Review by Joseph Ross – 05/04/2016 – 5:14pm

Data Request Number: 2016-0884 Recommendation for this data request: Not Approve

We appreciate the data requestor’s efforts to revise the submission in response to comments from the YODA Project. Unfortunately, as written, the proposal still does not offer sufficient clarity of purpose and methods. Our best guess is that this proposal has been written by a non-native English language speaker. We would strongly suggest collaborating with a native English language speaker in order to improve the clarify of the writing.

The requestor also notes plans to disseminate these findings via the Cochrane Library of Systematic Reviews – does this imply that the review is being done under the umbrella of the Cochrane Collaborative? Investigators associated with the organization might assist in improving the clarity of the writing. Furthermore, all Cochrane reviews require registration in PROSPERO – much of the information required by PROSPERO is required by the YODA Project. Sending a link to that registration page might also improve clarity.

In terms of the substance needed for revision, please address the following specific points:
Honestly, this is so poorly written. Even after revision. The original was worse.

Text is redundant in multiple places. They checked off each and every possible “purpose of analysis”.

Please clarify the “Brief Project Background and Statement of Project Significance”. This section should focus only on the project background and be longer than 2 sentences in length. 2 paragraphs should provide sufficient background for the YODA Project reviewers to understand the scientific context for the work. And please explicitly describe the scientific value, or significance, of the work. Also, please use this section ONLY to discuss background and significance. As currently written, many aspects of the methods are described within this section of the proposal as well.

In fact, the text remains redundant in multiple places. As another example, the “Specific Aims of the Project” repeat several sentences of text related to the methods, this is not appropriate. Please explicitly note the scientific aims of the project.

Each and every possible “purpose of analysis” has been checked off. Is this true?

With respect to the data sources, thank you for providing additional information. Do you expect to obtain IPD for these 14-16 trials? If the other trials will be limited to published reports, is IPD for the 2 requested trials needed? Would CSRs be sufficient for purposes of this work? We presume your goal is to conduct a meta-analysis (not a multivariable analysis) – for how many trials will you have IPD or can the meta-analysis be performed with summary-level data?

For the main outcome measure section, please remove the statistical analysis plans. Please pre-specify each and every time-point at which your 5 defined outcome measures (and please describe each explicitly) will be examined: Observed Survival (OS), Progression-Free Survival (PFS), Time to First Subsequent Treatment (TFST), Overall Response Rate (ORR – is this different than PFS?), and Treatment Related Serious Adverse Effects.

In general, please avoid use of abbreviations.

Please fix all examples of writing that does not make sense:
• “Fixed and Random effects when apply.”
• “This is a confirmatory and exploratory (depending on the effect size variable) analysis.”
• “Our aim to source as much as we canPatient Level Data, to allow for a truly effective Multivariate Analyses, when needed.”
• “Handling of missing data: Censoring or adjudication”

The narrative summary should be written for the lay public.