Innovative Medicines
Innovative, patent-protected drugs can be placed on the German market immediately after receiving European or national marketing approval. Once the drug has entered the market, the pharmaceutical company can freely determine the product’s price and the health insurance companies also reimburse the costs. Upon market entry, the pharmaceutical company has to submit a dossier to the Federal Joint Committee (G-BA) as part of AMNOG’s early benefit assessment. he Joint Federal Committee is formed by the unbiased representatives of the Joint Federal Committee, the German Association of Statutory Health Insurance Funds (Spitzenverband der gesetzlichen Krankenkassen), the National Association of Statutory Health Insurance Physicians (Kassenärztliche Bundesvereinigung) as the organ of physicians in private practice, the German Hospital Association (Deutsche Krankenhausgesellschaft) as the representative of hospitals and non-voting patient organisations. The benefit dossier has to comply with the formal criteria of the G-BA – in particular for its completeness – and has to be prepared on pre-specified formats.
Early Benefit Assessment according to AMNOG
An essential parameter for the preparation of an AMNOG benefit dossier is the comparison of the new drug with an appropriate comparative therapy determined by the G-BA, since the additional benefit of a drug is determined in comparison to an appropriate comparative therapy. It is generally advisable to consult the G-BA before preparing a benefit dossier in order to clarify the appropriate comparative therapy in the field of application. If several appropriate comparative therapies are provided, the pharmaceutical company can select one of the specified ZVTs for the early benefit assessment. urthermore, questions on patient-relevant endpoints and their validity as well as on the population or subpopulations can be discussed in the consultation. The Institute for Quality and Efficiency in Health Care (IQWiG) conducts the G-BA’s benefit assessment for innovative drugs; the G-BA decides on the benefits and additional benefits.
The benefit assessment process is structured in terms of time and content. The early benefit assessment is published by the IQWiG on the G-BA homepage within 3 months after submission of the AMNOG dossier. This is followed by a consultation phase, which consists of a written statement to be submitted within 3 weeks. Secondly, an oral hearing takes place at the Federal Joint Committee approx. 2 weeks after the submission of the written statement. The decision of the Federal Joint Committee on the additional benefit of an innovative drug is published 6 months after market entry / dossier submission. The Federal Joint Committee decides on the probability and extent of the additional benefit of a new drug compared to the appropriate comparative therapy. The definitions of the probability and extent of the additional benefit are described in IQWiG’s methods paper. It distinguishes between evidence, indication or indication of the likelihood of added benefit, whereby these categories are essentially determined by the supporting evidence (number and quality of randomised controlled trials). The effect sizes related to individual patient-relevant endpoints determine the extent of the additional benefit. In this context, the categories of significant, considerable, minor, non-quantifiable, no or minor additional benefit are distinguished. The categories are described in the Regulations on the Evaluation of the Benefit of Medicinal Products and are operationalised in IQWiG’s methods paper.
Price Negotiations
The result of the benefit assessment of the G-BA has consequences for the price negotiations on the reimbursement amount. Within 6 months after the benefit assessment, the price negotiations are conducted between the pharmaceutical entrepreneur and the GKV Spitzenverband. For this purpose, the GKV Spitzenverband specifies 4-5 negotiation dates in order to reach an agreement on the reimbursement amount within the time frame. Price negotiations above the price of the appropriate comparative therapy are in general only possible for drugs with an additional benefit. New drugs for which no additional benefit is available or cannot be proven are agreed at the level of the most economical comparative therapy. According to the law, deviations from this rule are only possible in exceptional cases.
For new drugs grouped in a reference price group, the benefit assessment is performed according to the reference price system. In the absence of any additional benefit, these medicinal products are assigned directly to the existing reference amount group, thus the reference amount is the maximum reimbursable amount. The reimbursement amount will apply 12 months after market entry. In case no agreement can be reached on the reimbursement amount, arbitration will take place within 3 months to determine the reimbursement amount retrospectively.
The new reimbursement amount therefore always takes effect 12 months after market entry / submission of the dossier. For drugs evaluated for a new indication, the already negotiated reimbursement amount applies first – for a period of 12 months – or for drugs placed on the market before the introduction of AMNOG, the existing price. During the negotiations, the reimbursement amount / price may be adjusted.
Market Access and Reimbursement in the Inpatient Area
The AMNOG generally only refers to outpatient drug prices regulated by the Drug Price Ordinance. In the inpatient area, drug prices are agreed directly between the pharmaceutical company and the hospitals. In this respect, the AMNOG reimbursement amount only has a signaling function for negotiations in the inpatient sector.
The reimbursement between the hospitals and the health insurance companies in the inpatient area is based on the inpatient reimbursement system. For the reimbursement of new drugs, hospitals can submit a so-called NUB application to the Institute for the Hospital Remuneration System (InEK). If the InEK states that the new drug is not yet properly remunerated with the DRG system, a NUB fee for the innovative drug may be agreed between the requesting hospital and the health insurance companies.
Thus, the new service is reimbursed in addition to the DRG system’s lump compensation. NUB applications are only accepted annually with the deadline of 31 October; the InEK decides on the applications by the end of January of the following year. Medicines that are used exclusively in the inpatient area can be exempted from the early benefit assessment according to AMNOG. An application for exemption had to be submitted to the G-BA at least 3 months before the drug is placed on the market.
The G-BA evaluates the patient-relevant benefits and additional benefits of an innovative drug with regard to the endpoint categories of mortality, morbidity, quality of life and side effects. The evaluation is based on the methodology of evidence-based medicine, whereby randomised controlled trials are generally required for drugs. A particular challenge arises if the appropriate comparative therapy in the approved indication or for individual subpopulations is not represented by the approval studies. In this case, indirect comparisons have to be performed to describe the additional benefit Besides assessing the additional benefit, the G-BA also decides on the number of patients in the indication / subpopulation, i.e. the prevalence of the disease in Germany. Furthermore, the costs of the new, innovative therapy are compared with the costs of the appropriate comparative therapy.