Misuse of the P value — a common test for judging the strength of scientific evidence — is contributing to the number of research findings that cannot be reproduced, the American Statistical Association (ASA) warns in a statement released today1. The group has taken the unusual step of issuing principles to guide use of the P value, which it says cannot determine whether a hypothesis is true or whether results are important. This is the first time that the 177-year-old ASA has made explicit recommendations on such a foundational matter in statistics, says executive director Ron Wasserstein. The society’s members had become increasingly concerned that the P value was being misapplied in ways that cast doubt on statistics generally, he adds. In its statement, the ASA advises researchers to avoid drawing scientific conclusions or making policy decisions based on P values alone. Researchers should describe not only the data analyses that produced statistically significant results, the society says, but all statistical tests and choices made in calculations. Otherwise, results may seem falsely robust. Véronique Kiermer, executive editor of the Public Library of Science journals, says that the ASA’s statement lends weight and visibility to longstanding concerns over undue reliance on the P value. “It is also very important in that it shows statisticians, as a profession, engaging with the problems in the literature outside of their field,” she adds. P values are commonly used to test (and dismiss) a ‘null hypothesis’, which generally states that there is no difference between two groups, or that there is no correlation between a pair of characteristics. The smaller the P value, the less likely an observed set of values would occur by chance — assuming that the null hypothesis is true. A P value of 0.05 or less is generally taken to mean that a finding is statistically significant and warrants publication. But that is not necessarily true, the ASA statement notes. A P value of 0.05 does not mean that there is a 95% chance that a given hypothesis is correct. Instead, it signifies that if the null hypothesis is true, and all other assumptions made are valid, there is a 5% chance of obtaining a result at least as extreme as the one observed. And a P value cannot indicate the importance of a finding; for instance, a drug can have a statistically significant effect on patients’ blood glucose levels without having a therapeutic effect. Giovanni Parmigiani, a biostatistician at the Dana Farber Cancer Institute in Boston, Massachusetts, says that misunderstandings about what information a P value provides often crop up in textbooks and practice manuals. A course correction is long overdue, he adds. “Surely if this happened twenty years ago, biomedical research could be in a better place now.” Criticism of the P value is nothing new. In 2011, researchers trying to raise awareness about false positives gamed an analysis to reach a statistically significant finding: that listening to music by the Beatles makes undergraduates younger2. More controversially, in 2015, a set of documentary filmmakers published conclusions from a purposely shoddy clinical trial — supported by a robust P value — to show that eating chocolate helps people to lose weight. (The article has since been retracted.) But Simine Vazire, a psychologist at the University of California, Davis, and editor of the journal Social Psychological and Personality Science, thinks that the ASA statement could help to convince authors to disclose all of the statistical analyses that they run. “To the extent that people might be sceptical, it helps to have statisticians saying, ‘No, you can't interpret P values without this information,” she says. More drastic steps, such as the ban on publishing papers that contain P values instituted by at least one journal, could be counter-productive, says Andrew Vickers, a biostatistician at Memorial Sloan Kettering Cancer Center in New York City. He compares attempts to bar the use of P values to addressing the risk of automobile accidents by warning people not to drive — a message that many in the target audience would probably ignore. Instead, Vickers says that researchers should be instructed to “treat statistics as a science, and not a recipe”. But a better understanding of the P value will not take away the human impulse to use statistics to create an impossible level of confidence, warns Andrew Gelman, a statistician at Columbia University in New York City. “People want something that they can't really get,” he says. “They want certainty.”
Tissue samples from a Hungarian mummy have revealed that people in the early 17th and 18th centuries suffered from colon cancer, long before the modern plagues of obesity, physical inactivity and processed food were established as causes of the disease, according to new research. In a new study of 18th-century Hungarian mummies, scientists found that the genetic predisposition to colon cancer predates modern impacts on health. One of the mummies in the study carried a mutation in the adenomatous polyposis coli (APC) gene, which physicians now know raises the risk of colon cancer, said lead study author Michal Feldman, a research assistant formerly at Tel Aviv University in Israel. If the APC mutation is confirmed in other samples, it could mean that inherited changes in DNA play a bigger role in cancer evolution than do modern environmental impacts, Feldman told Live Science in an email. [10 Do's and Don'ts to Reduce Your Risk of Cancer] "Today, colorectal cancer is the third most common type of cancer, and it has a clear genetic background that is well-researched in modern populations," Feldman said. "In light of the many lifestyle and environmental changes human society has undergone during the last few centuries, we found it important to compare the spectrum of historical mutations to the modern spectrum." Because mummification preserves tissue, samples from such remains can give scientists invaluable information on anthropological, historical and medical details, Feldman said. In the past, studies of mummified remains have provided clues about the history of tuberculosis, clogged arteries and even air pollution. In the new study, Feldman's team collected tissue samples from 20 mummies that were excavated from sealed crypts in a Dominican church in Vác, Hungary. These crypts were used for the burial of several middle-class families and clerics from 1731 to 1838, and more than 265 mummies were found there in 1995, the researchers said. The mummies are now housed at the Hungarian National Museum in Budapest. The low temperature in the crypts, combined with constant ventilation and low humidity, were ideal conditions for natural mummification of the corpses, the researchers said. Some 70 percent of the bodies found in the location were completely or partially mummified, providing a rich source of preserved tissue and DNA samples for the scientists. [8 Grisly Archaeological Discoveries] By extracting DNA from the mummies, Feldman and her team were able to sequence and assess the presence of APC gene mutations. "The interesting thing about this study is that the APC mutation in cancer that was recently discovered in the past couple of decades is not new," said Dr. Sidney Winawer, a gastroenterologist at Memorial Sloan Kettering Cancer Center in New York, who was not involved in the study. "This opens up a whole new way of thinking. If this mutation was present so many years ago, why was it present there?" Additional historical samples need to be investigated, he said, in order to better understand the relationships between cancer and environmental factors, such as lifestyle, and between cancer and genetic changes. The findings were published online Feb. 10 in the journal PLOS ONE. Copyright 2016 LiveScience, a Purch company. All rights reserved. This material may not be published, broadcast, rewritten or redistributed.
News Article | April 13, 2016
A project to speed development of cancer-fighting drugs that harness the immune system has academic and drug industry researchers collaborating and sharing their findings like never before. The newly created Parker Institute for Cancer Immunotherapy is being funded by a $250 million grant from Sean Parker, the co-founder of the file-sharing site Napster and Facebook's first president. It brings together partners at six top academic cancer centers, dozens of drugmakers and other groups. "Everybody knows that we need to move forward and change the model" for cancer research, Jeffrey Bluestone, an immunology researcher and the institute's CEO, told The Associated Press Tuesday. "The goal here is to rapidly move our discoveries to patients." For decades, fiercely competitive and secretive drugmakers protected their money-making discoveries with patents and lawsuits. Academic researchers likewise often guarded their work closely until it was published because their promotions, awards and sometimes revenue from licensing patents depended on individual achievement. That often slowed progress. With the increasing cost and complexity of research, drugmakers began licensing or buying patents and research programs from university researchers. Then big drugmakers began collaborating with each other and buying smaller companies, to share research costs, speed up the drug development process and get an edge on rivals. The Parker Institute, founded nine months ago, pushes those trends to a new level, by creating a virtual "sandbox" in which scientists at different institutions can work collaboratively, Bluestone said. About 300 scientists at leading cancer institutions - Memorial Sloan Kettering Cancer Center; Stanford Medicine; University of California, Los Angeles; University of California, San Francisco; University of Pennsylvania; and The University of Texas MD Anderson Cancer Center - will share their findings. They'll focus on early research. After initial patient testing, the institute's technology-transfer committee will strike licensing deals with drugmakers best able to develop those drugs, providing funding for other early research. Those drugmakers, from industry giants Amgen Inc. and Pfizer Inc., to small drug and diagnostic test developers, will fund the much-larger tests needed for drug approval, which can include hundreds or thousands of patients and cost hundreds of millions of dollars. Parker worked with hundreds of scientists to create a roadmap for the institute's work. It will quickly fund projects fitting its scientific targets and then rapidly enroll many of the 300,000 or more patients treated at the six centers each year in tests of resulting experimental drugs. "We'll make progress against three or four cancer types in the next several years," Parker predicts. He added that to be most effective, immunotherapy must become an initial treatment. Now it's usually reserved until patients relapse after chemotherapy and other standard treatments that weaken the immune system. Scientists have tried less-sophisticated strategies to use the immune system against cancer for about a century, with limited success, noted Dr. Eric Rubin, head of early stage cancer drug development at Merck & Co. It took recent advances in cell biology, genetics and related science to make progress. Now there are a handful of approved immunotherapy drugs that greatly extend lives of some patients with lung cancer and melanoma. Those include Merck's Keytruda and Bristol-Myers Squibb Co.'s Yervoy and Opdivo. They are so-called "checkpoint inhibitors," which block molecules that slow down or turn off the immune system's ability to attack cancer cells. Other immunotherapy approaches that will be part of the institute's initial work include CAR-T therapy, in which a patient's T-cells are removed from the blood, engineered to be "cancer assassins," then injected into the patient, Parker said. Researchers also will develop therapeutic viruses and vaccines to drive the immune system to recognize and attack tumors. "The Parker Institute does have the potential to accelerate development (of drugs) that will enable a greater number of cures," Rubin said. "We're very happy to be part of this."
Stathis A.,Oncology Institute of Southern Switzerland |
Younes A.,Memorial Sloan Kettering Cancer Center
Annals of Oncology | Year: 2015
Hodgkin lymphoma (HL) remains one of the most curable human cancers, as modern combination chemotherapy and radiation therapy cure ~80% of patients. Over the last two decades, the major efforts were focused on the development of more intensive front-line regimens for patients with advanced stage HL, decreasing the number of chemotherapy cycles and radiation therapy field and doses for patients with early-stage HL and incorporating positron emission tomography imaging in diagnostic, prognostic, and treatment planning. More recently, the improved knowledge of the molecular biology of the disease led to the development of highly active new agents, including the antibody-drug conjugate brentuximab vedotin and immune checkpoint inhibitors. Accordingly, the current efforts are focusing on incorporating these new agents into standard of care regimens, aiming at further improving cure rates, while reducing treatment-related toxicity. In this review, we will focus on the current status of HL therapy and how the development of new agents is re-shaping standard of care regimens. © The Author 2015. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. Source
Researchers have worked out how certain cancer cells go into hiding in the body and emerge later to cause the disease to recur. Cancer can reappear and spread through the body years after the primary tumour has been surgically removed. To find out more about this latent period, Joan Massagué at Memorial Sloan Kettering Cancer Center in New York and his colleagues isolated cells from human lung and breast cancers that formed tumours only months after being injected into mice. The team found that these cells entered a quiescent, slow-dividing state by inhibiting a signalling pathway driven by the protein WNT. The cells also expressed high levels of the stem-cell genes SOX2 and SOX9, which enabled the cells to grow into new tumours under certain conditions. Moreover, the cells downregulated the expression of molecules that are recognized by immune cells called natural killer cells, allowing the latent cancer cells to hide from immune surveillance until conditions permitted them to form metastases.