Masterstudiengang "Drug Regulatory Affairs"

Master-Thesis

In the Area of Tension between the Conditional Marketing Authorization and the Health Technology Assessment: Challenges for the Pharmaceutical Industry

Dr. Bastian Hoffmann (Abschlußjahr: 2019)

Summary
Language: English
In 2006 the conditional marketing authorization was introduced by EMA in order to make innovative therapies available for patients in a faster way. Life-threatening, seriously debilitating or new medicinal products with an orphan drug designation are applicable for this regulatory pathway and less-comprehensive data, than for the standard marketing authorization, are required. The comprehensive data set will be completed after the initial marketing authorization and the CHMP can impose specific obligations that the corresponding MAH must fulfill. From the beginning there were concerns regarding the conditional marketing authorization from the reimbursement perspective, since the efficacy and safety is not proven by the concept of evidence-based medicine.
In Germany the Health Technology Assessment is carried out by the G-BA and new medicinal products that with an orphan drug designation have an additional benefit by law. In case a new medicinal product has no orphan designation, then the G-BA applies the same requirements are applicable for medicinal products that were authorized through the conditional marketing authorization pathway as for medicinal products that have a standard marketing authorization. The fact, that less-comprehensive data are available for medicinal products with a conditional marketing authorization, makes it a great challenge for a pharmaceutical company, to get an additional benefit rating from G-BA.
Furthermore, G-BA only accepts patient relevant endpoints and the endpoints, that are accepted by CHMP, differ from the endpoints, that are accepted by G-BA. In combined scientific advices from EMA and European HTA bodies it was suggested that pharmaceutical companies should perform indirect comparisons, in case EMA and an HTA body could not agree on e. g. relevant endpoints or the active comparator. Indirect comparisons are frequently not accepted by G-BA. Furthermore, the actual comparator can change over time, since G-BA determines the comparator at the time of the assessment. This makes the HTA procedure in Germany even more challenging, besides the fact, that less-comprehensive data are available for a medicinal product with a conditional marketing authorization. Additionally, in cases where a re-assessment is performed by G-BA, the requirements from G-BA can change, what can result in an even lower benefit rating, than the initial one.
Of course, the question could be asked, if the conditional marketing authorization is well justified. Therefore, a report of EMA on the use of the conditional marketing authorization from 2006 until 2016 was analyzed. The fact, that it took in average 4 years to complete the comprehensive data set, for medicinal products where the conditional marketing authorization was turned into a standard marketing authorization and that some studies were delayed due to “better than expected results” shows that patients can benefit from the pathway. It should be noticed, that for one medicinal product in 2019 the conditional marketing authorization was withdrawn due to lack of efficacy. Furthermore, with the case of Venclyxto it could be shown, how important the orphan drug designation can be in the German HTA procedure.
Additionally, in the EEA every country has to date its own HTA procedures, like UK and France, with its own requirements. Therefore, the HTA procedures in England and France were analyzed. In both countries, the concept of the Quality Adjusted Life Years is used in the assessment, which is not used in Germany. Furthermore, it seems, that NICE in England and HAS in France are more flexible in their approach, since NICE involves clinical Experts in the assessment and HAS accepts indirect comparisons, if this is well justified.
Pages: 52