Human Subjects Protection

University of Houston - Downtown

The first step in the evolution of ethics is a sense of solidarity with other human beings.

Albert Schweitzer

Historical Background

5th Century – Hippocrates: “Primum non nocere” (First do no harm.)

1900 - Walter Reed conducted his yellow fever experiments with Spanish immigrant workers and soldiers in Cuba.

1941 to 1945 - Experimentation at concentration camps.

1947 - Judgment at Nuremberg Doctors Trial. Of the 23 physicians/scientists tried, 16 were found guilty and 7 were sentenced to death.

Historical Background (cont)

1932 – 1972 – the U.S. Public Health Service conducted an experiment in Tuskegee, Alabama. More than 400 uneducated, poor black men were enrolled to follow the natural course of syphilis.

1964 – World Medical Association adopts Helsinki Declaration. Recognized the difference between therapeutic and non-therapeutic research.

1966 – The Office for Protection from Research Risks (OPRR) was established in NIH. Established the use of local institutional review boards (IRBs).

Historical Background (cont)

1973 – Final Report of Tuskegee Syphilis Study – concluding that “Society can no longer afford to leave the balancing of individual rights against scientific progress to the scientific community.” 1974 – National Research Act – upgraded OPRR policies to regulations and is now known as the Common Rule. Established the National Commission for the Protection of Human Subjects.

1975 – HHS promulgates Title 45 of Federal Regulations titled “Protection of Human Subjects.”

Historical Background (cont)

1979 – National Commission for the Protection of Human Subjects issues the Belmont Report. Establishes 3 basic ethical principles – respect for person, beneficence and justice.

1991 – Subject commits suicide after participating in a study on relapse of schizophrenics withdrawn from medication at UCLA.

1999 – 18-year old subject dies in a gene therapy experiment at U of Pennsylvania.

Historical Background (cont)

2000 – OPRR becomes the Office of Human Research Protection (OHRP) and is moved from the NIH to the Department of Health and Human Services (HHS).

2001 – Healthy volunteer dies in an asthma study at Johns Hopkins University.

The moral test of any society is how it cares for the people in the dawn of life: the children; the twilight of life: the elderly; and the shadows of life: the sick and disenfranchised.

Hubert H. Humphrey

FEDERAL REGULATIONS

45 CFR 46, a.k.a. “the common rule,”is the federal regulation which applies to most research using human subjects.

21 CFR 50 & 56 applies to research which falls under the Food & Drug Administration.

WHAT IS RESEARCH?

Research is defined as “a systematic investigation, including research development, testing and evaluation, designed to develop or contribute to generalizable knowledge.” 45 CFR 46.102(d)

WHAT IS A HUMAN SUBJECT?

“Human subject means a living individual about whom an investigator (whether professional or student) conducting research obtains (1) data or (2) identifiable private information through intervention or interaction with the individual.” 45 CFR 46.102(f)

45 CFR 46Besides defining research and human subjects, 45 CFR 46 defines the responsibilities of institutions engaged in research and their Institutional Review Boards (IRB). At UHD, the Human Subjects Committee is the IRB charged with these responsibilities.

IRB membership: The committee must include at least five members with the professional competence necessary to review research activities, plus at least one member whose primary concerns are in nonscientific areas and one member not affiliated with UHD.

The IRB has the authority to approve, require modifications, or disapprove research.

45 CFR 46 In order to approve research, the IRB shall determine that all of the following have been

satisfied:

(1) risks to subjects are minimized; (2) risks to subjects are reasonable in relation to

anticipated benefits (if any) and the importance of the knowledge that may be expected; (3) selection of subjects is equitable; (4) informed consent will be sought; (5) informed consent will be documented; (6) when appropriate, data safety monitoring; and (7) when appropriate, there are adequate provisions made

to protect the privacy of subjects and maintainconfidentiality.

45 CFR 4645 CFR 46 also defines the required elements of informed consent, and gives standards for IRBs to use in deciding how informed consent must be documented and when it may be waived.

It sets up two special review categories for low-risk research: “exempt” and “expedited.” Both still require IRB review and approval, but may be reviewed by an IRB subcommittee instead of the full committee. In addition, IRBs may decide not to require the yearly periodic review of “exempt” projects that is required of all other research projects.

Finally, the federal code provides definitions and guidance on conditions that must be met to study vulnerable populations, such as prisoners, children, and pregnant women.

The UHD Application Form

The UHD application form was designed to assist the applicant in providing all the information needed by the Committee to approve a project. It can be downloaded and filled out on the investigator’s computer before being printed, signed, and copied. It must be submitted 4-6 weeks before IRB approval is needed.

The form can be found on the UHD Human Subjects Protection website:

http://www.uhd.edu/research/phs/

UHD Application (cont.)

The first page of the UHD application asks for contact information on the investigator(s), the type of review requested, the title of the project, and the projected time frame for your study. For student applicants, information must also be supplied about the faculty sponsor.

It then requests a lay summary of the project, which means a short summary that a nonscientist can understand. It specifically asks you to include information on the “who” (subjects), “where,” “how” (methodology) and “why” (thesis) of your project.

UHD Application (cont)

The second & third pages of the application ask for more specific information about procedures and your project’s risks & benefits.

Two requests frequently cause confusion:

The Informed Consent Process

Anonymity & Confidentiality Precautions

The Informed Consent Process must include these 8 basic elements:

Who you are

What you are doing

Why you are doing it

What subjects will be asked to do & how long your participation will take

That participation is voluntary

That there will be no penalty for not participating or for withdrawal from the study

How confidentiality/anonymity will be handled

Who to call with any questions or concerns regarding the research project

UHD Application (cont.)

Please note: Informed consent is a process – not a piece of paper. It must be obtained in a manner that allows subjects to voluntarily agree or decline to participate. Consent scripts and forms must therefore be requested in language easily understood by all potential subjects, generally considered an 8th grade reading level for the general public. They must include all 8 basic elements of informed consent, and you must give copies to all your subjects.

UHD Application (cont)

UHD Application (cont.)

Anonymity and confidentiality protect your subjects’ privacy, but in different ways:

Anonymity protects subjects’ privacy by maintaining no record of their identity. Even informed consent forms constitute a record, which is why they are sometimes waived.

Confidentiality protects subjects’ privacy by keeping identifying information separate from the data gathered, coding any identity category on the data set, and locking up the list of subjects by code until the list is destroyed.

UHD Application (cont.)

The last page of the application asks you to attach all the research materials your application refers to, or which are required. Examples:

Recruitment letter/ad/protocol Informed Consent script/form/letter Child Assent form Questionnaire Cover letter Debriefing script/form Certification of Human Subjects Training Consent from Site

For A Successful Review…

Don’t wait until you have a project pending to start preparing.

Learn about human subjects protection, including taking the online course required before applying.

Think through all the aspects of human subjects protection before planning your project.

Make sure your application specifies all of the information requested.

Submit your application to the committee 4-6 weeks before you need to start collecting data.

Summary

Human Subjects Protection is a professional and institutional responsibility, which requires:

education

conscious research planning

peer review

You have just taken the first steps to fulfill this responsibility.

Thank you!