NCI Cancer Genetics Network Promises To Widen Testing, Information Access

Testing, Information Access Many question whether the initiative can adequately address issues of privacy and the need for education. The National Cancer Institute (NCI) is planning to launch a potentially controversial national information network in the fall. It will provide cancer genetic testing information to physicians and patients in an attempt to help them stay up-to-date, as well as access to the latest genetic testing protocols that NCI offers. IN FAVOR: OncorMed's Doug Dolginow believes his firm will benefit from the network. The new program-dubbed the National Cancer Genetics Network-is the brainchild of NCI director Richard Klausner. He and other program officials hope this information will help them understand the usefulness of the tests and gauge the measures taken to reduce the disease risks the tests reveal. Eventually, they hope to offer testing and treatment guidelines based on these results. The network is conceived as a "two-way street," says Barbara L. Weber, associate professor and director of the Breast Cancer Program at the University of Pennsylvania Cancer Center. "The Cancer Genetics Network is envisioned as a system of data collection and data outflow that will allow [researchers] to collect data on people being tested for genetic susceptibility to cancer and in return provide educational materials and updates on advances to the people who are taking the tests," she explains. Weber cochairs a working group formed to advise Klausner on development of the network. "The idea is that the more people we get data on, the faster we can get data on risk, prevention, and surveillance that people who are getting tested want," she reports. Many scientists see the usefulness of such a network and they agree that the program will help keep doctors abreast of-and involved in-the latest testing choices. But they wonder if enough is known about what these tests reveal and potential treatments to offer adequate advice. "The reason that genetic testing is controversial is that we don't quite know what to do with the data," says Weber. "If we knew how to [use genetic testing results to] prevent people from getting breast cancer, for example, no one would argue against testing. The hope is that the more people we can get to contribute data, the faster we can get answers to what we can do." For example, one of the dilemmas of testing for BRCA1, the putative breast cancer susceptibility gene isolated in September 1994, is that, for the most part, the tests' usefulness seems to be confined to those with a family history of the disease. Their use for the general population is still questionable because the gene is large, with many potential mutations, and researchers aren't sure what each alteration may mean regarding disease risk. Some argue against testing because there is little to do against the disease, save prophylactic mastectomy or being more vigilant with mammograms. Yet psychologically, the effects can be devastating. Many suggest that more education of physicians as well as the public is needed before testing options are discussed outside the research arena. Others question the actual network design and whether a network can keep patient records anonymous. Patients who undergo genetic testing fear that companies will refuse them health insurance for the possibility of carrying predisposing cancer genes. INFORMATION: NCI's Richard Klausner cites patients' "right to know." "Because this is a field in which knowledge is accelerating so rapidly, it is increasingly important to find answers to the cascade of questions arising for each new gene discovery," comments Barbara Rimer, a professor of community and family medicine and director of cancer control research at Duke University Cancer Center. She also is chairwoman of the National Cancer Advisory Board, which advises Klausner and Health and Human Services Secretary Donna Shalala on matters related to NCI. "This network can provide the structure for the kind of cooperative work that can advance science," she adds. The network's development is being overseen by the 24-member working group cochaired by Weber and geneticist Alfred Knudson, special adviser to Klausner and senior member of the Institute for Cancer Research at Fox Chase Cancer Center in Philadelphia. The working group consists of three subcommittees. One is chaired by Kenneth Offit, director of the Clinical Genetics Service at Memorial Sloan-Kettering Cancer Center in New York. It is developing prototypes of national cancer genetics protocols. Another subcommittee, headed by Kenneth Buetow, leader of the human genetics program at Fox Chase, will develop a structure of an informatics system-essentially, a way to record and access patient- and clinical-trial information. The third subcommittee, focusing on developing educational materials, is chaired by geneticist Judy Garber, director of cancer risk and prevention at Dana Farber Cancer Institute in Boston. Final subcommittee reports are due August 5. These will be analyzed and incorporated into a working group report for NCI. According to a May 1 article in the Journal of the National Cancer Institute (88:579-80, 1996), NCI's 28 comprehensive cancer centers would form the network "hub." The network would then branch out to encompass other centers specializing in genetics research and counseling. Weber explains that the actual implementation will be up to the participating groups. "It's all to be done through peer-review proposals to NCI," she says. NCI will solicit project proposals through its standard RFA (request for application) procedure. Those chosen-probably several consortia of medical institutions-will then design the actual network. "This will be a research-based network that will allow the physicians to enter what happens to those patients who receive or don't receive testing," Klausner comments. He notes that members of the network will be able to get patient information from academic medical centers and other comparable institutions through an elaborate registry system. The system "will allow us to establish more intense clinical trials to answer questions about risk, prevention, detection, surveillance, and treatment," he says. Many scientists support the network, saying it is essential for keeping up with the breakneck pace of gene research. Ruthann Giusti, special assistant to the director of the NCI division of cancer epidemiology and genetics and executive secretary of the working group, says, "The question isn't, 'will testing be done'?-it already is. [Now the question is,] 'is it possible to develop a structure to provide guidelines surrounding genetic testing and to make information accessible to people about the availability of genetic studies?'" CURIOUS: Louise Strong sees public interest in cancer genes. "We're identifying cancer susceptibility genes very rapidly," observes Louise Strong, a professor of experimental pediatrics at the University of Texas' M.D. Anderson Cancer Center in Houston and a member of the working group. "There is high public interest in understanding what they are and mean, and what are useful interventions." At a news conference at the American Society of Clinical Oncology meeting in Philadelphia in May, Klausner suggested that a network was needed "in response to individuals demanding a right to know and the medical community realizing that genetic testing without information-knowing how to interpret test results, for example-is like giving a drug without knowing the dose and possible side effects [Notebook, The Scientist, June 10, 1996, page 30]." Strong thinks the proposed network will help resolve several issues. She explains that the network will collect information on patients, their families, and their family histories; follow them over time; and chronicle the results. "One goal will be to understand what to do with the information," she says. "Another will be that it will identify groups of individuals who might be candidates to enter early detection and intervention studies." Gloria Petersen, an associate professor of epidemiology at the Johns Hopkins School of Hygiene and Public Health, maintains that, because the incidence of any single genetic illness is low, a national information network makes sense. Dana Farber's Judy Garber, who is also an assistant professor of medicine at Harvard Medical School, agrees. "A problem has been that no one institution has enough patients [for effective trials]," she says. "The network is a great idea because it can facilitate interactions between clinical trials and researchers and physicians," who were often on the outside. "This is a very different kind of effort," Petersen points out, though she notes some similarities to multi-institutional NCI cancer cooperative groups that run clinical trials. "It's not strictly just the patient and doctor. It will take commitment to recognize the scientific value [of the information] and a willingness to be there five and 10 years from now when the consequences [of genetic testing] play out." According to Weber, genetic testing will expand beyond university settings. "As it becomes more commercially available, more physicians will have access to testing, and it's hoped that the network will enable the data on patients outside of university settings not to be lost." Likewise, many researchers, such as Fox Chase's Alfred Knudson and Duke's Barbara Rimer, note that presymptomatic genetic testing is poised "to take off," though the timetable is far from certain. Some companies already are moving forward. In April, Genetics and I.V.F. Institute, a private company in Fairfax, Va., announced that it would offer testing for the BRCA1 gene mutation that has been found in relatively high proportion in women of Ashkenazi Jewish descent. OncorMed Inc., a Gaithersburg, Md.-based company, has been offering genetic testing for a range of cancer genes for more than a year, according to president and chief operating officer Doug Dolginow. Myriad Genetics Inc. of Salt Lake City, Utah, is gearing up to offer testing later this year. Some scientists assert that by increasing the availability of testing, a network might convince more people to get tested. "This might encourage more widespread presymptomatic testing because of the theoretical increase in access to testing," says Strong. Indeed, attorney and working group member Karen Rothenberg, a professor of law and director of the law and health care program at the University of Maryland School of Law in Baltimore, wonders, with all of the caveats raised by genetic testing outside of a research arena, "is the government, in setting up a network legitimizing cancer genetic testing, actually saying that it should be encouraged? By placing so much attention on it, are we in fact increasing demand?" Weber notes that "if people use testing cautiously and companies are being responsible as they are now, it will be fine. If some are purely entrepreneurial, then there is some concern." Klausner has said he would welcome private testing companies' participation in the network. While the mechanism for such participation is far from being resolved, OncorMed's Dolginow is enthusiastic. He sees the "ability to determine the clinical implications of specific mutations accelerated by a national cooperative effort. "We'd want to participate in such [a national] effort," he says, noting that overall, "there's little down side." Most agree that among the greatest challenges faced by the organizing committee and, subsequently, those groups that will actually create the network, is how to establish a national system that meets research needs without compromising patient confidentiality. "I think there is controversy in respect to whether or not we have what it takes to make a network work," reports Rothenberg. "Do we have the [necessary] level of expertise and resources?" WANTED: Judy Garber notes a lack of patients for trials. One key to the network's success is the informatics portion of the project. The subcommittee is charged with laying the groundwork for the information system. "Informatics is by definition the backbone of the network-the network will enable physicians access to state-of-the-art genetic testing and counseling," explains chairman Kenneth Buetow. He adds that confidentiality remains a "technical hurdle." "Critics might say such a network is premature, that without ensuring confidentiality it is dangerous," says Garber. Until then, patients may simply opt to not participate. Many believe that national legislation is needed to protect patients from insurance and job discrimination based on genetic disease predisposition. Twelve states currently have some form of protection. "Whatever shape the network eventually takes, certain legal issues must be resolved, such as state and federal legislation preventing insurance and job discrimination from insurance agencies for getting coverage," asserts Weber. A key to the success of a national network is to make participation quick and painless. "One concern is to make this easy for the individual practitioner, making sure that it doesn't take a lot of time, requiring a long list of forms and make things simple and as streamlined as possible," Weber explains. Not everyone is convinced that the working group will make the best national genetics policy. Fran Visco, president of the Washington, D.C.-based National Breast Cancer Coalition (NBCC), worries that only one consumer representative-NBCC's Mary Jo Ellis Kahn-participates. She also notes a potential conflict of interest for those on the working group steering committee who have a stake in biotechnology companies. "The concern is legitimate," says Duke's Rimer. "Many of the people in the field have ties to the genetics industry. It's important that they disclose those relationships publicly, and that [advisory groups such as the working group] have a mix of people balanced by those without such ties." Visco points out that NBCC supports genetic testing in the context of research protocols and is wary of private testing companies offering services to hospitals, physicians, and others. Garber sees several obstacles to a network's success; among them is participation. "Getting patients to buy into the network as well as making sure patients and doctors continue to participate and follow up years down the road" will be difficult. SIMPLIFY: Barbara Weber urges an easy-to-use, streamlined system. "We want to increase access to genetic testing in a setting that ensures informed consent and facilitates linkage to cancer genetic studies," Garber points out. "As more information is learned about the benefits of genetic testing, there will be increasing demand." OncorMed's Dolginow notes that some clinical research centers may be "reluctant to give up their study for the benefit of a national study." Collaborating in a multicenter study, he contends, means scientists may lose opportunities to publish their own research data and perhaps enhance their own reputations, as well as that of their institutions. Such issues have yet to be addressed. "The people, resources, and infrastructure remain to be determined," notes Weber. "The components and the concept itself are still evolving."

NCI Cancer Genetics Network Promises To Widen Testing, Information Access

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