A blog from the Centre for Research Ethics & Bioethics (CRB)

Tag: empirical ethics (Page 1 of 3)

We do not know if cancer patients receive better treatment by participating in clinical trials

How do we know? That is the recurring question in a scientific culture. Do we have support for what we claim or is it just an opinion? Is there evidence?

The development of new cancer treatments provides many examples of the recurring question. The pharmaceutical company would like to be able to claim that the new treatment is more effective than existing alternatives and that the dosages recommended give good effect without excessive side effects. However, first we must answer the question, How do we know?

It is not enough to ask the question just once. We must repeat the question for every aspect of the treatment. Any claim on efficacy, side effects and dosages must be supported by answers to the question. How do we arrive at these answers? How do we check that it is not mere opinions? Through clinical trials conducted with cancer patients who agree to be research subjects.

A new research ethical study shows, however, that an ethically sensitive claim is often repeated in cancer research, without first asking and answering the question “How do we know?” in a satisfying way. Which claim? It is the claim that cancer patients are better off as participants in clinical trials than as regular patients who receive standard treatment. The claim is ethically sensitive because it can motivate patients to participate in trials.

In a large interview study, the authors first investigated whether the claim occurs among physicians and nurses working with clinical trials. Then, through a systematic literature review, they examined whether there is scientific evidence supporting the claim. The startling answer to the questions is: Yes, the claim is common. No, the claim lacks support.

Patients recruited for clinical trials are thus at risk of being misled by the common but unfounded opinion that research participation means better treatment. Of course, it is conceivable that patients who participate in trials will at least get indirect positive effects through increased attention: better follow-ups, more sample taking, closer contacts with physicians and nurses. However, indirect positive effects on outcomes should have been visible in the literature study. Regarding subjective effects, it is pointed out in the article that such effects will vary with the patients’ conditions and preferences. It is not always positive for a very sick patient to provide the many samples that research needs. In general, then, we cannot claim that research participation has indirect positive effects.

This is how the authors, including Tove Godskesen and Stefan Eriksson at CRB, reason in the clearly written article in BMC Cancer: Are cancer patients better off if they participate in clinical trials? A mixed methods study. Tove Godskesen was the leader of the study.

An ethically important conclusion drawn in the article is the following. If we suggest to patients who consent to participation in trials that research means better treatment, then they receive misleading information. Instead, altruistic research participation should be emphasized. By participating in studies, patients support new knowledge that can enable better cancer treatments for future patients.

The article examines a case where the question “How do we know?” has the answer, “We do not know, it is just an opinion.” Then at least we know that we do not know! How do we know? Through the studies presented in the article – read it!

Pär Segerdahl

Written by…

Pär Segerdahl, Associate Professor at the Centre for Research Ethics & Bioethics and editor of the Ethics Blog.

Zandra Engelbak Nielsen, Stefan Eriksson, Laurine Bente Schram Harsløf, Suzanne Petri, Gert Helgesson, Margrete Mangset and Tove E. Godskesen. Are cancer patients better off if they participate in clinical trials? A mixed methods study. BMC Cancer 20, 401 (2020). https://doi.org/10.1186/s12885-020-06916-z

We have a clinical perspective

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Clinical cancer trials convey a culture of hope

Activities that we may want to keep apart often overlap. An example is cancer research and care. Clinical cancer centers often conduct research and recruit patients as research participants. Such research is important if we want to offer future patients better cancer treatments. However, does this also apply to patients participating in studies? Are they offered better care as research participants?

Together with five co-authors, Tove Godskesen recently published an interview study with clinical physicians carrying out clinical cancer trials in Sweden, Denmark and Finland. The questions were about what ethical challenges the physicians perceived in the care of patients who participate in clinical trials. Does the overlap of care and research create ethical challenges? Although several physicians mentioned challenges, there were tendencies to downplay ethical difficulties and to associate the overlap between research and care with care benefit.

Tove Godskesen sees indications of a culture of hope in clinical cancer trials, where patients and physicians reinforce the image of research participation as an opportunity to access the latest therapy. However, uncertain patients can challenge the picture by asking the physician to affirm that the experimental treatment is as good as the standard treatment. You do not know that. That is why you are doing research!

The authors do not make any claims about whether a culture of hope in clinical cancer trials is good or not. However, they believe that the culture needs to become visible and discussed openly. So that the ethical challenges when care and research overlap do not disappear from sight.

The culture of hope has several aspects that you can read more about in the article. For example, the attitude that it is better to avoid giving patients bad news.

Pär Segerdahl

Written by…

Pär Segerdahl, Associate Professor at the Centre for Research Ethics & Bioethics and editor of the Ethics Blog.

Tove E Godskesen, Suzanne Petri, Stefan Eriksson, Arja Halkoaho, Margrete Mangset and Zandra E Nielsen. The culture of hope and ethical challenges in clinical trials: A qualitative study of oncologists and haematologists’ views. Clinical Ethics. First Published December 30, 2019. https://doi.org/10.1177/1477750919897379

We have a clinical perspective

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People want to be able to influence the risk

Pär SegerdahlWe need to do research to know what people think is important in genetic risk information. What they prefer to know. But how do we find out? One way is to ask people to answer questionnaires.

One problem with questionnaires is that they ask one thing at a time. Do you prefer a hotel room with a sea view when you are on vacation? You probably answer yes. But do you prefer the sea view even if the room is above the disco, or costs 500 EUR per night? If you only ask one thing at a time, then it is difficult to know how different factors interact, how important they are relative to each other.

One way to get past this limitation is to ask people to choose between two alternatives, where the alternatives have several different attributes.

  • Hotel room A: (1) View: sea (2) Price: 200 EUR per night (3) Distance to the center: 30 minutes walk (4) Sound level: high.
  • Hotel room B: (1) View: parking (2) Price: 100 EUR per night (3) Distance to the center: 40 minutes bus ride (4) Sound level: low.

Which room do you choose, A or B? The choice tasks are repeated while the attributes are varied systematically. In this way, one can learn more about what people prefer, than through a regular questionnaire. One can see how different attributes interact and which attributes are more important than others are. One can also calculate how much more important an attribute is over another.

The same kind of study can be done about genetic risk information instead of hotel rooms. Jennifer Viberg Johansson at CRB recently did such a study. Four attributes of the risk information were varied in the choice tasks:

  • (1) Type of disease (2) Probability of developing disease (3) Preventive opportunities (4) Effectiveness of the preventive measure.

Which of the attributes was most important to the people who participated in the study? How much more important was it?

It turned out that the most important attribute was the effectiveness of the preventive measure. If the information contained an effective preventive measure, the respondents clearly preferred that information. The effectiveness of the preventive measure was twice as important to know, compared to the probability of developing the disease.

Apparently, it is important for people to be able to influence the risk. One conclusion in the study is that when risk information says that there is an effective preventive measure, then risk communication can focus more on the preventive measure than on the probability of developing disease.

The method is called, “Discrete Choice Experiment.” If you want to look more closely at the method and get more results, read Jennifer Viberg Johansson’s article in Genetics in Medicine.

Pär Segerdahl

Viberg Johansson, J., Langenskiöld, S., Segerdahl, P., Hansson, M.G., Hösterey Ugander, U., Gummesson, A., Veldwijk, J. Research participants’ preferences for receiving genetic risk information: a discrete choice experiment. Genetics in Medicine, 2019

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ethics needs empirical input - the ethics blog

How about personally optimized treatment?

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

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We care about communication - the Ethics Blog

Thesis on reproductive ethics

Pär SegerdahlOn Thursday, February 28, Amal Matar defends her thesis in the field of reproductive ethics.

As genetic tests become cheaper and more reliable, the potential use of genetic tests also expands. One use could be offering preconception genetic screening to entire populations. Prospective parents could find out if they are carriers of the same recessive autosomal genetic condition, and could plan future pregnancies. Carriers of such genetic conditions can be healthy, but if both parents have the same predisposition, the risk is 25 percent that their child will have the disease.

Preconception genetic screening is not implemented in Sweden. Would it be possible to do so in the future? What would the ethical and social implications be? Is it likely that preconception genetic screening will be implemented in Sweden? These are some of the questions that Amal Matar examines in her thesis.

Amal Matar’s interviews with Swedish healthcare professionals and policymaking experts indicate that preconception genetic screening will not be implemented in Sweden. The interviewees expressed the opinion that such screening would not satisfy any medical need, would threaten important values ​​in Swedish society and in the healthcare system, and require excessive resources.

Amal Matar defends her thesis in the Uppsala University Main Building (Biskopsgatan 3), room IV, on Thursday, February 28 at 13:00. You find an earlier interview with Amal Matar here. If you want to read the thesis, you find a link below.

Pär Segerdahl

Matar, Amal. 2019. Considering a Baby? Responsible Screening for the Future. Uppsala: Acta Universitatis Upsaliensis

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Approaching future issues - the Ethics Blog

Ask the patients about the benefits and the risks

Pär SegerdahlAlmost no medications are without risks of side effects. When new drugs are approved, decision makers must balance risks and benefits. To make the balancing, they use results from clinical trials where the drugs are tested on patients to determine (among other things) efficacy and side effects.

But how do you balance risks and benefits? Is the balancing completely objective, so that all that is needed is results from clinical trials? Or can risks and benefits be valued differently?

It has been noted that decision makers can value risks and benefits differently from patients. Therefore, results merely from clinical trials do not suffice. Decision makers also need to understand how the patients themselves value the risks and the benefits associated with treatments of their disease. The patients need to be asked about their preferences.

Karin Schölin Bywall is a PhD student at CRB. She plans to carry out preference studies with patients suffering from rheumatoid arthritis. The task is complex, since risks and benefits are multidimensional. Rheumatoid arthritis is a chronic disease with several symptoms, such as pain, stiffness, fatigue, fever, weakness, deformity, malaise, weight loss and depression. Medications can be variously effective on different symptoms, while they can have a range of side effects. Which positive effect on which symptom is sufficiently important for the patients to outweigh a certain level of one of the side effects?

Many patients naturally want the drug to enable them to work, despite the disease. However, if the pain is relieved enough to enable carrying out the work, while the medicine has as a side effect such fatigue that the patient cannot get out of bed, then the desired benefit is not provided.

To prepare her preference study, Karin Schölin Bywall decided to approach the patient group immediately. From the very beginning, she wanted to engage the patients in her research, by interviewing them about how they perceive participating in preference studies on new drugs against rheumatoid arthritis.

The patients stated that they saw it as important to be involved in regulatory decisions about new treatments of their disease. So that decision makers understand the patients’ own experiences of the benefits and risks that such drugs may have, and what the benefits and risks mean in practice, in the daily life of a rheumatic.

Results from the interviews are reported in the journal, The Patient – Patient-Centered Outcomes Research. The article emphasizes that preference studies can lead to drugs that the patient group is more motivated to take according to the physician’s instructions, which can improve clinical outcomes in the patients. The patients further stated that as participants in preference studies they want good information about how the drug functions, about how the study will be used by decision makers, and about where in the decision-making process the study will be used.

Feedback from patients is likely to become increasingly important in future decisions on medical products.

Pär Segerdahl

Schölin Bywall, K.; Veldwijk, J.; Hansson, M. G.; Kihlbom, U. “Patient Perspectives on the Value of Patient Preference Information in Regulatory Decision Making: A Qualitative Study in Swedish Patients with Rheumatoid Arthritis.” The Patient – Patient-Centered Outcomes Research, 2018. DOI: 10.1007/s40271-018-0344-2

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Dissertation on the decision not to resuscitate

Pär SegerdahlSince the beginning of this blog, I have had the opportunity to write about Mona Pettersson’s research, which deals with decisions in cancer care not to resuscitate terminally ill patients through cardiopulmonary resuscitation. The physician makes the decision, if the patient has a too bad prognosis and is too weak to survive the treatment with good quality of life. Or if the patient has expressed a desire to not receive the treatment.

The latest post I published is from August this year: Ethical competence for the decision not to resuscitate. Since then, Mona Pettersson has not only published another article, but also defended her dissertation. In four sub-studies, she examines nurses and physicians’ experiences of the decision not to resuscitate. Among other things, she investigates their understanding of ethical competence as it relates to the decision, as well as what aspects of the decision they consider most important.

If you want to read the entire work, download the dissertation. You can also read more about Mona Pettersson in this Profile.

Pär Segerdahl

Pettersson, M. 2018. COMPETENCE AND COMMUNICATION. Do Not Resuscitate Decisions in Cancer Care. Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine 1499. 62 pp. Uppsala: Acta Universitatis Upsaliensis. ISBN 978-91-513-0459-5.

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We have a clinical perspective : www.ethicsblog.crb.uu.se

Patients find misleading information on the internet

Pär SegerdahlIn phase 1 clinical studies of substances that might possibly be used to treat cancer in the future, cancer patients are recruited as research participants. These patients almost always have advanced cancer that no longer responds to the standard treatment.

That research participation would affect the cancer is unlikely. The purpose of a phase 1 study is to determine safe dosage range and to investigate side effects and other safety issues. This will then enable proceeding to investigating the effectiveness of the substance on specific forms of cancer, but with other research participants.

Given that patients often seek online information on clinical trials, Tove Godskesen, Josepine Fernow and Stefan Eriksson wanted to investigate the quality of the information that currently is available on the internet about phase 1 clinical cancer trials in Sweden, Denmark and Norway.

The results they report in the European Journal of Cancer Care are quite alarming. The most serious problem, as I understand it, is that the information conceals risks of serious side effects, and in various ways suggests possible positive treatment outcomes. This lack of accurate language is serious. We are dealing with severely ill patients who easily entertain unrealistic hopes for new treatment options.

To give a picture of the problem, I would like to give a few examples of typical phrases that Godskesen, Fernow and Eriksson found in the information on the internet, as well as their suggestions for more adequate wordings. Noticing the contrast between the linguistic usages is instructive.

One problem is that the information speaks of treatment, even though it is about research participation. Instead of writing “If you are interested in the treatment,” you could write “If you want to participate in the research.” Rather than writing “Patients will be treated with X,” you could write “Participants will be given X.”

The substance being tested is sometimes described as a medicine or therapy. Instead, you can write “You will get a substance called X.”

Another problem is that research participation is described as an advantage and opportunity for the cancer patient. Instead of writing “An advantage of study participation is that…,” one could write “The study might lead to better cancer treatments for future patients.” Rather than writing “This treatment could be an opportunity for you,” which is extremely misleading in phase 1 clinical cancer trials, one could more accurately say, “You can participate in this study.”

The authors also tested the readability of the texts they found on the internet. The Danish website skaccd.org had the best readability scores, followed by the Norwegian site helsenorge.no. The Swedish website cancercenter.se got the worst readability scores. The information was very brief and deemed to require a PhD to be understandable.

It is, of course, intelligible that it is hard to speak intelligibly about such difficult things as cancer trials. Not only do the patients recruited as study participants hope for effective treatment. The whole point of the research is effective cancer treatment. This is the ultimate perspective of the research; the horizon towards which the gaze is turned.

The fact, however, is that this horizon is far removed, far away in the future, and is about other cancer patients than those who participate in phase 1 trials. Therefore, it is important not to let this perspective characterize information to patients in whom hope would be unrealistic.

Do not talk about treatments and opportunities. Just say “You can participate in this study.”

Pär Segerdahl

Godskesen, TE, Fernow J, Eriksson S. Quality of online information about phase I clinical cancer trials in Sweden, Denmark and Norway. Eur J Cancer Care. 2018;e12937. https://doi.org/10.1111/ecc.12937

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We have a clinical perspective : www.ethicsblog.crb.uu.se

Speaking to 5-year-olds about research (By Sara Frygner-Holm)

How should we talk to children about research? And how should we go about recruiting them to studies? For children to become research participants, their parents must consent. Regulation states children should also give assent themselves, to as great extent as possible. Our ethics committees require us to provide them with age-appropriate information. Health care providers and researchers think the system works well and is ethically “correct.”

From recruiting numerous children for various research projects, I have some thoughts on the subject. I have put together countless information letters for children of various ages; all reviewed and approved by the ethics committee. But what, exactly, is “age-appropriate information”? With support from developmental psychology and some paediatric research, the ambitious paediatric researcher can get it right. On a group level, that is. We can estimate what the average kid of a certain age group understands. But how appropriate is the “age-appropriate” information for individual children? In his poem Till eftertanke, Søren Kirkegard wrote “To help someone, I must indeed understand more than they do, but first and foremost understand what they understand.”

Today, I value a slow and calm recruiting process. I talk to the children about what research is, most 5-year-olds actually have an idea. We speak about what the project is about, and what we want them to contribute. Perhaps we draw or look at pictures. I tell them that it is absolutely fine to change your mind and leave at any time, and that no one will be angry or upset with them if they do. And then we talk some more… Lastly, and most importantly, I ask the child to tell me what we talked about, and what we agreed upon. It takes some time to understand their understanding. Give yourself that time.

Not until I understand that the child has understood do I ask them to sign the consent form.

Sara Frygner-Holm

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We care about communication - the Ethics Blog

Swedish policymakers on genetic screening before pregnancy

Pär SegerdahlSome genetic diseases do not develop in  the child unless both parents happen to have the same gene. Parents can be healthy and unaware that they have the same non-dominant disease gene. In these cases, the risk that their child develops the disease is 25 percent.

Preconception expanded carrier screening could be offered to entire populations, to make everyone who so wishes more informed about their genetic vulnerabilities and better equipped to plan their partner choice and pregnancies. In Sweden, this is not relevant, but the issue could be considered in the future.

In a new article in the Journal of Community Genetics, Amal Matar (PhD student at CRB) reports an interview study with Swedish policymakers: experts at the Swedish National Council on Medical Ethics, at the Swedish Agency for Health Technology Assessment and Assessment of Social Services, and at the National Board of Health and Welfare. Amal Matar wanted to investigate how these influential experts perceive ethical and social aspects of preconception expanded carrier screening, as a new health technology.

It is exciting to get insight into how Swedish policymakers reason about offering genetic screening before pregnancy. They consider alternative financing, prioritization and costs for healthcare. They discuss Sweden as part of the EU. They reflect on what services the healthcare system needs to offer people, depending on what the test results reveal about them. They talk about the need for more research and public engagement, as well as about long-term societal effects.

Questions about responsibility, both parental and societal, struck me as extra interesting. If friends and relatives test themselves, it may seem irresponsible not to do so. Couples can then feel a social pressure to undergo the test, which makes their voluntariness illusory. The experts also saw problems in actively going out looking for disorders in people who are not sick. Society has a responsibility to help people when they are ill, but looking for disease risks in people without symptoms changes the whole evaluation of the risks and benefits of a health technology.

Amal Matar’s conclusion is that Swedish policymakers believe that preconception expanded carrier screening currently is not appropriate in the Swedish healthcare system. The reason commonly used in favor of screening, that it supports well-informed reproductive decision-making, was considered insufficient by the experts if the screening is financed through taxes. They also saw long-term threats to important values ​​in Swedish healthcare.

Pär Segerdahl

Matar, A., Hansson, M.G. and Höglund, A.T. “A perfect society” – Swedish policymakers’ ethical and social views on preconception expanded carrier screening. Journal of Community Genetics, published online 26 September 2018, https://doi.org/10.1007/s12687-018-0389-x

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Approaching future issues - the Ethics Blog

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