{"id":741,"date":"2018-05-04T07:30:12","date_gmt":"2018-05-04T07:30:12","guid":{"rendered":"https:\/\/az.research.umich.edu\/medschool\/document\/evaluating-risks-participants\/"},"modified":"2026-02-24T13:13:39","modified_gmt":"2026-02-24T18:13:39","slug":"evaluating-risks-participants","status":"publish","type":"document","link":"https:\/\/az.research.umich.edu\/medschool\/guidance\/evaluating-risks-participants\/","title":{"rendered":"Evaluating Risks to Participants"},"template":"","categories":[24],"tags":[22],"content-type":[41],"topic":[42,30,43,75,67],"update-type":[96,94],"class_list":["post-741","document","type-document","status-publish","hentry","category-institutional-review-boards-irbmed","tag-u-m-resource","content-type-guidance","topic-application-types","topic-clinical-trial","topic-eresearch-regulatory-management-errm","topic-regulations-policies-federal-state-local","topic-subject-populations","update-type-research-staff","update-type-review-recommended"],"acf":{"use_legacy_editor":true,"updated_date":"2023-07-12 14:30:00","update_notice":false,"author":"IRBMED","summary":"In human research studies, the IRBs are responsible for evaluating the risks, weighing the probability <\/em>of each risk coming to pass, and assessing the magnitude <\/em>of harm that may result. It must then judge whether the anticipated benefit \u2013 e.g., improved health for the research participants (direct) or new knowledge that benefits society (indirect) \u2013 justifies inviting any person to undertake the risks.\r\n\r\nAn IRB cannot approve research in which the risks are judged unreasonable in relation to the anticipated benefits.\r\n\r\nThe risks associated with a specific research procedure are dependent on many factors, such as the research context (e.g., collecting public versus <\/em>private information), its scope and scale (e.g., a single punch biopsy \u22642mm performed on the forearm versus <\/em>multiple punch biopsies >2mm on the face), and the participant population (e.g., healthy young adults versus <\/em>children with cognitive impairment).","button_links":null,"related_content":[742,773,864,860],"legacy_path":"evaluating-risks-participants","legacy_node_id":279,"legacy_related_nids":"59, 280, 315","legacy_content_section":[{"legacy_section_type":"heading","legacy_heading":"Risk Classifications","legacy_subheading":"","legacy_section_text":"","legacy_media_position":"","legacy_media_file":"","legacy_media_url":"","legacy_glossary_term":"","legacy_glossary_nids":"","legacy_resource":"","legacy_resource_nids":"","legacy_buttons":null},{"legacy_section_type":"text_area_with_subheading","legacy_heading":"","legacy_subheading":"Definitions of minimal risk","legacy_section_text":"Minimal risk:<\/strong><\/a> The probability and magnitude of harm or discomfort anticipated in the research are not greater in and of themselves than those ordinarily encountered in daily life or during the performance of routine physical or psychological examinations or tests. (See 45 CFR 46.102<\/a>(j) and 21 CFR 56<\/a>.102(i)).\r\n

Specific to child participants:<\/strong> Minimal risk are those risks encountered during daily life by normal, average, healthy children living in safe environments or during the performance of routine physical or psychological examinations or tests. See SACHRP Recommendations<\/a> and Research A-Z\u00a0Children in Research<\/a> guidance.<\/p>\r\n

Specific to prisoner participants:<\/strong> Minimal risk is the probability and magnitude of physical or psychological harm that is normally encountered in the daily lives, or in the routine medical, dental, or psychological examination of healthy persons. See 45 CFR 46.303(d)<\/a> and Research A-Z\u00a0Prisoners in Research<\/a> guidance.<\/p>\r\n

Research that must comply with Department of Defense (DoD) special requirements:<\/strong> Minimal risk does not include the inherent occupational risks that certain subjects face in their everyday life, such as those:\r\n(1)<\/strong> Encountered by Service members, law enforcement, or first responders while on duty.\r\n(2)<\/strong> Resulting from or associated with high-risk behaviors or pursuits.\r\n(3)<\/strong> Experienced by individuals whose medical conditions involve frequent tests or constant pain.<\/p>\r\n

See DoD Instruction<\/a> 3216.02 and HRPP Guidance<\/a> \u201cAdditional Requirements for Investigators.\u201d<\/p>","legacy_media_position":"","legacy_media_file":"","legacy_media_url":"","legacy_glossary_term":"","legacy_glossary_nids":"","legacy_resource":"","legacy_resource_nids":"","legacy_buttons":null},{"legacy_section_type":"text_area_with_subheading","legacy_heading":"","legacy_subheading":"University of Michigan Risk Classifications","legacy_section_text":"No more than minimal risk<\/strong> applies to research that meets the definition of minimal risk.\r\n\r\nMinor increase over minimal risk<\/strong> applies to research activities that would be more harmful than those encountered in daily life but psychological, informational, and\/or physical harm(s) do not rise to the level of moderate risk. \u00a0For research involving adult participants with cognitive impairment\/diminished decision-making capacity (HRPP Operations Manual<\/a>\u00a0Part 7.II.D) or for children (45 CFR 46<\/a>.406; 21 CFR 50<\/a>.53), greater than minimal risk research with no prospect of direct benefit to participants<\/em> can be approvable if the risks do not exceed minor increase over minimal, and the research must present a reasonable opportunity to further understanding, prevention, or alleviation of a serious problem affecting the health or welfare of the participant population.\r\n\r\nModerate risk<\/strong> applies to research activities that do not rise to the severity of high risk, yet are incrementally greater than minimal -- e.g., the research could cause temporary or moderate psychological, informational, and\/or physical harm(s).\r\n\r\nHigh risk<\/strong> applies to research activities that present severe\/serious, long-lasting, or permanent potential harm(s).","legacy_media_position":"","legacy_media_file":"","legacy_media_url":"","legacy_glossary_term":"","legacy_glossary_nids":"","legacy_resource":"","legacy_resource_nids":"","legacy_buttons":null},{"legacy_section_type":"text_area_with_subheading","legacy_heading":"","legacy_subheading":"Clarification regarding FDA-regulated Investigational Devices","legacy_section_text":"Classifying an Investigational Device<\/a> \u2018Significant Risk\u2019 or \u2018Non-Significant Risk\u2019 according to FDA regulations at 21 CFR 812<\/a>.2(m) is a separate determination from whether the overall study poses minimal or greater than minimal risk to participants per 45 CFR 46<\/a>.102(j)\/21 CFR 56<\/a>.102(i). These two kinds of risk determination may not always coincide in the context of a given research study.","legacy_media_position":"","legacy_media_file":"","legacy_media_url":"","legacy_glossary_term":"","legacy_glossary_nids":"","legacy_resource":"","legacy_resource_nids":"","legacy_buttons":null},{"legacy_section_type":"heading","legacy_heading":"Types of risks to research participants","legacy_subheading":"","legacy_section_text":"","legacy_media_position":"","legacy_media_file":"","legacy_media_url":"","legacy_glossary_term":"","legacy_glossary_nids":"","legacy_resource":"","legacy_resource_nids":"","legacy_buttons":null},{"legacy_section_type":"text_area","legacy_heading":"","legacy_subheading":"","legacy_section_text":"There are many types of risks to which research participants may be exposed. The U-M IRBs generally consider three broad categories of risks: psychological<\/strong> (including invasion of privacy), informational<\/strong> (confidentiality, social, legal, employability-related), and physical<\/strong>.\r\n

Psychological<\/h3>\r\nParticipation in research may result in undesired changes in thought processes and\/or emotions (e.g., anxiety, depression, confusion, stress, guilt, and loss of self-esteem). These changes may be momentary, temporary, or permanent; they may also occur as a single episode or be recurrent.\u00a0 Some research has the potential for causing serious psychological harm.\u00a0 In the research context, invasion of privacy usually involves either covert observation or researchers participating in situations\/behavior that participants consider private.\r\n

Informational (including privacy, legal, financial, and social harm)<\/h3>\r\nConfidentiality relates to safeguarding research data and information that has been given voluntarily by one person to another. Some social and behavioral research may yield information about participants that could be stigmatizing (e.g., social harm) or put them at risk of legal or financial repercussions. Genetic research may uncover information about a participant\u2019s family or lineage that was previously unknown or may cause personal or interpersonal conflict (e.g., paternity concerns).\u00a0 Release of confidential research information\u00a0can also result in psychological harm to individuals (e.g. embarrassment, guilt, stress).\r\n

Physical<\/h3>\r\nResearch includes medical procedures that may result in pain, discomfort, or loss of physical functioning. Research may dictate the course of a participant\u2019s clinical care and may use unproven drugs or experimental procedures that could result in serious injury.\u00a0 Adverse outcomes can range from momentary and minimally discomforting to severe and permanently disabling.","legacy_media_position":"","legacy_media_file":"","legacy_media_url":"","legacy_glossary_term":"","legacy_glossary_nids":"","legacy_resource":"","legacy_resource_nids":"","legacy_buttons":null},{"legacy_section_type":"heading","legacy_heading":"Evaluating acceptability of risks","legacy_subheading":"","legacy_section_text":"","legacy_media_position":"","legacy_media_file":"","legacy_media_url":"","legacy_glossary_term":"","legacy_glossary_nids":"","legacy_resource":"","legacy_resource_nids":"","legacy_buttons":null},{"legacy_section_type":"text_area","legacy_heading":"","legacy_subheading":"","legacy_section_text":"If the reviewing IRB determines that the risk\/benefit assessment is not appropriately favorable, investigators will be asked to revise the study\u2019s methods to reduce these risks. For each study, risk must be minimized<\/em>: decreased to the lowest level consistent with the study aims and objectives<\/em>.\r\n\r\nModerate or high risk of physical harm is sometimes unavoidable in clinical trials<\/a> and is indeed common in oncology trials. High physical risk research procedures can have outcomes as severe as death, permanent dysfunction or harm to an organ or part of the body, or serious infection, harmful immune system response, or tumor development.\r\n\r\nOn the other hand, risks of psychological harm can often be decreased by appropriate screening for vulnerabilities, by a comprehensive informed consent process to ensure participants are making fully informed decisions, and sometimes by disclosure of additional information after research participation. Negative feelings induced by research interactions and interventions (e.g. impacts of feelings of sadness, tearfulness, preoccupation, or anger) are often milder and more transient for participants who are prepared for them.\r\n\r\nActual informational harms are usually the result of inappropriate disclosure of research information: the risks are decreased by robust confidentiality protections and data security practices. See HRPP Data Security Guidelines<\/a> and ITS Safe Computing<\/a> website, and note that multiple University policies<\/a> govern proper use of data.\r\n\r\nResearch involving moderate or high risk of psychological or informational harm is not approvable by the U-M IRBs unless (1) the probability of the risk is sufficiently small, and (2) the potential for direct benefit to the individual participant is sufficiently large.","legacy_media_position":"","legacy_media_file":"","legacy_media_url":"","legacy_glossary_term":"","legacy_glossary_nids":"","legacy_resource":"","legacy_resource_nids":"","legacy_buttons":null},{"legacy_section_type":"heading","legacy_heading":"SPECIAL CASE \u2013 Risks of methods to induce or measure pain","legacy_subheading":"","legacy_section_text":"","legacy_media_position":"","legacy_media_file":"","legacy_media_url":"","legacy_glossary_term":"","legacy_glossary_nids":"","legacy_resource":"","legacy_resource_nids":"","legacy_buttons":null},{"legacy_section_type":"text_area","legacy_heading":"","legacy_subheading":"","legacy_section_text":"The following guidance is for studies designed to induce pain (most commonly using pressure, temperature, or electrical impulses) for the purpose of generating research data. Understanding of the causes and mechanisms of pain responses can be valuable to the improvement pain management, especially in combination with monitoring of the brain\u2019s responses (e.g. functional MRI). Used here, the term pain threshold<\/em>\u00a0means the minimum point at which the research stimulus (e.g., heat) is perceived by the research participant as pain.","legacy_media_position":"","legacy_media_file":"","legacy_media_url":"","legacy_glossary_term":"","legacy_glossary_nids":"","legacy_resource":"","legacy_resource_nids":"","legacy_buttons":null},{"legacy_section_type":"text_area_with_subheading","legacy_heading":"","legacy_subheading":"IRB Assessment of Risk Level","legacy_section_text":"