December 28, 2022
Thank you for the opportunity to comment on FDA’s proposed rule to amend its regulations on the protection of human subjects and institutional review boards (IRBs). We appreciate the agency’s efforts to improve and streamline the current system of oversight while enhancing the protection of human subjects.
The National Center for Health Research (NCHR) is a nonprofit think tank that conducts, analyzes, and scrutinizes research on a range of health issues with a particular focus on which prevention strategies and treatments are most effective for which patients and consumers. We do not accept funding from companies that make products that are the subject of our work, so we have no conflicts of interest.
NCHR supports the FDA’s efforts to improve efficiency in the review and oversight of clinical trials involving multiple sites by requiring a single IRB for all the U.S. centers in a multi-center clinical trial. We concur with FDA’s assessment that a single IRB will help save time, improve the ability to respond to important safety issues, and contribute to greater efficiency in the FDA’s IRB inspection program.
In some instances, local IRBs may be more familiar with the specific characteristics of their communities based on socioeconomic status, language, regional, cultural or religious differences. These factors may be important to ensure that informed consent and other documents will be understood by patients participating in clinical trials. We recommend that the regulations specify that the IRB may evaluate and approve informed consent and other documents that are tailored to the features of specific communities when needed.
We support the FDA’s proposed changes to the requirements for informed consent, which are intended to help participants better understand the details of the research and how their information may be used in the future. We agree with the agency’s effort to present information in an organized and understandable manner. However, the FDA’s language is too vague, and leaves room for wide variation. Therefore, we recommend that the agency provide a more explicitly structured definition of what is required as a way to reduce inappropriate interpretations of the guidelines.
Unfortunately, many patients sign informed consent documents without carefully reading them; in fact, the average reading level for surgery consent forms at 616 U.S. hospitals is 12.6 years and only 7% are at or below the 8th grade reading level 1 – which is the average reading level for Americans. 2 The oral informed consent could potentially be more informative, but research
indicates that it is not. For example, an evaluation of 141 informed consent discussions regarding orthopedic surgery found that 41% [of conversations] did not include pros and cons, and 86% did not address the patient’s role in decision-making. 3 Another study found that patients are often intimidated and hesitate to question their physicians. 4 In two other studies, interviews with patients conducted 3 hours after consent for prostate surgery and 2 hours after consent for neurosurgery found that most patients could not recall the major risks of potential complications.5
FDA should require that informed consent documents are structured and designed using methods shown to support participants’ active engagement in decision-making. To make an informed decision about trial participation, the patient must have a clear understanding of the information provided and the ability to compare different courses of action. Studies show that patients generally have poor knowledge and understanding of basic elements of clinical trials and have difficulty determining how trial participation fits with their own personal values and goals.6 Some researchers have identified ways to measure and enhance participant understanding and decision-making such as decision aids developed with patient participation.5, 7 The agency should utilize such data to guide improvements to the informed consent process for clinical trials.
We strongly support the addition describing how participants’ information or biological specimens may be used or distributed in the future. This will help address bioethics issues that have gained increasing attention, especially in rapidly advancing fields like human genetics. These amendments improve transparency and allow for more personal autonomy for potential participants. Greater transparency fosters more public confidence in medical research and may encourage more participation in clinical trials. Also, the new language regarding whole genome sequencing is critical to keep up with rapid genetic research and technological advances.
Finally, we also strongly support the agency’s proposal to broaden diversity among IRB members by adopting the language of the revised Common Rule requiring each IRB to be “sufficiently qualified” based on professional experience and diversity regarding the race, gender, age, and cultural backgrounds of its members.8 In addition, informed consent documents in clinical trials will be more informative if they include information about the potential risks and benefits specific to demographic groups such as age, race, and gender. 5
1. Hopper KD, TenHave TR, Tully DA, Hall TE. The readability of currently used surgical/procedure consent forms in the United States. Surgery. 1998;123(5):496-503. doi:10.1067/msy.1998.87236\
2. Strauss V. Hiding in plain sight: The adult literacy crisis. The Washington Post. https://www.washingtonpost.com/news/answer-sheet/wp/2016/11/01/hiding-in-plain-sight-the-adult-literacy-crisis/?noredirect=on . November 1, 2016
3. Braddock C, Hudak PL, et al. “surgery is certainly one good option”: Quality and time-efficiency of informed decision-making in surgery. The Journal of Bone and Joint Surgery. 2008; 90(9):1830-8. doi:10.2106/JBJS.G.00840.
4. Frosch DL, May SG, Rendle KA, Tietbohl C, Elwyn G. Authoritarian physicians and patients’ fear of being labeled ‘difficult’ among key obstacles to shared decision making. Health Aff (Millwood). 2012;31(5):1030-1038. doi:10.1377/hlthaff.2011.0576
5. Zuckerman D, Silcox C. The Challenges of Informed Consent When Information and Time Are Limited. In: Informed Consent: Procedures, Ethics and Best Practices. Ethical Issues in the 21st Century. ; 2016. Accessed December 28, 2022. file:///Users/ealenacallender/Downloads/informed%20consent%20book%20chapter.pdf
6. Abhyankar P, Velikova G, Summers B, Bekker HL. Identifying components in consent information needed to support informed decision making about trial participation: An interview study with women managing cancer. Social Science & Medicine. 2016;161:83-91. doi:10.1016/j.socscimed.2016.05.040
7. HHS, OHRP. Meeting New Challenges in Informed Consent in Clinical Research.; 2018:37. https://www.hhs.gov/ohrp/sites/default/files/meeting-new-challenges.pdf
8. HHS. Revised Federal Policy for the Protection of Human Subjects (the revised Common Rule), 45 CFR 46.107 IRB Membership. Published online January 19, 2017. https://www.ecfr.gov/current/title-45/subtitle-A/subchapter-A/part-46/subpart-A/section-46.107