This article was downloaded by: [Seton Hall University] On: 04 April 2015, At: 16:39 Publisher: Routledge Informa Ltd Registered in England and Wales Registered Number: 1072954 Registered office: Mortimer House, 37-41 Mortimer Street, London W1T 3JH, UK
The American Journal of Bioethics Publication details, including instructions for authors and subscription information: http://www.tandfonline.com/loi/uajb20
Compassion for Each Individual's Own Sake a
a
Arthur Caplan & Alison Bateman-House a
New York University Langone Medical Center Division of Medical Ethics Published online: 17 Oct 2014.
Click for updates To cite this article: Arthur Caplan & Alison Bateman-House (2014) Compassion for Each Individual's Own Sake, The American Journal of Bioethics, 14:11, 16-17, DOI: 10.1080/15265161.2014.957622 To link to this article: http://dx.doi.org/10.1080/15265161.2014.957622
PLEASE SCROLL DOWN FOR ARTICLE Taylor & Francis makes every effort to ensure the accuracy of all the information (the “Content”) contained in the publications on our platform. However, Taylor & Francis, our agents, and our licensors make no representations or warranties whatsoever as to the accuracy, completeness, or suitability for any purpose of the Content. Any opinions and views expressed in this publication are the opinions and views of the authors, and are not the views of or endorsed by Taylor & Francis. The accuracy of the Content should not be relied upon and should be independently verified with primary sources of information. Taylor and Francis shall not be liable for any losses, actions, claims, proceedings, demands, costs, expenses, damages, and other liabilities whatsoever or howsoever caused arising directly or indirectly in connection with, in relation to or arising out of the use of the Content. This article may be used for research, teaching, and private study purposes. Any substantial or systematic reproduction, redistribution, reselling, loan, sub-licensing, systematic supply, or distribution in any form to anyone is expressly forbidden. Terms & Conditions of access and use can be found at http:// www.tandfonline.com/page/terms-and-conditions
The American Journal of Bioethics, 14(11): 16–31, 2014 Copyright © Taylor & Francis Group, LLC ISSN: 1526-5161 print / 1536-0075 online DOI: 10.1080/15265161.2014.957622
Open Peer Commentaries
Compassion for Each Individual’s Own Sake
Downloaded by [Seton Hall University] at 16:39 04 April 2015
Arthur Caplan, New York University Langone Medical Center Division of Medical Ethics Alison Bateman-House, New York University Langone Medical Center Division of Medical Ethics Walker, Rogers, and Entwistle (2014) frame the issue of access to unapproved medical interventions (via special access programs such as early access, expanded access, compassionate use, named patient programs, etc.) as grounded in an ethical conflict between individuals and populations. Specifically, they depict showing compassion to individuals who have no treatments for their various medical issues as hindering the clinical research and regulatory approval process by which treatments become available for everyone. Walker and colleagues think they can resolve the dilemma of individual interest competing against the public good. They would grant individuals access to unapproved medical interventions in the name of compassion as long as data is derived from the experience that those individuals have with the novel treatment. These clinical data are seen as an adjunct to the standard testing of new treatments. Thus, according to Walker and her co-authors, compassionate use in individuals can aid the general population—in their terms, promote a corporate good—while offering assistance to individuals in need. We agree with the authors that there are sometimes ways to allow individuals special access that do not compromise the ability to collect sufficient data to protect the health of the general public and future potential users. But we wish to underscore three points. First, desperately ill patients who receive access to unapproved treatments may not provide worthwhile clinical data, simply on account of their degree of illness or disability. The terminally ill and extremely sick can shed little light on safety concerns. Demanding that data be collected on these patients to satisfy the corporate or common good is useful only to the extent that it is scientifically meaningful; otherwise, it is simply make-work that costs time, money, and effort. Second, granting individuals compassionate access can still be at odds with the protection of the common good if
special access decreases the number of individuals willing to serve in clinical trials. Compassionate use and other special access programs provide individuals with the desired intervention, a much more appealing proposition than potentially being assigned to the placebo arm of a clinical trial. While data may be generated from giving individuals with a disease or a terminal illness access, it is not the gold standard data that would be produced by a randomized, blinded clinical trial (Caplan 2007). The latter serves the common good far more than the less powerful data produced by studying a group of sick individuals, all of whom are receiving a novel intervention. The key ethical point we wish to make is that there does not appear to be public demand for special access to unapproved treatments to be justified by appeals to utility or by furthering a public good. As we have seen in cases like that of Josh Hardy (Caplan and Moch 2014), the public is typically eager to grant individuals special access to drugs, devices, operations, and the like solely on the grounds of a duty to rescue those facing imminent, serious peril. When people face dire outcomes, we are compelled, morally and psychologically, to try to help them. We do not feel a need to justify this for any reasons other than compassion for their plight. It is important to face squarely this human desire to rescue. It is often a moral value that is omitted in debates over compassionate use, including the discussion by Walker and colleagues. Acknowledging our urge to rescue allows us to confront other facts: for instance, that we are commonly more compelled psychologically and emotionally to rescue some types of people (e.g., children, “innocent victims,” the photogenic) than certain others (e. g., members of stigmatized populations, the elderly). Furthermore, by acknowledging the powerful pull of rescue, we are better positioned to understand situations such as the case of Sarah Murnaghan, in which a dying child was given a donor organ even though, on medical grounds,
Address correspondence to Arthur Caplan, New York University Langone Medical Center Division of Medical Ethics, 227 E. 30th Street, New York, NY 10016, USA. E-mail: [email protected]
16 ajob
Access to Unapproved Medical Interventions
Downloaded by [Seton Hall University] at 16:39 04 April 2015
she was likely not the most appropriate recipient for the scarce resource (deSante et al. 2014). If compassionate use can lead to the creation of valuable data, then surely these data ought be collected. The moral case for granting access is far simpler in such cases. But when the very ill and the dying cannot provide much in the way of useful data or when granting access undermines any reasonable chance of obtaining the “best” data through blinded, randomized trials, then Walker and colleagues’ solution collapses. And since a combination of compassion, pity, and duty leads many to want to provide access even when there are no data to be had or the data that can be accrued will be less than optimal, we need to acknowledge that compassion toward individuals sometimes simply trumps the common good (Richardson 2012). When and how to manage that fact ought be the subject of far more moral and policy debate. &
REFERENCES Caplan, A. 2007. Is it sound public policy to let the terminally ill access experimental medical innovations? American Journal of Bioethics 7(6): 1–3. Caplan, A. and K. Moch. 2014. Rescue me: The challenge of compassionate use in the social media era. Health Affairs Blog. Available at: http://healthaffairs.org/blog/2014/08/27/rescueme-the-challenge-of-compassionate-use-in-the-social-media-era deSante, J., A. Caplan, B. Hippen, G. Testa, and J. D. Lantos. 2014. Was Sarah Murnaghan treated justly? Pediatrics 134(1): 1–8. Richardson, H. S. 2012. Moral entanglements. New York, NY: Oxford University Press. Walker, M. J., W. A. Rogers, and V. Entwistle. 2014. Ethical justifications for access to unapproved medical interventions: An argument for (limited) patient obligations. American Journal of Bioethics 14(11): 3–15.
FDA Implementation of the Expanded Access Program in the United States Michelle Roth-Cline, U.S. Food and Drug Administration Robert Nelson, U.S. Food and Drug Administration The key question that must be addressed when making investigational drugs available for treatment use is how to fairly balance the interests of various stakeholders— patients’ desire for access to investigational drugs prior to marketing authorization, society’s interest in the efficient development of new therapeutic options for life-threatening diseases or conditions, and the need to protect seriously ill patients from unacceptable risks. Walker and colleagues (Walker, Rogers, and Entwistle 2014) provide a perspective on the ethical justification for special access programs (SAPs). Noting the tension between the desire of individuals to access investigational drugs and society’s need for data establishing the safety and efficacy of those drugs, Walker and colleagues propose that patients who receive an investigational drug under an SAP have an obligation to agree to the collection of data to generate knowledge. We would like to provide an additional perspective on how the current implementation of the expanded access program (EAP) for investigational drugs and biological products by the U.S. Food and Drug Administration (FDA) addresses several concerns about SAPs that were raised by the authors.1
Although expanded access was allowed informally earlier, there was no recognition of treatment use in FDA’s regulations until 1987. In part to ensure that pivotal trials were not delayed by allowing expanded access, the agency updated and expanded its regulations on EAPs in 2009 (FDA 2009). Investigational drugs and biological products that may be sought by patients under the EAP in the United States are FDA-regulated products that have been the subject of a previous investigational new drug (IND) application (FDA 2009, 40901). The administration of an IND-regulated investigational drug or biological product to a human being is considered a “clinical investigation” (i. e., FDA-regulated research), even if the product is only administered to a single subject (FDA 1987). As such, all IND regulations pertaining to the conduct of FDA-regulated research apply, including initial and continuing FDA review, ethics oversight and informed consent, and data collection and reporting requirements. Contrary to the statement by Walker and colleagues that SAPs “are not clearly either research or routine clinical practice,” administering an investigational drug under the EAP in the United States is defined clearly as an FDA-regulated
This article is not subject to U. S. Copyright Law. Address correspondence to Robert M. Nelson, U.S. Food and Drug Administration, Office of Pediatric Therapeutics, 10903 New Hampshire Ave., WO32, Room 5126, Silver Spring, MD 20993, USA. E-mail: [email protected] 1. The views represented in this commentary are solely those of the authors and do not necessarily represent the position of the Food and Drug Administration or the Department of Health and Human Services.
November, Volume 14, Number 11, 2014
ajob 17
The American Journal of Bioethics Publication details, including instructions for authors and subscription information: http://www.tandfonline.com/loi/uajb20
Compassion for Each Individual's Own Sake a
a
Arthur Caplan & Alison Bateman-House a
New York University Langone Medical Center Division of Medical Ethics Published online: 17 Oct 2014.
Click for updates To cite this article: Arthur Caplan & Alison Bateman-House (2014) Compassion for Each Individual's Own Sake, The American Journal of Bioethics, 14:11, 16-17, DOI: 10.1080/15265161.2014.957622 To link to this article: http://dx.doi.org/10.1080/15265161.2014.957622
PLEASE SCROLL DOWN FOR ARTICLE Taylor & Francis makes every effort to ensure the accuracy of all the information (the “Content”) contained in the publications on our platform. However, Taylor & Francis, our agents, and our licensors make no representations or warranties whatsoever as to the accuracy, completeness, or suitability for any purpose of the Content. Any opinions and views expressed in this publication are the opinions and views of the authors, and are not the views of or endorsed by Taylor & Francis. The accuracy of the Content should not be relied upon and should be independently verified with primary sources of information. Taylor and Francis shall not be liable for any losses, actions, claims, proceedings, demands, costs, expenses, damages, and other liabilities whatsoever or howsoever caused arising directly or indirectly in connection with, in relation to or arising out of the use of the Content. This article may be used for research, teaching, and private study purposes. Any substantial or systematic reproduction, redistribution, reselling, loan, sub-licensing, systematic supply, or distribution in any form to anyone is expressly forbidden. Terms & Conditions of access and use can be found at http:// www.tandfonline.com/page/terms-and-conditions
The American Journal of Bioethics, 14(11): 16–31, 2014 Copyright © Taylor & Francis Group, LLC ISSN: 1526-5161 print / 1536-0075 online DOI: 10.1080/15265161.2014.957622
Open Peer Commentaries
Compassion for Each Individual’s Own Sake
Downloaded by [Seton Hall University] at 16:39 04 April 2015
Arthur Caplan, New York University Langone Medical Center Division of Medical Ethics Alison Bateman-House, New York University Langone Medical Center Division of Medical Ethics Walker, Rogers, and Entwistle (2014) frame the issue of access to unapproved medical interventions (via special access programs such as early access, expanded access, compassionate use, named patient programs, etc.) as grounded in an ethical conflict between individuals and populations. Specifically, they depict showing compassion to individuals who have no treatments for their various medical issues as hindering the clinical research and regulatory approval process by which treatments become available for everyone. Walker and colleagues think they can resolve the dilemma of individual interest competing against the public good. They would grant individuals access to unapproved medical interventions in the name of compassion as long as data is derived from the experience that those individuals have with the novel treatment. These clinical data are seen as an adjunct to the standard testing of new treatments. Thus, according to Walker and her co-authors, compassionate use in individuals can aid the general population—in their terms, promote a corporate good—while offering assistance to individuals in need. We agree with the authors that there are sometimes ways to allow individuals special access that do not compromise the ability to collect sufficient data to protect the health of the general public and future potential users. But we wish to underscore three points. First, desperately ill patients who receive access to unapproved treatments may not provide worthwhile clinical data, simply on account of their degree of illness or disability. The terminally ill and extremely sick can shed little light on safety concerns. Demanding that data be collected on these patients to satisfy the corporate or common good is useful only to the extent that it is scientifically meaningful; otherwise, it is simply make-work that costs time, money, and effort. Second, granting individuals compassionate access can still be at odds with the protection of the common good if
special access decreases the number of individuals willing to serve in clinical trials. Compassionate use and other special access programs provide individuals with the desired intervention, a much more appealing proposition than potentially being assigned to the placebo arm of a clinical trial. While data may be generated from giving individuals with a disease or a terminal illness access, it is not the gold standard data that would be produced by a randomized, blinded clinical trial (Caplan 2007). The latter serves the common good far more than the less powerful data produced by studying a group of sick individuals, all of whom are receiving a novel intervention. The key ethical point we wish to make is that there does not appear to be public demand for special access to unapproved treatments to be justified by appeals to utility or by furthering a public good. As we have seen in cases like that of Josh Hardy (Caplan and Moch 2014), the public is typically eager to grant individuals special access to drugs, devices, operations, and the like solely on the grounds of a duty to rescue those facing imminent, serious peril. When people face dire outcomes, we are compelled, morally and psychologically, to try to help them. We do not feel a need to justify this for any reasons other than compassion for their plight. It is important to face squarely this human desire to rescue. It is often a moral value that is omitted in debates over compassionate use, including the discussion by Walker and colleagues. Acknowledging our urge to rescue allows us to confront other facts: for instance, that we are commonly more compelled psychologically and emotionally to rescue some types of people (e.g., children, “innocent victims,” the photogenic) than certain others (e. g., members of stigmatized populations, the elderly). Furthermore, by acknowledging the powerful pull of rescue, we are better positioned to understand situations such as the case of Sarah Murnaghan, in which a dying child was given a donor organ even though, on medical grounds,
Address correspondence to Arthur Caplan, New York University Langone Medical Center Division of Medical Ethics, 227 E. 30th Street, New York, NY 10016, USA. E-mail: [email protected]
16 ajob
Access to Unapproved Medical Interventions
Downloaded by [Seton Hall University] at 16:39 04 April 2015
she was likely not the most appropriate recipient for the scarce resource (deSante et al. 2014). If compassionate use can lead to the creation of valuable data, then surely these data ought be collected. The moral case for granting access is far simpler in such cases. But when the very ill and the dying cannot provide much in the way of useful data or when granting access undermines any reasonable chance of obtaining the “best” data through blinded, randomized trials, then Walker and colleagues’ solution collapses. And since a combination of compassion, pity, and duty leads many to want to provide access even when there are no data to be had or the data that can be accrued will be less than optimal, we need to acknowledge that compassion toward individuals sometimes simply trumps the common good (Richardson 2012). When and how to manage that fact ought be the subject of far more moral and policy debate. &
REFERENCES Caplan, A. 2007. Is it sound public policy to let the terminally ill access experimental medical innovations? American Journal of Bioethics 7(6): 1–3. Caplan, A. and K. Moch. 2014. Rescue me: The challenge of compassionate use in the social media era. Health Affairs Blog. Available at: http://healthaffairs.org/blog/2014/08/27/rescueme-the-challenge-of-compassionate-use-in-the-social-media-era deSante, J., A. Caplan, B. Hippen, G. Testa, and J. D. Lantos. 2014. Was Sarah Murnaghan treated justly? Pediatrics 134(1): 1–8. Richardson, H. S. 2012. Moral entanglements. New York, NY: Oxford University Press. Walker, M. J., W. A. Rogers, and V. Entwistle. 2014. Ethical justifications for access to unapproved medical interventions: An argument for (limited) patient obligations. American Journal of Bioethics 14(11): 3–15.
FDA Implementation of the Expanded Access Program in the United States Michelle Roth-Cline, U.S. Food and Drug Administration Robert Nelson, U.S. Food and Drug Administration The key question that must be addressed when making investigational drugs available for treatment use is how to fairly balance the interests of various stakeholders— patients’ desire for access to investigational drugs prior to marketing authorization, society’s interest in the efficient development of new therapeutic options for life-threatening diseases or conditions, and the need to protect seriously ill patients from unacceptable risks. Walker and colleagues (Walker, Rogers, and Entwistle 2014) provide a perspective on the ethical justification for special access programs (SAPs). Noting the tension between the desire of individuals to access investigational drugs and society’s need for data establishing the safety and efficacy of those drugs, Walker and colleagues propose that patients who receive an investigational drug under an SAP have an obligation to agree to the collection of data to generate knowledge. We would like to provide an additional perspective on how the current implementation of the expanded access program (EAP) for investigational drugs and biological products by the U.S. Food and Drug Administration (FDA) addresses several concerns about SAPs that were raised by the authors.1
Although expanded access was allowed informally earlier, there was no recognition of treatment use in FDA’s regulations until 1987. In part to ensure that pivotal trials were not delayed by allowing expanded access, the agency updated and expanded its regulations on EAPs in 2009 (FDA 2009). Investigational drugs and biological products that may be sought by patients under the EAP in the United States are FDA-regulated products that have been the subject of a previous investigational new drug (IND) application (FDA 2009, 40901). The administration of an IND-regulated investigational drug or biological product to a human being is considered a “clinical investigation” (i. e., FDA-regulated research), even if the product is only administered to a single subject (FDA 1987). As such, all IND regulations pertaining to the conduct of FDA-regulated research apply, including initial and continuing FDA review, ethics oversight and informed consent, and data collection and reporting requirements. Contrary to the statement by Walker and colleagues that SAPs “are not clearly either research or routine clinical practice,” administering an investigational drug under the EAP in the United States is defined clearly as an FDA-regulated
This article is not subject to U. S. Copyright Law. Address correspondence to Robert M. Nelson, U.S. Food and Drug Administration, Office of Pediatric Therapeutics, 10903 New Hampshire Ave., WO32, Room 5126, Silver Spring, MD 20993, USA. E-mail: [email protected] 1. The views represented in this commentary are solely those of the authors and do not necessarily represent the position of the Food and Drug Administration or the Department of Health and Human Services.
November, Volume 14, Number 11, 2014
ajob 17
