First AMNOG benefit assessment based on mandatory patient registry

On April 2, 2020, the first precedent was published with the resolution on the benefit assessment of the substance asfotase alfa, in which the G-BA had requested data collection based on a mandatory patient registry in the past. The added benefit of asfotase alfa was first assessed in 2016. At that time, the added benefit of the orphan drug was considered proven based on the EMA approval. Nonetheless, the G-BA limited the resolution with the requirement to initiate a "prospective registry" in which "data from patients treated with asfotase alfa in Germany" were to be collected "in addition to the EMA requirements."

After exceedance of the 50 million-euro revenue threshold asfotase alfa was now re-assessed in comparison to the appropriate comparative therapy Best Supportive Care: The G-BA only granted a non-quantifiable added benefit for a small pediatric subpopulation based on a historical comparison. The data from the mandatory registry, however, was not considered for the benefit assessment. In the main grounds of the resolution the G-BA confirmed the formal fulfillment of the requirement of initiating a registry, but the consideration of the registry data was still not possible for several reasons. For the concrete formulation of these reasons, the G-BA partially took the exact wording of the harsh criticism the IQWiG had already published in their dossier assessment as well as in a tendentious press release on January 15, 2020.

This outcome was surprising as the Chair of the G-BA, Prof. Hecken, had made the consideration of the registry data a top-level topic in the oral hearing on February 24, 2020. In contrast to the IQWiG's criticism, Prof. Hecken made clear: "The fact is that the Federal Joint Committee had not requested a study in their resolution but the filling of a registry." Moreover, several advice meetings had taken place after the resolution with respect to the relevant endpoints of this registry. According to Hecken, this had to be taken into account "if you want to treat each other somewhat fairly." Despite these clear statements from the Chair, the G-BA almost fully adopted the IQWiG's evaluation. The IQWiG has already vehemently spoken out against the usability of registry data for some time, for instance, in a Rapid Report published on January 24, 2020. This benefit assessment may have prepared the ground for constantly high methodological requirements which may hardly be met based on, compared to randomized controlled trials, lower evidence levels often unavoidable in the case of rare diseases.

Sources:
G-BA resolution on the benefit assessment of asfotase alfa from March 17, 2016
Main grounds of the resolution on the benefit assessment of asfotase alfa from March 17, 2016
G-BA resolution on the benefit assessment of asfotase alfa from April 2, 2020 (reassessment of an orphan drug after exceedance of the 50 million-euro threshold)
Main grounds of the resolution on the benefit assessment of asfotase alfa from April 2, 2020 (reassessment of an orphan drug after exceedance of the 50 million-euro threshold)
Verbatim record of the oral hearing for the substance asfotase alfa from February 24, 2020
IQWiG dossier assessment asfotase alfa (published on January 15, 2020)
IQWiG Rapid Report
IQWiG press release from January 15, 2020