Global Trends in Risk Factors and Therapeutic Interventions for People with Diabetes and Cardiovascular Disease: Results from the WHO International Clinical Trials Registry Platform

Round 1

Reviewer 1 Report

The authors performed an interesting comprehensive analysis of clinical trial data on global trends in risk factors associated with diabetes and CVD providing valuable insights into the state of research in this critical area of public health concern.  The authors highligheted that the diversity in trial registration and recruitment patterns is noteworthy.

The study is well performed and described. My suggestion is to modify the legends of the axes in all figures: it should be written with a bigger font since they are hardly comprehensible sometimes.

1. The main purpose of this study is to highlight the importance of the International Clinical Trials Registry Platform (ICTRP) as the source of data for clinical trials targeting metabolic syndrome, CVDs, and T2D and the growing recognition of diverse intervention strategies to address this critical global health concern.

2. The topic can be considered original since it consists in a comprehensive analysis of data on clinical trials reporting on the global trends in CVD-risk in people with diabetes. This methodology could be used to describe other pathologies around the world.

3. This study analyses clinical data from registries across the globe, making a general overview of the pathology described. It summarizes all the other materials published before.

4. The methodology is well explained and clearly comprehensible.

5. The conclusions are consistent with the evidence and the arguments presented. The analysis of clinical trial data from the ICTRP provides a comprehensive overview of research trends in CVD risk among individuals with diabetes.

6. I confirm that the references are appropriate.

7. The text in the figures should be enlarged to be more readable.

Author Response

The authors performed an interesting comprehensive analysis of clinical trial data on global trends in risk factors associated with diabetes and CVD providing valuable insights into the state of research in this critical area of public health concern.  The authors highligheted that the diversity in trial registration and recruitment patterns is noteworthy.

We appreciate the time the reviewer to assess our manuscript. We also appreciate the positive comments.

The study is well performed and described. My suggestion is to modify the legends of the axes in all figures: it should be written with a bigger font since they are hardly comprehensible sometimes.

Thank you for this important comment. As suggested by the reviewer, we have now modified the figure captions, to be bigger/clear to the reader.

1. The main purpose of this study is to highlight the importance of the International Clinical Trials Registry Platform (ICTRP) as the source of data for clinical trials targeting metabolic syndrome, CVDs, and T2D and the growing recognition of diverse intervention strategies to address this critical global health concern.

We appreciate this positive comment from the reviewer, emphasis on such statement has been highlighted within the introduction, to be also clear to the reader.

2. The topic can be considered original since it consists in a comprehensive analysis of data on clinical trials reporting on the global trends in CVD-risk in people with diabetes. This methodology could be used to describe other pathologies around the world.

We appreciate the positive response from the reviewer. We agree, this methodology could be applied to describe other pathologies around the world, as has been reported through growing number of papers.

3. This study analyses clinical data from registries across the globe, making a general overview of the pathology described. It summarizes all the other materials published before.

We appreciate this positive comment from the reviewer.

4. The methodology is well explained and clearly comprehensible.

We appreciate this positive comment from the reviewer.

5. The conclusions are consistent with the evidence and the arguments presented. The analysis of clinical trial data from the ICTRP provides a comprehensive overview of research trends in CVD risk among individuals with diabetes.

We appreciate this positive comment from the reviewer.

6. I confirm that the references are appropriate.

We appreciate this positive comment from the reviewer.

7. The text in the figures should be enlarged to be more readable.

We appreciate this positive comment from the reviewer, we have enlarged figure captions to be more readable.

Reviewer 2 Report

While I find this article interesting, it is necessary for the authors to adhere rigorously to these major revisions in order for this article to be published:

Keywords:

-       Some keywords are repeated in the title of the article. I strongly recommend to remove them and look for other key words that help to search this article better to give it a better transfer.

Introduction:

-       The objectives of the study are not stated, nor are the hypotheses. The authors are kindly requested to include them as they are the most important part of the study.

Methodology.

-       The methodology is very scarce, not even the statistical analysis appears.

Discussion:

-       The discussion looks very poor, it should include more articles that reinforce or contradict its results as well as the possible reasons for similarity and/or discrepancy supported by scientific evidence. It should also include the practical implications and future lines of study derived from this study.

Author Response

While I find this article interesting, it is necessary for the authors to adhere rigorously to these major revisions in order for this article to be published:

We appreciate the time the reviewer to assess our manuscript, especially the constructive comments that have significantly enhance the quality of our manuscript. Comments concerning the introduction, validity of the methodology, and discussion have been addressed, while citing accurately as recommended by the reviewer. Changes are highlighted using track changes through the manuscript, to be clear to the reviewer. We hope you find the revised version of our manuscript improved, and acceptable at its current state.

Keywords:

Some keywords are repeated in the title of the article. I strongly recommend to remove them and look for other key words that help to search this article better to give it a better transfer.

We appreciate this important comment from the reviewer. As such, we have revised the keywords, to be not repetitive to what is mentioned within the title.

Introduction:

The objectives of the study are not stated, nor are the hypotheses. The authors are kindly requested to include them as they are the most important part of the study.

Thank you for this important comment. Please note, we have revised the last paragraph of the introduction manuscript to clearly indicate the study objectives.

Methodology.

The methodology is very scarce, not even the statistical analysis appears.

Thank you for this important comment. Please note, we have revised the methodology to be more informative, while citing relevant research that has been conducted to verify the use of the International Clinical Trials Registry Platform (ICTRP) to inform to access clinical trials of diverse pathologies that highlight the global health concerns. Because this an analysis of global trends in clinical data (as stated on the manuscript title) and the heterogenous nature of analyzed data, the statistical analysis could not be performed. However, where relevant, numbers/percentages for reported findings are added to provide quantitative value of results. The lack of statistical analysis has also been highlighted as part of the limitations for this report.

Discussion:

The discussion looks very poor, it should include more articles that reinforce or contradict its results as well as the possible reasons for similarity and/or discrepancy supported by scientific evidence. It should also include the practical implications and future lines of study derived from this study.

We appreciate this critical response from the reviewer. Please note, we have added more conversations, including relevant citations to strengthen the discussion. Modifications are highlighted using track changes throughout the discussion section.

Reviewer 3 Report

This research is the identification of trends, patterns, and emerging insights in the field of metabolic diseases. The topic is original and relevant to the field. It addresses a specific gap in the field. The growing recognition of the significance of CVD risk in individuals with diabetes and the urgent need for research in this field. This report addresses a broad spectrum of metabolic complications characterized- ing the metabolic syndrome. But it lacks clinical data from developing nations.

Also, the biomarkers such as blood lipid profiles and glucose levels are insufficient indicators for CVD risk. Cholesterol efflux capacity could be a better marker.

intervention for pediatric and elderly populations would add more benefit to this study.

It is better to read by a native English person.

Author Response

This research is the identification of trends, patterns, and emerging insights in the field of metabolic diseases. The topic is original and relevant to the field. It addresses a specific gap in the field. The growing recognition of the significance of CVD risk in individuals with diabetes and the urgent need for research in this field. This report addresses a broad spectrum of metabolic complications characterizeding the metabolic syndrome. But it lacks clinical data from developing nations.

We appreciate the time the reviewer to assess our manuscript, especially the constructive comments that have significantly enhance the quality of our manuscript. Critical comments raised by the reviewer, especially the validity of biomarkers for CVD-risk and lack of data informing on pediatric populations, have been addressed. In fact, some limitations from analysed data have been acknowledged and made clear to the reader. We hope you find the revised version of our manuscript improved, and acceptable at its current state.

Also, the biomarkers such as blood lipid profiles and glucose levels are insufficient indicators for CVD risk. Cholesterol efflux capacity could be a better marker.

We appreciate this important comment from the reviewer. We agree with the reviewer that “Cholesterol efflux capacity” could be a better marker to indicate the status of cardiovascular disease risk within the study population. However, this marker was rarely used within the analysed study population. In fact, we believe that blood lipid profiles, especially the level of cholesterol (which is reported within this manuscript) is an important marker/indicator of CVD-risk. We only relied on reporting data that was available within the ICTRP portal. Nonetheless, to agree with the reviewer, we have added this as part of the limitations within the conclusion section in this present report.

intervention for pediatric and elderly populations would add more benefit to this study.

We agree with the reviewer, data on the interventions for pediatrics could add value to the manuscript. However, as already presented within the Figure 4B, there is very limited trials that reported on children pediatrics. In fact, this is one of the major limitations, or future considerations that should be addressed in future clinical trials. This important fact has been highlighted within the revised manuscript.

It is better to read by a native English person.

Thank you for this important comment. Please note, we have allowed the manuscript to be proof-read by a native English speaker to enhance grammar and quality of presentation.

Round 2

Reviewer 2 Report

Suitable for publication