Obligation to Disclose Controversial Risk
Disclosing Controversial Risk in Informed Consent: How Serious is Serious? Jonathan M. Kocarnik, University of Washington A key aspect of informed consent is the “description of any reasonably foreseeable risks or discomforts to the subject” (Code of Federal Regulations Title 45: Section 46-116, n.d.). However, some risks may be neither proven nor disproven at the time of consent, and as such might not be included as potential risks in consent documents. In such cases where scientific consensus has not been reached on whether a risk exists, DeMarco and colleagues (2014) suggest the term “risk in equipoise.” Risk in equipoise is defined as “a serious risk of harm . . . when disputed evidence of risk has not been accepted as disproven by a consensus among specialists” (5). The authors recommend that such risks be disclosed in model informed consent documents, along with an explanatory statement regarding the researchers’ opinions on the applicability of the risk in equipoise to the current study. While this proposal for enhanced transparency is laudable and welcome, it is incomplete without further clarification and guidance. In particular, a defined threshold for determining which risks are sufficiently serious to warrant classification and disclosure as a “risk in equipoise” is needed. Without such clarification, the practical uptake of the proposed recommendations may be difficult. Missing from the proposed recommendations is a description of what is meant by “serious risk.” DeMarco and colleagues use excess death in the ACCORD trial as an example of a “risk in equipoise” that should have been reported in the consent document. Certainly, excess death is a serious and important potential research risk, and one that a “reasonable volunteer” would likely wish to know about in advance of trial enrollment (National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research 1979). Risks with disputed evidence, however, range across the severity spectrum. It is not clear whether controversial outcomes less extreme than “excess death” should similarly be eligible for inclusion as a “risk in equipoise.” For example, would disputed evidence regarding risk of depression meet the authors’ risk in equipoise standard? What about disputed evidence for nausea? Or intermittent hiccups? Should all potential risks, serious or not, be included as risks in equipoise? Because this threshold is not clearly defined by the authors, the group of risks that fall into the “risk in equipoise” category must be considered to be either all risks for which there is disputed evidence, or some subset of risks that meet currently undefined criteria.
As described in the following, both situations are potentially problematic. First, if all disputed risks meet the “risk in equipoise” framework, this may require a significant increase in the length of informed consent documents. The authors themselves cite evidence that “consent documents are already too long and onerous for research participants,” and that their framework helps in “avoiding the absurd need to list every conceivable harm that could befall a person” (4). Without explicit criteria regarding risk severity, however, all potential controversial risks could qualify as “risks in equipoise,” substantially lengthening these documents. On the other hand, if only members of some subset of disputed risks meet the “risk in equipoise” framework (i.e., are sufficiently serious), then the lack of a defined threshold potentially removes the primary benefit of the risk in equipoise model—that the risks reported to the participant do not rely on the view of the researcher. The authors suggest that applying the precautionary principle to risks in equipoise allows the prospective research participant to make his or her own determination in a transparent process. Without a clear threshold for which controversial risks qualify as risks in equipoise, however, the participant is still reliant on an evaluation by the researcher of whether a risk is serious enough to disclose. Requiring researchers to report their reasoning regarding a “risk in equipoise” is unlikely to provide the desired benefit to participants if the reasoning for whether a risk qualifies as a “risk in equipoise” is ambiguously left to the discretion of researchers. Hence, without explicit guidance, the reporting of “risks in equipoise” is unlikely to be very different from the current risk disclosure standard. In both cases, the larger the number of controversial risks that are included, the greater is the possibility that established risks get crowded out by disputed risks. This potentially dilutes the value of the information given to the prospective participant, and could lead to information overload and reduced decision-making capacity. This may be particularly problematic if such risks in equipoise are given the prominence suggested by the authors, who suggested in their ACCORD excess death example that “highlighting this serious and controversial risk should take priority and emphasis over the list of possible minor risks” (9). Since controversial risks might eventually be proven
Address correspondence to Jonathan M. Kocarnik, 1100 Fairview Ave N., Mailstop M4-B402, PO Box 19024, Seattle, WA 98109-1024, USA. E-mail: [email protected]
April, Volume 14, Number 4, 2014
ajob 13
The American Journal of Bioethics
spurious, this emphasis of potentially incorrect risks over correct risks might provide misleading information and lead participants to not consider established risks (minor or otherwise) as appropriately as they would otherwise. In conclusion, while the proposed “risk in equipoise” framework is promising, it requires additional clarification before it will be able to reach its full potential. The proposed framework would be strengthened by explicit criteria for how to define a “risk in equipoise,” particularly in regard to what constitutes a “serious and controversial” risk that might deserve emphasis over established minor risks. Such clarifications are necessary to ensure consistent disclosure of controversial risks across research protocols. Care will also need to be taken to ensure that the inclusion of “risks in equipoise” in informed consent documents does not lead to established risk factors being conflated as also being controversial by prospective participants. If these clarifications can be made, the proposed framework holds promise
for improving the transparency of the informed consent process, as well as increasing the autonomy of research participants to make informed decisions regarding their participation. REFERENCES Code of Federal Regulations. General requirements for informed consent. Public Welfare: Title 45 Section 46-116. Available at: http:// www.hhs.gov/humansubjects/guidance/45cfr46.html De Marco, J. P., P. J. Ford, D. J. Patton, and D. O. Stewart. 2014. Is there an ethical obligation to disclose controversial risk? A question from the ACCORD Trial. American Journal of Bioethics 14(4): 4–10. National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research. 1979. The Belmont Report. April 18. Available at: http://www.hhs.gov/ohrp/ humansubjects/guidance/belmont.html (accessed October 17, 2013).
Disclosure of Risks and Uncertainties Are Especially Vital in Light of Regenerative Medicine S. L. Niemansburg, University Medical Center Utrecht M. G. J. L. Habets, University Medical Center Utrecht J. J. M. van Delden, University Medical Center Utrecht A. L. Bredenoord, University Medical Center Utrecht In “Is There an Ethical Obligation to Disclose Controversial Risk?” De Marco and colleagues (2014) discuss the disclosure of disputed evidence of serious risk to future research participants. We agree with the authors that many ethical guidelines fail to provide certainty on disclosure of several types of risks. However, their proposed standard for conditions requiring disclosure of controversial evidence, risk in equipoise, fails, due to the confusing use of the concepts “risk” and “uncertainty,” the ambiguity of the concept equipoise in general, and flaws in their conception of risk in equipoise. In addition, we regret the authors’ omission of an elaborate discussion on the responsibility of researchers and institutional review boards (IRBs) to prevent proposing clinical research involving unreasonable risks to future research participants. Nevertheless, we believe the discussion on risk and uncertainty initiated by the authors is crucial, especially in the developing field of regenerative medicine (RM), where controversial
evidence is anticipated to take a prominent place in risk disclosure. THE EQUIVOCAL CONCEPTS “RISK” AND “EQUIPOISE” Although all ethical guidelines on clinical research require disclosure of risks, they do not, in general, provide specific statements as to what risks need disclosing. While it is not necessarily undesirable for guidelines to use broad terms like “possible risks,” “potential risks,” and “reasonable foreseeable risks,” we agree with DeMarco and colleagues that more clarity is necessary for uncertainty of harm. However, the proposal of DeMarco and colleagues does not provide clarity either, due to the lack of a clear conceptual ground for the different types of risks. In general, a risk can be defined in several ways, but it is common to consider it as a possible harm: a known
Address correspondence to S. L. Niemansburg, University Medical Center Utrecht, Julius Center, Department Medical Humanities, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands. E-mail: [email protected]
14 ajob
April, Volume 14, Number 4, 2014
Disclosing Controversial Risk in Informed Consent: How Serious is Serious? Jonathan M. Kocarnik, University of Washington A key aspect of informed consent is the “description of any reasonably foreseeable risks or discomforts to the subject” (Code of Federal Regulations Title 45: Section 46-116, n.d.). However, some risks may be neither proven nor disproven at the time of consent, and as such might not be included as potential risks in consent documents. In such cases where scientific consensus has not been reached on whether a risk exists, DeMarco and colleagues (2014) suggest the term “risk in equipoise.” Risk in equipoise is defined as “a serious risk of harm . . . when disputed evidence of risk has not been accepted as disproven by a consensus among specialists” (5). The authors recommend that such risks be disclosed in model informed consent documents, along with an explanatory statement regarding the researchers’ opinions on the applicability of the risk in equipoise to the current study. While this proposal for enhanced transparency is laudable and welcome, it is incomplete without further clarification and guidance. In particular, a defined threshold for determining which risks are sufficiently serious to warrant classification and disclosure as a “risk in equipoise” is needed. Without such clarification, the practical uptake of the proposed recommendations may be difficult. Missing from the proposed recommendations is a description of what is meant by “serious risk.” DeMarco and colleagues use excess death in the ACCORD trial as an example of a “risk in equipoise” that should have been reported in the consent document. Certainly, excess death is a serious and important potential research risk, and one that a “reasonable volunteer” would likely wish to know about in advance of trial enrollment (National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research 1979). Risks with disputed evidence, however, range across the severity spectrum. It is not clear whether controversial outcomes less extreme than “excess death” should similarly be eligible for inclusion as a “risk in equipoise.” For example, would disputed evidence regarding risk of depression meet the authors’ risk in equipoise standard? What about disputed evidence for nausea? Or intermittent hiccups? Should all potential risks, serious or not, be included as risks in equipoise? Because this threshold is not clearly defined by the authors, the group of risks that fall into the “risk in equipoise” category must be considered to be either all risks for which there is disputed evidence, or some subset of risks that meet currently undefined criteria.
As described in the following, both situations are potentially problematic. First, if all disputed risks meet the “risk in equipoise” framework, this may require a significant increase in the length of informed consent documents. The authors themselves cite evidence that “consent documents are already too long and onerous for research participants,” and that their framework helps in “avoiding the absurd need to list every conceivable harm that could befall a person” (4). Without explicit criteria regarding risk severity, however, all potential controversial risks could qualify as “risks in equipoise,” substantially lengthening these documents. On the other hand, if only members of some subset of disputed risks meet the “risk in equipoise” framework (i.e., are sufficiently serious), then the lack of a defined threshold potentially removes the primary benefit of the risk in equipoise model—that the risks reported to the participant do not rely on the view of the researcher. The authors suggest that applying the precautionary principle to risks in equipoise allows the prospective research participant to make his or her own determination in a transparent process. Without a clear threshold for which controversial risks qualify as risks in equipoise, however, the participant is still reliant on an evaluation by the researcher of whether a risk is serious enough to disclose. Requiring researchers to report their reasoning regarding a “risk in equipoise” is unlikely to provide the desired benefit to participants if the reasoning for whether a risk qualifies as a “risk in equipoise” is ambiguously left to the discretion of researchers. Hence, without explicit guidance, the reporting of “risks in equipoise” is unlikely to be very different from the current risk disclosure standard. In both cases, the larger the number of controversial risks that are included, the greater is the possibility that established risks get crowded out by disputed risks. This potentially dilutes the value of the information given to the prospective participant, and could lead to information overload and reduced decision-making capacity. This may be particularly problematic if such risks in equipoise are given the prominence suggested by the authors, who suggested in their ACCORD excess death example that “highlighting this serious and controversial risk should take priority and emphasis over the list of possible minor risks” (9). Since controversial risks might eventually be proven
Address correspondence to Jonathan M. Kocarnik, 1100 Fairview Ave N., Mailstop M4-B402, PO Box 19024, Seattle, WA 98109-1024, USA. E-mail: [email protected]
April, Volume 14, Number 4, 2014
ajob 13
The American Journal of Bioethics
spurious, this emphasis of potentially incorrect risks over correct risks might provide misleading information and lead participants to not consider established risks (minor or otherwise) as appropriately as they would otherwise. In conclusion, while the proposed “risk in equipoise” framework is promising, it requires additional clarification before it will be able to reach its full potential. The proposed framework would be strengthened by explicit criteria for how to define a “risk in equipoise,” particularly in regard to what constitutes a “serious and controversial” risk that might deserve emphasis over established minor risks. Such clarifications are necessary to ensure consistent disclosure of controversial risks across research protocols. Care will also need to be taken to ensure that the inclusion of “risks in equipoise” in informed consent documents does not lead to established risk factors being conflated as also being controversial by prospective participants. If these clarifications can be made, the proposed framework holds promise
for improving the transparency of the informed consent process, as well as increasing the autonomy of research participants to make informed decisions regarding their participation. REFERENCES Code of Federal Regulations. General requirements for informed consent. Public Welfare: Title 45 Section 46-116. Available at: http:// www.hhs.gov/humansubjects/guidance/45cfr46.html De Marco, J. P., P. J. Ford, D. J. Patton, and D. O. Stewart. 2014. Is there an ethical obligation to disclose controversial risk? A question from the ACCORD Trial. American Journal of Bioethics 14(4): 4–10. National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research. 1979. The Belmont Report. April 18. Available at: http://www.hhs.gov/ohrp/ humansubjects/guidance/belmont.html (accessed October 17, 2013).
Disclosure of Risks and Uncertainties Are Especially Vital in Light of Regenerative Medicine S. L. Niemansburg, University Medical Center Utrecht M. G. J. L. Habets, University Medical Center Utrecht J. J. M. van Delden, University Medical Center Utrecht A. L. Bredenoord, University Medical Center Utrecht In “Is There an Ethical Obligation to Disclose Controversial Risk?” De Marco and colleagues (2014) discuss the disclosure of disputed evidence of serious risk to future research participants. We agree with the authors that many ethical guidelines fail to provide certainty on disclosure of several types of risks. However, their proposed standard for conditions requiring disclosure of controversial evidence, risk in equipoise, fails, due to the confusing use of the concepts “risk” and “uncertainty,” the ambiguity of the concept equipoise in general, and flaws in their conception of risk in equipoise. In addition, we regret the authors’ omission of an elaborate discussion on the responsibility of researchers and institutional review boards (IRBs) to prevent proposing clinical research involving unreasonable risks to future research participants. Nevertheless, we believe the discussion on risk and uncertainty initiated by the authors is crucial, especially in the developing field of regenerative medicine (RM), where controversial
evidence is anticipated to take a prominent place in risk disclosure. THE EQUIVOCAL CONCEPTS “RISK” AND “EQUIPOISE” Although all ethical guidelines on clinical research require disclosure of risks, they do not, in general, provide specific statements as to what risks need disclosing. While it is not necessarily undesirable for guidelines to use broad terms like “possible risks,” “potential risks,” and “reasonable foreseeable risks,” we agree with DeMarco and colleagues that more clarity is necessary for uncertainty of harm. However, the proposal of DeMarco and colleagues does not provide clarity either, due to the lack of a clear conceptual ground for the different types of risks. In general, a risk can be defined in several ways, but it is common to consider it as a possible harm: a known
Address correspondence to S. L. Niemansburg, University Medical Center Utrecht, Julius Center, Department Medical Humanities, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands. E-mail: [email protected]
14 ajob
April, Volume 14, Number 4, 2014
