Health technology assessment (HTA) on the importance of growth factors for the treatment of diabetic foot ulcers (DFU)

Introduction: DFU are a serious problem with an enormous impact on the overall global disease burden due to the increasing prevalence of diabetes. Because of long healing processes often including ambulant, inpatient and social services they are costly. Therapy with growth factors could be an innovative add-on to standard wound care. The aim of the HTA on behalf of the German Institute of Medical Documentation and Information is to assess the safety and efficacy of growth factors alone or in combination with other technologies including medical, economical, social, ethical and juridical aspects. Methods: We systematically searched relevant data bases including publications since 1990 in English or German language. Price level was set for 2008 and converted into Euro. Review and assessment of quality of publications followed accepted standards for evidence-based medicine and health economics. Results: We identified 14 randomized controlled trials, nine cost-effectiveness analyses and two meta-analyses. Study duration ranged from 12 to 20 weeks, study population comprised in average 130 patients. Treatment with becaplermin, rhEGF, Dermagraft and Apligraf showed in eight studies an advantage concerning complete wound closure and time to complete wound healing with statistically significant differences. No benefit of treatment with bFGF could be found. In four studies the proportion of adverse events was 30% without differences between the treatment groups. Significant deficiencies affected the methodological quality of the studies. Economic evaluations showed becaplermin being cost-effective whereas no obvious statement can be made regarding Dermagraft and Apligraf. Discussion: Small sample sizes and other methodological flaws with high potential of bias limit the validity of the results. Duration of treatment and follow-up examinations are too short to observe sustainability of intervention, surveillance of recurrences or potential treatment related adverse events e.g. malignancy. Conclusions: There are indications of an advantage for the add-on therapy with growth factors. Further studies with adequate sample sizes and follow-up periods are necessary, also investigating patient-relevant parameters.