How about personally optimized treatment?

May 6, 2019

Pär SegerdahlIt is well known that patients who are asked to participate in cancer trials are tempted by the therapeutic misconception. They believe they are offered a newer and better treatment, when in fact it is about research into an untested treatment. When researchers use genetic tests to develop personalized oncology, even more misconceptions can arise. I will soon explain. But first, what is personalized cancer treatment? Here is an example.

Patients whose tumor is to be operated may undergo preparatory radiation or chemotherapy. Since the preparatory therapy has severe side effects, one wants to avoid giving it to patients whose tumors do not respond to it. The challenge is to distinguish patients who respond to treatment from patients who do not. This is to be accomplished through, among other things, genetic tests on the tumor cells. If this works, you can develop personalized cancer treatment. Patients with the “right” tumor cell genetics receive the preparatory therapy, while patients who, according to the genetic tests, only get the side effects, with no effect on tumor growth, do not receive the therapy.

What are the misconceptions that can arise in patients who are asked to participate in research on personalized cancer treatment? Here are some examples.

Patients who are told that the researchers will do genetic tests can feel a genetic responsibility to participate, considering their children and grandchildren. They believe the test results may be relevant to close relatives, who may have the same disease genes. However, the tests are done on mutated tumor cells and therefore say nothing about inherited cancer risk. A sense of genetic responsibility can thus be triggered by the word “genetics” and create a genetic misconception of research in personalized oncology.

Other misconceptions have to do with the positive language used to describe personalized medicine. One talks about personally “optimized” treatments, about “tailored” treatments, about treatments that are adapted “to the individual.” This language use is not intended to mislead, but it is easy to see how words such as “optimization” can cause patients to believe that research participation means special treatment benefit.

The biggest challenge is perhaps to explain the research purpose behind the positive language. The aim is to be able in the future to distinguish between patients, to “stratify” them, as it less positively is called. Personally optimized care actually means that some patients do not receive certain treatments. This is, of course, reasonable if genetic tests can show that they have no benefit from the treatments but only get the side effects. However, what do cancer patients themselves say about stratified cancer treatment, where some patients are identified as non-responders and therefore are not offered the same treatment as other patients? Finally, do participants understand that “tailored treatment” is a future goal of the study and not something they are offered to try?

Communication with patients recruited for studies in personalized oncology faces many challenges, as patients are tempted by even more misconceptions than just the well-known therapeutic misconception.

Do you want to know more? Read the German study that inspired this blog post.

Pär Segerdahl

Perry, J., Wöhlke, S., Heßling, A.C., Schicktanz, S. 2017. Why take part in personalised cancer research? Patients’ genetic misconception, genetic responsibility and incomprehension of stratification—an empirical‐ethical examination. Eur J Cancer Care. https://doi.org/10.1111/ecc.12563

This post in Swedish

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Direct-to-consumer genetic testing: empowering people to hurt themselves?

December 4, 2013

There are two tempting pictures of the human. One is that we (ideally) are autonomous individuals who make rational choices on the basis of information. The other picture is that our individuality is coded in our DNA.

These pictures work in tandem in the marketing of direct-to-consumer genetic testing. The website of the personal genomics company, 23andMe, features their DNA “spit kit.” On the half-open lid you can read: Welcome to you.

That’s the DNA picture: Your DNA contains the information about you. For 99 dollars and a saliva sample you’ll get to know who you are.

If you click Order now, you encounter the other picture: Knowledge is power. By buying this product, you’ll be empowered to better manage your health and wellness. You’ll get information about diseases you risk developing and diseases you are less likely developing, and can plan your life accordingly.

That’s the autonomy picture: You are the driver of your life. For 99 dollars and a saliva sample, you are empowered as rational decision-maker about your health.

The combination of the two pictures is a powerful marketing campaign that can be followed on YouTube.

The US Food and Drug Administration (FDA) recently sent a warning letter to 23andMe, urging them to immediately stop marketing the test. The device isn’t just any commercial product, but is to be seen as medical technology. This implies certain quality standards:

  • “…we still do not have any assurance that the firm has analytically or clinically validated the PGS for its intended uses…”

FDA also expresses concern about public health consequences if the test doesn’t work reliably. A false positive risk assessment for breast or ovarian cancer “could lead a patient to undergo prophylactic surgery, chemoprevention, intensive screening, or other morbidity-inducing actions, while a false negative could result in a failure to recognize an actual risk that may exist.”

Another concern is that patients who receive assessments of their personal drug responses may begin to self-manage their doses or abandon their therapies.

Genetic tests will no doubt play significant roles in the future. But genetic risk information is tremendously complex and its predictive value difficult to assess. The danger is that the deceptively simple marketing rhetoric of empowering individuals to take charge of their lives currently rather might empower people to hurt themselves.

The Swedish Foundation for Humanities and Social Sciences decided this autumn to support a joint European research program on genetic risk information. The program is led by Mats G. Hansson at CRB. Click the link below for a summary of the program:

FDA’s warning letter to 23andMe underlines the timeliness of the new program. More on this in the future!

Pär Segerdahl

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Being human; representing life

September 10, 2013

A new article reconsiders Henrietta Lacks and the immortal HeLa cells that were obtained from her rare cancer tumor in the 1950s; cells that still replicate and are used in biomedical laboratories all over the world:

The article is written by Anna Lydia Svalastog and Lucia Martinelli, both members of the Culture, Health and Bioethics network at CRB.

There is a lot going on in the article, making it difficult to summarize. As I understand it, though, the article focuses on two fields of tension when biological samples from humans are used in biomedical research – tensions between:

  1. being human; and representing biological life,
  2. the value of the one; and the value of the many.

Both fields of tension intersect in the case of Henrietta Lacks:

  1. Henrietta Lacks was a human being, existing in a human world; but HeLa cells function as “bio-objects” representing biological life.
  2. Henrietta Lacks was one unique individual; but HeLa cells have come to represent humanity.

These tensions highlight the interchange between research and society. We exist as human beings; but by donating samples to research, we also contribute to representing biological life. We are unique individuals; but through our samples, we also contribute to representing what is general.

The authors cite the European biobank infrastructure, BBMRI, as an approach to governance and ownership of knowledge and property that begins to address these tensions in interesting, new ways. The article also speaks in favour of interdisciplinary collaboration between the life sciences, the social sciences, and the humanities, to understand the fields of tension that arise when individual human beings contribute to medical research.

Pär Segerdahl

Part of international collaborations - the Ethics Blog


Commercial gene tests and incidental findings

October 25, 2012

I read Arthur Caplan’s criticism of the personalized gene tests that some companies insist we must buy to gain control over our future health. I could not help wondering if his criticism is applicable also to the idea that biobanks should inform research participants about incidental findings about their genes.

Caplan rejects the crystal ball view of genetic information that is utilized in the marketing for commercial gene tests: the image that genetic information is uniquely predictive about YOUR future health.

The crystal ball image is a prejudice. It is a gene myth that makes people believe they MUST get genetic information to control their future health. It is a myth that makes people think they have a RIGHT to look into the crystal ball, now that this uniquely powerful instrument is available.

But disease risk is the result of complex interactions between genes and environment, and “no one knows how a single person’s lifestyle, upbringing and environment interacts with their particular genes to create risks,” Caplan writes.

If this is true and genetic information in abstraction is far from predictive, then I cannot avoid worrying about how the crystal ball image shapes also the ethical discussion about incidental findings in genomic biobank research.

In this discussion, accidentally discovered individual genetic variation is sometimes described as a good that participants have a right to be informed about, in return for the biological material they donate to the biobank.

If Caplan is right and such information typically is not worth the money, how can it be a good that participants have a right to receive such information from the biobank in return for their sample?

Do well-meant ethical arguments sometimes resemble unethical marketing campaigns?

Pär Segerdahl

Approaching future issues - the Ethics Blog


How unspecific is broad consent?

September 13, 2012

In response to an informative article on personalized medicine and biobanking in Nature Biotechnology, a recent letter to the Editor defends broad consent for biobanking.

The three letter writers emphasize the patient and donor perspective:

  • “…patient donors actually express concern that study-specific consent can be burdensome and impede research.”

Given these donors’ desire to give so-called broad consent, I want to highlight two problematic aspects of the distinction between specific and broad consent.

The first is that the word “broad” consent may give rise to the impression that the consent is so general and vague that it cannot be seen as informed consent to anything specific at all. But broad consent is not “broad” in such an absolute sense, akin to vagueness. It is “broad” only in a relative sense: in relation to the historically more prevalent case of consenting to individual research projects.

The distinction between specific and broad consent is a distinction between two ways of being specific. One of these ways of being specific dominated the scene first. It therefore functioned as a linguistic standard. The other way of being specific had to put up with being called “broad.”

Specific consent, then, is specific only in a specific sense: one that is historically conditioned and changeable. It is not the golden standard of exactitude. Consent can therefore be “broad” without being vague.

The second problematic aspect is that when people donate samples to biobanks, the exact nature of the individual research projects that might use their samples is less relevant to them than when they consent to invasive procedures in clinical trials.

The risks are minimal in biobank research. Donors therefore look more to the practical utility of the research than to the research itself. Forcing them to consider the purposes and questions and procedures of individual research projects is forcing them to attend to a level of medical research that is less relevant to them as donors.

In short, a historically and linguistically insensitive demand for “specific consent” in biobanking may hinder donors from giving the kind of specific consent they authentically want to give in this new but more and more prevalent context.

Pär Segerdahl

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Collection of papers brings out neglected aspect of ethics

April 26, 2012

If you wrestle with ethical and legal difficulties associated with genetic science, a recent virtual issue of the Hastings Center Report could be good to think with.

The issue collects earlier material on ethics and genetics. There are pieces about the perils of genetic-specific legislation; about the difficulties of understanding behavioral genetics; about the prospects of personalized medicine; about the meaning of transhumanism; and much else.

Reading the virtual collection, it strikes me that our ethical difficulties surprisingly seldom are of a purely evaluative kind, or about what is morally right or wrong, or about what we ethically should or should not do.

Our ethical challenges are more typically about thinking well; about understanding complex facts properly; about avoiding tempting oversimplifications in our descriptions of reality.

In short, our ethical challenges are very much about facing reality well.

The philosopher Bernard Williams spoke of thick ethical concepts: notions like “courage” that seem to have both evaluative and descriptive content.

I am inclined to say that ethics is “thick” in this sense. Ethics is more often than not about describing reality justly. Ethical challenges are surprisingly often about coming to terms with oversimplified descriptions that prompt premature normative conclusions.

Just consider these two tempting oversimplifications of genetics, which produce an abundance of normative and political conclusions:

  1. The mistaken assumption that if the main source of variation is not genetic, it will be fairly easy to make environmental interventions.
  2. The mistaken assumption that if the primary source of variation is genetic, environmental interventions will be useless.

These assumptions are discussed in Erik Parens’ paper about why talking about behavioral genetics is important and difficult (on page 13).

Even though it is not its purpose, the virtual collection of papers on genetics makes it conspicuous how often our ethical challenges are of a descriptive kind.

Pär Segerdahl

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Introspective genomics and the significance of one

March 28, 2012

As a philosopher, I am familiar with the image of the solitary thinker who studies the human mind though introspective study of his own. A recent article in the journal Cell reminds me of that image, but in unexpected “genomic” guise.

To achieve statistical significance, medical researchers typically engage large numbers of research subjects. The paper in Cell, however, has only one research subject: the lead author of the paper, Michael Snyder.

Snyder and colleagues studied how his body functioned molecularly and genetically over a 14-month period. Samples from Snyder were taken on 20 separate occasions. A personal “omics profile” was made by integrating information about his genomic sequence with other molecular patterns gathered from the samples, as these patterns changed over time.

Early results indicated that Snyder was genetically disposed to type 2 diabetes. Strangely enough, the disease began to develop during the course of the study. Snyder could follow in detail how two virus infections and the diabetes developed molecularly and genetically in his body.

Snyder changed his life style to handle his diabetes. When he informed his life-insurance company about the disease, however, his premiums became dramatically more expensive.

The introspective paper illustrates the potential usefulness, as well as the risks, of what has been dubbed “personalized medicine.” Here I want speculate, though, on how this new paradigm in medicine challenges scientific and intellectual ideals.

When philosophers introspectively studied the human mind, they took for granted that what they found within themselves was shared by all humans. The general could be found completely instantiated in the particular.

The particular was for philosophers no more than a mirror of the general. What they saw in the mirror was not the individual mirror (it was intellectually invisible). What they saw in the mirror was a reflection of the general (and only the general was intellectually visible).

That simple image of the relation between the particular and the general was discarded with Darwin’s theory of the origin of species. A species has no essence shared by all individuals. Therefore, to achieve scientific generality about what is human, you cannot rely on one human subject only. You need many subjects, and statistics, to achieve intellectual vison of general facts.

A noteworthy feature of the paper under discussion is that we seem partly to have returned to the era of introspective research. We return to it, however, without the discarded notion of the particular as mirror of the general.

New molecular techniques seem to open up for study of what previously were simply individual cases without significance in themselves. For personalized medicine, each subject unfolds as a universe; as a world full of significant processes.

By studying the “genomic universe” of one person and following it over a period of time time, Snyder and colleagues could discern processes that would have been invisible if they had superimposed data from several distinct research subjects.

This new significance of the particular is fascinating and novel from an intellectual perspective. Has the traditional contempt for the particular case been overcome in personalized medicine?

Speaking personally as a philosopher, I cannot avoid seeing this aspect of personalized medicine as congenial with certain philosophical tendencies.

I am thinking of tendencies to investigate (and compare) particular cases without magnifying them on a wall of philosophical abstraction, as if only the general was intellectually visible. I am thinking of serious attempts to overcome the traditional contempt for the particular case.

We seem to have arrived at a new conception of one and many; at a new conception of the particular case as visible and worthy of study.

Pär Segerdahl

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