Original Title: MSAC application no. 1721

Authors' objectives: To assess the safety, effectiveness, and cost-effectiveness of small next generation sequencing (NGS) panels compared to sequential single gene testing for patients with non-squamous non-small cell lung cancer (NSCLC), to provide the evidence-base for the Medical Services Advisory Committee (MSAC) to decide its advice regarding funding on the Medicare Benefits Schedule.

Authors' results and conclusions: The evidence supported the clinical claim of superior effectiveness due to more patients being identified with variants by small NGS panels than sequential single gene testing (moderate level of confidence). The majority of these additional patients would be considered eligible for Pharmaceutical Benefits Schedule-listed targeted treatments with the proposed changes to restrictions. The additional patients with actionable variants identified are then able to be managed with targeted treatment, which may result in superior health outcomes (low confidence). The evidence also supported the clinical claim of superior safety, due to the likelihood that the more efficient use of tumour tissue by NGS than sequential single gene testing (moderate confidence) would result in fewer rebiopsies being performed (low confidence) and avoiding biopsies would reduce the risk of adverse events associated with biopsies (moderate confidence).

Authors' recommendations: The evidence supported the clinical claim of superior effectiveness due to more patients being identified with variants by small NGS panels than sequential single gene testing (moderate level of confidence). The majority of these additional patients would be considered eligible for Pharmaceutical Benefits Schedule-listed targeted treatments with the proposed changes to restrictions. The additional patients with actionable variants identified are then able to be managed with targeted treatment, which may result in superior health outcomes (low confidence). The evidence also supported the clinical claim of superior safety, due to the likelihood that the more efficient use of tumour tissue by NGS than sequential single gene testing (moderate confidence) would result in fewer rebiopsies being performed (low confidence) and avoiding biopsies would reduce the risk of adverse events associated with biopsies (moderate confidence).

Authors' methods: Scoping searches indicated that there was insufficient direct from test to health outcomes evidence (comparing health outcomes in those tested by NGS against to those tested sequentially by single-gene tests) on which to base the assessment. Therefore, a linked evidence assessment was also performed. PICO criteria were developed a priori for both the direct from test to health outcomes evidence, and the ‘test performance’ and ‘change in management’ steps of a linked evidence assessment. The protocol was registered on PROSPERO (CRD42022334620). PubMed, Embase, Cochrane, Australian Clinical Trials Registry, ClinicalTrials.gov, International clinical trials registry platform, INAHTA database and PROSPERO were searched to identify potentially relevant primary and secondary research. Search terms were developed, and tested using the SearchRefinery tool (Scells & Zuccon 2018), using relevant articles from DCAR 1495 and application 1721 as the seed citations. Relevant citations were downloaded into Endnote, where one assessor reviewed every citation based on title/abstract. A second reviewer assessed the most relevant 50% citations as determined by an algorithm in Rayyan. Full text articles determined potentially relevant by either reviewer were retrieved for assessment by one reviewer. Those which met the PICO criteria had their references assessed, and citations assessed, using Citation Chaser (Haddaway, Grainger & Gray 2021). A PRISMA flowchart was developed to summarise the number of citations identified at each step. Each included study had its risk of bias assessed, based on the outcomes it provided and the study design. Concordance studies were evaluated using the QUADAS 2 checklist (substituting assessment of the reference standard with assessment of the comparator). Studies on the success rate of testing or turnaround time, or studies on the effectiveness of targeted treatment in non-randomised controlled studies were assessed using a checklist for cohort studies developed by SIGN. The certainty of evidence was judged using GRADE for the key outcomes which fed into the assessment framework.

Project Status: Completed

URL for project: https://www.msac.gov.au/applications/1721

URL for protocol: based on PICO confirmation 1634 http://www.msac.gov.au/internet/msac/publishing.nsf/Content/1634-public

Year Published: 2021

URL for published report: https://www.msac.gov.au/sites/default/files/2024-11/1721_final_dcar-_updated_sept_2022_redacted.pdf

Requestor: The Australian Department of Health and Aged Care/ Medical Services Advisory Committee (MSAC)

English language abstract: An English language summary is available

Publication Type: Full HTA

Country: Australia

Organisation Name: Adelaide Health Technology Assessment

Contact Address: School of Public Health, Mail Drop 545, University of Adelaide, Adelaide SA 5005, AUSTRALIA, Tel: +61 8 8313 4617

Contact Name: ahta@adelaide.edu.au

Contact Email: ahta@adelaide.edu.au

Copyright: <p>Adelaide Health Technology Assessment (AHTA) on behalf of NICS</p>