Table 2.

Diabetic foot ulcer topical treatment study flaws described in published reviews of diabetic foot ulcer literature

Source	Study Findings	Most Common Flaws Described
Dumville et al.19	In order hydrocolloid dressings had highest odds of being associated with best DFU healing outcomes followed by hydrogel, then foam topical dressings	Only 3 of 15 RCTs reported DFU healing time
		Mainly less severe, less complex DFU were studied
		Most studies were at high or unclear risk of bias
		Most studies had small sample sizes leading to low certainty of outcomes
Gottrup and Apelqvist20	There is limited high quality evidence on topical DFU dressings and healing agents and an urgent need to increase the quality of DFU clinical studies	Most studies had inadequate sample size, short follow-up, nonrandom allocation to treatment arms, nonblinded assessment of outcomes, poor description of controls, with concurrent interventions unmatched on groups of heterogeneous samples of subjects and DFU
Shaw et al.21	One moderate quality RCT supported a healing effect of topical phenytoin on DFU	Most articles failed to adequately describe randomization, treatment allocation, and blinding techniques
Buchberger et al.22	There may be an advantage for add-on therapy with EGF or becaplermin growth factors in diabetic foot ulcers for complete wound closure and time to complete wound healing outcomes	Differences in standard wound care complicated the comparison of study results. Many RCTs had small to very small sample sizes and other methodological flaws with high potential for bias. The duration of treatment and follow-up examinations was not long enough to assess the sustainability of healing and surveillance of ulcer recurrences or treatment-related adverse events like the development of malignancy
Edwards and Stapley23	RCTs reported DFU healing outcomes using surgical, larval, autolytic, or gauze debriding interventions. Only topical application of autolytic hydrogels resulted in faster DFU healing compared with gauze	Most studies had inadequate power to find clinically significant effects, with unreported inclusion and exclusion criteria for example, neuropathy
		Study details for example, setting or primary pathology of enrolled subjects or random sequence generation were often unreported
		Subject assignment to group (allocation) was often not blinded, creating potential bias