What Needs CPHS/OPHS Review
Anyone uncertain as to whether or not their project requires review should contact OPHS for assistance.
All activities, regardless of funding source or whether the activity is funded, that involve the engagement of University of California Berkeley (UCB) employees or agents (including faculty, staff, and students) in the conduct of human subjects research must be reviewed and approved by the CPHS, or determined to qualify for exempt status by OPHS. In general, the activity must meet the definition of “research” and the research must involve “human subjects” in order to fall within the purview of CPHS/OPHS. Nevertheless, it is important to be aware that there are some exceptions to this rule.
(Note: These definitions are UC Berkeley’s interpretation of the definitions of “Research” and “Human Subject” set forth in federal regulations at 45 CFR 46.102. The FDA has a different definition of human subjects research, as detailed in the next section.)
1. Research means a systematic investigation, including research development, testing and evaluation, designed to develop or contribute to generalizable knowledge.
Systematic investigation means a study or examination involving a methodical procedure or plan.
Generalizable knowledge means conclusions, facts, or principles derived from particulars (individual subjects, medical records, etc.) that are applicable to or affect a whole category (members of a class, kind, or group, a field of knowledge, etc.) and enhance scientific or academic understanding.
Design refers to the purpose of the investigation. Some investigations are exploratory or are intended to train students and are not designed to produce generalizable knowledge. It is important to note that although some projects involving qualitative data collection or projects that are exploratory in nature may not have specific aims and hypotheses at the outset of the research, these are still systematic investigations designed to contribute to generalizable knowledge if the purpose of the project is to archive results for future research, compare results to other assessments, or draw conclusions.
2. Human Subject means a living individual about whom an investigator conducting research:
- Obtains information or biospecimens through intervention or interaction with the individual, and uses, studies, or analyzes the information or biospecimens; or
- Obtains, uses, studies, analyzes, or generates identifiable private information or identifiable biospecimens.
Intervention includes both physical procedures by which data are gathered (e.g., venipuncture) and manipulations of the subject or the subject’s environment that are performed for research purposes.
Interaction includes communication or interpersonal contact between investigator and subject.
Private information includes information about behavior that occurs in a context in which an individual can reasonably expect that no observation or recording is taking place, and information which has been provided for specific purposes by an individual and which the individual can reasonably expect will not be made public (e.g., a medical or school record). In order to meet the above definition, private information must be individually identifiable (i.e., the identity of the subject is known or may readily be ascertained by the investigator or associated with the information) in order for the investigation to constitute research involving human subjects. In general, private information is considered to be individually identifiable when it can be linked to specific individuals by the investigator(s) either directly or indirectly through coding systems, or when characteristics of the information obtained are such that by their nature a reasonably knowledgeable person could ascertain the identities of individuals.
3. *Exceptions to the above definitions
Coded Private Information or Biological Specimens: As explained above, private information is generally considered to be identifiable when it can be linked to specific individuals by the investigator either directly or indirectly through coding systems. However, under specific conditions, coded private information or biological specimens are not considered to be individually identifiable and their use would not be considered research involving human subjects. See Research with Coded Private Information or Biological Specimens below.
State of California Decedent Medical Records and Death Data Files: Although the above definition of a human subject includes only living individuals, thereby excluding decedents, health information of the deceased and death data files are protected under federal and State of California regulations. As a result, the use of these records for research purposes may require CPHS review. See Decedent Medical Records and Death Data Files below.
4. FDA definitions (21 CFR 56.102 and 50.3)
Clinical investigation means any experiment that involves a test article and one or more human subjects, and that either must meet the requirements for prior submission to the FDA…or the results of which are intended to be later submitted to, or held for inspection by, the FDA as part of an application for a research or marketing permit. FDA has defined “clinical investigation” to be synonymous with “research”.
Human subject means an individual who is or becomes a participant in research, either as a recipient of the test article or as a control. A subject may be either a healthy individual or a patient. This includes use of human biospecimens, even if the biospecimens are leftover and aren’t actively being collected by the researchers, and regardless of the biospecimens’ identifiability. One example would be a clinical investigation involving the use of existing blood samples to test the safety or efficacy of an investigational in vitro diagnostic (IVD) device.
Test article means any drug (including a biological product for human use), medical device for human use, human food additive, color additive, electronic product, or any other article subject to regulation under the act or under sections 351 and 354-360F of the Public Health Service Act (42 U.S.C. 262 and 263b-263n).
For more information on FDA-regulated research, see:
- CPHS Guidance on FDA-Regulated Research
- FDA-Regulated Research: Decision Trees for Investigational Device Studies
- FAQ on what research falls under FDA regulations
- 21 CFR 50.3
- 21 CFR 56.102
- FDA Guidance on Mobile Medical Applications
Still not sure whether your project meets the above-referenced definitions? Complete the following questionnaire to determine whether or not you are conducting human subjects research: Am I Conducting Human Subjects Research?
Activities that Generally Require Review
- Master’s Theses/Doctoral Dissertations involving human subjects.
- Pilot Studies involving human subjects.
- Clinical Investigations including research to increase scientific understanding about normal or abnormal physiology, disease states or development, and research to evaluate the safety, effectiveness or usefulness of a medical product, procedure, or intervention. Vaccine trials, medical device research, and cancer research are all types of clinical investigation.
- Behavioral and Social Sciences Studies such as investigations on individual and group behavior, mental processes, or social constructs. These usually generate data by means of surveys, interviews, observations, studies of existing records, and/or experimental designs involving exposure to some type of stimulus or environmental intervention.
- Epidemiological Studies such as investigations on health outcomes, interventions, disease states and conclusions about cost-effectiveness, efficacy, efficiency, interventions, or delivery of services to affected populations. This research may be conducted through surveillance, monitoring, and reporting programs. Other methods may include retrospective review of medical, public health and/or other records.
- Human Genetic Research such as pedigree studies, positional cloning studies, gene transfer research, longitudinal studies to associate genetic conditions with health, health care, or social outcomes, and gene frequency studies.
- FDA-Regulated Studies of drugs or medical devices with human subjects as the recipients of the test article(s) or control(s).
Activities that May Not Require Review
- Class Projects, Research Practica, and Undergraduate Thesis Projects involving research methodology and course-assigned data collection. These activities generally do not constitute research because their purpose is to provide training in research as part of the overall educational mission of a program and are not designed to contribute to new knowledge. However, if, for example, a student is involved in an activity designed to teach research methodologies and the instructor or student wishes to conduct further investigation and analyses in order to contribute to scholarly knowledge, the design of the project has changed such that it meets the above definition of research and requires CPHS/OPHS review. Regardless of when this change occurs, CPHS/OPHS must at this time review the research. Course instructors are responsible for assessing whether these activities meet the definition of research as delineated above and are encouraged to contact OPHS for assistance if needed
- Quality Assurance/Quality Improvement Activities that attempt to measure the effectiveness of programs or services, including program evaluations, model curriculums, or needs assessments. Such activities are not typically designed to be generalizable to the larger community and would not be considered research if results will not be compared with other assessments. Those responsible for such projects must be certain that their activities are not human research.
- Repository Research, Tissue Banking, and Databases utilizing stored data or materials (cells, tissues, fluids, and body parts). If the investigator cannot readily ascertain the identity of the subject from whom the data or materials originated (i.e. the data is stripped of identifying information, or coded and the investigator does not have access to the key), these activities would not require CPHS/OPHS review. However, repository research, tissue banking, and databases utilizing stored data or materials (cells, tissues, fluids, and body parts) from individually identifiable living persons must be reviewed by CPHS.
- Case Reports utilizing private identifiable information such as medical information collected from a clinical activity. Case reports are generally carried out by retrospective review of records and highlight a unique treatment, case, or outcome. As the collection and organization of information for such reports usually involves no data analysis or testing of a hypothesis, they do not involve systematic investigation. Therefore, single case reports are not research and would not require CPHS/OPHS review. However, retrospective record reviews that incorporate data collection and data analysis to answer a research question must undergo CPHS/OPHS review. Additionally, meta-analysis of multiple case reports to examine and compare interventions or cases is considered to be human subjects research.
- Research on Institutions or Social Processes when the intent or focus of the research is to gain knowledge of an institution or social process (e.g., a political party, labor negotiations) and this research is not intended to produce generalizable knowledge about any particular individual or groups of individuals. Often, investigators wish to collect information from individuals about institutions or social processes. Such an activity is not human subjects research when the focus of the research is not on characteristics of an individual or groups of individuals because the information collected from the informant is not about the informant. There is often a fine line between human subjects research and research that collects information from individuals in order to understand institutions or social processes. Research on institutions or social processes, the purpose of which is to create generalizable knowledge about the attitudes, beliefs, or behaviors of individuals or groups (e.g., voters, prisoners, employees, teachers) as being representative of these institutions or social processes, is human subjects research.
- Scholarly and Journalistic Activities (e.g., oral history, journalism, biography, literary criticism, legal research, and historical scholarship), including the collection and use of information, that focus directly on the specific individuals about whom the information is collected.
- Public Health Surveillance Activities, including the collection and testing of information or biospecimens, conducted, supported, requested, ordered, required, or authorized by a public health authority. Such activities are limited to those necessary to allow a public health authority to identify, monitor, assess, or investigate potential public health signals, onsets of disease outbreaks, or conditions of public health importance (including trends, signals, risk factors, patterns in diseases, or increases in injuries from using consumer products). Such activities include those associated with providing timely situational awareness and priority setting during the course of an event or crisis that threatens public health (including natural or man-made disasters).
- Criminal Justice or Criminal Investigative Purposes: Collection and analysis of information, biospecimens, or records by or for a criminal justice agency for activities authorized by law or court order solely for criminal justice or criminal investigative purposes.
- National Security: Authorized operational activities (as determined by each agency) in support of intelligence, homeland security, defense, or other national security missions.
Qualitative Interviews and Human Subject Research
The UCLA Office for Protection of Research Subjects (OPRS) contacted Dr. Michael Carome, HHS-OHRP Associate Director for Regulatory Affairs, to seek his guidance concerning the matter of whether qualitative research utilizing open-ended interviews, especially activities performed by oral historians and other social scientists, would require IRB review. The full outline of this discussion is available in a memorandum.
In short, Dr. Carome clarified that the decision concerning whether activities that consist of open-ended qualitative type interviews (such as oral history projects or ethnographies) require IRB review hinges upon whether the activity meets the above definition of research—specifically, whether the activity is “designed to contribute to generalizable knowledge.” The purpose of these activities is often to create a record of specific historical events and, as such, is not to generalize findings to a broader population or group. However, activities involving similar characteristics may be “designed to contribute to generalizable knowledge.” Below are examples of qualitative interviews that are considered to be research and examples of qualitative interviews that are not considered to be research.
- An oral history video recording of interviews with Holocaust survivors is created for viewing in the Holocaust Museum. The creation of the videotape is not intended to prove a hypothesis, inform policy, or draw conclusions. The sole purpose is to create a historical record of specific personal events and experiences related to the Holocaust and provide a venue for Holocaust survivors to tell their stories. Open-ended interviews that only document a specific historical event or the experiences of individuals without the intent to draw conclusions or generalize findings would not constitute research.
- Open-ended interviews are conducted with surviving Gulf War veterans to document their experiences in order to draw conclusions about those experiences, inform policy, and generalize findings. This would constitute research.
- Open-ended interviews are conducted with surviving Negro Baseball League players in order to create an archive for others to analyze and generalize findings in the future. Since the intent of the archive is to create a repository of information for others to use in research, the creation of such an archive would constitute research.
Research with Coded Private Information or Biological Specimens
Coded Private Information or Biological Specimens means that identifying information (such as name, social security number, medical record number) is replaced with a code comprised of numbers, letters, or a combination thereof; and a key to decipher the code exists, enabling linkage of the individual’s identity to specimens or data.
Non-FDA regulated research involving coded private information or biological specimens, under specific conditions, is not considered to involve “human subjects” (OHRP Guidance on Research Using Coded Private Information or Specimens (2008)). Coded private information or specimens are not considered to be individually identifiable and therefore would not fall within the definition of research involving human subjects, if the following conditions are both met:
- the private information or specimens were not collected specifically for the currently proposed project through an interaction or intervention with living individuals; and
the investigator(s) cannot readily ascertain the identity of the
individual(s) to whom the coded private information or specimens
pertain as a result of one of the following circumstances:
- the investigators and the holder of the key have entered into an agreement prohibiting the release of the key to the investigators under any circumstances, until the individuals are deceased (NB: DHHS regulations for humans subjects research do not require the IRB to review and approve this agreement);
- there are IRB-approved written policies and operating procedures for a repository or data management center that prohibit the release of the key to the investigator under any circumstances, until the individuals are deceased; or
- there are other legal requirements prohibiting the release of the key to the investigators, until the individuals are deceased.
Examples of research with coded private information that does not involve human subjects:
- An investigator receives only coded information on the treatment outcomes of patients treated for arthritis with Drug A versus Drug B from the patients’ treating physician. The only involvement of the treating physician is to provide coded information to the investigator. The investigator and the treating physician enter into an agreement prohibiting the release of the key to decipher the code to the investigator under any circumstances, until the individuals are deceased. In this example, the investigator is not conducting human subject research because the data was not collected specifically for the proposed project, but rather during the course of the patients’ treatment, and the investigator cannot readily ascertain the identity of the individuals.
- As part of her dissertation research Student G plans to examine the relationships between ADHD, oppositional defiance disorder, and teen drug abuse using data collected by agencies H, I, and J that work with “at risk” youth. The data will be coded and the key to identifiers will be destroyed before the data is given to the student. In this example, the student is not conducting research involving human subjects because the data was not collected for the purpose of her research, it was collected for the purposes of the individual agencies, and she cannot readily ascertain the identity of the individuals.
Examples of research with coded private information and biological specimens that does involve human subjects:
- An investigator obtains individually identifiable information on the treatment outcomes of patients treated for arthritis with either Drug A or Drug B by viewing patients’ existing individually identifiable medical records at the clinics where the patients were treated. The investigator records the patients’ treatment outcomes in a coded manner but has a key to decipher the code that could permit the identification of the patients. In this example, the investigator is conducting research with human subjects because the investigator is obtaining identifiable private information from patients’ (and now subjects’) medical records.
- Professor Q has finished a project on the intertribal exchange of healers and ritual experts in East Africa; however, the information she collected could provide insights into the processes generated by the encounter between biomedicine and African traditional medicine and she wishes to use the now-coded data for another study. Professor Q has retained the key to identifiers in case she decides to do a follow-up study at a later date. Although the information was not collected specifically for the current project (i.e., the new study), the current project is still human subjects research because the professor has retained the key to identifiers.
Decedent Medical Records and Death Data Files
Decedent Medical Records: The health information of deceased individuals is protected under federal and state regulations. The requirement for CPHS review is dependent on whether the health information associated with the data is “protected health information” (PHI) which is the health information protected under the HIPAA Privacy Rule. These requirements are applicable only to protected health information maintained at UC Berkeley’s Tang Center, Human Resources Health Plan, Intercollegiate Athletics, Optometry Clinic, and Psychology Clinic. Researchers planning to use decedent health information from outside UC Berkeley should follow the requirements of the institution(s) holding those records.
Records with No PHI: HIPAA allows patient information to be “…used and disclosed freely, without being subject to the Privacy Rule’s protections” if it has been de-identified. There are two acceptable methods for de-identifying PHI: (1) removal of 18 primary and secondary identifiers from the data set, or (2) statistical methods verify that the data could not be used to re-identify a patient. If the decedent study will not have direct access to PHI, CPHS review and approval is not required because the deceased individuals cannot be identified.
- Example: Data will be abstracted from the medical records so that researchers receive only de-identified data. In this case, although the information comes from the medical records, the research team does not have access to the PHI in the medical records. Therefore, no CPHS review or approval is required.
Records with PHI: If the decedent study will have direct access to medical records or PHI, even if identifiers will not be recorded by the researchers, an application must be submitted for CPHS review and approval.
- Example: Researchers plan to review medical records of deceased individuals to verify biological specimen data and will abstract the data without recording identifiable information. As the researchers will have access to PHI, an application must be submitted for non-exempt CPHS review and approval.
State Death Data Files: California law requires local IRBs to review research using death data files containing personal identifying information (i.e., state issued death certificates and indices) pertaining to the State of California. This law is more restrictive than federal human research protection regulations, which govern research on living individuals or identifiable information about living persons. UC Berkeley researchers wishing to obtain state death data files containing personal identifying information for research purposes are required to submit an application for review and CPHS must determine that the researcher has a “valid scientific interest” in the data. These requirements do not apply to death data files from outside the state of California.