Costs of Next-Generation Sequencing Assays in Non-Small Cell Lung Cancer: A Micro-Costing Study

Round 1

Reviewer 1 Report

Comments:

The manuscript “Costs of Next-generation Sequencing Assays in Non-small Cell Lung Cancer: A Micro-costing Study” submitted by Kumar et. al.  studied the costs of NGS assays using fine needle aspirates (FNAs) from clinical samples of NSCLC. This study highlights a micro-costing study of four NGS assays (TruSight 170 (Illumina), On-comine Focus (Thermo Fisher), Targeted DNA and RNA Panels (Qiagen), and KAPA HyperPlus/Se- qCap EZ (Roche)) at the StemCore Laboratories, The Ottawa Hospital, Canada. In general, the manuscript is good. Nevertheless, in my opinion, some revisions are needed in order to better clarify some points and avoid confusing the reader about the meaning of results achieved.

Major and minor issues are listed below:

1.     In the introduction author should clearly describe the prevalence of NSCLC (provide some number like how many people are affected in Canada and then narrow it down to Ottawa.

2.     Author should compare the cost with other location (it could be from other literature, meta-analysis). Comparing within a particular location is not sufficient to draw conclusion about the cost.

3.     Apart from budget what other significance this study could lead is completely missing. What other disease diagnosis uses NGS and comparison with that will make the result meaningful.

4.     What is the future direction of this project? How can people get benefited with this information?

Author Response

Comments:

The manuscript “Costs of Next-generation Sequencing Assays in Non-small Cell Lung Cancer: A Micro-costing Study” submitted by Kumar et. al.  studied the costs of NGS assays using fine needle aspirates (FNAs) from clinical samples of NSCLC. This study highlights a micro-costing study of four NGS assays (TruSight 170 (Illumina), On-comine Focus (Thermo Fisher), Targeted DNA and RNA Panels (Qiagen), and KAPA HyperPlus/Se- qCap EZ (Roche)) at the StemCore Laboratories, The Ottawa Hospital, Canada. In general, the manuscript is good. Nevertheless, in my opinion, some revisions are needed in order to better clarify some points and avoid confusing the reader about the meaning of results achieved.

Major and minor issues are listed below:

1. In the introduction author should clearly describe the prevalence of NSCLC (provide some number like how many people are affected in Canada and then narrow it down to Ottawa.

 

Response. Thank you for your suggestion. We have added the following sentences to the introduction section.

 

“In Canada, lung cancer accounts for 13% of new cancer cases and 25% of cancer deaths in 2022. Non-small cell lung cancer (NSCLC) is the most common type of lung cancer, with the prevalence of 80 – 85% of lung cancer cases [8]. Patients diagnosed with NSCLC are most often diagnosed at a late stage as NSCLC does not show symptoms at early stages, and the estimated 5-year net survival among late-stage NSCLC patients is as low as 0-36%”.

 

2. Author should compare the cost with other location (it could be from other literature, meta-analysis). Comparing within a particular location is not sufficient to draw conclusion about the cost.

Response. In the discussion section (Page 7 – 8, Lines 213 - 237), we compared our results to other studies, which used similar costing method (micro-costing) to estimate the cost of genomic sequencing procedures in NSCLC patients.

 

3. Apart from budget what other significance this study could lead is completely missing. What other disease diagnosis uses NGS and comparison with that will make the result meaningful.

Response. Thank you. We have revised our discussion section. On Page 7 to 8 (Lines 255 - 271), we have elaborated the potential implications of our study findings. The following sentences have been added.

 

“Based on our costing results, researchers could perform a cost-effectiveness analysis of commercially available platforms by comparing their costs and outcomes with respect to sensitivity, specificity, limits of detection, reproducibility, comprehensiveness, and turnaround time. Such an analysis could help select the optimal assay (s) for NSCLC FNAs in the clinical setting. Future studies should assess the impact of sequencing at scale on the NGS costs. Results from our study could also be used to inform future economic evaluations and budgetary impact calculation of genomic sequencing and targeted therapies for NSCLC. Furthermore, understanding the key drivers of costs for NGS assays could inform decisions on the implementation of these assays to the publicly funded health system.”

 

 

4. What is the future direction of this project? How can people get benefited with this information?

Response. As shown in our previous response. We have added sentences highlighting the direction of future research in the discussion section.

 

“Based on our costing results, researchers could perform a cost-effectiveness analysis of commercially available platforms by comparing their costs and outcomes with respect to sensitivity, specificity, limits of detection, reproducibility, comprehensiveness, and turnaround time. Such an analysis could help select the optimal assay (s) for NSCLC FNAs in the clinical setting. Future studies should assess the impact of sequencing at scale on the NGS costs. Results from our study could also be used to inform future economic evaluations and budgetary impact calculation of genomic sequencing and targeted therapies for NSCLC. Furthermore, understanding the key drivers of costs for NGS assays could inform decisions on the implementation of these assays to the publicly funded health system.”

Author Response File: Author Response.pdf

Reviewer 2 Report

The manuscript entitled “Costs of Next-generation Sequencing Assays in Non-small Cell Lung Cancer: A Micro-costing Study” by Srishti Kumar et al, performes a micro-costing study of four NGS assays (TruSight 170 (Illumina), Oncomine Focus (Thermo Fisher), Targeted DNA and RNA Panels (Qiagen), and KAPA Hyper-Plus/SeqCap EZ (Roche)) at the StemCore Laboratories, The Ottawa Hospital, Canada. In this study the authors used a time-and-motion approach to measure personnel time and a pre-defined questionnaire to collect resource utilization.

Authors have concluded that the study results could help inform future economic evaluations of NGS platforms and decisions to use these assays to guide treatment selections for NSCLC patients.

 

General comments:

Ø       Authors have used various approaches to study and determined that the costs of NGS assays using fine needle aspirates (FNAs) from clinical samples of NSCLC. They collected Data was collected at the StemCore Laboratories at The Ottawa Hospital over a 12-month period. They used a time-and-motion approach to measure personnel time associated with performing library preparation for each NGS assay, But I think the authors should present this study as a Report or perspective or review article and Not as a Research article, since this study describes about the future economic evaluations of NGS platforms and usage of these assays to guide treatment selections for NSCLC patients.

Author Response

The manuscript entitled “Costs of Next-generation Sequencing Assays in Non-small Cell Lung Cancer: A Micro-costing Study” by Srishti Kumar et al, performes a micro-costing study of four NGS assays (TruSight 170 (Illumina), Oncomine Focus (Thermo Fisher), Targeted DNA and RNA Panels (Qiagen), and KAPA Hyper-Plus/SeqCap EZ (Roche)) at the StemCore Laboratories, The Ottawa Hospital, Canada. In this study the authors used a time-and-motion approach to measure personnel time and a pre-defined questionnaire to collect resource utilization.

Authors have concluded that the study results could help inform future economic evaluations of NGS platforms and decisions to use these assays to guide treatment selections for NSCLC patients.

General comments:

Authors have used various approaches to study and determined that the costs of NGS assays using fine needle aspirates (FNAs) from clinical samples of NSCLC. They collected Data was collected at the StemCore Laboratories at The Ottawa Hospital over a 12-month period. They used a time-and-motion approach to measure personnel time associated with performing library preparation for each NGS assay, But I think the authors should present this study as a Report or perspective or review article and Not as a Research article, since this study describes about the future economic evaluations of NGS platforms and usage of these assays to guide treatment selections for NSCLC patients.

Response. Thank you for your suggestion. Our study aimed to estimate the costs, not the cost-effectiveness, of NGS assays. We believe it is appropriate to consider cost studies, like ours, as a research article because they involve the collection of original data specific to a particular research project. Indeed, Current Oncology published several cost studies in its past issues. A few examples are provided below:

Curr. Oncol. 2016, 23(3), 228-238; https://doi.org/10.3747/co.23.2998

Curr. Oncol. 2016, 23(5), 304-313; https://doi.org/10.3747/co.23.2987

Curr. Oncol. 2019, 26(2), 102-107; https://doi.org/10.3747/co.26.4555

Author Response File: Author Response.pdf

Round 2

Reviewer 2 Report

I would recommend that authors should read the manuscript properly for any grammatical, technical and typographical errors. 

Please check if the instruments details were given properly. And also discuss different types of sequencing when having heterogenous data.

Author Response

Reviewer 2:

Comments:

1. I would recommend that authors should read the manuscript properly for any grammatical, technical and typographical errors.

Response: Thank you. We have read and ensured that all grammatical, technical and typographical errors have been corrected.

2. Please check if the instruments details were given properly. And also discuss different types of sequencing when having heterogenous data.

Response: Thank you. We have corrected the details of each assay throughout the manuscript. Additionally, we have added the following sentences to the discussion section.

“It should be noted that each assay may have different performance characteristics and that Trusight Tumor 170 Kit is the largest panel which covers 170 tumor-related genes, meaning that the assay would allow sequencing many tumor genes, including those not yet approved for NSCLC diagnostics, without additional costs. However, the assay’s performance is beyond the scope of this study.”

Author Response File: Author Response.pdf

Round 3

Reviewer 2 Report

Authors have revised the manuscript.

Please check re-phrasing, typos and other small errors.

Just check once for plagiarism