The purpose of this webpage is to provide information about research. By reviewing the world history of human experimentation, one can understand the basis for the creation of federal regulations. Education regarding research is necessary in order to promote a healthy relationship between investigators and research participants. Finally, this site is designed to inform the research participant about the Institutional Review Board; a board designed to protect and advocate for the research participant.
As early as the 6th century B.C., there are records of meat and vegetable experiments conducted on young Jewish prisoners. As late as the 21st century A.D., there are still reports of unethical research being conducted within the United States, despite oversight by the Food & Drug Administration and the Office of Human Research Protection, a division of the Department of Health and Human Services. In between these centuries, the most horrific human experiment atrocities were committed during the WWII era – the medical experiments of the Nazi physicians and the Japanese’s Unit 731, and the Atomic Energy Commission and CIA of our own United States. As evidence shows, humans were and (still) are capable of overlooking the basic ethical principles when it comes to furthering our knowledge of science, further strengthening the adage - the end does not justify the means.
The following is a brief overview of how medical ethics evolved, beginning with the trial of the Nazi physicians post WWII:
- Nuremberg Military Tribunal of the Nazi physicians (1947)
Outcome: The Nuremberg Code which, in essence, states it is “essential to obtain subject’s voluntary consent for research” taking into consideration the capacity of the subject to provide consent, freedom from coercion to consent and comprehension of the risks and benefits involved in the research.
- World Medical Association (1964)
Outcome: Declaration of Helsinki adopts the Nuremberg Code and goes on to further delineate research as therapeutic vs. non-therapeutic.
- National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research (1978)
Outcome: The Belmont Report defined boundaries between “practice” and “research” and developed three basic tenets for research involving human subjects: respect for persons, beneficence and justice. Respect for persons involves the recognition that individuals are afforded dignity and autonomy in making their own choices; in addition, those persons with diminished autonomy are afforded special protection. Beneficence is the obligation to protect persons from harm by maximizing benefits while minimizing potential harm(s). Justice encompasses the fair distribution of research burdens among socioeconomic, race, age and gender strata.
In 1981, three years after the Belmont Report was issued, the Department of Health and Human Services (formerly Department of Health and Education Welfare) and the Food and Drug Administration restructured and revised their regulations regarding human subjects. The Department of Health and Human Services regulations are codified at Title 45 CFR (Code of Federal Regulations) Part 46 Protection of Human Subjects. The Food and Drug Administration’s regulations are codified at Title 21 CFR Parts 50 and 56; Part 50 outlines Informed Consent requirements and Part 56 addresses institutional review boards. Other FDA regulations regarding institutional review boards and how they relate to investigational new drugs and investigational device exemptions are found in Parts 312 and 812, respectively. (More information can be found at the DHHS and FDA websites. The links are found below.)
All research protocols that receive federal funding must comply with the federal regulations. The Institutional Review Board was created to ensure that investigators follow the federal regulations. It should be noted that non-federally funded research projects here at the University are also reviewed following federal regulations.
Synonyms Used in Research
The activity known as “research” can be called many different things:
- Research Study
Likewise, people recruited for research are referred to by many names:
- Study Participant
- Research Participant
- Research Subject
- Clinical Subject
(Please note: Research professionals do not refer to subjects as “guinea pigs;” unfortunately, this term is sometimes used by study participants.)
- http://www.hhs.gov/ohrp The Office of Human Research Protection, a division of the Department of Health and Human Services
- www.hhs.gov The Department of Health and Human Services
- www.ahrp.org The Alliance for Human Research Protection
- www.nih.gov The National Institutes of Health, a branch of the Department of Health and Human Services
- http://clinicaltrials.gov/ A service of the National Institutes of Health that provides information about federally and privately supported clinical research
- http://gcrc.ouhsc.edu/ The General Research Center at the University of Oklahoma Health Sciences Center
Additional Educational Opportunities Regarding Research
For reading material on Human Subject Research, the manual “Protecting Study Volunteers” by Dunn & Chadwick is also recommended.
Frequently Asked Questions
» What is Human Research?
Human research is defined as an activity designed to test a hypothesis (theory). The testing of this hypothesis lets an investigator draw conclusions as to whether the hypothesis is true, false or null (neither true nor false). The results of hypothetical investigations ultimately contribute to generalizable knowledge; that is to say these investigations, although tested in relatively small numbers, may be applied to larger numbers.
Human research begins when an investigator develops a study protocol to test a hypothesis. A study protocol is a uniform set of directions the investigator follows during a research project. The study protocol defines the objective, or goal, of the research project; for example, does substance B work better than substance A? The protocol defines what sort of activities or tests will be carried out in order to answer the hypothetical question.
Once the investigator has developed a protocol to test the hypothesis, the investigator sends this information to the Institutional Review Board. The Institutional Review Board makes sure the protocol follows Federal and University rules and regulations for protecting human subjects. Once the protocol has been approved, the investigator may begin the study. From that point on, the investigator will continue to give the Institutional Review Board (at least) yearly updates on the study. This is a Federal Requirement to help ensure that the conduct of the study continues to protect human research subjects.
» What is an Institutional Review Board (IRB)?
The federal government established the Institutional Review Board (IRB) as a way of uniformly regulating human research protocols across the United States. The IRB is designed to protect the rights and welfare of human research subjects who have been recruited to participate in research activities. Human subjects are defined as living individuals about whom an investigator (whether professional or student) conducting research obtains data through (1) intervention or interaction, or (2) identifiable private information.
The IRB functions in an autonomous role at the University. The IRB performs its federally mandated role without undue influence from either the University or the investigators conducting research at, or on behalf of, the University. The IRB’s primary responsibility is the protection of the human research subject.
An IRB is made up of men and women who meet and discuss all research-related protocols. By law, there are at least five (5) members who make up an IRB. Of these 5, at least one member is not associated with the IRB, or this institution. Additionally, the qualifications of these people should be varied so that many perspectives can be applied to the research protocols. Here at this University, there are four separate IRBs conducting reviews of all clinical research being carried out by University-employed investigators.
» What does the IRB do?
The men and women members of the IRB approve (or disapprove) submitted research protocols based on federal, state and local rules and regulations regarding human research. In addition, the IRBs at this institution make sure the research protocols follow University policy regarding human research.
After approval has been given, these men and women then re-evaluate these protocols (at least) once each year while the study is active. Again, they are monitoring to make sure the investigators and the research protocols are following federal, state, local and institutional rules and regulations regarding human subject protection.
The IRB members, as well as the IRB staff, also serve as a contact for research participants. This part of the IRB is called the Human Research Participant Protection Program. This program can answer research-related questions regarding study participant rights.
» What is the Human Research Participant Protection Program?
The Human Research Participant Protection (HRPP) Program is the University of Oklahoma's established program designed to support its commitment to the protection of human participants in research. This program incorporates individuals from the IRB, the University Director of Compliance and the University’s Vice Presidents of Research. The goals of this program are to ensure human participant safety, to educate the University’s researching body and to provide continuous quality improvement of the University’s research activities.
Beginning in 2000, steps were taken to formally train all investigators and clinical research staff regarding human research participant protection. All investigators have completed these requirements.
In addition to the required training, the Office of HRPP created a quality improvement program to assess research activities conducted. In the future, quality improvement may branch out and conduct surveys of former and current human research subjects. As mentioned earlier, the major goal of the HRPP Office is the protection of human research participants. By conducting site visits and quality improvement surveys, the HRPP Office is developing a strategic plan to address areas of concerns through education.
» How do I contact the Human Research Participant Protection Program?
The IRB can be contacted directly by calling (405) 271-2045, emailing email@example.com, or postal mail at: OUHSC HRPP, 1105 N. Stonewall Avenue, LIB 176, Oklahoma City, OK 73117. Please be assured that your comments or concerns will be treated in a confidential manner.
» Who Sponsors Research?
Research is funded by state and federal agencies, private industry, and non-profit organizations.
These companies are large corporations that develop drugs. They can be found in the United States as well as abroad. As far as the United States is concerned, if a company (whether US-based or based abroad) is developing and/or manufacturing a drug to be used in the United States, it is subject to the federal rules and regulations of the FDA (Food and Drug Administration). In order for a drug to be approved by the FDA, the drug must go through a series of clinical investigations to prove that the drug treats what it is intended to treat, while at the same time not causing any harmful effects.
How it all begins…
The process usually begins with a disease (or a condition). That disease is then studied in terms of its global occurrence and its impact on public health (called epidemiology). Using knowledge gained from past experience, scientists begin to develop a drug designed to treat (alleviate or prevent) the disease. After the drug is formulated, testing the hypothesis (“Will this help the disease… will this prevent the disease…?”) begins.
The drug is first tested using animal models. The data from those models is then reviewed and protocols are made for human investigations, usually “normal, healthy” human volunteers (Phase I research). The data collected from the “normal, healthy” volunteers is then analyzed and a protocol is developed for another set of human volunteers; those who actually have the condition which the drug is supposed to help (Phase II research). The number of people studied here is still very low and usually the drug is given in several different strengths in order to identify “the best” dose – a dose that provides a benefit for the condition while not causing any harmful effects. The data from this group of research subjects is then evaluated and a new protocol is developed. The number of study participants in this phase of drug research (Phase III) is typically in the thousands, and these participants all have the same condition being studied. With the help of local health care providers, typically medical doctors, clinical research sites are formed so that lots of people with the condition being studied can be recruited for this Phase III research.
The FDA reviews all phases of clinical research before the next phase can begin. Likewise, the Institutional Review Board monitors protocol and study progress on a more “local” level.
This is a tremendously shortened version of how drugs evolve. The process is actually quite slow and methodical. If interested, the FDA website contains the mechanics of drug development. This is referred to as New Drug Application and Pre-Market Approval.
Sometimes, health care professionals conduct research through their own efforts. Typically, these studies fall into Phase IV research – which is research on drugs (or products) that are already available “on the market.” In this phase of research, the investigator is looking at different uses of the drug; say, for instance, in treating a condition similar (or different) from the condition for which the drug is “labeled.” That is to say, drug A is approved to treat condition A. The investigator would like to see if drug A could also be used effectively in condition B. Before this sort of investigation begins, the investigator must take nearly the same steps as found in new drug production in proving the hypothesis. Again, the FDA has lots of information regarding this on its website. This is referred to as Investigational New Drug Application.
» Who Do I Contact for Questions?
1) If you would like to offer suggestions regarding the human research protection program or would like to obtain information, you are encouraged to contact the Director of the Office of Human Research Participant Protection (HRPP) at (405) 271-2045. The Director can also be reached via email at firstname.lastname@example.org or through regular mail at: 1105 N. Stonewall Avenue, LIB 176, Oklahoma City, OK 73117.
2) If you have:
- Questions about your rights as a research participant
- Questions regarding a research study
- Concerns or complaints about the research
- Experienced a research-related injury
You should contact the research investigator. Information for the investigator will be located in the Informed Consent Document when you volunteer to participate in a research study. This document will have the Study Title on the front page, along with a description of the study. Towards the back of the document, there will be a heading "Whom Do I Call if I Have Questions or Problems?" In this section, the name of the investigator will be listed, along with a telephone number and/or email address.
3) If you:
- Cannot reach the investigator, or
- Wish to discuss your questions or concerns with someone other than the investigator
You are encouraged to contact the Director of the Office of Human Research Participant Protection (HRPP) at (405) 271-2045. The Director can also be reached via email at email@example.com or through mail at: 1105 N. Stonewall Avenue, LIB 176, Oklahoma City, OK 73117. Please include the IRB number, study title, and investigator name (if possible). Based on the content of your communication, your comments or concerns will be appropriately directed. Please remember, our primary purpose is to protect participants involved in research.
4) If you are considering becoming a research participant and:
- Would like to discuss any concerns about volunteering to participate in a research study, or
- Have any questions about becoming a research participant
You are invited to contact the HRPP Director at (405) 271-2045. The Director can also be reached via email at firstname.lastname@example.org or through mail at: 1105 N. Stonewall Avenue, LIB 176, Oklahoma City, OK 73117.