Americans want a say in what happens to their donated blood and tissue in biobanks

[The following article was written by my collaborators Ray De Vries and Tom Tomlinson, and originally published in The Conversation]

Raymond G. De Vries, University of Michigan and Tom Tomlinson, Michigan State University

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.

Precision medicine, a promising new approach to treating and preventing disease, will require thousands, or even millions, of us to provide samples for genetic research. So how much privacy are we willing to give up in the name of cutting-edge science? And do we care about the kinds of research that will be done with our donations?

President Barack Obama makes remarks highlighting investments to improve health and treat disease through precision medicine on January 30, 2015.
Larry Downing/Reuters

Precision medicine needs you

In January 2015, President Obama announced his “Precision Medicine Initiative” (PMI), asking for US$215 million to move medical care from a “one size fits all” approach to one that tailors treatments to each person’s genetic makeup. In his words, precision medicine is “one of the greatest opportunities for new medical breakthroughs that we have ever seen,” allowing doctors to provide “the right treatments at the right time, every time, to the right person.”

The PMI is now being implemented, and a critical part of the initiative is the creation of a “voluntary national research cohort” of one million people who will provide the “data” researchers need to make this big jump in medical care. And yes, those “data” will include blood, urine and information from your electronic health records, all of which will help scientists find the link between genes, illness and treatments.

Recognizing that there may be some reluctance to donate, the drafters of the initiative bent over backwards to assure future donors that their privacy will be “rigorously protected.” But privacy is not the only thing donors are worrying about.

Together with our colleagues at the Center for Bioethics and Social Sciences in Medicine at the University of Michigan and the Center for Ethics and Humanities in the Life Sciences at Michigan State University, we asked the American public about their willingness to donate blood and tissue to researchers.

Data from our national survey – published in the Journal of the American Medical Association – reveal that while most Americans are willing to donate to biobanks, they have serious concerns about how we ask for their consent and about how their donations may be used in future research.

What are you consenting to?

We asked our respondents – a sample representative of the U.S. population – if they would be willing to donate to a biobank using the current method of “blanket consent” where donors are asked to agree that their tissue can be used for any research study approved by the biobank, “without further consent from me.”

A healthy majority – 68 percent – agreed. But when we asked if they would still be willing to give blanket consent if their specimens might be used “to develop patents and earn profits for commercial companies,” that number dropped to 55 percent. Only 57 percent agreed to donate if there was a possibility their donation would be used to develop vaccines against biological weapons, research that might first require creating biological weapons. And less than 50 percent of our sample agreed to donate if told their specimen may be used “to develop more safe and effective abortion methods.”

You may think that some of these scenarios are far-fetched, but we consulted with a biobank researcher who reviewed all of our scenarios and confirmed that such research could be done with donations to biobanks, or associated data. And some scenarios are real. For instance, biobanked human embryos have been used to confirm how mifepristone, a drug which is used to induce miscarriages, works.

Trust in science is important

Should we take these moral concerns about biobank research seriously? Yes, because progress in science and medicine depends on public trust in the research enterprise. If scientists violate that trust they risk losing public support – including funding – for their work.

Henrietta Lacks.
Oregon State University/Flickr, CC BY-SA

Witness the story of the Havasupai tribe of Arizona. Researchers collected DNA from members of the tribe in an effort to better understand their high rate of diabetes. That DNA was then used, without informing those who donated, for a study tracing the migration of Havasupai ancestors. The findings of that research undermined the tribal story of its origins. The result? The tribe banished all researchers.

Rebecca Skloot’s best-seller, “The Immortal Life of Henrietta Lacks,” revealed the way tissues and blood taken for clinical uses can be used for purposes unknown to the donors.

In the early 1950s, Ms. Lacks was unsuccessfully treated for cervical cancer. Researchers harvested her cells without her knowledge, and after her death they used these cells to develop the HeLa cell line. Because of their unique properties, Hela cells have become critical to medical research. They have been used to secure more than 17,000 patents, but neither she nor her family members were compensated.

In a similar case, blood cells from the spleen of a man named John Moore, taken as part of his treatment for leukemia, were used to create a patented cell line for fighting infection. Moore sued for his share of the profits generated by the patent, but his suit was dismissed by local, state and federal courts. As a result of these and similar cases, nearly all biobank consent forms now include a clause indicating that donations might be used to develop commercial products and that the donor has no claim on the proceeds.

Researchers can ill afford to undermine public trust in their work. In our sample we found that lack of trust in scientists and scientific research was the strongest predictor of unwillingness to donate to a biobank.

Those who ask you to donate some of yourself must remember that it is important not only to protect your privacy but also to ensure that your decision to do good for others does not violate your sense of what is good.

The “Proposed Privacy and Trust Principles” issued by the PMI in 2015 are a hopeful sign. They call for transparency about “how [participant] data will be used, accessed, and shared,” including “the types of studies for which the individual’s data may be used.” The PMI soon will be asking us to donate bits of ourselves, and if these principles are honored, they will go a long way toward building the trust that biobanks – and precision medicine – need to succeed.

The Conversation

Raymond G. De Vries, Co-Director, Center for Bioethics and Social Sciences in Medicine, University of Michigan and Tom Tomlinson, Chair Professor, Michigan State University

This article was originally published on The Conversation. Read the original article.


Testimony on Psychiatric PAD before the Canadian Senate Committee on Legal and Constitutional Affairs

The Canadian Parliament is debating a bill regulating physician aid in dying.  The deadline is early June 2016. On May 11, 2016, I testified before the Senate Committee on Legal and Constitutional Affairs, focusing on the policy aspects of psychiatric physician aid in dying.

I was one of three witnesses in the session.

Navigational guide:  My testimony begins at approximately 16:38 with a personal statement. Most of the hour is taken up by a Dr. Derryk Smith, a psychiatrist from Dignity in Dying Canada.  He is a forceful advocate of making available medically induced death to persons suffering from psychiatric disorders.

I provide a counterbalance to some of the assertions made by Smith in a closing set of comments at 17:26.

How worrisome is the ‘therapeutic misconception’?

For those interested in the debate over the therapeutic misconception, Paul Appelbaum wrote a critical commentary of our recent paper in Journal of Medical Ethics.  We published a response to his commentary here.  It is not easy to find our response at the journal’s website so we hope the above links will help the reader in evaluating the exchange.

The published exchange provides a glimpse into the very different ways in which people have approached this widely discussed phenomenon in research ethics.

Psychiatric Euthanasia: Too Few To Matter? Not so fast

Since the publication of our study on 66 cases of psychiatric euthanasia or assisted suicide (EAS) in the Netherlands, I have heard comments from people that the issue is of minor consequence given how few cases there are.  The relative numbers are indeed low. In the Netherlands in 2014, there were a total of about 5300 EAS cases, of which psychiatric cases were 41.

Bracketing for now arguments about the importance of each individual life regardless of number, it may be useful to consider this issue from a purely quantitative standpoint. This will require some speculations about numbers but I will try to stay with what is known as much as possible, focusing on the U.S.

Using per capita rates (rather than mortality rates) as a rough guide, there would be about 950 psychiatric EAS cases per year in the US using the current Dutch rates (US is 19x more populous; reporting rate in the Netherlands is about 80% or lower).  For a large country like US, that is a small number but it does not seem inconsequential that nearly a 1000 persons per year would receive EAS for psychiatric reasons in the US.

But the problem with dismissing psychiatric EAS based on current low numbers in the Netherlands is that it ignores three things: one, the tremendous potential for growth in numbers over the years; two, the large significance–quantitatively–of each false positive in terms of person-years lost; and three, the high likelihood of false positives given the broad and vague set of criteria for eligibility that are usually used (criteria which may be much less likely to be problematic in the terminal illness setting but extremely problematic to operationalize for psychiatric disorders–that is an issue for another discussion; here I focus on the numbers only).

In the US, there are almost 43,000 completed suicides per year.  For each completed suicide, there are about 25 suicide attempts.  So there are about 1 million suicide attempts per year. Over 90% of completed suicides are in persons with some serious psychiatric disorder. Most people who request psychiatric EAS have attempted suicide in the past (often multiple times)–this does not directly  help us in estimating how many people who attempt suicide might seek EAS, but we can make a rough, conservative assumption that about 1 in 10 persons who attempt suicide  would attempt to make use of legalized EAS.

I want to make clear that I do NOT mean that in fact there will immediately be that many people asking for EAS if it is legalized.  Because both the medical culture (physicians feeling uncomfortable with the practice–as in the Netherlands where 2/3 of MDs cannot conceive of aiding in psychiatric EAS) and lay culture (only 28% of the Dutch public approve of psychiatric EAS even in the paradigmatic case of refractory depression) are opposed to psychiatric EAS, even legalization will not immediately lead to high numbers. But in a country with a broken mental health care system such as ours, we probably should not underestimate the potential for the system to flow toward the path of least resistance.

Once the practice becomes established and accepted, there could be an increasing number of persons who apply, as is happening in Belgium and the Netherlands now. This number, even conservatively measured, could reach at least 100,000 persons per year in the U.S. based on above assumptions (i.e., 10% of all suicide attempts per year).

In addition, there will be people who desire to die who would not have attempted suicide. This number is impossible to guess but if you speak with any experienced psychiatrist, suicidal ideation (without attempts) in persons with serious psychiatric conditions is common.  I would imagine that given the large number of such patients, even if a tiny fraction sought EAS, the absolute numbers would be quite sizable.  But to be conservative, we will ignore this group since it is very difficult to estimate.

Thus, it is not unreasonable to assume that eventually the number of person who may ask for psychiatric EAS in the US, were it legalized, would over the years reach into six figures per year.

Only a minority of such patients would likely meet criteria for EAS, even under a liberal regime.  A longer discussion is necessary to argue this point but there are a variety of reasons to think this:  many patients change their minds, some may not be competent to make decisions, and most commonly many will, with support and treatment over time, be able to cope better which may in turn lead to improvements in their symptoms.  Still, a sizable minority might qualify for EAS.  Suppose 20% would truly meet criteria, and 80% would not–assuming perfect application of eligibility criteria.

The application of the criteria, if similar to the ones in the Netherlands, Belgium, and the ones proposed by the recent Canadian Parliament special committee, will not be easy in the psychiatric setting (‘grievous and irremediable’ condition, competent as measured by current medical practice, etc).  The criteria from the Netherlands are:

1. The attending physician has come to the conviction that the
request from the patient is voluntary and well considered.
2. The attending physician has come to the conviction that the
suffering of the patient is unbearable and without prospect of
3. The physician has informed the patient about his or her
situation and prospects.
4. There are no more reasonable alternatives for the patient.
5. The physician has consulted at least one other, independent
6. The physician has terminated the patient’s life or provided
assistance with suicide with due medical care and attention.

I have bolded the key substantive criteria having to do with competent decision-making, assessment of ‘unbearable suffering,’ and medical futility.  In case you are wondering if these broad criteria are further specified or operationalized to guide the physicians, the answer is no.  This is why there are disagreements in judgment.

We can explore what would happen if physicians’ judgments are 90% sensitive (pick of 9 of 10 cases of truly eligible persons) and 90% specific (eliminate 9 of 10 persons who are truly not eligible) in identifying persons who are eligible for EAS. Based on my experience conducting capacity evaluations and conducting several studies on how physicians make capacity determinations, this is a fairly optimistic estimate of physician accuracy.  Also, we already know that even in completed psychiatric EAS cases in the Netherlands, 90% reliability (i.e., agreement among physicians) is not achieved. Thus, the idea that the overall accuracy (sensitivity and specificity) can be 90% is probably too optimistic. Without reliability, we can’t have validity.  But let’s press on.

Under these assumptions, there will be about a 31% false positive rate.  As applied to our sample of 100,000 requestors, there will be 26,000 persons found to be eligible by physician judgment. But of those, 8000 will be false positives and would be incorrectly provided with EAS.

If we use instead a more realistic estimate of physician judgment accuracy–say, 80% for both, or even lower–we get the following results: if a physician says a request for psychiatric EAS meets all criteria, the chances that the person does not meet all criteria will be about 50%, i.e., a false positive rate of 50%.  For our sample of 100,000 requestors, this will result in 32,000 persons being judged to be eligible, of whom 16,000 per year would not be in fact eligible (false positives).  This would translate into about 320,000 person-years lost, using a conservative mean of 20 years lost per false positive.

For those who are skeptical of my 100,000 estimate of potential requestors of psychiatric EAS, you can instead use a lower estimate, say, of 1% of suicide attempters requesting EAS. Using that assumption, we have:

  • 3200 persons per year who would receive psychiatric EAS in US
  • 1600 of whom are false positives
  • Loss of 32,000 person-years due to false positives

Not an insignificant public health impact.












Euthanasia and assisted suicide (EAS) of psychiatric patients in the Netherlands

Although the original debates over legalization of assisted death (euthanasia or assisted suicide, or EAS) focused on the terminally ill, in some countries the practice has expanded to non-terminally ill patients, such as patients suffering from psychiatric disorders.

We recently studied 66 cases of psychiatric EAS from the Netherlands.  We examined the patients’ various psychiatric, medical, and social conditions; their histories (including treatment history, suicide attempts, treatment refusals); the physicians’ evaluation of the patients; and how the euthanasia review committees retrospectively reviewed the cases.

The study provides a relatively fine-grained, individual level picture of what is happening when patients suffering from psychiatric disorders are euthanised or given lethal doses of medications for ingestion under the Dutch system.  This is in contrast to the usual large scale population surveys connecting death registry data to physician self-reports that cannot tell us much about the practice of EAS at the individual level.

You can read the article here.  Paul Appelbaum has written an excellent editorial on the study.  You can also read coverage by New York Times and Reuters.  This issue is very much a live topic in Canada because their Parliament is currently debating how to regulate physician assisted death.  You can read a Canadian perspective on our study here.

What are the main findings?  You can of course read the paper for the numbers and the methods. But here I draw out some implications and themes.

My first surprise in doing this study was that despite the fact that the Dutch euthanasia committees (RTE) have been making anonymized case summaries of EAS patients public for years, no one (as far as we can tell) has published an in depth analysis using those documents.  I think that is significant.

The biggest surprise was that people who received EAS didn’t match the usual picture of the paradigm case of psychiatric EAS.  The debates over psychiatric EAS tend to focus on a particular picture: A patient with long history of severe treatment resistant depression who, after insightful assessment of her situation, exercises her autonomy to choose death and she receives euthanasia surrounded by a family who supports her.

But the reality is a bit more complicated.

First, there is a wide range of psychiatric conditions represented. 26% had some form of psychosis, for instance—some of them lifelong schizophrenia. Others had cognitive impairment.  There were cases of autism spectrum disorder, eating disorders, as well as an otherwise healthy woman who received EAS from ‘prolonged grief’ over her husband’s death a year prior to her EAS.

Second, in a majority of cases, what was notable in these patients was not their psychiatric conditions per se (for a psychiatrist, the patients will seem familiar) but that they tended to be persons who have reduced ability to cope—i.e., people with personality difficulties, social isolation, or feelings of loneliness.  One disappointing aspect of the reports we read was that they generally did not provide clear explanations about why a request for EAS by such patients is a rational, autonomous act rather than an act driven by psychopathology.  That is, the distinction is repeatedly invoked, but there is no further explanation than the pronouncement of the physicians.  For example, most patients had suicide attempt histories and some even attempted suicide during the clinical episode that led to their EAS. I had expected to see the physicians’ explanations for distinguishing between ‘suicidal due to a psychiatric condition’ and more ‘rational’ suicide to be more substantial than was contained in the reports.

Third, another notable finding is that the Dutch practice of psychiatric EAS seems to be more liberal than the practice Guidelines promulgated by the main Dutch psychiatric organization (which is in fact rather supportive of the practice).  For example, the actual practice (with approval by the review committee) does not have to involve any truly independent psychiatric input. But the psychiatric society’s Guidelines recommend not only an independent psychiatrist in each case but a subspecialist who is an expert on the disorder (for example, an eating disorder specialist).  That is an interesting discrepancy between the views of the Dutch psychiatric profession and how the laws are implemented.

In fact, given that the Dutch euthanasia committees generally do not have psychiatrists (or at least not until recently), it appears that the following is possible (and indeed occurs): a psychiatric patient could be euthanized without any independent expert input or oversight, and then the official review of the completed EAS is conducted with no psychiatric expert input.  That is a lot of trust in the judgment of the treating psychiatrist, or even a general practitioner.

Fourth, the Dutch system relies tremendously on physician judgment to implement fairly broad and vague rules and this is very problematic for psychiatric cases, even when experts are involved.

Now, for most terminal illnesses, we can be fairly sure what the eventual outcome for the patient is.  There’s not a lot of physician discretion involved in most situations.

But for psychiatric conditions, physicians must make tricky clinical determinations (for example, when patients refuse psychiatric treatment and instead want EAS, how should the doctor proceed?) without the help of a robust evidence base.  There is no evidence base to operationalize “unbearable suffering.” There are no prospective studies of decision-making capacity in persons seeking EAS for psychiatric reasons. And the prognosis of patients labeled as ‘treatment-resistant depression’ varies considerably, depending on the population and the kind of treatments they receive. We provide references to these points in the paper.

Thus, we found that many patients had been previously denied EAS, and even when it is granted, not infrequently there is disagreement among physicians as to whether the legal criteria (“unbearable suffering,” “hopeless” prospects, “voluntary and well-considered request,” among others) are met for EAS.  Most of the time the disagreement is not resolved before the person receives EAS–as that is not required by law (this point is presumed to be so well understood that the euthanasia review committees usually do not even comment on the disagreement). And those who are refused EAS eventually find doctors and consultants who see things differently–usually at a mobile End of Life Clinic whose sole purpose is to provide EAS.

Finally, we note in the paper–as does the editorialist Paul Appelbaum–various limitations to our study. Primarily, they are related to the nature of the source documents: case summaries drafted by the euthanasia review committees using the written reports (and rarely oral testimony) of the physicians involved.  They are not detailed medical notes, and they are certainly a form of ‘self-report’ since the physicians are describing how they complied with the law.  The limitations of such source documents should be obvious. Two observations are worth making on this. First, even with such limitations, it was not difficult to find rather concerning features of the cases (a testament to the integrity and transparency of the Dutch euthanasia committee). So despite the limitations, our study provides the most systematic and rich description of the practice of psychiatric EAS to date.  Second, to the extent that one might be tempted to discount our findings, one should realize the implication of such an assertion: despite decades of this controversial practice, there seems to be so little data to reassure us that all is well.


Waiving the requirement for informed consent?

When is it permissible to waive or alter the usual rules of informed consent in human subjects research?  It is a testament to the success of the modern system of regulating research with humans that such a question will seem odd, even disturbing, to many.  Isn’t informed consent always necessary?

Actually, our current regulations do allow waivers and alterations of informed consent but it is important to know what this means.  It means waiver or alteration of the specific regulatory requirements, rather than of the general ethical concept itself.  And such waivers or alterations must meet strict criteria. The regulations state that:

An IRB may approve a consent procedure which does not include, or which alters, some or all of the elements of informed consent set forth in this section, or waive the requirements to obtain informed consent provided the IRB finds and documents that:

 (1) The research involves no more than minimal risk to the subjects;

 (2) The waiver or alteration will not adversely affect the rights and welfare of the subjects;

 (3) The research could not practicably be carried out without the waiver or alteration; and

 (4) Whenever appropriate, the subjects will be provided with additional pertinent information after participation.

Until recently, there has been relatively little discussion about how to apply these criteria. Perhaps this is because most of the time the waivers were used for medical records research which most people do not either know about or would agree to anyway. But with the increasing interest in comparative effectiveness research, there has been a steady rise in calls for allowing waivers in settings that have not usually seen such waivers, namely, randomized clinical trials.

My colleague Frank Miller and I have been somewhat skeptical of this trend.  We just published a new paper on this topic.  In it, we use the principle of respect for persons as a way interpreting these criteria for waiver or alteration of informed consent.


Battles of terminology in bioethics

Back in 2008, Michigan voters were asked to approve the use of embryos in stem cell research. The names of the two opposing advocacy groups give a flavor for the strategic maneuvering by both sides: the opposition group called itself the Michigan Citizens Against Unrestricted Science & Experimentation and the pro-research group called itself CureMichigan.

This is of course just one example of many we can name where those on opposite sides try to influence the debate by labeling it in their favor.  (I am going to be lazy and not put quotes around the terms as I should in what follows).  Pro-choice vs pro-life. Research participants vs research subjects.  Patients vs clients (or, as in UK, service users).  And of course physician assisted suicide vs physician aid in dying (among others, the latest being simply ‘hastening death‘).  I’m trying very hard not to use the term _olitical _orrectness as that sets people off in different directions too.

Two things are certain about these battles. One, at some meeting or other in which one of the above issues is being debated, someone will insist on a certain terminology because the opposing party’s term is ‘offensive.’  Two, once the discussion about terminology starts, there is rarely a resolution, only occasional cowed acquiescence and more often many rolling of the eyes. (I must admit I have done my share of eye rolling.  I can happily report, however, that in my experience the tendency to eye roll seems to be one of temperament rather than ideology, as people on all sides seem to engage in it).

I think the following are true and widely accepted:

  1. Terms used in bioethics discussions and debates are often, or even usually, not neutral.
  2. Not all people, even on the same side of the debate, insist on terminological correctness.  This is true in assisted death debates in some places where, for example, in Belgium and Netherlands, assisted suicide and euthanasia are terms built into the laws.  In contrast, US laws permitting the practice usually reject the term assisted suicide.

The following premise may or may not be acceptable to all.

3.  An ethical issue should be something that should be resolved through, well…, reason, and not simply by asserting and manipulating power and influence.  The final terminology should be the result of a reasoned debate, not a means to wield power.

To insist on a universal use of one’s own preferred term while the debate is in progress therefore seems unreasonable (if you accept 3) since it is asking one’s opponent to adopt a position that is still being debated.  In fact, it is unclear, if you accept 3, that insisting on neutral (people who have not taken sides yet) parties using the preferred terms is a reasonable request either.

But doesn’t this ‘privilege’ the status quo position?  Not necessarily.

The most fair conclusion, it seems to me, is that we should respect the use of terms of each side’s own choosing, to the same extent that we should respect each side’s attempts to explain and persuade.  To insist that the other side, or even neutral parties, start using one’s own preferred term is to put the conclusion ahead of the premise. Or as logicians put it, it is begging the question.

Some implications:

  1. Academic journals should refrain from imposing on authors a specific terminology in an ongoing debate. It would be an unnecessary ideological intrusion to insist on a particular terminology while the debate is in progress.  For example, editors should not insist on either “research subject” or “research participant”–they should let the authors choose.
  2. It does not help to say that the other side’s terms are ‘offensive.’ This assertion is true only if the other side is wrong. But that is precisely what is being debated. Practically speaking, such a claim should be supported by an argument rather than simply insisted on; otherwise, it is a form of intellectual bullying.  Academics’ opinions and views are regarded with special weight because they are seen as objective arbiters (at least to some degree).  The duty to refrain from trying to win a debate by insisting on a more friendly terminology is therefore especially pertinent for academics.