Tag: precision medicine

Leonard Fleck presents on cancer care at annual American Society for Bioethics and Humanities conference

Leonard Fleck photo

Last month at the 23rd Annual Conference of the American Society for Bioethics and Humanities (ASBH), Center Professor Leonard Fleck, PhD, presented on “Precision Health, Ethical Ambiguity: How Much Cancer Can We Afford to Prevent?” as part of a session on health care allocation and cost. Dr. Fleck has provided a summary of his presentation below.

“Precision medicine” and “precision health” seem to complement one another. We want an effective targeted cancer therapy for our metastatic cancer, but would rationally prefer to prevent the emergence of a life-threatening cancer–the goal of precision health. In a recent book, The First Cell: And the Human Costs of Pursuing Cancer to the Last, Azra Raza, an oncologist, argues that we are wasting tens of billions of dollars annually on extraordinarily expensive cancer therapies that yield only marginal gains in life expectancy. Raza believes these resources (not resources from heart disease or anything else) should be redirected to destroying cancer in its earliest stages, those “first cells.”

A new liquid biopsy (GRAIL) can detect 50 different cancers in very early stages by examining cell-free DNA at a cost of $800. However, 200 million anxious U.S. adults would be candidates for this test annually at an aggregate cost of $160 billion. From the perspective of health care justice, who should pay for these tests? Who should be denied access to these tests at social expense? Should only individuals with a strong family history of cancer have a moral right to this test at social expense? That would cover only 10% of cancers diagnosed in any given year.

We might say individuals known to be at elevated risk for cancer should have these tests paid for as a social expense. That would include smokers and sun worshippers at risk for lung cancer and melanoma. Would non-smokers and responsible sunscreen appliers have just cause for a grievance, i.e., paying for the irresponsible?

Would justice or efficiency require foregoing $160 billion in metastatic cancer care to pay for this preventive effort? What would a “just enough” balancing of therapeutic objectives look like? The basic economic and ethical problem is that we would be paying $160 billion annually that we knew would yield negative results more than 99% of the time. This is not obviously either a wise or just use of social resources. Moreover, this situation calls attention to the “statistical lives vs. identifiable lives” problem.

The “statistical lives” are the lives we would hope to save from metastatic cancer with the liquid biopsy test. These are nameless and faceless lives, unlike the identifiable lives that are the patients with metastatic cancer who want access to the hyper-expensive targeted therapies that might extend their lives a few months, maybe an extra year or so. In contrast, the hope is that each statistical life saved would result in extra decades of life for that individual.

A key ethical question is whether statistical lives and identifiable lives in this situation are of equal moral weight. Or are the identifiable lives with metastatic cancer more “morally worthy” of social resources because they are suffering and near dying? Or, as Raza contends, are we ethically obligated to shift resources from metastatic cancer patients (who have been effectively treated up to this point) to preventive efforts associated with liquid biopsies hoping to save more lives and life years? How do you, my currently healthy readers, think we ought to decide?

Related reading: If Whole Genome Sequencing is So Cheap and Quick, Why Shouldn’t Everyone Have It Done?

Dr. Fleck presents on precision medicine at international virtual symposium

Leonard Fleck photo

Center Acting Director and Professor Dr. Leonard Fleck spoke earlier this month at a virtual symposium presented by University of Groningen in Groningen, Netherlands.

The event’s theme was “Barriers and future directions of personalized medicine: from the bench to the patients.” Dr. Fleck’s presentation was titled “Precision Medicine/Ethical Ambiguity: Rough Justice, Wicked Problems, fragmented Solidarity.” The symposium was funded by the European Union’s Horizon 2020 research and innovation program. As one of several keynote speakers, Dr. Fleck provided an ethicist perspective. Dr. Fleck has provided a summary of his presentation below.

Solidarity is a fundamental social value in many European countries, though its precise practical and theoretical meaning is disputed. In a health care context, solidarity means roughly equal access to effective health care for all. However, I argued that precision medicine represents a threat to solidarity. Precision medicine includes ninety targeted cancer therapies (mostly for metastatic cancer). The “targets” of these therapies are certain genetic features of a cancer, mutations responsible for “driving” that cancer’s expansion. These targeted therapies have prices of €100,000 (roughly 117,500 USD) to €150,000 (roughly 176,300 USD) annually or for a course of treatment. Our critical question: Must a commitment to solidarity mean that all these targeted cancer therapies are included in a benefit package guaranteed to all in the European Union, no matter the cost, no matter the degree of effectiveness? Such a commitment would imply that cancer was ethically special, rightfully commandeering unlimited resources. That in itself undermines solidarity. I offered multiple examples of how current and future dissemination of these drugs challenges a commitment to solidarity. An alternative is to fund more cancer prevention efforts. However, that too proves a threat to solidarity. Solidarity is too abstract a notion to address these challenges. We need instead the notion of “just solidarity.” We need to accept that we can only hope to achieve “rough justice” and “supple solidarity.” The precise practical meaning of these notions needs to be worked out through fair and inclusive processes of rational democratic deliberation, which is the real foundation of solidarity.

Listen: Ethics and Policy Issues of Targeted Cancer Therapies

No Easy Answers in Bioethics logoNo Easy Answers in Bioethics Episode 16

What kinds of challenges currently exist within precision medicine? This episode focuses specifically on targeted cancer therapies, featuring a discussion between Center Professor and Acting Director Dr. Len Fleck and College of Osteopathic Medicine student Stephanie Mackenzie. Dr. Fleck discusses ethics, economic, medical, and health policy issues related to these high-cost therapies. Additionally, he provides insight into how U.S. pricing models for these therapies compare with other countries.

Ways to Listen

This episode was produced and edited by Liz McDaniel in the Center for Ethics. Music: “While We Walk (2004)” by Antony Raijekov via Free Music Archive, licensed under a Attribution-NonCommercial-ShareAlike License. Full episode transcript available.

About: No Easy Answers in Bioethics is a podcast series from the Center for Ethics and Humanities in the Life Sciences in the Michigan State University College of Human Medicine. Each month Center for Ethics faculty and their collaborators discuss their ongoing work and research across many areas of bioethics. Episodes are hosted by H-Net: Humanities and Social Sciences Online.

Center faculty present at 20th annual American Society for Bioethics and Humanities conference

ASBH logo blueCenter faculty members Dr. Len Fleck and Dr. Devan Stahl recently presented at the 20th annual American Society for Bioethics and Humanities (ASBH) conference, held October 18-21 in Anaheim, CA.

Leonard Fleck photoDr. Fleck presented on “Parsimonious Precision Medicine: Wicked Problems.” The phrase “precision medicine” refers to targeted cancer therapies and immunotherapies that are aimed at defeating metastatic cancers with specific genetic signatures. There are more than ninety such FDA approved therapies, all of which have costs of more than $100,000 per year with some costing as much as $475,000 (CAR-T cell therapies). To date, none are curative. On the contrary, for the vast majority of patients gains in life expectancy are measurable in weeks or months, not years. These results suggest that for a just and caring society with limited resources to meet virtually unlimited health care needs, we ought to be more parsimonious in how we use these drugs and who we choose to treat.

The key point of the presentation was that whether we choose to be parsimonious in our use of targeted therapies or not, we will generate what the literature has come to describe as “wicked problems” (ethically, economically, and politically speaking). A “wicked” problem is essentially a problem for which every proposed solution (including doing nothing) generates even more problems that are equally, or more, challenging.

Devan Stahl photo

Dr. Stahl gave two panel presentations at ASBH this year. The first, “Theories of Identity and the Problem of Precedent Autonomy,” explored the ethical tensions that arise when patients in disordered states of consciousness appear to have current preferences that contradict their prior wishes. The panelists, including Dr. John Banja (Emory University) and Dr. Nancy Jecker (University of Washington), discussed the limits of philosophical analysis and theory regarding the status of precedent autonomy.

In her second presentation, Dr. Stahl was joined by Darian Goldin Stahl (Concordia University) and Dr. Jeffrey Bishop (Saint Louis University) to discuss their latest book Imaging and Imagining Illness, which explores the effect of medical imagining on patients and ways medical images can be transformed through art and philosophy.

Drs. Eijkholt and Fleck present at International Bioethics Retreat in Paris

Marleen Eijkholt photoLeonard Fleck photoCenter Professor Len Fleck and Marleen Eijkholt, former Assistant Professor with the Center, recently presented at the 2018 International Bioethics Retreat, held in Paris, France on June 27-29. The conference has been sponsored by Cambridge University for the past eighteen years.

Dr. Fleck presented on “Personalized Medicine? Precision Medicine? What is Just Enough?” He addressed a question raised by Warwick Heale in an article in the Journal of Medical Ethics.

Heale was writing about the use of a quality-adjusted life year (QALY) cost-effectiveness methodology to make allocation decisions in health care. Heale identifies himself as a utilitarian. He generally wants to obtain the most medical good for a population group at the lowest cost. However, Heale notes that the use of this methodology is about averages for a population group. He wants to argue that if a population group cannot be treated cost-effectively with some very costly cancer drug, then it would be unjust to deny that drug to any individuals in that group whom we could identify before the fact who would benefit very significantly and cost-effectively from that drug. This has a certain intuitive moral reasonableness about it.

However, Fleck argued Heale’s proposal has some morally problematic aspects as well. He asked his audience to consider Laurel and Hardy. Both have the same medical problem; both would benefit from access to a certain costly drug. The quantity of the drug is administered on the basis of weight. It is clear that the drug is cost-effective for the average 70 kilogram person. Laurel weighs 57 kilograms. The drug is even more cost-effective for him. But Hardy weighs 90 kilograms; the drug would not be cost-effective if given to him. The logic of Heale’s position would require denying the drug to Hardy. This would strike most physicians (as well as most patients) as clearly unjust, especially if we were talking about a drug that was not absolutely scarce.

Heale wrote this paper to suggest a better approach to allocating money from the UK Conservative government’s Cancer Drug Fund, which was mostly without ethical moorings for several years. However, Fleck concluded that Heale’s proposal might effectively address the economic challenges faced by the Cancer Drug Fund while adding to the moral challenges intrinsic to the creation of the fund in the first place.

Dr. Eijkholt spoke on “Medicine’s Collusion with False Hope: False Hope Harm.” She proposed a new argument to think about interventions that are offered for consumer demands rather than for medical reasons: i.e. the False Hope Harm. She proposed that hope serves important functions in medicine. Hope can be “therapeutic” and important for patients to “self-identity as active agents.” However, in consumer medicine, like in much of the U.S. health care context, hope could also take on a different role. Scenarios like Jahi McMath and Charlie Gard make us wonder if hope can be harmful too. In fields like stem cell medicine or cancer treatment, where providers justify their support for medical interventions with “it will make them feel better,” we can also identify the risk of such harm. While one might argue that we should not deny anyone such hope in the face of emotionally vivid stories, Dr. Eijkholt argued that the profession has an obligation to avoid false hope harms.

Dr. Fleck presents at Centre for Cancer Biomarkers Symposium in Norway

Leonard Fleck photoCenter Professor Dr. Len Fleck recently traveled to Bergen, Norway to present a keynote address at the 6th Annual Centre for Cancer Biomarkers (CCBIO) Symposium. Dr. Fleck’s presentation, “Just Caring Challenges: Visible Biomarkers and Invisible Rationing,” addressed some of the critical ethical issues related to the use of biomarkers in cancer research and clinical care.

Dr. Fleck addressed two main problems in his lecture. First, the ragged edge problem. One of the primary purposes of finding biomarkers is to determine whether a cancer drug is likely to be effective for a particular metastatic cancer patient. However, rarely will a biomarker yield a simple answer. Most often, the biomarker will be expressed along a continuum. If a drug were very inexpensive and side effects tolerable, it would be easy to say that the ethically right choice would be to respect patient autonomy. But these drugs all cost more than $100,000 for a course of treatment. Consequently, if a drug has a 20% chance of having a beneficial effect, there is a conflict between considerations of justice and respect for patient autonomy. Invisible rationing (just not offering the drug to the patient) can bypass this conflict, but invisible rationing is ethically problematic so far as justice is concerned.

Secondly, recent liquid biopsies can identify eight common cancers at a very early stage–in the form of circulating cancer cells in the blood–at a cost of $500. However, the critical question would need to be raised: How often would 170 million adults (all anxious about cancer) in the U.S. have a just claim to access that test? Every six months? Every year? Note that each such offering of that test to that population would cost $85 billion. Would that represent either a just or prudent use of health care resources?

The CCBIO symposium was well-attended by an international mix of junior and senior researchers and scholars. Dr. Fleck had the opportunity to meet with many European researchers to discuss their respective work in the field of cancer research.

Dr. Fleck also gave a public lecture at the University of Bergen’s Centre for the Study of the Sciences and the Humanities, titled “Precision Medicine, Ethical Ambiguity: Rough Justice, Ragged Edges.” Dr. Fleck addressed precision medicine as it currently exists, in particular the costly FDA-approved targeted cancer therapies. Treatments for patients with metastatic cancers, which are not curative, can cost $100,000 to $475,000 per treatment course. For example, 30% of patients who are candidates for CAR T-cell immunotherapy will not gain more than an extra year of life. As things are now, we do not know before the fact who those patients might be. But one goal of biomarker research is to identify before the fact who those marginal responders most likely will be, so that we could save money by denying those patients access to this therapy. As a citizen of a just and caring society, would you endorse the research to accomplish that result? Why or why not? This is what Dr. Fleck calls “rough justice.”

Dr. Fleck presents at Great Lakes Biorepository Research Network annual scientific meeting

Leonard Fleck photoCenter Professor Len Fleck, PhD, was a keynote speaker at the Great Lakes Biorepository Research Network (GLBRN) Annual Scientific Meeting, held at Beaumont Hospital-Royal Oak Campus on November 3. The title of Dr. Fleck’s presentation was “Precision Medicine, Ethical Ambiguity,” summarized below.

What is precision medicine? A short answer would be getting beyond “one size fits all” drug therapy, with all the side effects and misfits that implies (e.g. traditional chemotherapy). Instead, medicine would stratify patients with a specific disease, such as some cancer, into subgroups so that therapy could be tailored to the specific genetic features of their cancer. The overall goal is to maximize the beneficial effects of an available therapy for a specific patient, minimize debilitating or dangerous side effects, and save money for the health care system. How could there be ethical problems with goals such as that?

The most significant problem relates to health care justice, the fair distribution of access to the fruits of precision medicine. The basic problem is that these targeted cancer therapies are extraordinarily expensive. More than 70 of these cancer drugs have been approved by the FDA since 2000.

  • Cost: $70,000–$200,000+ for a course of treatment.
    • One form of combination therapy is priced at $86,000 per month.
    • Kymriah for Acute Lymphocytic Leukemia (ALL) is priced at $475,000 for a one-time treatment.
  • None of these drugs is curative.
  • Median gains in life expectancy for patients is measurable in weeks or months for the most part.
  • Several hundred more such drugs are in the pipeline.
  • Fojo and Grady have pointed out that these drugs yield incremental cost-effectiveness ratios (ICERs) of several hundred thousand dollars to more than a million dollars per Quality-Adjusted Life Year (QALY).

Imatinib (Gleevec) was approved in 2001 for the treatment of Chronic Myelogenous Leukemia (CML). It is extraordinarily effective for the 70% of these patients who have survived at least ten years beyond diagnosis. It was priced at $36,000 per year in 2001, and must be taken indefinitely. In 2016 imatinib was priced at $146,000, even though nothing at all changed with regard to the drug itself. Another drug, Iclusig, was priced at $120,000 for a year in 2015. In 2016 the price was raised to $200,000. We will pass over in stunned silence at the obvious ethical issues here.

As a society that seeks to be just and caring in meeting health care needs we struggle to identify the ethical norms that should govern access to these targeted cancer therapies. Keep in mind that these drugs are for metastatic cancer, almost always a terminal diagnosis. Consequently, we often appeal to inchoate (and problematic) ethical intuitions. We appeal to the “rule of rescue,” “last chance therapies,” “the pricelessness of human life,” and the “visibility of desperate patients,” all of which seem to generate an ethical obligation to fund access to these targeted therapies. Unfortunately, that obligation runs out of ethical steam once insurance runs out. In health care, our sense of obligation has evolved to select for money.

Some sad conclusions: (1) No moral theories or “compelling” moral arguments are going to yield clearly satisfactory ethical resolution to these allocation/ priority-setting challenges. Not just cancer counts (ethically speaking). (2) Ultimately, given limited resources (money) for meeting unlimited health care needs we will have to rely upon fair and legitimate processes of rational democratic deliberation constrained by relevant clinical evidence and broadly endorsed considered judgments of health care justice. (3) For the foreseeable future, precision medicine will remain infected with clinical uncertainty, ethical ambiguity, disingenuous politicking, and byzantine economic accounting (not to mention pharmaceutical philandering).

What level of risk will be tolerated for interventions that are developed for treating “pre-diseased” patients?

bbag-blog-image-logoCrossing the Biology to Pathobiology Threshold: Distinguishing Precision Health from Precision Medicine

Event Flyer

Diseases have long been defined by their symptoms, and therefore patients have typically been treated when they are symptomatic. However, through advances in “omics,” wearable sensors, insertable microscopes, liquid biopsies, point-of-care pathology, and other innovations, it is possible to make a molecular diagnosis prior to apparent symptoms. These tools will enable a transition from Precision Medicine where the molecular etiology is determined after symptoms appear, to Precision Health in which the molecular etiology of diseases can be anticipated and symptoms averted. However, is it ethical to treat “asymptomatic disease” and at what cost to the healthcare system? What level of risk will be tolerated for interventions that are developed for treating “pre-diseased” patients? Since many of these assays will predict likelihood of disease and not absolute progression to disease, what level of certainty is needed to intervene at all? Medicine is being redefined and we are behind in understanding what is meant by the simple terms health and disease.

October 11 calendar iconJoin us for Dr. Contag’s lecture on Wednesday, October 11, 2017 from noon till 1 pm in person or online.

Dr. Christopher H. Contag is the chair of the inaugural Department of Biomedical Engineering and founding Director of the Institute for Quantitative Health Science and Engineering at Michigan State University. Dr. Contag is also Professor emeritus in the Department of Pediatrics at Stanford University. Dr. Contag received his B.S. in Biology from the University of Minnesota, St. Paul in 1982. He received his Ph.D. in Microbiology from the University of Minnesota, Minneapolis in 1988. He did his postdoctoral training at Stanford University from 1990-1994, and then joined Stanford faculty in 1995 where he was professor in the Departments of Pediatrics, Radiology, Bioengineering and Microbiology & Immunology until 2016. Dr. Contag is a pioneer in the field of molecular imaging and is developing imaging approaches aimed at revealing molecular processes in living subjects, including humans, and advancing therapeutic strategies through imaging. He is a founding member and past president of the Society for Molecular Imaging (SMI), and recipient of the Achievement Award from the SMI and the Britton Chance Award from SPIE for his fundamental contributions to optics. Dr. Contag is a Fellow of the World Molecular Imaging Society (WMIS) and the recent past President of WMIS. Dr. Contag was a founder of Xenogen Corp. (now part of PerkinElmer) established to commercialize innovative imaging tools for biomedicine. He is also a founder of BioEclipse—a cancer therapy company, and PixelGear—a point-of-care pathology company.

In person: This lecture will take place in C102 East Fee Hall on MSU’s East Lansing campus. Feel free to bring your lunch! Beverages and light snacks will be provided.

Online: Here are some instructions for your first time joining the webinar, or if you have attended or viewed them before, go to the meeting!

Can’t make it? All webinars are recorded! Visit our archive of recorded lectures. To receive reminders before each webinar, please subscribe to our mailing list.

Announcing the Fall 2017 Bioethics Brownbag & Webinar Series

bbag-icon-decThe Center for Ethics and Humanities in the Life Sciences at Michigan State University is proud to announce the 2017-2018 Bioethics Brownbag & Webinar Series, featuring a wide variety of bioethics topics. The fall series will begin on September 13, 2017. You are invited to join us in person or watch live online from anywhere in the world! Information about the fall series is listed below. Please visit our website for more details, including the full description and speaker bio for each event.

Fall 2017 Series Flyer

sept-13-bbagExpanded Carrier Screening for an Increasingly Diverse Population: Embracing the Promise of the Future or Ignoring the Sins of the Past?
How do we explain to patients what results might mean for their baby when they have only been validated in other populations?
Wednesday, September 13, 2017
Kayte Spector-Bagdady, JD, MBioethics, is a Research Investigator in the Department of Obstetrics & Gynecology and leads the Research Ethics Service at the Center for Bioethics & Social Sciences in Medicine at the University of Michigan Medical School.

oct-11-bbagCrossing the Biology to Pathobiology Threshold: Distinguishing Precision Health from Precision Medicine
What level of risk will be tolerated for interventions that are developed for treating “pre-diseased” patients?
Wednesday, October 11, 2017
Christopher H. Contag, PhD, is a John A. Hannah Distinguished Professor of Biomedical Engineering and Microbiology & Molecular Genetics, Chair of the Department of Biomedical Engineering, and Director of the Institute for Quantitative Health Science and Engineering at Michigan State University.

nov-29-bbagProspects, Promises and Perils of Human Mind-Reading
What are the prospects for such technology to be widely used?
Wednesday, November 29, 2017
Mark Reimers, PhD, is an Associate Professor in the Neuroscience Program in the College of Natural Science at Michigan State University.

In person: These lectures will take place in C102 (Patenge Room) East Fee Hall on MSU’s East Lansing campus. Feel free to bring your lunch! Beverages and light snacks will be provided.

Online: Here are some instructions for your first time joining the webinar, or if you have attended or viewed them before, go to the meeting!

Can’t make it? Every lecture is recorded and posted for viewing in our archive. If you’d like to receive a reminder before each lecture, please subscribe to our mailing list.

Would you donate to a biobank?

Tom TomlinsonCenter Director Dr. Tom Tomlinson and Raymond G. De Vries, Co-Director of the Center for Bioethics and Social Sciences in Medicine at University of Michigan, have co-authored the article “Americans want a say in what happens to their donated blood and tissue in biobanks.” The authors discuss biobank donations, precision medicine, genetics, privacy, and consent.

The last time you went to a hospital, you probably had to fill out forms listing the medications you are taking and updating your emergency contacts. You also might have been asked a question about what is to be done with “excess tissues or specimens” that may be removed during diagnosis or treatment. Are you willing to donate these leftover bits of yourself (stripped of your name, of course) for medical research?

If you are inclined to answer, “Sure, why not?” you will join the majority of Americans who would agree to donate, allowing your leftovers, such as blood or unused bits from biopsies or even embryos, to be sent to a “biobank” that collects specimens and related medical information from donors.

But what, exactly, will be done with your donation? Can the biobank guarantee that information about your genetic destiny will not find its way to insurance companies or future employers? Could, for example, a pharmaceutical company use it to develop and patent a new drug that will be sold back to you at an exorbitant price?

These questions may soon become a lot more real for many of us.

Read the full piece at The Conversation.

Related reading: “Understanding the Public’s Reservations about Broad Consent and Study-By-Study Consent for Donations to a Biobank: Results of a National Survey” published July 14, 2016 in PLoS ONE, an open-access peer-reviewed journal. Authors: Raymond Gene De Vries, Tom Tomlinson, Hyungjin Myra Kim, Chris Krenz, Diana Haggerty, Kerry A. Ryan, Scott Y. H. Kim.