1. Focus on Clinical Research

2. RESPONSIBILITIES 1) Ensure the research responds to the health needs and priorities of the target community 2) Ensure any product or benefit developed will be made available to the community 2) Ensure any product or benefit developed will be made available to the community Entities With Limited Resources

3. Responsiveness to Community Health Needs Successful interventions that result from the research must be made available to the community. If this is not done, the research is exploitative.

4. Prior Agreement Before the research begins, offer a plan to make available the product to the host nation when the study is done. In planning investigators should include representatives of the government, local authorities, community members, and NGO groups.

5. Agreement The agreement should include decisions about payments, royalties, distribution costs, subsidies, technology, and intellectual property. In some cases, international organizations, public and private, may also be included in the discussions.

6. Need Community Approval Community must have legitimate, empowered spokesperson(s) Community must have a common health- related culture A communication network for the community must be in place

7. Ethical Issues Should investigators ever use the standards of care/ethics of a developing countries vs. developed countries in comparisons? Are investigators responsible for the health of their participants? Can participants in developing countries understand informed consent (e.g., is there an expectancy of benefit or treatment even if not stated in the informed consent)? Is it ethical to do research in developing countries on issues relevant to developed countries but not relevant to developing countries?

8. US IRB Requirements A. Investigator’s knowledge of the community B. Literacy level and language of population C. Status of women: 1. Ensure volunteer participation. 2. ? Supplemental male permission. 3. Potential benefit to women. 4. Procedures respecting women’s autonomy to consent. 5. Written assurance that in no case will a competent adult woman be enrolled in research solely on permission of another person.

9. D. Status of children E. How research aqddresses important question related to host community/country F. How to avoid therapeutic misconception G. How at least some of the national population will get beneficial health care

10. Definition Informed consent does not relate to what investigators think they need to disclose. but rather what the participant needs to know!

11. Ensuring Protections for Research Participants Avoiding the “therapeutic misconception. ” Helping the patient is not the reason for the research. Critical importance of INFORMED CONSENT Participants trust you more than a confusing piece of paper. Be worthy of their trust. Participate in the consenting process and make sure they understand.

12. Human Subjects Consent Form 1. Purpose of the study 2. Procedures 3. Potential risks and discomforts 4. Anticipated benefits to subjects 5. Anticipated benefits to society 6. Alternatives to participation 7. Payment for participation 8. Possible commercial products 9. Sample remaining at the end of the study 10 Financial obligation 11. Emergency care and compensation for injury 12. Privacy and confidentiality 13. Participation and withdrawal 14. Consequences of withdrawal 15. Withdrawal of participation by the investigator 16. New findings 17. Identification of investigators 18. Rights of research subjects 19. Adherence to HIPAA

13. Therapeutic Misconception Participants often enter clinical trials because they think they will benefit from the treatment. Sometimes the investigator is a little misleading to encourage them to enter, but often, they refuse to hear anything but the possibility of treatment.

14. Influences on Voluntary Informed Consent Is it voluntary? Is it informed? Vulnerability to incentives Impact of community pressure coercion Intimidating power of investigators Ability of participants to understand procedures, goals, benefits and risks

15. Additional Risks of Participation Stigmatization, Privacy, Confidentiality

16. Stigmatization = characterizing or branding (a persons) as disgraceful or ignominious (American Heritage Dictionary, 7 th Edition, 1992) Privacy = freedom from unsanctioned intrusion (American Heritage Dictionary, 7 th edition, 1992) Stolen From Detels Stolen From Detels

17. The poor Ethnic minorities Sex workers Drug users The uneducated (illiterate) Men/women who have sex with persons of the same gender HIV- infected persons Persons infected with sexually transmitted organisms Sexually promiscuous persons Marginalized groups

18. Investigator must arrange to guarantee freedom from stigmatization for participants

19. Privacy Respect for persons guarantees the participants RIGHT to privacy Lack of privacy also reduces willingness to participate. Assertion that privacy is guaranteed is insufficient Participant must perceive that privacy is guaranteed. Investigators must deliver on their promise.

20. Confidentiality vs Anonymity Name and identifying information are recorded Guarantee that identifying information will not be shared with unauthorized persons That is only as good as the integrity and care of the investigator and staff With anonymity, name and identifying information are not recorded Impossible to trace back results to informant

21. New HIPAA Rules on PHI PHI = private health information. HIPAA rules are designed to keep health information out of the wrong hands. Need a privacy review of all data collection and analysis. eyes only on need to know basis. anonymization very limited and specific. time limited access. Permission to use health data to screen for participants in some cases.

23. HIPAA and The Common Rule HIPAA uses the same definition of research as the federal Common Rule (45 CFR 46), which is “a systematic investigation designed to contribute to generalizeable knowledge.” Research that creates, uses, or discloses personally identifiable information in the course of providing health care services is protected health information (PHI) under the HIPAA Privacy Rule. Research that records personally identifiable health information to characterize and better understand disease processes without associated clinical intervention, is covered by the common rule but is not protected health information under HIPAA.

24. Research That Is Covered By HIPAA Studies that involve review of the medical record (PHI). Studies in which a health care service is being performed such as testing a new way of diagnosing a condition or a new drug or device for treating a health condition, i.e., creating new medical records. In general, if any part of the research is recorded in a medical record

25. Research That Is Not Under HIPAA but is Covered by the Common Rule The University of California HIPAA Task Force defined the term research-related health information (RHI) when individually identified health information is used during participation in a research study that is not part of any medical treatment. A large fraction of biomedical research using human subjects that is sponsored by NIH and other federal and not-for-profit entities is done to characterize and better understand disease processes without an associated intervention.

26. Was this an ethical study? 1. Was a placebo control justified a.If the subjects were children? b.If the subjects were adults? 2. Seven ethical requirements for clinical research as delineated by Emanuel et al are: a.scientific value b.scientific validity c.fair subject selection d.favorable risk/benefit ratio e.independent review f.informed consent g.respect for enrolled subjects

27. Ongoing Controversies Placebo groups International or local standards of care Should participants be assured care beyond the trials – if so, for how long? Should care be provided to the trial community? Should trials be evaluated for scale-up feasibility before implementation?