To Blog or To Jog? Genetic Tests and "Life-Changing" Decisions

In his November 26th post "AfricanDNA.com - A New Genetic Genealogy Company", Blaine Bettinger of The Genetic Genealogist reviews a new genetic test and genealogy information provider. The venture (launched by Henry Louis Gates, Jr.--an esteemed literary critic and the director of Harvard's W.E.B. Du Bois Institute for African and African American Research, but not a geneticist) was also the subject of an article by Ron Nixon in The New York Times ("DNA Tests Find Branches but Few Roots", 25 November 2007). In this article Dixon quotes NYU sociologist and former advisor to the Human Genome Project, Troy Duster:

“People are making life-changing decisions based on these tests and may not be aware of the limitations .... While I don’t think any of the companies are deliberately misleading customers, they may have a financial incentive to tell people what they want to hear.”

Bettinger takes issue with the comment and asks: "Do people really make 'life-changing' decisions based upon the results of a genetic genealogy test?" He adds "So, what type of decisions are being referred to, and how often are people really making them?" A quick look at Duster's co-authored editorial in Science (19 October 2007) suggests that these decisions include potentially unexpected and sometimes distressing changes in personal identity, changes in self-reported ethnicity, and the selective financial support of African communities. While Duster's comment was made in the context of a discussion of genetic genealogy testing, he may have also had other genetic testing applications in mind or, perhaps, the unwarranted reification of race in genetic research. [See Duster's "Race and reification in science". Science 2005 Feb 18;307(5712):1050-1.]

Although some individuals (for better or for worse) may make "life-changing" decisions following the receipt of genetic genealogy test results, many more are expected to make these decisions following medical genetic tests. Bettinger's question, however, deserves attention here as well: Do people really make "life-changing" decisions based upon the results of a broad genetic test for uncertain health risks? Many individuals requesting a test for specific genetic disorders (Huntington Disease, for example) do make some life-changing decisions based upon the results, but how will individuals interpret increases in risks for more common health conditions? Heart disease, diabetes, osteoporosis? Many of us already know that we have a family history of one or more these (and other) diseases, but how many of us successfully respond to this information. Will the results of a genetic test provide better motivation to change our lifestyles? How many of us expect to jog more than we blog? -- J.O.

Citations:

Bolnick DA, Fullwiley D, Duster T, and et al. The science and business of genetic ancestry testing. Science. 2007 Oct 19;318(5849):399-400.
PubMed ID: 17947567 | PredictER CiteULike [excerpt]

Duster T. Race and reification in science. Science. 2005 Feb 18;307(5712):1050-1.
PubMed ID: 15718453 | PredictER CiteULike [excerpt]

Barriers to Research and Strategies for Community Engagement: Three Recent Papers

PredictER Blog and the PredictER program have an ongoing interest in encouraging community engagement in genetic and predictive health research. Patrick Barrett introduced this mission in the previous PredictER Blog post (November 19, 2007.) For those with an interest in reading the latest research on this topic, here are brief summaries of three recent papers:

Grand challenges in global health: community engagement in research in developing countries ...
Tindana PO, Sing JA, and et al. provide a short review of community engagement (CE) concepts for research in developing countries and discuss two models in Africa. Although the authors note that community engagement goals "have become prominent in research policy", they point to divergent definitions of CE and the need for evaluation. They caution that "there is a growing recognition that communities, not just individuals, can suffer harm from participation in research. For example, with out adequate protections, population genetics research runs the risk of stigmatizing or discriminating against recognizable communities ....". The authors plan to document CE in developing countries and to develop preliminary guidelines to facilitate CE in research.

Community engagement in epidemiological research ...
Sapienza JN, Corbie-Smith G, Keim S, and Fleishcman AR outline the CE practices and plan of The National Children's Study (NCS). In introducing the project, they note that CE "can be quite complex, even within a single site due to the difficulty researchers have in defining communities". In addition to the difficulty of defining "community" they add that "finding key community leaders that will best represent [the] multitude of community views and perspectives" can be a challenge.

An examination of community members', researchers' and health professionals' perceptions of barriers to minority participation in medical research ...
Robinson JM and Trochim WMK, in a "concept mapping" study of perceived barriers to minority participation in research, demonstrate that the research system (in addition to the often discussed lack of trust in researchers) contributes to lower participation rates. The authors also discuss the discrepancy between how health professionals and community members define these barriers. They conclude with three recommendations for improved minority participation rates in health research: (1) improve relationships between the medical research community and the communities they serve; (2) increase the levels and improve the nature of community involvement in the research process; and (3) efforts must be multi-dimensional, addressing both community interrelations and research process issues.

Citations:

Robinson JM and Trochim WMK. An examination of community members', researchers' and health professionals' perceptions of barriers to minority participation in medical research: an application of concept mapping. Ethnicity and Health 2007; 12(5):521-39.
DOI: 10.1080/13557850701616987 PredictER CiteULike [abstract]

Sapienza JN, Corbie-Smith G, Keim S, and Fleishcman AR. Community engagement in epidemiological research. Ambul Pediatr 2007; 7(3): 247-52.
PubMed ID: 17512886 PredictER CiteULike [abstract]

Tindana PO, Singh JA, Tracy CS, Upshur RE, Daar AS, Singer PA, Frohlich J , Lavery JV. Grand challenges in global health: community engagement in research in developing countries. PLoS Med. 2007 Sep 11;4(9):e273
PubMed ID: 1785017 PredictER CiteULike [abstract]

Engaging the Community in Predictive Health Research: Reporting on PredictER's November 2nd Expert Panel

Research and the Community

In most predictive health projects, researchers need to obtain human biological materials that can be stored for immediate or later use and then linked to detailed health information from medical records. Building biobanks and predictive health research projects requires a supportive public. To succeed researchers need a representative sample of willing participants, good state and institutional policy, and (of course) funding. (This research also benefits from highly motivated advocacy groups such as Susan G. Komen for the Cure.) In a few words, predictive health is one of the most community saturated forms of medical research to date.

Ethical Issues

The great good that will be accomplished by predictive health research, with its ability to forecast a person’s health future with reasonable probability, must be pursued with careful consideration. These studies raise ethical, legal, and social questions beyond the scope of the current paradigm of medical research. Very basic examples of these questions include: What do researchers do when they find that an individual tests positive for a gene or other biomarker that puts them at significant risk for a disease in the future? Can an individual’s biological material be used first to study one type of disease or treatment and then later another? What protections need to be in place to ensure that the sensitive information in an individual’s health record and genes does not result in employment or health insurance discrimination?

The Pace of Translation

While questions like these may seem very scary when rattled off one after the other, the truth is that predictive health is the future of medicine--a future that hopes to fulfill the ambitions of the human genome project, by providing an individual with a personalized assessment of risk and response to treatment. The human genome project succeeded in decoding a great deal of information, but what that information means for individuals with heart disease, a family history of cancer, or a smoking addiction, has not been answered. If current research succeeds, this information will be translated into real clinical applications in the not too distant future. Research looking to define these types of predictors is well underway at most universities--some, as exemplified by Emory's Predictive Health Initiative and the TGen (Translational Genomics) project in Arizona, have worked to establish comprehensive predictive health research programs. Meanwhile, as The Wall Street Journal recently reported many (up to 1,400) genetic tests are already available for individuals interested in assessing their risks for a number of diseases. Moreover, many specific predictive tests are already being used to chart treatment paradigms in hospital care.

PredictER Engaging the Community

Still, the fact that predictive health is occurring does not answer any of the concerns voiced earlier. These are concerns that the PredictER program at the IU Center for Bioethics is working to address. On November 2nd, PredictER convened a panel of 35 experts and community advocates to begin to give shape to many of these concerns and to explore ways to reach out to the community, build collaboration, and encourage research while protecting individual and public interests. While the panel of experts shared an understanding of the progress of predictive health, it took an entire day of brainstorming and discussion to reach consensus on what issues may be present with respect to engaging the community. In the end, it was clear that predictive health will require physicians, researchers, and the community to join in constructive, mutually beneficial work. In the near future a white paper will be published by the Center for Bioethics with a more detailed account of the November 2nd event. This paper will also introduce the next step in PredictER's community outreach mission--a plan to engage central Indiana community leaders and to listen to their concerns about the future of predictive health research. -- Patrick Barrett

Newborn Screening: An Update on Minnesota

A recent article in the Minneapolis-St. Paul Star Tribune indicates that the controversy between the Minnesota Department of Health (MDH) and the Citizen’s Council on Healthcare (CCH) regarding collection and retention of newborn blood samples remains a live issue. Reporter Chen May Yee invoked our pathos by using the “sick baby” card, framing the debate as one between a camp committed to genetic screening to save newborns and a gang of privacy advocates, outlandishly exaggerating the harms resulting from applying the Minnesota Genetic Privacy Act. Yee describes the newborn screening program as a small intrusion necessary to save lives while characterizing CCH’s concerns as fear of the unknown.

The article misrepresents CCH’s objections and presents a mutually exclusive approach to newborn screening: perform newborn screening or apply the Minnesota Genetic Privacy Act which requires parents to consent to the blood collection, genetic screening tests, and retention of the blood samples for future research use. As the administrative courts have ruled, the Minnesota Genetic Privacy Act does in fact apply to newborn screening practices. In theory, application of this law provides even more public benefit: parents consent to allow newborn screening, they can consent to the MDH’s retention of blood samples for more research to develop new screening tests, and the law ensures parents have an informed understanding of each process and its value.

MDH’s chief legal counsel David Orren stated that “data in the hands of public health is very different from the data in the hands of an identity theft or hacker.” Yet, as long as the MDH was not in compliance with the law and they do not have specific permission to retain this information, can their status as a government agency change the fact they should not have or retain these samples and information? -- Katherine Drabiak

Get Your Genetic Test Results Online and Who Needs a Physician?

Ron Winslow’s “Is there a Heart Attack in Your Future?” published in last week's The Wall Street Journal recently introduced the public to Navigenics, Inc., a California based corporation offering direct to consumer genetic testing services. For $2,500, a customer may order a kit to collect a saliva sample to send to Affymetrix, Inc., which uses a SNP sorting chip and returns results to Navigenics. With a username and a password, customers may then view the results of their genetic predisposition to twenty genetic diseases and compare their risks to those of the generalized population. The fee includes telephone consultations with a genetic counselor and one year of updates on new SNP disease validations.

Navigenics professes a dedication to presenting “complex scientific and medical information to you in an easy-to-understand format.” Yet the very nature of evaluating disease risk based on a single SNP is inherently complicated. Disease risk must be interpreted in the context of an individual’s complete genetic sequence in addition to environmental factors. These limitations may frustrate consumers expecting immediate and definitive results from this online service.

Several critics of direct to consumer genetic tests (DTC), including David P. Hamilton of VentureBeat, have pejoratively referred to the process as “corporate genomics.” By selling these DTC genetic tests and services as merely another online product, these companies by-pass the physician-patient relationship and do not benefit from this traditional way of assessing the importance personal genetic and medical information. Navigenics’ co-founder and chief scientific officer Dietrich Stephan noted that eliminating this relationship may minimize individuals' concerns about breaches of patient confidentiality and the loss of genetic privacy. Responding to a deficiency of legal protection for the privacy of genetic information by attempting to circumvent recording and communicating that information with one’s physician constitutes a logically faulty solution and could lead to even more adverse effects to members of the public. Lay understanding of these tests may lead to over-inclusive or under-inclusive interpretation of the results, which (in both instances) potentially leaves the individual confused and isolated. Based on a (mis)understanding of their personal results, Individuals may be less likely to seek face-to-face treatment from their physicians and genetic counselors. Other individuals, burdened by an unnecessary anxiety, will increase their visits to primary care physicians and thereby exacerbate the inequitable allocation of health care--patients with more pressing medical needs may wait longer and pay more for treatment.

A survey published earlier this year by the Genetics and Public Policy Center (download the PDF) shows that some state legislatures have attempted to address the complexity of DTC genetic tests by placing restrictions on whether the state will allow consumers to circumvent physicians in the receipt of information about their genetic predisposition to disease. As Steve Murphy, of The Gene Sherpa, recently noted, several state laws explicitly prohibit DTC testing, or require an individual’s consent to perform each individual genetic test and a separate consent to retain the individual’s genetic sample. These extensive statutory requirements for separate consent reflect the principle that individuals should fully understand the limitations and implications of each genetic test- preferably through in-person interaction. This purchase has inordinately more significance than most other online transactions, and the law is designed to reflect this difference. What is the benefit of more genetic information, if patients lack the training to interpret its significance? And what will be the personal, legal and social consequences of evading of current informed consent requirements? -- Katherine Drabiak

Predictive Health Research: What Isn't It?

If you're a regular reader of this blog, if you receive PredictER News Brief, if you have attended any PredictER event; you've probably encountered definitions of "predictive health research". But, let's pretend you're not a regular PredictER Blog reader; imagine that! You might wonder … What's the big deal; aren't all medical professionals predicting health outcomes? Isn't most medical research conducted with the hope of better predicting health outcomes? Well, you're not alone. These are questions I regularly entertain when updating PredictER's shared headlines (see the panel on the right) or when adding items to PredictER's del.icio.us and CiteULike accounts. In fact, two recent news items seemed to be begging to stretch the scope beyond the typically featured genetic and neuroimaging research. First, on the 30^th of October, The Washington Post reported "Quality of Life Predicts Lung Cancer Survival". The story relays the news of recent cancer research findings and quotes the lead author, Dr. Nicos Nicolaou of the Fox Chase Cancer Center in Philadelphia:

"In the past, we've considered the stage of disease or tumor size along with other empirical data to predict how long a patient will survive, but now we know quality of life is a critical factor in determining survival".

The second story, also relaying research news on "survival" factors, appeared Wednesday in MedPage Today: "Mathematical Index Simplifies Survival Prediction After Liver Grafts". In the November 7^th report, Judith Groch writes:

The researchers [Michael L. Volk and colleagues at the University of Michigan] said that the modified comorbidity index predicted liver transplant survival as well or better than other available models that typically use recipient characteristics such as age, race, BMI, and etiology of liver disease. … Until now, "we have considered comorbidities in an informal way when deciding whether to put patients on the list for transplant, but nobody has ever quantified the impact of comorbidities on post-transplant survival," Dr. Volk said.

Sounds "predictive" to me, but is it relevant to PredictER? I can't say "no", but I have to admit that PredictER Blog has focused on research emphasizing long-term prediction … tests and methods revealing disease years (if not decades) prior to the onset of symptoms. This "predictive" research often requires the latest developments in research knowledge and technology; it also introduces a new emphasis on some familiar ethical and social issues. When research requires biobanks and databases for the collection of tissue samples and genetic data for potentially long-term and unexpected use, the task of assuring subject privacy, dignity, and autonomy faces new challenges. These challenges are multiplied when biobanks are coupled with longitudinal access to personal medical records. Thus, while reserving the opportunity to be inclusive, the interests of PredictER Blog can be distinguished from the "predictive" aspects of all biomedical research (exemplified by the Nicolaou and Volk studies) by a measure of degrees. PredictER Blog is interested in research aims marked by dramatic increase in the power and accuracy of health "prediction", the requisite ethical protections, and the much anticipated benefits ... a more personal "personalized medicine".

Related research:

Volk ML, Hernandez JC, Lok AS, Marrero JA. 2007. Modified Charlson Comorbidity Index for predicting survival after liver transplantation. Liver Transplantation. Volume 13, Issue 11 , Pages 1515 - 1520. [doi: 10.1002/lt.21172]

Nicolaou N, Moughan J, Sarna L, Langer C, Werner-Wasik M, Komaki R, Machtay M, Wasserman T, Bruner D, Movsas B. 2007. Quality of Life (QOL) Supercedes the Classic Predictors of Survival in Locally Advanced Non-Small Cell Lung Cancer (NSCLC): An Analysis of Radiation Therapy Oncology Group (RTOG) 9801. International Journal of Radiation Oncology, Biology, Physics. Volume 69, Issue 3, Pages S58-S59. [doi:10.1016/j.ijrobp.2007.07.107]

Remuneration for Healthy Workers: From Sticks to Carrot Sticks?

In July of this year Clarian Health of Indianapolis announced a new health and wellness program for its employees. Employees failing to meet minimum standards for body-mass index (BMI), blood pressure, tobacco use, glucose and cholesterol levels would have been fined $5 per condition per paycheck. Wednesday, NPR's Morning Edition reported that Clarian has revised its health program. The health care institution will not fine "unhealthy" employees, but will offer incentives to encourage healthier lifestyles. This news, also reported in the Indy Star (1 November 2007), will be welcomed by those who are concerned that personal health data, including genetic information, may someday be used in a discriminatory manner in the workplace. If the public strongly objects to requiring a person's BMI and tobacco use to be considered as conditions of employment, it seems even less likely an employer could successfully use a genetic test indicating, for example, an increased risk for breast cancer. Nevertheless, it is still possible, if not likely, that genetic information could be coupled with health-indicators to assess the health risks of individual employees. These individuals might also be encouraged with "incentives" to adopt healthier lifestyles. Before such practices are implemented, employers should think carefully about how employees will interpret these policies. When "unhealthy" individuals are identified with genetic or other bio-information and required to meet certain health goals to receive incentives, are "health incentives" nothing more than repackaged "disincentives"? Could it be that what was once a "stick", is now a "carrot stick"? - J.O.