Masterstudiengang "Drug Regulatory Affairs"

Master-Thesis

Impact of Clinical Trial Registration on the Future of Drug Research ***

Dr. Christiane Rothkegel (Abschlußjahr: 2010)

Mandatory clinical trial registration in publicly accessible trial registries as tool to speed up drug development was first proposed in the 1970s. The proposal was based on the fact that information about ongoing and completed clinical trials for the general public was very limited at that time. Mainly results of trials with a positive outcome were published and only limited or no information was available on unsuccessful trials. This publication bias led to several obstacles as data regarding drugs and clinical research in general was incomplete. For example, safety issues of drugs or drug classes were only recognized at late stages of development or even only after years of use. Also unsuccessful trial designs were not recognized soon which resulted in unnecessary duplication of trials. In addition patients, especially those with life-threatening diseases, increasingly demanded to be able obtaining information about ongoing trials to ensure fair access to trials with innovative and potentially effective drugs.

The increasing demand among all stakeholders involved in clinical research to improve transparency on clinical trials resulted in the establishment of several independent clinical trial registries around the globe over the last decades. Currently, the largest clinical trial register with over 60,000 registered trials is the US registry ClinicalTrials.gov. In parallel, several workgroups at independent non-profit organizations, like the WHO, were established to define quality standards for clinical trial registries. The need for harmonization of quality standards among clinical trial registries arose as the existing registries all include different functionalities and disclose different dataset which might confuse users and leads to a reduced acceptance of registries as clinical trial information source. The positive benefits clinical trial registries may have on clinical research in general were also increasingly recognized by national legislations and guidelines. Thus today several legislations require disclosure of trials in a publicly accessible register.

By the establishment of clinical registries the ability for the general public to retrieve information regarding clinical trials was dramatically increased. However, there is still some room for improvement to fully obtain the benefits clinical trial registration has to offer for drug development. In general, for overcoming the publication bias and full assessment of the available evidence for a drug result disclosure is even more important than publication of protocol information. Thus it must be ensured that beside protocol information the results of every trial conducted in patients is made publicly available. As today still not every trial outcome is published several legislations were revised recently in order to mandate that result related information is disclosed in due time after trial end. Only full availability of data enables assessing the benefit-risk profile of a drug and the effectiveness of trial designs. In addition, the targeted user group of clinical trial registries must be made increasingly aware of the existence of trial registries as independent source of information regarding clinical trials. To improve use of clinical trial registries by patients language barriers must be limited and easy access routes must be offered. Also further harmonization of clinical trial registration from a global perspective must be increased to avoid multiplicity of registration trials with different data sets which confuses users and reduces acceptance. Several initiatives are currently ongoing to address the identified issues. In case these initiatives are successful this will eventually lead to an increased trust in clinical trial registries as valid source for information by all stakeholders and potentially also improve trust in clinical trials in general.

Taken together, all these factors will potentially help that the purpose why clinical trials registries were created will be fulfilled and eventually drug development is speeded up.

Pages: 40
Annexes: 6 pages