clinical Laboratory Sciences 2011;48(5-6): Seegene. Seeplex RV15 OneStep ACE Detection V