Table 1.

Hallmarks of a high quality randomized clinical trial testing efficacy and safety of topical diabetic foot ulcer healing agents

Study Feature Location in Publication	Hallmarks of High Quality RCT Design, Conduct, or Reporting7–11 for a Topical DFU Healing Agent
Title	States randomized design, diabetic foot ulcer (DFU), topical agent, outcome
Abstract	Clear, accurate, succinct summary of objective, design, methods, including setting, subjects, outcome measures, significant results, and conclusions
Introduction (Background)	Brief summary of facts documenting the following:
Relevant clinical need	Clinical need to improve DFU healing in the population from which the study sample will be drawn establishing relevance
Rationale for study	Evidence that this topical agent may safely, effectively heal DFU
Hypothesis	The agent will safely improve healing beyond that achieved by an identical treatment and standard of care (SOC) without the agent.
Objective	Clearly states subjects, treatment, setting, and outcomes explored.
Methods	All stated below match Objective and are clearly, completely described
Trial design	Prospective, randomized, parallel (or factorial, randomized block etc.) clinical trial
Study sample	Subject inclusion and exclusion criteria are clearly stated and adhered to
	Sample size is sufficient for statistical power≥80% for primary outcome
	Groups are similar on baseline parameters affecting the primary healing outcome
Randomization schedule including allocation and implementation methods and allocation ratio to groups	Subjects are randomly assigned to groups, blocks, etc, using a clearly stated, concealed appropriate randomization method (e.g., 1:1 group assignments generated by a random number table, coin flip, or computer, learned at subject assignment by opening an opaque sealed envelope) Alternate or other quasi-randomization may introduce bias.
Procedures and observations (data collection and disposition)	Subject, care provider, and outcome evaluator are blinded to treatment, as feasible.
	Treatment procedures are clearly described to enable study replication, stating who did what to whom in what setting, how often and by when
Interventions and SOC	Clearly described, ideally varying only in active agent (e.g., identical placebo or vehicle or sham control, with the same SOC applied consistently to all subjects). If not, authors clearly state why this was not done and include it among study limitations discussed.
Outcomes	Clinically relevant, prespecified valid, reliably measured primary and secondary outcomes are ideally evaluated by an assessor blinded to treatment assigned.
Statistical analysis	Prespecified planned statistical comparisons for all stated outcomes are described, including any planned interim analyses and/or study stopping points.
	Baseline comparability of subjects and wounds in all compared treatment groups are described clearly and added subset analyses, ad hoc or adjusted analyses.
Results	Record or report all results that were measured clearly and accurately
Study subject flow diagram with study start and end dates and timelines for each study stage.	Disposition of all subjects enrolled (intent to treat or ITT set), those adhering to protocol (per protocol or PP set), those included in each analysis, withdrawals and excluded subjects (with reasons for each) are clearly described, including numbers of subjects completing each study stage and follow-up.
Reporting outcomes	All primary and secondary outcomes with effect sizes and 95% confidence interval are reported, with tabulated number of subjects experiencing adverse events of stated severity. Only facts are stated, avoiding conjecture and clearly distinguishing prespecified analyses from exploratory analyses.
Discussion	Results are accurately related to clinically relevant healing measures, patient needs, or economic outcomes based on related literature. Implications for clinical care and for future research are described.
Conclusions	Significant results are accurately described without embellishment or omission
Acknowledgment, access	All source(s) of support, funding, sponsorship, and accessibility are clearly stated.
Funding or sponsorship	Funding source(s) and influence(s) on data acquisition, analysis or reporting are cited.
Trial accessibility	Provide trial registration number, name of trial registry if applicable, and source(s) for further information about the RCT or its data.

ITT, intent-to-treat sample of all subjects randomized to and receiving at least one treatment; PP, per protocol sample of all subjects adhering to the study protocol per specified conditions; RCT, randomized clinical trial.