International Research 101

Presented by: The Office of the Human Research Protection Program

Dorean J. Flores, CIP and Selina Zydor, CIP

CME Disclosure • The North Shore LIJ Health System adheres to the

ACCME’s new Standards for Commercial Support. Any individuals in a position to control the content of a CME activity, including faculty, planners, and managers, are required to disclose all financial relationships with commercial interests. All identified potential conflicts of interest are thoroughly vetted by the North Shore-LIJ for fair balance and scientific objectivity and to ensure appropriateness of patient care recommendations.

• Course Director and Course Planner, Kevin Tracey, MD and Tina Chuck, MPH have nothing to disclose.

• Course Speakers: Dorean J. Flores and Selina Zydor have nothing to disclose

Objective: Discuss the regulatory framework when conducting international research. Topics: 1. Outline regulatory requirements and guidelines

pertaining to international research. 2. Discuss IRB requirements when conducting

international research 3. Provide an overview of common barriers when

conducting international research and provide tips & practical solutions to mitigate obstacles.

4. Provide examples of different types of vulnerabilities to be mindful of when conducting international research.

Regulatory Requirements • 2015 Edition of the International Compilation of Human

Subject Research. • The International Compilation of Human Subject Research

Protections lists laws, regulations, and guidelines governing human subjects research world-wide. These laws, regulations, and guidelines are classified into six categories: General, i.e., applicable to most or all

types of human subjects research.

Privacy/Data Protection

Drugs and Devices

Human Biological Materials

Research Injury

Genetics

Embryos, Stem Cells, and Cloning

Ethical Codes • The Belmont Report

•Respect for Persons - protecting the autonomy of all people and treating them with courtesy and respect and allowing for informed consent. Researchers must be truthful and conduct no deception;

•Beneficence - the philosophy of "Do no harm" while maximizing benefits for the research project and minimizing risks to the research subjects; and

•Justice – ensuring reasonable, non-exploitative, and well-considered procedures are administered fairly

Ethical Codes

• The Nuremberg Code 1. The voluntary consent of the human subject is absolutely

essential. The duty and responsibility for ascertaining the quality of the consent rests upon each individual who initiates, directs or engages in the experiment. It is a personal duty and responsibility which may not be delegated to another with impunity.

2. The experiment should be such as to yield fruitful results for the good of society, unprocurable by other methods or means of study, and not random and unnecessary in nature.

Ethical Codes (cont’d) 3. The experiment should be so designed and based on the results

of animal experimentation and a knowledge of the natural history of the disease or other problem under study that the anticipated results will justify the performance of the experiment.

4. The experiment should be so conducted as to avoid all

unnecessary physical and mental suffering and injury. 5. No experiment should be conducted where there is a prior

reason to believe that death or disabling injury will occur; except, perhaps, in those experiments where the experimental physicians also serve as subjects.

Ethical Codes (cont’d)

6. The degree of risk to be taken should never exceed that determined by the humanitarian importance of the problem to be solved by the experiment.

7. Proper preparations should be made and adequate facilities

provided to protect the experimental subject against even remote possibilities of injury, disability, or death.

8. The experiment should be conducted only by scientifically

qualified persons. The highest degree of skill and care should be required through all stages of the experiment of those who conduct or engage in the experiment.

Ethical Codes (cont’d)

9. During the course of the experiment the human subject should be at liberty to bring the experiment to an end if he has reached the physical or mental state where continuation of the experiment seems to him to be impossible.

10. During the course of the experiment the scientist in charge

must be prepared to terminate the experiment at any stage, if he has probable cause to believe, in the exercise of the good faith, superior skill and careful judgment required of him that a continuation of the experiment is likely to result in injury, disability, or death to the experimental subject.

Research Standards 1. Department of Health and Human Services (DHHS)

• 45 Code of the Federal Regulations 46

2. Food and Drug Administration • 21 CFR 50 (Protection of Human Subjects) • 21 CFR 56 (Institutional Review Boards)

3. Council for International Organizations of Medical Sciences

(CIOMS): International Ethical Guidelines for Biomedical Research Involving Human Subjects

Research Standards (cont’d)

4. International Conference on Harmonization - Good Clinical Practice E6 • An international ethical and scientific quality standard for

designing, conducting, recording, and reporting trials that involve the participation of human subjects.

• Objective: Provide a unified standard for the EU, Japan, and

the US to facilitate the mutual acceptance of clinical data by the regulatory authorities in these jurisdictions.

Research Standards (cont’d)

5. Canada – • Tri-Council Policy Statement: Ethical Conduct for Research

Involving Humans . • Canadian Institutes of Health • Natural Sciences and Engineering Research Council of

Canada • Social Sciences and Humanities Research Council of

Canada 6. India –

• Indian Council of Medical Research: Ethical Guidelines for Biomedical Research on Human Participants

IRB Requirements • When an investigator at NSLIJ Health System collaborates with or

plans to study subjects in a foreign country, additional requirements need to be satisfied.

• Care must be taken to ensure that the cultural norms of the host

country are respected and that the participants will not suffer adverse consequences from participation, such as being subjected to retaliation from local authorities or the local community.

• If the country of collaboration or investigation has regulations to

protect human subjects, then at a minimum they must be met in addition to local, state and federal regulations.

IRB Requirements (cont’d) • If no regulations are in place, then the investigator should apply all ethical, safety, and reporting standards used for local research

protocols. • All regulations that apply for domestic studies should be applied to

studies conducted in other countries. • When conducting research in countries outside the U.S., the PI

should submit the Application for Approval of International Research to the IRB, along with other required forms. The investigator should also consult with researchers familiar with the culture differences of international research and consider the different customs, habits and practices of international study subjects.

IRB Requirements (cont’d) The IRB will:

• Confirm the qualifications of the researchers and research staff for conducting research in that country, through review of the Application for Approval of International Research.

• Provide initial review, continuing review, and review of

modifications to previously approved research. • Handle complaints, non-compliance and unanticipated

problems involving risk to subjects or others in accordance with the NSLIJHS Human Research Policies & Procedures.

IRB Requirements (cont’d) • Obtain necessary information about the local research context

through one or more of the following mechanisms: Personal knowledge of the local context by an IRB member,

through direct experience with the research site, its population, and surrounding community

Participation by one or more consultants at convened

meetings or through written review. o Such consultants should be appropriately qualified with

local knowledge of the research context, population, and its surrounding community

IRB Requirements (cont’d)

Input from an IRB/Ethics Board, in the country where the research will take place. If an IRB is not available, an appropriate government agency may be consulted.

Other sources of help include the country’s health ministry

and consulate and/or non-governmental organization (NGO) working in the area.

Tips & Tricks

• When submitting your application to the IRB, it is important to include as much information about the conduct of human subject research in the foreign country as possible. This includes:

• Delineating the aspects of the study which are occurring locally versus internationally;

• Information about local laws; • Native language of potential research participants; • The age of majority; • Cultural sensitivities; and • Who is responsible for providing consent and whether written

or oral consent is customary.

Common Barriers: Language

Common Barriers: Language

Barriers

Technical Breakdown

Receiver Unable to

Understand

Attitudes towards

Investigator

No feedback

Poor Timing

Use of Jargon

Unclear Message

Wrong Format

Hierarchy

Common Barriers: Misinterpretation

https://www.youtube.com/watch?v=gmOTpIVxji8&feature=youtu.be

Common Barriers: Age of Majority

• The age of majority is the age that children become adults by law. • This can range from 14 to 21 depending on the country and may

differ from male to female.

• Designation may also change depending on married status.

Common Barriers: Age of Majority

• The age of majority is the age that children become adults by law.

• This can range from 14 to 21 depending on the country

and may differ from male to female.

• Designation may also change depending on status. • Single vs. Married

Common Barriers: Cultural sensitivities

Common Barriers: Cultural sensitivities

•Two dimensions of cultural sensitivities – • Surface structure = matching intervention materials

and messages to observable characteristics of a target population.

• Deep structure = incorporating the cultural, social,

historical, environment and psychological forces that influence the target population’s health behavior into the intervention.

Common Barriers: Consent

Common Barriers: Consent

• Obtaining consent in accordance with 45 CFR 46 and 21 CFR 50 in certain international settings may raise challenges due to a difference in the norms of the host country. These include:

• Differences in cultural and societal norms; • Differences in the role of women in society; and • Differences in the role of family and community in the

consent process.

Common Barriers: Consent

• Where local practices are inconsistent with U.S. requirements an equivalent process may be considered, e.g., in countries with spoken but no written language, and appropriate alterations to the consent process may be necessary.

• If the legal age of an adult differs in another country

from New York State (NYS), the IRB should accept the local age of majority when considering who may provide their own consent.

The Solution

Additional Vulnerabilities

Physically Handicapped

Mentally Disabled

Economically Disadvantaged

Educationally Disadvantaged

Racial or Class Minorities

Terminally Ill or Elderly/Aged

Religious Affiliation

Institutionalized

Women & Children

Individuals of Domestic Violence/Sexual Assault

Sexual Identification

Migration

Questions or Comments

Dorean Flores, CIP Manager, Office of the Human Research Protection Program

(516) 321-2112 dflores1@nshs.edu

Selina Zydor, CIP

Manager, Office of the Human Research Protection Program (516) 321-2114

szydor@nshs.edu