Tag: Gemeinsamer Bundesausschuss

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: Will IQWiG Go Medtech?

According to a report by Ärztezeitung, Germany’s healthcare cost watchdog IQWiG (Institute for Quality and Efficiency in Health Care) is aiming to also bring the cost-benefit assessment of medical devices and procedures, such as operation techniques and laboratory diagnostics, under the scope of IQWiG and or G-BA, the highest decision-making body of the joint self-government of physicians, dentists, hospitals and health insurance funds in Germany.

Jürgen Windeler, head of IQWiG, told Ärztezeitung there was a “considerable discrepancy in terms of regulatory density” between drugs and all other therapeutic and diagnostic means in medicine. He therefore called for an early benefit assessment of these other methods, too, and suggested to start with medicinal products with the potential for causing a “health risk”.

Food for Thought: Weekly Wrap-Up

The human genome of newborns contains an unexpectedly low number of mutations, writes Joachim Müller-Jung in Frankfurter Allgemeine Zeitung (FAZ). Contrary to earlier estimates of 100-200 mutations generated in the germ cells of parents, the number is only about 60. Results come from sequencing the entire genomes of two families with one child each. The results have implications for understanding human evolution and genetics.

Sonja Kastilian, also in FAZ, features a preliminary report of IQWiG, Germany’s watchdog agency appraising drugs and treatments for quality and cost effectiveness, on the benefits of HPV testing of women as a screening for ovarian cancer. IQWiG set out to compare DNA tests for HPV with common pap smear tests and reported that the HPV tests leas to an earlier diagnosis and better follow-up examinations, regardlesss of whether it is applied alone or in combination with the conventional test. A final decision on whether the test is to be reimbursed by Germany’s statutory healthcare system is expected for 2012. In 2006, the Joint Federal Committee (G-BA), the body in charge, had voted against reimbursement for cost reasons. Kastilian also points out that HPV vaccination rates at present are below 30% in young women in Germany, in contrast to up to 81% in the UK, Portugal, and Australia. Reason has been an unduly discussion in German media about potential risks, high costs and lack of efficacy.

Uta Neubauer in Neue Zürcher Zeitung (NZZ) reports on novel approaches to use cold plasma to disinfect wounds, hands, and food. A method and device developed by the German Max Planck Institute for Extraterrestrial Physics has already demonstrated safety and efficacy in treating wounds and disinfecting hands. At present, it is under investigation for the treatment of foods, e.g. food additives and berries.

Sven Titz, also in NZZ, deals with latest insights into the physics of the water surface. Using vibration spectroscopy, physicists of the University of Southern California at Los Angeles found that the surface is made up basically by -OH groups of the water molecules sticking out from the liquid. The discovery will lead to better understanding solubility of molecules in water.

Forbes this week introduces two innovations in optics. Jennifer Hicks writes about the “socialization of the microscope” by a technology that allows the display of microscopic images on an extremely large multitouch screen, just like an oversized iPad. Thereby, groups of students, pathologists or researchers can focus on tiny details by touching, gesturing, and zooming in and out. A video of the microscope at work can be found here.

Californian-based start-up Lytro has unveiled a camera that can take pictures without focusing, writes Tomio Geron in Forbes. Instead, focusing on any point of interest in the photo is done once the image is loaded on a computer. The consumer camera is based on the light field technology invented by Stanford University researchers. The camera is fitted with special lenses and a sensor that captures every ray of light hitting it, regardless of whether it is from the fore- or the background, and records its individual color, intensity and direction. The camera therefore also can be used to generate 3D-pictures. Examples can be found here.

The Economist this week introduces an intelligent drug delivery approach using nanoparticles. It can be used to deliver anti-cancer chemotherapeutic drugs and makes use of the blood-clotting mechanism: first, nano-sized golden rods are injected into the blood stream. They fit into the unusual pores common in capillaries nourishing tumors and thereby mark tumor sites. Once they are in place, the tumor site is treated with laser light bursts. Their energy is absorbed by the gold and converted to heat destroying the capillaries so that the body’s coagulation system is triggered to repair the damage. This is when the second nanoparticles come into play. They carry the chemotherapeutics together with a fibrin-binding protein fragment and are designed to release the drug upon fibrin-binding only. The treatment strategy therefore delivers the drug exactly to the site the coagulation system is active, that is, at the tumor. The method developed at the Massachusetts Institute of Technology (MIT) has proven safety and efficacy in mice and will be tested in humans soon.

Researchers from the University of Rochester have come up with just another idea to release drugs on target, the New Scientist reports. They found that nanocarbon tubes containing aqueous solutions can be made to pop open by heating them from the outside with infrared lasers. Patients could be administered nanocontainers carrying drugs to deliver it to a desired target where the drug then is released by laser light.

And finally, Die Welt this week deals with wrinkles and high tech attempts to avoid or get rid of them. Clinical studies in people with an average age of 87 prove that vitamin A1 (retinol) is useful to smooth skin. Also, light from LEDs is able to remove a water film caging the skin’s elastic fibers so that they become rigid. The method is best applied by pre-treating the skin with green tee polyphenols to deactivate free radicals generated by the LEDs. Moreover, scientists from Hamburg-based Skin Investigation and Technology SIT found out that eating one bar of dark chocolate a day also leads to a 34% improvement of skin elasticity after 6 months. Further attempts to eliminate wrinkles are being made by using signaling peptides activating collagen-producing cells and by polymers carrying nanoparticles that are injected between outer and inner skin layers. The resulting films disperse the compression forces within the skin, thereby “ironing” it from inside.

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.