The AMNOG process does not repeat the regulatory approval procedure. Marketing authorisation assesses whether a medicine has a positive benefit-risk balance. The German benefit assessment asks a different question: does the medicine offer a patient-relevant advantage over the treatment standard defined for Germany? The AMNOG legal framework defines the statutory basis for that process.
AMNOG process timeline at a glance
The regular AMNOG procedure connects dossier submission, scientific assessment, stakeholder comments, the G-BA resolution and reimbursement-price negotiation.
| Stage | Typical timing | Main output |
|---|---|---|
| Dossier submission | Start | AMNOG dossier submitted to the G-BA |
| IQWiG or G-BA assessment | Around month 3 | Published benefit assessment |
| Written comments | After publication | Stakeholder comments on the assessment |
| Oral hearing and G-BA resolution | Around month 6 | Binding added-benefit decision |
| Reimbursement negotiation | After the resolution | Negotiated reimbursement amount or arbitration |
The AMNOG process at a glance
What is the AMNOG process?
The AMNOG process is the German procedure for assessing the added benefit of a new medicine under Section 35a of Book V of the German Social Code. The assessment compares the medicine with an appropriate comparator therapy specified by the G-BA.
Who assesses the medicine?
IQWiG generally performs the scientific benefit assessment, while the G-BA makes the legally relevant decision on added benefit. Special arrangements apply to orphan medicines.
How long does the AMNOG process take?
The procedure from dossier submission to the G-BA resolution generally takes approximately six months. The benefit assessment is published three months after submission, followed by written comments, an oral hearing and the final G-BA decision.
What happens after the benefit assessment?
After the G-BA resolution, the pharmaceutical company and the GKV-Spitzenverband negotiate the reimbursement amount. If they cannot agree, an arbitration process may determine the price.
What is the AMNOG process in Germany?
The AMNOG process determines whether a newly launched medicine provides added benefit compared with the German standard of care. It connects the assessment of clinical evidence with the subsequent setting of a reimbursed price.
AMNOG stands for Arzneimittelmarktneuordnungsgesetz, commonly translated as the German Pharmaceutical Market Restructuring Act. The legislation introduced the mandatory early benefit assessment of new medicines in 2011.
Before AMNOG, pharmaceutical companies could generally set the launch price of a new medicine without an initial added-benefit assessment. Under the AMNOG framework, the medicine may still enter the German market after authorisation, but its longer-term reimbursement amount is linked to the national assessment and negotiation procedure.
The process therefore addresses three central questions:
- Which German patient population is relevant?
- Does the medicine offer patient-relevant advantages over the appropriate comparator therapy?
- What level and certainty of added benefit can be derived from the evidence?
These questions affect clinical development, evidence planning, dossier preparation and reimbursement strategy.
Which medicines enter the AMNOG process?
The AMNOG process generally applies to reimbursable medicines containing a new active substance that are launched in Germany. A new procedure may also be required for an extension of the authorised indication.
The source materials distinguish between medicines subject to the regular assessment and products or circumstances that follow different rules. They identify new reimbursable active substances, orphan medicines and certain hospital-only medicines as relevant categories for AMNOG planning. They also describe specific arrangements for vaccines, reserve antibiotics, non-reimbursable medicines, medical devices and products without continuing document protection.
Because exemptions, thresholds and submission requirements can change through legislation and G-BA rules, the current status of a specific product must be checked before publication or submission.
New active substances in the AMNOG process
A pharmaceutical company launching a reimbursable medicine with a new active substance must generally submit a benefit dossier at the time of market entry.
The dossier must reflect:
- the precise authorised indication,
- the relevant German patient groups,
- the appropriate comparator therapy,
- the evidence available at submission,
- and the analyses required for the German assessment.
The regulatory development programme may cover a broader or differently defined population. The AMNOG dossier must translate that programme into the population structure relevant to the G-BA decision.
Indication extensions in the AMNOG process
A new benefit assessment may also be triggered by an extension of the authorised indication. The evidence and comparator strategy must then be reassessed for the newly authorised population.
An indication extension cannot simply rely on the conclusions of an earlier procedure. The relevant comparator, treatment pathway and patient groups may differ from those considered in the original assessment.
Orphan medicines in the AMNOG process
For an orphan medicine, added benefit is initially regarded as established through marketing authorisation, subject to the applicable statutory conditions. The German procedure then focuses particularly on determining the magnitude of that benefit.
The source material describes a simplified dossier structure for orphan medicines below the applicable revenue threshold. In that situation, a comparative demonstration against an appropriate comparator therapy is not required in the same manner as in the regular assessment. It also notes that a regular procedure applies once the relevant threshold is exceeded.
Current thresholds and detailed legal conditions should be verified against the latest German legislation and G-BA requirements before publication.
The AMNOG process in six steps
The AMNOG process consists of six core stages: early consultation, dossier submission, benefit assessment, written commenting, oral hearing and G-BA resolution, followed by reimbursement-price negotiation.
The formal procedure begins with dossier submission. The strategic AMNOG process, however, begins much earlier during evidence generation and study planning.
Step 1: G-BA consultation and evidence planning
An early G-BA consultation can address the appropriate comparator therapy, study population, patient-relevant endpoints and other assessment questions.
The consultation can help the pharmaceutical company understand how the planned evidence may be viewed in the German benefit assessment. Relevant questions may concern:
- the proposed appropriate comparator therapy,
- implementation of the comparator in a clinical trial,
- the representativeness of the study population,
- the patient relevance of endpoints,
- epidemiology and target-population estimates,
- indirect comparisons,
- and the expected availability of additional data.
The G-BA consultation is particularly valuable before the pivotal study begins, when material changes to the study design may still be feasible.
What can a G-BA consultation clarify?
The source material identifies four recurring consultation areas:
- appropriate comparator therapy,
- study population,
- endpoints,
- further dossier and assessment questions.
For comparator questions, the company should explain its position against the G-BA’s criteria for selecting an appropriate comparator therapy. For population questions, it should map the planned trial population to the anticipated indication. For endpoint questions, it should explain patient relevance, validity and operationalisation.
Is the G-BA consultation legally binding?
A G-BA consultation provides strategic orientation but is not legally binding.
The consultation is based on the medical and scientific knowledge available at the time. The G-BA may later reconsider the comparator if the authorised indication differs from the assumptions used during consultation or if the German treatment standard changes.
The source material also emphasises that the G-BA does not provide a final advance assessment of statistical models, hypotheses or the complete evidence package. The final judgment remains part of the benefit assessment.
For the pharmaceutical company, the consultation record is therefore not a guarantee of a particular outcome. It is an important input into a wider evidence and risk-management strategy.
Step 2: Submission of the AMNOG dossier
The AMNOG dossier is the structured evidence submission used for the German early benefit assessment. It consists of five modules covering administrative information, the medicine and indication, the German treatment context, the clinical evidence and the underlying documentation.
The dossier is normally prepared in parallel with the later stages of the regulatory procedure. The source materials indicate that dossier compilation frequently takes approximately 12 months and that a formal completeness check before final submission is advisable.
When is the AMNOG dossier submitted?
For a first launch in Germany, the submission date is connected to the medicine’s market entry. The source materials describe market entry as the first listing in the German pharmaceutical price list.
Different rules apply to indication extensions. The exact deadline and the current formal submission requirements should always be checked against the applicable G-BA rules.
What are the five modules of an AMNOG dossier?
An AMNOG dossier consists of five modules.
| Module | Main content |
|---|---|
| Module 1 | Administrative information and summary of Modules 2 to 4 |
| Module 2 | Information on the medicine, mechanism of action and authorised indication |
| Module 3 | Comparator, disease, target population, epidemiology, costs and requirements for use |
| Module 4 | Methods, clinical evidence, analyses and derivation of added benefit |
| Module 5 | References, study reports, documentation and supporting material |
Modules 1 to 4 are published as part of the benefit-assessment procedure. Module 5 contains the supporting documentation used to substantiate the public dossier.
Why is the clinical study report not sufficient?
A clinical study report does not normally provide all analyses required for the German benefit assessment.
The AMNOG dossier may require:
- additional subgroup analyses,
- analyses by German benefit dimensions,
- systematic literature searches,
- detailed documentation of missing data,
- indirect-comparison methodology,
- responder analyses,
- and evidence structured by the relevant German patient populations.
The dossier does not merely reproduce regulatory documentation. It reformulates the evidence around the German assessment question.
Step 3: Benefit assessment by IQWiG or the G-BA
The benefit assessment is generally prepared by IQWiG and published three months after dossier submission. The assessment examines whether the evidence demonstrates added benefit over the appropriate comparator therapy.
IQWiG reviews the dossier from a methodological and evidence-based perspective. The assessment may agree with the company’s conclusions, accept only part of the claimed benefit or reach a substantially different conclusion.
What does IQWiG examine?
The assessment can address:
- completeness of the evidence base,
- eligibility of the submitted studies,
- correspondence between trial and target populations,
- appropriate implementation of the comparator,
- patient relevance of endpoints,
- risk of bias,
- missing data,
- statistical methods,
- subgroup effects,
- and the certainty of the results.
IQWiG does not make the final legally relevant decision. Its assessment provides a major scientific basis for the G-BA resolution.
Who assesses orphan medicines?
The source materials describe a different division of responsibilities for orphan medicines. The G-BA assesses the medical added benefit, while IQWiG may evaluate aspects such as the target population and treatment costs.
The applicable process depends on the legal status of the medicine and whether it remains within the conditions for the simplified orphan-drug procedure.
Step 4: Written comments on the benefit assessment
After publication of the benefit assessment, eligible parties have three weeks to submit written comments.
The written commenting procedure allows the pharmaceutical company and other stakeholders to address the findings of IQWiG or the G-BA. This stage can clarify misunderstandings, challenge methodological conclusions and provide further context for the final decision.
Potential issues include:
- interpretation of the target population,
- appropriateness of the comparator,
- relevance and validity of endpoints,
- treatment of missing values,
- subgroup analyses,
- safety analyses,
- epidemiological estimates,
- annual treatment costs,
- and the interpretation of newer data.
The comment should distinguish between general methodological arguments and issue-specific responses to the published assessment.
Can new evidence be submitted with the written comments?
The commenting procedure can include additional analyses and, within the applicable procedural rules, newer data or clarifications. It does not, however, provide an unrestricted opportunity to replace an incomplete dossier.
For Market Access teams, the three-week period requires substantial preparation before the benefit assessment is published. Likely criticism points, additional analyses and internal decision routes should be anticipated in advance.
Step 5: Oral hearing and G-BA resolution
The oral hearing gives the pharmaceutical company and other participating organisations an opportunity to explain their written comments and respond to questions from the G-BA.
According to the source material, the hearing generally takes place approximately two to three weeks after the deadline for written comments. The final G-BA resolution follows later in the six-month assessment period.
What happens during the oral hearing?
The G-BA may ask about:
- the clinical relevance of observed treatment effects,
- the appropriateness of endpoint definitions,
- population boundaries,
- implementation of the comparator,
- subgroup findings,
- safety differences,
- missing data,
- and the availability of additional evidence.
The hearing should not be treated as a presentation exercise. It is an assessment-related discussion in which precise, consistent and evidence-based answers are essential.
What does the G-BA decide?
The G-BA decides the magnitude and certainty of added benefit for the relevant patient population or populations.
The resolution may reach different conclusions for different subgroups. For example, added benefit may be recognised for one patient population but not established for another.
The G-BA publishes both the resolution and its supporting reasons. These documents explain how the committee interpreted the evidence, comparator, endpoints and population structure.
Step 6: Reimbursement-price negotiation
After the G-BA resolution, the pharmaceutical company and the GKV-Spitzenverband negotiate the reimbursement amount for the medicine.
The added-benefit decision is a central basis for the negotiation, but it does not mechanically determine a particular price.
The source materials describe several negotiation rounds. If the parties cannot agree, the matter proceeds to arbitration. Legal challenge may be possible after the arbitration decision.
Which factors influence the reimbursement amount?
Depending on the applicable legal framework, the negotiation may consider:
- the G-BA’s added-benefit decision,
- costs of the appropriate comparator therapy,
- costs of comparable medicines,
- the size of the target population,
- annual treatment costs,
- and further statutory pricing criteria.
The evidence strategy and pricing strategy are therefore connected. Comparator selection, population slicing and the strength of the added-benefit claim influence both the clinical assessment and the later economic negotiation.
How long does the AMNOG process take?
The German benefit-assessment stage lasts approximately six months from dossier submission to the G-BA resolution. The reimbursement negotiation follows the clinical assessment.
A simplified timeline is:
| Stage | Indicative timing |
|---|---|
| Dossier submission | Procedure begins |
| Benefit assessment | 3 months |
| Written comments | 3 weeks |
| Oral hearing | Approximately 2–3 weeks after the commenting deadline |
| G-BA resolution | Within approximately 6 months of submission |
| Price negotiation | Begins after the G-BA resolution |
The exact timing of individual procedural steps may vary. Current deadlines should be checked against the applicable G-BA procedural rules.
When should AMNOG preparation begin?
AMNOG preparation should begin during clinical development, not shortly before dossier submission.
Comparator alignment, patient populations, endpoint strategy and analysis planning can only be addressed effectively while the evidence programme is still adaptable. Once the pivotal data have been generated, the dossier can reorganise and analyse the evidence, but it cannot remedy every structural evidence gap.
What is the appropriate comparator therapy?
The appropriate comparator therapy is the German treatment standard against which the added benefit of the new medicine is assessed. In German, it is known as the zweckmäßige Vergleichstherapie or zVT.
The comparator is selected by the G-BA and reflects the treatment considered appropriate in the relevant German care setting.
Which criteria guide comparator selection?
The source materials identify four core considerations:
- A medicinal comparator should generally be authorised for the indication.
- A non-pharmacological comparator must be reimbursable within the German statutory insurance system.
- Existing G-BA decisions, assessments and recommendations are considered.
- The comparator should form part of appropriate treatment according to the generally accepted state of medical knowledge.
Medical guidelines, German treatment practice and input from scientific medical societies may support the G-BA’s determination.
Can there be more than one comparator?
The appropriate comparator therapy can take different forms. It may be:
- one specific medicine,
- a selection of several medicines,
- a non-pharmacological treatment,
- treatment according to physician choice,
- individualised treatment,
- best supportive care,
- or watchful waiting.
A placebo is not itself the appropriate comparator therapy. A placebo-controlled study can nevertheless represent the comparator if both study arms receive an appropriate background treatment.
What is population slicing?
Population slicing means that the authorised indication is divided into subpopulations with separate comparators and added-benefit conclusions.
Each subpopulation may have a different treatment standard. The medicine must then demonstrate added benefit separately against the comparator relevant to each subgroup.
Population slicing can produce a mismatch between a broad regulatory indication and the narrower populations for which the study provides directly usable German evidence.
How does the G-BA determine added benefit?
The G-BA evaluates added benefit by both magnitude and certainty. Magnitude describes the size of the patient-relevant advantage. Certainty describes the reliability of the evidence.
Categories for the magnitude of added benefit
The source materials identify the following categories:
- major added benefit,
- considerable added benefit,
- minor added benefit,
- non-quantifiable added benefit,
- no added benefit proven,
- less benefit.
The phrase “no added benefit proven” does not mean that the medicine has no medical effect. It means that the submitted evidence did not establish a patient-relevant advantage over the specified comparator for the assessed population.
Certainty of the evidence
The German framework also distinguishes levels of evidentiary certainty. These are commonly expressed through categories corresponding to proof, indication and hint.
The level depends on factors such as:
- study design,
- number of studies,
- risk of bias,
- consistency,
- missing data,
- and the robustness of treatment effects.
A randomised controlled trial may support a high certainty of evidence, but randomisation alone does not guarantee the highest category. Methodological limitations can reduce certainty.
Which endpoints are relevant in the AMNOG process?
The AMNOG process focuses on patient-relevant outcomes in mortality, morbidity, health-related quality of life and adverse events.
The benefit assessment asks whether the medicine changes outcomes that patients directly experience or that directly affect their survival, symptoms, function or quality of life.
Mortality
Mortality outcomes include death and overall survival. Overall survival is frequently a central outcome in oncology, although its interpretation still depends on study design, follow-up and subsequent treatment.
Morbidity
Morbidity covers symptoms, functional limitations and consequences of disease. The relevance of an outcome depends on what it measures and how it is operationalised.
A biomarker or laboratory measurement is not automatically a patient-relevant morbidity endpoint.
Health-related quality of life
Health-related quality of life captures how disease and treatment affect patients’ physical, psychological and social functioning.
The assessment considers whether the instrument is validated, whether the analysis is appropriate and whether the observed difference is interpretable.
Adverse events
Safety is assessed through patient-relevant adverse-event outcomes, such as:
- serious adverse events,
- severe adverse events,
- discontinuations due to adverse events,
- and specific adverse events of clinical relevance.
An improved safety profile can contribute to an added-benefit conclusion when the differences are robust and patient-relevant.
What evidence is required for the AMNOG process?
A pivotal regulatory trial is not automatically suitable for the German benefit assessment. The study must also address the German population, comparator, treatment context and patient-relevant endpoint requirements.
The source materials specify several central conditions:
- The trial population should correspond to the authorised indication.
- Treatment should follow the product information.
- Results should be transferable to German care.
- Endpoints should be patient-relevant.
- The comparator should reflect the appropriate comparator therapy.
- The dossier must provide the analyses required for benefit assessment.
Direct evidence
A randomised direct comparison against the German comparator usually provides the clearest evidence basis.
Problems arise when the regulatory comparator differs from the later zVT. A trial may establish regulatory efficacy yet fail to answer the German comparative question.
Indirect comparisons
When direct evidence is unavailable, adjusted indirect comparisons may be considered. Their suitability depends on:
- a valid connected evidence network,
- sufficient similarity between studies,
- comparable endpoint definitions,
- and transparent access to the necessary study information.
An indirect comparison is not accepted solely because it produces an estimate. Its methodological assumptions and data basis must be defensible.
Transferability to German care
An international study does not need to be conducted exclusively in Germany to be relevant. The critical question is whether the population, comparator and treatment conditions can be transferred to the German healthcare context.
A study may be clinically sound but only partially relevant if the treatment pathway does not reflect German care.
What is the difference between marketing authorisation and the AMNOG process?
Marketing authorisation determines whether a medicine may be placed on the market, while the AMNOG process determines whether it provides added benefit over the German comparator.
| Marketing authorisation | AMNOG process |
|---|---|
| Assesses efficacy, safety and quality | Assesses patient-relevant added benefit |
| Uses a regulatory benefit-risk standard | Uses a comparative German benefit standard |
| Results in authorisation or refusal | Results in a G-BA added-benefit resolution |
| Comparator supports regulatory efficacy assessment | Comparator must reflect the German zVT |
| May rely on surrogate or laboratory outcomes | Prioritises patient-relevant outcomes |
| Conducted by regulatory authorities | Decided by the G-BA, generally supported by IQWiG |
The same clinical study can therefore receive different interpretations in the two procedures. The difference does not necessarily represent disagreement about the data. The procedures answer different questions.
What are the roles of IQWiG, the G-BA and the GKV-Spitzenverband?
IQWiG assesses the evidence, the G-BA decides on added benefit and the GKV-Spitzenverband negotiates the reimbursement amount.
The role of IQWiG
IQWiG is an independent scientific institute. It evaluates the submitted evidence using its methodological framework and the specific commission issued for the procedure.
IQWiG has no final decision-making power over the added benefit.
The role of the G-BA
The G-BA is the central decision-making body of the German healthcare self-governance system.
In the AMNOG process, it:
- specifies the appropriate comparator therapy,
- commissions or conducts the benefit assessment,
- organises the commenting procedure and oral hearing,
- and adopts the final resolution.
The role of the GKV-Spitzenverband
The GKV-Spitzenverband represents Germany’s statutory health insurance funds. It negotiates the reimbursement amount with the pharmaceutical company after the G-BA decision.
The three institutions therefore operate at different stages and with different responsibilities.
How does EU HTA interact with the AMNOG process?
The EU Joint Clinical Assessment does not replace the German added-benefit decision or the national reimbursement negotiation.
The JCA can provide a European clinical evidence assessment, but the German procedure continues to apply national requirements to the comparator, population structure, endpoints and reimbursement consequences.
The G-BA consultation material notes that added-benefit decisions and pricing remain national responsibilities under EU HTA. It also highlights that national consultation remains relevant because Joint Scientific Consultations are limited and cannot resolve every Germany-specific evidence question.
Which questions remain specific to Germany?
Germany must still determine:
- the appropriate comparator therapy,
- relevant national patient subgroups,
- patient relevance of outcomes under German methods,
- required national analyses,
- target-population estimates,
- treatment costs,
- and the magnitude and certainty of added benefit.
The European and German evidence processes are therefore connected but not identical.
Why does the AMNOG dossier remain necessary?
The JCA dossier focuses on the European clinical assessment. The German AMNOG dossier must also address national requirements, including epidemiology, target population, costs, quality-assured use and the specific evidence needed for the G-BA decision.
The national task is not merely to reference the JCA. It is to determine which European evidence answers the German question and where adaptation or additional analysis is required.
Why should AMNOG planning begin during clinical development?
The most important AMNOG risks are usually created before dossier writing begins.
A dossier cannot retrospectively correct every problem caused by:
- an unsuitable comparator,
- a population that does not match the indication,
- missing patient-relevant endpoints,
- inadequate follow-up,
- or unavailable subgroup analyses.
Early planning should therefore test five questions:
- Does the trial population match the anticipated indication?
- Does the comparator reflect German treatment practice?
- Are the relevant patient outcomes measured?
- Are the endpoints valid and appropriately operationalised?
- Are the necessary analyses and data cuts available at submission?
The G-BA consultation can help reduce uncertainty, but the company must continue monitoring changes in guidelines, treatment practice and the expected authorised indication.
What does the AMNOG process mean for international Market Access teams?
International Market Access teams must treat Germany as a distinct evidence and reimbursement environment, not merely as a local implementation of regulatory approval.
The German process requires alignment between:
- global clinical development,
- the European regulatory strategy,
- German comparator expectations,
- national epidemiology,
- dossier analyses,
- and price-negotiation planning.
Three differences are particularly important.
The German comparator may differ from the global trial comparator
A globally accepted standard of care may not correspond to the G-BA’s appropriate comparator therapy. Comparator mapping should therefore begin before the pivotal study is finalised.
The German population may be divided into subgroups
The G-BA may slice the authorised indication into multiple populations. Evidence must be available separately for the relevant groups.
Regulatory outcomes may not satisfy German endpoint requirements
An endpoint accepted for marketing authorisation may not be considered directly patient-relevant in the benefit assessment. German endpoint acceptance should be reviewed during protocol development.
The AMNOG process links clinical evidence to reimbursement in Germany
The AMNOG process determines whether a newly launched medicine offers added benefit over the German standard of care and uses that conclusion as a basis for reimbursement-price negotiations.
The procedure formally begins with the AMNOG dossier, but successful preparation begins much earlier. Comparator choice, patient population, endpoint strategy and analysis planning must be coordinated during clinical development.
EU HTA changes the European evidence environment but does not remove the national German decision. The central Market Access task is therefore to connect the European evidence package with the specific requirements of the German benefit assessment.
Frequently asked questions about the AMNOG process
What does AMNOG stand for?
AMNOG stands for Arzneimittelmarktneuordnungsgesetz, the German Pharmaceutical Market Restructuring Act. It introduced the mandatory early benefit assessment of new medicines in 2011.
What is the AMNOG process?
The AMNOG process is Germany’s early benefit assessment and reimbursement procedure for newly launched medicines. It assesses added benefit over an appropriate comparator therapy and is followed by price negotiations.
Who submits the AMNOG dossier?
The pharmaceutical company responsible for placing the medicine on the German market submits the AMNOG dossier to the G-BA.
How many modules are in an AMNOG dossier?
An AMNOG dossier consists of five modules. Modules 1 to 4 contain the public benefit submission, while Module 5 contains supporting documentation.
Who performs the German benefit assessment?
IQWiG generally performs the scientific benefit assessment, while the G-BA makes the final decision. Special arrangements apply to orphan medicines.
How long does the benefit assessment take?
The benefit assessment is published three months after dossier submission. The full procedure up to the G-BA resolution generally takes approximately six months.
What is the appropriate comparator therapy?
The appropriate comparator therapy is the treatment standard specified by the G-BA for the relevant German patient population. Added benefit must be demonstrated against this comparator.
What does “no added benefit proven” mean?
It means that the submitted evidence did not establish a patient-relevant advantage over the specified comparator. It does not necessarily mean that the medicine is ineffective.
What happens after the G-BA decision?
The pharmaceutical company and the GKV-Spitzenverband negotiate the reimbursement amount. If no agreement is reached, the dispute may proceed to arbitration.
Does the JCA replace the AMNOG process?
No. The JCA does not replace the German added-benefit resolution, the AMNOG dossier or the reimbursement negotiation. European evidence must still be translated into the German population, comparator and endpoint framework.