PONE-D-24-51054Improved drug-screening tests of candidate anti-cancer drugs in patient-derived xenografts through use of numerous measures of tumor growth determined in multiple independent laboratoriesPLOS ONE

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Reviewer #1: Yes

Reviewer #2: Yes

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2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: Yes

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Reviewer #1: Yes

Reviewer #2: Yes

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Reviewer #1: Yes

Reviewer #2: Yes

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5. Review Comments to the Author

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Reviewer #1: Elizabeth et al. reported Improved drug-screening tests of candidate anti-cancer drugs in patient-derived xenografts through use of numerous measures of tumor growth determined in multiple independent laboratories. The goal of the work was to document improvements in the experimental design and statistical analysis of drug-screening tests based upon the criteria of sensitivity, specificity, and accuracy. They generated a drug-screening test based on a single measure and a single lab (SMSL; single p-value) and (Fisher’s Method p-values; one p-value per measure) and/or Storey’s method (m q-values for m measures in a single lab). They revealed that, for these data, the optimal drug screening tests employ the meta-analysis approach, while the SMSL produces the greatest uncertainty. meta-analysis results (accuracy, sensitivity, and specificity) indicate that the most reliable procedure to characterize the ability of a chemotherapeutic drug to inhibit tumor growth in a patient-derived xenograft is to use several different measures of tumor growth collected at multiple different laboratory sites. However, if data are collected at only one laboratory site, then multiple independent experiments should be done on different days and analyzed with several different measures of tumor growth

The manuscript is scientifically sound considering the need to develop newer drug screening tests in patient-derived xenografts. Its well drafted and the statistical analysis have been performed effectively. However, there are certain modifications to be made to increase the quality and readership of the article. Firstly, the authors should include the abbreviations below all the tables. For example, in Tables 7, 9 and 10, the abbreviations of the corresponding labs are suggested to be incorporated in the revised manuscript. Secondly, the authors can also mention if there were any similarities in both the datasets obtained from different labs. Thirdly, it would be ideal to summarize the sensitivity and specificities of the screening methods of meta analysis in a single table under results/conclusion section. Lastly, the figures look somewhat ‘blurry’ and quality of the figures can be enhanced.

Reviewer #2: The present work entitled: Improved drug-screening tests of candidate anti-cancer drugs in patient-derived xenografts through the use of numerous measures of tumor growth determined in multiple independent laboratories that may be useful as prospective anticancer agents. The purpose of this work is to develop methods for evaluating the results of preclinical drug screening tests. Several different measures of drug inhibition of tumor growth in patient-derived xenografts (PDX) are compared, and the benefit of determining inhibition in different laboratories are compared. The work is interesting and suitable for publication in the PLOS ONE after making minor revisions. I suggest the authors to make the necessary corrections as suggested below

1. Rewrite the keywords in alphabetical order. Additionally, add the other keywords preclinical, in vivo and invitro

2. Check the manuscript for grammatical and typographical errors. For example, keep the word et al, in vivo, in vitro in italics, and while writing the word figure “F” must be capital letter.

3. Table legends of all the tables mentioned in the manuscript have to be keep above the table

4. Double check the entire documents, different typos are present

5. To improve the quality of manuscript, add some of the recent findings related to anti-cancer in introduction and results

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Reviewer #2: Yes:  Danaboina Srikanth

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Improved drug-screening tests of candidate anti-cancer drugs in patient-derived xenografts through use of numerous measures of tumor growth determined in multiple independent laboratories

PONE-D-24-51054R1

Dear Dr. Gordon,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

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Kind regards,

Afzal Basha Shaik, Ph.D

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

The manuscript is much improved according to the reviewers comments and is now suitable for publication.

Reviewers' comments: