Recognizing and Minimizing Risks in VA Research

Kevin L. Nellis, M.S., M.T. (A.S.C.P.)

Program Analyst

Program for Research Integrity Development and Education (PRIDE)

March 28, 2011

Overview

•Regulatory background

•Individuals or populations vulnerable to risks

•Types of risks in research

•Minimizing risks

•Potential risks based on types of research

2

Minimization of Risks

• Risks to human subjects are minimized by using procedures that:

• Are consistent with sound research design

• Do not unnecessarily expose subjects to risk

• Are already being performed for diagnostic or treatment purposes

3

Risks and Benefits Analysis

• Risks to subjects must be reasonable in relation to

• Anticipated benefits (outcome or advantage)

• Importance of the knowledge that is expected as a result of the research

• When analyzing the risks to benefits ratio

• Consider only risks and benefits of the research

• Do not to consider possible long-range effects of applying knowledge gained in the research

4

Categorically Vulnerable Populations

• Additional protections required in VHA Handbook 1200.05, for research involving:

• Persons who lack decision-making capacity

• Prisoners

• Pregnant Women

• Children

5

Factors Contributing to Risk

• Complicated lives or time constraints

• Exposure to safety issues

• The immature or emotionally fragile

• Societal judgment

• The financially insecure

• Illegal behaviors

• Legal actions

• Certain populations6

Factors Contributing to Risk

• Employees

• The homeless or displaced

• Language or educational challenges

• Mental or physical disabilities

• Socio-economic disadvantages

• Poor access to healthcare

7

Third Parties at Risk

• Bystanders (family, community,

social groups, caregivers, etc)

• Consumers

• Institutions

8

Possible Types of Risks

• Physical (direct and indirect)

• Psychological or emotional

• Social or cultural

• Economic

• Legal

9

Physical Risks

• Injury

• Pain

• Fatigue

• Side effects of drugs

• Assault

• Death

10

Protections From Physical Risks

• Appropriate study design with appropriately trained individuals

• Appropriate recruitment, advertising, and informed consent process

• Careful monitoring of subjects

• More frequent IRB review

• Providing first aid or clinical care

• Compensate for harms

11

Psychological Risks

• Getting upset or worried

• Anxiety or depression

• Feelings of stress or guilt

• Confusion or hallucination

• Embarrassment or shame

• Loss of self-esteem or self-confidence

12

Protections From Psychological Risks

• Adequately and sensitively administered informed consent

• Respectful treatment

• Remind participants of their right to withdraw or to limit their participation

• When appropriate:

• Provide psychological support or counseling

• Thoroughly debrief subjects after participation

• Assure anonymity

• Provide contacts for suicide hotline

13

Social Risks

• Embarrassment

• Stigma (ostracism)

• Conflict

• Scapegoating

• Resentment

• Discrimination

14

Protections From Social Risks

• Adequately and sensitively administered informed consent

• Assure privacy, confidentiality, and data security

• Assure anonymity, when appropriate

• Ensure researchers follow professional codes

15

Economic Risks

• Loss of a money

• Loss of financial opportunity

• Loss of credit

• Identity theft

• Loss of insurability

• Loss of wages

• Loss of job or advancement

16

Protections From Economic Risks

• Compensate for harms

• Assure of privacy, confidentiality, and data security

• Keep research data separate from medical records to prevent employers and insurance companies from obtaining information

17

Legal Risks

• Lawsuits

• Disclosure of illegal activities

• Conviction of crime

• Subpoena of damaging data

18

Protections From Legal Risks

• Assure anonymity, when appropriate

• Assure of privacy, confidentiality, and data security

• Obtain Certificate of Confidentiality, if appropriate

19

Certificates of Confidentiality are Obtained From the NIH

• Helps researchers protect the privacy of human research participants

• Protect against compulsory legal demands (e.g., court orders and subpoenas)

• Does not protect against voluntary disclosures by the researcher (as specified in the informed consent form)

• Subjects are protected permanently- even if the subject gave the researcher data before the Certificate is issued

• NIH: http://grants.nih.gov/grants/policy/coc/

20

Examples of Research Areas Eligible for Certificates of Confidentiality

• HIV, AIDS, and other STDs

• Sexual attitudes, preferences, or practices

• Alcohol, drugs, or other addictive products

• Information on illegal conduct

• Studies that gather sensitive or risky information

• Mental health

• Behavioral interventions and epidemiologic studies

• Genetic studies

21

22

Potential Risks of Clinical Studies

• Drugs and devices

• Treatment-withholding studies

• Placebo-controlled clinical trials

• Phase I clinical trials in healthy subjects

• Phase I oncology trials

• Confusing language in informed consent

• Conflicts of interests

• High risk radioactive or other materials23

Potential Risks of Genetic Testing

• Psychological impact – emotions aroused by learning that one is (or is not) likely to develop a serious disease

• Change in family dynamics

• Involving minors or incapacitated

• Privacy – will a predisposition remain a secret or slip out?

• Incidental findings about paternity

• Risks of sharing information

• Impact on medical choices

24

Potential Risks of Focus Groups, Questionnaires, or Surveys• Breach of confidentiality or violation of privacy

• Inadvertent disclosures of media (audio, video, or photos)

• Validation of inappropriate or undesirable behaviors

• Presentation of results in a way that does not respect (or agree with) subjects’ interests

• Damage to dignity, self-image, or innocence

• Possible harm to secondary subjects

• Reportable situations (e.g., elderly or child abuse, threats, infectious disease, criminal activities)

25

Potential Risks of Focus Groups, Questionnaires, or Surveys

• Three weeks after answering the questionnaire for a cancer study; a man in his early 20s committed suicide, leaving a note stating that until he answered the questionnaire he did not really realize all of the experiences he had missed.

• A survey researcher was investigating attitudes toward rape. When filling out questionnaires, several subjects became visibly emotionally distressed and asked the investigator for help.

Ref: IRB Forum (January 2001)

26

Potential Risks of Focus Groups, Questionnaires, or Surveys

• A study involving adolescents with emotional difficulties included a few questions about sexual preferences. One subject interpreted the questions as if the researcher were suggesting she or he was a homosexual. The subject became very upset, attacked the researcher, and had to be restrained.

Ref: IRB Forum (January 2001)

27

Key Points

• All those involved in research must understand various risks of research

• Investigators must design the study to minimize risks

• IRBs must ensure that risks are minimized and reasonable in relationship to anticipated benefits before approving the research

28

Key Points

• Both the investigator and the IRB must ensure protections are specific to:

• Nature of the risks

• Individuals involved

• Type of research

• Location and culture

• Monitor and modify the research to minimize risks

29

References

• Bankert and Amdur. IRB Management and Function. (2006) http://books.google.com/books

• Risk and Harm: Social and Behavioral Sciences Working Group on Human Research Protections. (2004)

http://www.aera.net/humansubjects/risk-harm.pdf

• National Research Council. Protecting Participants and Facilitating Social and Behavioral Sciences Research. (2003) http://www.nap.edu/catalog.php?record_id=10638

• OHRP. IRB Guidebook. (1993) http://www.hhs.gov/ohrp/archive/irb/irb_guidebook.htm

• Clayton. Incidental Findings in Genetics Research Using Archived DNA. J. Law. Med. Ethics. 2008: 36(2):286-212 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2576744/

30

31