C-REGS 2 - Design and methodology of a high-quality comparative effectiveness observational trial.

Johannes Vester,Stefan Winter,Michael Brainin,Marion Jech,Herbert Moessler,Natan Bornstein,Wolf-Dieter Heiss,Milan Vosko

doi:10.25122/jml-2021-0362

Abstract

The main aim of this study is to systematically record Cerebrolysin treatment modalities and concomitant medication, according to local standards, in patients with moderate to severe neurological deficits after acute ischemic stroke and to assess the impact of these parameters on therapy outcome during early rehabilitation (day 21) and on day 90. An open observational treatment design based on the principles of high-quality comparative effectiveness research (HQCER) has been chosen to capture the therapies as applied in real-world clinical practice. HQCER opens a new horizon for strengthening the validity of the results from observational trials, thereby enhancing the associated level of evidence. Rigorous pre-specification of analytical procedures and tight risk-based centralized monitoring were additional measures to improve the impact of the observational approach. The value for real-world studies has become obvious, and such studies based on comparative effectiveness designs supplement the classical study designs by enabling the inclusion of larger proband numbers and more statistical reliability for practical use.

Highlights

Background informationMethodological Considerations Observational studies are best used to evaluate the real-world applicability of evidence derived from randomized trials [1]
An open observational treatment design based on the principles of high-quality comparative effectiveness research (HQCER) has been chosen to capture the therapies as applied in real-world clinical practice
In terms of rating quality of evidence, observational trials usually begin as low-quality evidence, limiting the validity and generalizability of the observational results GRADE Guidelines Rating the quality of evidence [2, 3]

Summary

Introduction

Background informationMethodological Considerations Observational studies are best used to evaluate the real-world applicability of evidence derived from randomized trials [1]. Recent suggestions for high-quality comparative effectiveness (CE) research GRACE principles for Good Research for Comparative Effectiveness OBSERVED [4, 5], in combination with rigorous risk-based centralized monitoring approaches (see EMA [6], FDA [7] risk-based guidance) open new perspectives for enhancing the level of evidence of observational trials. Stroke therapy has developed, and new treatment concepts have been implemented. Over time, Cerebrolysin treatment in stroke has evolved with different time windows, dosages, and duration of therapy, often being given pragmatically by physicians. The main aim of this study is to capture these variables of Cerebrolysin treatment and its comedication in patients with moderate to severe neurological deficits after acute ischemic stroke to guide further research

Objectives

Methods

Findings

Discussion

Conclusion