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Article
Peer-Review Record

Knowledge and Beliefs about Clinical Trials among Adults in Poland: A Cross-Sectional Study

Clin. Pract. 2024, 14(4), 1285-1295; https://doi.org/10.3390/clinpract14040104
by Natalia Cięszczyk 1,*, Marcin Czech 2, Łukasz Pronicki 1 and Mariusz Gujski 1
Reviewer 1: Anonymous
Reviewer 2: Anonymous
Reviewer 4: Anonymous
Clin. Pract. 2024, 14(4), 1285-1295; https://doi.org/10.3390/clinpract14040104
Submission received: 13 April 2024 / Revised: 24 June 2024 / Accepted: 28 June 2024 / Published: 2 July 2024

Round 1

Reviewer 1 Report (Previous Reviewer 2)

Comments and Suggestions for Authors

The authors have done an excellent job on this revised version of the paper. 

 

Just one comment for the record. 

Authors should replace “N” with “n” whenever referring to their sample. “N” is used to represent a population and “n” a sample, so it is more appropriate to use “n” throughout the manuscript (from the abstract to the discussion). For example, “Slightly more women (N = 568, 52.6%) than men (N = 511, 47.4%) took part in the study.” should be “Slightly more women (n = 568, 52.6%) than men (n = 511, 47.4%) took part in the study.” 

Author Response

Thank you very much for taking the time to review this manuscript. Below is the response to the comment submitted:  All "N" have been replaced with "n" throughout the manuscript (from the abstract to the discussion).

Reviewer 2 Report (New Reviewer)

Comments and Suggestions for Authors

The manuscript entitled “Knowledge and beliefs of clinical trials among adults in Poland” focuses on the assessment of public awareness of and opinions on clinical trials in Poland, as well as the wish to know more about clinical trials. The manuscript is very interesting and may be important for the medical community to adopt new strategies to improve patients’ knowledge and explain some misconceptions regarding clinical trials. To improve the current version of the manuscript, please refer to my comments below.

 

> In section 2.3, "Probably not" and "Hard to say" seem quite similar responses. Could be the reason why, in Table 2, the results are almost the same for both the answers. How did the authors define these answers? Did the preliminary questionnaire in a limited population help refining these answers with the responders’ feedback?

> In section 2.4, the authors should specify what test was used and include a citation.

> In Table 1, consider substituting “55 and more” by “55”.

> In Figure 1, did the authors asked the participants to specify the “Other” option, that accounts for 2.4%?

> In the Discussion section, the authors refer that “The differences in results between that and the current survey can be understood in the context of the passage of time.” Could the massive exposure of people to the COVID-19 vaccine development process, including clinical trials, have contributed to the increased awareness between 2018 and now? Please comment and add more information in the manuscript if you find it appropriate.

> "No other treatment is available" is very restrictive. If there were other available treatments, the response could be very different. Could the authors comment on this? Also, the authors compared the results with those of US reference [28]. Here, Schupmann and colleagues considered the “No other treatment/option is available” in Table 4. Have the authors considered this factor?

> In lines 322-325,  the phrase “Authors should discuss the results and how they can be interpreted from the perspective of previous studies and of the working hypotheses. The findings and their implications should be discussed in the broadest context possible. Future research directions may also be highlighted.” Is from MDPI’s template. Please remove it.

> Please revise the “Data Availability Statement”. Currently, it contains the MDPI’s template sentences.

> In the references list, please include the website when appropriate [2-6, 19, 31]. Reference [22] is quite vague. Please include more information. Also, references 12 and 14 are the same. Please, correct accordingly.

Comments on the Quality of English Language

English grammar requires revision.

Author Response

We sincerely thank you for your time and careful review of our manuscript. We appreciate your insightful review and valuable comments, which will certainly contribute to the further improvement of our scientific work. Below are detailed responses to your comments and the corrections made, which we hope will meet your expectations. Once again, we sincerely thank you for your constructive help and involvement in the process of improving our article.

 

Comments 1: In section 2.3, "Probably not" and "Hard to say" seem quite similar responses. Could be the reason why, in Table 2, the results are almost the same for both the answers. How did the authors define these answers? Did the preliminary questionnaire in a limited population help refining these answers with the responders’ feedback?

Response 1:  Thank you for bringing this issue to our attention. The questionnaire was developed based on an analysis of the results of previous studies and scientific literature related to the topic of our survey. The first version of the questionnaire was tested on a smaller group of people, which allowed us to examine respondents' reactions and make any adjustments before conducting the full survey.

In the first questionnaire, some respondents expressed difficulty in answering, marking "Hard to say." This was likely due to their limited knowledge and awareness of clinical trials, which prevented them from clearly stating their preferences. Our goal was also to explore how many people are unable to choose a clear answer, which may be important in the context of planning further educational and outreach activities on clinical trials.

It is worth noting that the answers "Probably not" and "Hard to say" were differentiated and defined in the questionnaire. The answer "Probably not" referred to the situation when the respondent was not convinced about clinical trials or had personal objections, while "Hard to say" meant the inability to clearly define the answer due to lack of sufficient knowledge or experience in the topic. This difference was taken into account in our survey to better understand respondents' motivations and limitations.

 

Comments 2: In section 2.4, the authors should specify what test was used and include a citation.

Response 2: In Section 2.4, we used the Spearman test (denoted by ρ) to examine correlations between variables. The significance of these correlations was assessed using a p-value based on Hollander and Wolfe's method. To account for multiple comparisons, we applied the Benjamini-Hochberg correction to the p-value. We considered a relationship to be significant when the p-value was less than 0.05. The analysis was carried out in the R language environment.

 

Comments 3: In Table 1, consider substituting “55 and more” by “≥ 55”.

Response 3: Thank you very much. The change has been made as suggested.

 

Comments 4: In Figure 1, did the authors asked the participants to specify the “Other” option, that accounts for 2.4%?

Response 4: In the questionnaire, we did not ask participants to specify the "Other" option, which accounts for 2.4%. The questionnaire contained only closed questions, there were no open questions.

 

Comments 5: In the Discussion section, the authors refer that “The differences in results between that and the current survey can be understood in the context of the passage of time.” Could the massive exposure of people to the COVID-19 vaccine development process, including clinical trials, have contributed to the increased awareness between 2018 and now? Please comment and add more information in the manuscript if you find it appropriate.

Response 5: Thank you very much for this comment. We fully agree with it. We have added a sentence to the article in the discussion section (pp. 7 lines 219-225): It is noteworthy that the mass public exposure to the COVID-19 vaccine development process, including clinical trials related to its efficacy and safety, may have significantly increased awareness of clinical trials among people. Since 2018, and especially over the past few years, the COVID-19 pandemic has become a major topic of discussion around the world, leading to increased public attention to research processes, including the clinical trial stage, as a key element in drug and vaccine development.

 

Comments 6: "No other treatment is available" is very restrictive. If there were other available treatments, the response could be very different. Could the authors comment on this? Also, the authors compared the results with those of US reference [28]. Here, Schupmann and colleagues considered the “No other treatment/option is available” in Table 4. Have the authors considered this factor?

Response 6: In Poland, it is often said that clinical trials are often seen as therapies of last resort, especially when other treatment options are exhausted or ineffective. Our aim was to explore parents' attitudes toward their children's participation in clinical trials when other treatment options are limited or ineffective. We also considered the “No other treatment/option is available”.

 

Comments 7: In lines 322-325,  the phrase “Authors should discuss the results and how they can be interpreted from the perspective of previous studies and of the working hypotheses. The findings and their implications should be discussed in the broadest context possible. Future research directions may also be highlighted.” Is from MDPI’s template. Please remove it.

Response 7: The indicated sentence has been deleted.

 

Comments 8: Please revise the “Data Availability Statement”. Currently, it contains the MDPI’s template sentences.

Response 8: The data availability statement has been changed to: The datasets used and/or analyzed during the current study are available from the correspondent author upon reasonable request.

 

Comments 9: In the references list, please include the website when appropriate [2-6, 19, 31]. Reference [22] is quite vague. Please include more information. Also, references 12 and 14 are the same. Please, correct accordingly.

Response 9: Thank you very much for these suggestions. The bibliography has been corrected according to the comment.

 

Comments 10: English grammar requires revision.

Response 10: The article has been re-checked for linguistic correctness.

 

 

 

Reviewer 3 Report (New Reviewer)

Comments and Suggestions for Authors

The manuscript titled "Knowledge and beliefs of clinical trials among adults in Poland" has been submitted to the Journal Clinics and Practice.

 

The objective of this study was to evaluate the understanding and attitudes of Polish individuals toward clinical trials. Findings reveal that Poles generally perceive their knowledge about clinical trials as limited and express a desire to enhance their understanding.

 

While the manuscript addresses a compelling issue, there are several concerns regarding the study.

 

Title: Include the type of study.

 

Abstract

The conclusions should focus on the results found. More emphasis should be placed on the conclusions and fewer recommendations should be included.

 

Keywords: Please ensure that all of them correspond to MeSH terms.

 

Introduction

References 8 and 9 are outdated and do not exactly correspond to the context of the study. Please review them.

The authors should detail the motivation that led them to conduct a study on this topic when a similar one was conducted in 2018 (reference 15). They should indicate the added value of this study compared to the previous one conducted in the same population.

 

Methods

- Lines 69-72. The objectives have already been described. Please revise.

- The authors describe in line 73 'we decided to conduct the survey on a group representing the Polish population.' How do the authors ensure that the sample is representative? The authors should detail the type of sampling performed, preferably by adding a sample size calculation.

- Line 121: Indicate the exact number of individuals.

- In the "Questionnaire Development" section, the process of validation and structuring of the questionnaire should be described in more detail. Please review relevant articles on this topic.

- Line 130: Indicate the statistical test used to determine the normal distribution of the data.

 

Results

- Please indicate the response rate.

 

Discussion

-Another limitation of the study could have been the response rate. However, this data is not provided in the results.

 

-As the validation and structuring of the questionnaire were not described, it could be another limitation.

-Recommendations and perspectives on this topic in the studied population should be added.

 

 

 

 

Comments on the Quality of English Language

moderate editing

Author Response

We sincerely thank you for your time and careful review of our manuscript. We appreciate your insightful review and valuable comments, which will certainly contribute to the further improvement of our scientific work. Below are detailed responses to your comments and the corrections made, which we hope will meet your expectations. Once again, we sincerely thank you for your constructive help and involvement in the process of improving our article.

Comments 1: Title: Include the type of study.

Response 1:  The title of the study was changed to “Survey Study: Knowledge and beliefs of clinical trials among adults in Poland”.

Comments 2: Abstract: The conclusions should focus on the results found. More emphasis should be placed on the conclusions and fewer recommendations should be included.

Response 2: Thank you very much for this comment. The abstract describes the most important results from the study.

 

Comments 3: Keywords: Please ensure that all of them correspond to MeSH terms.

Response 3: All keywords correspond to MeSH terms.

 

Comments 4: Introduction: References 8 and 9 are outdated and do not exactly correspond to the context of the study. Please review them. The authors should detail the motivation that led them to conduct a study on this topic when a similar one was conducted in 2018 (reference 15). They should indicate the added value of this study compared to the previous one conducted in the same population.

Response 4: Thank you very much for your comment. We have reviewed references 8 and 9, and upon careful examination, we have determined that they are appropriately cited and relevant to the context of our study. As for reference number 15, the massive public exposure to the COVID-19 vaccine development process, including clinical trials related to its efficacy and safety, may have greatly increased people's awareness of clinical trials. Since 2018, and especially over the past few years, the COVID-19 pandemic has become a major topic of discussion around the world, leading to increased public attention to research processes, including the clinical trial stage, as a key component of drug and vaccine development. A description of this situation has been added on page No. 7 lines 222-228.

 

Comments 5: Methods

Lines 69-72. The objectives have already been described. Please revise.

Response 5: The repetition has been removed.

 

Comments 6: Methods

The authors describe in line 73 'we decided to conduct the survey on a group representing the Polish population.' How do the authors ensure that the sample is representative? The authors should detail the type of sampling performed, preferably by adding a sample size calculation.

Response 6: A representative group of Poles was determined by Adriana, a company experienced in conducting surveys. Ariadna is an independent national research panel for implementation. Ariadna provides researchers with the ability to conduct nationwide research, including surveys and experiments, to the highest standards of accuracy and reliability. During the research, the Ariadna panel was the holder of a current certificate of the Interviewer Quality Control Programme, which is evidence of the high quality of the research services offered and is issued based on annual inde-pendent audits conducted by the Polish Association of Researchers in Public Opinion and Marketing.

 

Comments 7: Methods

Line 121: Indicate the exact number of individuals.

Response 7: The article was supplemented with the exact number of people, which is 43.

 

Comments 8: Methods

In the "Questionnaire Development" section, the process of validation and structuring of the questionnaire should be described in more detail. Please review relevant articles on this topic.

Response 8: A more detailed description of the questionnaire validation and structuring process has been added to the article, page 3, lines 111-125.

 

Comments 9: Methods

Line 130: Indicate the statistical test used to determine the normal distribution of the data.

Response 9: added. The analysis was carried out in the R language environment.

 

Comments 10: Results

Please indicate the response rate.

Response 10: We received no such information from Ariadna. We know that some dozen people have been excluded due to “clipping the survey”.

 

Comments 11: Discussion

Another limitation of the study could have been the response rate. However, this data is not provided in the results.

Response 11: That’s true, but we do not have data on the response rate.

 

Comments 12: As the validation and structuring of the questionnaire were not described, it could be another limitation.

Response 12: The article completes the description of the validation and structure of the questionnaire.

 

Comments 13:Recommendations and perspectives on this topic in the studied population should be added.

Response 13: Recommendations and perspectives have been added to the article: It seems appropriate to conduct an information campaign to raise public awareness of clinical trials. These activities should be carried out with the support of the media, health care institutions and patient organizations, which will allow for a wide reach and effectiveness of the message. The implementation of these activities has the potential to significantly contribute to increasing Poles' knowledge of clinical trials, which in the long run is crucial for the development of new, effective therapies. (page 10, lines 357-363).

 

Comments 14: moderate editing of English

Response 10: The article has been re-checked for linguistic correctness.

 

 

Reviewer 4 Report (New Reviewer)

Comments and Suggestions for Authors

Overall, this is an important and interesting topic.

Minor comments:

The background section needs to be expanded.
Summarizing the methods section in a table/chart would be helpful.
Please expand the statistical analysis section with detailed information.

Comments on the Quality of English Language

This manuscript has a few grammatical and punctuation errors and needs to be corrected.

Author Response

We sincerely thank you for your time and careful review of our manuscript. We appreciate your insightful review and valuable comments, which will certainly contribute to the further improvement of our scientific work. Below are detailed responses to your comments and the corrections made, which we hope will meet your expectations. Once again, we sincerely thank you for your constructive help and involvement in the process of improving our article.

Comments 1: The background section needs to be expanded.

Response 1: The background section has been completed, p. 1, lines 11-15.

 

Comments 2: Summarizing the methods section in a table/chart would be helpful.

Response 2: Added summary of methods in Table 1, page 4.

 

Comments 3: Please expand the statistical analysis section with detailed information.

Response 3: The description has been completed p. 3 lines 146-150.

 

 

Round 2

Reviewer 3 Report (New Reviewer)

Comments and Suggestions for Authors

After reviewing the manuscript again, it is evident that the authors did not follow the recommendations, and additionally, new, and very concerning shortcomings have emerged.

 

Title: Studies are classified into observational and experimental, and within them, there are further sub-classifications. Please revise.

 

 

Abstract

The conclusions should focus on the results found. More emphasis should be placed on the conclusions and fewer recommendations should be included.

 

 

Methods

- The authors describe 'we decided to conduct the survey on a group representing the Polish population.' How do the authors ensure that the sample is representative? The authors should detail the type of sampling performed, preferably by adding a sample size calculation.

 

The company "Adriana" must provide this information, which is essential to ensure the representativeness of the population.

 

 

-Indicate the statistical test used to determine the normal distribution of the data.

 

The authors described the statistical package used. The question refers to the test employed.

 

Results

- Please indicate the response rate.

 

This data is crucial and should be requested from the responsible government entity.

 

Discussion

-Another limitation of the study could have been the response rate. However, this data is not provided in the results.

 

This data is crucial and should be requested from the responsible government entity.

 

The recommendations and perspectives should be located at the end of the discussion.

Comments on the Quality of English Language

minor

Author Response

We sincerely thank you for your time and careful review of our manuscript. We appreciate your insightful review and valuable comments, which will certainly contribute to the further improvement of our scientific work. Below are detailed responses to your comments and the corrections made, which we hope will meet your expectations. Once again, we sincerely thank you for your constructive help and involvement in the process of improving our article.

 

Comments 1: Title: Studies are classified into observational and experimental, and within them, there are further sub-classifications. Please revise.

Response 1: The title of the study has been revised to: Cross-sectional observational study: Knowledge and beliefs about clinical trials among adults in Poland.   

Comments 2: Abstract: The conclusions should focus on the results found. More emphasis should be placed on the conclusions and fewer recommendations should be included.

Response 2: The abstract has reduced the number of recommendations, focusing on the results obtained (lines 14-28).

 

Comments 3: Methods: The authors describe 'we decided to conduct the survey on a group representing the Polish population.' How do the authors ensure that the sample is representative? The authors should detail the type of sampling performed, preferably by adding a sample size calculation. The company "Adriana" must provide this information, which is essential to ensure the representativeness of the population.

Response 3: The survey was conducted on a nationwide random-quota sample of n=1079 people aged 18 and over, where the totals were selected according to population representation for the variables gender (2 categories) * age (5 categories) * size of place of residence (5 categories), i.e. a total of 50 strata. Structure assumptions according to the Central Statistical Office in Poland. The group in study has a similar structure regarding age, education and living location as the general Polish population. The purpose of the study is to describe general trends in Poland. Selected group is larger than expected for any binary test. For example, the sample size needed to achieve a margin of error of ±5% with 95% confidence rarely exceeds 400 for any population size larger than 20,000, assuming a 50/50 split in a binary outcome.

Comments 4: Indicate the statistical test used to determine the normal distribution of the data.

The authors described the statistical package used. The question refers to the test employed.

Response 4: We did not assume normal (or any other) distribution in structure of responses due to lack of data for such assumption. Testing for normal distribution may be troublesome in such cases (see e.g., F.E. Harrell Regression Modeling Strategies for further references). Tests used in the analysis are non-parametric and do not need normal distribution to be effective.

 

Comments 5: Results: Please indicate the response rate. This data is crucial and should be requested from the responsible government entity.

Response 5: Below are the full figures for the response rate, which was 26.04%:

- invitations sent - 7330

- completed questionnaires - 1079

- discontinued surveys (pauses) - 287

- completed questionnaires (demographic cells completed) - 517

- persons excluded due to questionnaire ‘clipping’ - 17

- persons removed at collection cleaning level - 9

Response rate information has been added to the article (lines 145-147).

 

Comments 6: Discussion: Another limitation of the study could have been the response rate. However, this data is not provided in the results. This data is crucial and should be requested from the responsible government entity.

Response 6: Information has been added about the response rate, which may be a limitation of the survey (lines 353-357).

 

Comments 7: The recommendations and perspectives should be located at the end of the discussion.

Response 7: Recommendations and perspectives were added at the end of the discussion (lines 322-334).

 

Comments 8: Minor editing of English

Response 8: The article has been re-checked for linguistic correctness.

 

 

 

 

 

 

 

Round 3

Reviewer 3 Report (New Reviewer)

Comments and Suggestions for Authors

There are still three aspects that need to be reviewed, two minor issues and one of greater concern.

 

1.        The study design is always presented at the end of the title.

2.        Everything described by the authors in response 4 must be detailed in the respective section.

3.        The study referenced by the authors to support the low response rate of their study is misinterpreted. The low response rate of 20-25% does not correspond directly to the provided reference but to a reference within that study's introduction (Fosnacht, K., Sarraf, S., Howe, E., & Peck, L. K. (2017). How important are high response rates for college surveys? The Review of Higher Education, 40(2), 245–265. https://doi.org/10.1353/rhe.2017.0003). Furthermore, it is indicated there that such a low response rate is possible for surveys with small samples (fewer than 500), which is not the case for the study under review in this journal. This indicates that the authors are attempting to justify their shortcomings with incorrect data, failing to account for the responsibility we have as researchers to present accurate data. The referenced meta-analysis actually recommends a response rate of at least 44%, which is described as reasonable and is far from what was obtained in the current study.

Comments on the Quality of English Language

moderate

Author Response

We sincerely thank you for your time and careful review of our manuscript. We appreciate your insightful review and valuable comments, which will certainly contribute to the further improvement of our scientific work. Below are detailed responses to your comments and the corrections made, which we hope will meet your expectations. Once again, we sincerely thank you for your constructive help and involvement in the process of improving our article.

Comments 1: The study design is always presented at the end of the title.

Response 1: The title has been changed so that the study design is at the end of the article.

Comments 2: Everything described by the authors in response 4 must be detailed in the respective section.

Response 2: Added information that was described in response number 4. (lines 142-144).

 

Comments 3: The study referenced by the authors to support the low response rate of their study is misinterpreted. The low response rate of 20-25% does not correspond directly to the provided reference but to a reference within that study's introduction (Fosnacht, K., Sarraf, S., Howe, E., & Peck, L. K. (2017). How important are high response rates for college surveys? The Review of Higher Education, 40(2), 245–265. https://doi.org/10.1353/rhe.2017.0003). Furthermore, it is indicated there that such a low response rate is possible for surveys with small samples (fewer than 500), which is not the case for the study under review in this journal. This indicates that the authors are attempting to justify their shortcomings with incorrect data, failing to account for the responsibility we have as researchers to present accurate data. The referenced meta-analysis actually recommends a response rate of at least 44%, which is described as reasonable and is far from what was obtained in the current study.

Response 3: We respect the Professor's assignment and have no influence on the response rate. We are not trying to justify the level of this indicator. The data were collected fairly and correctly. We only left the response rate within the limits of the survey (lines 355-356).

 

 

 

 

 

 

 

 

 

 

Round 4

Reviewer 3 Report (New Reviewer)

Comments and Suggestions for Authors

Additional comments:

1. The correct term is: a cross-sectional study.

2. Everything described in point 4 of the second revision was not fully incorporated into this new version as indicated.

3. The pages indicated by the authors (355-356) do not describe anything about the low response rate. Additionally, the response is incomprehensible. Such a low response rate does not reflect a high-quality study. 

Comments on the Quality of English Language

minor

Author Response

Comments 1: The correct term is: a cross-sectional study.

Response 1: Thank you, the title has been completed, Knowledge and beliefs about clinical trials among adults in Poland: a cross-sectional study

 

Comments 2: Everything described in point 4 of the second revision was not fully incorporated into this new version as indicated.

Response 2: The description has been completed p.3 lines 146-150.

 

Comments 3: The pages indicated by the authors (355-356) do not describe anything about the low response rate. Additionally, the response is incomprehensible. Such a low response rate does not reflect a high-quality study.

Response 3: The data was collected fairly and correctly. We have no influence on the response rate.  The study used a random sample rather than a perceptual sample. Thanks to the random sample, we also avoided selection bias in the people selected for the study. The text has been completed, p. 10, lines 367-368.

 

 

This manuscript is a resubmission of an earlier submission. The following is a list of the peer review reports and author responses from that submission.


Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

 

Dear authors,

although it is a work designed and that complies with ethical principles.

I consider that the work presents a lack of originality and significance. The review needs to be improved, highlighting the need for this study. The objective of the study must be presented clearly.

Was a sample size calculation carried out?

 

What theory or model have the authors based on to design the questionnaire? 

Methodological risks make it difficult to understand the results.

 

 

Comments on the Quality of English Language

 Minor editing of English language required

Reviewer 2 Report

Comments and Suggestions for Authors

General comment

The manuscript aimed to assess the knowledge and beliefs of Polish adults about clinical trials. The findings are interesting and important for drawing up new strategies for attracting volunteers for clinical trials in Poland. I suggest some changes to the text to improve the quality of the study report. I encourage the authors to reflect on the questionnaires.  

 

Specific comments 

Abstract 

- Page 1, line 8. Correct "Abstract: Background:".

- Page 1, lines 14-22. Standardize the information in "n (%)". Presenting only the percentage needs to be clarified. 

- Page 1, line 12. Add the name of the external company. 

- Page 1, lines 13-14. Add the mean age and standard deviation for age. Use the format mean(sd).

 

Introduction 

- Page 2, lines 61-62. The authors could make the aim of the study clearer. Suggestion: "Therefore, this study aims to assess the knowledge and beliefs about clinical trials among Polish adults."

 

Materials and Methods 

- Page 2, line 66. The information on this line should be in a subsection entitled "Ethical Aspects". In addition, add the full name of the institution that approved the study (as described at the end of the document in the "Institutional Review Board Statement") and the registration number of the study protocol. It should also be made clear how the participants' consent was obtained. 

- Page 2, line 70. According to STROBE (Strengthening the Reporting of Observational Studies in Epidemiology), the number of individuals included should appear in the "Results" section.

- Was there a sample size calculation? If so, this should be included in the "Materials and Methods" section.

- Page 2, line 81. gender or sex? 

- Page 2, line 83. the authors need to make clear the name of the "external company" and its role in this study. 

- Page 3, line 106 What software was used to conduct the statistical analysis? This information should be added. 

 

Results

- Page 3, line 109. The authors should state how many invitations were sent out, how many were excluded, and the reasons for this. To make the process of composing this sample clearer, the authors could add a flowchart.

- Page 3, line 110. The authors state in the Statistical analysis that they will present the mean and standard deviation. This information should be provided for the age measure. Suggested format: mean (SD).

- Table 1: Using two categories with the same name and two different definitions for the medium town and larger city needs to be clarified and clarified. Perhaps adopting terms such as "Medium town upper" and "Medium town lower" would help with this definition. In addition, the information on the number of inhabitants for each classification of this variable is better placed at the bottom of the table and not within it. 

- Table 2. Numbers with decimal places are written with "," but in English, they should be reported with ".". For example, it's not "27,2" but "27.2".

- All tables. Authors should standardize the number of decimal places. There is information with none and others with one decimal place.

- Page 6, lines 165-166. This paragraph is extremely short, and it should be incorporated into the previous paragraph.

 

Discussion 

- The first paragraph of this section should be a summary of the main findings of this study. 

- The authors should add the strengths and limitations of the study. 

 

Comments on the Quality of English Language

Minor editing of English language required.

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