Archive: Food for Thought
Food for Thought: Future Benefit Assessment of Medtech in Germany
Germany´s Law on the Stabilization and Structural Reform of the Statutory Health Insurance (Versorgungsstrukturgesetz) came into effect January 1st, 2012. For medtech companies it is important that the law introduces a novel instrument of the statutory healthcare system’s Joint Federal Committee G-BA for the assessment of innovative medical technologies. This novelty – the so-called “trial provision” for innovative medtech methods – has the advantage of not summarily excluding methods whose benefit is not immediately clear.
Dr Rainer Hess, Chairman of G-BA, in January detailed the plans of G-BA for the assessment of innovative medical technologies: “We are not assessing medicinal products, such as pacemakers or endo-prostheses,” he said during the recent MedInform conference “Versorgungsstrukturgesetz 2012” hosted by BVMed, the German Medical Technology Association. “We are evaluating medical diagnostic and therapeutic procedures in which medical devices may play a role.”
The trial provision, he added, would offer the opportunity to conduct representative studies of novel procedures, if adequate evidence is not available and novel studies are not to be expected.
Hess said G-BA will expect the demonstration of an additional benefit as compared to existing methods. To determine this additional benefit, G-BA will lay out study requirements in a guideline and assign an institute with conducting the study. Manufacturers will have to contribute financially to the study – otherwise the device can be excluded from reimbursement.
Germany’s Institute for Quality and Efficiency in Healthcare (IQWiG) will then furnish a scientific opinion. Finally, G-BA will host a hearing, including experts, and subsequently make a decision about reimbursement.
Assessment can be demanded by the manufacturers but also from a statutory health insurance company.
Further information can be found at the webseite of BVMed – The German Medical Technology Association
Food for Thought: Germany Lags Behind in Biotech
These days, everybody has his own opinion about the quality and prospects of the German biotechnology industry. It even seems to be difficult to determine if biotech funding in Germany has increased, remained stable – or dramatically decreased, as recently published by the German industry organization BIO Deutschland.
If you look at key intangibles, such as the extent of media coverage on the biotech sector and the attractiveness of German biotech companies for investment banks, it is obvious that German biotech is not on the rise.
An article by Roland Benedikter and James Giordano published by German newspaper Die Welt suggests a bleak scenario if Germany is not willing to accelerate and intensify its biotech efforts. According to the authors, biotechnology is not only the most important success factor in future economic development – it will also change the global power balance: “the one who controls the chips also controls the game”. Asia and the Far East are quickly catching up in the biotech space, while the U.S. and other European countries continue to heavily invest into the sector. Therefore, Germany might gradually evolve from an export-oriented country to an import-oriented one – unless there will be a fundamental change of mind in the German government and society.
Almost two decades ago, the German biotech industry started out with the clear goal to narrow the gap to the U.S., where biotechnological markets and ventures were (and still are) much more mature. Since then, the German biotech sector has successfully produced a number of promising companies, innovations and products. However, the most attractive and advanced companies and technologies have been acquired by foreign, mostly U.S.-based, companies. Amgen´s take-over of Micromet, an oncology company with academic roots at the University of Munich, is the most recent example.
Therefore, lack of innovation is clearly not the problem. And lack of funding is only the symptom of an underlying German (and partly European) biotech phenomenon – wide-spread risk aversion combined with limited availability of true executive leadership qualities. Moreover, the public sentiment towards biotechnological innovation remains skeptical or even hostile and is mirrored by a “we don’t need this”-attitude of politicians and even Germany’s healthcare system, in which IQWiG, a decision body responsible for drug reimbursement, does its best to belittle innovative medicines.
It may not surprise you that an often-heard German term, “technologiefeindlich” (i.e. a negative attitude towards technological innovation), lacks any English equivalents.
Food for Thought: It’s becoming a habit – IQWiG takes approval studies apart
Germany’s Institute for Quality and Efficiency in Health Care (IQWiG) this year put out several negative assessments of newly introduced drugs, stating the data did not prove “additional benefit” over existing treatments. In all cases, IQWiG came to the conclusion after deviating from the study design the companies had discussed with the regulators. Instead, IQWiG’s experts divided the patient population into subgroups, saying those subgroups needed different comparator treatments. As a result, these data were either not available or the subgroups were too small to demonstrate statistical significance.
One example is Pfizer’s Xiapex injectable collagenase, approved in early 2011 to treat Dupuytren’s contracture. IQWiG stated that Xiapex does not provide an additional benefit to patients because “it was not possible to derive such additional benefit from the dossier and because the manufacturer did not provide additional or suitable data” to substantiate the claim.
While the manufacturer had compared the Xiapex injection to a surgical treatment, partial fasciectomy (PF), IQWiG for its assessment established six subgroups of patients according to the severity of the disease and chose three different treatment options as comparator: no therapy, percutaneous needle fasciectomy (PNF) and partial fasciectomy (PF). As a result, IQWiG was able to state that Pfizer did not provide evaluable data because the company’s selected comparators differed from IQWiG’s comparators for all but one patient subgroup.
In the case of Eisai’s breast cancer drug Halaven eribulin, IQWiG’s verdict ruled that it could not find evidence for eribulin resulting in a prolonged life expectancy. IQWiG added that Halaven might provide an overall survival benefit for patients for whom taxanes or anthracyclines are no longer an option, but it was unclear whether the benefit was significant. Again, the assessment was made by subdividing the patient group. IQWig defined two subpopulations – one for which an additional anthracycline or taxane treatment was thought to be an option and one for which this was not.
Eisai, in contrast, had compared Halaven to a “Treatment of Physician’s Choice” (TPC) as there are no established national or international treatment guidelines for a standard therapy of women with metastatic or locally advanced breast cancer after failure of two standard chemotherapies including an anthracycline or taxane. This design of Eisai’s EMBRACE was established in discussions with the European Medicine’s Agency (EMA). Being a European study, the participating physicians sometimes opted for therapies not approved in Germany – a reason for IQWiG to not include these data in its assessment. As a result, only 69% of the EMBRACE study patients were regarded as suitable for an assessment.
The same approach was taken in the assessment of Novartis’ Gilenya fingolimod, the first oral treatment for Multiple Sclerosis (MS) approved in 2011. IQWiG once again performed separate assessments of the drug in three groups of patients, choosing three different comparators. Following this operation, IQWiG was able to find data only for one of these subgroups in the study, not enough to establish an additional benefit with sufficient statistical significance. However, one of the comparisons chosen by IQWiG – fingolimod against glatiramer acetate in patients with relapsing/remitting MS – would have been impossible as fingolimod is approved as second-line therapy in this indication while there are no studies of glatiramer acetate differentiating between first-line and second-line treatments.
In all cases, manufacturers may respond to the assessment, after which the Federal Joint Committee (G-BA) will review IQWiG’s recommendation before making a final decision. If G-BA deviates from IQWiG’s negative assessment, the manufacturers have to negotiate the price with the Statutory Health Insurance Funds Association (GKV-Spitzenverband) under the AMNOG pricing scheme. If G-BA agrees with the IQWiG assessment that a drug has no clinical benefit beyond available treatments, the drug will be added to the reference pricing system, which gives the same base price to all comparable drugs in the respective therapeutic group.
Food for Thought: “Forget Alzheimer’s”? – A Book Review
“Forget Alzheimer’s” is the title and the message of a book by German journalist Cornelia Stolze who is claiming to tell the “truth about a disease which isn’t one” (Cornelia Stolze, Vergiss Alzheimer. Die Wahrheit über eine Krankheit, die keine ist, Köln/Cologne 2011: Kiepenheuer & Witsch).
The book is strongly criticizing the handling of dementia, in particular Alzheimer’s disease (AD) in today’s medicine, pointing out the lack of adequate diagnostics and therapies and contrasting this sad reality with the often exaggerated promises of imminent breakthroughs by experts.
Stolze starts by explaining that to date, it is extremely difficult to diagnose Alzheimer’s disease. Most claims about new methods to confirm a diagnosis or, even better, to predict the onset have turned out to be false. She also points out that about 50 diseases and at least 150 medications may cause dementia symptoms. She concludes that most physicians are overextended to differentiate and often too early and too easily put the patient down as having Alzheimer’s, thereby impeding a causal treatment and condemning the patient to unnecessary mental derangement.
Examples are cognitive impairments associated with dehydration and depression, but also a variety of drugs, in particular, if patients take cocktails of drugs prescribed by different specialists who neglected potential interactions and side effects. Complications during surgery or anesthesia, too, can cause dementia symptoms. Stolze summarizes that about 75% of all dementia diagnoses are false.
She also points out that most medications on the market for the treatment of AD are ineffective, do not provide causal therapy and may at best slow down disease progression for a limited period of time.
These chapters are a strength of the book and can be read as a roll call to relatives, patient advocacy groups and the health care system in general to raise awareness about the various forms of dementia and to demand better diagnosis and better drugs.
Stolze then tells the 1970s story of how Alzheimer’s disease was put on the agenda of the then newly founded US National Institute on Aging (NIA). Back then, little was known about Alzheimer’s disease, but using a fancy name describing a threatening disease was way more efficient in raising awareness and money from governments and private sponsors than by talking in general terms about senility or dementia.
Subsequently, Stolze’s story gets astray as she tries to convince the reader that AD has been and still is a mere invention by the medical industry, and that every scientific description of the disease – whether in terms of pathology, biochemistry or cellular and molecular biology – is full of errors, inconsistencies and contradictions.
The author makes no efforts to go into the details to substantiate this claim. As an example, Stolze writes that plaques – long viewed as the hallmarks of AD – can be found in the brains of mentally wide awake elderly as well. She ignores that this fact has puzzled researchers since long and that there is an explanation to it already: plaques in the brain of healthy people do have a different molecular composition than those in people with AD, in which they predominantly consist of a certain, very toxic variant of the A beta peptide. The details have been elucidated by researchers from the German biotech company Probiodrug, with the first publications appearing in the late 1990s. The hypothesis meanwhile has been confirmed independently by various research groups around the world and a first drug addressing the underlying mechanism already has reached clinical stage.
Moreover, Stolze completely ignores that there are inherited forms of AD such as Familial Alzheimer’s disease (FAD) or Early Onset Familial Alzheimer’s disease (EOFAD), uncommon forms of Alzheimer’s disease which usually strike quite early in life. They are inherited in an autosomal dominant fashion and the genes involved have been characterized years ago. Moreover, studies in these inherited forms have revealed further details of the pathophysiological mechanisms involved in AD in general.
Further parts of the book deal with selected German Alzheimer specialists and their connections to industry and politics, raising questions about conflict of interest disclosures. This is an ongoing debate in medicine in general, and Stolze seems to share the widely held beliefs in Germany that a researcher or medical doctor, who files for a patent, already has crossed the line to unethical behavior.
Most regrettable about the book is that it shakes the confidence in medicine of patients, relatives and people involved in the care of dementia patients without providing any valuable guidance what to do and whom to trust if a loved one is showing signs of confusion, disorientation or loss of memory.