PONE-D-20-14126

A Multi-Criteria Sorting algorithm based method to infer authenticity of medications

PLOS ONE

Dear Dr. Salmon,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

Please submit your revised manuscript by Sep 10 2020 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

Please include the following items when submitting your revised manuscript:

• A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.
• A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.
• An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: http://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols

We look forward to receiving your revised manuscript.

Kind regards,

Fausto Cavallaro, PhD

Academic Editor

PLOS ONE

Journal Requirements:

When submitting your revision, we need you to address these additional requirements.

1. Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. The PLOS ONE style templates can be found at

https://journals.plos.org/plosone/s/file?id=wjVg/PLOSOne_formatting_sample_main_body.pdf and

https://journals.plos.org/plosone/s/file?id=ba62/PLOSOne_formatting_sample_title_authors_affiliations.pdf

2. Thank you for stating the following in the Financial Disclosure section:

"the authors received no specific funding for this work"

We note that one or more of the authors are employed by a commercial company: Daymark.

2.1. Please provide an amended Funding Statement declaring this commercial affiliation, as well as a statement regarding the Role of Funders in your study. If the funding organization did not play a role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript and only provided financial support in the form of authors' salaries and/or research materials, please review your statements relating to the author contributions, and ensure you have specifically and accurately indicated the role(s) that these authors had in your study. You can update author roles in the Author Contributions section of the online submission form.

Please also include the following statement within your amended Funding Statement.

“The funder provided support in the form of salaries for authors [insert relevant initials], but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the ‘author contributions’ section.”

If your commercial affiliation did play a role in your study, please state and explain this role within your updated Funding Statement.

2.2. Please also provide an updated Competing Interests Statement declaring this commercial affiliation along with any other relevant declarations relating to employment, consultancy, patents, products in development, or marketed products, etc. 

Within your Competing Interests Statement, please confirm that this commercial affiliation does not alter your adherence to all PLOS ONE policies on sharing data and materials by including the following statement: "This does not alter our adherence to  PLOS ONE policies on sharing data and materials.” (as detailed online in our guide for authors http://journals.plos.org/plosone/s/competing-interests) . If this adherence statement is not accurate and  there are restrictions on sharing of data and/or materials, please state these. Please note that we cannot proceed with consideration of your article until this information has been declared.

Please include both an updated Funding Statement and Competing Interests Statement in your cover letter. We will change the online submission form on your behalf.

Please know it is PLOS ONE policy for corresponding authors to declare, on behalf of all authors, all potential competing interests for the purposes of transparency. PLOS defines a competing interest as anything that interferes with, or could reasonably be perceived as interfering with, the full and objective presentation, peer review, editorial decision-making, or publication of research or non-research articles submitted to one of the journals. Competing interests can be financial or non-financial, professional, or personal. Competing interests can arise in relationship to an organization or another person. Please follow this link to our website for more details on competing interests: http://journals.plos.org/plosone/s/competing-interests

[Note: HTML markup is below. Please do not edit.]

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

Reviewer #2: Yes

**********

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

Reviewer #1: Yes

Reviewer #2: N/A

**********

3. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: No

Reviewer #2: Yes

**********

4. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: Yes

**********

5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: Very relevant use of MCDA approach for a societal problem. However, the introduction of the problem has to more clearly done, by giving the required definitions for understanding the ideas. It will be also the case for the choice of ELECTRE-Tri and the highlighting of the used methodology. References should be enriched. Figures and overall schemes would be appreciated for better getting the point of this approach. Please take time also for talking about the MCDA philosophy and its potential application in this sector.

Reviewer #2: Review on PONE-D-20-14126

This paper provides an interesting application of multiple criteria decision aiding (MCDA) model used to infer the authenticity of medications. From a methodological point of view, this is an interesting and well-founded study. The use of ELECTRE and MCDA as a supporting methodological concept is appropriate and well explained. However, several serious concerns need to be addressed. They are mostly related to the structure of the manuscript, precision of the message, and clearness of the whole method presented in the study.

MAJOR REMARKS

1. The structure of the paper is troublesome. In the section “Methods” where you introduce us to your model and the idea behind two components, you are heavily relying on the results of the study we are yet to be introduced with. This paper needs to be significantly restructured. Either you introduce us with the methodology in a formal way and then start with your results, or you create some other smart way. This structure is not a valid one for a reader to fully understand both the method and the idea of your proposal and corresponding results.

2. There are several methods within the ELECTRE family of methods. Claiming that you use ELECTRE TRI is not clear enough. The first one, at the start, was called just ELECTRE TRI (Yu, 1992). Later on, after the development of other methods, it was named ELECTRE Tri-B. Its characteristic is that the categories in the method are defined via boundary profiles set by decision-maker (DM). The newest method within the family is ELECTRE Tri-nB (Fernández et al., 2017). The “n” in the name suggests that DM is now allowed to set any number of boundary profiles between two categories. On the other hand, ELECTRE Tri-C (Almeida-Dias et al., 2010) introduced a novel way of thinking by setting, not boundary profiles, but characteristic profile, factoring as the most representative alternative for each category. In a similar fashion ELECTRE Tri-nC is a method where you can have any number of characteristic profiles.

Reading the paper, it becomes clear which model you use, but it is necessary to be precise. Moreover, the reason for my comment is the complete omission of the references at the moment when you introduce the method. More on reference later. Also, as ELECTRE Tri-B is a doctoral dissertation written in French, using reference (12) at that point is justified.

3. I have a major problem with the organization and the names of the subsection in the “Methods” section. Are definitions necessary in the manner you introduced them? It is very uncommon, and it goes in line with a very strange structure of the paper. Moreover, you put heading as if it is the section of the same level. It is not needed as a subsection. Introduce them in brackets after the first mention like you already at that point did with the LQ/C, for example. No need to repeat yourselves.

Also, naming the next subsection “Introduction to Developing Components 1,2 and Validation” without explanation of the concept is not advised, to say at least (apart from the brief mention in the introduction, but here you have to be much more precise).

4. Line 131. Validation of the BSF-S method required 50 samples… Why did it “require” 50 samples precisely?

5. The references in the paper are even strange and some moments. In some parts, there is a clear void where it should be supported with apparent references. The most striking example is with the notion of ELECTRE TRI, as I already mentioned. Also, when it comes to the elaboration of the ELECTRE and its (completely justified) use in your research, it should be supported with the references of applications based on the ELECTRE family of methods. Preferably in similar studies in the field, but in general as well. You can always check on most prominent journals, check the last two years of publications in top-rated journals in the OR/MS field, and you will find numerous applications of MCDA models in sorting.

If you find a significant number of applications in the field, it speaks in favor of your concept.

If you do not find many applications in your field (either in medical or OR journals), it would be beneficial to elaborate on such a finding. Why is that the case? Was there a reason to opt for some other methods? Is that a gap that could be beneficial? Could this yield several novel applications in the field of the known problems? As you see, this can be a very valid point for the deeper elaboration of your concept and contribution.

6. Even though you provide “conceptual” illustrations, proper definitions would be needed. And again, in figures, you use concepts from the study and your results. Even though I understand your desire to explain the model as clearly as possible with these conceptual illustrations, I had big trouble in understanding some parts (Figure 4 as a clear favorite).

A side note is that both pictures and figures are not of good quality, you should try to make it with higher quality standards.

7. Line 205. You name subsection “Part 1 – CAT-A”. Part 1 of what? These are very uncommon terms, let alone to be used as subsections. This goes in line with comments 1 and 3.

8. References in the paper are not according to the submission guidelines and, at some moments, not accurate. A good example is a reference (12) I already mentioned. First of all, the author is not the only editor of that handbook. Stating the date when you checked the book is not common, and it is not according to instructions. Authors need to follow guidelines to the very end and be very precise. This is not a minor mistake at all.

9. I was very interested in the results presented in tables 2 and 3. I’ll state this example to explain my interest here. Was (Would) the conclusion of the decision-maker (and make clearer how did you derive table 3), for a wavelength 240, that there exists a difference in samples 17 and 18 with the results 0.423 and 0.414?

MINOR REMARKS

1. Citations used at the end of the sentences should be before dots. For example, line 47 or at line 50.

2. It is a common practice to introduce the readers at the end of the introduction about the structure of the remainder of the paper (another paragraph after a paragraph ending at line 90).

3. Line 184. Your sentence starts “ELECTRE was chosen as has an”

4. Line 240. Figure 5, instead of Figure 4.

5. Line 302. Dot is missing at the end.

CONCLUSION

The idea of the manuscript is sound. It has the potential to pinpoint some relevant results as well as give a path for future applications of this methodological concept in the field. However, the manuscript is far away from publishable. It is difficult to understand it in some parts. They talk about the results in the section about the method where they use the data from the tables that are yet to be defined. References worryingly differ from the guidelines for authors. Such small problems are present throughout the manuscript. This manuscript has to be heavily restructured and revised in order to be ready for publication.

References

[1] Yu, W. (1992). Aide multicritère à la décision dans le cadre de la problématique du tri: concepts, méthodes et applications, LAMSADE, Université Paris Dauphine, Paris (Ph.D. thesis)

[2] Fernández, E., Figueira, J. R., Navarro, J., & Roy, B. (2017). ELECTRE TRI-nB: A new multiple criteria ordinal classification method. European Journal of Operational Research, 263(1), 214-224.

[3] Almeida-Dias, J., Figueira, J. R., & Roy, B. (2010). ELECTRE Tri-C: A multiple criteria sorting method based on characteristic reference actions. European Journal of Operational Research, 204(3), 565-580.

[4] Almeida-Dias, J., Figueira, J. R., & Roy, B. (2012). A multiple criteria sorting method where each category is characterized by several reference actions: The Electre Tri-nC method. European Journal of Operational Research, 217(3), 567-579.

**********

6. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: Yes: Lamia Berrah

Reviewer #2: No

[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step.

PONE-D-20-14126R1

Ultraviolet fingerprints and a sorting algorithm:  A portable way to authenticate medications

PLOS ONE

Dear Dr. Salmon,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

Please submit your revised manuscript by Aug 27 2021 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

Please include the following items when submitting your revised manuscript:

• A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.
• A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.
• An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: http://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols. Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols.

We look forward to receiving your revised manuscript.

Kind regards,

Fausto Cavallaro, PhD

Academic Editor

PLOS ONE

Journal Requirements:

Additional Editor Comments: Dear Authors the reviewers ask for further improvement of your paper. Please address all their comments.

[Note: HTML markup is below. Please do not edit.]

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #2: (No Response)

Reviewer #3: (No Response)

**********

2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #2: No

Reviewer #3: Partly

**********

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

Reviewer #2: (No Response)

Reviewer #3: N/A

**********

4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #2: Yes

Reviewer #3: Yes

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #2: Yes

Reviewer #3: Yes

**********

6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #2: The paper has improved. However, I still have significant issues with the manuscript, especially with the new parts.

1. Reading my comments you could have seen that I was talking about the ELECTRE Tri-B, and your response was that you used ELECTRE Tri-C, which is not accurate. If you have boundary profiles (Figure 2 for example is a place where you can see it), you are clearly talking about Tri-B. Please correct such mistakes.

2. The whole model setting is very problematic.

2.1. Please clearly define in the manuscript what are the alternatives, and more importantly criteria.

2.2. Biggest confusion causes Table 3. Are the values for the indifference, preference and veto threshold same for all wavelengths? One cannot understand it from the table.

3. I am not familiar with the concepts of indifference and non-compatibility in ELECTRE sorting models. Please clarify and check that part.

4. Please do a thorough proof reading before sending the manuscript. Page 5, line 100 you did not finish the name of the section; page 7, line 130, no dot at the end of the sentence; page 8, line 157 same thing. There are double spaces on several spots.

Finally, although improved, manuscript still has several sloppy mistakes and I urge authors to carefully read everything, including background methodological material and correct all the issues present in the current version of the manuscript.

Reviewer #3: The paper presents an interesting testing procedure to authenticate drugs applying a sorting algorithm based on ELECTRE TRI.

The problem is clearly stated, and the main contribution of the proposal is discussed. However, there are still some concerns with the sorting procedure proposed in the BSF test. Additionally, some statements in the manuscript are vague and could be rewritten. These statements are commented below.

# Line 82 – a multi-criteria sorting algorithm which can be used to compensate for the uncertainty when a pharmaceutical compound is analyzed “in the field” …

It is not clear that a multi-criteria sorting algorithm can be used to compensate for uncertainty. This terminology can be confusing in the decision analysis field.

As a suggestion, I would change the term uncertainty for imprecise , that is more appropriate.

# Line 91 - To compensate for samples prepared in the field using less than ideal equipment (i.e randomness in concentrations) the ELECTRE TRI-C multi-criteria sorting algorithm was adapted and applied to increase the likelihood of sorting a sample to the correct authentic/inauthentic category.

The sorting method presented is more related to the ELECTRE TRI-B, in which boundaries of the categories are defined. ELECTRE TRI-C does not depend on boundaries profiles but references examples. Please correct it in the manuscript.

I would not use the term “increase the likelihood of sorting a sample”, as the method ELECTRE was not designed for dealing with likelihood.

# Line 99-102 –difficult to read

# Line 149 – ELECTRE TRI-C is an algorithm that has specific attributes that allow for uncertainty and variability in collected data (or variability in sample preparation) that makes it ideal for the purposes of this method [17,18, 19, 20].

I disagree with this statement. Electre tri being the IDEAL method is very strong. The BSF is itself an interesting method to analyze the drugs. Besides the relevance of the studied problem, the sorting algorithm based on ELECTRE TRI does not seem to be the most appropriate one. (please consider that this comment does not invalidate the results). The point is, the study is using a sophisticated sorting technique that deals with the conflict of criteria and preferences of a decision-maker. However, the BSF problem seems to be more related to the calibration of measures by a specialist. The main point is that a similar result (dugs being considered authentic or not) could be reached by a procedure based on fuzzy logic. A Fuzzy method, including a similar calibration step, could be applied to define if a sample is authentic or not. Fuzzy systems (Zadeh, 1965) are well-known methods used to account for the knowledge of a specialist (in this case, the pharmaceutics). This is because a sample to be considered authentic must have all measures (for each wavelength of 240, 250, 260 and 270 – the criteria) under a specific value interval, but with some imprecise boundaries.

(observe that criteria weights are equal, and the credibility thresholds is 0,85)

Line 173 – mention ELECTRE TRI-C.

# Line 181 – Presents the sorting procedure.

In this case, the author could mention that an adapted procedure is used to sort the samples, based on the combined notion of the pessimistic and optimistic procedure of ELECTRE TRI-B. The explanation of left-to-right is interesting for a non-specialist in the area.

# Line - 282 Raw transmitted light absorbance data collected for 25 samples prepared in order to optimize ELECTRE TRI uncertainty parameters.

And

# Line 287. “This data displays three uncertainty parameters for ELECTRE TRI sorting algorithm. Values were selected by optimizing the minimize number of false positive and false negatives out of 50 samples of random substances (with 4 being factually positive)”.

It is not clear how the parameters have been optimized. This is quite important because the sorting procedure will depend on these established values.

In the response letter, the authors says that the solver function was applied to calibrate the categories. This should be mentioned in the text and explained in the supplement material, for instance.

# Line 350 - “There are a number of sorting algorithms that consider uncertainty in data, PROMETHEE II being one, that were also investigated.”

PROMETHEE II does not mean to sort alternatives.

# Line 361 - “Whereas ELECTRE TRI-C fails to sort this sample to any category, other methods would require that this be sorted to the best, if not correct, category. Thus, ELECTRE –TRI-C avoids the false positives challenge to a higher degree than other methods explored.”

I cannot see how ELECTRE can deal with false positives and negatives with such a sample. I don’t think this is the best argument. The procedure is not statistical.

There are some real applications of ELECTRE TRI method that could support this application. Consider Human Development Index Based on ELECTRE TRI Multicriteria Method, Social Indicators Research, 2016.

**********

7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #2: No

Reviewer #3: No

[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step.

PONE-D-20-14126R2Fake Drugs:  Using Baseline Spectral Fingerprinting and a sorting algorithm to infer quality of medicationsPLOS ONE

Dear Dr. Salmon,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

Please submit your revised manuscript by Jan 06 2022 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

Please include the following items when submitting your revised manuscript:

• A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.
• A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.
• An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: https://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols. Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols.

We look forward to receiving your revised manuscript.

Kind regards,

Fausto Cavallaro, PhD

Academic Editor

PLOS ONE

Journal Requirements:

Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice.

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #2: (No Response)

Reviewer #3: All comments have been addressed

**********

2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #2: Partly

Reviewer #3: Yes

**********

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

Reviewer #2: N/A

Reviewer #3: N/A

**********

4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #2: Yes

Reviewer #3: Yes

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #2: Yes

Reviewer #3: Yes

**********

6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #2: The paper is improved. However, I still have a major concern regarding your main findings in Table 4. I raised the issue in the previous round of review, but the response from the authors is not adequate. There is no possibility that the sorted category for some samples is “Indiferent” or “Not Compatible”. You have three categories, CAT-A, CAT-B, and CAT-C. ELECTRE TRI methods sort alternatives using two approaches. You even use the reference in response (Fontana & Cavalcante, 2011), where everything is correctly stated. In that paper, the authors define these two approaches as pessimistic and optimistic.

What can happen is that ELECTRE provides an interval as the solution (even [CAT-A, CAT-C]). Still, your claim is not correct. We cannot have an “indifferent”, nor “not compatible” category. Also, if the sorted category is “indifferent” how come you claim that this represents correct sorting?

I have put my recommendation as a minor revision, but this is a major issue requiring correction.

I have spotted a missing dot, line 88, at the end of the sentence.

Reviewer #3: The authors have addressed most of the comments in a satisfactory way. Although the new version of the manuscript has been improved, some minor mistakes need to be corrected.

Considering the tracked version of the manuscript, it seems that a reference is missing:

Line 461 – “There are a number of sorting algorithms that consider randomness 461 uncertainty in data, PROMETHEE Sort being a relevant example (cite).” (??)

Another issue is the term “uncertainty parameters”. Please change “uncertainty parameter” to “threshold parameter”, which is more appropriate.

“uncertainty parameter” is used repeatedly along with the text. For instance, Line 305, line 311, Line 371, Line 443, and Line 456

Line 372 – The previous version was more appropriate: “To define the preference and veto threshold …”

In Electre methods, threshold are used to account for the imperfect knowledge of data, vagueness and some arbitrariness when building the criteria.

**********

7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #2: No

Reviewer #3: No

[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step.

PONE-D-20-14126R3Fake Drugs:  Using Baseline Spectral Fingerprinting and a sorting algorithm to infer quality of medicationsPLOS ONE

Dear Dr. Salmon,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

Please submit your revised manuscript by Jun 05 2022 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

Please include the following items when submitting your revised manuscript:

• A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.
• A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.
• An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: https://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols. Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols.

We look forward to receiving your revised manuscript.

Kind regards,

Fausto Cavallaro, PhD

Academic Editor

PLOS ONE

Additional Editor Comments: I strongly suggest to reply point by point to Reviewers 2's comments

[Note: HTML markup is below. Please do not edit.]

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #2: (No Response)

Reviewer #3: All comments have been addressed

Reviewer #4: (No Response)

**********

2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #2: No

Reviewer #3: Yes

Reviewer #4: Partly

**********

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

Reviewer #2: N/A

Reviewer #3: N/A

Reviewer #4: No

**********

4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #2: Yes

Reviewer #3: Yes

Reviewer #4: Yes

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #2: (No Response)

Reviewer #3: Yes

Reviewer #4: Yes

**********

6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #2: I thank the authors for an attempt to clarify the reasoning. Several critical issues emerged from the response.

1. What authors refer to in Fantana and Cavalcante's article are ways to obtain pairwise relations between two alternatives. This has nothing to do with the pessimistic and optimistic rules where you actually have the major problem. Each rule defines a category with certainty, i.e., the upper and lower boundary of the sorting procedure.

2. Note that you do not have this reference in the reference list in the manuscript. Generally, you have mainly missed the good references in presenting ELECTRE Tri-B method, even though you had good suggestions from reviewers.

Overall, the idea behind the work is good. The idea behind the method is very solid, and it can work well. The execution is poor. I was very sympathetic toward the authors, addressing the main issues several times, but this has still not improved. In the end, you remain with the clear methodological mistake of using indifferent and not compatible samples and evaluating them as correct classification.

Reviewer #3: The authors have justified the proposed sorting procedure applied in the paper, based on the notions of ELCTRE-TRI-B.

In this way, the authors should avoid generalizations regargind applicarons of ELECTRE-TRI. For instance, I would recommend changing the following sentence (line 236, pg 10): "In the general application of ELECTRE TRI-B this situation defines Sample-Y as being defined as “incomparable” to the sorting system. In other words, the sample cannot logically be sorting to any category of the sorting system as defined by the decision maker" to: "This situation defines Sample-Y as being defined as “incomparable” to the sorting system"

Reviewer #4: This paper presents a novel method for inferring quality of medications specifically.The current study represents an interesting subject to improve the healthcare system. However, the authors have to detail the results. Some comments have to be revised.

1- Authors have integrated the multi-criteria tool for sorting. However, the theoretical content is missing in the paper. It would be preferable to include a section about the multi-criteria tools.

2- The authors should present a comparative study of the multi-criteria sorting tools.

3- There are several multi-criteria sorting algorithms that can realize the study. The authors have chosen the use of ELECTRE TRI-B. They should justify the choice of this sorting algorithm.

4- To prove this classification proposed by the authors, it is preferable to study the sensibility analysis according to the cut-value λ.

**********

7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #2: No

Reviewer #3: No

Reviewer #4: Yes: Layla AZIZ

[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step.

Attachments

Attachment

Submitted filename: Review PLOS.docx

PONE-D-20-14126R4Fake Drugs:  Using Baseline Spectral Fingerprinting and a sorting algorithm to infer quality of medicationsPLOS ONE

Dear Dr. Salmon,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

Please submit your revised manuscript by Dec 18 2022 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

Please include the following items when submitting your revised manuscript:

• A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.
• A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.
• An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: https://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols. Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols.

We look forward to receiving your revised manuscript.

Kind regards,

Fausto Cavallaro, PhD

Academic Editor

PLOS ONE

Additional Editor Comments:

The reviewer asserted that his comments are not addressed. Please proceed to revise carefully your paper on the base of his suggestions.

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #4: (No Response)

**********

2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #4: Partly

**********

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

Reviewer #4: No

**********

4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #4: Yes

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #4: Yes

**********

6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #4: Tha authors have not revised the fourth comment(To prove this classification proposed by the authors, it is preferable to study the sensibility analysis according to the cut-value λ.). The authors are asked to add a new section to include the sensitivity analysis study.

**********

7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #4: No

**********

[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step.

Fake Drugs:  Using Baseline Spectral Fingerprinting and a sorting algorithm to infer quality of medications

PONE-D-20-14126R5

Dear Dr. Salmon,

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.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

An invoice for payment will follow shortly after the formal acceptance. To ensure an efficient process, please log into Editorial Manager at http://www.editorialmanager.com/pone/, click the 'Update My Information' link at the top of the page, and double check that your user information is up-to-date. If you have any billing related questions, please contact our Author Billing department directly at authorbilling@plos.org.

If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org.

Kind regards,

Fausto Cavallaro, PhD

Academic Editor

PLOS ONE

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #4: All comments have been addressed

**********

2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #4: Yes

**********

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

Reviewer #4: Yes

**********

4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #4: Yes

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #4: Yes

**********

6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #4: (No Response)

**********

7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #4: Yes: layla aziz

**********