NIH CLINICAL CENTER GRAND ROUNDS
Episode 2009-004
Time: 57:11
Recorded Feb. 4, 2009
ARE RISKS TO FAMILY MEMBERS GROU NDS FOR EXCLUSION?
Dr. David Magnus
Director of the Stanford Center for Biomedical Ethics
Associate Professor of Pediatrics, Stanford University
ANNOUNCER: Discussing Outstanding Science of the Past, Present and Future – this is NIH Clinical Center Grand Rounds.
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ANNOUNCER: Greetings and welcome to NIH Clinical Center Grand Rounds. On this edition, we'll hear from Dr. David Magnus, director of the Stanford Center for Biomedical Ethics and Associate Professor of Pediatrics at Stanford University discussing the topic, "Are Risks to Family Members Grounds for Exclusion?" If you would like to see a close-captioned videocast of today's subject, log on to http://videocast.nih.gov and click the "Past Events" link. We take you to the Lipsett Ampitheater in the NIH Clinical Center in Bethesda, Maryland, where Dr. David Wendler, head of the Unit on Vulnerable Populations in the Department of Bioethics at the NIH Clinical Center, will introduce today's speaker.
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WENDLER: So today, we're going to talk about risks to family members and the context of clinical research and what if anything we should do about them. Just remind people of a couple of things about ethics ground rounds. One of the important things is that I always change at least some of the details of the case for confidentiality purposes. This is a real case that happened at the NIH and I think one of the relevant details of the case remain the same but some of the details have been changed and we won't talk about those so the issue for today is risks to family members and what we should do about them. For people who were here last time remember, we had a nice introduction to our speaker and talked about the number of publications and talks the speaker had done on that issue.
Well, most of the issues we do are ones where there is a lot published. This is one of the clear exceptions where there turns out to be surprisingly little written on this topic in the literature on bioethics in research ethics. And I think a lot of that is because primarily we had two perspectives for thinking about the ethics of clinical research. One is the perspective of protecting subjects from risks. We expose them to risky procedures. We ask them to contribute to the research. And a lot of the focus, if you look through regulations, guidelines, is on minimizing the risks that the subjects face in that process and try to protect them from risks as much as possible. More recently, people have been talking about the importance of allowing access to the potential benefits of at least some clinical research, some of which probably started with people in the aids community in the 80s who were clamoring for access to at least certain clinical trials. So there you have the argument that we shouldn't restrict access of subjects to potentially beneficial trials. So either way, it looks like the family falls out or never gets into the analysis in the first place. You have protecting the subjects and allowing subjects access to potential benefits and it's not clear how any risk to family members should fit into that. So, that's for people to have in the background as we think about how we should start considering if at all, these issues.
And to help us think about them is Dr. Richard Chang, who is from Diagnostic Radiology and I want to thank him. We can't do these without having real cases. The clinicians who present these have to do a little bit of work and have the opportunity of standing in front of a bunch of smart people who might criticize them for what they did. And they don't get pay raises as a result or tenure as a result of this. So I was going to start a new grand rounds tradition, if you see any of the presenters in the hall, you should at least smile at them extra and maybe even go up to them and say what a great job they did and how much you appreciate them. For the next month, when you see Dr. Chang in the hall, give him an extra smile. That's our goal for today. Sorry about that, Dr. Chang.
CHANG: Okay, I have a protocol for treatment of patients with deep vein thrombosis. Most patients are treated with anticoagulation but that doesn't restore the leg function, it usually protects you from the pulmonary embolism aspect of DVT. So we have a treatment that involves administering thrombolytic therapy to dissolve the clot quickly to prevent damage to the veins of the leg. So, patients who have a DVT are at in risk for reoccurrence. We hope when we clear the veins quickly we reduce that risk. Recurrent DVT creates significant risk and the risk is the recurrent pulmonary embolism. That's life-threatening. Also if you have recurrent DVT, your risk for post syndromes in which you get discomfort and swelling of the leg and sometimes even leg ulcers.
Now, we have a study designed to make thrombolytic therapy safer and cheaper. And I think we made some progress towards that goal. Treatment, however, requires that we start within 14 days of diagnosis, some people insist that you start within 10 days of diagnosis. And this is because the clot that we are treating becomes resistant to thrombolytic enzymes at the longer you delay therapy. We have done more than 40 patients that this point and had no serious complications. No blood transfusions, which is really remarkable for thrombolytic therapy. The reason it hasn't been used in a wide-spread manner is because the history of serious internal bleeding that occurred with previous trials, including intracranial hemorrhage. You don't want to trade off saving a leg verses a life-threatening intracranial hemorrhage. Our efforts have been in the direction of making this a safer treatment. So far we have no complications.
So, I received a call from the mother, as a single parent, 24-year-old male patient with DVT. The patient appears to be excellent candidate. The study of treatment would have to start in 3 days and the treatment itself would probable one take around three days. The patient has a non-identical twin brother just released from the hospital following episode of sepsis. From the mother's report, it appears the brother is somewhat unstable. I’m not entirely sure the source of the infection has been pinpointed yet. The mother and brother have a fear of flying and refuse to fly. The mother is willing to drive the patient to NIH from their home in Minnesota. The problem is, the mother is a single parent and principle caretaker. No one is available to care for the brother and the mother proposed to drive 20 hours in 2 days bringing the patient and the brother. Because the patient is in a wheelchair, the time in the car doesn't pose an increased risk of DVT to him. The NIH is concerned that a long drive may pose serious risks to the patient's sibling and place substantial burdens on the mother.
I was concerned that diagnosis hasn't been perfect newly-established. Infection is under control but -- perfectly identified. Since an organism hasn't been identified, I’m not sure the treatment has been on solid ground. Should researchers take into account risk and burdens to family members when deciding whether to enroll individuals in their studies and: so these issues, we don't write this into protocols that we have to take into account the health of family members when we propose to do a research study. So, for this reason, I contacted our ethics division to help me with some of these questions.
WENDLER: So before we go on to thinking about these questions and getting david to help us think through how we might answer them, stop for a minute to see, are there any facts, medical facts of about the case that we didn't present here that would be helpful, useful to you in thinking about the ethics issue that is it raises? So, just as a reminder we streamed this on to the web. So we want to make sure all the questions get picked up by the mic. If you could go to the aisle that's preferrable. If not, let me repeat the question before we get it answered.
QUESTION: He's a 24-year-old patient. That's going to be a subject enrolled. Is it not possible for that individual to be transported another way without the mother? That would take away the issue.
CHANG: First of all, the mother did not want to leave her children, both of them. Secondly, there was a factor of economics here. She's not well off. She's in the lower income group and I think she's already under Medicaid and really thought to travel by car would be the least expensive for her.
WENDLER: Anything else? >> [low audio] The question ss how did the family find out about the study at the NIH?
CHANG: NIH doesn't do a good job of advertising their studies but it is on the web. That's how most of our patients find out about our study.
WENDLER: Thank you, Dr. Chang. So to help us think through the ethical issues is David Magnus who is director for the Center of the Bioethics Community at Stanford.. When I was trying to get somebody for this case, I thought, let's see if we can get a smart person who would be fun to listen to and an added bonus, if we could get somebody who has been living in 70-degree weather and force them to experience some of our weather for a day or two, that seems like an added bonus. Thank you for coming.
MAGNUS: My pleasure. And you asked for somebody smart but you got me instead. Sorry. They said I had to start with a disclosure. So here is my disclosure. I’m really not sure about all of this stuff because this was in some ways a new topic and there is some relevant literature for this but really focused on this kind of issue more broadly, we are cutting some new turf here. My real disclosure, no financial relationships and here are the objectives for the talk.
So identifying frameworks for analyzing this kind of research, especially way that is family members can influence an evaluation of burdens and recognizing the limits of standard limits of the evaluation of research. So there is a standard way of looking at research protocols and how we evaluate them, which has already been indicated. In a recent article, some other folks called this the individual analysis. I thought about just calling it the wrong analysis. But it's the standard analysis -- focuses on the individual. When we think about risks and benefits, they are usually fairly narrowly defined and direct. And we decontexturalize patients from family and broader social context in a way we think about what it means to offer benefits or burdens to that patient. And then with this decontexturalized understanding, when we try to evaluate whether such research can take place, we figure out what the ratio of those things are and then think about informed consent. Some say this is not adequate.
There has been some history that I'll talk about in a minute but in the last year, an article talking about a case of genetics and possible benefits and risks between family members, they argue for an expanded analysis in which the interest of individuals in the context of family is taken into account in the way we do our assessment. The psychological risks and benefits as a function of interrelationships between family and groups need to be taken into account. I'll talk a little bit about the data showing that these are real, that there are harms to individuals as a function of the facts that they are members and participants in family interactions and harm to other family members can harm them.
Sometimes in the language in this particular article that is cited here, they talk about a family focused approach. And I think in a way it's misleading. It really isn't family focused. It's really just a contextualized understanding of the individual. It's still a focused approach but just expanding the concept. One sees the family of a primary unit of care. It reevaluates how we take the interest of other family members and associate groups independent of the impact they have on the individual subject.
Now, trying to figure out how this would work and how to apply if is something in some literature, especially starting in the 90s, there was a lot of literature in family medicine about how to move away from an individual focused approach to providing clinical care towards thinking of the family as a unit. And there are a number of approaches that have been developed to try and think about this. One of them, a concept of a family covenant. You can solve this problem in our individualistic system by having family members also sign a contract, all agree that everybody's interests are going to be taken into account as a way of finding a mechanism for making that work out where some of the details get negotiated. There is something called triangulation theory where when you're thinking about the individual, you think about the individual, you think about the research or the physician, but you also take into account the family in figuring out what the right thing to do is. Each of these approaches is trying to build on what we have as fundamentally an individualistically oriented system and find ways of expanding beyond that. Another possibility is rethinking of the entire framework. A number of social scientists have suggested that maybe we needed to do a much more radical rethink that will require broader changes in the way we carry out bioethics and changes in our regulatory system.
Some of the kinds of context where people said, you need to at least go from a standard model some kind of notion of an expanded concept where we have to take into account the very real impact that families have on even the individual, have included discussion of genetics, genetic testing, there has been a lot of discussion about this in that context. There has been some discussion about this in the context of HIV. Live solid organ transplants, bone marrow, cell transplantation, save your siblings, there has been a lot of data about the impact of serious childhood illness and death on siblings as well as gamete donations.
And just again, a little bit of sense of this. If you look at the courts back as far as 1957, there was a case where you had a proposal to do a renal transplantation between 19-year-old twins back in 1957, 19-year-olds were considered to be minors in Massachusetts, and the family wanted to be forward and the hospital refused to do the transplant because it wouldn't benefit the twin who would be the donor. One of the state Supreme Court justices who was the one ruling on this case claimed that the operation was necessary for the continued good health of the healthy twin, not just the at-risk twin, but the healthy twin, and would in fact confer benefit because of the fact that it would help avoid the tremendous psychological loss that would result from the death of a twin.
1969 in the Kentucky Supreme Court, similarly permitted kidney transplantation went from a situation where you had 19-year-olds, even if they were legally minors, consenting to a situation where you had somebody not capable of giving consent. A 27-year-old who was institutionalized with an IQ of 35 and the court said there was enough of a relationship even though the donor was institutionalized that person would feel the loss of the sibling and be able to appreciate that and that would constitute a harm and the transplant would constitute a benefit to the mentally impaired 27-year-old.
In Connecticut, 1972, the courts on the same grounds permitted a 7-year-old to donate to her twin. There are a lot of legal exceptions where courts have not allowed transplantations to take place, particularly when other donor sources were available. Where there is one source, there is a history of courts saying that harm does accrue to somebody as a result of loss to their sibling. Similarly, over 30 years of research on sibling -- the impact of death or illness on siblings. Studies in cancer, there has been Joanna Fanos, who is affiliated with my center has done research for many years on the impact of different genetic disorders on the unaffected siblings are for CF and a number of other diseases and one common finding you see coming out is that there is a large impact. Often guilt. Guilt over a relationship with a sibling, survivor guilt, global anxiety, fears, illness, early death for themselves. An article just published last year in a very, very short study of sibling donors, on the whole found attitude of donors to be positive. They did identify there was guilt over graph versus host disease. Guilt over complications and regret when failure.
Just to summarize, courts have long recognized that helping or saving a family member is good for people and having a death in the family causes problems and there is a large body of evidence to support this. So in a way, this is the “duh”. Refigured out that when somebody in the family dies, the appropriate response is, I’m very sorry for your loss, not interesting, let's go have lunch. So we feel it's bad for you, psychologically when something bad happens to your family.
So, one question is whether or not this recognition should be something that is part of the new paradigm or simply an exception. If you look at the article, they start off by talking about some of these different context I have identified and say, such family-grounded procedures like genetics, HIV, certain other kinds of exceptions involve ethical considerations that differ from most other decision. So the picture that we had is, sort of an exceptional area like genetics and a few other areas where families matter, though the standard paradigm, or the standard analysis we started with is adequate for the vast majority of cases.
I think there is at least a little bit of a push to recognizing that that's not really going to necessarily be adequate. That's highlighted by this case. Because this case actually doesn't have any of those kinds of context, at least on the surface. There is no reason why DVTs or a condition to try to avoid occurrence would automatically seem to fall into this category, but it's because of the psychosocial situation and the particular risks having to do with the particular details of that family show that these kinds of considerations could arrive in any situation. That's because not all necessarily but most patients, most research subjects are parts of families.
In commentary that article, they started to articulate a little bit more radical view that might really shift us towards that recognition that the fact that people in families should almost always be taken into account. Membership in families matters and is often expressed in the family for genetic and medical health factors and for the ethical obligations that ensue from such membership. So I think there is a possibility for us with a bit more radical conception.
Before I do an analysis of how these different frameworks look at this the different case, I want to highlight something that came up in one of the questions. Which is whenever in practice, we have a clinical consult service and a research consult service. The first thing we do in practice when we get a case like this is try not to resolve it but dissolve it. The first instinct, the first thing to do is make it go away. I had the same thought, is there any way we can work at it to find someone willing to care for the patient's brother so mom could drive the subject to the trial or any way the subject can travel by himself or with another family member. The first thing to do is to think through other options. But to figure out if you could make the problem go away without having to address whether or not we are going to make the decision about whether to allow this patient to be enrolled in the trial.
For the sake of the analysis going forward, I’m going to assume that all attempts to try and dissolve the problem failed. If you can, that's great. If you can't, then what would we say? So on the standard analysis, if the subject has capacity and consents, and if the risk-benefit ratio to the subject is favorable, which is in this case, it's not the investigational new treatment but the results look very, very promising. It is although there are treatments, the condition is serious. The research itself has value and so, all things being equal or being close to equal, there is a good reason for going forward because of the value of the research itself and so on the standard or wrong analysis, we should allow enrollment. What about the expanded analysis? On the expanded analysis, the risk to subjects include harm that may result if sepsis were to occur because it's not been adequately resolved or identified. And the fact that the brother may be exposed to risk, the fact that the participants brother might be harmed is itself a kind of harm to the participant. We should also recognize that other treatments exist -- recognize -- not successful for DVT prevention and more importantly to avoid PEs or symptoms produced by DVT. The treatment under investigation isn't proven although it is looking very promising.
When you put all these things together, you can argue taking into account that psychological harm to the subject that may be putting that all together in this particular case, you have an unfavorable benefit-burden ratio to the subject in this case. The expanded context by allowing that psychological harm to enter into the equation and a benefit-burden ratio that while positive, isn't so overwhelmingly positive this harm might not tip it the other way. Or at least that's how you start to try and evaluate it. Although you have to weigh that against the fact that you got informed consent, potentially in the case and the value of the research. And therefore, probably you should exclude from participating in the research although it's not clear and depends on a lot of details on figuring out on what that expanded benefit-burden ratio is once you take that psychological harm to the individual into okay account. That's how you to at it.
What about the radical analysis? The radical analysis takes into account the risk to all family members. Harm to the sibling would be a reason not to proceed independently of a psychological harm produced in the participant and consider the possible psychological harms to the patient's brother if he stops the participant from enrolling in a trial that might benefit him. So it's going to be a much more complicated analysis in which take all of these different very complicated things, including the interrelationships into account in deciding whether to go forward. We should consider whether all the family are enthusiastic. We want to do an analysis of the family as a unit rather than thinking about just the participant themselves. And I would suspect that you would likely exclude from participating such a family in this particular research.
So, going back to our first 3 questions, should researchers take into account risks and burdens to family members when deciding whether to enroll individuals into their studies? On the standard analysis, no. That's why I think the standard analysis is generally not adequate. On the expanded analysis, yes, researchers should take into account rink and burdens to family members on the grounds that it may harm the participant as a result of harm to family members. And of course obviously yes on the radical analysis.
Can eligible subjects be excluded on the grounds of significant risk or burdens to family members? Not on the standard analysis, which is wrong but potentially yes on the expanded analysis as long as the psychological harm to the participant as a result of the other harm to the family members is sufficient to alter the risk-benefit ratio to the individuals sufficiently to rule out the research. And of course, it would be much more straightforward on the radical analysis.
Should researchers prospectively therefore investigate whether research would pose significant burdens or risks to family members? On the standard or wrong analysis, there is clearly no obligation to make such an investigation and it's not clear there is an obligation to act if you know of such risks or burdens. On the expanded analysis, I think there is probably no obligation or at best only a weak obligation to actively investigate to determine whether or not there is harm to other family members, however, if you know of such things and you know that those might be harms to the patient, to the individual participant, then there is an obligation take those into account on the grounds of those might affect the participant.
On the radical analysis, I think there might be an obligation to explore or investigate over and above the impact on the participant. So, in this particular case, I’m not going to come down on one of the one or two analysis as the correct one. From a practical point of view, it's hard to see how we're going to get from the expanded analysis to the radical analysis but in this particular case, I think you can make a pretty good case that is on either of those analysis, the appropriate thing to do would be not to enroll the patient in this particular research. Thank you.
[applause]
WENDLER: I guess the questions will be mostly for you. So you might want to -- if people have questions, ideally if you could go to the mics in the aisles, otherwise you have to hear me talk more as I repeat them.
QUESTION: Thank you for that analysis. It's an interesting issue. I haven't thought about this very much. I guess I was wondering about whether the radical analysis has to be so radical. I’m thinking about instead of a model they'll uses social value as the test. And this would say basically the family members, the harm to family members is in essence a negative externality of enrolling this particular subject and then say, is enrolling the subject going to cause more over all harm to society and that meaning the familiar plea members who are part of society, compared to the benefit society gets out of the research participation as a benefit that the patient might get himself. On that analysis, I think he would probably have to be excluded given the sepsis risk and the burdens of the two days of travel.
MAGNUS: That's interesting. It's interesting there is an asymmetry. If you look at the guidelines and regulations, if you look at Nurenburg, Helsinki, there is an asymmetry. So while risks tend to focus on the individual, benefits have to take into other things into account when they are charged with making the calculations are worth it. They are not just charged with the benefits of the individual but to the value that will result from the research. Is it worth it? There is an asymmetry with that. The risks always focused on the individual. Now trying to say we need to take a more utilitarian approach, I think it would be very hard and it makes me nervous about going quite that far. I think even with the radical analysis, you're simply recognizing that the units that you deal with are not individuals. People often come as families and so maybe that would be a way of going down there. The expanded version, arguably, is one that is least different from the current system because you're really just saying, current but the standard way we have of treating it fails to account for some of the genuine harms and risks that research subjects or participants are exposed to. That's the safest within the current regulatory system.
QUESTION: I want to bring to the discussion the concept of autonomy, individual autonomy, which is of course a key consideration in terms of participation and research projects for informed consent or to withdraw from a study if the subjects so decides. Can you look this from the point of view of autonomy for each one of the individual members of this family group? They are adults. They have considered the issues. And each of them decides that they want to join in this effort in terms of participating in this clinical trial at NIH. Could you please comment on that?
MAGNUS: Sure. And one of the things that is already a complication is, whose autonomy and who do you need to get consent from? In the standard way of looking at this, the only person whose consent is relevant is the participant. So if the brother who has just come out of the hospital were to say, “I really don't want this to happen, Mom don't go,” it's not relevant in the standard way we have of thinking about things for the decision about whether you have got consent from the actual individual. So, already to decide that you have to take the fact that these other people will consent into account, you have to already go down the road of either expanded concept, because it's possible if you're doing this research and some of the family is not in favor of it, that could have impact on the patient or the subject themselves. So on the expanded analysis, that fact, I’m not sure consent is the right word, but the cooperation and the support of the other people might be relevant on the expanded concept and then obviously on the radical concept, whether people are in favor of it or not as a group would be relevant.
In terms of the assessment over all, the two things that you're supposed to weigh or think about, if you're evaluating research, are the two pieces of the consent part and the autonomy behind that, versus the benefit-burden ratio. If it's risky enough, we don't say no, even if people are willing to consent. It may be that there would be healthy subjects willing to expose themselves to chemotherapeutic agents. We don't let them do that because it's too risky. So you have to take both of those things into account in the evaluation. But you do have to take the consent into account. But whose consent depends on which analysis you opt for.
QUESTION: Is it really the responsibility of the researcher to take into consideration how or to be involved with the dynamics of a family discourse and how they are going to evaluate the risks which they may or may not be subjecting themselves to. And as a consequence of the argument you make, is it the responsibility of the researcher to ask, are you driving? How far are you driving? What is the age of the driver? At what hours are you planning to drive given a center like NIH, where people are traveling long distances to get here.
MAGNUS: So that is one the appealing things that I think about the expanded analysis. Because the expanded analysis says, if you think that there is this harm or problems in the family, that is likely to have an impact on the participant, you have to take that into account. But I don't think it says there is an obligation to do an investigation into every family situation. If the participant is clear in talking with the participant about the research or during the course of your -- as in this case, of the preparation or the initial conversation busy enrollment, you identify these kinds of problems, then you would be obligated to act but I don't think on the expanded analysis you are obligated to do any kind of investigation. In contrast, I think it's hard to see how on a more radical interpretation you can avoid at least having communication with people beyond the participant themselves to the other family members which would necessary taillight finding out some of this other kind of information -- necessitate. The fact that going into that direction, whatever the advantage is has a disadvantage of potentially making the research harder to do, and that's a significant downside to a more radical approach and in favor of a expanded approach when it comes across the radar, you have to act but if it doesn't, then you're not obligated to go out and find out things. It's fairly similar to a lot of the discussion about things like incidental findings and genetics where if you find out something, you may have an obligation, that doesn't mean you have to go look for things.
QUESTION: I’m wondering to what extent informational risk of genetic information to family members would come into play under each of these analysis and especially of the expanded analysis, how it would be justified to the original subjects.
MAGNUS: So, I think it would depend on the case or what you mean by genetic analysis. So, in the case that was originally discussed in that original paper, who stated they didn't want certain kinds of genetic information, but they were also identified as the best possible match to be a bone marrow donor for an elder sibling and as part of routine screening to do a rule out for that transplant, they found out that the 13-year-old had an indication that person was at risk. Now what do you do now that you have this information? If we tell the person they won't be a donor, they will know their genetic background. If you allow them to serve as donors, you jeopardize the life of the patients. And the conclusion that was reached in that case by the folks who did it was, in that particular case, the welfare of the sibling should be taken into account and given the dire nature of that, that out weighed the promise or -- it wasn't explicit to cover all contingencies but the sense this is not information that the patient wanted in their initial communication or the subject wanted. So that expanded analysis allowed you to sometimes break those boundaries.
The more radical view, in an article in 2001 in which they tried to develop a family covenant model to apply for the fact that it's not uncommon for conflicts to emerge in family settings where it's realistic. It's hard to hide genetic information. As a parent if you don't want to know if you have Huntington's Disease and their adult child goes ahead and gets tested and it's positive, it's going to be very hard to imagine really keeping that secret and then that is going to impact them. And so, here is a suggestion, we should have a family covenant in which families agree about how information is going to be handled and really say that the whole family as a unit is going to be taken into account in the way everything is conducted.
>> [low audio]
WENDLER: If there is some independent rationale, why the family as a unit gets put in there -- so on the expanded analysis, if the underlying worry is, this person is concerned about other people and what happened to other people, they may impact them psychologically, we have connections to people we are not related to. And on the expanded analysis, if you just care about other people who get hurt, why do we stop at the boundaries of the family?
MAGNUS: I don't think it's just the family that matters. So it was mentioned in a couple of articles. You can imagine situation whereas other kinds of cultural groups or factors might be relevant and that even also happened in genetic cases as well. But I do think, however, families are particularly important and neighbor comes from the fact that I’m -- I do a lot of adult ethics consults but I’m in the department of pediatrics. In our ethics cases there, the family centeredness comes out so clearly all the time and there will is a tendency to think of a family as a unit in pediatric cases and the question is, what happens when we go to adults? We throw that away yet I have an ethics case going on with the people who are certainly they are elderly going on like this week. But the family dynamics are everything in that particular case. And that is my experience often that we kind of ignore it or try and abstract that out as much as possible until the way we think about things. And I think that comes from the fact that bioethics is largely started with adults and then we have just gone from there to pediatrics and they are like these little cognitively-impaired people. And you do think that you need to start with a pediatric-centered focus where families are the units in which things come and taking that as a paradigm, it isn't always the case. We have patients where that's not true. But I think for a lot of people, the family unit matters a lot. And it's this kind of family and this kind of case, it's clear that that is playing a big role in the Mom serving as a care giver. So in a lot of ways, even if the subjects have capacity to make decisions as autonomous agents, that doesn't change the fact that in a very real sense, this case, the nature of those relationships in the interdependence much more like a pediatric case. It may be cases where the people have more independent separate lives and where the standard analysis might work. But I don't think that should be our starting point.
WENDLER: So it's starting from the patient. It's not families have independent moral status so we need to take them into account. It's rather, individual patients and subjects care about their families and they are embedded in their families in most cases. Therefore, we should think about them.
MAGNUS: Certainly on the expanded analysis. That's true. On a more radical analysis, you might start with them but not just because they care about them. It's because it's fundamentally part of who they are. They are not atoms. They are -- they come as part of a group. Not all subjects do. But if a subject comes as part of a group, whether it's a family or a different cultural or social set up or arrangement or what that family means, it might be dependent on the individual and the more radical view, I think would have to take that into account.
QUESTION: You touch only briefly on the economic considerations. One unique aspect at NIH is that research participants get free medical care. So, under the radical analysis, does that create an obligation for NIH to give free medical care to a first degree relative of a study participant if some unexpected severe medical condition arises?
MAGNUS: That's a really interesting question. I don't finish it creates a obligation always but I can imagine scenarios where you might think that would be defensible, especially if the person who is the participant is dependent upon somebody else as a caregiver. So for them to bring the person here, the participant themselves is very dependent. I mean as in a pediatric case, for example, that might not be implausible. There might be something owed -- if a woman travels and is taking care of herr kid, that is there might be something that is owed to her in that kind of a context. Although I wouldn't think it would be generalizable. But that's an interesting question.
QUESTION: Would the expanded analysis and the radical analysis have similar problems to utilitarianism? So like in a family setting, a brother may have a lot of interest in not seeing his brother get treatment? And what that offset?
MAGNUS: I think they would differ. So on the radical analysis, it might be that you take into account if one person has a greater need that that might out weigh the need of a participant. That wouldn't be true in the case of the expanded analysis unless the need of the brothers and the harm that it produces is great enough that would negatively impact the participant. It's important in the expanded analysis, you're still essentially focused on the individual. You're just taking into account all these other things that psychologically harm that individual. So I think they would differ on that essentially.
QUESTION: I'd like to ask the investigator what sort of process you went through to make your initial decision and whether having these different analysis individual changed the outcome of your decision?
CHANG: Okay. I must say that there are a number of considerations that I had in this case. This is a particularly unusual case, I think, because the family is indigent. And some of you raised these questions already. If the relative should get sick, does NIH have an obligation to take on the problems with that relative who is not under protocol. That hasn't been answered here to my satisfaction. For that reason I don't have the security in thinking that this patient with no insurance, only Medicaid in their state, would be able to get care here. So that was the primary consideration in my mind, what to do for the patient's relative. Now, I’m old enough, older than most of you here, they remember when we didn't all see specialists. We are an institute of specialists, internal medicine, vascular surgery, I see a different doctor than my wife. My children see a different doctor. So, it's not like when I was young when we all saw the same doctor. He was or he took care of all of us in the family. He was family physician, family practice. And his considerations were different. He knew everybody in the family and knew them well and knew all their conditions. Today we are sort of disjointed in our care we only see each of our patients as individuals. And so now I’m surprised I would find this discussion quite interesting because it's a throw-back in a way to an early era in medicine where physicians saw everybody in the family.
WENDLER: Did you want to comment on that, david?
>> [low audio]
QUESTION: I have a question that could be a complete other grand rounds. But the expertise you preside. I’m thinking of cases particularly with adolescents or in other situations where the good of the individual -- and this may be more clinical than it would be related to research -- is being destroyed by the wishes of the family or the parents. And I know we all could think of examples of that, not wanting to give care in certain cultures, et cetera. And I wondered if you would apply some analysis to the issue where you want to say, no to the family, and do something for the individual.
MAGNUS: Yes. So, I have a couple of cases sort of coming to mind. That's another good example of how we need to think about recognize at least, an expanded analysis. Because if you just think of this from an individual standard perspective on the clinical side it is different because it's not research. But even there, I think it would be straightforward. If it's bad for the child or sufficiently bad, it crosses some threshold, we call child protective services. The reality is that even if families are doing things that are very detrimental to the child, the reality is, taking them away from that family, and the only family they may have known depending on their condition, we had to grapple with these cases where taking them away for a dying child where they are not getting the treatments we believe that the adolescent wants, but taking them away would be harmful, has to also be taken into account. So an expanded analysis would take into account factors that are critical to be taken into account.
Fortunately, I don't think there is such a thing as the standard account in the clinical side of things at least in the pediatric setting. Nobody would ever -- it's a non-starter. So we always take that into account and then try and do the job you can of negotiating between all those different things. So I think that at a minimum the expanded view is something that we use all the time in those kinds of clinical settings. I don't think anybody would ever say, well, we ignore the fact that we are going to take this 15-year-old who spent her whole life in this family and we're going to have to send her off to foster care so that we can get the optimal or have the medical foster care so we can get her the treatment we think is optimal for her. We wouldn't just do that without taking into account what that would do in the harm that would do and that might number some cases you try and figure out some sort of halfway solution or some other way of dissolving the problem.
QUESTION: I have a question regarding in this case, the family at least has 3 members, because the mother is the caregiver called to tell of the situation. How much information should we give to define the unit as a family? We don't know if there is a father or other siblings or somebody who is opposed to this procedure.
MAGNUS: So, I think it depends. So once you know there is a problem, and it's identified, in this particular case, when he knows that you have got a kid who has just been released from the hospital with sepsis and you're not satisfied that's been worked out and the they are planning on a long drive of many, many hours, I think at that point, there is some obligation to try and figure out something whether it's figuring out another option or finding out more about the social situation as a way of solving this problem. Especially if for some reason, from a scientific point of view, there is some reason why you would be particularly interested in enrolling that particular subject in the trial. One thing you could do is exclude them f there was some reason why you thought this patient might be valuable, which might be the case in this particular case, then, I think you would have to go down that road to some extent. Beyond that, just in general, whether you have an obligation, or when you first come in contact with people, I think depends on your perspective. If you have got the expanded view, I think there is at least an obligation to be aware of the fact that this is happening in a context and that would frame a little bit the conversation you have with the participant. But they think it doesn't go very far. The radical view would require or be more burdensome for investigators.
QUESTION: I was wondering, do you have thoughts on issues that might be characterized as fairness issues that seem like they could come in on both expanded the radical analysis and push back the other way? So I was imagining if you take seriously the idea that investigators at the NIH, when they decide whether or not to enroll subjects have to at least think about, if the information comes across the radar screen, maybe take into account potential psychological, social, physical harms to other family members, whether you end up in situations where you're forced to take into account things that seem unfair. So, I can't enroll you because you have got this sick brother but I can enroll this other guy in the study instead because as it turns out, he doesn't have a brother. Or we are going to do genetic analysis and what we'll try to do when looking for mutations is exclude anybody who has more than 2-3 siblings in the family. Because then there is a lot of people who can get upset by a positive finding as maybe one or two.
MAGNUS: So I definitely agree there is a difference that would happen but I’m not sure I agree that's necessarily an injustice. Because these are relevant differences that especially if you take or don't think of them individuals as atoms, then their families and in the nature of their relationships, the benefit burdens are different between them and other people. It means that on the expanded view, that would be not unjust. It would be appropriate. And the same just like you might rule out somebody because they have a co-morbidity. So somebody who just happens to have a little better liver function gets to enroll in the trial and you don't have that liver function. I don't think anyone would say it's unjust because your liver function isn't right. These are relevant harms that happen to be more social and psychological in nature that are kind of on the expanded view, think of them as lie co-morbidities that would be relevant for exclusion criteria. That wouldn't necessarily be injustice. It counts.
WENDLER: Okay. Any other parting last questions? You get the last question.
QUESTION: The only part here is DVT a common condition that can be managed anywhere and everywhere. This particular patient had a rare exotic condition that only NIH physicians have the expertise to take care of. Will your analysis change any?
MAGNUS: Yes, it would. Because the risk benefit ratio would be different in that case. On the expanded view, with your weighing psychological harm to somebody else, verses a life-saving treatment, for example, let's say or the only chance of somebody that might be of benefit to somebody where they are facing a very serious life-threatening condition, that of course, the benefit burden ratio would change for both analysis. So for the expanded analysis, I think it would be pretty straightforward even on the more radical analysis they would still take that into account and the relative harms there and again, you also take into account the fact that the harms to the subject also individual psychological impact on the rest of the family. So I think probably it's possible depending on the details that the ratios would switch on any of these analysis.
WENDLER: Thank you. Tell people who are interested in the outcome of this particular case, tell me my memories is not right. Dr. Chang worked very hard to –
CHANG: One last comment. We are doing research on patients. And there is one other thing to consider, the principle investigator. Now in this case, the treatment is really to improve quality of life. It's not -- as someone said, DVT can be treated and the therapy we give will improve the quality of life in the sense of preserving their veins and their vein function better. The risk on this side was not to the patient but really to the sibling and the sibling's risk is sepsis. If she had recurrent sepsis and couldn't get care, that's life-threatening. That's potential life loss. And imagine if you're the principal investigator and sure, you could get an extra case and it would add to your numbers and improve your data set, but it cost the life of a sibling of one of your patients. How would you deal with that? You have to live with that. These are not just numbers. These are real patients. I voted against taking that patient for that reason. And the best I could do was contact other individual radiologists who have tinkered treating DVT aggressively and I found the name from our society list and gave the patient the number and also gave the or talked to the doctor and gave them the patient's initiative and I hope they got together. It's in their state and covered under Medicaid and I hope they got treatment. So the patient did not come to NIH.
WENDLER: All right. Thank you Dr. Magnus and Dr. Chang.
[applause]
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ANNOUNCER: You’ve been listening to discussion on the topic, "Are Risks to Family Members Grounds for Exclusion?" Our speaker was Dr. David Magnus, director of the Stanford Center for Biomedical Ethics and Associate Professor of Pediatrics at Stanford University. Once again, you can see a closed-captioned videocast of this lecture by logging onto http://videocast.nih.gov -- click the "Past Events" link. The NIH CLINICAL CENTER GRAND ROUNDS podcast is a presentation of the NIH Clinical Center, Office of Communications, Patient Recruitment and Public Liaison. For more information about clinical research going on every day at the NIH Clinical Center, log on to http://clinicalcenter.nih.gov. From America’s Clinical Research Hospital, this has been NIH CLINICAL CENTER GRAND ROUNDS. In Bethesda, Maryland, I’m Bill Schmalfeldt at the National Institutes of Health, an agency of the United States Department of Health and Human Services.
