{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2024,6,29]],"date-time":"2024-06-29T17:40:07Z","timestamp":1719682807741},"reference-count":192,"publisher":"Cambridge University Press (CUP)","issue":"3","license":[{"start":{"date-parts":[[2021,1,1]],"date-time":"2021-01-01T00:00:00Z","timestamp":1609459200000},"content-version":"unspecified","delay-in-days":1827,"URL":"https:\/\/www.cambridge.org\/core\/terms"},{"start":{"date-parts":[[2016,1,1]],"date-time":"2016-01-01T00:00:00Z","timestamp":1451606400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["J. Law. Med. Ethics"],"published-print":{"date-parts":[[2016]]},"abstract":"<jats:p>This Essay examines the elegantly simple idea that consent to medical treatment or participation in human research must be \u201cinformed\u201d to be valid. It does so by using as a case study the controversial clinical research trial known as the Surfactant, Positive Pressure, and Oxygenation Randomized Trial (\u201cSUPPORT\u201d). The Essay begins by charting, through case law and the adoption of the common rule, the evolution of duties to secure fully informed consent in both research and treatment. The Essay then utilizes the SUPPORT study, which sought to pinpoint the level of saturated oxygen that should be provided to extremely low birth weight infants to demonstrate modern complexities and shortcomings of the duty to secure informed consent. This Essay shows how the duty is measured by foreseeability of risks and benefits in human research and why federal regulators believed the tradeoffs in risk and benefits from differing oxygen levels administered in the support study were foreseeable. It then explores the contours of the duty to secure informed consent when applied to researchers who also serve as treating physicians, highlighting how common law duties differ in jurisdictions that apply the professional standard and those that apply the patient-centered material risk standard. This Essay provides new insight into what the law must do to make real the notion that [e]very human being of adult years and sound mind has a right to determine what shall be done with his body.\u201d<\/jats:p>","DOI":"10.1177\/1073110516667938","type":"journal-article","created":{"date-parts":[[2017,12,12]],"date-time":"2017-12-12T10:22:15Z","timestamp":1513074135000},"page":"402-418","update-policy":"http:\/\/dx.doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":3,"title":["Realizing Informed Consent in Times of Controversy: Lessons from the SUPPORT Study"],"prefix":"10.1017","volume":"44","author":[{"given":"Robert J.","family":"Morse","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robin Fretwell","family":"Wilson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"56","published-online":{"date-parts":[[2021,1,1]]},"reference":[{"key":"S1073110500020544_bib48","doi-asserted-by":"crossref","unstructured":"48. Culbertson v. Mernitz, 602 N.E.2d 98, 98\u2013103 (Ind. 1992); id.","DOI":"10.1080\/07434619212331276143"},{"key":"S1073110500020544_bib163","unstructured":"164. Id."},{"key":"S1073110500020544_bib44","unstructured":"44. Id., at 172."},{"key":"S1073110500020544_bib24","unstructured":"24. Id., at 3."},{"key":"S1073110500020544_bib139","unstructured":"140. Id., at 9."},{"key":"S1073110500020544_bib92","unstructured":"92. Berman v. Hutchinson Cancer Center, available at <http:\/\/biotech.law.lsu.edu\/research\/wa\/Berman_v_Hutchinson.pdf> (last visited July 6, 2016)."},{"key":"S1073110500020544_bib100","unstructured":"100. See Carlo, supra note 5, at 1959."},{"key":"S1073110500020544_bib144","unstructured":"145. See, e.g., Lantos and Feudtner, supra note 114, at 37."},{"key":"S1073110500020544_bib131","unstructured":"132. Id. (emphasis added)."},{"key":"S1073110500020544_bib87","unstructured":"87. Cho, M. K. and Magnus, D. , \u201cTherapeutic Misconception and Stem Cell Research,\u201d Nature.com, September 27, 2007, available at <http:\/\/www.nature.com\/stem-cells\/2007\/0709\/070927\/full\/stemcells.2007.88.html> (citing P. Appelbaum, C. Lidz, and T. Grisso, \u201cTherapeutic Misconception in Clinical Research: Frequency and Risk Factors,\u201d IRB: Ethics of Human Research 26, no. 2 (2004): 1-8) (last visited July 6, 2016)."},{"key":"S1073110500020544_bib4","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1513\/pats.200706-072JK","article-title":"\u201cUsual Care as the Control Group in Clinical Trials of Nonpharmacologic Interventions,\u201d","volume":"4","author":"Thompson","year":"2007","journal-title":"Proceedings of the American Thoracic Society Journal"},{"key":"S1073110500020544_bib23","unstructured":"23. See Wilson, , \u201cPromise of Informed Consent,\u201d supra note *, at 4."},{"key":"S1073110500020544_bib21","unstructured":"21. General Requirements for Informed Consent, 45 C.F.R. \u00a7 46.116."},{"key":"S1073110500020544_bib146","unstructured":"147. See Drazen, supra note 142, at 1930."},{"key":"S1073110500020544_bib184","unstructured":"185. See, e.g., Transcript, supra note 8."},{"key":"S1073110500020544_bib13","doi-asserted-by":"publisher","DOI":"10.1093\/oso\/9780195126778.003.0023"},{"key":"S1073110500020544_bib59","unstructured":"59. Id., at 776."},{"key":"S1073110500020544_bib99","unstructured":"99. Oxygen saturation is a measurement of the level of oxygen in the blood. Target oxygen saturation rates for physicians treating adult patients is typically somewhere between 88 and 98 percent. Patients with low oxygen saturation levels are treated with \u201cinspired oxygen\u201d (FiO2)\u2014that is, air with a higher concentration of oxygen then that found in the atmosphere. See, e.g., Driscoll, B. R. et. al., \u201cBTS Guideline For Emergency Oxygen Use in Adult Patients,\u201d British Thoracic Society, available at <https:\/\/www.brit-thoracic.org.uk\/document-library\/clinical-information\/oxygen\/emergency-oxygen-use-in-adult-patients-guideline\/appendix-1-summary-of-recommendations-emergency-oxygen-use-in-adult-patients-guideline\/> (last visited July 6, 2016). This essay shorthands oxygen saturation as oxygen throughout."},{"key":"S1073110500020544_bib70","unstructured":"70. Id. (citations omitted)."},{"key":"S1073110500020544_bib62","first-page":"557","article-title":"\u201cInformed Consent Law and the Forgotten Duty of Physician Inquiry,\u201d","volume":"31","author":"Gatter","year":"2000","journal-title":"Loyola University Chicago Law Journal"},{"key":"S1073110500020544_bib135","unstructured":"136. March 7, 2013 Letter, supra note 126, at 2, 9. Amended to remove an institution not involved in SUPPORT and resent on March 7, 2013. Id."},{"key":"S1073110500020544_bib166","unstructured":"167. Id. (emphasis added)."},{"key":"S1073110500020544_bib102","unstructured":"102. Surfactant Positive Airway Pressure and Pulse Oximetry Trial in Extremely Low Birth Weight Infants (SUPPORT Study), University of Alabama at Birmingham Protocol 2 (emphasis added), Updated March 28, 2005, available at <https:\/\/www.nih.gov\/sites\/default\/files\/institutes\/foia\/support-protocol.pdf> [hereinafter UAB Protocol]."},{"key":"S1073110500020544_bib55","unstructured":"55. Id., at 1156."},{"key":"S1073110500020544_bib161","unstructured":"162. See June 4, 2013 Letter, supra note 119, at 2 (emphasis added)."},{"key":"S1073110500020544_bib2","author":"Young","year":"2010","journal-title":"The Healthcare Imperative: Lowering Costs and Improving Outcomes"},{"key":"S1073110500020544_bib134","unstructured":"135. Memorandum from Suzanne Murrin, Deputy Inspector General for Evaluations and Inspections, to Jerry Menikoff, Director, OHRP (Sept. 14, 2014), available at <http:\/\/oig.hhs.gov\/oei\/reports\/oei-01-14-00560.pdf> (last visited July 6, 2016)."},{"key":"S1073110500020544_bib176","unstructured":"177. Id., at 19 (forbidding the use of steroids within the first 21 days of an infant's life)."},{"key":"S1073110500020544_bib153","unstructured":"154. Id."},{"key":"S1073110500020544_bib34","unstructured":"34. Corn v. French, 74 Nev. 329, 330 (1958)."},{"key":"S1073110500020544_bib56","unstructured":"56. 519 P.2d 981 (Wash. 1974) (holding that custom was not determinative of the reasonableness inquiry in a medical negligence case)."},{"key":"S1073110500020544_bib88","unstructured":"88. Wilson, Estate of Gelsinger, supra note *, at 251\u2013253."},{"key":"S1073110500020544_bib78","unstructured":"78. The trial was sponsored by the University of Pennsylvania and the Children's Hospital of Philadelphia. See Wilson, Estate of Gelsinger, supra note *, at 230."},{"key":"S1073110500020544_bib125","unstructured":"126. See Letter from the Office of Human Research Protections to the University of Alabama at Birmingham at 5, March 7, 2013, available at <http:\/\/www.hhs.gov\/ohrp\/detrm_letrs\/YR13\/mar13a.pdf> [hereinafter March 7, 2013 Letter] (last visited July 6, 2016)."},{"key":"S1073110500020544_bib112","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1080\/15265161.2013.849303","article-title":"\u201cInformed Consent and Standard of Care: What Must Be Disclosed,\u201d","volume":"13","author":"Macklin","year":"2013","journal-title":"American Journal of Bio-ethics"},{"key":"S1073110500020544_bib170","unstructured":"171. Id., at \u00b6 54."},{"key":"S1073110500020544_bib114","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1002\/hast.407","article-title":"\u201cSUPPORT and the Ethics of Study Implementation: Lessons for Comparative Effectiveness Research from the Trial of Oxygen Therapy for Premature Babies,\u201d","volume":"45","author":"Lantos","year":"2015","journal-title":"Hastings Center Report"},{"key":"S1073110500020544_bib31","unstructured":"31. Id."},{"key":"S1073110500020544_bib43","unstructured":"43. Id., at 180."},{"key":"S1073110500020544_bib109","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/1471-2431-11-6","article-title":"\u201cNeoprom: Neonatal Oxygenation Prospective Meta-Analysis Collaboration Study Protocol,\u201d","volume":"11","author":"Askie","year":"2011","journal-title":"BMC Pediatrics"},{"key":"S1073110500020544_bib11","unstructured":"11. See Transcript, supra note 8."},{"key":"S1073110500020544_bib90","unstructured":"90. Wilson, Estate of Gelsinger, supra note *, at 248."},{"key":"S1073110500020544_bib75","first-page":"74","volume-title":"The Tuskegee Syphilis Study","author":"Gray","year":"1998"},{"key":"S1073110500020544_bib108","doi-asserted-by":"crossref","first-page":"1415","DOI":"10.1542\/peds.112.6.1415","article-title":"\u201cResolving Our Uncertainty about Oxygen Therapy,\u201d","volume":"112","author":"Cole","year":"2003","journal-title":"Pediatrics"},{"key":"S1073110500020544_bib6","unstructured":"6. Id."},{"key":"S1073110500020544_bib10","doi-asserted-by":"crossref","first-page":"1864","DOI":"10.1056\/NEJMp1305086","article-title":"\u201cRisk, Consent, and SUPPORT,\u201d","volume":"368","author":"Magnus","year":"2013","journal-title":"New England Journal of Medicine"},{"key":"S1073110500020544_bib93","unstructured":"93. Id., at 2."},{"key":"S1073110500020544_bib149","unstructured":"150. Id. (emphasis added)."},{"key":"S1073110500020544_bib179","unstructured":"180. See UAB Protocol, supra note 102, at 17\u201318."},{"key":"S1073110500020544_bib173","unstructured":"174. Looney v. Moore, 2015 WL 4773747 at *8 (N.D. AL. 2015) appealed sub. nom. Lewis v. Moore (11th Cir. 2015)."},{"key":"S1073110500020544_bib16","unstructured":"16. Id."},{"key":"S1073110500020544_bib41","unstructured":"41. Id., at 172."},{"key":"S1073110500020544_bib130","unstructured":"131. UAB Consent Form, supra note 128, at 4."},{"key":"S1073110500020544_bib177","unstructured":"178. Id., at 17."},{"key":"#cr-split#-S1073110500020544_bib140.1","unstructured":"141. See March 7, 2013 Letter, supra note 126, at 12. While it is true that these other trials were shut down based in part on SUPPORT findings, depending on how early the trade-off between blindness and death emerged during the SUPPORT study, SUPPORT researchers may have had a duty to-as two international counterparts had done-\"shut down [the study] early.\" N. Feldman, \"Courts Can't Mend a Parent's Broken Heart,\" Bloomberg View, September 10, 2015, available at <http:\/\/www.bloombergview.com\/articles\/2015-09-10\/courts-can-t-mend-a-parent-s-broken-heart> (making this observation about the international studies). Investigators should be cognizant of \"negative adverse reactions or events that a trial participant experiences during the conduct of the trial[,] [and these] should be documented. The investigators monitor for adverse reactions or events to determine safety during a clinical trial.\" J. P. E. Karlberg and M. A. Speers, eds., Reviewing Clinical Trials: A Guide for the Ethics Committee (2010): at 38, available at <https:\/\/www.pfizer.com\/files\/research\/research_clinical_trials\/ethics_committee_guide.pdf> (last visited July 6, 2016)"},{"key":"#cr-split#-S1073110500020544_bib140.2","doi-asserted-by":"crossref","unstructured":"see also Sica, D. A. , \"Premature Termination of Clinical Trials - Lessons Learned,\" 4(3) Journal of Clinical Hypertension (2002): 219-225, at 220 (discussing the \"[s]everal factors [that] can influence the decision to terminate an ongoing clinical trial including ethical concerns, alterations in accepted clinical practice that make the continuation of a clinical trial unwise, and\/or reaching a positive or negative statistical end point earlier than anticipated\") (emphasis added)","DOI":"10.1111\/j.1524-6175.2002.01094.x"},{"key":"#cr-split#-S1073110500020544_bib140.3","unstructured":"141. See March 7, 2013 Letter, supra note 126, at 12. While it is true that these other trials were shut down based in part on SUPPORT findings, depending on how early the trade-off between blindness and death emerged during the SUPPORT study, SUPPORT researchers may have had a duty to-as two international counterparts had done-\"shut down [the study] early.\" N. Feldman, \"Courts Can't Mend a Parent's Broken Heart,\" Bloomberg View, September 10, 2015, available at <http:\/\/www.bloombergview.com\/articles\/2015-09-10\/courts-can-t-mend-a-parent-s-broken-heart> (making this observation about the international studies). Investigators should be cognizant of \"negative adverse reactions or events that a trial participant experiences during the conduct of the trial[,] [and these] should be documented. The investigators monitor for adverse reactions or events to determine safety during a clinical trial.\" J. P. E. Karlberg and M. A. Speers, eds., Reviewing Clinical Trials: A Guide for the Ethics Committee (2010): at 38, available at <https:\/\/www.pfizer.com\/files\/research\/research_clinical_trials\/ethics_committee_guide.pdf> (last visited July 6, 2016); see also Sica, D. A. , \"Premature Termination of Clinical Trials - Lessons Learned,\" 4"},{"key":"#cr-split#-S1073110500020544_bib140.4","unstructured":"(3) Journal of Clinical Hypertension (2002): 219-225, at 220 (discussing the \"[s]everal factors [that] can influence the decision to terminate an ongoing clinical trial including ethical concerns, alterations in accepted clinical practice that make the continuation of a clinical trial unwise, and\/or reaching a positive or negative statistical end point earlier than anticipated\") (emphasis added); see Niemann, supra note 10 (detailing a study that was terminated after a negative endpoint became evident)."},{"key":"S1073110500020544_bib33","unstructured":"33. Id. Mrs. Corn also failed to adduce sufficient evidence of Dr. French's negligence to reach the jury, the trial court found. Her own expert admitted that he also would have removed Mrs. Corn's her breast without a biopsy, even though \u201cordinarily[,]\u2026 a biopsy would have been done\u201d first. Id., at 287."},{"key":"S1073110500020544_bib64","first-page":"1386","article-title":"\u201cEmergency Contraceptives or \u2018Abortion-Inducing\u2019 Drugs? Empowering Women to Make Informed Decisions,\u201d","volume":"71","author":"Hrobak","year":"2014","journal-title":"Washington and Lee Law Review"},{"key":"S1073110500020544_bib63","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1371\/journal.pone.0058603","article-title":"\u201cInteractive Informed Consent: Randomized Comparison with Paper Consents,\u201d","volume":"8","author":"Rowbotham","year":"2013","journal-title":"PLOS ONE"},{"key":"S1073110500020544_bib45","unstructured":"45. Id., at 181."},{"key":"S1073110500020544_bib67","unstructured":"67. See Wilson, Promise of Informed Consent, supra note *, at 3."},{"key":"S1073110500020544_bib29","unstructured":"29. Id., at 283."},{"key":"S1073110500020544_bib49","volume-title":"Health Law and Bioethics: Cases in Context","author":"Meisel","year":"2009"},{"key":"S1073110500020544_bib81","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1177\/009885881003600202","article-title":"\u201cThe Death of Jesse Gelsinger: New Evidence of the Influence of Money and Prestige in Human Research,\u201d","volume":"36","author":"Fretwell Wilson","year":"2010","journal-title":"American Journal of Law and Medicine"},{"key":"#cr-split#-S1073110500020544_bib76.1","unstructured":"76. This protection was enacted as part of the National Research Act of 1974 and codified with the Church Amendment. 42 U.S.C. \u00a7 300a-7(c) (2012)"},{"key":"#cr-split#-S1073110500020544_bib76.2","unstructured":"76. This protection was enacted as part of the National Research Act of 1974 and codified with the Church Amendment. 42 U.S.C. \u00a7 300a-7"},{"key":"#cr-split#-S1073110500020544_bib76.3","unstructured":"(c) (2012); see also McLellan, D. , \"Ernest Hendon, 96; Tuskegee Syphilis Study's Last Survivor,\" L.A. Times, January 25, 2004, available at <http:\/\/articles.latimes.com\/2004\/jan\/25\/local\/me-hendon25> (last visited July 6, 2016)."},{"key":"S1073110500020544_bib168","unstructured":"169. 79(206) Federal Register 63629, 63632."},{"key":"S1073110500020544_bib95","unstructured":"95. Id., at 4."},{"key":"S1073110500020544_bib137","unstructured":"138. Id., at 4 (citing UAB Protocol at 2, 3)."},{"key":"S1073110500020544_bib121","unstructured":"121. BPD is a \u201cform of chronic lung disease that affects newborns (mostly premature) and infants. It results from damage to the lungs caused by mechanical ventilation (respirator) and long-term use of oxygen.\u201d Bronchopulmonary Dysplasia, American Lung Association http:\/\/www.lung.org\/lung-health-and-diseases\/lung-disease-lookup\/bronchopulmonary-dysplasia\/ (Last visited May 5, 2016)."},{"key":"S1073110500020544_bib141","doi-asserted-by":"crossref","first-page":"1929","DOI":"10.1056\/NEJMe1304996","article-title":"\u201cInformed Consent and SUPPORT,\u201d","volume":"368","author":"Drazen","year":"2013","journal-title":"New England Journal of Medicine"},{"key":"S1073110500020544_bib14","unstructured":"14. See, generally, Presidential Commission for the Study of Bio-ethical Issues, \u201c\u2018Ethically Impossible\u2019: STD Research in Guatemala from 1946 to 1948,\u201d (2011): at 99-101, available at <http:\/\/bioethics.gov\/node\/654> (last visited July 6, 2016). U.S. Dept. of Health and Human Services (DHHS), The Common Rule, available at <http:\/\/www.hhs.gov\/ohrp\/humansubjects\/commonrule\/> (last visited July 6, 2016)."},{"key":"S1073110500020544_bib145","unstructured":"146. See UAB Protocol, supra note 102, at 3."},{"key":"S1073110500020544_bib54","unstructured":"54. Id."},{"key":"S1073110500020544_bib82","unstructured":"82. See id., at 299; Wilson, Estate of Gelsinger, supra note *, at 233."},{"key":"S1073110500020544_bib35","unstructured":"35. Corn, 71 Nev. at 285. Mrs. Corn's negligent diagnosis claim also should have gone to the jury. Id., at 290-91, 296."},{"key":"S1073110500020544_bib69","unstructured":"69. Id."},{"key":"S1073110500020544_bib38","unstructured":"38. Berg, , et al., supra note 13, at 44."},{"key":"S1073110500020544_bib19","unstructured":"19. Fifteen governmental departments have codified the Common Rule, requiring that the human research they fund adhere to it: Department of Agriculture, Department of Energy, National Aeronautics and Space Administration, Department of Commerce - National Institute of Standards and Technology, Consumer Product Safety Commission, Agency for International Development (USAID), Department of Housing and Urban Development, Department of Justice - National Institute of Justice, Department of Defense, Department of Education, Department of Veterans Affairs - Office of Research Oversight - Office of Research and Development, Environmental Protection Agency - Research and Development, Department of Health and Human Services, National Science Foundation, and the Department of Transportation. Three additional agencies follow the Common Rule via executive order: the Central Intelligence Agency, Department of Homeland Security, and Social Security Administration. U.S. Dep't of Health and Human Services, Federal Policy for the Protection of Human Subjects (\u2018Common Rule\u2019), supra note 14."},{"key":"S1073110500020544_bib172","doi-asserted-by":"crossref","unstructured":"173. Looney v. Moore, 2015 WL 4773747 at *8 (N.D. AL. 2015).","DOI":"10.17016\/FEDS.2015.058"},{"key":"S1073110500020544_bib185","unstructured":"186. Id., at 120\u201321 (quoting a parent of Dagen Pratt)."},{"key":"S1073110500020544_bib122","unstructured":"122. See UAB Protocol, supra note 102, at 19."},{"key":"S1073110500020544_bib42","unstructured":"42. Id., at 177\u201378."},{"key":"#cr-split#-S1073110500020544_bib181.1","unstructured":"182. The T.J. Hooper, 60 F.2d 737, 740 (2d Cir. 1932)"},{"key":"#cr-split#-S1073110500020544_bib181.2","unstructured":"see, e.g., Helling v. Carey, 519 P.2d 981 (1974) (holding that custom was not determinative of the reasonableness inquiry in a medical negligence inquiry, and citing The T.J. Hooper)."},{"key":"S1073110500020544_bib36","unstructured":"36. Mrs. Corn asked for and received \u201c[i]nstructions fixing defendant's liability if he operated without plaintiff's consent or after revocation of her consent.\u201d The trial judge also instructed the jury that Dr. French would be liable if he did not follow \u201cstandard practice in the community;\u201d in the end, the jury remained unconvinced. Id."},{"key":"S1073110500020544_bib25","unstructured":"25. 71 Nev. 280 (1955)."},{"key":"S1073110500020544_bib57","unstructured":"57. Id., at 983."},{"key":"S1073110500020544_bib18","unstructured":"18. General Requirements for Informed Consent, 45 C.F.R. \u00a7 46.116 (2015)."},{"key":"S1073110500020544_bib164","unstructured":"165. See Transcript, supra note 8."},{"key":"S1073110500020544_bib7","unstructured":"7. Id., at 1967."},{"key":"S1073110500020544_bib126","unstructured":"127. See Editorial, \u201cAn Ethical Breakdown,\u201d New York Times, Apr 15, 2013, available at <http:\/\/www.nytimes.com\/2013\/04\/16\/opinion\/an-ethical-breakdown-in-medical-research.html?_r=0> (last visited July 6, 2016)."},{"key":"S1073110500020544_bib158","unstructured":"159. Id."},{"key":"S1073110500020544_bib178","unstructured":"179. Transcript, supra note 8, at 120 (quoting parents of Dagen Pratt, an infant enrolled in SUPPORT, as testifying that \u201c[w] e want to know as information comes in, why the risks and intent of the study were not clear. If it were clear, we wouldn't have taken part in the study.\u201d)."},{"key":"S1073110500020544_bib71","unstructured":"71. Id."},{"key":"S1073110500020544_bib17","unstructured":"17. See Wilson, , Promise of Informed Consent, supra note *, at 2 (citation omitted)."},{"key":"S1073110500020544_bib60","unstructured":"60. Id., at 787 (citation omitted)."},{"key":"S1073110500020544_bib68","unstructured":"68. See Ethically Impossible, supra note 14, at 99."},{"key":"S1073110500020544_bib123","unstructured":"123. See Carlo, supra note 5, at 1960 (noting ROP also causes \u201cother visual disabilities in preterm infants. The incidence of [ROP] was increased with exposure to unrestricted oxygen supplementation in preterm infants in randomized controlled trials performed in the 1950s\u201d). Id."},{"key":"S1073110500020544_bib136","unstructured":"137. Id., at 10."},{"key":"S1073110500020544_bib30","unstructured":"30. Id., at 281. Mrs. Corn also sued Dr. French for negligently removing her breast because he never performed the promised biopsy. Id."},{"key":"S1073110500020544_bib73","unstructured":"73. Centers for Disease Control and Prevention, \u201cThe Tuskegee Timeline,\u201d December 10, 2013, available at <http:\/\/www.cdc.gov\/tuskegee\/timeline.htm> (last visited July 6, 2016)."},{"key":"S1073110500020544_bib106","unstructured":"106. Id,. at 2."},{"key":"S1073110500020544_bib28","unstructured":"28. Id."},{"key":"S1073110500020544_bib155","unstructured":"156. See June 4, 2013 Letter, supra note 119, at 5 n.8 (citing the BOOST Study Consent Form (emphasis modified))."},{"key":"S1073110500020544_bib182","doi-asserted-by":"crossref","unstructured":"183. Looney v. Moore, 2015 WL 4773747 at *8 (N.D. AL. 2015).","DOI":"10.17016\/FEDS.2015.058"},{"key":"S1073110500020544_bib119","unstructured":"119. Letter from the Office for Human Research Protections to the University of Alabama at Birmingham at 3, June 4, 2013, available at <http:\/\/www.hhs.gov\/ohrp\/detrm_letrs\/YR13\/jun13a.pdf> [hereinafter June 4, 2013 Letter] (last visited July 6, 2016)."},{"key":"S1073110500020544_bib84","unstructured":"84. Wilson, Death of Gelsinger, supra note 81, at 303 (quoting the consent form for the study)."},{"key":"S1073110500020544_bib110","unstructured":"110. See UAB Protocol, supra note 102, at 2."},{"key":"S1073110500020544_bib103","unstructured":"103. See Carlo, supra note 5, at 1960."},{"key":"S1073110500020544_bib9","doi-asserted-by":"crossref","DOI":"10.1093\/oso\/9780195147971.001.0001","author":"Menikoff","year":"2006","journal-title":"What the Doctor Didn't Say: The Hidden Truth About Medical Research"},{"key":"S1073110500020544_bib5","doi-asserted-by":"crossref","first-page":"1959","DOI":"10.1056\/NEJMoa0911781","article-title":"\u201cTarget Ranges of Oxygen Saturation in Extremely Preterm Infants,\u201d","volume":"362","author":"Carlo","year":"2010","journal-title":"New England Journal of Medicine"},{"key":"S1073110500020544_bib156","unstructured":"157. Id."},{"key":"S1073110500020544_bib79","unstructured":"79. Id., at 229."},{"key":"S1073110500020544_bib20","unstructured":"20. See DHHS, supra note 14."},{"key":"S1073110500020544_bib117","unstructured":"117. Id."},{"key":"S1073110500020544_bib175","unstructured":"176. See UAB Protocol, supra note 102, at 17."},{"key":"S1073110500020544_bib162","unstructured":"163. See id., at 2 n.2, 5 n.8 (collecting studies that recognized these risks); Part II.A, supra."},{"key":"S1073110500020544_bib128","unstructured":"129. Id., at 2 (emphasis added)."},{"key":"S1073110500020544_bib61","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1111\/j.1740-1461.2007.00083.x","article-title":"\u201cGeographic Variation in Informed Consent Law: Two Standards for Disclosure of Treatment Risks,\u201d","volume":"4","author":"Studdert","year":"2007","journal-title":"Journal of Empirical Legal Studies"},{"key":"S1073110500020544_bib40","unstructured":"40. Id. (citations omitted)."},{"key":"S1073110500020544_bib51","unstructured":"51. Id., at 1151."},{"key":"S1073110500020544_bib105","unstructured":"105. Id."},{"key":"S1073110500020544_bib15","unstructured":"15. American Medical Association Ethics, \u201cOpinion 8.08: Informed Consent,\u201d 2006, available at <http:\/\/www.ama-assn.org\/ama\/pub\/physician-resources\/medical-ethics\/code-medical-ethics\/opinion808.page?> (last visited July 6, 2016)."},{"key":"S1073110500020544_bib180","unstructured":"181. See, e.g., Lantos and Feudtner, supra note 114, at 37."},{"key":"S1073110500020544_bib129","unstructured":"130. See Macklin and Shepherd, supra note 112, at 11."},{"key":"S1073110500020544_bib171","unstructured":"172. See, e.g., Dr. Carlo's Motion for Summary Judgment at 1\u20138, Looney v. Moore, 2015 WL 4773747 (N.D. AL. 2015) (No. 2:13-cv-00733-UNAS-KOB)."},{"key":"S1073110500020544_bib151","unstructured":"152. Id."},{"key":"S1073110500020544_bib27","unstructured":"27. Id."},{"key":"S1073110500020544_bib142","unstructured":"143. Drazen, supra note 142, at 1930."},{"key":"S1073110500020544_bib52","unstructured":"52. Id."},{"key":"S1073110500020544_bib72","volume-title":"Medical Apartheid: The Dark History Of Experimentation From Colonial Times To The Present","author":"Washington","year":"2006"},{"key":"S1073110500020544_bib120","unstructured":"120. See Carlo, supra note 5, at 1960."},{"key":"S1073110500020544_bib101","unstructured":"101. CLD describes long-term respiratory problems that sometimes result from premature birth. See, e.g., Behrman, R. E. and Stith Butler, A. , eds., Preterm Birth: Causes, Consequences, and Prevention (2007): 319\u2013321."},{"key":"S1073110500020544_bib46","unstructured":"46. See Wilson, , Promise of Informed Consent, supra note *, at 6."},{"key":"S1073110500020544_bib147","doi-asserted-by":"crossref","first-page":"1949","DOI":"10.1056\/NEJMc1304827","article-title":"\u201cOxygen-Saturation Targets in Extremely Preterm Infants,\u201d","volume":"368","author":"Carlo","year":"2013","journal-title":"New England Journal of Medicine"},{"key":"S1073110500020544_bib1","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1258\/jrsm.2011.110176","article-title":"\u201cWhat Can Quality Improvement Learn From Evidence-Based Medicine?\u201d","volume":"105","author":"Banerjee","year":"2012","journal-title":"Journal of the Royal Society of Medicine"},{"key":"S1073110500020544_bib148","doi-asserted-by":"crossref","DOI":"10.1056\/NEJMc1308015","article-title":"\u201cThe OHRP and SUPPORT\u2014Another View,\u201d","volume":"369","author":"Macklin","year":"2013","journal-title":"New England Journal of Medicine"},{"key":"S1073110500020544_bib3","doi-asserted-by":"publisher","DOI":"10.2105\/AJPH.94.6.923"},{"key":"S1073110500020544_bib96","unstructured":"96. Id."},{"key":"S1073110500020544_bib22","unstructured":"22. See Transcript, supra note 8, at 24 (statement of Lois Shepard)."},{"key":"S1073110500020544_bib26","unstructured":"26. Id. at 282."},{"key":"S1073110500020544_bib32","unstructured":"32. Id., at 284."},{"key":"S1073110500020544_bib157","unstructured":"158. Id. (citing Surfactant Positive Airway Pressure and Pulse Oximetry Trial in Extremely Low Birth Weight Infants (SUPPORT Study) Tufts University Consent Form (Oct. 1, 2004) available at <http:\/\/www.citizen.org\/documents\/support-study-consent-form.pdf> (noting that \u201cat that center, for clinical purposes, oxygen saturation was \u2018kept between 88 and 94%,\u2019\u201d rather than the minimum 85% and maximum 95% used at UAB) (last visited July 6, 2016)."},{"key":"S1073110500020544_bib37","unstructured":"37. 317 P.2d 170 (Cal. App. 1957)."},{"key":"S1073110500020544_bib94","unstructured":"94. Id., at 2\u20133."},{"key":"S1073110500020544_bib138","unstructured":"139. June 4, 2013 Letter, supra note 119, at 2."},{"key":"S1073110500020544_bib104","unstructured":"104. The Protocol outlined the trade-offs from oxygen therapy: [O]xygen toxicity can result in increased risk for CLD, retinopathy of prematurity (ROP), and other disorders. Alternatively, oxygen restriction may impair neurodevelopment.\u2026 While prevention of hyperoxia [excess oxygen] may decrease the risk for ROP and CLD, efforts to maintain lower oxygenation levels may result in an increase in periods of hypoxemia [low oxygen] because of the marked variability in oxygen in ELBW infants.\u2026 Thus, it is necessary to determine if lower oxygenation levels that may prevent ROP and CLD are deleterious for brain development and result in impaired neurologic outcome. UAB Protocol, supra note 102, at 2-3 (emphasis added)."},{"key":"S1073110500020544_bib167","unstructured":"168. See June 4, 2013 Letter, supra note 119, at 4."},{"key":"S1073110500020544_bib98","doi-asserted-by":"crossref","first-page":"474","DOI":"10.1111\/j.1748-720X.2004.tb00160.x","article-title":"\u201cLitigation in Clinical Research: Malpractice Doctrines Versus Research Realities,\u201d","volume":"32","author":"Morreim","year":"2004","journal-title":"Journal of Law, Medicine and Ethics"},{"key":"S1073110500020544_bib159","unstructured":"160. See Raab, L. , \u201cSen. Howard Baker Asked: What Did Nixon Know and When Did He Know It?\u201d Los Angeles Times, June 26, 2014, available at <http:\/\/www.latimes.com\/nation\/politics\/politicsnow\/la-na-pn-howard-baker-watergate-20140626-htmlstory.html> (last visited July 6, 2016)."},{"key":"S1073110500020544_bib86","doi-asserted-by":"crossref","first-page":"20","DOI":"10.2307\/3562038","article-title":"\u201cFalse Hopes and Best Data: Consent to Research and the Therapeutic Misconception,\u201d","volume":"17","author":"Appelbaum","year":"1987","journal-title":"Hastings Center Report"},{"key":"S1073110500020544_bib47","unstructured":"47. Id."},{"key":"S1073110500020544_bib80","unstructured":"80. Id., at 237-238, 242 (citing Letter from Dennis E. Baker, Assoc. Comm'r for Regulatory Affairs, FDA. Ctr. for Biologics Evaluation & Research to James M. Wilson, Inst. for Human Gene Therapy, Univ. of Pa. Health Sys. (Feb. 8, 2002), available at <http:\/\/www.fda.gov\/RegulatoryInformation\/FOI\/ElectronicReadingRoom\/ucm144564.htm> (notice of opportunity for hearing))."},{"key":"S1073110500020544_bib91","unstructured":"91. Id., at n.21"},{"key":"S1073110500020544_bib66","first-page":"697","article-title":"\u201cRevitalizing Informed Consent and Protecting Patient Autonomy: An Appeal to Abandon Objective Causation,\u201d","volume":"64","author":"Tenenbaum","year":"2012","journal-title":"Oklahoma Law Review"},{"key":"S1073110500020544_bib160","unstructured":"161. Black's Law Dictionary defines \u201cForeseeability\u201d as \u201c[t]he quality of being reasonably anticipatable.\u201d See Black's Law Dictionary 10th ed., s.v., \u201cForeseeability,\u201d (2014)."},{"key":"S1073110500020544_bib39","unstructured":"39. Salgo, 317 P.2d at 181."},{"key":"S1073110500020544_bib124","unstructured":"124. Id."},{"key":"S1073110500020544_bib85","unstructured":"85. Id., at 304 (emphasis added)."},{"key":"S1073110500020544_bib65","first-page":"327","article-title":"\u201cWalking the Talk of Trust in Human Subjects Research: The Challenge of Regulating Financial Conflicts of Interest,\u201d","volume":"52","author":"Gatter","year":"2003","journal-title":"Emory Law Journal"},{"key":"S1073110500020544_bib165","unstructured":"166. Although the notice and comment period has closed, final guidance has yet to be issued. OHRP, HHS, \u201cDraft Guidance on Disclosing Reasonably Foreseeable Risks in Research Evaluating Standards of Care,\u201d Federal Register 79, (Oct. 24, 2014): 63629-63634, at 63632."},{"key":"S1073110500020544_bib115","unstructured":"115. UAB Protocol, supra note 102, at 17."},{"key":"S1073110500020544_bib169","unstructured":"170. Fifth Amended Complaint at \u00b6 50, Looney v. Moore, 2015 WL 4773747 (N.D. AL. 2015) (No. 2:13-cv-00733-UNAS-KOB)."},{"key":"S1073110500020544_bib12","unstructured":"12. Schloendorff v. Soc'y of N.Y. Hosp., 105 N.E. 92, 93 (N.Y. 1914)."},{"key":"S1073110500020544_bib113","doi-asserted-by":"crossref","unstructured":"113. Id. (\u201cAccording to the available evidence, however, the likelihood that infants outside the study would have been intentionally maintained at the lower oxygen target range was very low.\u201d) (citing C. G. Anderson, W. E. Benitz, and A. Madan, \u201cRetinopathy of Prematurity and Pulse Oximetry: A National Survey of Recent Practices,\u201d Journal of Perinatology 24, no. 3 (2004): 164-168, at 164-168) (surveying 120 NICUs).","DOI":"10.1038\/sj.jp.7211067"},{"key":"S1073110500020544_bib152","unstructured":"153. Id., at 2."},{"key":"S1073110500020544_bib77","unstructured":"77. General Requirements for Informed Consent, 45 C.F.R. \u00a7 46.116 (2015)."},{"key":"S1073110500020544_bib107","unstructured":"107. UAB Protocol, supra note 102, at 2 (\u201c[T]here is no current agreement on the accepted SpO2 ranges for managing the ELBW infant from birth.\u201d)."},{"key":"S1073110500020544_bib83","unstructured":"83. Wilson, Estate of Gelsinger, supra note *, at 237 (reproducing the consent form for the study)."},{"key":"S1073110500020544_bib174","first-page":"1","article-title":"\u201cLegally Blind: The Therapeutic Illusion in the SUPPORT Study of Extremely Premature Infants,\u201d","volume":"30","author":"Annas","year":"2014","journal-title":"Journal of Contemporary Health Law and Policy"},{"key":"S1073110500020544_bib50","unstructured":"50. 479 So. 2d 1150, 1152 (1985)."},{"key":"S1073110500020544_bib183","unstructured":"184. Schloendorff v. Soc'y of N.Y. Hosp., 105 N.E. 92, 93 (N.Y. 1914)."},{"key":"S1073110500020544_bib150","unstructured":"151. See June 4, 2013, Letter, supra note 119, at 5."},{"key":"S1073110500020544_bib143","doi-asserted-by":"crossref","DOI":"10.1056\/NEJMc1307008","article-title":"\u201cThe OHRP and SUPPORT,\u201d","volume":"368","author":"Wilfond","year":"2013","journal-title":"New England Journal of Medicine"},{"key":"S1073110500020544_bib53","unstructured":"53. Id., at 1152."},{"key":"S1073110500020544_bib97","unstructured":"97. Heath, D. , \u201cHutch Settles Consent Case Out of Court,\u201d Seattle Times, January 15, 2003, available at <http:\/\/community.seattletimes.nwsource.com\/archive\/?date=20030115&slug=hutch15> (last visited July 6, 2016)."},{"key":"S1073110500020544_bib58","unstructured":"58. Canterbury, 464 F.2d at 772."},{"key":"S1073110500020544_bib154","unstructured":"155. Id., at 4."},{"key":"S1073110500020544_bib89","unstructured":"89. Wilson, Death of Gelsinger, supra note 81, at 305; see also id., at 237-238 (summarizing University of Pennsylvania documents valuing Wilson's equity interest in a sponsor of the research as between $28.5 and 33 million)."},{"key":"S1073110500020544_bib133","unstructured":"134. See UAB Protocol, supra note 102, at 17\u201318."},{"key":"S1073110500020544_bib74","unstructured":"74. Id."},{"key":"S1073110500020544_bib116","unstructured":"116. Id. (\u201cThese interventions will be delivered using specially developed pulse oximeters whose displays (the actual readings seen by caretakers) will be adjusted so that the randomized range of SpO2 (either 85%\u201389%, or 91%\u201395%) will be indicated by a range of 88%\u201392%.\u201d)."},{"key":"#cr-split#-S1073110500020544_bib8.1","unstructured":"8. Transcript, \"Matters Related to Protection of Human Subjects and Research Considering Standard of Care Interventions,\" August 28, 2013, available at http:\/\/www.hhs.gov\/ohrp\/sites\/default\/files\/ohrp\/newsroom\/rfc\/Public%20Meeting%20August%2028%2C%202013\/supportmeetingtranscriptfinal.pdf [hereinafter Transcript] (testimony of Lois Shepherd)"},{"key":"#cr-split#-S1073110500020544_bib8.2","doi-asserted-by":"crossref","unstructured":"see also Editorial, \"Subject to Question: Even When Conducting Clinical Trials to Study Widely Used Therapies, Researchers Must Ensure That They Disclose the Full Risks to Patients,\" Nature 500 (2013): 377-377.","DOI":"10.1038\/500377a"},{"key":"S1073110500020544_bib127","unstructured":"128. Surfactant Positive Airway Pressure and Pulse Oximetry Trial in Extremely Low Birth Weight Infants (SUPPORT Study), University of Alabama at Birmingham Consent Form 2 (Oct. 1, 2004) (emphasis added) available at <http:\/\/www.citizen.org\/documents\/support-study-consent-form.pdf> [hereinafter UAB Consent Form] (last visited July 6, 2016)."},{"key":"S1073110500020544_bib111","unstructured":"111. Id., at 17."},{"key":"S1073110500020544_bib132","unstructured":"133. Id."},{"key":"S1073110500020544_bib118","unstructured":"118. Id., at 17\u201318."}],"container-title":["Journal of Law, Medicine &amp; Ethics"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/1073110516667938","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/1073110516667938","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.cambridge.org\/core\/services\/aop-cambridge-core\/content\/view\/S1073110500020544","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,6,29]],"date-time":"2024-06-29T17:02:00Z","timestamp":1719680520000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.cambridge.org\/core\/product\/identifier\/S1073110500020544\/type\/journal_article"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016]]},"references-count":192,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2016]]}},"alternative-id":["S1073110500020544"],"URL":"https:\/\/doi.org\/10.1177\/1073110516667938","relation":{},"ISSN":["1073-1105","1748-720X"],"issn-type":[{"value":"1073-1105","type":"print"},{"value":"1748-720X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016]]}}}