Tag: Germany’s statutory healthcare system

Food for Thought: Greek Ghosts Haunting Pharma

Up to the end of 2010, pharma companies were able to set the price for innovative new medicine at will upon introduction to the German market. Under the new AMNOG law, however, the price is dependent on the degree of innovation, as assessed by G-BA (Federal Joint Committee). G-BA requires pharma and biotech companies to provide information on medical benefits and advantages as compared to existing medicines across all indications the drug is approved for, and statistics on the (sub)sets of patients who will benefit from the drug. In addition, they have to provide spending figures of the statutory healthcare system and need to explain how quality can be assured during treatment.

G-BA can mandate the Institute for Quality and Efficiency in Healthcare (IQWiG) with the assessment (to make matters more complex, IQWiG can assess drugs and treatments also without assignment by G-BA) and once it has come to a conclusion, it needs to call for opinions of all parties (manufacturers, reviewers/experts, head organizations of patient/self-help groups and medical associations, etc.) – written statements as well as hearings.

If at the end of the process G-BA comes to the conclusion that the respective drug does not provide additional benefit, the medicine is subject to reimbursement under Germany’s fixed-price system and will be reimbursed in the price range of drugs already marketed in the same indication(s).

However, if the new medicine is ruled innovative, the bazaar is open: lobby groups of the pharmaceutical industry, including generics manufacturers, start debating with G-BA and representatives of the statutory healthcare system. The interesting part of this procedure is that pharma companies have to provide data on the selling price in “other European countries”.

But which are these “other” countries? With the European debt crisis, the debate has become heated: while manufacturers demand to select countries with similar economic power as comparators (such as France or UK), the statutory healthcare insurers are advocates of including Europe’s weakest economies: Greece, Portugal, The Czech Republic, Slovakia, etc. To resolve the problem, an arbitration board was founded.

Since last week, the jury is out, and it is not in favor of manufacturers. The arbitration board selected 15 European countries as reference countries for price fixing. The list comprises Austria, Belgium, the Czech Republic, Denmark, Finland, France, Greece, Ireland, Italy, The Netherlands, Portugal, Sweden, Slovakia, Spain, and the UK. At least five of them are economically weak countries with low drug prices.

The ruling will have consequences not only for Germany. If, as a result, prices for innovative medicines in Germany come down, prices elsewhere in Europe might follow as Germany is a reference country for pricing in many other European countries. To avoid a downward spiral, manufacturers may choose to introduce novel innovative drugs in Germany only with a considerable delay.

Food for Thought: Future Reimbursement of Novel Cancer Drugs in Germany

Germany’s new law regulating the reimbursement of drugs, the so-called Arzneimittelmarktneuordnungsgesetz – AMNOG, requires companies planning to introduce a novel drug to the German market to provide a value dossier, if they want reimbursement of the full price for the first year of marketing (See the akampioneer, “Germany’s New Reimbursement Law“). This value dossier not only needs to demonstrate efficacy and safety, but also has to provide evidence that the drug is more advantageous to existing treatments in terms of patient-relevant endpoints such as morbidity, mortality and quality of life.

This is difficult to prove as many novel cancer drugs are approved on the basis of surrogate endpoints such as slowing or stopping cancer growth (objective response rate ORR, time to tumor progression TTP, time to treatment failure TTF or progression-free survival PFS).

Late last month, Germany‘s Institute for Quality and Efficiency in Health Care (IQWiG) has published details on how it is going to evaluate the patient benefit in these cases. IQWiG usually is evaluating drugs on behalf of the so-called Gemeinsamer Bundesausschuss G-BA (Federal Committee), a decision body within Germany´s statutory healthcare system.

In cancer, IQWiG plans to primarily address „the question as to whether a therapy can prolong the life of affected patients. In addition, a new therapy should alleviate symptoms, prevent complications, and improve quality of life.“ If surrogate endpoints have been used for approval, IQWiG will only accept them as evidence for patient benefit, if the validity of these endpoints for demonstrating patient benefit can be proven by correlation-based approaches based on randomized controlled trials.

In a 160 page „rapid report“ (available in German only) IQWiG details its approach to search available literature for studies on the correlation between surrogate and patient-relevant endpoints. In addition, it describes how it is performing a meta-analysis of these studies for assessing the strength of the correlation (three levels) and the reliability of the validation studies (four levels) to reach an overall conclusion about the validity of the surrogate endpoint for a decision whether the new drug is providing patient benefit.

While the institute so far has only differentiated between „proof“ of surrogate endpoint validity and „indication“ of validity (meaning medium reliability), it proposes to introduce a third category called „hint“ for the fulfillment of certain minimal requirements for the available studies. This category will be applied in cases where the validity of a surrogate endpoint is unclear – a situation IQWiG expects to be quite common. In these cases, IQWiG states, „it can also be taken into account how strong the effect of a treatment turns out to be“. IQWiG would then seek to find a threshold value for the surrogate marker and evaluate whether the new treatment exceeds this value, e.g. whether it decelerates tumor growth for longer than a specified period of time.

Last not least, IQWiG appeals to drug makers and study groups to make accessible their analyses on the validity of surrogate endpoints and the specification of threshold values, e.g. in special registries.

A short English summary of IQWiG‘s basic assumptions on how to recognize at an early stage whether a new cancer therapy prolongs life can be found here. IQWiGs proposals for the early benefit assessment of cancer drugs can be read, also in English, here.