Clinical Research Operations

Points to Consider when conducting research in an international setting:

Regulations

State clearly on the protocol facesheet which regulatory bodies apply to the protocol, provide the FWA# for each participating institution.

HHS (45 Part 46) and FDA (21 Parts 50, 56, 312, 812) regulations apply for HHS supported research, do ICH-GCP, Declaration of Helsinki or CIOMS apply as well*?
Does the local institution have an international FWA** or is a reliance in place?
Is there an in-country Ethics Committee (EC) or IRB?

Is it experienced?

Proper in-country approvals to conduct research?
Clinical site monitoring means that ICH-GCP applies.
What are issues related to differences in regulations between countries**?
What about conflict of interest issues?

Setting- Is this type of research appropriate in this setting?

What is the local epidemiology? State in the background of the protocol.
Is the research related to diseases/health concerns of this population?
Does the research provide treatment, if so, who will provide SOC after research ends?
Is this a resource-poor setting, how are those challenges addressed
- See “Infrastructure” below
- Will this research build capacity?

How much other research is taking place in this setting?
How are differences in cultural norms addressed?

Infrastructure- Is infrastructure adequate?

Adequacy of facilities
Qualifications of local research staff
Standards of professional conduct and practice
Local/National Human subjects protection oversight (EC/IRB)
Clinical resources
- Realistic expectations, will 1^st- world clinical care be provided in a third-world setting?

Will labs be processed in-country or sent away?
- How will specimens/data that are being sent out-of-country be handled?***
Is there adequate confidentiality in place for records/data/subjects
- For example, could stigma occur if a subject merely walks into the clinic?
Adequate security

Structural Issues

Order of reviews: NIH, then in-country
Maintenance of records
- Security and confidentiality protections
- Version control for protocols and consents
- Storage: How long will records be retained (follow NIH policy and FDA requirements)

Who will provide site monitoring****
Lapse in local oversight/review
Lapse in review/resources (US)
How will study closure/termination be handled?
Is this capacity building, how does that differ from the research?

Adequate oversight of local investigators/researchers

Safety of subjects
- Adverse event tracking/reporting/treatment?
  - One possible area of difference: UP at NIH, SAE at other site
Risk/benefit assessment: are risks of research greater than those experienced in daily life (may be different than those normally encountered here)
Is there a national treatment protocol in place; is it easy for subjects to access?
How far do subjects have to travel?
Does compensation impact subject safety? (see Compensation below)
Privacy: Are subjects comfortable disrobing in front of the opposite sex, even for clinical care?
Confidentiality: Could partner notification put a female subject at risk?
Confidentiality: Are records and equipment secure?
Compensation
- Form of compensation: money (what is the local value, US equivalency), versus goods (millet, sugar, rice) or services (clinical care, new clinic, etc…)
- Is it coercive?
- Does it place subjects at risk for robbery?
- How is it paid out, (all at once, pro-rated, etc…)?

Informed consent

Note that the informed consent must contain all the required elements under 45 CFR Part 46, 21 CFR Part 50 as applicable, but there are additional issues related to international research:

What are the norms for Informed Consent?
- Community Consent
- Familial Consent (spouse, head of family, etc)
- Individual Consent
- Neo-natal/pediatric consent/assent
- Is autonomy affected?
Age of emancipation/majority?
Language barriers,
- Illiteracy
- What about non-written languages?
How will specimens and data be handled?
- How will subject be informed about specimens/data that are being sent out-of-country?
- What about genetic information and incidental findings, issues of stigma and available care?
- Secondary research use?
Stigma (for example partner notification for HIV testing)
How will subjects be informed about new information and/or results of research?
Conflict of interest issues