PONE-D-23-43710Adaptive clinical trials in surgery: A scoping review of methodological and reporting qualityPLOS ONE

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Reviewers' comments:

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Reviewer #1: Yes

Reviewer #2: Yes

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Reviewer #1: Yes

Reviewer #2: Yes

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Reviewer #1: Yes

Reviewer #2: Yes

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Reviewer #1: Yes

Reviewer #2: Yes

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5. Review Comments to the Author

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Reviewer #1: I congratulate the authors for a well written manuscript on an important topic. The manuscript systematically addresses the application of adaptive RCTs in the surgical speciality. It describes the utility of the captive design, the current surgical literature employing this and goes on to evaluate its future application in the surgical field and recommendations on improving the methodological quality.

I have some minor suggestions as follows:

Abstract:

The conclusion mentions that “Surgical trialists should consider implementing adaptive components to help improve patient recruitment and reduce trial duration”.

Along with this line, the conclusion should also mention that the reporting of the adaptive design needs to be consistent and adherent to the existing CONSORT adaptive extension guidelines as heterogeneity in the reported trials was one of the main findings of this review.

Methods:

In the data extraction section, the authors have mentioned that methodological details pertaining to

adaptive design were collected. It may be useful to the readers to actually list all the details collected as it is the main outcome of this review.

Results:

1. Referencing of the studies needs to be consistent in all the 3 paragraphs of the results.

For example, the references of the 6 studies need to be added after the sentence “All six included studies were published after 2015 (Table 2).”

The references of the 5 studies need to be added after “Five studies published their study protocol in advance of trial registration.” Similarly, references need to be added whenever the studies are described for their characteristics at other places in this paragraph.

2. The paragraph on adaptive methodology details should be rephrased for better understanding to the readers. It should mention the results of the number of studies that described the adaptive design, pre-specified interim analysis, changes to trail design at the interim analysis in that order. At present, the information presented appears random in the paragraph.

Also, the use of standard terminology to describe an attribute would be important. The term "unplanned changes to trail design or outcomes appears at several places in the abstract, results and discussion. But it is not mentioned in the study summary table (Table 2). It is my understanding authors refer to the "changes to design after start of trial" in the table as the unplanned changes in design and outcomes. But using the same term in the table will add clarity to the readers.

3. The authors have to reference the studies they are describing in the paragraph on adaptive methodology (needs to be rephrased as above) and bias assessment as well.

Discussion:

In the second paragraph, the authors describe the covariate adaptive randomization which is altering randomization considering the prognostic factors. In the next line, they reference the studies for response adaptive randomization, which may actually be done during an interim analysis.

It is unclear to the readers if the 2 concepts are the same or different. It may be useful to describe the concepts in a bit more detail here.

Reference needs to be added after the sentence “Reardon et al. (2017) utilized a Bayesian analysis plan to design and perform analysis within their trial.” There are other places in the discussion where studies are mentioned and reference not added, that need to be looked into.

Reviewer #2: Summary: There are no issues with the approach to the topic; I like the adaptive clinical trials and their review, as well as the approach used by the authors for the summary. The manuscript scores well for the novelty, significance, interest, and impact of the finding on the current state of RCTs in the literature. The authors have done extensive hard work on literature search and summarizing the information; very good descriptive analysis, well-organized results, and nicely covered discussion. The tables are compact, the flow chart is clear, and the methods are appropriately used. Overall, it has a good methodology and approach.

Major Strengths: This topic is very interesting and adds good knowledge/information to the upcoming researchers on how to address some concerns while conducting RCTs.

Major Weaknesses: NIL.

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Reviewer #1: No

Reviewer #2: Yes: Mahesh Nagappa

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Adaptive clinical trials in surgery: A scoping review of methodological and reporting quality

PONE-D-23-43710R1

Dear Dr.Staibano

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Kind regards,

Frances Chung, M.B.B.S,  MD, F.R.C.P.C

Academic Editor

PLOS ONE

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