Masterstudiengang "Drug Regulatory Affairs"

Master-Thesis

Off-Label Use of Medicines – General Aspects, Challenges and Strategies ***

Dr. Sonja Obermann (Abschlußjahr: 2013)

Summary
Language: English
Before a medicinal product is placed on the European market, it has to have undergone a stringent approval process. This is to ensure that the drug is safe, effective and of high quality. The usage of an authorized medicinal product outside the terms of its marketing authorization (MA) is internationally described as off-label use.
Off-label use of medicines is a widespread medical practice which is neither restricted to special clinical situations nor to single countries. There are situations where off-label prescribing is considered to be of significant value (e.g. to fulfill a public health need). However, due to the lack of rigorous and thorough scientific scrutiny drug usages outside the scope of the MA may be associated with potential harm to patients. Accordingly, off-label prescribing should be regarded as an exception to the rules and measures should be undertaken for its identification, monitoring and control.
Off-label use is challenging for the various stakeholders including regulatory agencies, health care professionals, pharmaceutical companies, health care payers and consumers.
There are no harmonized rules existing at EU level. Instead, each MS has its own policy with regard to off-label prescribing and reimbursement. Some countries have already implemented strategies in order to curb the widespread off-label use of medicines. However, these measures do not seem to be able to adequately address the problem.
The French authority approach may serve as an example of such local regulation. In December 2011, the French legislator introduced a new regulatory framework (law number 2011-2012) aiming at strengthening the safety of medicines. Based on this reform, France fundamentally changed the way how to regulate and monitor the off-label use of drugs. Among others, a new kind of marketing authorization, called “recommendation of temporary use” (RTU) was introduced. RTUs may be temporarily granted for an off-label use if there is an unmet therapeutic need and the benefit-risk ratio of the intended use is assumed to be favorable. Key elements of RTUs are strict monitoring of efficacy and safety of the drug use in question, a possible commitment of the pharmaceutical company to submit an application for a MA extension within a specified timeframe and a high likelihood for reimbursement. The RTU system together with other introduced measures tightens the identification and control of off-label prescriptions and may contribute to an overall safer use of medicines outside the scope of the MA. However, beside these advantages, the new framework has also some drawbacks. One of the main problems is that RTUs only focuses on “medically justified” off-label prescriptions. Therefore, only part of off-label uses will be covered by this approach. Overall, this new strategy is not expected to be comprehensive enough to adequately address the off-label issue and further progress should be made. Nevertheless, it can be considered a valid contribution to regulate the off-label use of drugs.
In the literature, several other approaches for regulating the off-label use of medicines have been proposed. They are summarized and discussed in this master thesis.
It can be concluded that the regulatory rules with regard to off-label use require an improvement not only in France, but also in the European Union and other countries. It is likely that only a  combination of various strategies will be able to solve the widespread off-label use problem. To ensure access to high-quality and safe medicines for the entire EU population an EU-wide harmonized solution is needed.
Pages: 41, Annexes: 11