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).

Dr. Tomlinson presents at 3rd Annual Great Lakes Biorepository Network Scientific Meeting

tomlinson-crop-2016The 3rd Annual Great Lakes Biorepository Network (GLBRN) Scientific Meeting was held on October 28, 2016 at the University of Michigan in Ann Arbor. Center Director and Professor Dr. Tom Tomlinson spoke on “Preferences for Biobank Consent Policy are Sensitive to Concerns about Future Research Uses.”

The current research ethics framework gauges the level of ethical protections to the degree of risk to the participant. The lower the risk, the less stringent the requirements for informed consent; when the risk is virtually zero, as with the research uses of de-identified biospecimens and related clinical and demographic data, it is no longer research on a human “subject.”

This framework forgets why people donate their specimens and data to biobanks. They are not merely concerned with what later research will do to or for them. They are hoping their donation may do some good; and correlatively, assuming that it will do no wrong, in ways they would find morally concerning:

  • Some research might threaten a donor’s world view –such as research to better understand human evolution and history.
  • Some donors might be concerned by research that might lead to the stigmatization of others –such as research that looks at genes associated with violence.
  • Or some research may be contrary to the moral, cultural, or political values of the donor – such as research related to abortion or research leading to large commercial profits.

To emphasize the contrasts with the conventional framework, Dr. Tomlinson and his colleagues call these people’s non-welfare interests in later research uses of their donations.

In the talk Dr. Tomlinson presented evidence that such concerns affect people’s preferences among various biobank consent policies, drawn from both a national survey that his research team conducted in 2014 and a series of democratic deliberations held in 2015. The evidence shows that the more people are aware of the range of possible research uses of biobank donations that might be of concern to them or others, the more negative their attitudes are toward blanket consent. In this consent, a donor gives permission up front to any future uses that the biobank would allow, without any further consent or information provided. This is the most common form of biobank consent, but their research shows that a bare majority finds it “acceptable,” and a sizeable minority (38%) think it’s the “worst” option among those presented. Interestingly, the team found similar attitudes expressed toward specific, study-by-study consent, the option that gives each donor the most control over later research uses.

For more analysis of the national survey, see: De Vries RG, Tomlinson T, Kim HM, Krenz C, Haggerty D, Ryan KA, Kim SY. Understanding the Public’s Reservations about Broad Consent and Study-By-Study Consent for Donations to a Biobank: Results of a National Survey. PLoS One. 2016 Jul 14;11(7).

Dr. Tomlinson is an Executive Board Member of the Great Lakes Biorepository Network and Incoming President for 2017.