Comments on abstract, title, references

The title is long but is very detailed. It provides the reader with an idea of what the article entails.

The abstract is lengthy but contains all relevant aspects. The authors provide background information which tells the reader what is known and unknown about the topic being addressed. The aim is clearly stated and the findings and methodology of the study are also clear. It is also obvious that the aim of the study was answered as it was stated "At the first scheduled interim analysis, non-inferiority was shown and the sponsor terminated the study".

Majority of the references are very recent and they all relate to this area of study. They also contain similar studies to this one. Consistency of the format is maintained and all are referenced correctly.

Comments on the introduction/background information

Before the introduction, the authors provide evidence of the knowledge gap in the study by stating some of the articles they reviewed and included in the references. They also highlight the value which this research adds to this field of study. The implications are also stated in this section. I believe this is a good way of isolating the justification and purpose of the research.

The introduction gives a good overview of the history surrounding the topic being addressed. A very detailed summary of the findings from the literature review is provided and the information correlates with the authors aims and objectives for this study. The aim of the study is also reiterated.

The introduction is clear, concise and interesting, encouraging the reader to read beyond.

Comments on methodology

The authors clearly state the sample and how the subjects were selected. A very detailed description of the procedures are given and also the randomisation (allocation to groups) of the subjects. There is also consistency in the method of treatment applied in this research. Approval was obtained from local Institutional Review Boards.

The methods and regulations stated were found to be appropriate for the study and the variables are defined. The study methods are considered to be valid and reliable for a study comparing two interventional treatments. I also think this left no room for bias in the patient selection. The information provided should allow reproducibility of the study.

A declaration of interests is given, in which many of the contributors serves on an advisory board to a pharmaceutical company.

The methodology is very wordy. I suggest that flow charts or diagrams could be added for less complexity in reading the material.

Comments on data and results

Sample size and randomisation of the subjects are presented in a flow chart (Figure 1: Trial Profile); this is a very good representation of the treatment arms. Adequate explanations are also given to guide the reader where figures are concerned in this chart.

All subjects are accounted for and properly referred to according to the groups in which they were assigned.

The tables were also easy to understand. The data and statistical analyses are presented very well using a mixture of graphical and tabular formats in addition to diagrams/charts which are also properly labelled.

I am unable to comment on the graphs (Figure 2: Laboratory parameters of the intention-to-treat population) as I am unfamiliar with it.

The results section provide very detailed and significant data and also shows validity and reliability of the study.

Comments on discussion and conclusion

The discussion shows an explanation of the results and not simply reiteration. Advantages of the hydroxycarbamide treatment are stated and factors concerning its success are also identified and explained.

The aims of the research were answered, and the conclusions were supported by the results of the study.

Recommendations and limitations were given, providing guidance for future research. This was a very informative discussion.

Overall Statements

The design of this study was appropriate in addressing the aims and objectives of this research. The value this study adds is providing significant and valid information on a non-inferior treatment for the long-term management of children with sickle cell anaemia and established cerebrovascular disease. No major flaws were found within the article and consistency was maintained especially with the results.

Weakness: The article was very detailed, however the methodology could be edited to include some charts.

Strength: The article was very well organized, and very informative.