Toward Practical Integration of Omic and Imaging Data in Co-Clinical Trials

Round 1

Reviewer 1 Report

In this concept paper, the authors present a prototype usage of their web based portal concept for storing/viewing/analyzing both molecular and imaging data arising from co-clinical trials called MIRACCL (Molecular and Imaging Response Analysis of Co-Clinical Trials). The online tool does seem like it would be a very useful tool for initial investigations of results and/or sharing results with collaborators. Their tool is a clever integration of many existing tools linked together to interact with the data in a meaningful way. As such, it is an excellent concept and I applaud the authors for their effort on this project. Also, great acronym! 

I do have some suggestions that I think will help the paper. As this is not a traditional research paper, it is understandably difficult to determine the appropriate pieces for sections such as “materials and methods” and “results”. As it is currently written, it is a little difficult for a reader to fully understand the importance and the key parts that make up this “concept.”

The flow of text in the introduction goes from justifying co-clinical trials are relevant (1 page) with a small paragraph listing the challenges (not really justified why they are challenges), describes MIRACCL (half page), and then describes the prototype problem with the specifics of data types (half page). The emphasis here seems wrong. If the concept is the tool, the focus should be on why the challenges (data management, interrogation, and visualization) are challenges and how the tools can improve current methods. (What are the current methods?) There should be minimal justification of co-clinical trials. Discussion of prototype specifics should also be minimal with more details later, which I might suggest should be supplemental material.

Similarly, the methods section seems to have an odd emphasis, especially as the second part of the document. All materials and methods subsections are referencing the prototype example specifics rather than tool specifics. I do appreciate that readers will likely want this information and it isn’t obvious where it should all go. But, I strongly encourage the majority of these sections to be put in a supplement or at least put the results section first. I believe you want the reader to be inspired by what a cool tool you are building instead of getting bogged down in the specifics of a clinical trial that, honestly, you don’t need to fully understand to see the utility of the tool. The current “Results” section is more what I would expect for methods in this type of paper, certainly the first few subsections. Perhaps in this “concept” paper, you should/could rethink your large section names and not have “Methods” or “Results”?

As a broader comment on this “concept”, it is unclear why this is specifically helpful to co-clinical trials. This tool seems like it would be great for single clinical trials and/or meta-analysis of multiple “standard” clinical trials. While I appreciate this may be “future work”, to really make it co-clinical trial specific, it would be great to have some way of separating out the biologically similar groups, i.e. if it was patient derived PDX, be able to easily pull out the PDX/human match for comparison. Of course, you could also just slightly tweak your acronym (keep the sound) and make sell it more broadly for clinical trials.

Author Response

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Author Response File: Author Response.docx

Reviewer 2 Report

Dear Authors,

The submitted manuscript focus on "MIRACCL' a web based analysis tool. The authors performed a very nice study in a very well organized manner. The authors cover all the study point and describe 

1. It will be better to show the patient inclusion and exclusion criteria in a very descriptive way. 

2. Authors need to provide few lines regarding the limitation of the use of MIRACCL platform for PDX based trials.

Overall manuscript representation is very nice to cover all the broad area using PDX based model.

Thank you.  

Author Response

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Author Response File: Author Response.docx

Reviewer 3 Report

Abstract: OK

Introduction: OK

Materials: OK.

Please refer if the diagnosis of TNBC was made by 2 independent pathologists. And that the patients were not under anti-hormone therapy (pseudo triple negative)

PG.10, Line 272?

Results: OK

Discussion: OK

Conclusions: OK

Author Response

Please see attachment.

Author Response File: Author Response.docx