CLINICAL TRIALS
Perspective
Commentary on Wilson et al.
Clinical Trials 2014, Vol. 11(5) 530–531 Ó The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav DOI: 10.1177/1740774514545337 ctj.sagepub.com
Nancy MP King1,2
Discussions of no-consent protocols like Wilson et al.’s study of an alert system for acute kidney injury (AKI) in hospitalized patients1 often leave me feeling like Inspector Clouseau in The Return of the Pink Panther.2 When Clouseau confronts a street musician, he asks, ‘‘Do you have a license? City ordinance 47 B prohibits the playing of any musical instrument in a public place for the purpose of commercial enterprise without a license. You play that thing and people give you the money.’’ The musician replies, ‘‘People give the monkey the money.’’ To which Clouseau responds, ‘‘It is the same.’’ ‘‘Oh, not at all, monsieur,’’ he is told. ‘‘I am a musician, and the monkey is a businessman. He doesn’t tell me what to play, and I don’t tell him what to do with his money.’’ This kind of hairsplitting is increasingly common and, some would argue, increasingly necessary to understand and justify large, complex studies like comparative effectiveness research (CER), to distinguish research from quality improvement interventions, and to make appropriate use of cluster randomization designs. But it is also increasingly troubling for what it emphasizes and what it omits, especially with regard to the role of individuals affected by these interventions. Wilson et al.’s extensive discussion of the ethical issues they addressed in their study design begins by asserting that ‘‘the study includes neither direct intervention on patients nor any contact between study investigators and patients.’’1 The lack of contact between investigators and patient-subjects is true but trivial, as the investigators chose not to obtain prospective consent. And in a study the objective of which is to determine whether sending an alert message to providers will change their treatment of patients with AKI, and whether changes in treatment will effect changes in outcome, the assertion that the investigators are not directly intervening with patient-subjects seems like hairsplitting. It is certainly true that studies like these pose significant ethical challenges, and the investigators are to be applauded for their attention to them. It is also true that big-data studies, the learning healthcare systems model, and research using biobanks and data
repositories were not contemplated when the Belmont Report and the Common Rule were promulgated, and that a great deal of productive scholarly discussion, disagreement, and proffered guidance on these topics now graces the literature as a result of attending to the issues raised by these designs. My overall concern, however, is that research like the alert study and similar studies employing no-consent designs have the potential to significantly alter our views about the roles and rights of research subjects, and that this alteration is by no means an improvement. I have two broad concerns about this no-consent design. First, it is difficult to determine until the very end of the paper whether the investigators or their institutional review board (IRB) recognize that providers who are or are not sent alerts about AKI patientsubjects are also subjects in this research. Obviously they are; moreover, they are directly intervened upon by the investigators. It appears that notice of the study is offered only to those who receive an alert and are invited to visit the study website for more information. And because the investigators have reason to be concerned about contamination effects, it is unclear how much information is actually available to providers who visit the website. Thus, it is worth considering not only how patient-subjects are regarded in this and similar research but also how providers who are research subjects are treated. Second, the investigators argue persuasively, and their IRB agreed, that this research meets the conditions for waiver of consent. I agree that the risks of harm to both patient-subjects and provider-subjects are low. I also agree that obtaining prospective consent 1
Department of Social Sciences and Health Policy, Wake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine, WinstonSalem, NC, USA 2 Graduate Program in Bioethics, Center for Bioethics, Health, and Society, Wake Forest University, Winston-Salem, NC, USA Corresponding author: Nancy MP King, Department of Social Sciences and Health Policy, Wake Forest School of Medicine, Medical Center Blvd., Winston-Salem, NC 27157, USA. Email: [email protected]
Downloaded from ctj.sagepub.com at UNIV OF NORTH DAKOTA on May 16, 2015
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would take time and effort, but I cannot agree that it ‘‘would undermine both feasibility and scientific validity.’’1 The meaning and applicability of terms like ‘‘feasible’’ and ‘‘impracticable’’ are notoriously debatable in research ethics, but the argument that seeking consent results in too many decisions not to participate, and thus in invalid research, is really an argument that the consent process is working. The decision not to participate in research should not be reduced to concern about selection bias. If the results are insufficiently representative, then it is the task of investigators, and of the field as a whole, to increase potential subjects’ understanding of what their participation can contribute to scientific knowledge. Obtaining prospective consent for the alert study would require talking to a lot of inpatients. It would also require finding good ways of talking about the research: ways that are informative, but not alarming, given that only a small percentage of those asked for prospective consent will become subjects. But the principal requirement for doing this well is recognizing that the consent form and process are not merely IRB-created hurdles, that instead they actually matter, for reasons unrelated to either investigator burden or risks of harm. And that leads directly to my principal concern, which is that consent waivers and no-consent designs are too often justified by an analysis of burdens and harms, with no consideration given to what really matters: respect for the subjects of research, acknowledgment of their contributions, and engagement of investigators with communities of potential subjects to increase scientific literacy and to improve mutual understanding. Attending carefully to the consent form and process takes time and effort, not more effort than it takes to reduce risks of harm and ensure data integrity, but a different kind of effort. Indeed, there are some alternatives to traditional research informed consent that may go far enough toward accomplishing informed consent’s goals with less investigator burden. The AKI alert study and its IRB could have explored several such alternatives, such as short-form consent, notice with opt-out, and broad notice models. All of these have been discussed in the debate over pragmatic trials, CER, and learning healthcare systems, and all offer at least something more than silence.3–6 For instance, the investigators could perhaps have piloted a
notice with an opt-out model when they collected their baseline sample by running their algorithm without sending alerts. Determining which, if any, alteration to traditional research consent is best suited to the circumstances of a given trial requires more than consent/no-consent reductionism. Indeed, it calls for flexibility, inventiveness, and collaboration among investigators, IRBs, and scholars in research ethics and health communication in order to design, share, and discuss novel ways of informing and involving research subjects in big-data studies. But doing so also means believing that research subjects deserve to know when and why they are playing that role. Kim and Miller put it well: ‘‘We ordinarily judge that bypassing a person’s agency . for that person’s own good is unacceptable. Accordingly, the idea that ‘rights and dignity’ are respected as long as the study participant’s welfare interests are not violated is mistaken.’’5 Unfortunately, it is becoming far too easy for even valuable research like the AKI alert study to make this fundamental mistake. Declaration of conflicting interests None declared.
Funding This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.
References 1. Wilson FP, Reese PP, Shashaty MGS, et al. A trial of inhospital, electronic alerts for acute kidney injury: design and rationale. Clin Trials, IN PRESS. 2. Edwards B (director). The Return of the Pink Panther. ITC/United Artists, 1975. 3. Faden RR, Beauchamp TL and Kass NE. Informed consent, comparative effectiveness, and learning health care. N Engl J Med 2014; 370: 766–768. 4. Correspondence. Informed consent for comparative effectiveness trials. N Engl J Med 2014; 370: 1958–1960. 5. Kim SYH and Miller FG. Informed consent for pragmatic trials—the integrated consent model. N Engl J Med 2014; 370: 769–772. 6. Sugarman J and Califf RM. Ethics and regulatory complexities for pragmatic clinical trials. JAMA 2014; 311: 2381–2382.
Downloaded from ctj.sagepub.com at UNIV OF NORTH DAKOTA on May 16, 2015
Perspective
Commentary on Wilson et al.
Clinical Trials 2014, Vol. 11(5) 530–531 Ó The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav DOI: 10.1177/1740774514545337 ctj.sagepub.com
Nancy MP King1,2
Discussions of no-consent protocols like Wilson et al.’s study of an alert system for acute kidney injury (AKI) in hospitalized patients1 often leave me feeling like Inspector Clouseau in The Return of the Pink Panther.2 When Clouseau confronts a street musician, he asks, ‘‘Do you have a license? City ordinance 47 B prohibits the playing of any musical instrument in a public place for the purpose of commercial enterprise without a license. You play that thing and people give you the money.’’ The musician replies, ‘‘People give the monkey the money.’’ To which Clouseau responds, ‘‘It is the same.’’ ‘‘Oh, not at all, monsieur,’’ he is told. ‘‘I am a musician, and the monkey is a businessman. He doesn’t tell me what to play, and I don’t tell him what to do with his money.’’ This kind of hairsplitting is increasingly common and, some would argue, increasingly necessary to understand and justify large, complex studies like comparative effectiveness research (CER), to distinguish research from quality improvement interventions, and to make appropriate use of cluster randomization designs. But it is also increasingly troubling for what it emphasizes and what it omits, especially with regard to the role of individuals affected by these interventions. Wilson et al.’s extensive discussion of the ethical issues they addressed in their study design begins by asserting that ‘‘the study includes neither direct intervention on patients nor any contact between study investigators and patients.’’1 The lack of contact between investigators and patient-subjects is true but trivial, as the investigators chose not to obtain prospective consent. And in a study the objective of which is to determine whether sending an alert message to providers will change their treatment of patients with AKI, and whether changes in treatment will effect changes in outcome, the assertion that the investigators are not directly intervening with patient-subjects seems like hairsplitting. It is certainly true that studies like these pose significant ethical challenges, and the investigators are to be applauded for their attention to them. It is also true that big-data studies, the learning healthcare systems model, and research using biobanks and data
repositories were not contemplated when the Belmont Report and the Common Rule were promulgated, and that a great deal of productive scholarly discussion, disagreement, and proffered guidance on these topics now graces the literature as a result of attending to the issues raised by these designs. My overall concern, however, is that research like the alert study and similar studies employing no-consent designs have the potential to significantly alter our views about the roles and rights of research subjects, and that this alteration is by no means an improvement. I have two broad concerns about this no-consent design. First, it is difficult to determine until the very end of the paper whether the investigators or their institutional review board (IRB) recognize that providers who are or are not sent alerts about AKI patientsubjects are also subjects in this research. Obviously they are; moreover, they are directly intervened upon by the investigators. It appears that notice of the study is offered only to those who receive an alert and are invited to visit the study website for more information. And because the investigators have reason to be concerned about contamination effects, it is unclear how much information is actually available to providers who visit the website. Thus, it is worth considering not only how patient-subjects are regarded in this and similar research but also how providers who are research subjects are treated. Second, the investigators argue persuasively, and their IRB agreed, that this research meets the conditions for waiver of consent. I agree that the risks of harm to both patient-subjects and provider-subjects are low. I also agree that obtaining prospective consent 1
Department of Social Sciences and Health Policy, Wake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine, WinstonSalem, NC, USA 2 Graduate Program in Bioethics, Center for Bioethics, Health, and Society, Wake Forest University, Winston-Salem, NC, USA Corresponding author: Nancy MP King, Department of Social Sciences and Health Policy, Wake Forest School of Medicine, Medical Center Blvd., Winston-Salem, NC 27157, USA. Email: [email protected]
Downloaded from ctj.sagepub.com at UNIV OF NORTH DAKOTA on May 16, 2015
King
531
would take time and effort, but I cannot agree that it ‘‘would undermine both feasibility and scientific validity.’’1 The meaning and applicability of terms like ‘‘feasible’’ and ‘‘impracticable’’ are notoriously debatable in research ethics, but the argument that seeking consent results in too many decisions not to participate, and thus in invalid research, is really an argument that the consent process is working. The decision not to participate in research should not be reduced to concern about selection bias. If the results are insufficiently representative, then it is the task of investigators, and of the field as a whole, to increase potential subjects’ understanding of what their participation can contribute to scientific knowledge. Obtaining prospective consent for the alert study would require talking to a lot of inpatients. It would also require finding good ways of talking about the research: ways that are informative, but not alarming, given that only a small percentage of those asked for prospective consent will become subjects. But the principal requirement for doing this well is recognizing that the consent form and process are not merely IRB-created hurdles, that instead they actually matter, for reasons unrelated to either investigator burden or risks of harm. And that leads directly to my principal concern, which is that consent waivers and no-consent designs are too often justified by an analysis of burdens and harms, with no consideration given to what really matters: respect for the subjects of research, acknowledgment of their contributions, and engagement of investigators with communities of potential subjects to increase scientific literacy and to improve mutual understanding. Attending carefully to the consent form and process takes time and effort, not more effort than it takes to reduce risks of harm and ensure data integrity, but a different kind of effort. Indeed, there are some alternatives to traditional research informed consent that may go far enough toward accomplishing informed consent’s goals with less investigator burden. The AKI alert study and its IRB could have explored several such alternatives, such as short-form consent, notice with opt-out, and broad notice models. All of these have been discussed in the debate over pragmatic trials, CER, and learning healthcare systems, and all offer at least something more than silence.3–6 For instance, the investigators could perhaps have piloted a
notice with an opt-out model when they collected their baseline sample by running their algorithm without sending alerts. Determining which, if any, alteration to traditional research consent is best suited to the circumstances of a given trial requires more than consent/no-consent reductionism. Indeed, it calls for flexibility, inventiveness, and collaboration among investigators, IRBs, and scholars in research ethics and health communication in order to design, share, and discuss novel ways of informing and involving research subjects in big-data studies. But doing so also means believing that research subjects deserve to know when and why they are playing that role. Kim and Miller put it well: ‘‘We ordinarily judge that bypassing a person’s agency . for that person’s own good is unacceptable. Accordingly, the idea that ‘rights and dignity’ are respected as long as the study participant’s welfare interests are not violated is mistaken.’’5 Unfortunately, it is becoming far too easy for even valuable research like the AKI alert study to make this fundamental mistake. Declaration of conflicting interests None declared.
Funding This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.
References 1. Wilson FP, Reese PP, Shashaty MGS, et al. A trial of inhospital, electronic alerts for acute kidney injury: design and rationale. Clin Trials, IN PRESS. 2. Edwards B (director). The Return of the Pink Panther. ITC/United Artists, 1975. 3. Faden RR, Beauchamp TL and Kass NE. Informed consent, comparative effectiveness, and learning health care. N Engl J Med 2014; 370: 766–768. 4. Correspondence. Informed consent for comparative effectiveness trials. N Engl J Med 2014; 370: 1958–1960. 5. Kim SYH and Miller FG. Informed consent for pragmatic trials—the integrated consent model. N Engl J Med 2014; 370: 769–772. 6. Sugarman J and Califf RM. Ethics and regulatory complexities for pragmatic clinical trials. JAMA 2014; 311: 2381–2382.
Downloaded from ctj.sagepub.com at UNIV OF NORTH DAKOTA on May 16, 2015
