How will German early benefit assessments change in the future?

Welcome to the last post in the HTA series, focusing on the changes to HTA and early benefit assessments in Germany in the near and far future!

Next week, I’ll be focusing on another one of G-BA’s key tasks, the quality assurance in German health care.

Future changes to early benefit assessments

Over the last few months, several groups have published their ideas on changes to the early benefit assessments and pricing system. Last week, on 16 March 2022, the new German health minister, Prof Dr Karl Lauterbach shared his draft of a new law to stabilise the finances of the SHI funds (German: “GKV–Finanzstabilisierungsgesetz“).

The proposed changes are affecting 8 key areas of the early benefit assessments and pricing of products:

The final price negotiated between the manufacturer and the GKV-SV should be applied retroactively from month 7 after launch onwards. Currently, the price applies from month 13 onwards.
The price negotiations can now include price-volume agreements or caps on annual prescription volumes.
A full early benefit assessment will be triggered for orphan drugs when annual sales exceed a €20mn threshold, instead of the current €50mn.
For certain drugs that are used in combination, the price negotiations will include an additional 15% discount.
The discount which manufacturers are obliged to grant SHI funds increases from the current 7% to 19% in 2023, and then gradually reduced again to 10% by 2026.
The mandatory discount that pharmacies have to grant SHI funds increases from €1.77 to €2.00.
The price cap for products outside of reference price groups has been extended to the end of 2026.
The VAT on drugs will be reduced from 19% to 7%.

This non-authorized draft has been withdrawn again a few days after publication.

Joint HTAs

Last year, the G-BA had agreed to joint EU HTAs coming to Germany. For a long time, the G-BA did not want changes to the current early benefit assessments and replace them with joint assessments. However, they agreed to a compromise in July 2021. The G-BA will accept the joint scientific assessment of the clinical evidence but wants to independently interpret the data.

On 14 December 2021, the EU Parliament adopted the EU Regulation on joint HTAs. While EU member states previously had already voluntarily collaborated within EUnetHTA, this new regulation is a binding cooperation between the national HTA authorities of the EU member states. It will be applicable to new drugs, including ATMPs, but also medical devices.

While the chair of the G-BA, Prof. Hecken, sees the most value of these joint HTAs for “member states that were previously unfamiliar with this systematic, comparative analysis of clinical data”, there will also be an impact on the early benefit assessments in Germany. In the future, the G-BA must take these joint clinical assessments at the European level into account, provided that these data are suitable for the national decision-making and meet quality requirements. However, the joint HTA at the European level will not replace the decisions on the additional benefit or on reimbursement. The additional benefit as determined by the G-BA will remain to be the basis for price negotiations between the GKV-SV and the manufacturers.

Process and methodology

The EUnetHTA21 consortium, which consists of 13 organizations, will be implementing the new regulation. Amongst these are not just one, but two German groups, the IQWiG and G-BA. The other countries represented within EUnetHTA21 are Spain, Austria, Belgium, France, Italy, Portugal, Ireland, Hungary, Norway, Sweden, and the Netherlands.

The IQWiG already participated in joint HTAs as a EUnetHTA founding member since 2006. Over the years, EUnetHTA worked on three overarching projects, called Joint Actions 1 to 3. The IQWiG has supported these on the topics of method development, information gathering, and quality assurance, especially the introduction of a modern quality management system.

Between 2021 and 2023, EUnetHTA21 will determine the methodological basis for joint assessments. These would be mainly based on the EUnetHTA project Joint Action 3. The overarching goal is to establish uniform standards for joint benefit assessments of health technologies in Europe. The G-BA will now develop the procedural and structural requirements as well as methods for clinical consultations. The aim is a binding agreement on the methods, e.g. on how to assess different types of evidence. While comparative controlled data will remain the best scientific basis, there is a growing need for RWE.

Timeline

The G-BA plans to roll out the inclusion of joint HTAs in the German early benefit assessments in stages.

From 2025 onwards, the G-BA will use joint clinical assessments to assess oncology drugs, including orphan drugs and ATMPs.
After 3 years, this will be widened to also include non-oncology drugs.
After another 2 years, the G-BA will assess all drugs, as well as medical devices, in a joint HTA.

The assessment of the additional benefit and reimbursement decisions will remain at the national level, so will stay in the hands of the G-BA.

Are joint HTAs suitable for the German market?

Shortly after the announcement of the plan for joint HTAs in the EU, Kisser et.al. published their assessment on the compatibility of the joint HTAs with German early benefit assessments.

From 2025, the G-BA should use joint clinical assessments from EUnetHTA21 as the basis for determining the additional benefit. The group, therefore, asked if the data produced in the joint clinical assessments will be sufficient for G-BA decision-making.

To this end, they reviewed all 5 joint clinical assessments that EUnetHTA produced according to Joint Action 3 and compared these with the G-BA early benefit assessments of the same products.

They found several differences between the produced and required data that can have a major impact on the early benefit assessment outcomes:

Data missing for early benefit assessments

Sometimes, the EUnetHTA and G-BA defined different subpopulations within the target indication. This also meant that both groups defined different comparators for these subpopulations. Therefore, joint clinical assessments did not always produce the required data for all subpopulations and all comparators.
In addition, German early benefit assessments require more subgroup analyses, e.g. by age, gender, weight, disease stage, prior treatments, etc., across more endpoints.

Differences resulting in different conclusions on the benefit or value of an intervention

EUnetHTA assessments include more types of evidence. They accept data from ITCs or single-arm trials. Instead, the G-BA does generally not accept ITCs and doesn’t consider them in their decision-making. They view single-arm studies only as complementary evidence.
Also, EUnetHTA and G-BA differed in their views on the acceptance of surrogate or intermediate endpoints, and EUnetHTA generally included a broader range of morbidity endpoints. The G-BA considers PRO endpoints from the EORTC QLQ-C30, EORTC QLQ-LC13, EQ-5D VAS and MSIS-29 instruments as morbidity outcomes, while EUnetHTA classes them as HRQoL outcomes.
The views on the risk of bias and the quality of evidence associated with overall survival and morbidity endpoints differed between both groups. Interestingly, EUnetHTA regarded OS data as less robust in some studies compared with the G-BA.
Lastly, both assessments lead to different conclusions on the safety profile, since EUnetHTA and the G-BA applied different operationalizations on AEs and different weights on individual endpoints. For example, the G-BA uses effect estimates on safety outcomes that are adjusted for different treatment durations between treatment arms, while EUnetHTA did not include an adjustment.
The EUnetHTA also was more lenient in accepting study interventions when the trials did not use them according to the marketing authorization.

To overcome these differences, the proposal for future joint HTAs includes consultations with HTA bodies and stakeholders to discuss the relevance of the proposed patient groups, comparators and endpoints during the scoping phase, with the aim that EUnetHTA produces clinical assessment that all member states can use.

Reference: Kisser, A., Knieriemen, J., Fasan, A. et al. Towards compatibility of EUnetHTA JCA methodology and German HTA: a systematic comparison and recommendations from an industry perspective. Eur J Health Econ (2021). https://doi.org/10.1007/s10198-021-01400-2

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