ZVT in AMNOG: now new with off-label use?

>> As is well known, AMNOG is a “learning system”. But in some cases the system is taught a lesson. This was done by the Federal Social Court (BSG) in February 2023 in the so-called regadenoson ruling: The G-BA's decision on this active ingredient was declared ineffective. This (in short) is because of the insufficient consideration of soloist status and because of the consideration of drugs in off-label use as appropriate comparative therapy (CVT).
“Compared to an approval-based soloist, the off-label use of drugs is not an appropriate comparator therapy” or “the use of drugs for off-label use cannot in principle be an appropriate comparator therapy,” according to the BSG (1). This also resulted in the sobering consequence: “If an appropriate comparator therapy cannot be determined, a decision on a benefit assessment cannot be made.”
What does that mean?
First of all, it should be noted that when determining an appropriate comparator therapy, it was actually already the case that
that a suitable medicinal product “basically has to have approval for the area of application” and must be “fit for purpose”. The G-BA has been avoiding this problem for years by using so-called therapy according to medical instructions as a collective term in cases where off-label use was to be determined as a comparator therapy (2).
This meant the off-label use, which was not allowed to be named. However, the G-BA took into account the off-label therapies as comparators of the approval studies and listed them as such in the supporting reasons. This was, among other things, The reason for this was that there was a discrepancy between the drugs approved for the indication and those used in care or recommended in guidelines. For example, only shortly before the BSG ruling in the case of the benefit assessment in the indication for the treatment of breast cancer, where trastuzumab in combination with cepacitabine was included in the assessment as a suitable comparator (3). As a rule, the G-BA did not explicitly identify off-label use as an appropriate comparator therapy. There was also no information about annual therapy costs in the decision for these therapies precisely for the reasons of the lack of approval.
But after the BSG ruling, this practice was initially completely thrown into disarray. Because it was initially clear: no off-label use as an appropriate comparative therapy and no AMNOG benefit assessment for therapeutic soloists. This was followed by a lot of discussion about the future of AMNOG, but above all a clear reaction from the G-BA with the rigorous removal of off-label therapies as acceptable comparator therapy in ongoing evaluations and consultations (4).
This was problematic because, in fact, off-label therapies are primarily used in the oncology area as comparators in clinical approval studies, as they occasionally fall short of the therapeutic standard of care, among other things. also correspond in Germany (see example above).
This means that some approval studies would not be usable in AMNOG. With the possible consequence that an additional benefit cannot be adequately represented and the drug would not be available in Germany.
A way out of this situation can be
now from the current changes in the ALBVVG (medicine delivery bottleneck control)
and Supply Improvement Act). Because it states (in shortened form) that the G-BA has to focus “on the actual supply situation as it would appear without the drug being evaluated”. “Exceptionally” off-label use can be designated as an appropriate comparative therapy if “according to the generally accepted state of medical knowledge in the area of application to be evaluated, this is considered to be the standard of therapy or as part of the standard of therapy in the care situation” and is used for the first time with the drug to be evaluated approved medicinal product is available, off-label use is generally preferable to previously approved medicinal products or, for relevant patient groups or indication areas, is generally preferable to medicinal products previously approved in the area of application (5).
Exactly how this will affect the AMNOG procedures remains to be seen. However, the law is likely to lead to a change in the determination practice at the G-BA. This means that it is at least clear that off-label use can be named as an appropriate comparative therapy in narrowly defined cases. This means that the so-called therapy according to medical standards should no longer be necessary as a cover for the G-BA. Above all, it is to be hoped that care-relevant registration studies with off-label use of drugs in the comparison arm will be taken into account in the AMNOG benefit assessment. This would be beneficial for everyone involved, especially for patients.
Finally, it should be noted that the publication (2) published a year ago in the “Monitor Healthcare Research” on the topic of determining and changing the appropriate comparative therapy may soon be out of date, at least with regard to the integration of off-label therapies. The AMNOG remains a learning system for everyone. <<

Literature:
(1) Federal Social Court. Judgment of February 22, 2023, B 3 KR 14/21 R. https://www.bsg.bund.de/
SharedDocs/Decisions/DE/2023/2023_
02_22_B_03_KR_14_21_R.html
(2) Rasch A. Changes to the appropriate use
equal therapy, Monitor Care Research 05/2022. http://doi.org/10.24945/MVF.05.22.1866-0533.2440
(3) G-BA. Main reasons for the decision of the Federal Joint Committee on trastuzumab-deruxtecan (breast cancer, HER2+, at least 2 previous therapies). https://www.g-ba.de/downloads/40-268-9240/2023-02-02_AM-RL-XII_Trastuzumab-Deruxtecan_D-837_TrG.pdf
(4) G-BA. Tragende Gründe zum Beschluss des Gemeinsamen Bundesausschusses zu Lisocabtagen maraleucel (Diffus großzelliges B-Zell-Lymp-hom, primär mediastinales großzelliges B-Zell-Lymphom und follikuläres Lymphom Grad 3B, nach ≥ 2 Vortherapien). https://www.g-ba.de/downloads/40-268-9410/2023-04-06_AM-RL-XII_Lisocabtagen%20maraleucel_D-867_TrG.pdf
(5) German Bundestag. Printed matter 20/7397. https://dserver.bundestag.de/btd/20/073/2007397.pdf