AMNOG Seven Learnings Strategic Access Germany

AMNOG: Seven Learnings for Strategic
Market Access Decisions in Germany

An IMS Consulting Group White Paper on the impact of the AMNOG
reforms based on the evidence of early benefit assessments
TM
TM
Figure 1
AMNOG: Seven Learnings for Strategic

Market Access Decisions in Germany
The AMNOG process in summary
Institute for Quality

and Efficiency in
Health Care
(IQWiG)
The introduction of a mandatory benefit assessment process in early 2011 the Act
Benefit assessment
Commission
possible
Dossier
Manufacturer
Market launch
on the Reform of the Market for Medicinal Products (AMNOG) radically changed the
Report
Hearing
Federal Joint
Committee (GBA)
Benefit
assessment
(internet
publication)
Additional
benefit
Federal Joint
Committee (GBA)
Benefit
assessment
(Decision)
No additional
benefit
Manufacturers
price
(set freely)
Market launch
FRP
reference
price
3 months
Source: IMS Consulting Group
Figure 2
Reference price
not possible
6 months
No
agreement
Manufacturer
Head association
of the
SHI scheme
(GKV)
Arbitration Panel
Rebate negotiations
Agreement
Discounted
net price
Retroactive
market access environment for products with a new active ingredient in Germany. The
Not
accepted
act created new requirements for comparator-driven evidence in clinical trials and
Decision
(e.g. based
on international
prices)
Institute for
Quality
and Efficiency in
Health Care
Cost/benefit
assessment
Decision
Decision
Discounted
net price
Valid until the end of

the process
although the focus has so far been on new products, the law also covers products
already on the market, opening up the possibility of cuts to the reimbursed prices
of both new and existing products. Following publication of the first early benefit
assessments in January 2012, IMS Consulting Groups Justus Dehnen and Michael
12 months
15 months
FRP = reference price
What does additional benefit mean?
No additional benefit
significantly altered the pricing process to include discount negotiations. In addition,
Additional benefit
Schmoeller review the results and present the key learnings to date.
THE AMNOG LAW
The manufacturer then has the opportunity to
The price setting procedure for new drugs in Germany
comment on the decision at a hearing, after which
changed on 1 January 2011 with the introduction of the
the GBA will reach a final decision within a further
AMNOG law, which added a reimbursement price to the
three months.
existing manufacturer-set list price. While the list price
For new products with orphan drug status, a simplified
remains unchanged, the reimbursed price will be set at
submission process applies. The manufacturer has
the latest 12 months after a new products launch, based
only to submit an extract of the dossier and the
on discount negotiations or reference pricing following

an assessment of the clinical benefits provided by the
benefit, as the additional benefit in general is
If the drug is considered to offer no additional benefit,
If the new drug is considered to offer an additional
it will be given a reimbursement price in relation to
benefit (there are different levels of additional benefits
the price of the comparator used during the benefit
possible: major, important, slight or non-quantifiable
Additional benefit
assessment. Should that comparator belong to an
additional benefits) then a discount will be negotiated
For every new product launched in Germany (excluding
existing reference price group (festbetragsgruppe),
between the manufacturer and the lead association of
generics and hospital-only products), manufacturers
the new drug will be classified immediately into that
the German sick funds (GKV-SV) based on the reimbursed
are now required to submit a benefit dossier for
group if possible. If there is no existing reference
price of the comparator and the additional benefit
assessment to the Federal Joint Committee (GBA).
price group, the GBA will consider the possibility of
demonstrated. Any discounts will be taken from the
The GBA usually commissions the Institute for Quality
The reimbursement price of products with no
creating a new group. If a new group cannot be set
list price set by the manufacturer. The new reimbursed
and Efficiency in Health Care (IQWiG), which operates
additional benefit is set based on a reference price or
up, the reimbursement price will be discounted from
price will be effective at the latest from month 13 after
as a GBA support function, to evaluate the evidence
in price negotiations, while manufacturers of products
the list price to the price level of the comparator. The
launch, while the original manufacturer-set list price
provided by the manufacturer.
with additional benefit enter price negotiations with
reimbursement price will be effective at the latest from
stays unchanged.
The result whether the drug offers an additional
the lead association of the German sick funds
benefit or not against a GBA selected comparator
(GKV-SV). Should negotiations fail, the reimbursed
is published on the internet within three months
price is set by an arbitration panel based on
(see Figure 2).
international prices in 15 EU countries (Austria,
the beginning of the 13th month after launch.

manufacturer (see Figure 1).
GBA will only decide on the level of additional
Copyright IMS Consulting Group 2012
considered demonstrated by the orphan designation.

This exception applies to orphan drugs as long as
anticipated peak sales stay below the threshold of 50
million a year. If the threshold is exceeded after the
GBA decision, a complete dossier has to be submitted
by the manufacturer.
TM
Belgium, Czech Republic, Denmark, Finland, France,
drug development process for manufacturers to consult
Greece, Ireland, Italy, Netherlands, Portugal, Sweden,
the GBA, with approaches especially welcome before
Slovakia, Spain, UK).
starting phase III. The dossier must contain all clinical

trial data known to the manufacturer, including both
published and unpublished data for aborted and
On the basis of the evaluations to date, it is possible to draw seven early learnings on
The benefit dossier supplied by the manufacturer is
investigator-driven trials. Dossiers will be judged
the implications of AMNOG on strategic market access decisions for companies planning
critical to the benefit assessment and the negotiation
incomplete and not qualify for an additional benefit if
process. The dossier is comparable to the kind of health
clinical data is missing. The same applies to products
to launch new molecular entities in Germany.
technology assessments (HTAs) previously undertaken
that do not include a comparator and products for
by IQWiG and must be structured according to the
which no dossier is submitted.
Benefit dossier
GBAs code of practice. At its core, it must present
LEARNING 1: SELECT THE RIGHT CLINICAL

COMPARATOR
a second comparator was accepted but only with a
Choice of comparator has been shown to be the
indirect trial data limited a products achievable level of
convincing and objective rationale. However, the use of
evidence of the drugs additional benefit over the
EVALUATIONS TO DATE
appropriate comparator defined as the clinically
The first early benefit assessment was published in
single most important factor in AMNOG benefit
additional benefit. In the case of Brilique, for example,
appropriate standard of care in the indication. Where
January 2012, just over a year after the AMNOG law
assessments with head-to-head evidence against the
the GBA showed that it will accept indirect comparison
more than one such product is available, the lowest
came into effect. A total of 29 assessment procedures
comparator key for a positive assessment.
but that it considers the evidence of limited value.
price comparator should be selected. If there is no
had been initiated at the time of writing (April 2012),
drug alternative, the comparator can be a non-drug
of which results from IQWiG were available for 25. Of
IQWiG and GBA have underlined several times that they
IMPLICATION
treatment.
this number, the GBA had reached a final decision on
Additional benefit should ideally be demonstrated on
16 new drugs, four of which were not supported by
the basis of head-to-head trials with the appropriate
their manufacturers with dossiers and were therefore
comparator. There are opportunities throughout the
deemed of no additional benefit (see Figure 3).
Figure 3
AMNOG evaluations to date (1 Jan 2011 11 May 2012)
GBA procedures
(status of 11th May 2012)
Early benefit assessment procedure
Available GBA assessments

2
started
Exemption from early benefit assessment
BRILIQUE
HALAVEN
ESBRIET
RASILAMLO
GILENYA
TRAJENTA
will not consider evidence based on comparators that do

not meet their definition of the appropriate comparator.
Arguments for the use of other comparators have been
rejected and products that used the wrong comparator
ruled by the GBA to have no additional benefit. This has
Evidence based on hard endpoints is strongly

preferred by IQWiG and GBA to ensure acceptance of
negotiation with the benchmark set at the level of
an additional benefit.
comparable products in the market.
Soon after the AMNOG law was passed, and long before
Alignment with the GBA on choice of comparator is
the first benefit assessments were published, IQWiG
therefore essential to a positive outcome and price
and GBA made it clear that they would consider trial
negotiation the earlier, the better as it helps to
outcomes on four patient relevant hard endpoints:
shape appropriate trials. On the evidence of completed
mortality, morbidity, quality of life and side effects.
assessments, IQWiG and GBA fully accepted the
Benefit assessments containing these hard endpoints
manufacturers choice of comparator in just three of the
would therefore have a greater chance of demonstrating
12 completed assessments so far (Halaven, Victrelis,
an additional benefit.
Zytiga). In another five cases, the comparator was only
Surrogate parameters, on the other hand, are not
Hearing procedure started
JEVTANA
XIAPEX
accepted for a specific sub-population, but not for all
Final decision making in preparation
EDARBI
defined sub-populations (Brilique, Esbriet, Gilenya,
Total
Incivo, Jevtana). The comparator was rejected for a

LIVAZO
RAPISCAN
29
YELLOX
Restricted add.
benefit granted
No additional
benefit granted
No dossier
submitted
Source: GBA (2012): bersicht der Wirkstoffe; in: http://www.G-BA.de/informationen/nutzenbewertung

the best chance of achieving a positive outcome.
via a reference price group or a more challenging price
TROBALT
ZYTIGA
present high quality evidence to give their products
LEARNING 2: FOCUS ON HARD ENDPOINTS
INCIVO
16
to choose the right comparators against which to
because products with no additional benefit are priced
VICTRELIS
Manufacturers should engage early with the GBA
direct implications on the achievable price in Germany
No status
Early benefit assessment procedure

completed
THE SEVEN AMNOG LEARNINGS
further four products that were consequently found to
generally defined as appropriate endpoints though they

are considered as long as their use is well justified. In
the case of Victrelis, for example, sustained virologic
response (SVR) was accepted as a surrogate endpoint for
have no additional benefit (Rasilamlo, Trajenta, Trobalt,
two reasons. First, because the percentage of patients
Xiapex).
with complications (e.g. hepatocellular carcinoma)
Alongside the right choice of comparator, manufacturers
in following years under the patients with SVR was
must also provide compelling evidence to support the
significantly lower than the percentage in patients
positioning of their product against the comparator.
without SVR. Second, the percentage of patients with
Available benefit assessments demonstrate that head-to-
SVR relapsing was very low. In effect, SVR was seen as a
head evidence against the right comparator was included
surrogate for curing subsequent complications. But while
in all positive outcomes, while indirect comparison versus
IQWiG and GBA will accept surrogate endpoints
TM
AMNOG case study 1: Jevtana

Cabazitaxele (JEVTANA)
In combination with prednisone or prednisolone treatment of patients with hormone refractory metastatic
prostate cancer previously treated with a docetaxel-containing regimen
Indication
MNF dossier
Patient population
Grown up patients with mHRPC having been treated with docetaxel
Comparator
Best supportive care
Patient population(s)
Best supportive care population (no further docetaxel therapy

possible)
LEARNING 4: PREPARE WITHOUT RELYING

ON QUALITY OF LIFE OUTCOMES
In the meantime, manufacturers face a dilemma over
Quality of life outcomes are rarely considered in
submissions. Once more, the best advice is to open an
the benefit assessments of IQWiG and in the final
early dialogue with the GBA on generating acceptable
decisions of the GBA.
quality of life outcomes for inclusion on dossiers. It
Despite public pronouncements to the contrary, there

is little evidence that patient-oriented quality of life
Docetaxel-retherapy population
measures hold as much weight in IQWiG/GBA assessments

as hard endpoints related to mortality, morbidity and side
IQWiG assessment
Comparator choice
Docetaxel in combination with prednisone or

prednisolone
(Additional) benefit
Indicator for important additional benefit for patients >65

Weak indicator for not quantifiable additional benefit for patients
<65 years
Indicator for slight additional benefit
evidence as inferior to hard endpoints.
level of additional benefit granted to a product.
A further consideration for manufacturers is the way
In eight of 12 assessed benefit dossiers, IQWiG and GBA
in which IQWiG and GBA use hard endpoints in their
have defined additional or new sub-populations to those
assessments. In the evaluation, they select a limited
presented by manufacturers. In such cases, evidence
number of high quality hard endpoints, ignoring the
designed to support a different sub-population has been
rest gathered by the manufacturer. As with the choice
deemed insufficient to warrant an additional benefit in
of comparator, this suggests that manufacturers consult
the newly defined GBA sub-population. As a result, the
early with the GBA on the choice of relevant endpoints
overall additional benefit for the product as a whole,
in clinical trials. This will give the manufacturer the
defined as a combination of the additional benefit in
best opportunity to gather and develop evidence that
each patient segment, has been diluted and found to
meets the IQWiG and GBAs rigorous standards and
be lower than that claimed by the manufacturer.
the best chance of securing an additional benefit.
The message for manufacturers is once again to plan
IMPLICATION
early and engage with the GBA on the definition of
of additional benefit on a limited number of hard

endpoints and/or well justified and accepted
surrogate endpoints developed in conjunction
with IQWiG and the GBA, rather than presenting a
broader range of endpoints that might be judged
irrelevant.
LEARNING 3: ANTICIPATE PATIENT

SEGMENTATION BY IQWiG/GBA
to the eventual acceptance by IQWiG and GBA of

methodologies and standards that have proven their
use in practice.
IMPLICATION
Manufacturers are advised in the current
environment not to be over-reliant on quality of life
endpoints in their benefit assessments but to work
in most instances it was found statistically insignificant
with IQWiG/GBA on the longer term development of
or the methodology was considered inappropriate to
acceptable methodologies and standards.
practice relates to IQWiG/GBAs failure to map out and
manufacturer, with the effect of reducing the overall
might be a long term investment but it could lead
life data was taken into account on a case-by-case basis,
The apparent contradiction between theory and
in cases like Victrelis, they still consider this type of
Manufacturers should focus their demonstration
basis of quality of life related evidence. While quality of
demonstrate an additional benefit on this endpoint.
Source: GBA (2012): Nutzenbewertungsverfahren zum Wirkstoff Cabazitaxel:

http://www.g-ba.de/informationen/nutzenbewertung/10/
effects. Of the total AMNOG assessments to date that have

demonstrated additional benefit, none has done so on the
GBA decision
Palliative treatment with dxamethason, prednisone, prednisolone or

methylprednisolone as well as best supportive care
how to leverage quality of life endpoints in their
communicate a viable methodology for producing quality

of life outcomes. Unlike the other three endpoint types
identified by IQWiG/GBA, in the absence of a viable
methodology, quality of life remains a work in progress.
It has yet to be seen whether IQWiG and GBA will address
LEARNING 5: ASSUME THE GBA WILL

NOT REFERENCE INTERNATIONAL CLINICAL
BENEFIT AND ACCESS DECISIONS
The AMNOG process operates relatively
independently of international price comparisons
and reimbursement decisions, despite the inclusion
of a reference price solution for products with an
this gap proactively by presenting guidelines, or whether
additional benefit that fail in price negotiations.
they will gradually accept manufacturer-submitted
A comparison of products assessed under AMNOG that
methodologies.
have already undergone HTA evaluations in other
AMNOG case study 2: Brilique

Ticagrelor (BRILIQUE)
Brilique is indicated for the prevention of atherothrombotic events in adult patients with Acute Coronary Syndromes
(unstable angina, non ST elevation Myocardial Infarction [NSTEMI] or ST elevation Myocardial Infarction [STEMI])
Indication
MNF dossier
the patient sub-populations for their product. For each

potential sub-population, manufacturers should then
identify the appropriate comparator (Learning 1) and
Patient population
Total ACS population
Comparator
Clopidogrel + ASA
Patient population(s)
Unstable Angina and MI w/o

ST segment elevation
(IA/NSTEMI)
MI with ST elevation
(STEMI) in patients on
medication
MI with STEMI in patients with

previous Percutaneous Coronary
Intervention (PCI)
MI with STEMI in
patients with previous Coronary Artery
Bypass Graft (CABG)
Comparator choice
Clopidogrel + ASA
Clopidogrel + ASA
Prasugrel + ASA
ASA monotherapy
Evidence for important

additional benefit
No additional
benefit
Exception: Weak indicator for not
quantifiable additional benefit for
(1) patients >75 inappropriate for
Prasugrel (2) patients with transitoric ischemic attacks/stroke
No additional
benefit
the patient relevant endpoints (Learning 2) to obtain

the best chance of demonstrating an additional benefit
for their product in development.
IQWiG
assessment
IMPLICATION
Manufacturers should identify and consider all
potential sub-populations in a risk assessment prior
to the submission of the dossier ideally in the
Completed assessments indicate that IQWiG and GBA
planning phase of the clinical trials in order to
have often segmented the patient population into
anticipate segmentation by IQWiG and the GBA after
different sub-populations to those defined by the
submission of the dossier.

GBA
decision
Evidence for important

additional benefit
Source: GBA (2012): Nutzenbewertungsverfahren zum Wirkstoff Ticagrelor:

http://www.g-ba.de/informationen/nutzenbewertung/18/
TM
Differences in IQWiG and GBA decisions on level of additional benefit (N = 16)
The AMNOG law and the GBA Verfahrensordnung define
owing to IQWiG/GBAs unique methodologies. For
the general methodology for benefit assessments by
Brilique, the European Medicines Agency (EMA) granted
IQWiG and the GBA (see Figure 4). The main elements
marketing authorization for the total acute coronary
of that methodological standard include the definition
syndrome (ACS) patient population and accepted the
of the level of benefit (major, important, slight, not
comparison of ticagrelor with clopidogrel demonstrated
quantifiable, no additional benefit or smaller benefit
in one trial. Brilique had already been assessed in
than comparator) and the definition of the likelihood
England, Scotland, Wales and Denmark before the
of additional benefit (evidence, indicator, weak
benefit assessment in Germany and was granted full
indicator). The clarity of these definitions increases the
access and reimbursement also for the total ACS
transparency and, in theory at least, the predictability of
patient population.
the IQWiG evaluation and GBA decision making process
In Germany, however, IQWiG and GBA defined four sub-
(Lesson 5).
populations and for each of these identified appropriate
In contrast, specific details on how trial outcomes
comparators. In its final decision, the GBA accepted
per endpoint translate into the level of additional
evidence for an important additional benefit in just
benefit have not been defined. The first proposal on
one sub-population, while in the other three it found
the quantitative definition of the different levels of
no additional benefit (with the exception of a weak
additional benefit was provided by IQWiG in the first
Source: GBA (2012): bersicht der Wirkstoffe; in: http://www.G-BA.de/informationen/nutzenbewertung
indicator for a non-quantifiable additional benefit in a
benefit assessment on Brilique. It defined for each of

the main endpoints different thresholds for confidence
IMPLICATION
between the two and the IQWiG recommendation
segment of one of the four sub-populations).

In further examples of the AMNOG process not
In the absence of quantitative definitions of benefit
features prominently in the GBAs decision making.
intervals and relative risks, and linked expected clinical

outcomes to one of the levels of additional benefit.
levels, the most reliable source of information on
In total, 6 out of 12 completed GBA decisions did not
following other EMA/health technology assesments in
The GBA did not accept or comment on IQWiGs proposal,
the AMNOG process is the back catalogue of publicly
follow exactly the IQWiG recommendations (see Figure
Europe, Gilenya, Halaven, Incivo, Jevtana, Victrelis and
instead stating that the issue would have to be resolved
available benefit assessments, which can help
6). For example, IQWiG recommended in its report
Zytiga were all granted full access and reimbursement
by an expert panel which has not yet been convened.
manufacturers stratify risk and estimate the potential
on Brilique to split the patient population into four
in France, but only limited or no additional benefit in
It remains uncertain whether the GBA is willing to
outcomes of benefit assessments.
different sub-populations, from which only one received
Germany.
In all cases, IQWiG and the GBA explained their
define quantitative thresholds for each of the additional
positions on the basis of the new AMNOG legal
benefit levels in each endpoint. On the one hand,
LEARNING 7: NEGOTIATE WITH THE GBA

AFTER PUBLICATION OF IQWiGs RESULTS
framework in Germany. Further, by adopting a high
it would improve transparency and predictability for
The GBA represents the highest authority in the
benefit for a further sub-population.
degree of transparency and sticking to its clearly
manufacturers; on the other, it would burden IQWiG and
benefits assessment process and has demonstrated

its independence by not always following
Additionally, the GBA does not always follow IQWiG in
defined procedures, standards and rules, Germany has
the GBA with another layer of procedure.
been able to go its own way and justify its deviation
Figure 4
recommendations from the IQWiG; this opens
from other European markets.
IMPLICATION
For manufacturers, the best predictors of benefit
assessments are AMNOGs own defined procedures,
as German pricing and reimbursement decisions do
not automatically follow the label, HTA or market
access decisions of other European countries.
LEARNING 6: CLARIFY WHAT IS MEANT BY

ADDITIONAL BENEFIT
The general methodologies outlined in the legal
documentation and implemented in the first
AMNOG benefit assessments remain in use, though
specific guidance on different benefit levels has
yet to be defined.
Figure 5
countries shows a high level of deviation partly
71%
63%
IQwiG
GBA
19%
13%
AMNOG definition of level and quality of

additional benefit
Level of additional
benefit
Major additional benefit
Important additional
benefit
Slight additional benefit
Quality of additional
benefit
Evidence for additional
benefit
Indicator for additional
benefit
Weak indicator for
additional benefit
Not quantifiable
additional benefit
Smaller benefit than
comparator
Source: GBA (2012): Verfahrensordnung http://www.

g-ba.de/downloads/62-492-598/VerfO_2012-01-19.pdf
7% 6%
major additional benefit
important additional
benefit
14%
7%
slight additional
benefit
up opportunities for manufacturers to present

additional arguments in the hearing before the
GBA takes its final decision.
IQWiG is exclusively commissioned by the GBA and has a
very specific mandate to draw clinical conclusions on the
basis of scientific evidence. The GBA, on the other hand,
has a more pragmatic approach that applies clinical
data in actual medical practice hence the inclusion of
payers, providers and patients on the GBA.
not quantifiable
additional benefit
no additional benefit
a label of additional benefit. In its decision, the GBA

granted evidence for an important additional benefit
and a weak indicator for a non-quantifiable additional
its definition of sub-populations. In the case of Victrelis,

the GBA did not follow IQWiGs advice to split the
patient population into four different sub-populations,
accepting only the distinction of two sub-populations.
For manufacturers, this could well mean that there
is scope beyond the initial submission of evidence
to shape and influence IQWiG and GBA thinking with
supporting evidence. While the dossier will always be
the bedrock of the submission, manufacturers should
make the most of these additional opportunities.
Just as the AMNOG process as a whole has not always
IMPLICATION
followed European precedents, so the GBA has shown a
IQWiGs recommendations are not final and
degree of self-confidence in rejecting some of IQWiGs
manufacturers should see the hearing after the
recommendations on the level and likelihood of
Institutes assessment as a key step in discussing
(additional) benefit for a new product (see Figure 5). At
the extent to which IQWiGs scientific view is
the same time, there is a certain degree of dependency
applicable when treating patients in the real world.
TM
CONCLUSION
Although the pricing and market access environment
has become more regulated and more evidence-based
Figure 6
Differences in IQWiG and GBA decisions on

definition of patient population and extent
of additional benefit
since the introduction of AMNOG, Germany remains one

of the worlds most attractive markets for innovative
new products. By mitigating the risks and learning from
their experience of the new process, pharmaceutical
manufacturers can continue to launch their innovative
new products successfully in Germany.
GBA follows
IQWiG
(n=10)
GBA did not

follow IQWiG
(n=6)
It is still very early in the evolution of the AMNOG reforms
Figure 7
AMNOG: Seven learnings for market access (summary)
Learning
Commentary
Implication
1: S ELECT THE RIGHT

clinical COMPARATOR
Choice of comparator has been shown to be

the single most important factor in AMNOG
benefit assessments with head-to-head
evidence against the comparator key for a
positive assessment
Manufacturers should engage early with the GBA

to choose the right comparators against which
to present high quality evidence to give their
products the best chance of achieving a positive
outcome
2: F OCUS ON HARD
ENDPOINTS
Evidence based on hard endpoints is strongly

preferred by IQWiG and GBA to ensure
acceptance of an additional benefit
Manufacturers should focus their demonstration

of additional benefit on a limited number of
hard endpoints and/or well justified surrogate
endpoints developed in conjunction with IQWiG
and the GBA, rather than presenting a broader
range of endpoints that might be judged
irrelevant
3: A NTICIPATE PATIENT
SEGMENTATION BY
IQWiG/GBA
Completed assessments indicate that IQWiG

and GBA have often segmented the patient
population into different sub-populations
to those defined by the manufacturer, with
the effect of reducing the overall level of
additional benefit granted to a product
Manufacturers should identify and consider all

potential sub-populations in a risk assessment
prior to the submission of the dossier ideally
in the planning phase of the clinical trials in
order to anticipate segmentation by IQWiG and
the GBA after submission of the dossier
4: P
REPARE WITHOUT
RELYING ON QUALITY
OF LIFE OUTCOMES
Quality of life outcomes are rarely considered

in the benefit assessments of IQWiG and in
the final decisions of the GBA
Manufacturers are advised in the current

environment not to be over-reliant on quality
of life endpoints in their benefit assessments
but to work with IQWiG/GBA on the longer term
development of acceptable methodologies and
standards
5: ASSUME THE GBA

WILL NOT REFERENCE
INTERNATIONAL
CLINICAL BENEFIT AND
ACCESS DECISIONS
The AMNOG process operates relatively

independently of international price
comparisons and reimbursement decisions,
despite the inclusion of a reference price
solution for products with an additional
benefit that fail in price negotiations
For manufacturers, the best predictors

of benefit assessments are AMNOGs own
defined procedures, as German pricing and
reimbursement decisions do not automatically
follow the label, HTA or market access decisions
of other European countries
6: CLARIFY WHAT IS
MEANT BY ADDITIONAL
BENEFIT
The general methodologies outlined in the

legal documentation and implemented in the
first AMNOG benefit assessments remain in
use, though specific guidance on different
benefit levels has yet to be defined
In the absence of quantitative definitions

of benefit levels, the most reliable source
of information on the AMNOG process is the
back catalogue of publicly available benefit
assessments, which can help manufacturers
stratify risk and estimate the potential outcomes
of benefit assessments
7: N
EGOTIATE WITH
THE GBA AFTER
PUBLICATION OF
IQWiGs RESULTS
The GBA represents the highest authority

in the benefits assessment process and has
demonstrated its independence by not always
following recommendations from the IQWiG;
this opens up opportunities for manufacturers
to present additional arguments in the hearing
before the GBA takes its final decision
IQWiGs recommendations are not final and

manufacturers should see the hearing after
the Institutes assessment as a key step in
discussing the extent to which IQWiGs scientific
view is applicable when treating patients in the
real world
Other definition of the

patient population
(n=3)
Other definition of the
extent of additional
benefit (n=3)
to reach robust conclusions. But on the evidence of

benefit assessments to date, it is possible to draw some
preliminary learnings for the pharmaceutical industry to
action as it works with the new process to secure the best
Source: GBA (2012): bersicht der Wirkstoffe; in:

http://www.G-BA.de/informationen/nutzenbewertung
outcomes for its new products (see Figure 7).

Several common themes emerge. First and foremost, it
International launch sequences
is vital to engage constructively with the GBA at the
One recurring feature of the new process has been its
earliest possible opportunity ideally before starting
unrelenting focus on cost savings sometimes at odds
phase III clinicals. This affords the greatest opportunity
with international HTA and market access decisions.
to choose the appropriate comparator in the right patient
As a consequence, the evidence requirements in more
populations with the endpoints of most interest to IQWiG
independent-minded Germany might not be suitable
and the GBA. Second, be prepared to switch courses as
for a global pricing and market access strategy, and
the AMNOG process has thrown up a few surprises. The
manufacturers might want to rethink their global
GBA in particular has demonstrated a self-confidence
launch strategy. Tailoring trial designs to meet specific
and independence of mind by apparently ignoring such
requirements defined by IQWiG and the GBA might well
factors as quality of life data and such institutions
be counter-productive in other countries. Manufacturers
as EMA, international HTA agencies and even the
should therefore think through the entire commercial
recommendations of IQWiG. Finally, given that AMNOG is
opportunity across regions USA included when
working to its own unique standards and procedures, the
considering the merits of a GBA-driven approach
best guide to what it might do in the future is what it
internationally.
has done in the past.
In the case of Trajenta, for example, Boehringer
But many questions remain unanswered. The first step
Ingelheim (BI) and Lilly decided not to launch their oral
of the new process has been completed for selected new
anti-diabetic Trajenta in Germany because of the GBAs
products and the GBAs initial decisions will form the
choice of comparator. The manufacturers were concerned
basis of phase two price negotiations and arbitration.
that the therapeutic benefit of Trajenta would not be
However, that takes longer and there is so far little
properly demonstrated, resulting in a low price that other
evidence on the final outcomes for the first wave of
countries could reference. The Trajenta case demonstrates
products going through the negotiations. As a result, cuts
how AMNOG is already changing the way manufacturers
to reimbursement prices remain a distinct possibility and
have to consider their launch strategy in Germany and
would seem to be in line with AMNOGs overall objectives.
how that is having ramifications internationally.
REFERENCES
Federal Joint Committee (G-BA). Frhe Nutzenbewertung (35 a SGB V), in:
http://www.g-ba.de/informationen/nutzenbewertung/
Institute for Quality and Efficacy in the Health care system (IQWiG). Projekte, in:
https://www.iqwig.de/projekte-ergebnisse.915.html
10
11
TM
IMS Consulting Group is the worlds leading,

specialized advisor on critical strategic and
commercial issues in life sciences.
If you have questions about this

white paper or related issues you
would like to explore, please contact
our Pricing and Market Access group.
With a global presence and local expertise

across five continents, we know the pulse of
the market anticipating change, understanding
its impact and resolving the challenges it brings.
From pricing and market access and marketing
issues to product, portfolio and geographic
investment decisions our life sciences
consulting teams offer insights that drive
results. All backed by the strongest evidence
and analytics.
GERMANY
Justus Dehnen, Engagement Manager
jdehnen@imscg.com
+49 89 457912 6418
Additional information is available at

http://www.imsconsultinggroup.com
Michael Schmoeller, Consultant

mschmoeller@imscg.com
+49 89 457912 6416
UK
Katia Berg, Principal
kberg@imscg.com
+44 203 075 4000
EDITOR
Neil Turner, Senior Manager
nturner@imscg.com
+44 1223 273430

AMNOG Seven Learnings Strategic Access Germany

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AMNOG Seven Learnings Strategic Access Germany

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AMNOG: Seven Learnings for Strategic

Market Access Decisions in Germany

AMNOG: Seven Learnings for Strategic

The AMNOG process in summary

Institute for Quality

Source: IMS Consulting Group

Valid until the end of

FRP = reference price

What does additional benefit mean?

significantly altered the pricing process to include discount negotiations. In addition,

The manufacturer then has the opportunity to

The price setting procedure for new drugs in Germany

comment on the decision at a hearing, after which

changed on 1 January 2011 with the introduction of the

the GBA will reach a final decision within a further

AMNOG law, which added a reimbursement price to the

existing manufacturer-set list price. While the list price

For new products with orphan drug status, a simplified

remains unchanged, the reimbursed price will be set at

submission process applies. The manufacturer has

the latest 12 months after a new products launch, based

only to submit an extract of the dossier and the

on discount negotiations or reference pricing following

benefit, as the additional benefit in general is

If the drug is considered to offer no additional benefit,

If the new drug is considered to offer an additional

it will be given a reimbursement price in relation to

benefit (there are different levels of additional benefits

the price of the comparator used during the benefit

possible: major, important, slight or non-quantifiable

assessment. Should that comparator belong to an

additional benefits) then a discount will be negotiated

For every new product launched in Germany (excluding

existing reference price group (festbetragsgruppe),

between the manufacturer and the lead association of

generics and hospital-only products), manufacturers

the new drug will be classified immediately into that

the German sick funds (GKV-SV) based on the reimbursed

are now required to submit a benefit dossier for

group if possible. If there is no existing reference

price of the comparator and the additional benefit

assessment to the Federal Joint Committee (GBA).

price group, the GBA will consider the possibility of

demonstrated. Any discounts will be taken from the

The GBA usually commissions the Institute for Quality

The reimbursement price of products with no

creating a new group. If a new group cannot be set

list price set by the manufacturer. The new reimbursed

and Efficiency in Health Care (IQWiG), which operates

additional benefit is set based on a reference price or

up, the reimbursement price will be discounted from

price will be effective at the latest from month 13 after

as a GBA support function, to evaluate the evidence

in price negotiations, while manufacturers of products

the list price to the price level of the comparator. The

launch, while the original manufacturer-set list price

provided by the manufacturer.

with additional benefit enter price negotiations with

reimbursement price will be effective at the latest from

The result whether the drug offers an additional

the lead association of the German sick funds

benefit or not against a GBA selected comparator

(GKV-SV). Should negotiations fail, the reimbursed

is published on the internet within three months