Objective: The aim of this meta-epidemiologic (ME) pilot study is to give an overview of single-arm studies (SaS) provided as ultimate proof of treatment efficacy for authority approval, to highlight weakness and potential sources of biases of this type of clinical trials (CT).

Method:  SaS of antineoplastic agents were selected in Medline database with a combination of MeSH terms. The design was reviewed and potential approval checked. Descriptive statistics will be used to identify the key features of the methodology of these studies.

Results: A total of 2451 articles have been found with the combination of MeSH terms on Medline. Concerning the pilot study, on the 12 articles we identified that external comparisons were informal in 25% of studies, 33% were done with an historical control and 33% with a prefixed norme. A confirmatory study (to confirm results of phase II) was done in only 36% of studies and was inconclusive in 25% of studies.

Conclusion: SaS design raises many questions, such designs are source of biases specific to descriptive studies: confounding factors and methods used for external comparisons which that do not  allow the same level of evidence as a RCT. These elements call into question the internal validity of SaS and the clinical relevance of their results. In addition, there is a need of evidence-based guidelines, or scientific recommendations for the use of this study design. The ICH E10 guidelines describe the use of external control design as “ restricted to situations in which the effect of treatment is dramatic and the usual course of the disease highly predictable”. This definition question the threshold of “dramatic”. It seems clear that the simplistic design of SaS can not replace RCT to assess the benefit of a treatment, because of its many limitations making it very difficult to interpret the results

Could we do without RCTs? The emergence of single-arm studies as a basis for approval, a meta epidemiologic study

DIA Europe 2019

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