AMNOG process in Germany: benefit assessment, evidence requirements and preparation

The AMNOG process is Germany's national pathway for the early benefit assessment of new medicines and the subsequent determination of a reimbursed price. For international market access and evidence teams, the key point is that AMNOG is not simply a post-launch dossier exercise. German requirements can affect comparator strategy, population definitions, endpoints and analyses well before the national dossier is submitted.

The formal early benefit assessment starts with submission of the AMNOG dossier. The Federal Joint Committee (Gemeinsamer Bundesausschuss, G-BA) defines the German assessment framework, including the appropriate comparator therapy (zweckmäßige Vergleichstherapie, zVT). The Institute for Quality and Efficiency in Health Care (IQWiG) is frequently commissioned to assess the submitted dossier. The G-BA ultimately decides whether an additional benefit has been demonstrated for the relevant patient population or populations.

The stages are connected: early G-BA advice can inform German evidence planning; the AMNOG dossier aligns the available evidence with the German assessment question; IQWiG and the G-BA assess that evidence; and the written commenting procedure and oral hearing address remaining assessment issues before the final G-BA resolution.

Regulatory status: October 2026. Timelines, formal requirements and methodological standards should be checked against the current primary sources for each individual procedure.

For guidance on individual stages, the guide to G-BA advice covers preparation for the consultation, the AMNOG dossier guide explains submission requirements, the appropriate comparator therapy guide covers comparator planning, and the guide to written comments and the G-BA oral hearing explains how to prepare for the discussion with the G-BA.

The AMNOG process at a glance

The AMNOG process combines Germany's early benefit assessment with the subsequent reimbursement price process. The statutory assessment starts with dossier submission, but preparation for the German assessment question starts earlier.

G-BA advice and evidence planning → AMNOG dossier → early benefit assessment → written comments and oral hearing → G-BA resolution → reimbursement price

The statutory timeline is only part of AMNOG readiness. Whether the submitted evidence can answer the German assessment question depends on decisions made during clinical development and before dossier preparation.

AMNOG preparation starts before dossier submission

The formal early benefit assessment starts with dossier submission, but the conditions for assessable evidence are created much earlier. Study design, comparator choice, study population, endpoints and statistical planning can determine which evidence is usable in the German assessment.

For international teams, four levels need to be connected:

clinical development programme → authorised indication → German assessment question → assessable evidence

A study that supports regulatory approval does not automatically address every requirement of the German benefit assessment. This becomes relevant, for example, when the trial comparator differs from the later zVT, when the authorised indication is divided into several German patient populations, or when trial endpoints are only partly accepted for the German assessment.

Statistical requirements also need early consideration. Existing trial data can be reanalysed after study completion, but endpoints that were never collected or data that are unavailable for relevant patient populations cannot be created retrospectively.

AMNOG preparation is therefore broader than producing a dossier on time. The earlier question is whether the clinical development programme can support the expected German assessment question.

G-BA advice links evidence planning to the later AMNOG process

G-BA advice can address central elements of the future German benefit assessment before the AMNOG dossier is submitted. It can be particularly relevant while information on comparator, population or endpoints can still inform evidence planning.

Potential topics include:

• the appropriate comparator therapy (zVT),

• study and target populations,

• patient-relevant endpoints,

• planned evidence generation,

• other methodological questions relevant to the German assessment.

G-BA advice is not a pre-decision on the later additional benefit. The benefit assessment is based on the evidence available at the time of the procedure and the medical and scientific knowledge applicable at that point.

The practical value of advice therefore lies in understanding what the feedback means for the development programme, analysis planning and later dossier strategy.

These aspects are covered in more detail in the guide to G-BA advice.

The zVT defines the comparator for the German benefit assessment

The zweckmäßige Vergleichstherapie (zVT) is the appropriate comparator therapy defined for the German AMNOG assessment and provides the reference against which additional benefit is assessed. It is a Germany-specific concept and should not be treated as interchangeable with comparator concepts used in other HTA systems.

Where an appropriate randomised study directly compares the new medicine with the relevant zVT, the evidence can address the German comparison directly. If the trial comparator differs from the zVT, teams need to assess which evidence remains usable for the German question and whether an indirect comparison may be feasible.

An indication may also be divided into several patient populations with different comparator therapies. The evidence then needs to be considered separately for the respective German assessment questions.

The zVT may change during development as treatment standards, guidelines, clinical evidence or available treatment options evolve. Comparator assumptions made early in development therefore need to be reviewed against the current German treatment landscape.

A separate guide to the zVT in AMNOG covers comparator determination and changing comparator scenarios in more detail.

Population and endpoints determine whether evidence is usable in AMNOG

Clinical evidence is fully usable for AMNOG only if the population, endpoints and analyses adequately address the German assessment question. Evidence can be sufficient for regulatory approval while addressing only part of the subsequent German HTA question.

Three population levels need to align:

trial population → authorised indication → German assessment populations

Differences in prior therapy, disease stage, biomarkers or other patient characteristics can result in separate German patient populations and potentially different comparators.

The German benefit assessment focuses on patient-relevant effects, particularly:

mortality → morbidity → health-related quality of life → adverse events

The existence of an endpoint in a clinical trial does not by itself determine whether it will be usable in AMNOG. Patient relevance, measurement instruments, endpoint operationalisation, data quality and statistical analysis can all affect the assessment.

The same applies to subgroups and additional analyses. Planning should therefore consider which analyses may be required for the German assessment before pivotal studies are completed. Additional analyses can reinterpret existing data, but they cannot replace information that was never collected.

The AMNOG dossier aligns the evidence with the German assessment question

The AMNOG dossier structures the available evidence around the specific German assessment question. It links the authorised indication with the relevant patient populations, the zVT, the available studies and the claimed additional benefit.

Dossier preparation therefore requires a clear view of which evidence is available for each patient population and against which comparator. Relevant considerations include endpoints, statistical analyses, subgroup analyses and limitations of the evidence.

Potential issues may include:

• differences between the trial comparator and the zVT,

• differences between the study population and the relevant German population,

• uncertainty around individual endpoints,

• missing or problematic subgroup analyses,

• limitations of the study design,

• missing data,

• uncertainty in statistical analyses.

Dossier submission changes the perspective. The focus moves from the manufacturer's rationale for the additional benefit claim to the assessment of whether the submitted evidence supports that claim.

The structure, modules and evidence requirements are covered in the AMNOG dossier guide.

IQWiG and the G-BA assess the evidence for additional benefit

The German early benefit assessment examines whether, and to what extent, a new medicine provides additional benefit compared with the zVT for the relevant patient population or populations. The assessment is based on the dossier submitted by the pharmaceutical company.

The G-BA is responsible for the early benefit assessment and may commission IQWiG to assess the dossier. IQWiG evaluates the submitted evidence and may reach conclusions that differ from the company's assessment.

The assessment can be understood as a sequence:

dossier → zVT and patient population → patient-relevant endpoints → certainty of results → magnitude of effects → overall conclusion on additional benefit

For individual patient-relevant endpoints, the assessment considers the effects versus the zVT and the certainty of the underlying results. Study design, risk of bias and consistency of findings can all influence the conclusion.

For positive or negative effects, the magnitude is then assessed. Categories for a positive additional benefit include minor, considerable and major, as well as non-quantifiable where the magnitude cannot be quantified.

Separately, the certainty of the conclusion is classified. Depending on the evidence, the German categories distinguish between an indication (Anhaltspunkt), a hint (Hinweis) and proof (Beleg) of additional benefit. These German categories have specific methodological meanings and should not be treated as generic English evidence labels.

The endpoint-level findings are then brought together into an overall conclusion. Benefits in one endpoint are not considered in isolation; disadvantages, uncertainty and findings in other patient-relevant outcomes can affect the overall assessment.

Additional benefit can also differ between patient populations. One authorised indication may therefore result in several German assessment questions with different zVT and different conclusions on additional benefit.

The benefit assessment is published no later than three months after the relevant dossier submission date. Publication starts the commenting procedure. The assessment is an important intermediate step, but it is not the final G-BA decision.

Written comments and the oral hearing address outstanding assessment issues

After publication of the benefit assessment, relevant issues can be addressed through the written commenting procedure and the subsequent oral hearing. This stage responds to the specific findings of the published assessment rather than reopening the entire dossier.

The written commenting period is three weeks after publication of the benefit assessment. Depending on the procedure, relevant topics can include the zVT, inclusion of studies, patient-relevant endpoints, statistical analyses, patient populations or the derivation of additional benefit.

Not every criticism has the same relevance for the later G-BA resolution. The focus is therefore on assessment issues that can be addressed with additional evidence, analyses or scientific argumentation and that may be material to the final decision.

The oral hearing complements the written procedure and allows remaining issues to be discussed directly with the G-BA. Its role is to focus on unresolved questions relevant to the subsequent resolution.

A separate guide covers written comments and the G-BA oral hearing in more detail.

The G-BA resolution concludes the early benefit assessment

The G-BA resolution contains the final decision on additional benefit and concludes the early benefit assessment. The decision takes account of the benefit assessment and the written and oral commenting procedure.

Different conclusions may apply to different patient populations. The relevant zVT and the magnitude and certainty of additional benefit are central elements of the resolution.

dossier → benefit assessment → written comments and oral hearing → G-BA resolution

The G-BA resolution does not end the overall AMNOG process. It is followed by reimbursement price negotiations between the pharmaceutical company and the National Association of Statutory Health Insurance Funds (GKV-Spitzenverband). This guide focuses on the clinical evidence and early benefit assessment through the G-BA resolution.

EU HTA changes the interface with the AMNOG process

For medicines subject to Joint Clinical Assessment (JCA), EU HTA does not replace the German early benefit assessment. Germany retains its national decision on additional benefit against the German zVT.

AMNOG preparation therefore needs to determine which European assessment questions cover the later German question and where national requirements remain additional or different.

Particularly relevant are:

• German patient populations,

• the zVT,

• patient-relevant endpoints,

• relevant subgroups and analyses,

• national methodological requirements,

• evidence available at the start of the German AMNOG process.

JCA PICO → German assessment question → zVT → national evidence requirements

European and German evidence planning should therefore be connected. The key question is whether evidence assessed at European level also supports the German national assessment and which updated or additional content is required for AMNOG. For background, see EU HTA in Germany and the JCA process. How JCA PICOs are defined is covered in the guide on JCA scoping and PICO; the JCA dossier should be distinguished from the AMNOG dossier, which continues to be submitted nationally. The implications for Germany are discussed in the insight Five theses on the Delta-Dossier.

Evidence preparation across the AMNOG process

The stages of the AMNOG process are methodologically connected. Evidence planning affects dossier preparation; the submitted dossier defines the evidence base for the benefit assessment; and the findings of that assessment determine which issues become relevant during the commenting procedure and oral hearing.

The AMNOG process is therefore more than a sequence of statutory deadlines. For evidence teams, the important connection runs from the early German assessment question through the dossier and benefit assessment to the final G-BA resolution.

Frequently asked questions about the AMNOG process

What is the AMNOG process in Germany?

The AMNOG process is the German pathway that includes the early benefit assessment of a new medicine and the subsequent determination of a reimbursement price. The early benefit assessment starts with dossier submission and concludes with the G-BA resolution on additional benefit.

When does the AMNOG benefit assessment start?

The formal early benefit assessment starts at the relevant dossier submission date. Preparation starts earlier because the zVT, patient populations, endpoints and available evidence can already affect the later German assessment question.

How long does the German early benefit assessment take?

The benefit assessment is published no later than three months after the relevant dossier submission date. Following the commenting procedure and oral hearing, the G-BA adopts its resolution within the statutory procedure timeline.

What is IQWiG's role in the AMNOG process?

The G-BA may commission IQWiG to assess the submitted dossier. IQWiG evaluates the evidence and derives conclusions on the certainty and magnitude of additional benefit against the zVT. The final decision is made by the G-BA.

What is the zVT in AMNOG?

The zVT, or zweckmäßige Vergleichstherapie, is the appropriate comparator therapy defined for the German benefit assessment. It can differ between patient populations and is central to determining which clinical evidence is relevant to the German assessment question.

What happens after the IQWiG benefit assessment?

Publication of the benefit assessment is followed by a written commenting procedure and an oral hearing. The G-BA then decides on additional benefit.

Does EU HTA replace the German AMNOG process?

No. Joint Clinical Assessment provides a common European clinical assessment, but it does not replace Germany's national decision on additional benefit or the subsequent national reimbursement process. German patient populations, the zVT and national methodological requirements remain relevant.