Personalized Medicine: PredictER Collaborator Featured in NY Times

David A Flockhart, MD, PhD, Division Chief of the IU Department of Medicine’s Division of Clinical Pharmacology and PredictER Collaborator, was featured in a December 29th New York Times article that is part of a compelling series examining steps taken toward medicine based on evidence. The article, Patient’s DNA May Be Signal to Tailor Medicine, provides a highly readable overview of personalized medicine, illustrates the field’s inherent potential to increase positive outcomes and decrease costs, and then discusses some of the conundrums that genetically-tailored medicine presents. The author, Andrew Pollack, uses the outcomes of Flockhart’s extensive tamoxifen research to aptly illustrate the medical promise of genetic testing and its broader implications. Flockhart’s research demonstrates that a particular enzyme, CYP2D6, is responsible for converting tamoxifen into a different substance, called endoxifen, which is then directly responsible for fighting breast cancer. The CYP2D6 gene, however, varies between people such that the mechanism is inactive in about 7% of the population, and only moderately active in 20-40%. As the article points out, most patients are now treated with a more expensive class of drugs that demonstrated greater efficacy in clinical trials conducted before the role of CYP2D6 was fully understood. For those women with active CYP2D6, however, tamoxifen may well be the better alternative for the patient, both medically and economically. Genetic testing to determine gene activity in this scenario may therefore have vast economic implications for the pharmaceutical industry.

Amy Lewis Gilbert

Predictive Health, Insurance & Security: A Spiritual Perspective

Over the last few days, I have heard two discussions – one on the radio and the other at the Indiana University Center for Bioethics – that have given me a new and deeper understanding of the meaning of health insurance and of the challenges of incorporating Predictive Health information into healthcare. These two presentations came together to give me a new understanding of the spiritual dimension of health insurance.

The first discussion occurred on the NPR program "Speaking of Faith," hosted by Krista Tippett. This week the program featured an interview with Parker Palmer, a Quaker writer and educator, and focused on themes related to the current economic meltdown. When discussion turned to the role of greed in causing the crisis, Palmer commented that greed stems at least partly from a sense of isolation and a lack of feeling of being part of a community. If a person feels that he cannot rely on others for help at times of need, he will understandably develop the impulse to acquire as much as possible, to attempt to amass a sort of fortress against possible danger to him and his family.

This immediately reminded me of the state of healthcare and health insurance in this country. As premiums rise and increasing numbers of businesses cut back on health insurance for employees and retirees, more and more Americans are living without health insurance or facing the very real possibility of this. And what could cause a greater feeling of isolation – of living without support from others – than finding yourself without available or affordable health insurance? Even those of us who do have health insurance must feel insecure as we observe the growing ranks of uninsured and underinsured people. The historic economic downturn has made the trend only worse, of course.

Palmer’s comment highlights one of the many destructive effects of fearfulness. And it highlights the importance of making health insurance available and affordable. In short, universal health insurance, in my view, would play a significant role in helping to combat the feeling of isolation and helplessness that many feel in the current situation.

And here’s where Predictive Health information comes into the picture. Predictive Health Research (PHR) promises to provide new ways to identify individuals’ specific level of health risk and provide new, more targeted medical care. A healthcare system that provided excellent preventive care, guided by breakthroughs in PHR, could greatly reduce mortality and morbidity. We could improve the sense of safety and trust that supports a healthy spiritual life. But here’s where the fly lands in the ointment. At our biweekly meeting of the PredictER program this week at the IU Center for Bioethics, Eleanor Kinney JD, MPH, and Jennifer Girod JD, PhD, RN, presented a talk about the ways that Predictive Health information threatens to undermine the current system of health insurance. In short, identifying people’s risk levels creates perverse incentives for patients and for insurance companies. Individuals with lower risk have less reason to join the insurance “pool,” since their premiums disproportionately support care for others, rather than themselves. At the same time, insurance companies have the incentive of excluding those at higher risk, or at least charging them higher premiums. As Kinney and Girod pointed out, there are various schemes for blocking this destructive dynamic, although things get difficult pretty fast.

But sitting there listening to them, I realized that once again we were talking about the challenge of how to bind us together as a society and take care of everybody – the high risk and the low risk alike. How tragic if the same scientific breakthroughs that could allow for improved preventive care for all were to result in worse care and isolation for those at the highest risk. That would truly be a situation where isolation, not trust and community, would have its day.

Peter Schwartz, MD, PhD

Genetic Testing and Personalized Drugs: PredictER at Spirit and Place

As part of the 2008 Spirit & Place Festival, a panel of experts from the Indiana University Center for Bioethics and the Indiana University School of Medicine will join together to illustrate the complex intersection of ethics, medicine and science. Dr. Eric M. Meslin, director of the Center for Bioethics; Dr. Kimberly A. Quaid, professor of medical and molecular genetics; and Dr. David Flockhart, chief of the division of clinical pharmacology, will present Imagining Our Medical Future: The Ethics of Predictive Genetic Testing and the Search for Personalized Drugs this Sunday, November 9th, 2:00-4:00 p.m. at the Indiana Medical History Museum, 3045 W. Vermont Street, Indianapolis. Free tours of the museum will be available both before and after the panel discussion. More information regarding the Spirit & Place Festival, which is runs now through November 16th, is available at www.spiritandplace.org - ALG

Genetics, Ethics, and Tasmania

If you're in the Indianapolis, Indiana area on November 10th, join us at the IU Center for Bioethics with Mark Stranger, Ph.D., from the University of Tasmania. Our guest will be delivering a talk on Genetics, Ethics and the Law Down Under: A Tasmanian Perspective from 3:00-4:00PM in the HITS Building, Suite 3100 [Flyer - PDF 74 KB]. Dr. Stranger, a sociologist with expertise in risk assessment, social change, biobanking and social research methodologies, is a Senior Research Fellow and Executive Director for the Centre for Law and Genetics at the University of Tasmania. He also manages the Centre’s multidisciplinary and international Biotechnology, Ethics, Law and Society Network.

This event will be convened by the Indiana University Center for Bioethics; IUPUI Consortium for Health Policy, Law and Bioethics; and the IUPUI Office of International Affairs. - ALG

PredictER News Brief - Published Today

The most recent edition of PredictER News Brief is now online. PredictER News Brief provides a digest of news and research relevant to the ethical, legal and social implications of predictive health research. Join the PredictER News Brief listserv or view past issues in the archive.

The October 14th edition includes links to stories related to deCODE's new genetic test to screen for breast cancer risks and (as always) a list of recent journal articles on the ethical issues of predictive health and genetic research. Including:

Alpert S. Privacy issues in clinical genomic medicine, or Marcus Welby, M.D., meets the $1000 genome. Camb Q Healthc Ethics. 2008 Fall;17(4):373-84.
[View abstract or record.]

Goodman KW and Cava A. Bioethics, business ethics, and science: bioinformatics and the future of healthcare. Camb Q Healthc Ethics. 2008 Fall;17(4):361-72.
[View abstract or record.]

Hogarth S, et al. The Current Landscape for Direct-to-Consumer Genetic Testing: Legal, Ethical, and Policy Issues. Annu Rev Genomics Hum Genet. 2008 Sep 22;9:161-182.
[View abstract or record.]

Singer E, et al. Trends in U.S. Attitudes Toward Genetic Testing, 1990-2004. Public Opin Q. 2008 September 1, 2008;72(3):446-458.
[View abstract or record.]

Wallace S, et al. Governance mechanisms and population biobanks: building a framework for trust. GenEdit. 2008;6(2):1-11.
[View abstract | PDF]

PredictER Year-End Review

Join us Monday afternoon (August 4th, 3-4pm) at the Center for Bioethics for a year-end review of PredictER's progress. PredictER's director, Eric M. Meslin, will share his assessment of the program's accomplishments and goals for the coming year. This is an excellent opportunity to learn about the services we provide to our constituents with an interest in predictive health research, medicine, and the associated ethical and legal issues. Refreshments will be served.

IU Center for Bioethics, 410 W 10th Street, Suite 3100. Indianapolis, IN 46202 | 317-278-4034

IndyStar - Do you want to know? Direct-to- consumer DNA tests ...

PredictER's Kimberly Quaid and Indiana University Department of Medical and Molecular Genetics' Dr. Gail Vance comment on direct-to-consumer genetic testing in today's issue of The Indianapolis Star. Quaid notes:

"For a lot of genetic conditions, there is not much we can actually do to change them. So, what are people getting out of the tests?" … While legitimate genetic tests exist, such as one to detect the BRAC mutations for breast cancer, Quaid said, she doesn't see the sense in identifying risks for every disease. She also doubts the validity of tests used by some firms. … Traditionally, health-related genetic tests have been available only through health-care providers, who decide whether they are based on family history and symptoms, and who interpret results for patients. Quaid said that method better safeguards consumers.

Translating ELSI – From a Conference at Case Western to the World

An exciting conference occurred last week in Cleveland, Ohio on the past, present, and future of research into the ethical, legal, and social implications genetics (so-called "ELSI" research). If the large number of interesting presentations at this conference is any indication, the field is flourishing. Although I saw relatively few presentations (I was only there for part of the conference), the discussions, the turnout, and the book of abstracts show the rigor and creative energy of a thriving, international group of scholars.

As part of a panel on Saturday morning (May 3rd), I presented a short talk entitled "PredictER: Indiana University's Experience in Translating Predictive Health Ethics Research into Practice". The presentation covered the work that we've been doing at the IU Center for Bioethics on the ethical and legal aspects of predictive health research. Other speakers in the same session described similar work under way in Kyoto, Japan and in Newfoundland, Canada. Genetics is truly a global field, and, thus, so is the project of examining the ethical, legal and social implications of the science and medicine. If we want to insure the ethical practice of genetic science and the equitable sharing of its benefits, the global participation exemplified by the work at this conference, must become a common feature in the investigation of the ELSI of predictive health research. – Peter H. Schwartz

One Year of PredictER Blog

PredictER Blog turns one today! To mark the date, here is a list of the 10 most popular posts:

1. HIPSA: The Health Information Privacy and Security Act of 2007 - Thursday, July 19, 2007

2. Texas: Your Boss, Your Medical Records and the Information Economy - Saturday, March 22, 2008

3. Get Your Genetic Test Results Online and Who Needs a Physician? – Katherine Drabiak, Thursday, November 15, 2007

4. Predictive Health Legislative Update: GINA, HIPSA and more ... - Monday, December 17, 2007

5. Smith-Lemli-Opitz Syndrome and a Florida “Wrongful Birth” Case - Wednesday, July 25, 2007

6. Biomedical Research Ethics 2.0: MySpace and Pediatrics - Tuesday, January 8, 2008

7. Minnesota and Genetic Privacy: Why the Rule of Law is Good for Research – Katherine Drabiak, Wednesday, September 26, 2007

8. Navigenics Enters Personal Genomics Game ... Meanwhile: "What's a SNP?" – Katie Carr, Wednesday, April 16, 2008

9. Health Risk Assessments in the Workplace: Clarian Health, Indianapolis. - Sunday, August 19, 2007

10. Newborn Screening: An Update on Minnesota – Katherine Drabiak, Friday, November 16, 2007

Disclosing Risk: Good Communication or "Doctor-Knows-Best"?

A newly published paper from PredictER's Peter H. Schwartz and Eric M. Meslin, examines the challenges of balancing beneficence and the respect for autonomy in preventive and predictive medicine. In "The ethics of information: absolute risk reduction and patient understanding of screening" (J Gen Intern Med. 2008 Apr 18; [Epub ahead of print] | PMID: 18421509) the authors question whether providing absolute probabilities of risk based, for example, on genetic screening for breast cancer, is always in the best interest of the patient's health. While many argue the respect for the patient's autonomy demands that risk is communicated numerically or graphically, Schwartz and Meslin argue that the disclosures should be made "in the light of careful consideration of patient understanding and possible impacts on uptake and well-being".

Red Herrings and Sexy Science

Anyone feeling a bit overwhelmed by the frequency of news stories reporting new targets for personalized and predictive medicine, will grab some moral support from a recent article in The Washington Post. In "Science Is Leading Us to More Answers, but It's Also Misleading Us" (22 April 2008; HE08) David A. Shaywitz examines the ups and downs of the new biology. In contemporary genetic medical research the paradigm has shifted from investigating "a few favorite genes" to surveying "thousands of initial candidates" and browsing for "important players and pivotal networks". In Shaywitz's view, this has resulted in a lot of noise – sexy science headlines pointing to journals "littered with studies reporting 'disease genes' or 'molecular signatures' that are likely red herrings". This is exasperated by the fact that journals "have little appetite for negative results" and "erroneous results are almost never retracted". To address the hype in genetics, Shaywitz recommends better, more rigorous statistical analysis on the research front and increased caution and scrutiny by information providers and consumers.

One can hardly disagree with a call for better research methods, smarter journalism, and better reading habits, but where does that leave services like PredictER Blog and PredictER News Brief? Here at PredictER we are committed to investigating and addressing the attitudes and concerns of our communities – including: researchers, physicians, legislators and patients. Undoubtedly, some members of these communities will form opinions and pursue projects that leave them fishing for the sexy red herrings of genetic science. Others will develop policies and regulations based on the latest, suspect catch. Knowing this, I'm trying to keep up with the hype. I try to monitor the information, both to identify quality sources, but also to help our investigators assess the impact of the hype. Although the news headlines may not reflect the best science, they do have the potential to influence the public's willingness to participate in and support new medical research. Therefore, we're doing our best to engage the community, even if this means beginning the discussion with the latest hot topics and sexy headlines.

Purdue Bioethics: Ethical Issues in Constructing and Using Biobanks

PredictER's Eric M. Meslin, PhD, Director, IU Center for Bioethics, will address the Purdue Bioethics lecture series this Wednesday, April 16th, from 6 to 7 pm. Meslin will provide an overview of the ethical issues in developing and using biobanks for genetic research. The Purdue lecture series (now in its second year) intends "to build opportunities for engagement between philosophy, policy, and science at a campus-wide level and to raise awareness of the ethical implications of biotechnological development for our environment both local and global". The current year's series focuses "on two central themes in bioethics: the ethical issues of climate change and those of issues in medical technologies". Read more about Meslin's lecture or to learn more about the series contact Jonathan Beever or Nicolae Morar at Purdue Bioethcs. Also see the international blog, BlogEthics Purdue.

Gene Sherpas for CME

Steve Murphy at Gene Sherpas: Personalized Medicine and You has often asserted that physicians will need continuing medical education to understand the latest advances in genetic research and to interpret clinical genetic information. In a recent post, however, he provides a few hints about what he will be doing to make these educational opportunities a reality. Murphy writes:

There is a new hope. An institution being set up by myself and others. We are currently looking for donors and we endeavor to set up educational events and group sessions. We will work with Corporate Genomics, Academic Genetics, Corporate Labs, Academic Medicine to develop training workshops. Interested?

Well Steve, I'm interested (obviously), PredictER has been working on continuing medical education programs for physicians with patients participating in genetic research. We have made plans to offer two initial programs in local clinics here in Indianapolis this summer—we hope to stream these programs to a wider audience as well. While this is one step removed from the clinical use of consumer genomics (we're really focusing on research ethics in the clinic), I hope that our work on the ethical issues of genetic medicine will be of use to your hoped for institution. At the very least, don't forget the ethicists and community advocates when designing your curriculum. Good luck finding donors and keep us posted! – J.O.

Weighing Hope: Living at Risk for Huntington Disease

If you had a parent with Huntington Disease, you would have a 50:50 chance of also having the disease. That's a very high risk - flip a coin - for a disease that has no cure. To make matters worse, the risk itself could strain relationships, lead to social stigmatization and even discrimination. So, if you were at risk for the disease, but had thus far declined a diagnostic, genetic test, would you tell your co-workers, friends and family members about your risks?

Before assuming that you would share news of this risk with all the important people in your life, you might want to read a recent publication by lead author Kimberly A. Quaid, a PredictER team member. In "Living at risk: concealing risk and preserving hope in Huntington Disease" (Quaid KA, Sims SL, Swenson MM, et al. J Genet Couns. 2008 Feb;17(1):117-28. Epub 2007 Oct 18. PMID: 17943424), Quaid et al report the results of open-ended, qualitative interviews of 55 individuals at risk for the disease. Although research on the psycho-social impact of living with the knowledge of genetic risk for Huntington Disease often focuses on the decision of whether or not to be tested and/or whether or not to share the test result, this paper is unique in that it examines: 1) the decisions of those who have not received a genetic test and 2) the ongoing, daily decisions to both disclose and conceal this risk information. After reviewing the unstructured interviews, the authors conclude that some people chose to conceal their risks for many valid reasons, including: to protect themselves from discrimination, to identify the best circumstances in which to share the information with loved ones (especially young children) and to preserve personal hope that they will not succumb to the disease. Quaid et al also remind us that: "Choosing to be tested is, in a way, a decision to disclose one's real risk to oneself. Participants' choosing not to be tested is not denial but a positive way to preserve both hope and their identities as people with a future". The authors encourage clinicians to respect a patient's desire not to be tested. For some patients a genetic test for an incurable disease will not provide helpful information; in fact, for some, the "knowledge … of HD may serve to destroy hope".

Biobanks: Consent or Re-Consent?

Participants donating samples to research biobanks are, often, contributing to a research resource that may be used for unanticipated research purposes in the future. For example, a participant may donate to a cardiovascular research biobank, but this donation might also be of value for future diabetes research. If a secondary use for this donation is discovered, should researchers be required to re-contact participants to secure consent for the previously unspecified research? Many researchers consider the labor of re-contact and re-consent to be a burden that will inhibit future research. Acquiring one-time, general consent for research, therefore, would seem to be the best and most efficient way to encourage the pace of medical research.

Many ethicists, and the World Health Organization (WHO), however, argue that one-time consent violates a research participant's autonomy. If a participant does not have the opportunity to evaluate these possible future uses and to decide whether their sample and information can be used for them, is the importance of informed consent being undermined?

Wednesday, at a noon seminar hosted by the IU School of Medicine's Department of Medical and Molecular Genetics, PredictER's Peter Schwartz critically evaluated some of the most prominent ethical arguments against one-time consent and described the complexity of deciding the role of autonomy in this realm. In his presentation, "Changing the Rules? Consent and Re-Consent in Predictive Health Research", Schwartz argued that it is not clear that a carefully constructed policy of one-time consent violates autonomy of subjects. While it would be inappropriate to justify such “one-time consent” simply on the basis of the social value of the research involved, or public support for such a policy, a careful reconsideration of autonomy may allow certain kinds of “blanket consent” policies. In his assessment, the path forward for consent for research involving biobanks is far from clear, but a possibility like one-time consent cannot be dismissed simply by appealing to a simple notion of autonomy. The crafting of responsible policies in this area will require more careful reflection on the relevant ethical notions.

Additional Reading:

45 CFR §46.116 - General requirements for informed consent. Department of Health and Human Services.

Caulfield T, Upshur RE, Daar A. DNA databanks and consent: a suggested policy option involving an authorization model. BMC Med Ethics. 2003 Jan 3;4:E1. PMID: 12513704

Genetic databases. Assessing the benefits and the impact on human and patient rights. World Health Organization, 2003. [PDF]

MCI and Predictive Neuroimaging

Monday ( March 3, 2008) at the weekly PredictER meeting, Andrew Saykin, PsyD, Director, Indiana University Center for Neuroimaging, shared his work on the neuroimaging of Alzheimer's disease. Saykin's study of Alzheimer's began with a small cohort at Dartmouth. Except for the control population, most of participants in this research were diagnosed with MCI (Mild Cognitive Impairment). As his research developed his cohorts began to include individuals reporting memory complaints, but who were not yet diagnosed with MCI. Interestingly, Dr. Saykin has observed changes in the brain scans of both MCI patients and patients with memory complaints compared to his control. Today Saykin is working to build (and collaborate with) larger, more diverse cohorts—cohorts which are easier to find at research institutions, like the Indiana University School of Medicine, located in "sunny" Indianapolis. In addition to representing a more diverse demographic, these developing cohorts will also examine ways to identify, with new imaging technologies and genetic research tools, the earliest biomarkers of the disease. As with many predictive health research studies, the ultimate goal is to identify the disease early enough to develop therapeutic and preventative interventions.

Some of the ethical issues discussed include:

How much to tell research participants: Do participants want to know the results of every memory test and each neuroimaging procedure?

Should researchers be prepared to disclose this information even when a reliable interpretation of the risks is not available?

The value of this research to public health: At the moment and into the foreseeable future, the ability to diagnose the onset of Alzheimer's disease exceeds medicine’s ability to treat the disease … will early diagnostics result in inappropriate marketing of unproven interventions to at-risk individuals?

Will there be a way to protect individuals from wasted expense, discrimination and questionable experimental treatments while at the same time encouraging continued research to understand the disease?

To join us at a future PredictER meeting, check our Center's calendar to verify the time and topic: www.bioethics.iu.edu - calendar

PredictER News Brief - 25 February 2008

The latest edition of PredictER News Brief (25 February 2008) is now available online. PredictER News Brief is a biweekly digest of news, blogs, and research publications relevant to the ethics, law and policy of predictive health research.

To receive PredictER News Brief as an email newsletter send an email to listserv@listserv.iupui.edu with "subscribe PREDICTER-L" in the message body.

Ethics Meetings at PredictER

PredictER holds a semi-regular weekly meeting to discuss the ethical, legal and social issues relevant to the latest predictive health research. These meetings frequently include presentations from distinguished guest speakers. Recent speakers have included:

Greg Sachs, M.D. - Chief of the Division of General Internal Medicine and Geriatrics, Department of Medicine, Indiana University School of Medicine.

Anantha Shekhar, M.D., Ph.D. - Associate Dean for Translational Research, Indiana University School of Medicine.

David W. Crabb, M.D. - Director of the Indiana Alcohol Research Center, Chair of the Department of Medicine, Indiana University School of Medicine.

Eric Wright, Ph.D. – Director, Center for Health Policy, Indiana University-Purdue University, Indianapolis.

Eleanor DeArman Kinney, J.D., M.P.H. - Hall Render Professor of Law, Co-director of the William S. and Christine S. Hall Center for Law and Health, Indiana University School of Law - Indianapolis.

Jim Wolf, M.S. - Director, Survey Research Center, Indiana University-Purdue University, Indianapolis.

Most recently, Jennifer Girod, J.D., Ph.D., R.N. (IU Center for Bioethics/Sommer Barnard, PC) introduced and moderated a discussion of PredictER’s developing agenda for predictive health policy research. Four domains for potential public policy research were identified: the growing life sciences research and development sector, predictive health information and the future of insurance underwriting, the use and misuse of modestly predictive health information in clinical settings (including patient understanding of risk and related professional liabilities), and the impact of genomic information on public health.

The schedule for the rest of the month includes:

February 18 – 3:00: Elda Railey, Cynthia Burkhardt and Mary Lou Smith from the Research Advocacy Network will present their current activities and will discuss the influence advocates have had on tissue banking.

February 25 – 3:00: Anna Maria Storniolo, M.D., (Director, Catherine Peachey Breast Cancer Prevention Program) will share the progress of the Mary Ellen Tissue Bank.

If you are in the Indianapolis area and would like to attend, visit the Indiana University Center for Bioethics website for more information. - J.O.

PredictER News Brief - 14 January 2008

The latest edition of PredictER News Brief (14 January 2008) is now available online. PredictER News Brief is a biweekly digest of news, blogs, and research publications relevant to the ethics, law and policy of predictive health research. The current issue features: a synopsis of recent news coverage of the genetics of autism, a list of several upcoming events and conferences, and references blog entries from Brandon Keim at Wired Science, Jacob Goldstein at The Wall Street Journal Health Blog, Myles Axton of Free Association, and Blaine Bettinger of The Genetic Genealogist.

To received PredictER News Brief as an email newsletter send an email to listserv@listserv.iupui.edu with "subscribe PREDICTER-L" in the message body. - J.O.

PredictER's News Digest

PredictER News Brief (a bi-weekly, electronic newsletter) is now published on the PREDICTER-L listserv. PredictER Blog's readers (and any other interested person with an email address) may subscribe to this publication by sending an email to listserv@listserv.iupui.edu with "subscribe PREDICTER-L" in the message body.

If you would like to see the most recent issue of PredictER News Brief before subscribing to the listserv, visit the News Digest tab on the PredictER Portal. Also see the archive of ten prior issues, accessible from the PredictER Resources tab.