New pharmaceuticals are subject to approval by drug authorities. The approval is preceded by a lengthy and expensive clinical drug development process. These comprehensive clinical trials are performed to ensure the drug’s efficacy and safety in human beings.
The application for drug marketing approvals in the various member states of the European Union is currently not only time-consuming, but also very expensive. This is one of the reasons why many clinical trials are conducted outside the EU, for example in Africa and India. Experts estimate that a pharmaceutical manufacturer can reduce trial costs by 30 to 50 percent when testing a new compound in India rather than in the EU.
In July 2012, the European Commission adopted a proposal for a “Clinical Trials Regulation” to ensure that the rules for conducting clinical trials are identical throughout the EU and make it easier to conduct multinational clinical trials. The new authorisation procedure for clinical trials will allow for more transparency, simplified reporting procedures and a faster assessment of the application (see link “EuroConsults” on the right-hand side).
The proposal was heavily criticised in Germany by the German Medical Council and the Working Group of Medical Ethics Committees in Germany, amongst other organisations. They saw in the regulation an infringement of the Declaration of Helsinki which, in 1964, laid down the ethical guidelines of clinical research involving human subjects and human experimentation based on the findings of the Nuremberg trials in order to ensure that human subjects were never again misused in the service of science. The critics believed that the rights of minors and patients who are unable to give their consent were no longer sufficiently guaranteed. In addition, they were also of the opinion that the responsibilities of ethics committees were limited. 2013 will show how the proposal will be implemented. The new regulation will come into force in 2016.
AMNOG came into force on 1st January 2011 with the objective of curbing the growing expenditure on medicinal products by the statutory health insurance funds. AMNOG is not aimed at preventing innovative pharmaceutical research, but at paving the way towards greater affordability. AMNOG obliges pharmaceutical companies to subject their new products to an early evaluation of their additional benefit by the Joint Federal Committee (G-BA) after being launched on the market. The G-BA is in charge of coordinating the evaluation of drugs and may commission the Institute for Quality and Efficiency in Healthcare (IQWIG) or other organisations to evaluate a new compound and prove any additional benefit in comparison to a comparative therapy.
If any additional benefit is proven, the pharmaceutical company can negotiate with the National Association of Statutory Health Insurance Funds (GKV-Spitzenverband, GKV-SV) on a supplement over and above the price of the expedient comparative therapy. If it is not possible to prove any additional benefit, the pharmaceutical is allocated to a fixed group with comparable active ingredients. Since the introduction of AMNOG, 24 of a total of 37 drugs were rated positive and evaluated as follows (as of May 2013): The G-BA attested seven drugs a considerable additional benefit, fourteen a reduced benefit and was unable to quantify the benefit of three drugs. However, the G-BA decided in many of the evaluations to limit the additional benefit to small patient groups. Another major criticism of the AMNOG procedure is the selection of a comparative therapy by the G-BA, as this therapy sets the basis for the evaluation of the additional benefit and subsequent price negotiations.
In Germany, the introduction of AMNOG has led to a paradigm change. The benefit evaluation is generally considered positive, but there is criticism with regard to procedural matters. At present, two years after AMNOG came into force, it is still too early for a comprehensive review.
Clinical trials are conducted in order to provide the basis for assessing whether a drug can receive marketing authorisation or not. This requires the complete documentation of all study results, whether positive or negative for the manufacturer. However, many examples from the recent past demonstrate that clinical studies are often glossed over in order to manipulate the public. In 2009, Pfizer only made clinical trial data on the antidepressant Edronax (active ingredient: reboxetine) available to the IQWIG following massive public pressure. The IQWIG could not attest any additional benefit to reboxetine.
Another example is Tamiflu (Roche), which is the best-selling drug for the treatment of flu worldwide. Scientists have long had doubts about the efficacy of the drug. In 2002, the WHO was still recommending that governments around the world stockpiled Tamiflu and other antivirals. Tamiflu was again prescribed in huge quantities during the 2009 swine flu pandemic. Since the introduction of Tamiflu in 2002, Roche has achieved revenues of more than ten billion Swiss Francs (as of 2013). However, research carried out by the independent Cochrane Collaboration showed that the selective publication of the Tamiflu study results has led to an incorrect public perception of the drug. Although the Cochrane review concluded that Tamiflu alleviated the symptoms of flu, the reviewers also found that the duration of flu symptoms was only reduced by about one and a half days from the typical six or seven days. The reviewers could not confirm that it reduced hospitalisations. Roche has in the meantime thrown in the towel and stated that it intends to disclose the results of all Tamiflu studies.
In Germany, the publication of clinical trial results is stipulated in § 42 b of the German Medicines Act, according to which all study data must be made available to the competent federal authority. Although the obligation to disclose all clinical trial results is regulated by law, pharmaceutical companies are rather reluctant to do so.
CL - 21.05.2013© BIOPRO Baden-Württemberg GmbH