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The G-BA assesses the additional benefit (“Zusatznutzen”) a product provides over current treatment availability. The G-BA uses a scale of 4 levels of additional benefit but may also assess the additional benefit as unquantifiable under certain conditions. Companies must submit to the G-BA within three months of gaining marketing authorisation in order for the G-BA to recognise any additional benefit claimed over the appropriate comparator.
The final G-BA resolution, which is released at the end of the assessment procedure, will contain a rating of the drug’s additional benefit. This rating will be the basis of the subsequent price negotiations with the statutory payer groups (“GKV-SV“) and will have a major influence on the reimbursement price of the drug.
What is the additional benefit?
The G-BA rules of procedure contain a two-step definition to explain what the additional benefit is, referring to the basic definition of the benefit of a drug.
- The benefit (“Nutzen”) is defined as “the therapeutic effect relevant for patients especially with regard to improvements of the patient’s general condition, reduction of the sickness period, extension of survival time, reduction of side effects or an improvement of the quality of life”.
- The additional benefit (“Zusatznutzen”) is defined as “benefit of a drug (as defined above) which is higher in quality or in quantity than the benefit of the appropriate comparator therapy”.
The additional benefit is, therefore, in theory, the result of the comparison between the benefits of a drug and its appropriate comparator therapy:
|Drug to be assessed||Comparator|
|Benefit (therapeutic effect of the drug):
||Benefit (therapeutic effect of the drug):
How will the G-BA rate the additional benefit and which criteria will be applied?
The G-BA uses a scale of 4 levels of additional benefit but may also assess the additional benefit as unquantifiable under certain conditions:
- Major Additional benefit
- Considerable additional benefit
- Minor additional benefit
- No additional benefit
- Unquantifiable additional benefit
Positive MAP InsightsCompanies must submit to the G-BA within three months of gaining marketing authorisation in order for the G-BA to recognise any additional benefit claimed over the appropriate comparator.
In its rules of procedure, the G-BA has defined, under which conditions which additional benefit rating will apply.
Major Additional Benefit:
A sustainable large improvement of the therapeutic benefit over the appropriate comparator therapy that has not been reached before, in particular:
- a full recovery from the illness
- a significant extension of the survival period
- a long-term absence of severe symptoms
- an almost complete avoidance of severe adverse side effects
Considerable Additional Benefit:
A significant improvement of the therapeutic benefit over the appropriate comparator therapy that has not been reached before, in particular:
- an easing of severe symptoms
- a moderate extension of the survival period
- a noticeable easing of the illness for patients
- a relevant avoidance of severe adverse events
- a significant avoidance of other side effects
Minor Additional Benefit:
A moderate but not an insignificant improvement of the therapeutic benefit over the appropriate comparator therapy, in particular:
- a decrease of non-severe symptoms of the illness
- a relevant avoidance of side effects
No Additional Benefit:
Unquantifiable Additional Benefit:
G-BA Additional Benefit Assessment
What does that mean?
To prove an additional benefit the new drug must, in theory, be “better” than the appropriate comparator therapy in at least one of the following endpoints:
- Mortality: extension of the survival period
- Morbidity: reduction of severe symptoms of the drug
- Quality of life: enhancing the patients’ subjective wellbeing
- Side effects/adverse events: avoid or at least limit the frequency of side effects
To achieve a major additional benefit rating, according to the G-BA’s above-mentioned definition the improvement must be “sustainable”, for a considerable rating the improvement must be “significant”. Both of these terms are not clearly defined and thus reserve some discretion for the G-BA when applying them. From the literal meaning, it can be concluded that “sustainable” refers to a longer lasting effect of the drug while “significant” refers to a certain quality of the effect. To achieve a minor additional benefit, it may be sufficient to prove some improvement over the appropriate comparator’s therapeutic effects.
Please note that the endpoint of morbidity may refer to various kinds of symptoms, depending on the specific nature of the illness.
In addition to the above-named endpoints, the G-BA in some cases accepts other endpoints that are of specific relevance for the disease. Manufacturers planning to submit data on such alternative endpoints are strongly advised to consult the G-BA at the earliest time possible on whether these endpoints will be accepted when proving a therapeutic improvement. In any case, the use of alternative endpoints will require a thorough explanation of their relevance for the treatment of the disease or for the patients’ wellbeing.
How to prove the additional benefit
Generally, the additional benefit must be demonstrated on the basis of randomised, blinded and controlled direct comparative studies, whose methodology comply with international standards and evidence-based medicine, and which are carried out on populations, or under conditions that are representative and relevant to the usual treatment situation and have been conducted with regards to the appropriate comparator therapy.
Negative MAP InsightsThere are no clear provisions for the determination of subpopulations which has led to significant variations in the company’s dossier and the G-BA / IQWiG’s assessment.
Divergence in subpopulations leads to different results with regards to the overall additional benefit. Different results in different patient populations are used by GKV-SV to bring down the price in the negotiations by creating a mixed price depending on the size and the benefit rating of the subgroups.
Positive MAP InsightsCompanies are advised to include subgroup analyses from the very beginning and also evaluate third-party studies concerning additional benefit in their dossiers.
It must be emphasised that the G-BA will only use the data that have been provided by the manufacturer for the assessment. In particular, G-BA will not investigate any additional data.
Find out more information on the data required to submit during the G-BA assessment on our dossier submission page.
Manufacturers are not only obliged to submit the required data for the assessment of the additional benefit but also to provide an estimate of the extent of the additional benefit (minor, considerable or major). Additionally, manufacturers shall explain the certainty with which a statement about the presence of an additional benefit can be taken.
All conclusions drawn with regards to the additional benefit must be done according to the international standards of evidence-based medical science. The G-BA will generally only accept the highest scientific evidence level and will require the pharmaceutical manufacturer to justify whether the evidence level used was the highest one. Exceptions from the obligation to use the highest available evidence level may be accepted by the G-BA in cases where it would be impossible or inappropriate to conduct clinical studies at that level. In these cases, the manufacturer needs to prove that the highest available evidence level has been used and needs to justify whether this level was appropriate to prove the additional benefit. The lower the evidence level used, the more the manufacturer needs to justify the appropriateness of the evidence.
Overview: How to prove the additional benefit
|Step One||Step Two||Step Three|
|Submit data from randomised, blinded and controlled direct comparative studies that refer to the appropriate comparator set by the G-BA||Estimate the extent of the additional benefit
Manufacturers are well advised to check at the earliest possible time whether the data basis and evidence level used will be sufficient from the G-BA’s perspective. Otherwise, they risk that the G-BA might reject their scientific conclusions and will subsequently not grant the additional benefit rating that has been aimed at by the manufacturer. In some cases, this may lead to the complete denial of an additional benefit, with negative consequences for the pricing of the product.
Find out more information on the G-BA’s early scientific advice service, which should be made use of by all manufacturers can be found here.