A Diagnostics & Imaging Week

Makers of diagnostics may want to take note of a new round of funding for a program at the National Institutes of Health (NIH) that promises to boost scientific understanding of a relatively novel set of biomarkers for cancer. According to a recent announcement at the NIH web site, the National Cancer Institute (NCI), one of the NIH’s centers, has come up with about $15 million to fund a five-year effort “to discover, develop, and clinically validate cancer biomarkers by targeting the carbohydrate (glycan) part of a molecule.”

This branch of medical science, dubbed glycobiology, is apparently not utterly new. It is the subject of a scientific society, the Society for Glycobiology (St. Louis) as well as a journal titled Glycobiology that has been in production since before 1990.

According to the agency, carbohydrate structures attached to protein and lipid molecules can serve as an index of carcinogenicity for several forms of cancer, including cancers of the prostate, breasts, lungs, colon and pancreas.

NCI director John Niederhuber, MD, said in a statement that medical science has long known about glycobiology, but that “[w]hile this area has compelling scientific interest, its biological and chemical complexities have often discouraged investigation.” However, investment in medical technology has improved the understanding of protein and carbohydrate chemistry, and as a result, “research into this intriguing area has experienced renewed interest,” he said.

The NIH press release also said that numerous studies that compared “normal and tumor cells have shown that changes in the glycan structures of cells correlate with cancer development.” The release said that glycans are “extremely abundant,” but that a systematic study of their correlation with cancer cells is only just now practical.

“Many protein biomarkers also have glycan components, and analysis of these two molecular structures together may improve the value of tests such as those for prostate-specific antigen (PSA), CA-125, and carcinoembryonic antigen, which are sometimes used in prostate, ovarian, and colon cancer detection, respectively,” the NIH statement noted.

Sudhir Srivastava, PhD, chief of the Biomarkers Research Group in the cancer prevention division at NCI said that examination of biomarkers and ways to identify them are “critically important to both the basic understanding of cancer and the ability to identify early cancer and risk for cancer.” In reference to a new alliance of glycobiologists from across the NIH’s various offices, Srivastava said the improved focus on glycans “will accelerate the pace of biomarker development and discovery.”

Srivastava was referring to what the press release described as “the new trans-NIH Alliance of Glycobiologists for Detection of Cancer and Cancer Risk.” According to NIH, this group consists of scientist from the NCI Tumor Glycome Laboratories, the Consortium for Functional Glycomics, and the NCI Early Detection Research Network.

Among the academic centers participating in this branch of research is the University of Georgia (UGA; Athens). J. Michael Pierce, PhD, and others at UGA are working to identify glycoprotein and glycolipid biomarkers for pancreatic cancer that are known to show up in pancreatic ductal fluid. Pierce and his team hope to establish whether these biomarkers can be detected in blood samples.

Another of the NIH-funded projects is headed by Margaret Huflejt, PhD, of Cellexicon (La Jolla, California). Huflejt and others at Cellexicon are examining how far in advance several cancers can be predicted by looking at the signatures left by anti-glycan auto-antibodies.

CMS issues doc self-referral rule

The Centers for Medicare & Medicaid Services recently published the third phase of rules dealing with physician self-referral under the Stark law, and although the agency bills this as a final installment, previous experience with federal rulemaking suggests that this view is optimistic. The fact that Congress has yet to pass a bill for healthcare information technology also suggests that this set of regulations is not yet cast in stone.

CMS said the final rule enhances the flexibility regarding hospital recruitment and retention of physicians, in that payments related to such efforts “are expanded to permit recruitment of more physicians into extended areas when needed.”

The final rule also states that any doctors whose compensation from a hospital exceeds the limit is off the hook so long as the payment does not exceed the cap by more than 50% and the excess is reimbursed to the hospital within 180 days or by the end of the calendar year, whichever comes first.

Herb Kuhn, acting deputy administrator at CMS, said in a statement that the rules “protect beneficiaries from receiving services they may not need and the Medicare program from paying potentially unnecessary costs.”

Stark law dates back to 1989 when the legislation was passed. In its original form it was designed to deal with physicians who recommend tests by labs in which the physician had a financial interest, thus providing an incentive for unnecessary procedures.

The legislation is named after Rep. Pete Stark (D-California), the primary author of the original bill. Stark now chairs the House Ways and Means Health subcommittee, which has jurisdiction over many of CMS’s functions.

Stark and anti-kickback laws have both served as a flashpoint for efforts to pass legislation designed to boost roll-out of electronic health records in both the current and the previous iterations of Congress.

According to the text of the CMS rule, the agency posted the first phase of the final rule in the Federal Register in January 2001, while Phase II was published in the FR in March 2004.

The rule, in part, responds to comments concerning Phase II of the final rule objecting to the requirement that any arrangements that are not barred by regulations under the Stark law cannot violate anti-kickback laws. According to CMS, those comments included the observation that “the condition is unnecessary and undercuts our efforts to create ‘bright lines.’”

The agency’s position is that its authority is limited, which necessitates inclusion of anti-kickback statutes “to ensure that the exceptions promulgated under that authority do not pose a risk of program or patient abuse.”

CMS is also said that since physician practices have to comply with anti-kickback rules in any case, “any additional burden associated with the requirement is minimal.”

The final rule is a 516-page document and is available at the CMS web site. It will be published in the Federal Register Sept. 5. Given the 90-day lag between the publication date and the effective date, the rule goes into force Dec. 4.