https://orcid.org/0000-0002-9234-6126
Peer Review History
| Original SubmissionSeptember 16, 2019 |
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PONE-D-19-25977 Implementation of the new integrated algorithm for diagnosis of drug resistant tuberculosis in Karnataka State, India: How well are we doing? PLOS ONE Dear Dr. Shankar S, 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. In particular, concerns regarding statisical analysis should be addressed and some parts of manuscript should be clarified e.g. Introduction, as recommended by the reviewers. We would appreciate receiving your revised manuscript by Mar 14 2020 11:59PM. When you are 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. If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. To enhance the reproducibility of your results, we recommend that if applicable you deposit your laboratory protocols in protocols.io, where a protocol can be assigned its own identifier (DOI) such that it can be cited independently in the future. For instructions see: http://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols Please include the following items when submitting your revised manuscript:
Please note while forming your response, if your article is accepted, you may have the opportunity to make the peer review history publicly available. The record will include editor decision letters (with reviews) and your responses to reviewer comments. If eligible, we will contact you to opt in or out. We look forward to receiving your revised manuscript. Kind regards, Igor Mokrousov, Ph.D., D.Sc. Academic Editor PLOS ONE Journal Requirements: 1. When submitting your revision, we need you to address these additional requirements. 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 http://www.journals.plos.org/plosone/s/file?id=wjVg/PLOSOne_formatting_sample_main_body.pdf and http://www.journals.plos.org/plosone/s/file?id=ba62/PLOSOne_formatting_sample_title_authors_affiliations.pdf 2. We note that you have stated that you will provide repository information for your data at acceptance. Should your manuscript be accepted for publication, we will hold it until you provide the relevant accession numbers or DOIs necessary to access your data. If you wish to make changes to your Data Availability statement, please describe these changes in your cover letter and we will update your Data Availability statement to reflect the information you provide. 3. Please amend the manuscript submission data (via Edit Submission) to include authors Reena Kingsbury, Ramamurthy Padmesha, Magesh Velu, Suganthi P, Joydev Gupta, Jameel Ahmed, Puttaswamy G, Somashekarayya Hiremath, Ravi K Jaiswal and Rony Jose Kokkad. [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: Partly Reviewer #2: Partly Reviewer #3: Yes Reviewer #4: Yes ********** 2. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: No Reviewer #2: Yes Reviewer #3: Yes Reviewer #4: Yes ********** 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 Reviewer #3: Yes Reviewer #4: 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 Reviewer #3: Yes Reviewer #4: 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: Summary: This manuscript examines a new diagnostic algorithm in Karnataka state for the identification of drug resistant TB. The authors have presented results for 1660 patients diagnosed over a two-month period in 2018, and indicate that the while there are some specimens that did not reach the second testing lab or complete the testing algorithm, overall they are encouraged by the proportion that made it through the complex algorithm. Factors associated with specimens not making it through the testing process were examined, and the turn-around-times were reported. I enjoyed reading this manuscript and found it to be generally clear despite the challenges of describing complicated algorithms. There are however some concerns with the statistical methods used to examine factors that may be associated specimens reaching the reference labs and not completing the testing algorithm. There are some minor issues related to clarity of message and grammar/wording which I will offer suggestions as PLoS ONE does not copyedit accepted manuscripts. Major issues: Line 290. Unless I am misunderstanding the data, a poisson regression model would be the incorrect choice given the binary outcome variable (Not reaching vs reaching; completion vs non-completion). The measure of the association would be an odds ratio. Please revise accordingly. Line 291. An exploratory data analysis is often necessary to conduct initially to understand the dataset and variables; however, for reporting results all variables included in a model should make sense. They should either be chosen a priori based on literature and experience, and/or because an association was observed on bivariate analysis. Could you please elaborate on what support there would be for an association between not reaching or not completing, for variables related to the patient such as age, sex and key population? Do the laboratory personnel processing specimens have access to this information and would make a choice not to send or process specimens and samples based on this information? It seems more likely that an association is possible with respect to variables related to the specimens themselves or facilities. If there is no statistical, literature, or common knowledge that would indicate that patient-level variables be considered in the multivariable model please update the analysis without these and revise accordingly. If there is clear rationale to support their inclusion please update the methods to include this information. Table 4. Analysis for non-completion. Kolar district is no longer significant when covariates are added to the model. Did you investigate why this might be? What is the relevant confounder to the association? Given my concerns regarding the covariates included this warrants further investigation. It does not appear there was an assessment of model fit, and there may be issues related to overfitting. There are quite a few variables included, and a some of these have many levels. Cell sizes were quite low in some instances in the non-completion model. It is recommended that the model building approach and assessment of fit be carefully considered. Minor issues: Abstract: 1. Line 65. Capitalize Line Probe Assay for consistency with the manuscript text. 2. Line 67. Insert the word ‘phenotypic’ before drug susceptibility testing 3. Line 75. Please change ‘till’ to ‘until’ (more formal for scientific writing) 4. Line 78. Were there any duplicate patients in the 1660 (more than one specimen/patient) if so then patients should be updated to ‘specimens’ here, and throughout the manuscript as necessary. It would also be helpful to indicate in the methods or results if each patient is represented by a single specimen, or if not please report the number of patients with multiple specimens and an indication of how many specimens/patient were represented in this study. 5. While I agree that putting this complex algorithm into place is encouraging and having a considerable proportion of specimens make it through testing, I am also concerned that only about a quarter of RIF resistant TB completed the testing algorithm – which is the TB that is most in need of full testing. It would be beneficial to include a few words in the abstract and again in the manuscript indicating that while encouraging there is also significant concern about this. Introduction: 1. Line 113. Please add the word ‘phenotypic’ in front of drug susceptibility 2. Line 118. A better word for ‘heartening’ in scientific writing may be ‘encouraging’ 3. Line 126. Can you clarify here if by non-diagnosis it is meant that resistance was not tested/diagnosed? If patients weren’t diagnosed at all they wouldn’t be treated and therefore not part of the statistic for treatment failure. 4. Line 184. Reference #15 does not link to the pdf for the correct province, please update. 5. Line 185. The reference #15 does not appear to contain the statistic for prevalence, please update the reference to the correct one and ensure that the statistic reported is indeed prevalence rather than incidence. Methods: 1. Line 195-196. The company that produces the products listed should be included, Hain Lifescience, BD Biosciences BACTEC, and which version of the line probe assays were used. 2. Line 199. Could you elaborate on the human carriers and how this differs from a courier service? 3. Line 215. It may be better to specify ‘one day’ rather than ‘a day’. 4. Line 219. Perhaps reword to read: ‘testing is required, and the second sample…’ 5. Line 224. Please specify in the methods or introduction which second line drugs are being tested, not all readers may be familiar with the Hain assay and the version number was not indicated. 6. Line 224. I assume that further testing is for those that were resistant to second line drugs in the SL-LPA? Perhaps clarify this in the sentence. 7. Line 229. It appears that a word is missing. Either ‘a sample’ or ‘their sample’ 8. Line 230. Could you clarify the use of poly resistant treatment? As I understand the sentence these cases are RIF-S and INH-R, so initiation of poly-resistant treatment would be indicated by FL-LPA indicating resistance to EMB or PZA. 9. Line 245. I assume the data was collected at the time of specimen collection and testing, and here you mean the data was extracted between February and April 2019 from the laboratory registers? 10. Line 274-275. Quotation marks are not needed here. 11. How were the laboratories selected for this study? Was there specific criteria? Results: 1. Line 309. This is the first time “key population group” has been introduced and does not include an explanation of what this represents. Information regarding this should be included in the methods as it is not a standard variable. 2. Line 310. In the context of this sentence, it should be ‘persons living with HIV’ 3. It is not clear what happened to the specimens with indeterminant or no information? – Where do they fit in the algorithm? What was the outcome? Indicate in the methods sections how these were handled for the analysis. 4. Line 347. It is stated that culture was done for 41 samples. however, in Figure 2 it indicates culture was done for 43 samples? 5. Lines 361-363. This sentence is a bit hard to follow. Perhaps something along the lines of “on eight samples, under the following SL-LPA conditions: (i) resistance, (ii) was not done, or (iii) no result.” 6. Line 373. Based on Figs 2 and 3, the number that reached the laboratory was 1170+35 = 1205 and therefore n=455 did not reach the laboratory? which also affects the calculation of those that completed the algorithm. Please clarify. 7. Line 379. Please report the precise number of samples that reached within one day for the results section. 8. Lines 380 and 383. IQR should be included with the median. Discussion: 1. Line 451. It may be helpful to provide a reference here regarding the standard or recommended turn around times to support this statement that there were no major delays. 2. Line 452. Please expand briefly on the SL-LPA testing delays. 3. Line 455. How far away? 4. Line 457. One-fourth is not commonly used in this context. ‘Approximately 25%’ or ‘approximately one quarter’ 5. Lines 457-463. What are the reasons that extrapulmonary specimens do not get tested? Do you have any recommendations on how to improve this? 6. Line 465. Intrigued is an interesting choice of word here. I would have thought surprised or dismayed. 7. Lines 465-470. Is this similar or different to the findings of other studies? A common issue that RIF-R samples are not submitted for further testing? This result is a major finding and should be discussed further and stressed as important. Instead of ‘This needs further investigation’ at the very least something like ‘This is an important issue and requires further investigation’. 8. Lines 472. How was is better? 9. Line 473. Please reword to: “This may be due to the presence of a system of…” 10. Line 475. Instead of gaps, “proportion of specimens that did not reach” 11. Line 479. You may want to include the percentage here to highlight how excellent they were. 12. Line 480-483. Could you please clarify why delays related to culture would result in non-completion of the algorithm? 13. Line 480. If evidence of this was not provided as a result for why there were delays than this is speculation? If you do not have results demonstrating this please rephrase to “This may be explained” 14. Line 481. Correct wording to ‘…must be cultured before’ or ‘…require culture before’ 15. Line 489. See previous comment. If evidence is not presented in the results, “This may explain” as it is an assumption. 16. Lines 501-503. Following STROBE is not a strength of the study, but of the manuscript writing. Please remove. 17. Line 511. Briefly expand on this, and how it limits your ability to recommend changes/improvements. What information would be needed to inform these gaps and how would you propose to gather it? 18. Lines 515-519. Here you have given specific examples of things to improve; however, there were no results proving that these were the specific issues to be addressed. Please revise. 19. Line 529. ‘Approximately’ is a preferred word to ‘about’. This sentence could be more concise. 20. Line 531. ‘gaps’ should be expanded here – delays? not reaching the reference laboratory? not completing the algorithm? 21. Lines 532-534. This should be included in the acknowledgements section rather than conclusions. Tables Please be consistent across tables with capitalization and variable names. e.g. Table 2 non-key population; Table 4 Not Key population. Similarly, use consistent term for unavailable data for each variable. ‘Missing’ or ‘Not recorded’ or ‘Not available’. Also, with the site and laboratory. Table 2. 1. Under key population: reword to ‘persons living with HIV’ 2. Under key population: Footnote should indicate what population is represented in ‘Others’ 3. For Specimen condition of receipt at Xpert lab – these categories only apply to sputum specimens? The table should reflect this. Table 3. 1. The last line FL-LPA result was resistant – to any first line drug? Table 4. 1. Male reference is not indicated in aRR column 2. There is no footnote for the abbreviation PLHIV 3. The N and (%) columns presumably refer the those that did not reach the laboratory. Please clarify this in the column header. Table 5. 1. As in Table 4, please be specific for the column header N (%) 2. Age 0-14 is not an appropriate reference given that the N = 0 for non-completion. 3. Please indicate what the NA values represent. 4. Under Specimen type, remove the word sample for Extra-pulmonary Figures Figure 2. 1. The denominator for culture done does not appear to add up. 39+21+43+4 = 107 2. For the 3 Xpert RIF-S samples that were then RIF-R as the reference laboratory what was the pattern of INH resistant? This could be included as a footnote. Reviewer #2: Overall comments: Thank you for the opportunity to review this manuscript. It is a well written manuscript that addresses a topic that is of fundamental importance to TB care in India. Abstract: No major comments Introduction: • Line 106: Is this prevalence of MDR-TB among all cases, if so I think specify. • Line 108: Spell out XDR TB at first use • Line 112: I think it would be good to have a brief explanation of what PMDT is. • Line 116-117: is this statistic of 29% from India? Pls kindly clarify so that the context is clear. • Line 126: You talk about non diagnosis as being one of the reasons for low treatment success but treatment success is really only measured for diagnosed cases, pls clarify. • Paragraph starting at line 130: I would have liked to know about more about the rollout of Xpert in India, can you provide a couple more sentences about this including the dates of rollout and how quickly it happened? • Line 133: When did the policy of universal DST start? A date would be helpful. Methods: • Line 183: I think this sentence about the population size needs a reference. • You mention the human carriers or couriers in lines 199-200 and then again in lines 208-209 which I think is repetitious. • Line 216-217: Is this second sample also tested using Xpert or LPA? • Line 223: I think it would be better to say “If additional resistance” rather than “If resistant” as I think this is what is meant, i.e. if there is additional resistance then a pre XDR or XDR regimen is started. • I was wondering why a mobile phone number was used as the second method of identifying people rather than the name-age-sex combination which may be more unique. How well does a mobile phone number identify the user? Has this method been previously validated for matching people in population based studies? I think this needs further discussion and justification. • In Table 1 I think some additional clarity is needed, i.e. for the third to fifth bullet points what is the resistance or sensitivity to? I think some additional detail is needed here. It should also be clear why completion of the diagnostic algorithm was constructed the way it was including having the denominator start at the reference laboratory as the diagnostic algorithm actually seems to start before then, i.e. in the Xpert laboratory. Results: Overall the results section was well constructed and clear. My main comment relates to the numbers and Figures 2 and 3 and the definition of having completed the diagnostic algorithm. For Figure 2 I am not 100% sure how you got the figure of 103 in the culture done box, should this be 107 (i.e. 4 plus 43 plus 21 plus 39)? If I follow the lines on all of the boxes that lead the culture done box I get 107 instead of 103. And I wondered why the people who are susceptible or who had culture are the only ones who are deemed eligible to have completed the algorithm? If there is resistance on FL LPA and then that person goes on to have the appropriate tests, they have also completed the algorithm haven’t they? In Figure 3 should there be a lone from the box results not available to the box culture done so that the total is 26 and not 24? I also wondered if your denominators should really be 1590 and 64 rather than the denominators that you have as this is where the algorithm starts. For Figure 3 I also wondered if the people who completed the algorithm should be the 14 who had SL LPA and then any additional people who had culture when it was indicated. I think the 9 people who were FQ and SLI susceptible are include in the numerator of 17 but if you are resistant doesn’t it also mean that you have completed the algorithm? Discussion: • Line 461: I think you should reference the “previous studies” referred to here and as a general comment I think there could be more use of other studies in the Discussion section as it mainly focuses on the findings of the study rather than comparing and contrasting with other literature from India, the region or elsewhere. There is one study mentioned in lines 461-463 but it is not clear what date this was and it is a study on EPTB so may not be directly comparable to your overall sample as the majority of your sample were PTB (although admittedly it does seem that EPTB samples were less likely to be referred to the reference laboratory). • I think it could be emphasized a bit more the loss of specimens going from the Xpert lab to the reference lab and the implications of this. I think you could also emphasise the losses for the RR cases as well as these are the very cases that you would want to know have completed the diagnostic algorithm. • Under the section on Strengths you talk about sensitivity and specificity of individual tests but you did not do this so I would recommend leaving this out Reviewer #3: Comments: The subject of the manuscript has merit and describes important findings related to Drugs resistant TB diagnostic algorithm under routine programme settings in India. The authors may address following queries to strengthen the manuscript. Major concerns: 1) Introduction- Introduction may need restructuring. - The first paragraph seems general and it discusses about prevention, diagnosis and treatment while the manuscript is only about diagnostic cascade. - Line 124-128: It describes about treatment success and its linkage to delay in diagnosis. This section could be mentioned in the discussion. 2) Methods: - Line 241: How were these ten districts selected for the study? Please provide some information. - The study mentions about gap in UDST, however the last steps of the algorithm is considered as Culture done. I wonder if it must end at DST level (for how many had DST was done). Though the operational definition mentions the algorithm finishes at culture done, the authors may want to describe about this concern in the manuscript. 3) Results: - Line 347-348: Please check if the total eligible for culture was 107 instead of 103. 4) Discussion: - Line 448-449: Since the integrated DR-TB diagnostic algorithm is specific for India, you may tone down the first statement. - Line 457-459 seems a repeat of the results, please review. - Line 489: when the authors mention about the delays, they may consider that availability of dates for SL-LPA was quite low. The claims could be toned down. Minor concerns: - Please update the references. For example, Line 105 must include the recent literature (Global TB Report 2019). - Line 167: no systematic assessment.. do we mean .. in India? If yes, you may want to mention this. - Line 199: change ‘…were transported..’ to ‘..are transported..’ - Line 200-202: This should be mentioned under the Programme implementation part of the Methods section. - Line 204-237: The integrated diagnostic algorithm: Can the authors summarize the section, as the same is described in the Figure 1. - Line 251- double entry and validation, wherever possible: please explain where it was carried out and where it was not possible. - Line 309: Were the key population mutually exclusive group. If someone was urban slum dweller and PLHIV, in which category they were considered? - Table 2: It is good to mention in the title of the table that 13 Xpert laboratories were included in the study - Line 461: Please add reference to the statement. - Line 474: In Methods it was mentioned that the NGO was working in all selected districts of study, please review and change the statement. END Reviewer #4: I wish to congratulate the authors on this very clear and helpful paper. It is a transparent analysis of an operational challenge in TB control, which will be of benefit to others working in the same field. I however do have a small number of concerns that I would suggest the authors address, before recommending this manuscript for publication: 1) This study on the performance of the UDST in Karnataka was conducted only a few months after its implementation (data from July-August, for a system implemented in April). Could the authors comment on whether the results are likely to be affected by the study being conducted in this early phase? Could there be "teething troubles" with the UDST, or conversely could there be an ambitious start, which then deteriorates over time? 2) In the same vein: the study was conducted only over 2 months (July-August) - do the authors anticipate any seasonality in the performance of the UDST? 3) The study hinges to a large extent on the matching algorithm that was used between database 1 and database 2, relying on the Nikshay number, phone number, and a name/age/sex match. This is a commendable effort, but it is not without risk. I would recommend that the authors report on how well the matching worked (which proportion was matched on Nikshay, which on phone number, etc.); possibly as supplemental material. Additionally, if I understand well, all entries in database 2 should have a corresponding match in database 1 (as no patients would end up directly at the reference lab) - any "unmatched" individuals in database 2 would therefore represent a measure of how many incorrect matchings resulted from the algorithm, and this may be worth reporting on. 4) Line 290-291: I am not entirely clear on the "exploratory approach" applied, and/or why *all* factors were included in the adjusted analysis. 5) While I appreciate the various ethics reviews done, I would suggest to expand on how patient confidentiality was protected, given the extensive use of phone numbers and names in this study. 6) Line 348-350 ("Thus, a total of 1106 (95%) of rifampicin-sensitive TB patients were considered to have completed the diagnostic algorithm.") is perhaps phrased a bit too optimistically, given that a large proportion of RS TB samples did not even show up at the reference lab. I would suggest correcting to "(...) of rifampicin-sensitive TB patients whose samples were successfully received at the reference laboratory were considered to have completed the diagnostic algorithm." Same comment for line 363-364. 7) On a minor note: one of the percentages in table 3 is incorrect (9.1 should read 91.4). 8) In the methods section the authors refer to "selected districts", and in the limitations to "selected laboratories". Could they clarify the selection process, and which criteria were used? ********** 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: No Reviewer #2: No Reviewer #3: No 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 to be viewed.] 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 us at figures@plos.org. Please note that Supporting Information files do not need this step. |
| Revision 1 |
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PONE-D-19-25977R1 Implementation of the new integrated algorithm for diagnosis of drug resistant tuberculosis in Karnataka State, India: How well are we doing? PLOS ONE Dear Dr. Shankar S, Thank you for submitting your manuscript to PLOS ONE. Its was re-reviewed by one of the initial reviewers who reiterated his/her criticisms and further revision is required based on the recommendations made by the reviewer. Please submit your revised manuscript by Nov 22 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:
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, Igor Mokrousov, Ph.D., D.Sc. Academic Editor PLOS ONE [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 #1: (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 #1: Partly ********** 3. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: I Don't Know ********** 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 #1: 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 #1: 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 #1: Comments: Thank you for the opportunity to review this revised manuscript. The authors have made changes to clarify statements in the paper and fix errors as recommended by the reviewers. However, the authors have declined to address issues raised by reviewers that would allow the reader to properly assess their findings and that would improve the manuscript overall, particularly in the methods, results and discussion. Major issues: 1. The rationale for including patient-level variables in the model was not included in the methods section as requested. As the manuscript is currently written, it remains unclear to the reader why these variables would confound the association between specimen-specific variables and ‘not reaching’. If they are being used as proxies for something related to the specimen then this information should be included in the methods section. If for example, the authors in their response to reviewers have identified that specimens are inherently different when collected from children and this may be associated with ‘not reaching’, then perhaps use broader age categories that have only 2 or 3 levels (children, adult, older adult age groups). Same for key population. These populations are not mutually exclusive and treating them as discrete populations is likely to create noise in the model and not provide a meaningful result. I suspect there are individuals that are HIV positive, reside in a slum and use tobacco. It is recommended that this variable be aggregated to a simple Yes/No of belonging to a key population. Please include in the methods the justification for including patient variables. It is understandable why key population would be associated with being tested, but once a specimen is collected the reason the specimen wouldn’t make it through the algorithm is not clearly outlined in the manuscript with respect to key population or other patient-centered variables. Please support where possible with references and explanation. While this may be the first such TB study in India there are many studies of other similar algorithms, diseases and/or populations from which to draw information from. Without clear rationale it will be assumed that this was the data available to the authors and so it was included in the model without any consideration of how to best incorporate it (appropriate levels within variables) and why it should be. 2. It was requested that model fitting information be reported. The authors declined to do this. Key practices of model building and validation, and reporting of results are required for reviewers and readers to assess the findings. It will be necessary to include: • Standard (ANOVA table) model output, either in the body of the paper or as supplementary materials. All statistics packages produces this as output. A table for each of the final models showing the estimate, SE, df, test statistic and p value for each term in the model. • Tests of model assumptions (e.g. tested for overdispersion and found…) 3. Typically, calculation of RR from a Poisson model should use robust error variance as the standard confidence intervals are not valid. Based on the information available regarding the models it is not clear if this was done. Please ensure the appropriate measure of variation was used and detail what was done in the methods section. 4. The authors should also address limitations of the models in the Discussion (e.g., no examination of interaction terms, possibility of low statistical power for some tests) Minor: 1. It was requested that the authors indicate if multiple specimens were included for individuals. Information regarding this was provided in the response but not incorporated into the manuscript. Please include this in the methods section to provide the reader with this pertinent info. 2. The number not reaching was not clear based on the figures and clarification of why this is was provided in the response to reviewers but not incorporated into the manuscript. A separate figure or inclusion of another cascade in either figure 2 or 3 would be helpful to make this clear to readers. In addition details regarding these 6 negative/indeterminate should be included prior to the “Overall, out of the total 1660 samples,” otherwise it is not clear why the numbers from the RS and RR do not add to the overall numbers. ********** 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 #1: 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". 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| Revision 2 |
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Implementation of the new integrated algorithm for diagnosis of drug resistant tuberculosis in Karnataka State, India: How well are we doing? PONE-D-19-25977R2 Dear Dr. Shankar S, 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, Igor Mokrousov, Ph.D., D.Sc. Academic Editor PLOS ONE Additional Editor Comments (optional): 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 #1: 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 #1: Yes ********** 3. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: 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 #1: 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 #1: 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 #1: (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 #1: No |
| Formally Accepted |
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PONE-D-19-25977R2 Implementation of the new integrated algorithm for diagnosis of drug-resistant tuberculosis in Karnataka State, India: How well are we doing? Dear Dr. Shankar S: I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department. If your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. 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. If we can help with anything else, please email us at plosone@plos.org. Thank you for submitting your work to PLOS ONE and supporting open access. Kind regards, PLOS ONE Editorial Office Staff on behalf of Dr Igor Mokrousov Academic Editor PLOS ONE |
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