Brief History of Clinical trials

Recently, it was thought, in a EurActiv article “EU medical trials law 'putting brakes on science'by researchers such as Professor Dietger Niederwieser from the University of Leipzig that current research standards and patient protection standards needed to be improved as they are being let down by increased costs and bureaucracy . The 2001/20/EC directive concerning how clinical trials were to be conducted sought to do this as well as increase the competiveness of clinical research. In addition, it was meant to permit researchers to get approval for medical trials and to enhance the standards for the testing and manufacture of new medicines. However, recently, researchers claimed that these rules have not brought any benefits to patients, themselves or the industry on the whole. Instead it has increased costs and administrative responsibility.

Current Cover offered by Directive 2001/20/EC governing clinical trials

It governs the clinical practice of conducted clinical trials performed on medicinal products for human use which includes multi centre trials but not non – interventional trials. This directive also contains provisions on protection of those who participate in clinical trials. This directive also established an ethics committee which is to give its opinion before any trial begins. As well as giving member states competence on the commencement and governance of clinical trials, it highlights the importance of the exchange of information on clinical trials between countries through a database. Member states are also given the power to stop a clinical trial if they feel that it is not safe or lacks scientific validity.   

The effect of this directive is also strengthened by Directive 2005/28/EC which not only provides guidelines on clinical practice as regards conducted trials on medicinal products for human use but is also the authority on manufacturing or importing such products.

If clinical trials are performed outside of the EU, but still require market authorization in the EU, then Directive 2001/83/EC on “Community Code relating to medicinal products for human use” is to be consulted instead of Directive 2001/20/EC. This directive is not specific and is only meant to offer general protection against medicinal products for members of the public. Additionally, the European Commission has sponsored an FP7-funded project – the Impact on Clinical Research of European Legislation – in order to measure the effect of the directive on the pharmaceutical industry, academics, research ethics committees and medicines regulators.

Further Guidelines for Clinical Trials

Generally, additional guidelines on these trials give advice on the information to be provided to the relevant authorities and to the ethics committees, the requirements concerning safety monitoring, the reporting of adverse reactions, good clinical practice, including the documentation, of the clinical trials as well as the specific requirements regarding the products and the clinical trials and the inspections of relevant authorities and the applicable procedures. Some of these guidelines are produced by the European Commission and are then published in Volume 10 of the EudraLex which has the title of “the rules governing medicinal products in the European Union”.

The European Medicines Agency (EMA) has also published guidelines of a similar nature. To summarise, these guidelines mainly cover the area of  inspection procedures and guidance for GCP inspections carried out in the context of the centralised procedure requirements relating to the quality, safety and efficacy of products, as well as specific types of products. These specific guidelines are also contained within volume 3 of EudraLex. A Clinical Trials Facilitation Group (CTFG) has been established by the Heads of Medicines so as to discuss any current technical issues.

EudraCT – a further creation of Directive 2001/20/EC

This European database compiles a list of all current and completed clinical trials within the scope of the directive that have had the involvement of the member states, the EMEA and the Commission so that they can communicate on clinical trials and govern the relevant developments. This involvement strengthens the protection of clinical trials and also improves the service offered to patients. EC legislation also allows some information within this database to be accessible to the public. The effect of this legislation is enhanced further by the main guidelines of 2008/C168/02 and supporting guidelines of 2009/C28/01. The initiative to allow public accessibility is expected to fully finish at the beginning of 2010 after procedural requirements have been met.    

Government measures to reduce bad effects: Backfire or Success?

The Commission tried to reduce any burdens of the current directive by reinstating certain requirements for reporting side – effects arising during research, as part of the directive. So, instead, of reporting “serious adverse effects” (SAE's) reporters would only be expected to report “suspected unexpected serious adverse reactions” (SUSAR's). In other words, only those effects directly relevant to the research would be reported. However, this change did not result in the rest of the world switching to the new requirement which meant that now companies had to take account of SAE's and SUSAR's. In addition, this difference in reading the directive has not been useful for multinational trials.    

Public Consultation with the release of the Commission communication on “Safe, Innovative and Accessible Medicines: a Renewed Vision for the Pharmaceutical Sector”

Following the Commission's failed attempts to improve what it had already, on the 10^th of December 2008, the Commission released a communication in order to carry out an assessment of the current directive. A public consultation into this assessment was then started and then the responses were released on the 30^th of March 2008.

On the 3^rd of March, 2010, the Commission released a ‘roadmap' or a ‘legislative proposal on a Regulation/Directive amending the Clinical Trials Directive 2001/20/EC'. The problems as defined in this roadmap include unnecessary costs and delays and difficulties in conducting the trials due to strict regulatory requirements. For instance, the main objectives of this roadmap include a regulatory framework that takes into account the current research environment and pharmaceutical sector without compromising the needs of clinical trials patients and practical requirements. In addition, the defined policy options to meet these objectives include clarification of certain provisions of the current clinical trials directive, revision of guidelines for trials and procedures and replacing part of the directive with measures of Community law that requires no further implementation by national member states. It is also proposed to increase scrutiny of trials conducted in third countries and making the clinical trials authorization process more streamlined and simplified. The Commission hopes to adopt this proposal around October 2011.

New Guidance on Clinical Trials Published 30 March 2010

The commission has released a communication containing detailed guidance for applicants seeking authorisation of clinical trials in "Detailed guidance for the request for authorisation of a clinical trial on a medicinal product for human use to the competent authorities, notification of substantial amendments and declaration of the end of the trial". This relates to the Clinical Trials Directive (2001/20/EC)

The new guidance replaces and significantly revises the previous version of October 2005. This was necessary after many changes to the regulatory framework for pharmaceuticals and clinical trials in the European Union arising from new legislation on paediatrics and advanced therapies.

 The new guidelines state that the directive does not relate to the following areas:

• Medical devices
•  Cosmetic products
•  Food

As well as referring to the directive, it also refers to other sets of guidelines and in this regard it cannot be read alone.

Guidance is provided on the following issues:

• Time lines for a member state concerned to consider a request for authorization of a clinical trial, as quickly as possible   and not more than 60 days, as well as time lines to be followed when an application is not valid.
• The documents to be submitted to the competent authority as part of the application
• The content of documents to be submitted
•  The requirements for competent authority to provide their notification of amendments and the notification of the end of a  clinical trial.

 All of these revised documents are now available in Volume 10 of Eudralex on the European Commission's website.                  

 (http://ec.europa.eu/enterprise/sectors/pharmaceuticals/documents/eudralex/vol-10/index_en.htm).  

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