Rather, it was that babies in the high oxygen arm had a survival rate that was higher than predicted and higher than that of any comparable group of babies anywhere in the world. So should that difference in mortality be considered a harm or a benefit? Many critics say that it was a harm that should have been anticipated. Supporters see it as a surprising benefit of being in the study. This leads to the second point: many of the criticisms are based on twentytwenty hindsight, rather than on what was known and believed at the time the study was designed. Many commentators believe that the investigators should have known that babies assigned to the lower target oxygen saturation would experience higher mortality. At the time, though, many of the investigators thought that mortality would be higher in the higher oxygen arm, just as it was for oxygen therapy given as part of resuscitation of babies at birth. We now know that they were wrong. That doesn’t mean that they should have known this at the time. These post-SUPPORT controversies suggest the complexities that we face going forward. If experts cannot agree about how to quantify the risks and benefits of a study even after the results are available, it is hard to imagine how we will ever agree on an appropriate way to describe the risks and benefits of studies before the results are known. Solving this problem will be more important than coming to consensus about the specific issues of SUPPORT. • John D. Lantos Children’s Mercy Bioethics Center, Kansas City • Chris Feudtner Children’s Hospital of Philadelphia DOI: 10.1002/hast.439
u The
Potential Harms and Benefits from Research on Medical Practices
John D. Lantos and Chris Feudtner’s article “SUPPORT and the Ethics May-June 2015
of Study Implementation: Lessons for Comparative Effectiveness Research from the Trial of Oxygen Therapy for Premature Babies” (January-February 2015) is very thoughtful. We concur that the study design was ethical, a position buttressed by our appreciation of the genuine uncertainty about relative potential benefits and harms of this study compared to usual practice. We also concur that what is communicated during a consent process must contextualize the risks and benefits of such research to those of usual care. However, two issues warrant further consideration. First is the challenge of what to label this research. The Office for Human Research Protections refers to “standard of care” research. This is a problematic construct because “standard of care” is a legal threshold for negligence and does little to clarify that the focus of this research is to improve upon the variability of usual practices above this threshold. Lantos and Feudnter use the more common term “comparative effectiveness research.” We agree that it is appropriate to distinguish this from research for developing innovative interventions. But the ethical analysis, and more importantly, patient understanding, can be enhanced by a more descriptive term, “research on medical practices.” Working with colleagues on an empirical ethics project, we have used focus groups and surveys to assess the public’s and institutional review board members’ understanding of and attitudes toward this category of research. “Comparative effectiveness research,” we have found, may be clear to the research, bioethics, and regulatory communities but less clear to patients. The term does not make explicit that interventions already in standard use are being compared. When describing ROMP to patients, we can emphasize that it can also involve observational research, including medical record review. Awareness of medical record review is important for two reasons. First, it provides the context for understanding the rationale for randomized designs. Just as patients need to contextualize the risks and benefits of a randomized
ON THE WEB n Bioethics Forum http://www.bioethicsforum.org DNA Phenotyping and Baby’s First Portrait By Timothy F. Murphy If we start to use DNA phenotyping at embryonic stages, it may well be that some parents will pass over one embryo in favor of another because of the expected appearance of the future child and adult. The Drug That Cried “Feminism” By Alessandra Hirsch, Rebecca Holliman, and Adriane FughBerman Flibanserin, a failed-antidepressantturned-libido-boosting drug, has already been rejected twice by the FDA due to a lack of proven efficacy in the face of possible safety concerns. Rather than putting this drug to sleep, Sprout [Pharmaceuticals] attacked the FDA for, of all things, sexism. New York City’s Compromise on Dangerous Circumcision Practice Leaves Infants at Risk By Elizabeth Reis For years now ultra-Orthodox Jews, the mayor of New York, and the New York Department of Health have been trying to balance the demands of religious belief with the protection of vulnerable infants. Mayor Bill de Blasio has come up recently with a new “compromise”— if a baby contracts herpes or another infection that can be attributed, using a DNA test, to a particular mohel, then that mohel would be barred from performing metzitzah b’peh in the future. Cognition Enhancement and Technological Unemployment By Michele Loi Most economists dismiss as a “Luddite fallacy” every forecast of technological innovation having harmful consequences on society. But some recent papers . . . suggest that technological advancement has played a central role in the jobless recovery and stagnant median income of recent decades . . . H AS TI N GS C E N TE R RE P O RT
5
design to usual-care variation, it must be contextualized to alternative research approaches. While medical record review can contribute to generalizable knowledge, it has important limitations and can lead to incorrect determinations of risks and benefits. Therefore, ROMP, and its inclusion of observational and randomized designs, is conceptually important for patient understanding of the context. Second, patients may actually make less of a distinction between these two approaches than researchers, ethicists, and regulators. The regulatory framework includes distinctions between randomization and observational research as well as between uses of identifiable and deidentified data, but our study results indicate that the framework does not reflect how much of the public views these distinctions. Many studies, including some of our own, have shown that most people want to be aware of their involvement in research, regardless of whether they are randomized or whether their data is identifiable. A second issue related to the assessment of potential harms and benefits and its communication is addressed only tangentially, in the final section of Lantos and Feundter’s paper. We agree with the model language proposed for potential participants. But this does not explicitly talk about the potential harms and benefits of participating in such research. The critics of SUPPORT have rightly pointed out that the consent forms, which conveyed the potential for direct benefit from participation but did not convey risks, were problematic. But the problem with these forms was the overstatement of benefits, not the understatement of risks. Because of the uncertainty that the research was intended to address, we do not think that there were any substantial benefits or risks from participation compared to usual care. Communicating that there were substantial potential harms and benefits from the decision to Contributions to Exchange may be submitted to editorial@thehastingscenter. org. They should be no more than eight hundred words and without endnotes. They may be edited for style and length. 6 HASTIN G S C E N T E R R E P ORT
join the study would have profoundly misled patients. As the authors point out early in their paper, population benefit and harms are not the same as benefits and harms to individual patients. While a decision to participate in research can be important to many people, perhaps because of different views about communitarian obligations, we do not think that participating in ROMP compared to usual care presents sustainable benefits and risks to patients. We would propose adding a paragraph to the consent message: “Because of our uncertainty about the differences between the approaches to be used in this research and our usual practices, there are no expectations of different benefits or harms whether you decide to have your child be part of this research or to have your child receive usual care. If you join the study, we will learn more from your child’s experiences compared to if you decide to have your child receive usual care. This may help other children in the future.”
This is not simply a communication issue but is important in the ethical evaluation of the research. Conceiving of ROMP that compares differential mortality or serious adverse effects as providing no potential benefit or harm compared to thinking of such research as posing substantial potential benefits and harms has profound regulatory implications for waivers or alterations of informed consent. We are committed to developing innovative approaches to improving patient understanding of ROMP, and conceiving of ROMP as minimal risk research allows regulatory options, which can permit research on how to improve patient understanding and make the research even more ethical. • Benjamin S. Wilfond Seattle Children’s Hospital • David C. Magnus Stanford University DOI: 10.1002/hast.440
In Memoriam: Alan Wertheimer We mourn the loss of Alan Wertheimer, who died on April 10, 2015. Alan’s contributions to bioethics were thought-provoking and far-reaching. He joined the National Institutes of Health Clinical Center Department of Bioethics in 2005 after retiring from the University of Vermont. Alan made his newness to bioethics a strength. Insulated from the reigning views in bioethics, he brought innovative discussions of coercion, exploitation, and consent—developed in three significant books written between 1987 and 2003—to bear on the ethics of clinical research, producing insights that shook up the conventional wisdom in research ethics. Alan practiced a fruitful method that was reflected in the subtitle of his 2011 book, Rethinking the Ethics of Clinical Research: Widening the Lens. Conventional views about informed consent in medicine and clinical research, for example, are taken for granted without thought to how different these views are from the way we think about other domains in which consent is morally significant, such as employment or sexual relations. Alan applied a wider lens to clarify concepts and refute some of what he saw as “medical exceptionalism”: “the view that participation in research is a distinctive activity that requires moral principles that we do not adopt or reject in other social contexts.” One example of this is the widespread view that payment of research participants is “coercive.” Alan demonstrated that this view cannot withstand critical scrutiny. Alan was a top-notch philosopher, an inquisitive and adventuresome scholar, and a generous and engaging colleague, collaborator, and mentor. He was conscientious almost to a fault and disarmingly humble given his extraordinary accomplishments. He was a mensch—a wonderful person and friend. All of us who knew him are better off because of it, and we will miss him greatly. —Franklin G. Miller and Christine Grady, National Institutes of Health May-June 2015
Copyright of Hastings Center Report is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
u The
Potential Harms and Benefits from Research on Medical Practices
John D. Lantos and Chris Feudtner’s article “SUPPORT and the Ethics May-June 2015
of Study Implementation: Lessons for Comparative Effectiveness Research from the Trial of Oxygen Therapy for Premature Babies” (January-February 2015) is very thoughtful. We concur that the study design was ethical, a position buttressed by our appreciation of the genuine uncertainty about relative potential benefits and harms of this study compared to usual practice. We also concur that what is communicated during a consent process must contextualize the risks and benefits of such research to those of usual care. However, two issues warrant further consideration. First is the challenge of what to label this research. The Office for Human Research Protections refers to “standard of care” research. This is a problematic construct because “standard of care” is a legal threshold for negligence and does little to clarify that the focus of this research is to improve upon the variability of usual practices above this threshold. Lantos and Feudnter use the more common term “comparative effectiveness research.” We agree that it is appropriate to distinguish this from research for developing innovative interventions. But the ethical analysis, and more importantly, patient understanding, can be enhanced by a more descriptive term, “research on medical practices.” Working with colleagues on an empirical ethics project, we have used focus groups and surveys to assess the public’s and institutional review board members’ understanding of and attitudes toward this category of research. “Comparative effectiveness research,” we have found, may be clear to the research, bioethics, and regulatory communities but less clear to patients. The term does not make explicit that interventions already in standard use are being compared. When describing ROMP to patients, we can emphasize that it can also involve observational research, including medical record review. Awareness of medical record review is important for two reasons. First, it provides the context for understanding the rationale for randomized designs. Just as patients need to contextualize the risks and benefits of a randomized
ON THE WEB n Bioethics Forum http://www.bioethicsforum.org DNA Phenotyping and Baby’s First Portrait By Timothy F. Murphy If we start to use DNA phenotyping at embryonic stages, it may well be that some parents will pass over one embryo in favor of another because of the expected appearance of the future child and adult. The Drug That Cried “Feminism” By Alessandra Hirsch, Rebecca Holliman, and Adriane FughBerman Flibanserin, a failed-antidepressantturned-libido-boosting drug, has already been rejected twice by the FDA due to a lack of proven efficacy in the face of possible safety concerns. Rather than putting this drug to sleep, Sprout [Pharmaceuticals] attacked the FDA for, of all things, sexism. New York City’s Compromise on Dangerous Circumcision Practice Leaves Infants at Risk By Elizabeth Reis For years now ultra-Orthodox Jews, the mayor of New York, and the New York Department of Health have been trying to balance the demands of religious belief with the protection of vulnerable infants. Mayor Bill de Blasio has come up recently with a new “compromise”— if a baby contracts herpes or another infection that can be attributed, using a DNA test, to a particular mohel, then that mohel would be barred from performing metzitzah b’peh in the future. Cognition Enhancement and Technological Unemployment By Michele Loi Most economists dismiss as a “Luddite fallacy” every forecast of technological innovation having harmful consequences on society. But some recent papers . . . suggest that technological advancement has played a central role in the jobless recovery and stagnant median income of recent decades . . . H AS TI N GS C E N TE R RE P O RT
5
design to usual-care variation, it must be contextualized to alternative research approaches. While medical record review can contribute to generalizable knowledge, it has important limitations and can lead to incorrect determinations of risks and benefits. Therefore, ROMP, and its inclusion of observational and randomized designs, is conceptually important for patient understanding of the context. Second, patients may actually make less of a distinction between these two approaches than researchers, ethicists, and regulators. The regulatory framework includes distinctions between randomization and observational research as well as between uses of identifiable and deidentified data, but our study results indicate that the framework does not reflect how much of the public views these distinctions. Many studies, including some of our own, have shown that most people want to be aware of their involvement in research, regardless of whether they are randomized or whether their data is identifiable. A second issue related to the assessment of potential harms and benefits and its communication is addressed only tangentially, in the final section of Lantos and Feundter’s paper. We agree with the model language proposed for potential participants. But this does not explicitly talk about the potential harms and benefits of participating in such research. The critics of SUPPORT have rightly pointed out that the consent forms, which conveyed the potential for direct benefit from participation but did not convey risks, were problematic. But the problem with these forms was the overstatement of benefits, not the understatement of risks. Because of the uncertainty that the research was intended to address, we do not think that there were any substantial benefits or risks from participation compared to usual care. Communicating that there were substantial potential harms and benefits from the decision to Contributions to Exchange may be submitted to editorial@thehastingscenter. org. They should be no more than eight hundred words and without endnotes. They may be edited for style and length. 6 HASTIN G S C E N T E R R E P ORT
join the study would have profoundly misled patients. As the authors point out early in their paper, population benefit and harms are not the same as benefits and harms to individual patients. While a decision to participate in research can be important to many people, perhaps because of different views about communitarian obligations, we do not think that participating in ROMP compared to usual care presents sustainable benefits and risks to patients. We would propose adding a paragraph to the consent message: “Because of our uncertainty about the differences between the approaches to be used in this research and our usual practices, there are no expectations of different benefits or harms whether you decide to have your child be part of this research or to have your child receive usual care. If you join the study, we will learn more from your child’s experiences compared to if you decide to have your child receive usual care. This may help other children in the future.”
This is not simply a communication issue but is important in the ethical evaluation of the research. Conceiving of ROMP that compares differential mortality or serious adverse effects as providing no potential benefit or harm compared to thinking of such research as posing substantial potential benefits and harms has profound regulatory implications for waivers or alterations of informed consent. We are committed to developing innovative approaches to improving patient understanding of ROMP, and conceiving of ROMP as minimal risk research allows regulatory options, which can permit research on how to improve patient understanding and make the research even more ethical. • Benjamin S. Wilfond Seattle Children’s Hospital • David C. Magnus Stanford University DOI: 10.1002/hast.440
In Memoriam: Alan Wertheimer We mourn the loss of Alan Wertheimer, who died on April 10, 2015. Alan’s contributions to bioethics were thought-provoking and far-reaching. He joined the National Institutes of Health Clinical Center Department of Bioethics in 2005 after retiring from the University of Vermont. Alan made his newness to bioethics a strength. Insulated from the reigning views in bioethics, he brought innovative discussions of coercion, exploitation, and consent—developed in three significant books written between 1987 and 2003—to bear on the ethics of clinical research, producing insights that shook up the conventional wisdom in research ethics. Alan practiced a fruitful method that was reflected in the subtitle of his 2011 book, Rethinking the Ethics of Clinical Research: Widening the Lens. Conventional views about informed consent in medicine and clinical research, for example, are taken for granted without thought to how different these views are from the way we think about other domains in which consent is morally significant, such as employment or sexual relations. Alan applied a wider lens to clarify concepts and refute some of what he saw as “medical exceptionalism”: “the view that participation in research is a distinctive activity that requires moral principles that we do not adopt or reject in other social contexts.” One example of this is the widespread view that payment of research participants is “coercive.” Alan demonstrated that this view cannot withstand critical scrutiny. Alan was a top-notch philosopher, an inquisitive and adventuresome scholar, and a generous and engaging colleague, collaborator, and mentor. He was conscientious almost to a fault and disarmingly humble given his extraordinary accomplishments. He was a mensch—a wonderful person and friend. All of us who knew him are better off because of it, and we will miss him greatly. —Franklin G. Miller and Christine Grady, National Institutes of Health May-June 2015
Copyright of Hastings Center Report is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
