Masterstudiengang "Drug Regulatory Affairs"

Master-Thesis

Standard for Outcome Measures in Clinical Trials for the treatment of plaque psoriasis supporting Labelling Claim and their application in practice – a critical review of the EMA Guideline CHMP/EWP/2454/02corr and a proposal for future development ***

Dr. Ina Zschocke (Abschlußjahr: 2016)

Summary
Language: English
Marketing authorisation of medicinal products within the European Union follow a complex regulatory framework comprising regulations, directives and guidelines. For some medical conditions guidelines have been released aiming to provide concrete guidance for the planning of clinical development studies to evaluate efficacy and safety of new compounds.
In June 2005 the EMA-Guideline on Clinical Investigation of medicinal products for the treatment of psoriasis has come into operation. Among other aspects regarding clinical trials in psoriasis this guideline specifies the requirements for primary outcome parameter and comments on Patient Reported Outcomes (PROs).
Since the release of the Guideline the indication plaque psoriasis has been subject to intensive research activities and eight new compounds have been marketed, amongst them four products have reached marketing authorisation as originators and four medicinal products have been marketed as generic biological (Biosimilars).
The present master thesis aims at comparing the regulatory requirements for primary efficacy objectives as laid down in the European Guideline CHMP/EWP/2454/02 corr with the actual practice in clinical trials in the indication plaque psoriasis. As state of the art study designs to evaluate safety and efficacy in the indication of plaque psoriasis have changed over time it is assumed that recommendations given more than ten years ago in the Guideline CHMP/EWP/2454/02 corr could benefit from a revision.
In the present master thesis an overview is given of regulatory requirements applicable for clinical trials for the treatment of plaque psoriasis, followed by on outline regarding the medical condition itself and current treatment options.
All pivotal trials that have been conducted for new compounds under development between 2005 and 2015 in the indication plaque psoriasis have been analysed with respect to outcome parameter.
The analyses revealed that a high level of consistency has been reached with regards to the selection of PASI as primary outcome parameter; however, studies differ with regards to its use as primary or co-primary endpoint as well as to the time point of the assessment of the primary outcome measure. The definition of the severity grading of plaque psoriasis according to PASI as established is not fully in line with the Guideline. In addition to that, Patient Reported Outcome Measures have a much higher relevance in clinical research compared to its meaning as outlined in the Guideline.
Given the fact, that the Guidelines stresses the restrictions that come along with several aspects of the PASI as well as the increased relevance of Patient Reported Outcome as admitted by the EMA, a new attempt should be made to develop outcome measures in the treatment of plaque psoriasis further.
Future development should envisage the integration of physician and patient assessed aspects of severity scoring in one holistic severity score. One attempt, that is currently undertaken by a group of researchers to develop a novel holistic patient-centered scoring tool is presented; it could in the future close the gap between physician’s and patient’s assessment of the severity as two separate outcome measures as well as overcome the limitations of the currently used Outcome Measures.
In this sense, the Guideline on Clinical Investigation of Medicinal Products indicated for the treatment of psoriasis would profit from a revision.
Pages: 52
Appendices: 4, Pages: 5