To date, the focus of discount agreements has generally been on generics. However, in recent years, there has also been increased activity to contractually agree discounts on patented pharmaceuticals for individual indications and in specific markets. After all, one in every 15 prescriptions in the patented sector is already discounted. In the future, the discount business will change significantly due to the Pharmaceutical Market Reorganization Act (AMNOG). In addition to the decentralized contracts between manufacturers and individual health insurance funds, centralized agreements with the Federal Association of Statutory Health Insurance Funds (GKV-Spitzenverband) will also be introduced.

> In Germany, approximately 2.2 million rebates have currently been agreed between health insurance funds and pharmaceutical manufacturers based on the pharmaceutical central number (PZN). This rather theoretical value corresponds to the number of discounted pharmaceutical products reported as discounted according to the Lauer-Taxe (Lauer-Taxe) in May 2010, regardless of whether these products are also prescription-relevant. Just under one percent, or approximately 21,000 agreements, are concluded for patent-protected pharmaceuticals. Considering the healthcare relevance of the concluded agreements based on the current prescription situation, this relevance is present despite the relatively small number of individual agreements: Currently, 3.7 million discounted prescriptions for patent-protected pharmaceuticals per year (June 2009 - May 2010) have been billed to the statutory health insurance funds. This corresponds to 6.6 percent of all statutory health insurance prescriptions or 6.4 percent of gross expenditures for patent-protected pharmaceuticals (see Figure 1).
In the recent past, there have been repeated efforts to include innovative pharmaceuticals as part of discount agreements pursuant to Section 130a Paragraph 8 of the German Social Code (SGB V). In addition to "classic" product-related discount agreements with a focus on "price" – such as discount agreements in the wake of a patent expiration – accompanying services are sometimes linked to discounts (so-called bundling) or defined therapeutic outcomes are integrated into the contract design.

Focus on added value and outcome instead of price
A purely price-based approach has proven ineffective for discount negotiations on patented pharmaceuticals. Since substitution within the pharmacy is not possible due to the diversity of innovations – as is the case with generic discount agreements – the health insurance provider cannot guarantee the discount partner higher sales as compensation for the discount granted. The same applies to the coupling of additional services to a product. Here, more complex added value must be found for the discount partner (the manufacturer) to make such a contract attractive to both parties. This could, for example, include a term that extends beyond the patent expiration date.
A focus on treatment success could also be interesting. An example of a focus on treatment endpoints is the agreement for the osteoporosis product "Aclasta," which the manufacturer Novartis concluded with the health insurance companies BARMER GEK and DAK as a risk-share contract: The drug, which is intended to help prevent bone fractures, is administered once a year as an infusion. Under a risk-share contract, the risk of treatment failure is shared between the health insurance company and the pharmaceutical company. In the event of failure, i.e., a bone fracture, partial cost coverage or reimbursement of the drug price is provided. Such an outcome orientation is not trivial for all indications, as the outcome is often difficult to measure directly. This also represents an obstacle to widespread implementation of these contract models.

Main indication areas of discount agreements for patent-protected medicinal products
Innovative medications for diabetes therapy, in particular, are subject to rebate agreements. Based on current prescription activity (June 2009 to May 2010), diabetes medications account for 68.8 percent of prescriptions of discounted, patented medications (see Figure 2). This is due to the special situation of insulin analogues (ATC3: A10C): After the Federal Joint Committee (G-BA) decided in July 2006 that short-acting insulin analogues are only reimbursable in exceptional cases for the treatment of type 2 diabetes, manufacturers concluded rebate agreements with almost all health insurance companies, allowing the continued prescription of insulin analogues. In this case, rebate agreements are therefore a necessary vehicle for securing market access. Decentralized contracts are also increasingly being concluded for long-acting insulin analogues. The manufacturers have already concluded 126 and 54 discount agreements for their active ingredients insulin glargine (Lantus, Sanofi-Aventis) and detemir (Levemir, Novo Nordisk), respectively, which together reach approximately 60 percent of statutory health insurance (GKV) members. Since, according to the Federal Joint Committee (G-BA) resolution of July 14, 2010, these active ingredients may only be prescribed at the expense of health insurance funds if there are no additional costs compared to human insulin (see Federal Gazette No. 103, p. 2422), further discount agreements are sure to follow.
In addition to insulin analogues, discounted patented medications originate primarily from prescriptions for blood and blood-forming organs, as well as the cardiovascular system. Here, market peculiarities such as the specific competitive situation for the platelet aggregation inhibitor clopidogrel (ATC3: B01C with 15.9 percent) or in the competitive market for antihypertensive drugs, where the various sartans (angiotensin II antagonists; ATC3: C09C with 4.4 percent and C09D with 4.0 percent) are the most important factors shaping the picture of discounting under patent protection on the prescription side.
The picture is almost comparable when focusing on the expenditure side, albeit with a few peculiarities. In terms of pharmaceutical expenditures, the most important discounted, patent-protected product is the anti-TNF drug "Enbrel" from Wyeth, which is used, among other things, to treat rheumatic diseases and psoriasis. Nearly 50 percent of statutory health insurance prescriptions for this drug were discounted in May 2010. Patent-protected drugs from the oncology and nephrology fields, an Alzheimer's disease drug, and an erythropoietin drug complete the revenue-side overview. Table 1 provides information on the most important patent-protected discounted products by revenue (basis: June 2009 to May 2010).

Changes to the discount situation due to the AMNOG
To date, discount agreements for patented pharmaceuticals have played a rather minor role. The described discount situation in the patented market is based on a decentralized structure: Pharmaceutical manufacturers conclude discount agreements with individual health insurance funds or a group of health insurance funds under Section 130a Paragraph 8 of the German Social Code (SGB V). With the Pharmaceutical Market Reorganization Act (AMNOG), which is expected to come into force on January 1, 2011, the focus is on centralized agreements on reimbursement amounts with the National Association of Statutory Health Insurance Funds (GKV-Spitzenverband) (see Figure 3).
On the market side, this will likely lead to an increase in discount agreements for patented substances starting at the end of 2011, although the first effects are not expected until 2012. Whether, and if so, how, more complex decentralized bundled contracts (e.g., linking discounts with accompanying services) or even outcome-oriented contractual constructs (e.g., a "price-back guarantee") will find their way into the market alongside this form of centralized reimbursement agreement is currently unclear. These contracts would be welcome in terms of improved, not just more cost-effective, patient care.
In conclusion, from the perspective of health services research, several points remain to be critically discussed regarding the AMNOG: According to health experts, the Pharmaceutical Market Restructuring Act (AMNOG) is merely another cost-containment law. However, it would be important to place the individual patient and their care at the center of the pharmaceutical market restructuring.
AMNOG – a step backwards for health services research?
The AMNOG does not legally enhance the role of health services research. Rapid assessments of pharmaceuticals with new active ingredients can only be conducted without considering everyday care, since patient benefits and harms generally only become apparent after extended periods of use. Furthermore, cost-benefit assessments and contract-related health services research studies are only included in the AMNOG as optional and subsequent "may" clauses. There is no mandatory nature of these, thus missing a significant opportunity to make health services research mandatory for manufacturers.
Furthermore, the legislature has not provided for an evaluation of the new measures introduced by the AMNOG. Consequently, the AMNOG does not promote the urgently needed transparency in everyday healthcare provision, as would be permitted by the implementation of Section 303a-f of the German Social Code (SGB V), but ultimately creates further opacity. This also applies to the results of negotiations on reimbursement for given additional benefits: It is unclear whether these results must be published or not. This is the only way to conduct a detailed evaluation of the effectiveness of measures such as discount agreements for patented pharmaceuticals.
It can therefore be stated that the AMNOG will not significantly strengthen the role of health services research and its fundamental demands, such as patient orientation and transparency. A patient-centered design of the health care system requires a profound analysis of the reality of health care provision. Health services research must therefore become a natural and continuous element of decision-making in the health care system.
Christian Bensing, Dr. André Kleinfeld*