PONE-D-24-55586Socioeconomic inequalities of 3-year survival in formal employees with colorectal cancer between 2012 and 2019 in ColombiaPLOS ONE

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2. Thank you for stating in your Funding Statement: 

DSS and GB were partially supported by a research grant from the NIHR GHPSR researcher-led grant NIHR150067, which used UK aid from the UK Government to support global health research. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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3. Thank you for stating the following in the Acknowledgments Section of your manuscript: 

We thank Colombia's Ministry of Health and Social Protection for providing the administrative databases that made this study possible. We also thank the Clinical Research Student Group at the Faculty of Medicine of the National University of Colombia for their valuable contributions. This study's preliminary findings were presented and discussed within this group, enriching the interpretation and scope of our results.

The School of Medicine at Universidad Nacional de Colombia supported the study. Additionally, this research was partially funded by the NIHR GHPSR researcher-led grant NIHR150067, which used UK aid from the UK Government to support global health research.

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DSS and GB were partially supported by a research grant from the NIHR GHPSR researcher-led grant NIHR150067, which used UK aid from the UK Government to support global health research. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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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: Partly

Reviewer #3: Partly

Reviewer #4: Partly

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

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

Reviewer #4: Yes

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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: Yes

Reviewer #2: Yes

Reviewer #3: Yes

Reviewer #4: No

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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

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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:  This manuscript evaluated the survival after a colorectal cancer diagnosis among formal employees among different wages strata as a proxy for socio-economic status.

The study is well conducted and statistically analysis well done.

I just have one question for the authors, why did you choose to stop the follow-up after 3 years for everyone instead of just following until the end of the death registry/last date of update of this registry? I would like to see the median and IQR of the follow-up time for deaths, to see if they occurred more close to the start of the follow-up or closer to the 3 years. It could be added to the table 1 I suppose.

I also noticed few typos (example figure 2 « quartil » instead of « quartile »).

Reviewer #2:  On line 87, the study's objective is described as assessing socioeconomic inequalities in three-year survival among formal workers with colorectal cancer. However, the study primarily outlines the socioeconomic characteristics of these patients, particularly income, age, sex, and place of residence in Colombia. It does not provide sufficient evidence to support the inference that the socioeconomic factors studied directly determine survival outcomes. The statistical analysis focuses on the association between income and survival, based on two outcomes: three-year survival or death. I suggest revising the objective to better align with the results, which are significant deserve emphasis. For example: "To analyze the association between income and survival in patients with colorectal cancer in a country with low socioeconomic development."

Regarding the geographic location in Colombia, the characteristics of the regions and the geographic barriers faced by each were not described. Without this context, it is unclear to the readers how these factors could influence the study results. Moreover, the functioning of the country's health system was not addressed. If the authors are referring to geographic barriers, more detail is needed, as these barriers can indeed affect access to care and may ultimately influence patient survival. However, the study does not provide specifics about the characteristics of these regions.

Additionally, in reference to the statement "Although administrative databases provide reliable data on healthcare utilization, they lack detailed clinical variables that could offer a more nuanced understanding of cancer characteristics," I believe that important clinical details, such as the type of cancer and its histopathology (which may indicate more aggressive lesions, leading to shorter survival), are not available. This is a crucial factor to consider when analyzing mortality.

Reviewer #3:  Using a retrospective cohort study, the authors look at socioeconomic inequalities in three-year survival of employees diagnosed with colorectal cancer in Colombia, 2012-2019. The paper reports that individuals in the highest quartile had a 25% lower risk of death than those in the lowest quartile, and concludes that significant income-related differences in colorectal cancer survival were observed among employees in the Colombian formal sector.

The research questions explored in this study – if repeated in a number of robust studies – can be of significance for the improvement of healthcare delivery and outcomes by providing insights and recommendations for healthcare practitioners and policymakers on necessary support processes, aligned with attainable patient-centered goals.

With that in mind, this reviewer has the following to remark:

1. Abstract

1.1 The text of this section can be improved.

1.2 The authors could consider adding a short background paragraph.

2. Methods

2.1 How did the authors address the possibility of selection bias and detection bias?

2.2 The authors mention that they used an artificial intelligence language model to enhance clarity and coherence.

It must be noted that the text appears to be in need of some editorial attention to improve readability. There seems to have been too much reliance on AI. It is evident from a number of observations, one of which is that the phrase “this study” was repeated many times.

While there are areas where AI can support academic writing, too much reliance may backfire. The use of AI must be coupled with an appropriate level of human oversight and control. It is advisable, therefore, that the authors edit/revise their manuscript to ensure its overall coherence.

3. Results & Discussion

3.1 Even though the authors have accounted for a number of potential confounding factors, there is always the possibility of residual confounding due to unmeasured or unknown factors.

Have the authors been mindful of the latter?

3.2 If so, why haven't they mentioned it in the discussion section?

3.3 The authors write, “Thus, while our findings are significant, they may underestimate the true extent of socioeconomic disparities in cancer outcomes across broader or more disadvantaged populations.”

This sentence may be perceived as a generalized statement – something that the authors need to avoid. Their study looked at colorectal cancer, not at cancer development in general. It is prudent to stick to the type of cancer the authors state to have examined.

I hope this review is helpful and wish the authors the very best with their research!

Reviewer #4:  Summary

The authors conducted a retrospective cohort study in Colombia to quantify the impact of social in-equailities on survival in colorectal cancer related deaths.

Major points

- While there's no problem of requiring patients to have multiple codes to confirm their eligibility to the study, indexing patients on a timepoint based on them meeting a condition in the future can be problematic and can open the door for immortal time bias. This is actually clear in the survival curve being flat at the beginning of the follow up. I recommend the authors to re-define the cohort entry date to be at the latest date in which the eligibility criteria was satisfied.

- Lines 143:152

- This goes into the first issue as well. It's not clear from the text whether these coavariates were measured during the follow-up or before the follow-up. Based on the text, the follow-up started from the first occurrence of the cancer identification algorithm code. This means that many of those covariates might've been measured during the follow-up, which can lead to overadjutment due to adjustment for potential mediators.

- I am wondering whether the exposure variable was turned into quartiles based on the dataset for analysis or other outside resource. The issue of relying on the data is that such classification scheme is highly arbitrary and might not lead to good replication in other studies. I would recommend the authors to rely on previous literature to define the bounadries of their exposure variable classes.

- Why didn't the authors adjust for healthcare utilization and concurrent medications?

- Another source of concern is that secondary type of exposure that the authors used to show social inequality. After we saw non-significant difference in HRs across different income categories with a straightforward exposure (MMW), the authors resorted to two indices to show that indeed inequality exists. The authors need to provide a clear justification in the switch of their choice of the exposure. Do they believe these indices are more reflective of social inequality? What is the evidence for this?

Minor points

- Is 'formal employee' the same thing as government employee?

- Line 169 needs a citation.

- In the flowchart, I am wondering if the numbers in the very first boxes represent records or patients. I understand that patient can have multiple records. For this flowchart, the authors should be consistent and should report numbers related to the patients not records.

- In table 2, the comma of the hazard ratios should be corrected to a decimal point.

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Reviewer #1: No

Reviewer #2: Yes:  NAIDHIA ALVES SOARES FERREIRA

Reviewer #3: No

Reviewer #4: No

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Socioeconomic inequalities of 3-year survival in formal employees with colorectal cancer between 2012 and 2019 in Colombia

PONE-D-24-55586R1

Dear Dr. Sánchez-Santiesteban,

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

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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

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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

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

Reviewer #1: Yes

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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

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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

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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: Thanks for taking in account all reviewers's comments, great work was done to address all of them. I do not have further comments.

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Reviewer #1: No

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