Designs used in published therapeutic studies of rare superficial vascular anomalies: a systematic literature search

Abstract

Background Rare superficial vascular anomalies represent a wide range of diseases. Their management is difficult given the broad spectrum and the lack of clinical trials assessing treatment efficacy. A randomized clinical trial of vascular anomalies is difficult because of the rarity of the diseases and is enhanced by the population of interest often being children. Therefore, suitable designs are needed. We conducted a methodological systematic literature search to identify designs implemented for investigating the treatment of rare superficial vascular anomalies. Methods We conducted a literature search on January 25, 2021, of the PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), Embase, ClinicalTrials.gov and European Union Clinical Trials Register databases. This systematic methodological literature search was registered at the Prospective Register of Systematic Reviews (PROSPERO: CRD42021232449). Randomized and non-randomized studies were included if they met the following criteria: were prospective studies of rare superficial vascular anomaly therapies, dealt with humans (adults and children) and were published in English from 2000. We excluded case reports/case series reporting fewer than 10 patients, reviews, retrospective studies, animal studies, studies of systemic or common vascular anomalies and non-therapeutic studies. We did not assess risk of bias in the included studies because our review was a methodological one focused on the design used. The review provided a descriptive analysis of relevant features of eligible research studies. Results From 2046 articles identified, we included 97 studies (62 reports and 35 ongoing studies): 25 randomized controlled studies, 7 non-randomized comparative studies, 64 prospective cohorts and 1 case series. Among the 32 comparative studies included, 21 used a parallel-group design. The 11 other studies used different designs such as cross-over, randomized placebo phase, delayed-start, within-person, or challenge–dechallenge–rechallenge or used a historical control group or an observational run-in period. Conclusions Our systematic literature search highlights the lack of randomized control trials in superficial vascular anomalies due to the rarity of patients and their heterogeneity. New designs are emerging and can overcome the limitations of testing treatments in parallel groups.

Sample Size Calculation for an Individual Stepped‐Wedge Randomized Trial

“…It has been used in studies of obstructive sleep apnea (Truby et al 2019), chronic constipation (Grossi et al 2022), fine particulate matter exposure (Benka-Coker et al 2021), juvenile idiopathic arthritis (Ilowite et al 2014), myositis (Aggarwal et al 2016;Oddis et al 2013), or even vascular malformations (ClinicalTrials.gov, 2019;Maruani et al 2021). However, its use is reviewed among multiple designs addressing challenges in small clinical trials (Allemang-Trivalle et al 2023;Cornu et al 2013) to study rare disorders (Abrahamyan et al 2016) or studies of fragile populations such as children (Balevic While several publications focused on the analysis of ISW-RTs 2 designs, none, to our knowledge, proposed a sample size derivation. There is a recent study that focused on deriving the optimal allocation of individuals to treatment sequences in ISW-RT designs, considering the nesting of repeated measurements and possible attrition (Moerbeek 2023).…”