ARE YOUR PARTICIPANTS AT INCREASED RISK? Keren Nicole Insalaco, MS, CIP Phone: Office of Human Research Administration

O VERVIEW The Basics The Basics Beyond The Regs Juggling Act Let’s Practice Resources Questions Helpful Tips 2

Human Subjects (HS) Research Governed by several statutes and norms. Common Provisions:  45 CFR 46 (DHHS)  21 CFR 50 and 56 (FDA)  Privacy Rule (HIPAA)  Belmont Report (Ethics Code)  State and/or Local Laws  Institutional Policies T HE B ASICS 3

T HE B ASICS ( CONT.) 4 Key issues when evaluating a study  Risks to subjects are minimized.  Risks to subjects are reasonable.  Subject selection is equitable.  Informed consent will be adequately sought or waived.

Federal regulations risk level classification. T HE B ASICS ( CONT.) Minimal Risks Greater Than Minimal Risks Greater Than 5

How do the federal regulations define ‘minimal risk’? The probability and magnitude of harm or discomfort anticipated in the research that 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. T HE B ASICS ( CONT.) 6

Prisoners have their own ‘minimal risk’ definition Standard DefinitionPrisoner’s Definition Refers to harm or discomfortRefers to physical or psychological harm Compares the probability and magnitude of harm in the research to those encountered in daily life or “routine physical or psychological examinations or tests.” Compares the probability and magnitude of harm in the research to those encountered in daily life, or in “routine medical, dental, or psychological examinations.” Unspecified comparison group against which the risks of the research should be measured. ‘Healthy persons’ are identified as the comparison group against which the risks of the research should be measured. 7

B EYOND THE R EGS But wait a minute, how are ‘risks’ defined?  Federal regulations define only "minimal risk.“  Risk: The probability of harm or injury occurring as a result of participation in a research study.  So a risk is a ‘stressor’ associated with a study- related activity. 8

B EYOND THE R EGS ( CONT.) The risk definition can be confusing because:  Risk can refer to probability.  Chances a person might be willing to take to achieve a desired goal.  Risk can also refer to a condition or situation that is potentially dangerous. 9

B EYOND THE R EGS ( CONT.) About Risks:  Real or perceived  Differ in nature  May vary in frequency, probability and/or magnitude  Extent may be transitory, long-term, or permanent  Could impact more than one individual 10

B EYOND THE R EGS ( CONT.) ‘Risks’ include but or are not limited to: Anxiety or Distress (e.g., recalling trauma) DiscriminationIssues of Self Esteem Congenital Anomaly Birth Defect EmbarrassmentLife Threatening (e.g., organ failure) ControversialFatigue (Mental or Physical) Loss of Time Criminal/Civil LiabilityFinancial StandingPerceived Exploitation Damage ReputationHarassment/ConflictSide Effect (e.g., allergic reaction) Damage to Financial StandingImpact Relationships (e.g., with family members) Stigmatization DeathInconvenience or Expense (e.g., travel, babysitter, etc.) Therapeutic Misconception Deprivation (e.g., abstinence, fasting) Inequality in PowerUndue Influence Disability or IncapacityInvasion of PrivacyUnpleasant Emotions (e.g., guilt, fear,) 11

J UGGLING A CT (C ONT.) How do we place risks in perspective? Anonymous Survey Adults Sexual Practices. Anonymous Survey Kids age ≥ 16 Sexual Practices. Identifiable Survey Kids age ≥ 11 Sexual Practices, Abortion, Abuse, Use of Illicit Drugs 12 Minimal Risks Greater Than Minimal Risks Greater Than

J UGGLING A CT ( CONT.) Balanced Risk:Benefit Analyses IRBs can only approve research when risks are judged reasonable in relation to benefits. Potential Risks Expected Benefits 13

J UGGLING A CT ( CONT.) Conducting a project is like cooking… Research Team Study Plan Study Materials ResourcesDesired Outcome We should be able to replicate your project with the info provided! 14

H ELPFUL T IPS Study Population 15

H ELPFUL T IPS ( CONT.) Vulnerable Populations with Specific Regulatory Requirements  Pregnant Women  Human Fetuses  Neonates  Children | Wards of State  Prisoners 16

H ELPFUL T IPS ( CONT.)  Economically Disadvantaged  Employees  Terminally Ill  Homeless  Illiterate | Low Literate 17 Special Classes of Participants  Involuntarily Confined  Non-English Speakers  Refugees  Soldiers | Veterans  Students

H ELPFUL T IPS ( CONT.) Factors that can increase participants risks 18  Addictions  Adversity and Trauma  Diminished Quality of Life  Discriminated Against  Extreme Poverty  Illicit Markets  Mental Illness  Mistrust of Outsiders  Natural Disasters  Political Conflict  Reduced Access to Care  Socially Marginalized  Stigmatized Conditions  Violence

H ELPFUL T IPS ( CONT.) Including a ‘vulnerable population’ does not necessarily or automatically increase the overall study risk level. 19

H ELPFUL T IPS ( CONT.) ‘Healthy’ participants may be considered ‘vulnerable’ within the context of your research. 20

H ELPFUL T IPS ( CONT.) Address any aspects of the research that may raise specific cultural issues (e.g., local context and values). 21

H ELPFUL T IPS ( CONT.) When necessary, consult with experts (e.g., local IRB, mentor, etc.). 22

H ELPFUL T IPS ( CONT.) Research Application (Plan + Materials) 23

H ELPFUL T IPS ( CONT.) The greater the risk(s) posed in the study, the more information we’ll need. 24

H ELPFUL T IPS ( CONT.) For every study task, list any potential or expected risks or discomforts. Whenever applicable describe the steps to mitigate risks. 25

H ELPFUL T IPS ( CONT.) Be clear on the logistics of the study!! 26

H ELPFUL T IPS ( CONT.) Use plain language! Not everyone knows as much about your research field as you do! 27

H ELPFUL T IPS ( CONT.) Submit all materials that participants will hear, see, or receive. 28

H ELPFUL T IPS ( CONT.) Please make sure your Research Protocol is consistent with your study materials and grant, if applicable. 29

H ELPFUL T IPS ( CONT.) Piggyback! Whenever appropriate, use procedures already being performed on participants for diagnostic or treatment purposes. 30

H ELPFUL T IPS ( CONT.) Remember to explain how you are going to identify prospective participants and how they are going to be invited. 31

H ELPFUL T IPS ( CONT.) Avoid excessive contact to persuade prospective participants to take part in your research. 32

H ELPFUL T IPS ( CONT.) Do you really need to collect personally identifying info? 33

H ELPFUL T IPS ( CONT.) Don’t confuse confidentiality with anonymity. 34

H ELPFUL T IPS ( CONT.) Compensation is not a study benefit. 35

H ELPFUL T IPS ( CONT.) Some studies may need a Certificate of Confidentiality. We’ll let you know. 36

H ELPFUL T IPS ( CONT.) Consider providing participants a separate ‘contact info card’ in addition to the consent form if the consent form includes sensitive information. 37

H ELPFUL T IPS ( CONT.) A flawed research plan can increase the study’s inherent risks. 38

H ELPFUL T IPS ( CONT.) Team Expertise 39

H ELPFUL T IPS ( CONT.) Make sure your staff has adequate training and any applicable current licensure. 40

H ELPFUL T IPS ( CONT.) Study-Related Resources 41

H ELPFUL T IPS ( CONT.) It is important that you submit information about your funding. 42

H ELPFUL T IPS ( CONT.) Be specific about which practices and methods will be used to protect privacy and confidentiality. 43

H ELPFUL T IPS ( CONT.) Do you have adequate resources to comply with Harvard’s Data Security policy? 44

L ET ’ S P RACTICE Congratulations! You are now ready to serve as an IRB Review Specialist at the very prestigious G. Gryffindor School of Public Health (formerly Hogwarts School of Public Health). The School is still known as HSPH. 45

L ET ’ S P RACTICE Case 1: Dr. Flitwick (also the chair of the department of social health) would like to recruit her students and the technicians of her lab to participate in a study about the School’s sexual harassment and drug- free polices. Participants will be asked about their experiences with the topics in question and be compensated $150 for taking part in a 1hr audio-recorded focus group that would take place during lunch time in the conference room near the cafeteria. 46

L ET ’ S P RACTICE Case 2: Dr. Flitwick would like to conduct a study about the School’s sexual harassment and drug-free polices.  She is planning to post fliers to invite the School’s students, faculty, and staff.  Participants will be asked to complete a paper-based questionnaire which may have some sensitive questions, but will not ask for identifying information.  Dr. Flitwick is hiring an independent group to conduct the interviews.  Participants will not need to sign the consent form  No compensation will be offered to participants. However, participants will be provided with information from the Ombudsman and other resources available in/outside of the School on the topics in question. 47

L ET ’ S P RACTICE Case 3: Dr. H. Potter conducted a study that involved data on maternal vitamin supplementation. All participants have completed all research-related activities and the data have been stripped of all personally identifying information. Dr. Potter has received additional funding to conduct research specifically on the effect of maternal B12 supplementation so he would like to submit a new study to the HSPH IRB to conduct this analyses. 48

L ET ’ S P RACTICE Case 4: You received a call from an investigator that would like to conduct a study that involves asking participants to (i) participate on an exercise program; (ii) complete several questionnaires; (iii) body measurements; and (iv) provide blood (while fasting) and urine samples on multiple occasions. The study requires 12 study visits in addition to the time necessary to take part in the exercise program. 49

L ET ’ S P RACTICE Case 5: A PI would like to conduct a study aimed at the design and implementation of a tool for the assessment and management of pain in elderly with a diagnosis of dementia. The study will include hospitalized patients. Qualitative data will be collected with a mix methods including audio-recorded interviews with participants and family caregivers, focus groups with clinical staff and observation of care at this multi-site study. The investigators are also planning to collect image data (e.g., photographs) from participants as well as the hospital settings to use in presentations. 50

R ESOURCES  The Office of Human Research Administration (OHRA) website has many useful links (including to regs, etc.)!   The OHRA Quality Improvement Program (QIP) offers many services to the Longwood research community.   ESTR (HU’s IRB online submission system) has a ‘library’ page in which you can see the worksheets and checklists that the IRB uses to evaluate studies.   Harvard T. H. Chan School of Public Health Research Ethics Guidelines International Online Navigation Map (Region)   IRB Forum  51

Q UESTIONS ? OHRA  Leslie Howes, Director |  Delia Wolf, Institutional Official, Associate Dean Regulatory Affairs & Research Compliance | QA/QI Specialists  Stanley Estime |  Lisa Gabel |  Alyssa Speier | IRB*  Julie Kaberry, IRB Administrative Chair | *See OHRA website for department-assigned IRB Review Specialists. ( 52

Helpful Tips ( CONT.) ‘If in the field there is no time to think, reflecting on events and thinking about ethics whilst outside of the field can better prepare the researcher for the next ethical ‘snap decision’ to be faced. It can help the researcher gain ‘a way of thinking’, an ‘alertness’ to situated moral dilemmas.’ M. Guillemin, L. Gillam, Ethics, reflexivity, and “ethically important moments” in Research, Qualitative Inquiry 10 (2004),