Informed Consent for Comparative Effectiveness Research Should Not Consider the Risks of the Standard Therapies That Are Being Studied as Risks of the Research

Abstract

There is a debate at the highest levels of government about how to classify the risks of research studies that evaluate therapies that are in widespread use. Should the risks of those therapies be considered as risks of research that is designed to evaluate those therapies? Or not? The Common Rule states, “In evaluating risks and benefits, the IRB should consider only those risks and benefits that may result from the research (as distinguished from risks and benefits of therapies subjects would receive even if not participating in the research).” (CFR 46.111 (a)(2)). By contrast, the Office of Human Research Protections, in a proposed “guidance” states, “The reasonably foreseeable risks of research include already-identified risks of the standards of care being evaluated as a purpose of the research.” (emphasis added).

In this paper, I argue that the Common Rule got it right and OHRP got it wrong. When treatments are in widespread use, the risks of those treatments are ever-present for all patients. By enrolling in formal studies that use rigorous methods to compare one treatment with another and that carefully monitor outcomes and adverse events, patients are protected from the risks of idiosyncratic practice variation. Their risks are decreased, rather than increased.

If OHRP's approach becomes the law of the land, patients will be misinformed about the relative risks of treatment and research in ways that undermine autonomy rather than promoting it and that make truly informed consent impossible.

Get full access to this article

View all access options for this article.

References

Office for Human Research Protections. Draft Guidance on Disclosing Reasonably Foreseeable Risks in Research Evaluating Standards of Care, available at <https://www.hhs.gov/ohrp/regulations-and-policy/requests-for-comments/draft-guidance-disclosing-risk-in-standards-of-care/index.html> (last visited August 10, 2017) (emphasis added).

F. T.

Bourgeois ,

M. C.

Monuteaux ,

A. M.

Stack , and

M. I.

Neuman , “Variation in Emergency Department Admission Rates in US Children's Hospitals,” Pediatrics 134, no. 3 (2014): 539-545.

J. D.

Birkmeyer ,

B. N.

Reames ,

McCulloch ,

A. J.

Carr ,

W. B.

Campbell , and

J. E.

Wennberg , “Understanding of Regional Variation in the Use of Surgery,” The Lancet 382, no. 9898 (2013): 1121-1129.

A. M.

Capron

, “The Real Problem Is Consent for Treatment, Not Consent for Research,” American Journal of Bioethics 13 (2013): 27-29.

Katz

, “The Education of the Physician Investigator,” Daedalus 98, no. 2 (1969): 480-501.

A. R.

Tait ,

Voepel-Lewis ,

B. J.

Zikmund-Fisher , and

Fagerlin , “Presenting Research Risks and Benefits to Parents: Does Format Matter?” Anesthesia & Analgesia 111, no. 3 (2010): 718-723.

Wennberg and

Gittelsohn , “Small Area Variations in Health Care Delivery,” Science 182, no. 4117 (1973): 1102-1108.

J. E.

Wennberg

, “Dealing with Medical Practice Variations: A Proposal for Action,” Health Affairs 3, no. 2 (1984): 6-32.

F. J.

Fowler Jr. ,

P. M.

Gallagher ,

J. P.

Bynum ,

M. J.

Barry ,

F. L.

Lucas , and

J. S.

Skinner , “Decision-Making Process Reported by Medicare Patients Who Had Coronary Artery Stenting or Surgery for Prostate Cancer,” Journal of General Internal Medicine 27, no. 8 (2012): 911-916.

10.

S. R.

Woodrow and

A. P.

Jenkins , “How Thorough Is the Process of Informed Consent Prior to Outpatient Gastroscopy? A Study of Practice in a United Kingdom District Hospital,” Digestion 73, nos. 2-3 (2006): 189-197.

11.

A. M.

Knops ,

D. A.

Legemate ,

Goossens ,

P. M.

Bossuyt ,

D. T.

Ubbink , “Decision Aids for Patients Facing a SurgicalTreatment Decision: A Systematic Review and Meta-analysis,” Annals of Surgery 257, no. (2013): 860-866.

12.

SUPPORT Study Group of the Eunice Kennedy Shriver NICHD Neonatal Research Network,

W. A.

Carlo ,

N. N.

Finer , and

M. C.

Walsh et al., “Target Ranges of Oxygen Saturation in Extremely Preterm Infants,” New England Journal of Medicine 362 (2010): 1959-1969.

13.

Letter from OHRP to University of Alabama at Birmingham, available at <http://www.hhs.gov/ohrp/detrm_letrs/YR13/jun13a.pdf> (last visited August 4, 2017).

14.

HHS, OHRP Draft Guidance on Disclosing Reasonably Foreseeable Risk in Research Evaluating Standards of Care, available at <https://www.hhs.gov/ohrp/regulations-and-policy/requests-for-comments/draft-guidance-disclosing-risk-in-standards-of-care/index.html> (last visited August 4, 2017).

15.

Letter from Public Citizen to HHS, April 10, 2013, available at <http://www.citizen.org/documents/2111.pdf> (last visited August 4, 2017).

16.

K. J.

Barrington

, “Personalized Medicine in the NICU,” American Journal of Bioethics 13, no. 12 (2013): 33-35.

17.

L. R.

Churchill

, “Physician-Investigator/Patient-Subject: Exploring the Logic and the Tension,” Journal of Medicine and Philosophy 5, no. 3 (1980): 215-224.

18.

G. J.

Annas and

C. L.

Annas , “Legally Blind: The Therapeutic Illusion in the SUPPORT Study of Extremely Premature Infants,” Journal of Contemporary Health Law and Policy 30, no. 1 (2013): 1-36.

19.

Hellman and

D. S.

Hellman , “OfMicebut NotMen. Problems of the Randomized Clinical Trial,” New England Journal of Medicine 324, no. 22 (1991): 1585-1589.

20.

Macklin and

Shepherd , “Informed Consent and Standard of Care: What Must Be Disclosed?” American Journal of Bio-ethics 13, no. 12 (2013): 9-13.

21.

Letter from OHRP to University of Alabama at Birmingham, available at <http://www.hhs.gov/ohrp/detrm_letrs/YR13/jun13a.pdf> (last visited August 4, 2017).

22.

Brody and

F. G.

Miller , “The Research-Clinical Practice Distinction, Learning Health Care Systems, and Relationship,” Hastings Center Report 43, no. 5 (2013): 41-47.

23.

See Churchill, supra note 17.

24.

Martin

, “The Addict Also Rises,” Chronicle Higher Education, November 11, 2013, available at <http://chronicle.com/article/Book-Review-The-Addict-Also/142861/> (last visited August 4, 2017).

25.

Fost

, “Waived Consent for Emergency Research,” American Journal of Law & Medicine 24, nos. 2-3 (1998): 163-184.

26.

Barrington

, “What Are the Responsibilities of Clinical Researchers?” available at <http://neonatalresearch.org/2013/09/18/what-are-the-responsibilities-of-clinical-researchers/> (last visited August 4, 2017).

27.

Wakabayashi ,

Delhaye ,

Maluenda et al., “Prognosis of Asymptomatic Coronary Artery Disease after Percutaneous Coronary Intervention,” American Journal of Cardiology 105, no. 11 (2010): 1507-1512.

28.

See Bourgeois et al., supra note 1.