The

n e w e ng l a n d j o u r na l

of

m e dic i n e

Informed Consent for Comparative Effectiveness Trials To the Editor: We reject the argument by Faden et al. (Feb. 20 issue)1 that certain research with randomized assignment of interventions can be conducted without the consent of patients. Whether or not these studies are embedded in the routine processes of medical care, randomization equals research, and such studies are subject to all of the standard requirements for research, including approval by an institutional review board and patient consent. Patients have the right to choose whether to participate after they have been informed about the interventions, risks, and potential benefits and alternatives, irrespective of the risk levels of the interventions. Patients are the ultimate arbiters of what is done to them. Integrated consent, as proposed by Kim and Miller in the same issue of the Journal,2 is fine in theory but difficult in practice. Few studies involve the comparison of agents delivered in the same way with similar side effects. In most research settings, written disclosure of the treatments being compared, including their risks and potential benefits, is necessary. Written documentation of the patient’s agreement to be a research subject remains essential. James R. Anderson, Ph.D. Frontier Science and Technology Research Foundation Madison, WI

Children’s Hospital of Philadelphia Philadelphia, PA

[email protected] Dr. Schreiner reports serving as the chair of the committees for the protection of human subjects (the institutional review boards) of Children’s Hospital of Philadelphia. No other potential conflict of interest relevant to this letter was reported. 1. Code of Federal Regulations, Title 45, Public Welfare. De-

Emory University Atlanta, GA No potential conflict of interest relevant to this letter was reported.

partment of Health and Human Services. Part 46, Protection of human subjects, Section 46.116. 2. Code of Federal Regulations, Title 21, Public Welfare. Department of Health and Human Services. Part 312, Investigational new drug application, Section 312.2(b). 3. Code of Federal Regulations, Title 21, Public Welfare. Department of Health and Human Services. Part 50, Protection of human subjects, Section 50.25.

1. Faden RR, Beauchamp TL, Kass NE. Informed consent, com-

DOI: 10.1056/NEJMc1403310

[email protected]

Toby L. Schonfeld, Ph.D.

parative effectiveness, and learning health care. N Engl J Med 2014;370:766-8. 2. Kim SYH, Miller FG. Informed consent for pragmatic trials — the integrated consent model. N Engl J Med 2014;370:769-72. DOI: 10.1056/NEJMc1403310

To the Editor: In their articles, Faden et al. and Kim and Miller propose alternative approaches to consent for comparative-effectiveness trials. Both articles describe hypothetical studies comparing two medications with risks and benefits that appear to be similar. Faden et al. recommend that prospective patients could be informed about the trial through streamlined procedures, whereas Kim and Miller suggest that an abbreviated 1958

consent procedure would suffice, and they cite the requirements for alteration of informed consent as the justification.1 Unfortunately, even when study drugs are eligible for exemption from the investigational new drug requirements of the Food and Drug Administration (FDA), the investigator must ensure that the “investigation is conducted in compliance with the requirements for institutional review set forth in part 56 and with the requirements for informed consent set forth in part 50” of the human-subjects protection regulations of the FDA.2 In contrast to the Common Rule, these FDA regulations do not permit alteration or waiver of consent except under very limited circumstances. The informed-consent documentation and process for the two hypothetical trials described by Faden and colleagues and Kim and Miller would need to fully comply with these regulatory requirements.3 Mark S. Schreiner, M.D.

To the Editor: Faden et al. claim that current consent and oversight practices too often underprotect patients from medical error because they make research to reduce these problems very burdensome to conduct. The authors use the procedural difficulty of certain consent processes as part of their justification for their argument that informed-consent processes are not always ethically necessary. However, the doctrine of informed consent is intended to protect a patient’s decision-making ability and to respect the person’s dignity.1 Although policymakers ought to minimize the difficulties researchers and physi-

n engl j med 370;20 nejm.org may 15, 2014

The New England Journal of Medicine Downloaded from nejm.org on August 14, 2015. For personal use only. No other uses without permission. Copyright © 2014 Massachusetts Medical Society. All rights reserved.

correspondence

cians face while conducting their studies, these difficulties are irrelevant to the topic of consent. Furthermore, although medical errors may result from the increased burdens of the consent processes, that does not mean that policymakers have reason to simply forgo the consent process in certain circumstances. Instead, they should attempt to find ways to better reduce these medical errors without potentially compromising a patient’s decision-making ability. Ahmed Elsayyad Johns Hopkins University Baltimore, MD

[email protected] No potential conflict of interest relevant to this letter was reported. 1. Wu WC, Pearlman RA. Consent in medical decision making:

the role of communication. J Gen Intern Med 1988;3:9-14.

DOI: 10.1056/NEJMc1403310

To the Editor: In response to Kim and Miller: there are examples of pragmatic trials that replace physician selection of care with randomized selection and do not require individual informed consent. Enhanced Peri-Operative Care for Highrisk patients,1 a cluster-randomized trial of a quality intervention for patients undergoing emergency laparotomy, is currently recruiting patients in the United Kingdom. Patients undergo randomization at the institutional level. There is no requirement for the physician to conceal inclusion in the study, since the patient receives the same care as any other patient in his or her care. Individualized consent is not a requirement, since the data will be collected by the National Emergency Laparotomy Audit of the United Kingdom and returned anonymized for data analysis. It is not unduly paternalistic to randomly assign patients this way, because their interests are democratically represented by a patient and public involvement group (the National Institute for Clinical Excellence Patient and Public Involvement Programme)2 and the intervention, a care pathway, presents little opportunity for meaningful objection. This method of randomization is unsuitable, but the requirement for independent lay members on research ethics committees acts as a check; this makes this method a useful tool for closely integrated health care trials.

To the Editor: Faden et al. propose that written, prospective informed consent is not ethically necessary for all comparative-effectiveness research (CER) in a mature learning health care system. Although their intention to make such research less burdensome is commendable, there are potential pitfalls to streamlining the informedconsent process. First, the authors propose “transparent mechanisms” to ensure that the public and patients will be aware of ongoing CER Robin T.W. Williams, M.B., B.S. studies. Often, however, the patients who are 15 Holmes Rd. most in need of the protection afforded by the London, United Kingdom current arduous informed-consent process have No potential conflict of interest relevant to this letter was repoor health literacy and are unable to navigate ported. the complex health care system in the United Enhanced Peri-Operative Care for High-risk patients (EPOCH) States. Second, the current informed-consent dis- 1. trial home page (http://www.epochtrial.org/epoch.php). cussion serves a purpose beyond simply educat- 2. INVOLVE briefing notes for researchers: involving the pubing the patient. The clinician-researcher wears lic in NHS, public health and social care research. Eastleigh, Kingdom: INVOLVE (http://www.invo.org.uk/wp-content/ two hats in the care of patients, and he or she United uploads/2012/04/INVOLVEBriefingNotesApr2012.pdf). must be cognizant of the different goals of these enterprises to be able to identify and avoid con- DOI: 10.1056/NEJMc1403310 flicts of interest. A distinct consent process is a reminder to the researcher of this dual role. The Authors Reply: The criticism by Anderson Parth K. Modi, M.D. and Schonfeld that randomization constitutes reRutgers Robert Wood Johnson Medical School search misses our point. CER with randomizaNew Brunswick, NJ [email protected] tion is undeniably research but, in ethically maNo potential conflict of interest relevant to this letter was re- ture learning health care systems, we challenge ported. whether the use of randomization in CER should automatically trigger written informed-consent DOI: 10.1056/NEJMc1403310

n engl j med 370;20 nejm.org may 15, 2014

The New England Journal of Medicine Downloaded from nejm.org on August 14, 2015. For personal use only. No other uses without permission. Copyright © 2014 Massachusetts Medical Society. All rights reserved.

1959

The

n e w e ng l a n d j o u r na l

requirements. What matters morally in appropriate oversight and consent practices is not whether an activity is labeled research, but how the activity affects the rights and interests of patients.1 Even in the current health care context, we question the assumption that randomized CER always compromises these rights and interests. When CER introduces few if any compromises while furthering patients’ interests in improving care, a streamlined consent process is ethically acceptable. As Schreiner notes, some of our views may not comport with federal regulations. Our article is not about current regulations or oversight practice; it is about what ethically should exist for CER, both in the future, when morally robust learning health care systems are in place, and in the current health care environment. Elsayyad rightly says that respecting the dignity of patients should remain fundamental, and it is one of seven core obligations in our Common Purpose Framework.2 We merely challenge whether written informed consent is always the only or the best mechanism for respecting patients in CER. Modi correctly states that attention must be devoted to low health literacy. A moral objective in developing transparent mechanisms for learning health care systems and in soliciting informed consent is that patients acquire adequate understanding. Consent practices too often work against the goal of patient understanding, especially among patients with low literacy.3,4 In one review, the median length of 124 consent forms was 27 pages.5 Our proposal for a learning health care system further requires that patients be substantively engaged in ethics oversight of research. The moral objective here is that the perspectives and interests of all patients, including those with low health literacy, figure prominently in ethics review. Kim and Miller mischaracterize our view as a “no consent” model. We maintain that what should be required in the way of consent depends not only on characteristics of the research but also on the degree to which morally relevant background conditions are present, including patient engagement, transparency, and account-

1960

of

m e dic i n e

ability, as well as on having all patients benefit from CER quality improvements. We support a fundamental obligation to respect the rights of patients that in many research contexts will continue to require individual informed consent. Kim and Miller ignore our core positions on these subjects. They also wrongly conclude that practices and policies grounded in our framework would condone or even require untruthful answers by physicians when patients ask why a particular treatment is chosen. We have consistently maintained that randomized CER without consent requires that patients appreciate that some learning activities, including those with randomization, occur routinely and always with appropriate review and oversight in which patients are engaged. Physicians in this environment must answer patients’ questions about randomization truthfully, as in all other matters. Concealment has no place in a learning health care system or any other health care system. Ruth R. Faden, Ph.D., M.P.H. Johns Hopkins University Baltimore, MD

Tom L. Beauchamp, Ph.D. Georgetown University Washington, DC

Nancy E. Kass, Sc.D. Johns Hopkins University Baltimore, MD Since publication of their article, the authors report no further potential conflict of interest. 1. Kass NE, Faden RR, Goodman SN, Pronovost P, Tunis S,

Beauchamp TL. The research-treatment distinction: a problematic approach for determining which activities should have ethical oversight. Hastings Cent Rep 2013;43(1):Spec No:S4-S15. 2. Faden RR, Kass NE, Goodman, SN, Pronovost P, Tunis S, Beauchamp TL. An ethics framework for a learning health care system: a departure from traditional research ethics and clinical ethics. Hastings Cent Rep 2013;43(1):Spec No:S16-S27. 3. Nishimura A, Carey J, Erwin PJ, Tilburt JC, Murad MH, McCormick JB. Improving understanding in the research informed consent process: a systematic review of 54 interventions tested in randomized control trials. BMC Med Ethics 2013;14:28. 4. Tamariz L, Palacio A, Robert M, Marcus EN. Improving the informed consent process for research subjects with low literacy: a systematic review. J Gen Intern Med 2013;28:121-6. 5. Kass NE, Chaisson L, Taylor HA, Lohse J. Length and complexity of US and international HIV consent forms from federal HIV network trials. J Gen Intern Med 2011;26:1324-8. DOI: 10.1056/NEJMc1403310

n engl j med 370;20 nejm.org may 15, 2014

The New England Journal of Medicine Downloaded from nejm.org on August 14, 2015. For personal use only. No other uses without permission. Copyright © 2014 Massachusetts Medical Society. All rights reserved.

Informed consent for comparative effectiveness trials.

Informed consent for comparative effectiveness trials. - PDF Download Free
304KB Sizes 0 Downloads 3 Views