External validity of randomized controlled trials of interventions in venous leg ulceration: A systematic review

Abstract

We set out to evaluate quality of reporting of data related to external validity from randomized controlled trials (RCTs) assessing treatment interventions for active venous leg ulcers. Using a systematic review study design, we identified 144 full‐text RCTs of treatment interventions, where the wound was assessed and published in English from 1998 to 2018. We found that the median study sample size was 75.5. Weighted mean wound size was 13.22 cm2 and weighted mean wound duration was 22.20 months. Forty‐six (32%) reported numbers screened for eligibility and 27 (19%) reported the number who declined to participate; 19 (13%) reported on patient ethnicity; 60 (42%) reported comorbidities; and 5 (4%) reported current medication use. When reported, 60/102 (59%) excluded patients with an ankle‐brachial pressure index <0.8; 68/135 (50%) were conducted in Europe, 6/135 (4%) in Asia, and 74/104 (71%) were conducted in outpatient facilities; 3 (2%) reported socioeconomic factors and 88 (61%) reported on adverse events. We concluded that there is inadequate reporting of data related to external validity in reports of RCTs assessing venous leg ulcers treatment interventions. Significant variability exists in the ankle‐brachial pressure index cutoff point for inclusion or exclusion, making generalizability difficult to assess.

Assessing the uncertainty of treatment outcomes in a previous systematic review of venous leg ulcer randomized controlled trials: Additional secondary analysis

“…We did not perform a comprehensive analysis of every factor that could potentially influence bias and uncertainty of outcomes in RCTs; for example, publication bias and consistency of treatment effects were not analysed in this review. However, allocation concealment, blinding, power analysis, attrition rates, primary outcome measures, the inclusion of an ITT analysis, and multiplicity adjustment of secondary endpoints are all major factors influencing uncertainty of outcomes and external validity that were not considered in the systematic review by Gethin et al 1,14,17‐19 Finally, given our bundling of unclear with negative assessment categories, we recognize that in some instances, our results may be seen as too conservative. Nevertheless, the large dataset compiled from 142 VLU RCTs is a major strength of our analysis, and the results of our study demonstrate that more critical analysis of the uncertainty of outcomes in wound care is needed for other wound types and outcomes.…”

“…In 2019, Gethin et al published a systematic review of 144 RCTs involved in the treatment of VLUs to assess the quality of reporting of data related to their external validity 19 …”

First-Line Interactive Wound Dressing Update: A Comprehensive Review of the Evidence

“…The meaning of evidence-based practice concept has shifted towards reliance on the methodological quality and epidemiological rigor of studies, which may hinder research translation, rather than foster a combined approach using best quality evidence, clinical judgement and including patient values (Pagnamenta, 2017). The need to improve the quality of studies in wound care remains (Weller and McNeil, 2010;Gethin et al, 2019). However, this is challenging within the real world clinical practice scenarios that include comorbid conditions and wound complexity to ensure the chosen dressing 'does no harm, .…”

Rationale for participation in venous leg ulcer clinical research: Patient interview study

“…28,29 Evidence of effective interventions to improve compression adherence is limited 30 and there is a need for better quality clinical trials to address these gaps. 31 A large number of participants need to be recruited in the Randomised Controlled Trials (RCTs) to ensure that high quality research is carried out. 32,33 Study-related, patient-related, clinician-related, and health system-related factors may influence participation in wound research.…”

“…Compression adherence is a common barrier to evidence‐based VLU management from patients' perspective, 26,27 although the rationale and understanding of compression therapy adherence is poorly understood by patients 28,29 . Evidence of effective interventions to improve compression adherence is limited 30 and there is a need for better quality clinical trials to address these gaps 31 . A large number of participants need to be recruited in the Randomised Controlled Trials (RCTs) to ensure that high quality research is carried out 32,33 .…”