ANALYTICAL MEMORANDUM To: Dr.

Nasser From: Marwah Alameri Date: October 30, 2012 Subject: Is waiver of informed consent in trauma research ethical?

Informed consent plays an imperative role for human protection in clinical research. It ensures protection of subjects autonomy and prevents their exposure to undue risk. It is obtained for treatment and for research enrollment (Largent, Wendler, Emanuel, & Miller, 2010). However, obtaining subjects consent is challenging under stressful conditions. In traumatic situations, treatment is never withdrawn if obtaining informed consent from a critically ill patient is infeasible or postponed while in quest of a surrogates consent (Coats, 2012). Therefore, trauma research with the absence of subject or surrogate consent is ethical as it can proceed only if informed consent is waived. To provide informed consent, individuals must be accurately and fully informed about the researchs purpose, methods, risks, benefits and other alternatives. The patient is expected to comprehend the information and its effect on his own medical condition; and make a voluntary decision whether or not to enrol (Health Insurance Portability and Accountability Act, 2002). Simply, such requirements are absent in traumatic situations. In such catastrophic conditions, patients are either unconscious, i.e. lack decision-making capacity, or conscious but with compromised mental status due to acute physical or mental illness. These situations pose an obvious challenge for emergency physician to obtain consent of patients (John, 2006). During sudden, life-threatening events like cardiac arrest, traumatic brain injury or shock states, the autonomy of the acutely ill or injured patient has already been removed by the devastating nature of the pathology involved. At such critical times, the patient is vulnerable, and his opinion of whether to accept or reject a potentially life-sustaining intervention cannot be concluded (Lemaire, 2007). In addition, it is not the physician or the institutional review boards (IRBs) that remove the patients autonomy in these critical circumstances, but the efforts made to save his life (Morrison, Horwitz, & Carrick, 2009). In fact, the Final Rule, a set of regulations outlining situations in which emergency research could be conducted in humans under an exception of informed consent, states that under such circumstances the focus must be on the preservation of life (FDA Final Rule, 21 C.F.R 50.24, 1996). On the same line, in most trauma research, the investigator doesnt have the luxury of time. Investigational agents are likely to be effective only if administered within a certain period of time from the onset of the acute life threatening condition. Therefore to obtain the patients consent at the spot is infeasible (Graham, Judy, Lois van, Ron, Tom, Jim, & Al, 2006). In addition, obtaining patients consent prior to enrolment in a trauma research means there shouldnt be clinical trials in this critical field of medicine. Hence, it will deprive current and future patients from participation. In fact this has resulted in little research conducted in trauma settings to improve survival outcomes and has played a major role in causing trauma to be the main cause of death in the United States for individuals between ages 1 and 45 years (Minio, Anderson, Fingerhut, Boudreault , & Warner, 2006). On the other hand, there is disproportionate representation of racial minorities and people of low socioeconomic status in trauma research. For that reason, they are potentially at risk of being exploited, not only because of their compromised neurological or medical
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ANALYTICAL MEMORANDUM To: Dr. Nasser From: Marwah Alameri Date: October 30, 2012 Subject: Is waiver of informed consent in trauma research ethical?

status, but because they are easily influenced as a result of their socioeconomic condition (Emanuel, 2000). Therefore, researchers have an obligation to justify any proposed research study that utilizes this patient population. Furthermore, researchers also have an obligation to respect the autonomy of the potential patients, and they must consider the possibility that some ethnic groups might be reluctant to participate due to religious reasons. Additionally, waiver of informed consent contradicts the three basic ethical principles, beneficence, justice and respect for persons, of research of the Belmont report (The Belmont Report, 1979). On a related point, surrogate consent in patients incapable of expressing their views due to cognitive impairment is an alternative. Health Insurance and Probability Act (HIPPA) requires informed consent from the patient or his surrogate (Health Insurance Portability and Accountability Act, 2002). Moreover, the Final rule was created for situations where there is no existing or alternative treatment; however physicians during emergency research use investigative treatment though proven medicine exist (FDA Final Rule, 21 C.F.R 50.24, 1996). Therefore, extending the same waiver of consent to research settings should be prohibited due to the unknown dangers of implementing unproven treatment compared with an existing treatment, whose safety and efficacy has already been clinically proven. For those reasons, waiver of informed consent is considered unethical. Trauma research can proceed only if informed consent is waived or deferred. It can be argued that those who suffer most from the lack of advancement and innovation in trauma research are individuals from minority populations. These same vulnerable groups also tend to have worse outcomes when treated with current treatment modalities. It is in such cases that obtaining informed consent, a practice that was originally instituted to protect vulnerable populations, is probably one of the major reasons that such little trauma research exists to benefit these populations today. Additionally, deferment from abiding to the principles of the Belmont report during trauma research is justified. Title 45 codes of federal regulations 46, also known as the Common Rule and derived from the Belmont report, clearly outlines separate regulations for research involving foetuses, children, and prisons as requiring additional protections, but leaves it up to individual IRBs to determine whether additional protections are needed for other groups of individuals who might also have diminished autonomy (FDA Protection of Human Subject, 45 C.F.R 46, 2009). In addition, international guidelines identify a list of potentially exploitable vulnerable populations including patients in emergency situations, which is relevant to patients in trauma research (Druml, 2004). In life threatening situations, consenting for the incapacitated patients is uncommon, as the possible surrogates are rarely on the spot. In situations where the surrogate is available, one cannot seriously consider that during such stressful situations, the conditions ensuring a
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ANALYTICAL MEMORANDUM To: Dr. Nasser From: Marwah Alameri Date: October 30, 2012 Subject: Is waiver of informed consent in trauma research ethical?

satisfactory informed consent are met. Furthermore, surrogates decisions might vary from that of patients. Newman and colleagues concluded from observational cohort study significant discrepancies in the willingness to participate in hypothetical critical research studies between the critically ill and their surrogates (Newman, Smart, Reese, Williams, & Moss, 2012). Finally, though the Final rule was created for situations where there is no existing or alternative treatment, given the relative scarcity of prospective randomized clinical trials for many strategies currently used in trauma research, it can be difficult to pin down a definitive gold standard treatment. Furthermore, in many cases, standards of management have failed to significantly reduce morbidity and mortality. In such scenarios, it might be unethical to continue with the standard of care if it will result in poor outcomes where a better, but yet to be proven, option potentially exists (Morrison, Horwitz, & Carrick, 2009). In fact, there are situations in which access to experimental treatments may be directly beneficial to research subjects. Annane and colleagues showed that there was a link between the waiver of consent approved by French Competent Authority and the completion of their landmark study on the use of low doses of corticosteroids in the treatment of septic shock (Annane, Sebille, Charpentier, Bollaert, Francois, Korach, & ... Troche, 2002). This study had an impact on the current guidelines for septic shock management. In conclusion, given the priority of preserving patients life, the narrow time frame of treatment administration, the inherited absence of patients autonomy, the infeasibility of applying the informed consent requirements and the need to advance research for the benefit of the society, wavier of informed consent is ethically justifiable in trauma research. References Annane, D. D., Sebille, V. V., Charpentier, C. C., Bollaert, P. E., Francois, B. B., Korach, J.M., & ... Troche, G. G. (2002). Effect of treatment with low doses of Hydrocortisone and Fludrocortisone on mortality in patients with septic shock. Journal- American Medical Association, 288, 862-884. Belmont Report (1979). The Belmont Report: Ethical principles and guidelines for the protection of human subjects of research. Retrieved from http://www.hhs.gov/ohrp/policy/belmont.html Coats, T. (2012). Ethical and practical issues in trauma care research. The British Journal of Surgery, 99 Suppl 16-7. Druml, C. Informed consent of incapable (ICU) patients in Europe: existing laws and the EU directive. (2004). Current Opinion in Critical Care, 10(6), 570-73.

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ANALYTICAL MEMORANDUM To: Dr. Nasser From: Marwah Alameri Date: October 30, 2012 Subject: Is waiver of informed consent in trauma research ethical?

Emanuel et al, E. J. (2000). What makes clinical research ethical?. JAMA: Journal of the American Medical Association,283(20), 2701. Food and Drug Administration. (1996). 21 CFR 50.24. Guidance for Institutional Review Boards, Clinical Investigators and Sponsors. Retrieved from: http://www.fda.gov/downloads/RegulatoryInformation/Guidances/UCM249673.pdf Graham, N., Judy, P., Lois van, O., Ron, M., Tom, R., Jim, C., & Al, H. (2006). Review paper: Consent in resuscitation trials: Benefit or harm for patients and society?. Resuscitation, 70, 360-368. Health Insurance Portability and Accountability Privacy Rule. , 45 C.F.R. pt. 160 (2002). Retrieved from http://www.hhs.gov/ocr/privacy/hipaa/administrative/privacyrule/prdecember2000all8 parts.pdf John C., M. (2006). Informed consent and refusal of treatment: Challenges for emergency physicians. Emergency Medicine Clinics of North America, 24(Ethical Issues in Emergency Medicine), 605-618. Largent, E., Wendler, D., Emanuel, E., & Miller, F. (2010). Is emergency research without initial consent justified?: The consent substitute model. Archives of Internal Medicine, 170(8), 668-674. Lemaire, F. (2007). Emergency research: Only possible if consent is waived?. Current Opinion in Critical Care, 13(2), 122-125. Minio, A., Anderson, R., Fingerhut, L., Boudreault, M., & Warner, M. (2006). Deaths: injuries, 2002. National Vital Statistics Reports: The Centres for Disease Control and Prevention, National Centre for Health Statistics, National Vital Statistics System, 54(10), 1-124. Morrison, C., Horwitz, I. B., & Carrick, M. M. (2009). Ethical and legal issues in emergency research: Barriers to conducting prospective randomized trials in an emergency setting. Journal of Surgical Research, 157(1), 115-122. Newman, J. T., Smart, A., Reese, T. R., Williams, A., & Moss, M. (2012). Surrogate and

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ANALYTICAL MEMORANDUM To: Dr. Nasser From: Marwah Alameri Date: October 30, 2012 Subject: Is waiver of informed consent in trauma research ethical?

patient discrepancy regarding consent for critical care research. Critical Care Medicine, 40(9), 2590-2594. Protection of Human Subjects, 45 C.F.R. pt. 46 (2009). Retrieved from http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.html

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