The AMNOG process occupies a central position within Europe, as it is considered to be very detailed and scientifically sound. It is one of the most important European HTA procedures and key to accessing Europe's largest healthcare market: Germany.
The German HTA procedure for medicinal products is referred to as the "AMNOG procedure", named after the “Arzneimittelmarktneuordnungsgesetz“ (German Medicines Market Reorganization Act -AMNOG), which came into force on January 1, 2011.
The significance of the AMNOG procedure in the European context
The AMNOG procedure occupies a central position within Europe, as it is considered to be very detailed and scientifically based. Therefore, decisions of this procedure are important for the HTA procedures of other EU countries (especially smaller EU countries). The AMNOG procedure was controversial when it came into force in 2011, but it is now generally accepted. Nevertheless, individual aspects of the German benefit assessment continue to cause controversy. This applies, for example, to the choice of endpoints in clinical trials. AMNOG covers the benefit assessment of reimbursable drugs with new active ingredients on the basis of evidence provided by the manufacturer. It also applies to newly approved indications for these drugs, which means that a the manufacturer has to go through the same AMNOG process again for each new indication.
The Dossier in the AMNOG Framework
When launching a new drug on the market, the manufacturer is initially free to set the price for a maximum of twelve months. In Germany, the manufacturer is therefore privileged to the extent that he only has to take into account the competitive landscape when setting the price for the first twelve months; formally, there are no other restrictions when setting the price. At the same time as the market launch, the manufacturer must submit a dossier to the Federal Joint Committee (G-BA) that proves the additional benefit of the drug. This dossier contains all documents, including all clinical trials commissioned or conducted by the manufacturer in electronic form. The dossier is sent to the G-BA by mail as a CD or DVD.
The individual steps of the benefit assessment are described in Chapter 5 of the G-BA's Rules of Procedure. Annex II is of particular importance for pharmaceutical companies. In this appendix, the details regarding the requirements for the proof of additional benefit, for the determination of the appropriate comparator and for the dossier submitted by the pharmaceutical company are outlined. The G-BA may involve the Institut für Qualität und Wirtschaftlichkeit im Gesundheitswesen (Institute for Quality and Efficiency in Health Care (IQWIG)) in the assessment. Pharmaceutical companies may submit the dossier to the G-BA in advance for review for formal completeness without assessment of the content of the data it contains. The G-BA will then inform the company in writing, if necessary, which additional documents or information are required.
The Modules of the AMNOG Dossier
An AMNOG dossier consists of a total of 5 modules:
- Module 1 contains administrative information as well as a summary of the statements made in modules 2, 3 and 4.
- Module 2 contains the description of the drug for which the procedure is being conducted, as well as information on the approved indications.
- Module 3 contains information on the appropriate comparative therapy for each indication for which the procedure is performed. Module 3 further contains information on the number of patients for whom a therapeutically significant additional benefit exists, information on the therapy costs that can be expected for the statutory health insurance and information on the formal conditions which must be met to ensure the patient is treated in line with legally mandatory quality standards.
- Module 4 contains information on the therapeutic benefit and the additional therapeutic benefit in comparison to the appropriate comparative therapy for each therapeutic area for which the procedure is performed.
- Module 5 contains documents that are used to support the statements made in modules 2 to 4, as well as a checklist for checking the formal completeness of the dossier as an annex to module 1.
All documents included in Module 5 must generally be submitted in German or English. For clinical study reports that are not prepared in German or English, the following rules apply: The study report must be submitted completely in the original language. The core report of the study, the study protocol including all amendments, the statistical analysis plan and all tables of contents, including the table of contents for the appendices must also be submitted in German or English.
Which studies are to be submitted by the pharmaceutical entrepreneur in the AMNOG dossier is also regulated: In the dossier, the G-BA must be provided with the clinical study reports of the pivotal studies including the study protocols and the assessment report of the regulatory authority. In addition, all studies which have been submitted to the regulatory authority (usually EMA) must be included in the dossier. Furthermore, all results, study reports and study protocols of studies of the drug for which the manufacturer was the sponsor are submitted. In addition, the manufacturer must also include in the AMNOG dossier all available information on ongoing or discontinued studies with the medicinal product for which he was or is currently the sponsor. This also includes studies in which the manufacturer is financially involved in some other way without being a sponsor. Finally, the AMNOG dossier must also include information on third-party studies on the drug, if available.
Global Value Dossier and AMNOG Dossier
Many pharmaceutical companies create a Global Value Dossier from which they extract the relevant elements for the individual HTA procedures in Europe as if from a library. Since the AMNOG procedure is very detailed, it often makes sense to create a Global Value Dossier in parallel to the AMNOG dossier.
The Assessment of the AMNOG Dossier by the G-BA and the Impact
After three months, the reimbursement authorities’ assessment of the dossier is published and the manufacturer now has the opportunity to respond to the assessment. After a further three months, the G-BA then publishes its decision regarding the additional therapeutic benefit of the new drug. If this recognizes an additional therapeutic benefit compared to the standard therapy, the GKV-Spitzenverband (the umbrella organization of the German statutory health insurance funds) and the manufacturer negotiate the price at which the drug will be reimbursed by the statutory health insurance funds. These price negotiations must reach agreement within six months. If no agreement can be reached, an arbitration board will decide on the reimbursed price within three months on the basis of European reference prices. If the manufacturer objects to this, IQWIG may again be commissioned to conduct a cost-effectiveness assessment and the decision of the arbitration board can be adjusted.
However, if the decision is made that the drug was not able to demonstrate any additional therapeutic benefit, the drug is included in the so-called reference group price system. This system divides drugs into certain groups of comparable drugs, for example in terms of quality and identical composition, and sets maximum amounts for reimbursement by the statutory health insurers for these reference price groups. If the reference price group is characterized by drugs for which patent protection has expired (generics), then the pharmaceutical entrepreneur will not be able to market the innovative drug economically under normal circumstances. In this case, it is usually withdrawn from the German market because it is not profitable for the pharmaceutical company. If, on the other hand, only patent-protected, innovative drugs are included in the reference price group, the price level may be relatively high and thus adequate for the manufacturer, even if no additional therapeutic benefit has been granted.