As economies in the Western world have veered from struggling to collapsing over the past five years, Germany has emerged as one of Europe’s most financially stable countries.
Part of the reason for this has been strong government efforts to keep costs low, taking in all aspects of public spending, including the much-revered area of healthcare.
When it comes to reducing the cost of national healthcare programmes, it’s rare that a government doesn’t look to cutting back the cost of medicines to help fulfil this goal, with the emerging relevance of health technology assessment (HTA) to assess the cost-effectiveness of new drugs reflecting this change.
Germany is no different, and its HTA body – the Institute for Quality and Efficiency in Healthcare (IQWiG) – has become one of Europe’s most influential and renowned bodies in the world of market access.
“We provide evidence reports for decision-making in the German healthcare system,” explains Dr Beate Wieseler, head of the department of drug assessment at IQWiG.
IQWiG’s recommendation is not final, however, and once an evidence report is create, it is then passed to a public legal entity called the Federal Joint Committee (G-BA). This body, which comprises doctors and hospital representatives, makes a decision based on the IQWiG review before a final decision is made by the Ministry of Health.
Both the G-BA and IQWiG have only been around since 2004, taking over from previous organisations in order to create a more robust system for drug reimbursement and healthcare guidelines.
However, their busiest period, certainly in terms of medicines, has been in the past three years with the introduction in 2011 of AMNOG – a pricing system that requires new drugs to show additional benefit in a cost-effectiveness comparison to a corresponding established therapy, which can often be very inexpensive generic medicines.
The impact of AMNOG drug pricing
The main reason for the introduction of AMNOG was to reduce drug spend, according to Dr Wieseler.
“I think Germany was facing the same problems as all countries,” she says. “There were growing costs in healthcare and people thought that wasn’t sustainable anymore.”
Another key aspect of AMNOG for Dr Wieseler is that it prevents manufacturers from setting their own prices for drugs.
“Previously there was no negotiation or any other regulation of prices,” she says. “The price was set by the manufacturer and this had resulted in higher prices and high healthcare costs. “
This negotiation takes a year to work out, however, and Dr Wieseler explains that once a drug is licensed for use in the EU, it can immediately enter the German market at a price set by the manufacturer before a regulated price is worked out one year later.
“Most other countries have decided for a forced hurdle, so in other countries drugs can’t enter the market before there has been an assessment and a price negotiation,” she says. “In Germany, after the first year, there is a regulation of the price.”
The big question is whether AMNOG has actually led to a reduction in the price of medicines, or, as some industry voices have said, it has just made it harder for patients to have access to new drugs.
From a healthcare point of view, asking whether a new drug has a proven added benefit is exactly the question to ask
For Dr Wieseler, there is not an easy answer, and discussion between healthcare stakeholders is needed. “So first of all, the majority of drugs on the German market still are unregulated, so AMNOG so far covers only drugs introduced after January, 2010,” she explains. “Also the price reductions have been limited so far.”
The future of German drug reimbursement
One thing that is needed is a clear plan on how to assess the price of drugs already on the market before AMNOG, according to Dr Wieseler. For the moment though, this is set to be part of a political discussion on the future of AMNOG between the partners of Germany’s coalition government led by Angela Merkel’s Christian Union.
As for IQWiG’s role in this discussion, the organisation may not be directly involved, but Wieseler says it will provide “information on how we think AMNOG is working and what is working well”.
The debate on the future of AMNOG will also take into account industry criticism, which has come from individual pharma companies as well as the trade bodies the European Federation of Pharmaceutical Industries and Associations (EFPIA) and the German Association of Research-Based Pharmaceutical Companies (VFA).
This includes Germany-based Boehringer Ingelheim’s disapproval of the generic comparator used in IQWiG’s AMNOG assessment of the diabetes medicine Trajenta (linagliptin). In addition fellow German firm Bayer criticised IQWiG’s assessment of trial designs after the HTA body deemed data for eye drug Eylea (aflibercept) unsuitable in order to judge its cost-effectiveness over Novartis’ Lucentis (ranibizumab) in the treatment of wet age-related macular degeneration (AMD).
Dr Wieseler takes a pragmatic approach when addressing these concerns about AMNOG.
Regarding the choice of a generic comparator, she says: “New drugs should be assessed against the established brand of therapy, and at the same time against a therapy for which we have good evidence for its benefit.
“Of course, it sometimes might turn out then to be an older drug, which maybe already has a generic price.
“From a healthcare point of view, I think that is exactly the question to ask though. Does the new drug have a proven added benefit compared to our standard we are using right now?”
Companies also have a suitable chance to fight their case if they disapprove of a scientific decision made by IQWiG, according to Dr Wieseler,
“There is a hearing at G-BA in which criticism can be discussed,” she says. “I think that is the appropriate way to go because you can always disagree on scientific things and on the communication of data. You then just have to provide a transparent forum to discuss it.”
The previous lack of negotiations meant prices were set by manufacturers and this resulted in high healthcare costs
Although there is still a discussion to be had, for Dr Wieseler, AMNOG has been a positive step for healthcare in Germany in terms of gaining additional information about medicines.
“From IQWiG’s view overall, AMNOG is a very positive development, not only because it supports the pricing of drugs in Germany, but also because it has changed how new drugs are discussed in Germany. “
Ultimately, for Dr Wieseler, AMNOG will remain (“we need an assessment of new drugs”) although changes may be necessary if lower medicine prices do not emerge.
“It depends on whether AMNOG meets the requirements also on maybe controlling cost in the system, whether it will be developed further or not,” says Dr Wieseler. “That is still open.”
IQWiG and clinical trial transparency
In addition to its role in German drug pricing, IQWiG has also emerged as one of the leading organisations in the campaign for greater transparency of clinical trial detail, becoming one of the first major groups to sign up to the AllTrials campaign led by Dr Ben Goldacre.
This decision was partly down to the struggle for IQWiG in its early years to obtain the correct data to assess the cost-effectiveness of drugs, according to Dr Wieseler.
“Our aim is to produce unbiased assessments – to correctly describe the benefits and harms of the drug. And while everybody accepts that a regulatory agency should see all study data, that hasn’t been true for HTA agencies.”
Instead of seeing all clinical reports as the European Medicines Agency (EMA) does, IQWiG initially just had access to publicly-available data published in journals and registry reports.
This was a problem as “we knew published data were biased” says Dr Wieseler, with her words backed by a recent study by IQWiG published in PLOS Medicine.
At the time, IQWiG tried to prise clinical data from pharma companies directly, but struggled to get anywhere. This was especially true in the “landmark” case of Pfizer’s antidepressant reboxetine, with IQWiG spending two years obtaining all the data it needed from Pfizer.
“In the end when we had all the data, after an intense public debate, we found that when we looked at all data, the drug didn’t have a benefit, while the published literature showed otherwise,” says Dr Wieseler.
This was a high-profile case in Germany and led to changes in the law, including eventually a requirement in AMNOG that companies submit a full clinical study report as part of the HTA process. “This has been a major issue with us for years,” says Dr Wieseler. “And therefore we were happy to support the AllTrials campaign.”
As for Dr Wieseler’s views on what level of transparency is suitable, she is supportive of the EMA’s plans to make pharma companies provide greater access to clinical trial data. “What we need, first of all, is a full overview of all trials, so we know which trials have been done so that we can compile all the trials important for our research questions,” she says.
“We also need a full study protocol and an analysis plan and all the analysis,” she adds. “This is best provided by a full clinical study report. And this is sitting on the shelves anyway, so there is no additional need to produce new documents.”
And all this is crucial considering the rise of HTA. “I can’t see that the situation could go on like now,” says Dr Wieseler. “I mean, I think the situation we now have comes from a time where main decisions were only made at regulatory agencies. But we have gone beyond that.”
HTA and the EMA
Closer workings with the EMA are also part of the future of IQWiG and HTA, according to Dr Wieseler, referencing the recent plan by the Agency and the HTA body EUnetHTA to work together on making sure that data required by the EMA in its regulatory process aligns with market access requirements later down the line.
“I think very often it’s a pity to see that there are high-calibre phase III studies, which for example didn’t collect data on how it’s related to quality of life,” says Dr Wieseler. “This could be used in our assessment. So that is a very important area of cooperation – evidence generation.”
“While the EMA and the HTA bodies have in principle different tasks, I think that the overall goal is the same; that is bring good drugs to patients. There are things we can do together to support that.”
