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Table 1 Consensus meeting discussions and advisory decisions for the main checklist reporting items

From: Development process of a consensus-driven CONSORT extension for randomised trials using an adaptive design

Main checklist item Summary of the discussion and advisory decisions and suggestions made
3a Description of the trial design Queried the need for the modification. However, it was noted that the allocation ratio for some ADs can change over time and therefore needs greater prominence or some alternative language in the E&E document to indicate that the initial allocation ratio can be fixed or change during the course of the trial
Decision: 16 (61.5%) voted to drop the modification and keep the original item
3b Rationale for an AD Noted the importance of the rationale especially when interacting with key stakeholders particularly at the planning stages. In addition, from a regulatory perspective, a well-explained rationale is important in the evaluation process. However, the need for a standalone item covering the rationale for the AD was questioned, especially given that no justification for fixed sample size designs is required. Some suggested to drop 3b as a standalone item but make it clear in the E&E document that 2a ‘scientific background and explanation of the rationale’ should also be about ‘scientific rationale for choosing an AD’
Decision: 17 (65.4%) voted to drop the standalone item and find a compromise solution
3c Specification of pre-planned adaptations Described as the essential part of the trial design. The importance of separating planned adaptations from unplanned changes was highlighted. It was suggested that the new text from 3a could be added to 3c to ensure that all material is adequately covered
Decision: 21 (80.8%) voted to keep the new item as standalone
3d Unplanned changes to the trial design or methods Importance of covering both planned adaptations and unplanned changes adequately, as this is key to ADs.
Decision: 21 (80.8%) voted to keep the modified item as standalone and address ordering issues
3e Adaptive design properties Importance of AD properties from a regulatory perspective was highlighted. Noted that statistical and operational properties of the ADs are broad and include sample size. There was a discussion about whether the AD properties should be covered here or under sample size (7a) since the aspects covered by 3e and 7a overlap but not identical. Some suggested this should be under the section heading ‘Sample size and operating characteristics’. Some felt that 3e, 7a, and 7c overlap, so some further work is needed to clarify this.
Decision: 13 (50.0%) voted to keep the item and address structural issues
6a Pre-specified outcomes Discussion reflected that a trial could be adapted based on an ‘intermediate’ outcome that may or may not be a secondary outcome. The need for ‘clinical rationale’ was questioned and clarification given as it relates to the rationale for selecting an ‘intermediate’ outcome to adapt the trial or help make interim decisions. Some suggested rewording to ensure that pre-specified primary and secondary outcomes, together with additional ‘intermediate’ outcomes are all adequately covered. The complexity of material covered by this item was acknowledged.
Decision: 23 (88.5%) voted to keep the modified item and address wording issues
6b Unplanned changes to outcomes Mixed views on the necessity of the modification. Some were concerned that this part of studies is often poorly reported. Some concern that modifying the item may obscure the original meaning. Reflecting on the discussion, we failed to clarify that some AD trials can change the outcome in a planned manner reflected under 3c. To retain the intention of the original item, this modification a clarification to capture unintended changes to outcomes (outside the scope of the planned adaptations)
Decision: 12 (46.2%) voted to keep the modified item. Steering Committee to review
7a Sample size Mixed views on whether the modification was necessary or proportionate. Suggestions that the wording could be simplified or shortened so that content on sample size is not obscured. For example, by adding AD properties, as per discussion of 3e above, modifying section heading, and further details would be better added to the E&E document
Decision: 17 (65.4%) voted to keep the modified item and address raised issues
7b Decision-making criteria to guide trial adaptation Importance acknowledged and suggestions to simplify the wording and discuss details in the E&E document
Decision: 23 (88.5%) voted to keep the modified item and address wording issues
8c Randomisation updates after trial commencement Importance reflected in the discussion and suggestions to merge the material of items 8b and 8c
Decision: 16 (61.5%) voted to discard this item as a standalone, but keep the content of the suggested new item by merging with item 8b
11c Confidentiality and minimisation of operational bias General agreement that the information included was essential
Decision: 26 (100.0%) voted to keep the new item as a standalone
12c Methods for statistical inference;
12d Methods to combine data across stages;
12e Dealing with over-run participants;
12f Methods for dealing with multiple treatment comparisons/outcomes;
12g Prior selection
Extended discussions about whether the material covered by 12c–12g should be addressed via individual checklist items or a merger. Some concern that the use of a long, compound item would not improve the quality of reporting, as authors retreat to the bare minimum to complete the checklist. Cross-referencing the protocol or the statistical analysis plan was suggested to capture the complexity of statistical inferential methods in the AD. Some suggested discussing the potential sub-items in the E&E document. Discussed whether the approach to methods used for futility analyses should be covered here; some suggested rewording 3c such that it also captures methods used to derive statistical information used to adapt a trial. Acknowledged the need to reword the material such that key aspects of the dropped items 12d–12g are reflected in some way
Decisions:
25 (96.2%) consensus to keep 12c but address rewording and reflection of dropped items
21 (80.0%) consensus to drop 12d as a standalone item
22 (84.6%) consensus to drop 12e as a standalone item
20 (76.9%) consensus to drop 12f as a standalone item
21 (80.8%) consensus to drop 12g as a standalone item
13a Randomised, received intended treatment… Extended discussions about the definition of ‘intermediate’ and interim outcomes/analysis and need for simplification. Discussion on the meaning of ‘subpopulations’ and its limited applicability to population enrichment designs, which suggests it should be removed and discussed in the E&E document. Mixed views expressed on coverage of reporting and whether this can be differentiated for all adaptations; graphical complexities highlighted for some trial adaptations
Decision: 20 (76.9%) consensus to keep the modified item and address rewording
14a Dates defining recruitment periods Important to ensure the meaning of the original 14a is not lost with respect to study dates
Decision: 14 (53.8%) voted to keep the modified item
14b Unexpected termination Decision: 17 (65.4%) voted to drop the modification and keep the original item
14c Adaptation decisions Acknowledged that adaptation dates and decisions should be included, but query on whether items 14a and 14c are the correct place and need for rewording. Discussion on the need for implementation resources to help with reporting. Some confusion about details/coverage of item 14c evident in discussions
Decision: 12 (46.2%) voted to keep the item. Steering Committee to review
15a Appropriate baseline data for comparability The necessity of modifying 15a was queried and the need to reword ‘subpopulation’. Query over whether using baseline is correct, but acknowledged that changing this would require a change to CONSORT 2010. Suggestion to drop extended 15a but include an explanation of the need to present information differently for some AD trials such as population enrichment, with an example in the E&E document
Decision: 13 (50.0%) voted to drop an item and consider expanding the explanatory text. Steering Committee to review
15b Representativeness of patient population No specific issues raised
Decision: 20 (76.9%) consensus to keep the new item
16 Numbers analysed at interim and final analysis The distinction for AD trials with examples could be adequately covered in the E&E document without the need to modify the original item wording
Decision: 19 (73.1%) voted to drop the item and expand the explanatory text
17a Primary outcome results
17c Suitable representation of interim outcome results
Suggestion that it is unnecessary to modify 17a, but rather ensure that new material is all captured under 17c. Queries about whether CONSORT 2010 already covers the relevant content, and whether additional content is just required for the E&E document (similar to items 15a and 16). Highlighted the importance of understanding important changes relative to the feasibility of covering all adaptation aspects within a standard journal article. Importance of transparency about the location of more detailed analyses was suggested as a compromise—it is more about access to key information. Suggestion that reporting of treatment arms that have been dropped should be mandatory.
Decisions:
16 (61.5%) voted to drop item 17a and expand the E&E text
21 (80.8%) consensus to retain 17c but needs rewording
20 Limitations, sources of bias, imprecision, and deviations Questioned the necessity of the modification given that the original item is already broad. Making reporting more stringent for ADs relative to fixed sample size designs was questioned. Clarification of AD-related issues could be given in the E&E document without the need to reword the item
Decision: 25 (96.2%) voted to drop the item and expand the explanatory text
21 Generalisability (external validity and applicability) The necessity of modification queried on the ground that this is too specific to only a small type of ADs such as population enrichment. Again, clarification of AD-related issues could be given in the E&E document without the need to reword the item
Decision: 25 (96.2%) voted to drop the item and expand the explanatory text
22b Contribution to future-related research Consensus group appreciated the sentiment of this new item, but the necessity was strongly questioned
Decision: 23 (88.5%) voted to drop the item
24b Intentionally withheld information
24c Statistical analysis plan
24d Simulation protocol and report
24e Data Monitoring Committee Charter
24f Statistical code
Discussed the feasibility and necessity of including all proposed individual items, and whether these could be merged into one larger item covering additional trial information. Some delegates felt that 24b and 24c should be kept as standalone items and merge 24d to 24f under the heading ‘Availability of other trial documents, if available’
Decisions:
17 (65.3%) voted to keep item 24b as a standalone and merge with 24d, 24e, and 24f
14 (53.8%) voted to keep item 24c as a standalone and address merging issues