Tag: cancer

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.

Food for Thought: Weekly Wrap-Up

In Germany, science pages were dominated by Japan’s nuclear disaster. Apart from topics such as radioactivity as a threat to human health and the environment, Christiane Hucklenbroich in Frankfurter Allgemeine Zeitung (FAZ) deals with an upcoming new definition of autism. Instead of seeing autism as a defined disease category, physicians have come to the conclusion that one should rather use the term “autism spectrum”, comprising several aspects of autism. The medical community also has started focusing on co-morbidity aspects as well as autism-like symptoms in other psychiatric diseases.

Susanne Kutter in Wirtschaftswoche summarizes latest advances in stem cell medicine. Among others, she features a clinical trial conducted at the University of Rostock in which the heart muscle of patients suffering from an infarction is injected with adult stem cells to initiate regeneration of muscle. The trial includes more than 150 patients and will be finished end of 2012. A method already successful has been established in India, where more than 700 people with blindness caused by Vitamin A deficiency regained eyesight after injection of stem cells into the cornea.

Roni Caryn Rabin in The New York Times reports on a Lancet study that pooled data from 58 studies involving more than 220,000 people with a mean age of 58 to find out whether the idea that obese people with an apple shape (carrying the overweight predominantly in the belly) are more at risk for heart disease than overweight people with a pear shape. The answer is: they are not. Overweight matters, but shape does not.

Ferris Jabr in New Scientist introduces a small implantable device developed by researchers from the  Massachusetts Institute of Technology (MIT) that can track tumor growth in the body of cancer patients. The device contains magnetic nanoparticles covered with monoclonal antibodies able to bind cancer-related molecules, e.g. human chorionic gonadotrophin (hCG), a hormone released by testicular and ovarian cancers. The first generation had read-out by MRI scans that detect formation of clusters within the device due to binding of the molecules. However, the researchers now improved detection so that readout can now be done by a hand-held device. The principle can also be adapted to monitor other changes in the body, e.g. silent heart attacks.

For blood transfusion, medical doctors need to carefully choose the right blood group from 29 possible combinations of the AB0, Rhesus, the MNS and other systems. This challenge sometimes needs to complications and logistic problems. The Economist reports on a successful approach by researchers from the University of Montreal to disguise the antigenic proteins from red blood cells. The trick is done by first dressing the fatty surface membrane of the cells and then attaching another cover so that the immune system does not pay attention to the cells. The cover is fully permeable by oxygen and carbon dioxide.

David Whelan in Forbes calls for a psychological study of people investing in biotech stocks, in particular those writing rude comments on articles featuring the ups and downs of stocks. He claims the phenomenon is only seen with articles on biotech stocks.

And finally, David M. Ewalt in Forbes reports about errors in Craig Venter’s first synthetic life form in which Venter inserted DNA composed on a computer. The DNA included quotes from James Joyce and Richard Feynman, however Craig used the Joyce quote without written permission from Joyce’s estate and misquoted Feynman by obtaining the quote from the internet. Craig said he was now going back to the organism to correct the error.

Food for Thought: Weekly Wrap-Up

Joachim Müller-Jung in Frankfurter Allgemeines Zeitung (FAZ) this week deals with the ethic implications of non-invasive prenatal diagnosis, describing that a huge number of tests based on fetal DNA entering the mother’s blood stream is ready to enter the market. His recommendation is to start an immediate discussion about which tests should be applied and which ones should not.

Ulrich Bahnsen in Die ZEIT interviews Norbert Donner-Banzhoff, Professor at the University of Marburg’s Department of General Practice, Preventive and Rehabilitative Medicine. Donner-Banzhoff conducted a study published in the Canadian Medical Association Journal CMAJ investigating the influence of pharmaceutical advertising on the drug recommendations made in articles in 11 German journals that focus on medical education. Donner-Banzhoff and his team come to the conclusion that journals financed by advertisement from the pharma industry and given away for free almost exclusively recommended the use of specified drugs, whereas journals financed entirely with subscription fees tended to recommend against the use of the same drugs. In the interview, Donner-Banzhoff suggests that a lot of articles published in the free journals have been written by ghost writers and/or members of the pharmaceutical industry.

Matthew Herper in Forbes this week deals with the latest setback in developing drugs to treat Alzheimer’s Disease (AD). He features the failure of Eli Lilly’s semagacest in a Phase III trial in more than 2,600 patients with mild-to-moderate AD. According to an interim analysis, patients receiving the drug, a gamma secretase blocker, worsened to a statistically significant greater degree than those treated with placebo. In addition, the drug was associated with an increased risk of skin cancer. Herper concludes that there is something fundamentally wrong with current hypotheses on the onset of AD and that the failure of the drug may set AD drug development back by many years (see also akampioneer’s recent comment on Probiodrug’s AD hypothesis).

While William Pentland, also in Forbes, reports a potential biofuel breakthrough in producing isobutanol directly from cellulose by using a microbe thriving in decaying grass, Josh Wolfe, co-founder and managing partner of Lux Capital Management, in Forbes states it is time to realize that investing in biofuels may be foolish. He states that while it is hyped as biotech 2.0, there is in fact a fundamental difference to biotech 1.0 which is often overlooked. While biotech 1.0 drugs and molecules can be protected by IP, biofuels cannot. In addition, the marginal cost of producing IP-protected molecules is really low once you did the discovery and first synthesis work (as compared to your margins) – so you can make big profits. Biofuel molecules however have to compete from the onset with the generic fuels already on the market. Biofuel is a commodity, he states, and instead of going back to an agrarian-based economy we should focus on materials and processing based on high energy density, such as uranium.

Donald G. McNeil jr in The New York Times reports on a panel of independent experts from 24 countries that reviewed the handling of the swine flu by the World Health Organization (WHO) in 2009. The draft report – “posted in an obscure corner of the W.H.O.’s Web site” – criticizes the WHO’s “needlessly complex” definition of a pandemic, its inability to deploy 78 million doses donated by rich nations for use in poor ones and its “clumsy communications”.

Colin Barras in New Scientist writes about the origin of cancer and features recent contributions by astrobiologists. While many researchers think that cancer is triggered by a malfunction of the genes trying to control replication which needs to be limited in multicellular organisms, some astrobiologists think a tumor is switching back to some forms of basic cellular cooperation found in the earliest ancestors of multicellular organisms. The distinction is far from being academic: if cancer is some sort of “living fossil” revived it would have only a limited set of survival strategies. In contrast, contemporary medicine regards a tumor as independently evolving cells with nearly unlimited evolutionary potential to escape treatment strategies. The hypothesis explains the co-ordinated survival strategies of cancer, such as angiogenesis and metastasis, and will be further tested soon by genetic profiling.

 

Food for Thought: Weekly Wrap-Up

John Markoff reports in the New York Times about scientists who created online video game EteRNA in which players can come up with novel ways of folding RNA. The scientists claim it is “democratizing science” by attracting thousands of citizens to participate in constructing new ways to understand and use the folding of RNA.

Finally, the NYT reports about wine. While archaeologists discovered the earliest winemaking facility of the world in Armenia where wine was being made there as early as 7,400 years ago – proving that mankind must have found something positive in consuming red wine, today’s scientists still grapple at understanding the benefits. Dealing with the halt of the last resveratrol trial in which biotech company Sirtis (now GSK) tried to prove that this particular ingredient of red wine is able to extend the life span of obese Rhesus Monkeys, Nicholas Wade casts doubt about the usefulness of resveratrol and resveratrol-mimicking chemicals as anti-aging drugs.

The Economist this week deals with epigenetics in a story featuring that not only mothers but fathers as well may be able to pass on a propensity to obesity if they themselves have been starved during their life before fathering offspring. The findings are from mice.

A separate story deals with attempts by British researchers to attach glowing proteins to cancer cells so that they emit red light. However to detect it doctors would have to use a specially developed camera that scans the body slice by slice. Such cameras are expensive, and the £500,000 ($750,000) they cost may be the greatest hurdle to deploying the technique.

Djuke Veldhuis reports in New Scientist about a simple blood test for Down’s syndrome that successfully detected all 86 cases confirmed by other methods. The validation study is published in BMJ 2011; 342:c7401.

In The Scientist, Vanessa Schipani elaborates why it is not a good idea to use the usually well-fed, parasite-free and genetically similar lab animals to study immunology. Instead, she makes a case for ecoimmunology, a new field studying immunology in wild animals and still trying to attract more researchers and funding. Jef Akst reports about cancer researchers identifying an increasing number of proteins that have a dual nature in cancer: they may initially promote the development of tumors, but in the long run make them less aggressive, or vice versa. “One problem in identifying such two-faced proteins may stem from the fact that these opposing effects are rarely demonstrated in the same research paper,” Jef writes, adding that both reviewers and funding agencies do not like this kind of complex stories and rather prefer focusing on one side of the coin.

Speaking of peer reviews, Martina Lenzen-Schulte in the German Frankfurter Allgemeine Zeitung (FAZ)  reports about efforts of peer-reviewed journals like the British Medical Journal or the EMBO Journal to make the peer review process more transparent by disclosing the names of the reviewers and the review or even the complete review process. Goals are to improve the quality of the process and of reviews in general and to prevent reviewers from either stealing ideas or putting a spoke in competitors’ wheels.

Volker Stollorz in Frankfurter Allgemeine Sonntagszeitung (FAS) provides a concise review of the ongoing debate whether the chronic fatigue syndrome (CFS) is caused by the newly discovered retrovirus XMRV or whether contamination of specimens, the lab or chemicals used in experiments have produce results that could be mistaken for XMRV. The article clarifies that there are increasing doubts about the hypothesis as many independent researchers have not been able to find the virus in the blood of CFS patients and/or from blood banks.

Focus reports on new efforts to combat AIDS by learning from the about 1% of humans resistant to the virus. The article cites James Hoxie, of Penn Center for AIDS Research, who is trying to cure AIDS by removing from immune cells of AIDS patients those genes that provide entry to HIV. Subsequently, the immune cells are transferred back to the patient. Focus states the approach goes back to findings in Germany at Charité Berlin where a patient suffering from both AIDS and leukemia received a bone marrow transplant from a HIV resistant donor. Citing an article in Blood (DOI 10.1182/blood-2010-09-309591), Focus states the patient is now virus-free and off AIDS medications.

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