Appraising the Costs of Genomic Testing for Histology-Independent Technologies: An Illustrative Example for NTRK Fusions

Beresford, Lucy; Murphy, Peter J.; Dias, Sofia; Claxton, Lindsay; Walton, Matthew; Metcalf, Robert; Schlecht, Hélene; Ottensmeier, Christian H.; Pereira, Marta; Hodgson, Robert

doi:10.1016/j.jval.2021.11.1359

Cited by 6 publications

(5 citation statements)

References 8 publications

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“…Pricing for laboratory reagents and molecular tests may vary by an order of magnitude between different countries; nevertheless, some rough comparison is possible. The cost of RNA-based NGS per sample is generally above 300–400 EURO or USD [ 23 , 44 ]. IHC is often regarded as a relatively cheap method, although its budget usually exceeds 150 EURO/USD [ 44 ].…”

Section: Discussionmentioning

confidence: 99%

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Cost-Efficient Detection of NTRK1/2/3 Gene Fusions: Single-Center Analysis of 8075 Tumor Samples

Romanko,

Mulkidjan,

Tiurin

et al. 2023

IJMS

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The majority of NTRK1, NTRK2, and NTRK3 rearrangements result in increased expression of the kinase portion of the involved gene due to its fusion to an actively transcribed gene partner. Consequently, the analysis of 5′/3′-end expression imbalances is potentially capable of detecting the entire spectrum of NTRK gene fusions. Archival tumor specimens obtained from 8075 patients were subjected to manual dissection of tumor cells, DNA/RNA isolation, and cDNA synthesis. The 5′/3′-end expression imbalances in NTRK genes were analyzed by real-time PCR. Further identification of gene rearrangements was performed by variant-specific PCR for 44 common NTRK fusions, and, whenever necessary, by RNA-based next-generation sequencing (NGS). cDNA of sufficient quality was obtained in 7424/8075 (91.9%) tumors. NTRK rearrangements were detected in 7/6436 (0.1%) lung carcinomas, 11/137 (8.0%) pediatric tumors, and 13/851 (1.5%) adult non-lung malignancies. The highest incidence of NTRK translocations was observed in pediatric sarcomas (7/39, 17.9%). Increased frequency of NTRK fusions was seen in microsatellite-unstable colorectal tumors (6/48, 12.5%), salivary gland carcinomas (5/93, 5.4%), and sarcomas (7/143, 4.9%). None of the 1293 lung carcinomas with driver alterations in EGFR/ALK/ROS1/RET/MET oncogenes had NTRK 5′/3′-end expression imbalances. Variant-specific PCR was performed for 744 tumors with a normal 5′/3′-end expression ratio: there were no rearrangements in 172 EGFR/ALK/ROS1/RET/MET-negative lung cancers and 125 pediatric tumors, while NTRK3 fusions were detected in 2/447 (0.5%) non-lung adult malignancies. In conclusion, this study describes a diagnostic pipeline that can be used as a cost-efficient alternative to conventional methods of NTRK1–3 analysis.

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Section: Discussionmentioning

confidence: 99%

“…The cost of RNA-based NGS per sample is generally above 300–400 EURO or USD [ 23 , 44 ]. IHC is often regarded as a relatively cheap method, although its budget usually exceeds 150 EURO/USD [ 44 ]. The price for a single PCR reaction may be around 1.5 EURO/USD or even lower [ 45 ].…”

Section: Discussionmentioning

confidence: 99%

Cost-Efficient Detection of NTRK1/2/3 Gene Fusions: Single-Center Analysis of 8075 Tumor Samples

Romanko,

Mulkidjan,

Tiurin

et al. 2023

IJMS

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“…To date, the targeting of treatment populations has not introduced significantly different appraisal challenges. However, the next generation of TCT, such as histology-independent therapy, might present more decision-making challenges, including identifying the eligible population and appropriate prices across the different populations in the future [ 30 ]. Overall, TCT appraisals have fewer sources of uncertainty in the evidence despite the concerns about the poor quality of evidence.…”

Section: Discussionmentioning

confidence: 99%

Exploring uncertainty and use of real-world data in the National Institute for Health and Care Excellence single technology appraisals of targeted cancer therapy

Kang

Cairns

2022

BMC Cancer

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Objectives Dealing with uncertainty is one of the critical topics in health technology assessment. The greater decision uncertainty in appraisals, the less clear the clinical- and cost-effectiveness of the health technology. Although the development of targeted cancer therapies (TCTs) has improved patient health care, additional complexity has been introduced in drug appraisals due to targeting more specific populations. Real-world data (RWD) are expected to provide helpful information to fill the evidence gaps in appraisals. This study compared appraisals of TCTs with those of non-targeted cancer therapies (non-TCTs) regarding sources of uncertainty and reviewed how RWD have been used to supplement the information in these appraisals. Methods This study reviews single technology appraisals (STAs) of oncology medicines performed by the National Institute for Health and Care Excellence (NICE) over 11 years up to December 2021. Three key sources of uncertainty were identified for comparison (generalisability of clinical trials, availability of direct treatment comparison, maturity of survival data in clinical trials). To measure the intensity of use of RWD in appraisals, three components were identified (overall survival, volume of treatment, and choice of comparators). Results TCTs received more recommendations for provision through the Cancer Drugs Fund (27.7, 23.6% for non-TCT), whereas similar proportions were recommended for routine commissioning. With respect to sources of uncertainty, the external validity of clinical trials was greater in TCT appraisals (p = 0.026), whereas mature survival data were available in fewer TCT appraisals (p = 0.027). Both groups showed similar patterns of use of RWD. There was no clear evidence that RWD have been used more intensively in appraisals of TCT. Conclusions Some differences in uncertainty were found between TCT and non-TCT appraisals. The appraisal of TCT is generally challenging, but these challenges are neither new nor distinctive. The same sources of uncertainty were often found in the non-TCT appraisals. The uncertainty when appraising TCT stems from insufficient data rather than the characteristics of the drugs. Although RWD might be expected to play a more active role in appraisals of TCT, the use of RWD has generally been limited.

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“…IHC and fluorescence in situ hybridisation (FISH) may be used for fusion detection and are widely available. Triaging samples by IHC to select for molecular NTRK testing has been suggested as a strategy to optimise workflow and reduce costs [ 20 ]. In fact, ESMO recommendations for NTRK fusion detection suggest either RNA-NGS or pre-screening by pan-TRK IHC followed by confirmatory RNA-NGS for unselected populations where NTRK1/2/3 fusions are uncommon [ 19 ], such as those with TC.…”

Section: Methodological Considerations For Molecular Testing In Tcmentioning

confidence: 99%

Improved guidance is needed to optimise diagnostics and treatment of patients with thyroid cancer in Europe

de la Fouchardière,

Fugazzola,

Locati

et al. 2023

Endocrine

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Although thyroid cancer (TC) is generally associated with a favourable prognosis, there are certain high-risk groups with a clear unmet therapeutic need. Unravelling the genomic landscape of TC has recently led to the development of novel effective targeted treatments. To date, these treatments have mostly been evaluated in non-randomised single-arm phase II clinical trials and are consequently non-reimbursed in several countries. Furthermore, most of these agents must be tailored to individual patient molecular characteristics, a context known as personalised cancer medicine, necessitating a requirement for predictive molecular biomarker testing. Existing guidelines, both in Europe and internationally, entail mostly therapeutic rather than molecular testing recommendations. This may reflect ambiguity among experts due to lack of evidence and also practical barriers in availability of the preferred molecular somatic screening and/or targeted treatments. This article reviews existing European recommendations regarding advanced/metastatic TC management with a special focus on molecular testing, and compares findings with real-world practice based on a recent survey involving TC experts from 18 European countries. Significant disparities are highlighted between theory and practice related to variable access to infrastructure, therapies and expertise, together with the insufficient availability of multidisciplinary tumour boards. In particular, practitioners’ choice of what, how and when to test is shown to be influenced by the expertise of the available laboratory, the financing source and the existence of potential facilitators, such as clinical trial access. Overall, the need of a collaborative initiative among European stakeholders to develop standardised, accessible molecular genotyping approaches in TC is underscored.

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Appraising the Costs of Genomic Testing for Histology-Independent Technologies: An Illustrative Example for NTRK Fusions

Cited by 6 publications

References 8 publications

Cost-Efficient Detection of NTRK1/2/3 Gene Fusions: Single-Center Analysis of 8075 Tumor Samples

Cost-Efficient Detection of NTRK1/2/3 Gene Fusions: Single-Center Analysis of 8075 Tumor Samples

Exploring uncertainty and use of real-world data in the National Institute for Health and Care Excellence single technology appraisals of targeted cancer therapy

Improved guidance is needed to optimise diagnostics and treatment of patients with thyroid cancer in Europe

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