Add-On Payments and Price Evolution for Orphan Drugs in Oncology in Germany From 2011 to 2019

Mareike Konstanski, MSc, Thomas Mittendorf, PhD, Ulrike Kuchenbecker, PhD, Hanne Bubendorfer-Vorwerk, PhD, Xcenda GmbH, Hannover, Germany

In Germany, inpatient drug costs are reimbursed as part of the individual diagnosis-related group (DRG) payment rates. Since DRGs are being adjusted annually based on historic costs, there is a time lag between the point where a new technology is introduced into the market and when these costs are reflected in the DRG payment system. To address possible funding gaps for new and innovative treatments within the DRG system, hospitals can apply for extra budgetary reimbursement for a specific innovative technology for the subsequent year—the so-called Neue Untersuchungs- und Behandlungsmethoden (NUB).¹ The application period for a NUB is every year from the beginning of September until the end of October, a process that is led by the Institute for the Hospital Remuneration System (InEK) via an electronic tool. The InEK evaluates the applications and assigns a status that determines the eligibility for the negotiation of extra funding between a hospital and a health insurance (Table 1).

Table 1. Overview of possible NUB status.

Reimbursement for Inpatient Drugs in Germany
If the NUB status is 1, 3, or 4, hospitals can negotiate (add-on) reimbursement with the health insurances. NUB applications can be repeated yearly until the cost for the new drug is reflected within the German DRG system.^2,3 For all newly approved drugs in Germany, the Federal Joint Committee (G-BA) assesses the additional benefit by conducting a formal assessment according to the Act on the Reform of the Market for Medicinal Products (AMNOG) as a basis for price negotiations to determine the drug’s maximum reimbursable price. The National Association of Statutory Health Insurance Funds (GKV-SV) and the manufacturer will negotiate the final price, which is then applicable for the inpatient and outpatient settings. Because hospitals are autonomous in making purchasing decisions, manufacturers must negotiate twice. First, with GKV-SV to find the maximum reimbursable price to be paid within the Statutory Health Insurance (GKV) that will be listed in the public price tariff. Second, with the individual hospital or purchasing groups to determine the maximum purchase price, for which negotiated discounts are confidential.

The questions for this analysis were: (1) how NUB status changes over time for new and innovative drugs; (2) what is the timeframe from status approval until implementation into the DRG system; and (3) what implications it might have for the price.^1,4

We analyzed orphan drugs in oncology and the respective AMNOG dossiers submissions from the beginning of AMNOG until December 31, 2019.⁵ InEK data were screened determining the result of the NUB applications.⁶ The price history was derived from the official price tariff (Lauertaxe).⁷ Only descriptive statistics were applied.

Since the beginning of AMNOG, 31 oncology drugs with orphan status were assessed (Table 2).

Table 2. Orphan drugs with an oncology indication and complete AMNOG assessment.

Within the first year of market entry, NUB status 1 was granted for 3 of the 31 products (~10%). In the second year, NUB status 1 was granted for 28 of the 31 (~91%) products. In the first year, 8/31 (26%) products received status 2 (denied), and 7/31 (23%) received status 4 (reimbursement under exceptional individual circumstances). For 13/31 (42%) products, no hospital applied for a NUB in the first year of market entry. The reason for this might be the timing of the launch date near or after the deadline for NUB submission and the likelihood of success of the NUB application. If an application is made too early, the data show that in most cases, only a status 2 was granted, negating the possibility of negotiating extra funding.

NUB Status: Bridging Potential Reimbursement Gaps
For 7 out of 8 products with a status 2 in year 1, the status changed in the subsequent year (year 2). The remaining product received status 1 in the third year of application. All cases with a status 4 in the first year of application received status 1 in the second year. Changes from NUB status 1 to 2 are often accompanied by an integration of the drug into the DRG system through additional supplementary payments, or additional charges. Within the given timeframe, the mean duration of granted NUB status 1 and implementation into the DRG system was 4 years (range: 1–7 years) (Figure).

Figure. Time elapsed before a product loses a positive NUB status (change from status 1 to 2).

Ponatinib and pomalidomide maintained their NUB status for the longest period with a still ongoing status 1 for 7 years. The shortest duration was 1 year for Zalmoxis^®. Of the analyzed drugs, 13 (~40%) had a status 1 for over 3 years at the time of this assessment. The observed mean duration of 4 years with status 1 was longer than that assessed by Freiberg, et al in 2016.⁸ The reason for this might be because the orphan status limits the available information for the yearly assessment by the InEK, causing longer periods of data collection.

For the majority (8/10 with NUB status change from 1 to 2) that lost status 1 over time, an additional fee was implemented. The 2 other drugs—Zalmoxis^® and olaratumab— changed from NUB status 1 to 2 without the implementation of any additional charges. Both Zalmoxis^® and olaratumab are no longer available on the German market. Another drug lost its orphan status since the first assessment (ramucirumab) without consequences for the additional charges. Important events for price changes were (1) the AMNOG price negotiation and (2) change in NUB status. In the given timeframe, all prices (without considering discounts) decreased on average by 26% (range: 7%–44%), mainly after the AMNOG price negotiation or a change in NUB status. For granting a status 1, the price level does not seem to be a key driver, as there was no relation between price and NUB status to be detected. Nevertheless, the funding of the related DRG and available data for the calculation seem to be influential.

Conclusion
Even in orphan indications with only a limited number of patients, ensuring a NUB status 1 for new drugs is of paramount importance for hospitals to cope with individual high-cost cases. The main factors of success for a NUB application are (A) the hospital perspective of economic consequences and (B) the stakeholder involvement to draft the application.

References

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2. GKV-Spitzenverband. Neue Untersuchungs-und Behandlungsmethoden (NUB). Published 2020. https://www.gkv-spitzen-ver-band.de/krankenversicherung/krankenhaeuser/drg_system/neue_untersuchungs_und_behandlungsmethoden_nub/neue_untersuchungs_und_behandlungsmethoden_nub.jsp. Accessed November 30, 2020.

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