Dressings and Topical Agents for Chronic Wounds - NIHR Health ...

Health Technology Assessment 1999; Vol. 3: No. 17 (Pt 2)both of which are oxygen free radical scavengersand were evaluated in the same trial. This trialneeds to be replicated as the possibility that thecomparator (an inert powder) may have had adetrimental effect on healing cannot be ruled out.DMSO has also been found to be effective in thetreatment of diabetic foot ulcers and is worthy offurther investigation. 139Biologically active topical agents, cells ormembranes, were not found to be more effectivethan control dressings, such as paraffin gauze orculture medium. Similarly, growth factors were notdemonstrated to be more effective than the tissueculture medium alone. This is in contrast withevaluations in the treatment of diabetic foot ulcerswhere they have been shown to be effective. 139There may be two explanations for this.• There may be differences in microcirculatorypathology between diabetic and venous ulcers;the former being amenable to treatment bygrowth factor.• Growth factors are effective in the treatment ofvenous leg ulcers but the method of applicationand/or the power of the studies has resultedin a type 2 error. One striking difference in theapplication of growth factors to the two differentwound types is the amount of debridementperformed. During the treatment of diabeticfoot ulcers, the skin and wound are frequentlydebrided to remove dead tissue. 139 A bleedingwound bed may be prepared prior to the applicationof the growth factors. Sharp debridementis rarely performed on venous leg ulcers andthere was no pretreatment debridement in thetrials reported here. 127–130Comparisons between dressings and topical agentsindicated that a collagen dressing was preferableto the daily application of an antiseptic, while ahydrocolloid dressing healed more ulcers thanmagnesium paste. However, neither magnesiumpaste nor topical antiseptic are widely used todayin the UK suggesting that the generalisability ofthese results is limited.Publication biasFunnel plots indicated that publication bias may bepresent for trials that compared hydrocolloids withtraditional treatments. Asymmetry of the funnelplot can result from: 140• publication bias• language bias• multiple publication bias• poor methodological design amongstsmaller studies• true heterogeneity (i.e. ES differs accordingto study size due to intensity of intervention)• chance.It is inevitable that despite searching forunpublished studies this review relies heavilyon published trials. There is at present nostandardised method to ensure a comprehensivesearch for unpublished data. Careful screeningof all included studies was undertaken to reducethe potential for multiple studies and the searchstrategy was designed to improve sensitivity fornon-English publications. True heterogeneity isunlikely to have influenced publication bias asthe largest studies did not employ interventionsthat differed from the smaller ones. The almostuniform direction of the bias suggests that itwas not purely a chance result. Poor methodologicaldesign of the smaller studies could beresponsible for skewing the funnel plot; thesmaller effect size demonstrated in the larger,more rigorous studies may indicate this.However, publication bias remains the mostlikely cause of asymmetry. 140 This type of biasmay result from restrictive practices that preventall the evaluative research entering the publicdomain. There are several reasons why publicationbias could skew the data, two of the mostcommon causes are:• pharmaceutical companies are unlikely tofavour the publication of sponsored trialswhere a result favoured the standard, genericalternative. Such suppression of publicationis more likely for small, under-poweredstudies than for large, multicentre trials• journal editors or researchers may notfavour publication of small studies with‘null’ (i.e. non-significant) results, particularlyif they have been preceded by largerstudies that indicated a positive benefit foran intervention. This does not appear tobe the case here as the majority of trialswere non-significant.Analysis of the funnel plot by date of publicationsuggests there is little evidence that the year ofpublication was related to the outcome reported.In other words, commercial considerations maybe the causative factor of asymmetry (Figure 24).Hydrocolloid dressings were amongst the firstmodern dressings to be intensively marketed andcompanies would be unlikely to publish researchwith negative results. A similar publication bias41