Basic Information about Human Subjects Research
Program in Human Research Ethics and Oversight (PHREO) Overview
OSA’s Program in Human Research Ethics and Oversight (PHREO) supports the ethical conduct and regulatory compliance of human subjects research conducted or supported by the EPA. This support is accomplished through project review, cross-agency partnership, and education and training. The PHREO reviews, supports, and guides the work of EPA affiliated or supported researchers involved in human subjects research to ensure that the rights and welfare of human research subjects are protected. The PHREO is in place to ensure that all EPA employees, contractors, grant recipients, and parties to other EPA agreements adhere to the highest standards of ethical conduct and are properly informed of the regulatory aspects of research involving human subjects. All research involving human subjects proposed by EPA staff or EPA supported researchers must be approved by the EPA Human Subjects Research Review Official (HSRRO) before human subjects work may begin.
Human subjects research (HSR) at the Environmental Protection Agency (EPA) allows for the collection of valuable information necessary for characterizing and controlling risks to public health. Research involving human subjects informs decision-making and the formulation of regulatory standards at the Agency. HSR is critical for EPA’s program offices to consider when making regulatory decisions under many of the programs it administers, e.g., National Ambient Air Quality Standards, water quality criteria and drinking water standards, pollution mitigation techniques, and pesticide registration. HSR studies advance scientists’ understanding of the links between human health and the environment so that the EPA is better able to carry out its mission.
What is Human Subjects Research?
Human subjects research (HSR) is any research that systematically collects data or information about living individuals through intervention, interaction, or the use of identifiable private information with the intent of developing or adding to generalizable knowledge.
EPA Regulation, codified at 40 CFR Part 26, defines the terms research and human subject as follows:
- Research is a systematic investigation, including research development, testing and evaluation, designed to develop or contribute to generalizable knowledge (40 CFR 26.102.d).
- Human subject is defined as a living individual about whom an investigator (whether professional or student) conducting research obtains (1) Data through intervention or interaction the with individual, or (2) Identifiable private information (40 CFR 26.102.f).
It is very important to make the human subjects research determination by proceeding in a particular order. This is because if your project does not constitute research, then it does not matter if the project involves human subjects! Only if a project is both considered research AND involves human subjects (both according to the federal definitions) is the project then considered human subjects research and subject to additional oversight.
What types of human subjects research does EPA conduct and fund?
EPA conducts and funds a wide variety of human subjects research (HSR). Some examples of HSR at the EPA include fish consumption surveys, surveys on household practices or demographics, analysis of biological specimens, use of focus groups, controlled exposure studies and epidemiology studies.
Each of the study examples listed above serves a particular research need. For example, epidemiology studies enable researchers to learn more about environmental exposure that individuals encounter in everyday life. The National Epidemiological and Environmental Assessment of Recreational (NEEAR) water study is an example of an epidemiological study in which researchers investigated the human health effects associated with exposure to pollutants at recreational swimming sites. The goal of the study was to evaluate whether real-time water quality measurement techniques could be utilized to alert and prevent beachgoers from entering the water and possibly becoming ill if high levels of pollutants were being recorded. Results are intended to enable EPA's Office of Water to develop new state and federal guidance for water quality indicators of fecal contamination.
Another category of human subjects research that is often utilized in EPA studies is survey research. Any time researchers administer a survey, questionnaire, or other data collection instrument, they are interacting with human subjects. If the data that researchers collect from subjects is about the subjects themselves, then the research meets the definition of human subjects research at 40 CFR Part 26. Even if a survey is completely anonymous, if people are providing information about themselves, it constitutes human subjects research! For example, if a researcher passes out anonymous surveys on a beach and asks about the individual's frequency of swimming at the beach or opinion about the cleanliness of the water, it still qualifies as human subjects research since the individual is answering questions about themselves. Often times, survey research is just one component of a larger study but it is still subject to HSR review.
A final example of human subjects research at the EPA is controlled exposure research. EPA conducts controlled exposure studies in healthy individuals or those with mild medical conditions, for example mild asthma who are at minimal risk to the effects of particulate matter (PM), to understand the biological pathways by which air pollution particles exert their effects. Scientists can extrapolate the results from these studies to understand how PM may lead to illness or death in at-risk populations such as individuals with heart or severe lung disease. These studies help EPA fulfill its legal requirements to establish a National Ambient Air Quality Standard that protects Americans from the harmful effects of PM.
Why does EPA conduct controlled exposure studies?
We can (and do) learn much from research in test tubes or using animal or computer models. But these are not all equally good predictors of ways the human body is affected by common pollutants. Even epidemiological studies rely heavily on statistical inferences and assumptions, and there are some things researchers can only learn by interacting directly with people, controlling variables and methods to allow firm conclusions to be drawn.
Over the years, scientific research with human subjects has provided much valuable information to help characterize and control risks to public health. This type of research enables investigators to test the effectiveness of insect repellants, measure the rates and pathways of human processing of environmental chemicals, measure occupational exposure of workers to chemicals, and measure the effects of a substance on exposed human subjects. EPA’s program offices use results from these studies to support decisions and set regulations such as National Ambient Air Quality Standards, water quality criteria and drinking water standards, cleanup levels, and pesticide registration.
Other types of human subjects research are intended to collect information about an individual’s behavior, opinions, and/ or characteristics in order to contribute to generalizable knowledge. Examples include surveys, focus groups, and interviews.
The focus of controlled exposure research is to gain a better understanding of changes in the body that are associated with exposure to the substance that is being studied. By understanding exactly how commonly-occurring pollutants affect various people, the EPA can make appropriate recommendations to Congress and other State and Local governments about enacting laws that protect us and our environment.
Controlled exposure research also contributes to testing the effectiveness of insect repellents, measuring the rates and pathways of human processing of environmental chemicals, measuring occupational exposure of workers to chemicals, and measuring the effects of a substance on exposed human subjects. These studies advance the EPA’s understanding of the links between the environment and human health so that the Agency is able to carry out its mission of protecting human health.
How does EPA Protect Human Subjects?
EPA follows strict safety protocols for all of its studies to protect the health and safety of volunteers, including engineering controls for the facility and protocols for the medical oversight of the exposures. In addition, all EPA research is conducted in compliance with federal regulations and best practices in ethics. The primary regulation that governs human subjects research at EPA is 40 CFR Part 26 Subpart A. It is known as the "Common Rule" because 18 federal departments and agencies have agreed to hold this regulation "in common."
All human subjects research is evaluated by an administrative body, known as an Institutional Review Board (IRB), which is designated with protecting the rights and welfare of human research subjects in research activities. IRB authority is codified at 40 CFR 26. The IRB has the authority to approve, require modifications in (to secure approval), or disapprove all research activities that fall within its jurisdiction.
EPA holds a Federal-Wide Assurance (FWA), which is an assurance of compliance that covers the engagement of the Agency in any Human Subjects Research conducted or supported by any Common Rule agency, including EPA. This assurance covers all Agency components and therefore provides a basis for the participation of EPA personnel anywhere in the Agency in HSR under conditions that are compliant with applicable regulations.
EPA Order 1000.17 A (Policy and Procedures on Protection of Human Subjects in EPA Conducted or Supported Research) establishes EPA procedures and responsibilities for implementing the requirements set forth in 40 CFR Part 26. The Order requires that all human subjects research conducted or supported by EPA must either be approved or be acknowledged as exempt research by the EPA Human Subjects Research Review Official (HSRRO) before any work involving human subjects research can begin. Preliminary (or “conditional”) review by the HSRRO is not required, but can be requested, for any research project, contract, grant application, cooperative agreement, cooperative research and development agreement (CRADA), interagency agreement or any formal agreement involving EPA support of such studies. The Order describes the requirements for review, as well as the responsibilities of all parties involved in EPA research in protecting the rights and welfare of human research subjects.
EPA’s National Exposure Research Laboratory (NERL) published SEAOES as a resource document for researchers to consult as they develop and conduct observational human exposure studies. EPA Order 1000.17 A requires that all human observational exposure studies conducted or supported by EPA adhere to the principles set forth in SEAOES. SEAOES provides information on regulatory requirements, sound scientific practices, and ethical issues to consider when performing observational human exposure studies.
What are the special requirements for Human Subjects Research at EPA?
In 2006, the EPA amended its regulation at 40 CFR Part 26 to include additional protections for vulnerable subjects within its subparts. Subpart B of the regulation is a ban on intentional exposure research involving pregnant women, nursing women, and children. Research involving intentional exposure of a human subject is defined in 40 CFR Part 26.202 as the “…study of a substance in which the exposure to the substance experienced by a human subject participating in the study would not have occurred but for the human subject’s participation in the study.”
Subparts C and D of 40 CFR Part 26 seek to ensure that vulnerable subjects are protected in observational research. Subpart C provides additional protections for observational research conducted with pregnant women as participants. Subpart D adds protections for observational research conducted or supported by EPA involving children as participants. Observational research is defined in 40 CFR Part 26.302 as any human research that does not meet the definition of research involving intentional exposure of a human subject.
The distinction between intentional exposure research and observational research is extremely important for EPA researchers in the development and approval process for studies involving human subjects. Since intentional exposure research involving pregnant women, nursing women, and children is banned, researchers must pay close attention to the details of their study in order to ensure that it does not meet the definition of intentional exposure if the study involves these protected populations.
EPA also added special regulations at 40 CFR Part 26, subparts K-Q, which are related to the review of third-party pesticide research involving human participants. These regulations were updated in 2013. For more information, please see the links below.
What is the approval process for human subjects research at the EPA?
Every project involving human subjects research conducted or supported by the EPA goes through multiple levels of approval. The specific path for review differs slightly depending on the origin of the research, but all human subjects research projects must be approved by the Human Subjects Research Review Official before any work involving human subjects can begin.
EPA's approval process guidelines exceed what is generally accepted and required by universities, industry, and other government agencies. In those organizations, human subjects research is often proposed by an investigator, reviewed by a supervisor, and finally, reviewed by an Institutional Review Board (IRB). Research conducted or supported by EPA, on the other hand, has additional levels of oversight. For example, projects that are funded by grants through the National Center for Environmental Research (NCER) are required to go through the steps mentioned above as well as gain approval from the Human Subjects Officer (HSO) and the Human Subjects Research Review Official (HSRRO). Controlled human exposure studies conducted at EPA's National Health & Environmental Effects Research Laboratory (NHEERL) often undergo up to 13 levels of both internal and external review.
What is required for Human Subjects Research Review Official (HSRRO) Approval?
The HSRRO's responsibility is to ensure that all research studies supported by EPA are in compliance with EPA regulations concerning research with human subjects. All human research studies at the EPA must be approved by the HSSRO before work can begin.
The HSRRO makes certain that a variety of components are in place before giving his/her approval. For example, the HSRRO must review proof of external oversight of the study, specifically IRB approval and documentation. The HSRRO also reviews the research plan to ensure that researchers are using best practices in study design and methodology. He/she pays close attention to the description of subject selection to ensure that it is equitable and reviews the informed consent process to confirm that subjects are respected. The HSRRO is interested in ensuring that subjects will learn the goals of the project and expectations of participation before providing their voluntary consent to participate. Finally, the HSRRO confirms that the value of the research to society justifies the risk to research participants and that researchers take precautions to minimize risks to subjects.
Please note that if pregnant women, nursing women, or children are likely to be included as subjects of a study, the HSRRO will closely review the study to determine whether it involves intentional exposure. Research involving intentional exposure of pregnant women, nursing women, or children is prohibited pursuant to 40 CFR 26.203. "Research involving intentional exposure of the substance experienced by a human subject participating in the study would not have occurred but for the human subject's participation in the study." Studies in which researchers intervene to reduce or mitigate the level of exposure to a substance that participants would otherwise experience, and do not administer a dose of a substance or deliberately cause or bring about participants' exposure to a substance, generally would not fall into the category of intentional exposure research.
In determining whether studies involving pregnant women, nursing women, or children could be considered intentional exposure research, the HSRRO will look for a change in the pre-existing source or delivery mechanism of a pollutant regulated by the EPA as part of the research plan. Interventions that do not involve the administration of a dose of a substance and which reduce participants' exposure from the pre-existing source of that exposure will generally not be categorized as instances of intentional exposure research. Additionally, if the substance in question is not regulated by the EPA, then that also will not constitute intentional exposure research as defined at 40 CFR 26. 202.
In addition to complying with the applicable regulations, EPA conducted or supported studies must also comply with EPA Oder 1000.17A, Policy and Procedures on Protection of Human Subjects in EPA Conducted or Supported Research. This document was updated in 2016 to ensure that it is consistent with contemporary research practice and applicable regulations.To obtain approval or a concurrence of exemption by the HSRRO, researchers must submit the IRB-approved research package or documentation of exemption, including evidence of IRB approval and any correspondence between the IRB and the researchers.
If you are an EPA researcher, you can find more information about required documentation for each project type and instructions on how to submit your project for HSRRO review on the Program in Human Research Ethics and Oversight's (PHREO) intranet site.
If you are applying for a grant or fellowship through the National Center for Environmental Research (NCER) you can find specific information on what to submit on their website.
For other parties interested in requirements for human subjects review at EPA, please contact the HSRRO.
Why is the National Academy of Sciences (NAS) investigating EPA's research studies?
The NAS is not investigating EPA research. One of the regulatory requirements for informed consent is to describe “reasonably foreseeable risks” to potential research subjects, and this was one of several topics examined by EPA’s Office of Inspector General in their 2014 Report “Improvements to EPA Policies and Guidance Could Enhance Protection of Human Study Subjects.” Despite the fact that thousands of research institutions, both inside and outside of government, follow these same regulations, there is no guidance or consensus as to what constitutes “reasonably foreseeable risk,” and what information should be included in research consent forms.
EPA recognized that having subject matter experts provide guidance for our research, and in particular for controlled exposure studies, would further enhance the protection of study subjects at EPA. In 2015, the EPA commissioned the NAS to convene a committee of experts to look at the complicated issues of risk and benefit in our exposure studies. While this was not required, it reflects EPA’s commitment to continuous quality improvement and upholding the highest standards in research. The NAS has followed its standard process which is not controlled by the EPA. The NAS report is expected in December of 2016; information about the current status of the project is available on the public website of the NAS.
What did the OIG investigate about human subjects research at EPA?
In response to a congressional request, the OIG conducted a review to determine whether the EPA followed applicable laws, regulations, policies, procedures and guidance when it exposed human subjects to diesel exhaust emissions or concentrated airborne particles in 5 studies that were conducted during 2010 and 2011. The OIG was specifically interested in whether the agency (1) obtained sufficient approval to conduct these studies; (2) obtained adequate informed consent from the human study subjects; and (3) adequately addressed adverse events that occurred during the studies.
What were the OIG's findings?
On March 31, 2014 the Office of the Inspector General issued a final report reviewing EPA’s human studies research program, entitled “Improvements to EPA Policies and Guidance Could Enhance Protection of Human Study Subjects.” The findings of the OIG report confirm that EPA followed all laws and regulations concerning human subjects research, and has internal guidelines in place that exceed those normally required by universities, industry and other government agencies conducting human studies research.
As with many reports of this nature, the OIG also made recommendations for improvements and enhancements, primarily related to updating and clarifying EPA’s internal policies and procedures. The report recognized the importance and efficacy of such high standards, and identified opportunities to strengthen our internal procedures even further. The EPA embraced the OIG’s recommendations, including: (1) incorporating extra levels of feedback and review as study procedures are changed through the review process, (2) strengthening how we communicate internally, and (3) standardizing information about potential risks that is provided to study volunteers, even when these risks are minimal. In addition, many of the recommendations made by the OIG have been implemented agency-wide, even though they were directed solely at the work done in the Human Studies Facility.
(How) is it ethical to expose humans to known toxic substances or carcinogens?
The International Agency for Research on Cancer (IARC) has labeled outdoor air pollution and diesel exhaust as “carcinogenic to humans,” but these classifications are based on studies examining the risk from high lifetime exposures and in the case of diesel, occupational exposure. The human exposure studies that EPA conducts last only a few hours and the additional total particle exposure encountered by an individual in these studies is so low that its effect on cancer risk is negligible.
It is important to make the distinction between lifetime (or long term) exposure to uncontrolled levels of pollutants, and the very short term exposure to controlled levels of pollutants that occurs in research studies. An analogy could be made to the difference between a lifetime of smoking as compared to smoking a single cigarette in a research study.
There are many agents that are included under the IARC classifications, but the critical factor is the intensity and duration of exposure. For example, sunlight and working the night shift are also classified as agents that fall under Group 2A carcinogens, in the same category as indoor emissions from household combustion of biomass fuel (primarily woodsmoke). Fluorescent light and coffee are classified under Group 2B. These examples illustrate the fact that exposure is likely to be more harmful in higher doses or over longer periods, than in low doses for short periods of time.
Have there ever been permanent harms to participants in EPA research?
There have never been any permanent adverse effects as a result of EPA research.
You will need Adobe Reader to view some of the files on this page. See EPA’s About PDF page to learn more.Other Human Subjects Research (HSR) Resources
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- DHHS Office for Human Research Protections (OHRP)
- DHHS Secretary's Advisory Committee on Human Research Protections (SACHRP)
- University of North Carolina at Chapel Hill IRB and Office of Human Research Ethics
- Public Responsibility in Medicine Research (PRIM&R)
- Association for the Accreditation of Human Research Protection Programs (AAHRPP)
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