<?xml version="1.0" encoding="utf-8"?>
<recommendedContent xmlns="http://api.mspoke.com">
    <recommendedItem id="20100101_19_377"
                     title="Advisory Panel Rates Genomic Cancer Tests"
                     score="0.01"
                     href="http://www.medpagetoday.com/PublicHealthPolicy/Medicare/tb/18269?impressionId=1265792147691"
                     
      &lt;p&gt;Some genomic tests aimed at identifying patients most likely to respond to cancer drugs won a thumbs-up from a Medicare advisory panel, but others didn&apos;t make the grade.&lt;/p&gt;
&lt;p&gt;As part of a national coverage determination under way at the Centers for Medicare and Medicaid Services, members of the Medicare Evidence Development &amp;amp; Coverage Advisory Committee (MEDCAC) last week rated the clinical value of several pharmacogenomic cancer tests now available.&lt;/p&gt;
&lt;p&gt;The tests would be used to select patients for treatment with drugs including tamoxifen, irinotecan (Camptosar), trastuzumab (Herceptin), and imatinib (Gleevec).&lt;/p&gt;
&lt;p&gt;CMS has not previously decided whether such tests should be reimbursed by Medicare, although testing is already routine for some of these treatments.&lt;/p&gt;
&lt;p&gt;The FDA-approved labeling for trastuzumab requires such testing. Imatinib&apos;s approvals include chronic myeloid leukemia featuring the BCR-ABL &quot;Philadelphia chromosome&quot; mutation, although the label doesn&apos;t explicitly mention testing.&lt;/p&gt;
&lt;p&gt;&quot;CMS is aware that the body of evidence on the role of pharmacogenomic testing in cancer continues to evolve,&quot; according to the agency&apos;s notice of the meeting.&lt;/p&gt;
&lt;p&gt;&quot;Recognizing the rapid accumulation of such evidence, CMS seeks guidance from the panel to inform future coverage determinations. We want to ensure that Medicare beneficiaries have access to any demonstrated improved health outcomes of pharmacogenomic testing, and are protected from inaccurate or inappropriate pharmacogenomic testing that could compromise therapy or increase the risks of adverse events during therapy.&quot;&lt;/p&gt;
&lt;p&gt;MEDCAC panelists were asked to rate their confidence in the clinical utility of five tests and in the scientific evidence available for review.&lt;/p&gt;
&lt;p&gt;The five tests cover: &lt;ul&gt; &lt;li&gt;Polymorphisms in the CYP2D6 drug-metabolizing enzyme for breast cancer patients who are candidates for tamoxifen&lt;/li&gt; &lt;li&gt;Polymorphisms in the UGT1A1 gene for colon cancer patients considered for irinotecan treatment&lt;/li&gt; &lt;li&gt;Presence of HER/neu epidermal growth factor receptor expression in patients with breast cancer, indicating suitability for trastuzumab&lt;/li&gt; &lt;li&gt;Presence of the BCR-ABL mutation in patients with chronic myeloid leukemia who would be candidates for imatinib&lt;/li&gt; &lt;li&gt;Mutations in the K-ras gene for metastatic colorectal cancer patients eligible for cetuximab (Erbitux) or panitumumab (Vectibix)&lt;/li&gt; &lt;/ul&gt;&lt;/p&gt;
&lt;p&gt;The 15 panel members assigned values of one to five, reflecting low to high confidence, to each test. A score of two reflected medium-low confidence, while a four meant medium-high confidence.&lt;/p&gt;
&lt;p&gt;Most of the panelists agreed that the evidence underlying the tests for CYP2D6 and UGT1A1 polymorphisms was still too scant for an assessment of their clinical value. Mean scores for these tests were 2.07 and 1.83, respectively, with nearly all votes either a one or two.&lt;/p&gt;
&lt;p&gt;But MEDCAC members were more confident that the usefulness of the other three tests for diagnostic and monitoring purposes could be evaluated. Mean scores for those tests were all well above four.&lt;/p&gt;
&lt;p&gt;For the HER/neu, BCR-ABL, and K-ras tests, since members believed the evidence was adequate for assessment, MEDCAC also voted on whether their use actually would improve health outcomes in cancer patients.&lt;/p&gt;
&lt;p&gt;A third ranking provided the committee&apos;s views on whether the conclusions could be generalized to the Medicare population and patients in the community.&lt;/p&gt;
&lt;p&gt;Mean scores for those rankings were all also above four, indicating the panel&apos;s support for these tests as clinically beneficial.&lt;/p&gt;
&lt;p&gt;On the other hand, when asked whether there was enough evidence to assess the utility of the BCR-ABL test in detecting treatment failure, panelists didn&apos;t think so. Most of those votes were twos, and the mean was 2.47.&lt;/p&gt;
&lt;p&gt;CMS has not given a time line for deciding whether to approve Medicare coverage for the tests.&lt;/p&gt;

    </recommendedItem>
    <recommendedItem id="20100101_19_304"
                     title="&apos;Virtual&apos; Colon Scans Effective in Seniors (CME/CE)"
                     score="0.004"
                     href="http://www.medpagetoday.com/HematologyOncology/ColonCancer/tb/18164?impressionId=1265792147691"
                     
      Patients 65 and older are as suitable as younger individuals for CT colonography, said researchers conducting a large retrospective study.&lt;br&gt;
&lt;br&gt;Advanced neoplasias were detected with CT colonography  --  often called &quot;virtual colonoscopy&quot;  --  in older patients at more than double the rate in the general screening population, reported David H. Kim, MD, of the University of Wisconsin in Madison, Wis., and colleagues in the February issue of &lt;em&gt;Radiology&lt;/em&gt;.&lt;br&gt;
&lt;br&gt;They found that 7.6% of older patients had advanced neoplasias, compared with 3.2% of all patients screened in the university&apos;s clinic (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.001).&lt;/p&gt;
&lt;p&gt;On the basis of this and other findings in 577 individuals 65 and older versus the entire group of 3,120 patients undergoing the procedure, Kim and colleagues concluded that &quot;CT colonography performance is maintained in an older cohort.&quot;&lt;/p&gt;
&lt;p&gt;&quot;Overall, the observations from this clinical experience confirm that CT colonography may be a valuable screening modality in the older population,&quot; they wrote.&lt;/p&gt;
&lt;p&gt;On the other hand, the study did not address several objections raised by the Centers for Medicare and Medicaid Services (CMS) in its decision last year to deny Medicare coverage for the procedure. (See &lt;a href=&quot;http://www.medpagetoday.com/PublicHealthPolicy/Medicare/14186&quot; mce_href=&quot;http://www.medpagetoday.com/PublicHealthPolicy/Medicare/14186&quot; target=&quot;_blank&quot;&gt;Medicare Finalizes Denial of Virtual Colonoscopy Coverage&lt;/a&gt;)&lt;/p&gt;
&lt;p&gt;CMS had pointed to relatively low sensitivity of CT colonography compared with optical colonoscopy in prospective trials, especially for small lesions.&lt;/p&gt;
&lt;p&gt;The agency also determined that CT colonography increased the costs of positive findings, since abnormalities in the CT scans must be confirmed with optical colonoscopy. In addition, CMS said there was no evidence to support claims that the less invasive imaging procedure would be more acceptable to patients and therefore would raise screening rates.&lt;/p&gt;
&lt;p&gt;The data analyzed by Kim and colleagues did not allow for calculations of false-negative rates or predictive values of positive or negative findings. Nor did the researchers report cost information.&lt;/p&gt;
&lt;p&gt;Mean age of their older cohort was 69.2 (SD 3.8). The oldest was 79.&lt;/p&gt;
&lt;p&gt;The researchers reported that 15.3% of the older patients were referred for optical colonoscopy on the basis of the CT results, compared with 7.9% of the overall screening group.&lt;/p&gt;
&lt;p&gt;Less than 4% of positive findings were determined to be false with the optical procedure (3.6% for polyps 6 to 10 mm in diameter, 2.1% for larger lesions).&lt;/p&gt;
&lt;p&gt;Of the 59 advanced neoplasias identified in the older patients, all but three were at least 10 mm in size.&lt;/p&gt;
&lt;p&gt;The scans also suggested abnormalities outside the colon in 89 (15.4%) patients. Of these, 45 received a full workup, which revealed substantial and previously unsuspected diagnoses in 21 cases  -- 18 were vascular aneurysms. The other three included one lung tumor, a femoral hernia, and a malrotation.&lt;/p&gt;
&lt;p&gt;Kim and colleagues reported that no &quot;substantial complications&quot; such as perforations or major hemorrhage occurred in the older patients, either with the CT scan or follow-up colonoscopy.&lt;/p&gt;
&lt;p&gt;They also indicated that the ratio of large to small neoplasias was similar in the older patients compared with their CT screening group as a whole. Histologic and morphologic findings were similar as well.&lt;/p&gt;
&lt;p&gt;The researchers cited the observational nature of the study, in which negative findings were not corroborated with optical colonoscopy, and its restriction to a single center as its main limitations.&lt;/p&gt;
&lt;div style=&quot;float:left;border-style:solid;border-width:1px;border-color:#8dabbc;font-family:arial;font-size:12px;background-color:#DBE9F2;padding:5px;&quot;&gt;&lt;p&gt;No external funding for the study was reported.&lt;/p&gt;&lt;p&gt;Kim and one co-author reported relationships with Viatronix and Medicsight and are co-founders of a company called VirtuoCTC, which produces educational materials on CT colonography.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <recommendedItem id="20100101_19_250"
                     title="Cancer Research &quot;Giant&quot; Lawrence Garfinkel Dies at 88"
                     score="-0.001"
                     href="http://www.medpagetoday.com/Pulmonology/Smoking/tb/18108?impressionId=1265792147691"
                     
      &lt;p&gt;Epidemiologist Lawrence Garfinkel, MA, a legendary researcher for the American Cancer Society whose work helped establish a link between cancer and smoking and other activities, died of cardiovascular disease Thursday in Seattle, Washington at 88.&lt;/p&gt;
&lt;p&gt;&quot;The American Cancer Society today mourns the loss of one of its most important historical figures,&quot; said John R. Seffrin, PhD, the society&apos;s chief executive officer.&lt;/p&gt;
&lt;p&gt;&quot;Larry Garfinkel joined the American Cancer Society as a young scientist in 1947, and for more than four decades played an instrumental role in expanding knowledge of and reducing death from smoking.&quot;&lt;/p&gt;
&lt;p&gt;Garfinkel&apos;s 1982 Cancer Prevention Study-II (CPS-II) is the largest contemporary study of tobacco and mortality, with 1.2 million participants and 77,000 data-compiling volunteers across 50 states, the District of Columbia, and Puerto Rico.&lt;/p&gt;
&lt;p&gt;CPS-II uncovered the effects of lifestyle factors, such as obesity, alcohol consumption, medications, genetic elements, that affect cancer and other chronic diseases, the analysis of which still reveals important clues about cancer today.&lt;/p&gt;
&lt;p&gt;The study also found lung cancer mortality rates in women increased five-fold from data collected in the original Cancer Prevention Study, while cancer rates among non-smoking women remained the same. This information provided strong evidence that lung cancer was almost exclusively a disease found in smokers.&lt;/p&gt;
&lt;p&gt;Garfinkel was born on January 11, 1922 in Manhattan&apos;s Lower East Side and was raised in the South Bronx.&lt;/p&gt;
&lt;p&gt;He served in the army during World War II, where he was seriously injured in northern France in August, 1944.&lt;/p&gt;
&lt;p&gt;Ultimately, Garfinkel graduated from the City College of New York and received a Masters Degree from Columbia University. He also received several honorary doctorates.&lt;/p&gt;
&lt;p&gt;Garfinkel began work for the ACS in 1947.&lt;/p&gt;
&lt;p&gt;He assisted E. Cuyler Hammond, MD, and Daniel Horn, MD, in the first ACS prospective mortality study of 187,783 males in the late 1940&apos;s by coordinating much of the field work, including training thousands of ACS volunteers in data collection techniques.&lt;/p&gt;
&lt;p&gt;Garfinkel acted as the co-principal investigator of the larger Cancer Prevention Study I (CPS-I) in 1959. The study enrolled 1 million participants across 25 states and required over 68,000 volunteers to collect data.&lt;/p&gt;
&lt;p&gt;In the 1960s, he contributed to more than two dozen major papers on the relation between smoking and health. He was co-author of one of the first reports combining epidemiology with pathology and provided some of the first direct evidence of lung damage related to smoking.&lt;/p&gt;
&lt;p&gt;Garfinkel also contributed to issuance of the landmark 1964 Surgeon General&apos;s report on smoking and health.&lt;/p&gt;
&lt;p&gt;He was appointed director of ACS research in 1979 after Hammond&apos;s retirement.&lt;/p&gt;
&lt;p&gt;Garfinkel retired from the ACS in 1989. Over the course of his career, he had contributed to more than 100 journal articles.&lt;/p&gt;
&lt;p&gt;Richard D. Klausner, MD, then-director of the National Cancer Institute, said at the time: &quot;Few individuals have contributed as much to our present-day knowledge about the disease consequences of smoking.&lt;/p&gt;
&lt;p&gt;&quot;His remarkable achievement is an important reminder what a tremendous impact an individual can make, and inspires all of us to continue the fight against cancer.&quot;&lt;/p&gt;
&lt;p&gt;Garfinkel continued to volunteer with the ACS after his retirement and taught biostatistics at the New York University Dental School.&lt;/p&gt;
&lt;p&gt;He is survived by his brothers, Harold and Melvin; his sons, Martin and Herb; a daughter-in-law, Margaret Cary, and two grandchildren.&lt;/p&gt;

    </recommendedItem>
    <recommendedItem id="20100101_19_200"
                     title="Debate Surges on Composite Endpoints"
                     score="-0.004"
                     href="http://www.medpagetoday.com/PublicHealthPolicy/ClinicalTrials/tb/18046?impressionId=1265792147691"
                     
      &lt;p&gt;Composite endpoints can obscure the real findings of clinical trials, two researchers charged in a &lt;em&gt;JAMA&lt;/em&gt; commentary this week, but others who had led trials using such outcomes defended the practice.&lt;/p&gt;
&lt;p&gt;Composite endpoints  --  where a study&apos;s main outcome is a combination of two or more different types of events, such as death and nonfatal myocardial infarction  --  can serve useful purposes, George Tomlinson, PhD, and Allan S. Detsky, MD, PhD, both of the University of Toronto, wrote in the Jan. 20 &lt;em&gt;Journal of the American Medical Association&lt;/em&gt;.&lt;/p&gt;
&lt;p&gt;But the benefits of composite endpoints come with a price, they argued  --  confusion to physicians and patients.&lt;/p&gt;
&lt;p&gt;&quot;Clinicians want to know if all events in the composite outcome are affected equally by the intervention,&quot; Tomlinson and Detsky wrote.&lt;/p&gt;
&lt;p&gt;Physicians can usually find results for the endpoint&apos;s individual components, they acknowledged, but it may &quot;result in some confusion, because the component relative risks may have broad confidence intervals and differ widely, at times even extending in opposite directions.&quot;&lt;/p&gt;
&lt;p&gt;Moreover, the Toronto researchers argued, if readers must examine results of the individual components of the composite endpoint to grasp the study&apos;s clinical implications, it defeats the composite endpoint&apos;s original purpose.&lt;/p&gt;
&lt;p&gt;&quot;While [readers] were enticed by a trial performed according to rigorous principles and based on the primary composite outcome, once the results have been reported they find that their interest has been redirected to individual outcomes of questionable importance,&quot; Tomlinson and Detsky wrote.&lt;/p&gt;
&lt;p&gt;They acknowledged that composites may sometimes make clinical sense, or are necessary because no single outcome is a natural primary endpoint by itself. Another practical rationale is to reduce the number of patients necessary in a study to detect a significant treatment effect.&lt;/p&gt;
&lt;p&gt;For example, if an outcome is expected to occur at a 5% annual rate and the trial is planned to last five years, more than 2,500 patients are needed to establish a hazard ratio of 0.75 with &lt;em&gt;P&lt;/em&gt;&amp;lt;0.05, Tomlinson and Detsky noted.&lt;/p&gt;
&lt;p&gt;But if several outcomes can be combined into a composite endpoint that has an annual rate of 20%, fewer than 800 patients will provide adequate power.&lt;/p&gt;
&lt;p&gt;That&apos;s generally fine when the individual component events occur at approximately equal rates, are of similar seriousness, and change in the same way with treatment, but that is frequently not the case, Tomlinson and Detsky contended.&lt;/p&gt;
&lt;p&gt;Steven Nissen, MD, a Cleveland Clinic cardiologist, agreed in a phone interview with &lt;em&gt;MedPage Today&lt;/em&gt;.&lt;/p&gt;
&lt;p&gt;Noting that composites of death, heart attack, and stroke are common in cardiovascular therapy trials, &quot;one would argue that all three of those outcomes are fairly grave [and] involve death or permanent injury,&quot; he said, and thus can be appropriate to combine into a single outcome.&lt;/p&gt;
&lt;p&gt;But, he added, &quot;what if the combination of endpoints is illogical, where you&apos;re combining grave endpoints with endpoints that are much less serious.&quot; In that case, the composite is much more difficult to interpret and may actually mislead readers about the study&apos;s true findings, Nissen suggested.&lt;/p&gt;
&lt;p&gt;&quot;Composite endpoints are a necessary evil, but they have to be thought through very carefully,&quot; he said.&lt;/p&gt;
&lt;p&gt;One trial with composites of serious and not-so-serious outcomes was reported last month at the American Society of Hematology meeting.&lt;/p&gt;
&lt;p&gt;Presented by Jeffrey Carson, MD, of the University of Medicine and Dentistry of New Jersey in New Brunswick, N.J., it tested different postoperative blood transfusion volumes. (See &lt;a href=&quot;http://www.medpagetoday.com/MeetingCoverage/ASHHematology/17418&quot; mce_href=&quot;http://www.medpagetoday.com/MeetingCoverage/ASHHematology/17418&quot; target=&quot;_blank&quot;&gt;ASH: Lower Threshold for Post-op Transfusion Proves Safe&lt;/a&gt;)&lt;/p&gt;
&lt;p&gt;Its primary outcome was a combination of death and walking ability, and a secondary endpoint was a composite of death, myocardial infarction, infection, congestive heart failure, stroke, and venous thromboembolism.&lt;/p&gt;
&lt;p&gt;In a recent phone interview with &lt;em&gt;MedPage Today&lt;/em&gt;, Carson said composites are frequently chosen to reduce the necessary sample size, but in his study the rationale was more about finding an outcome that best reflected the clinical issue.&lt;/p&gt;
&lt;p&gt;Including death alongside less serious outcomes such as inability to walk or infections was intended to capture the possibility that a transfusion regime might improve the lesser outcome but increase mortality.&lt;/p&gt;
&lt;p&gt;&quot;You wouldn&apos;t want to declare that, well, it improves your chances of walking and not consider its impact on death,&quot; Carson explained.&lt;/p&gt;
&lt;p&gt;Another study with a composite endpoint was a 2006 study of rosiglitazone (Avandia) called DREAM. Its primary endpoint combined death with incidence of new-onset diabetes. (See &lt;a href=&quot;http://www.medpagetoday.com/Endocrinology/Diabetes/4115&quot; mce_href=&quot;http://www.medpagetoday.com/Endocrinology/Diabetes/4115&quot; target=&quot;_blank&quot;&gt;EASD: Avandia Prevents Progression to Diabetes in High-Risk Patients&lt;/a&gt;)&lt;/p&gt;
&lt;p&gt;Tomlinson and Detsky held up DREAM in the very first paragraph of their &lt;em&gt;JAMA&lt;/em&gt; commentary as an example of a questionable composite endpoint.&lt;/p&gt;
&lt;p&gt;&quot;Death and diabetes are quite far apart in the spectrum of severity,&quot; they wrote, suggesting that clinicians would find the outcome  --  a 60% reduction in the two events  --  hard to interpret.&lt;/p&gt;
&lt;p&gt;&quot;Two questions arise,&quot; they wrote. &quot;Was there a 60% reduction in both death and diabetes? Are the two outcomes just as likely to occur?&quot;&lt;/p&gt;
&lt;p&gt;Nissen agreed that DREAM well illustrated the problems that can arise from composite endpoints.&lt;/p&gt;
&lt;p&gt;&quot;I do not like the situation where endpoints that have a great deal of difference in gravity and seriousness are combined,&quot; he told &lt;em&gt;MedPage Today&lt;/em&gt;. &quot;This was a great example.&quot;&lt;/p&gt;
&lt;p&gt;But the lead investigator on DREAM defended the composite outcome in a phone interview with &lt;em&gt;MedPage Today&lt;/em&gt;, insisting that sample size or other cost-based rationales never entered into the decision to use it.&lt;/p&gt;
&lt;p&gt;&quot;I&apos;ll quote from the paper,&quot; said Hertzel Gerstein, MD, of McMaster University in Hamilton, Ontario. &quot;It was to account for the possibility that diabetes might develop at a different rate in individuals who died than in individuals who survived. . . . It had nothing to do with any suggestion that the drug might prevent death. In fact, what we did in the DREAM trial, it was explicitly designed to [enroll] people at low risk of having serious outcomes including death.&quot;&lt;/p&gt;
&lt;p&gt;Gerstein continued, &quot;It was designed that way in order to be careful that we did not overestimate the benefit of the drug and provide the most conservative estimate of the benefit of the drug on diabetes prevention.&quot;&lt;/p&gt;
&lt;p&gt;Nissen, however, argued that composites chosen for legitimate scientific reasons are subject to misinterpretation when the results are published or submitted to regulators.&lt;/p&gt;
&lt;p&gt;Consider the composite of death, myocardial infarction, stroke, or hospitalization for unstable angina or revascularization, a common endpoint in registration trials for cardiovascular drugs, he said. Very often it&apos;s the hospitalizations that dominate the composite outcome, as they are far more common than the more serious events.&lt;/p&gt;
&lt;p&gt;&quot;When these companies go to the FDA, they often ask for a label related to the composite outcome. &apos;This drug is approved to reduce the risk of death, heart attack, stroke, and hospitalization for revascularization.&apos; Is that a good regulatory decision or a bad regulatory decision?&quot; Nissen asked.&lt;/p&gt;
&lt;p&gt;Jeffrey Carson said such composites are frequently criticized, but they can be reported in such a way as to minimize the chance of misinterpretation.&lt;/p&gt;
&lt;p&gt;&quot;It&apos;s likely that readmission to the hospital is the predominant reason for an event [in the composite] in studies of that sort,&quot; he said. &quot;You shouldn&apos;t say that it affects mortality, and you shouldn&apos;t say it affects myocardial infarction. What you should say is that it looks like the predominant effect here is on readmissions.&quot;&lt;/p&gt;
&lt;p&gt;Tomlinson and Detsky suggested that one way around this problem would be for authors and readers to assign weights to the various components of a composite outcome to reflect their clinical importance, &quot;similar to the way quality of life is measured.&quot;&lt;/p&gt;
&lt;p&gt;Alternatively, they wrote, when a composite outcome is driven by effects on the most numerous but least severe component, it should be understood to have shown an &quot;effect on surrogate outcomes and not definitive ones.&quot;&lt;/p&gt;

    </recommendedItem>
    <recommendedItem id="20090101_1_67"
                     title="Infant Botulism Drug Safe And Effective"
                     score="-0.005"
                     href="