KKU Human Research Ethics conference

1. KKU Human Research Ethics conference Ethical Consideration in Research involving Vulnerable groups

2. Declaration of Helsinki (about vulnerable subjects) 17. Medical research involving a vulnerable population or community is only justified if • the research is responsive to the local health needs • reasonable likelihood that this population or community stands to benefit from the results of the research. 27. the research cannot instead be performed with competent persons • the research entails only minimal risk and minimal burden.

3. Declaration of Helsinki(about vulnerable subjects) 27. For an incompetent research subject • the physician must seek informed consent from the legally authorized representative 28. When an incompetent subject is able to give assent to decisions the physician must seek that assent in addition to the consent of the legally authorized representative • The incompetent subject’s dissent should be respected

4. Declaration of Helsinki 29. Research involving subjects who are physically or mentally incapable of giving consent, for example, unconscious patients, may be done only if thecondition that prevents giving informed consent is a necessary characteristic of the research population. • In such circumstances the physician should seek informed consent from the legally authorized representative. • If no such representative is available and if the research cannot be delayed, the study may proceed without informed consent. • The specific reasons for involving subjects with a condition that renders them unable to give informed consent have been stated in the research protocol and the study has been approved by a research ethics committee. • Consent to remain in the research should be obtained as soon as possible from the subject or a legally authorized representative.

5. Case scenario • A randomized, placebo-controlled trial aimed to study the efficacy of investigational drug to stop intracranial hemorrhage in patients with closed head trauma with moderate brain injury. • This study will start treatment within 8 hoursafter motorcycle accident. • The treatment will continue to complete 16 hours. The subject will be evaluated by second CT Brain within 24 – 48 hours after injury.

6. Point to be concerned • What is the standard treatment of such cases? • Is it justified to use placebo that mean “no treatment” for 16 hours? • Information about preclinical study (animal experiment) • Evaluation of risk/benefit ratio • Close monitoring and withdrawal criteria to receive standard treatment • The longest period to contact with legally authorized representative (LAR) is 8 hours = will not start any treatment if cannot contact LAR? • Which clinical phase of this investigational new drug? (phase 2 or 3)

7. Drug development • Phase I • the first introduction of a drug into humans • Normal volunteer subjects (healthy young males usually enrolled) • to determine safety and tolerability (dose-ranging studies) • first single dose for pharmacodynamic and pharmacokenetics, • then multiple dose escalation • Phase II • controlled clinical trials designed to demonstrate effectiveness and relative safety • performed on a limited number of closely monitored patients.

8. Case scenario • Recruitment for early phase drug trial • Exclusion criteria “30 days interval” • Genetic study in drug users – where? and why all recruitment places are in Southeast Asia – researcher team is from top ten university in western country plus Thai investigators