Research Team Resources

Many activities fail to meet the definition of research and therefore do not require IRB review and approval.  Most case reports and much of Quality Improvement (QI) activities that take place do not meet the definition of research; however, only the IRB may make the determination that your activities do not involve research and therefore do not fall under the IRB's purview.

How does the Common Rule define research?

HHS regulations (45 CFR 46.102(d)) define research as: 

A systematic* investigation, including research development, testing and evaluation, designed to develop or contribute to generalizable knowledge. Activities that meet this definition constitute research for purpose of this policy, whether or not they are conducted or supported under a program that is considered research for other purposes.

*Systematic means that the activity follows a written plan and adheres to scientifically accepted principles for research design.

How does the Food & Drug Administration (FDA) define research?

FDA regulations (21 CFR 53.102(c)) define the term, clinical investigation or research, as:

Any experiment that involves a test article* and one or more human subjects, and...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.

The FDA considers the term clinical investigation as being synonymous with the following: research, clinical research, study, and clinical study. 

*regulated by the FDA, including food or color additives, drugs for human use, medical devices for human use, biological products for human use, and electronic products.  This includes any new or unapproved item regulated by the FDA and the application of approved items to new populations or indications.

What kind if activities are included in these definitions of research?

Many different types of research activity are encompassed by these two definitions.

For example, research objectives may range from understanding normal and/or abnormal physiological or psychological functions or social phenomena, to evaluating diagnostic, therapeutic or preventive interventions and variations in services and practices.

The activities or procedures involved in research may be invasive or noninvasive, and include removal of body tissues or fluids; administration or application of chemical substances or forms of energy; surgical interventions; modification of diet, daily routine or service delivery; alteration of environment; observation; administration of questionnaires or tests; randomization of subjects; review of records, and so forth.

Research activities may also be conducted or supported within a program or activity that otherwise may not be considered research, such as some demonstration and service programs. As such, the research aspect of the program falls under the jurisdiction of the WCM IRB.

For IRB review and project implementation, a research project must be described in a protocol or, for an exempt submission, in the IRB initial review application.

Examples of activities that do not meet the definition of research

• Activities not designed to produce generalizable knowledge;
• Innovative clinical care;
• Off-label use of drugs or biologics as part of usual clinical care;
• Work Preparatory to Research;
• Case reports and small case series;
• Scholarly and journalistic activities, including the collection and use of information, that focus directly on the specific individuals about whom the information is collected;
• Educational presentations;
• Quality Improvement activities that implement known interventions and that do not use research methodologies;
• Public health surveillance activities (e.g. the collection and testing of information or biospecimens, conducted, supported, requested, ordered, required, or authorized by a public health authority);
• 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;
• Authorized operational activities (as determined by each agency) in support of intelligence, homeland security, defense, or other national security missions.

Research involving human subjects means any activity that either: 

• Meets the DHHS definitions of "research" involving a "human subject", or 
• Meets the FDA definitions of "clinical investigation" ("research") involving a "human subject". 

How does the Common Rule define Human Subjects?

HHS regulations define a human subject as:

A living individual about whom an investigator (whether professional or student) conducting research obtains data through intervention or interaction with the individual, or identifiable private information.

• Living Individual: Means that human subjects research involving decedents is not covered under the Common Rule. Decedents are still covered by HIPAA's Privacy Rule. Research that includes both decedents and living subjects must be reviewed by the IRB. 
  
  
• Identifiable Private Information: Identifiable private information is private information for which the identity of the subject is or may readily be ascertained by the investigator or associated with the information [45 CFR 46.102(e)(5)].
  
  
• Intervention: A procedure or treatment such as a drug, nutritional supplement, gene transfer, vaccine, behavior or device modification that is performed for clinical research purposes (45 CFR 46.102(f)). Interventions can also include noninvasive approaches such as surveys, education, and interviews.
  
  
• Interaction: An interaction may be communication or interpersonal contact between the investigator (or research team) and the living individual. Examples include interviews, questionnaires, surveys, observations, manipulations of subject behavior, diet, or environment, physical measurements, specimen collection (e.g. blood tissue), and administration of experimental drugs or devices. Projects which collect information about policies, practices or procedures - even if the person who provided that information is identified - do not constitute human subject research.
  
  
• Private Information: 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 that has been provided for specific purposes by an individual and that the individual can reasonably expect will not be made public.
  
  

How does the FDA define Human Subjects?

FDA regulations define a human subject as:

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. For research that evaluates the safety or effectiveness of a device, the definition includes a human on whom or on whose specimen an investigational device is used.  A subject may be in normal health or may have a medical condition or disease.

(The terms research, clinical research, clinical study, study, and clinical investigation are deemed to be synonymous for purposes of this part)  

The difference between these definitions relate to the FDA's role in regulating investigational test articles (drugs, biologics or devices). If a person receives an investigational test article, then they are human subjects, regardless of the study design. Therefore, treatment with an investigational agent in a protocol designed to treat a single individual is enough to sufficient that individual a human subject even though generalizable knowledge will not result.

The OHRP provides a decision tree to help you determine if an activity meets human research criteria:
Chart 01: Is an Activity Human Subjects Research Covered by 45 CFR Part 46?

Who is not a Human Subject?

It is often unclear to investigators whether or not an individual should be considered human subject. The following are common scenarios where individuals are involved in the research but their involvement does not fit the definition of human research subject.

• Decedents: The definition of human subject includes the requirement to be "living individuals".
  
  
• Third Parties: This includes individuals who perform study procedures, make measurements, or perform assessments of study subjects. Their role in the research is to serve as collaborators, not subjects. For example, a teacher or driving instructor who completes an assessment of the study subject is a third party. However, if the investigator also obtains information about the teacher/instructor (number of years of teaching experience, age, qualifications, etc.) then they become secondary research subjects.
  
  
• Individuals Not Readily Identifiable: De-identified data and individuals who are not readily identifiable are not human subjects. A dataset may contain HIPAA identifiers but might still not be readily identifiable. For example, data obtained from the PHIS dataset or Medicaid is not considered readily identifiable even though there are birth dates because the data comes from the entire nation.
  
  
• Inanimate Objects: The subject of the research could be about institutions, programs or hospitals and not about the individuals who are in those programs. For example, a survey could inquire about a training program, hospital or other institution and requiring factual information that doesn't contain information about individuals. In this case, even though a person fills out the questionnaire, the research is not about them as individuals - its about the program in which they work.

Secondary Subjects

When information is obtained about individuals other than the research participant, then these individuals become secondary subjects of the research. If the medical history includes information about family members or others and it is recorded in a way so that the investigator can readily identify the other individuals, then both the index subject and the other family members must be considered human research subjects. Common secondary subjects include:

• Parents of child participants
• Children of adult participants
• Family members of adult or child participants

The investigator must justify the need to gather identifiable data from secondary subjects. For example, a relative could be identified as Maternal Uncle 1 rather than by name.

If the secondary subjects will be contacted and offered an opportunity to participate, the research should include plans for the following:

• Who will introduce the secondary subject to the research? The investigator should not contact these individuals without an introduction from the participant or parent of the participant?
• How will the confidentiality of the index subject's private information be protected?

The informed consent form must include statements on the signature page to make clear that consent is being granted for all research participants. If family members will not be present, a waiver of consent and HIPAA Authorization will be needed.

At WCM, only the IRB can make the determination that an activity is exempt from IRB review.  Thus, studies involving human subjects research must be submitted to the IRB for a determination of exemption. Submit an Intake Form through WRG-HS to formally request an IRB determination.  Please note: Initial IRB applications are required for exempt studies - do not submit research determinations forms.  See this KB article for instructions on how to submit an initial application.

Federal regulations recognize eight categories of research that are exempt from IRB review, listed below. For a full description of these categories, please visit the OHRP website.

The OHRP provides helpful decision trees to assist you in determining whether or not your research meets any of the exemption criteria:

• Chart 02: Is the Research Involving Human Subjects Eligible for Exemption Under 45 CFR 46.104(d)?
• Chart 03: Does Exemption 45 CFR 46.104(d)(1) for Educational Practices Apply?
• Chart 04: Does Exemption 45 CFR 46.104(d)(2) for Educational Tests, Surveys, Interviews, or Observation of Public Behavior Apply?
• Chart 05: Does Exemption 45 CFR 46.104(d)(3) for Benign Behavioral Interventions Apply?
• Chart 06: Does Exemption 45 CFR 46.104(d)(4) for Secondary Research that Does Not Require Consent Apply?
• Chart 07: Does Exemption 45 CFR 46.104(d)(5) for Public Benefit or Service Programs Apply?
• Chart 08: Does Exemption 45 CFR 46.104(d)(6) for Food Taste and Acceptance Studies Apply?

If you are preparing an NIH application and your grant proposes use of a single IRB for non-exempt multi-site research, please go to our webpage Single IRB (sIRB) Reliance.

The policy is applicable to new and competing renewal applications/proposals for NIH funding.  It is applicable to NIH-funded multi-site domestic studies involving non-exempt human subjects research, whether supported through grants, cooperative agreements, contracts, or the NIH Intramural Research Program.

For more information on fulfilling the requirements of the NIH sIRB Policy, please read the NIH Single IRB Request Process document.

Quality improvement activities are an important component of hospital operations. Because QI activities are data-driven and involve human participants, it is not surprising that there can be overlap with research methodologies common to human subjects research. Where there overlap exists between QI and research methodologies, the federal regulations that protect human research participants may apply. Whether the QI activity is human subjects research or not, it is vital that it be executed in a manner that is ethical and respects the rights and welfare of the human participants.

How does QI differ from research?

Both research and quality improvement are systematic investigations that may involve human participants but they differ in important ways.  The table below is based on information adapted from The Ethics of Using QI Methods to Improve Health Care Quality and Safety.

When is IRB approval needed for QI activities?

IRB approval may be required when the activity involves some of the following characteristics:

• seeks to develop new knowledge or validate new treatments rather than to assess the implementation of existing knowledge;
• when the methodology employs a standard research design, such as randomization;
• when the protocol is fixed with a rigid goal, methodology, population, time period, etc.;
• when the funding for the activity comes from the outside organizations such as the NIH or those with a commercial interest in the results;
• when the risks from the intervention to participants are greater than minimal

If there is uncertainty about whether or not WCM or an investigator at WCM is engaged in the research, the Office of Human Research Protections (OHRP) provides a Guidance on Engagement of Institutions in Human Subjects Research. The FAQs for this section provide examples of when IRB Review is needed and when it is not.

Institutions are engaged if their agents or employees:

1. receive an award through a grant, contract, or cooperative agreement directly from HHS
2. intervene for research purposes with any human subjects of the research by performing invasive or noninvasive procedures (see limited exceptions in column to right);
3. intervene by manipulating the environment;
4. interact with subjects for research purposes;
5. obtain consent of subjects;
6. obtain for research purposes identifiable private information or identifiable biological specimens from any source

It is important to note that, in general, institutions whose employees or agents obtain identifiable private information or identifiable specimens for non-exempt human subjects research are considered engaged in the research, even if the institution’s employees or agents do not directly interact or intervene with human subjects.

Institutions are NOT engaged if their agents or employees:

1. perform commercial or other services for investigators (somewhere else) provided that all of the following are also met:
   • the services performed do not merit professional recognition or publication privileges;
   • the services performed are typically performed by those institutions for non-research purposes; and
   • the institution’s employees or agents do not administer any study intervention being tested or evaluated under the protocol.
2. provide clinical trial-related medical services that are dictated by the protocol and would typically be performed as part of routine clinical monitoring and/or follow-up of subjects enrolled at a study site by clinical trial investigators;
3. administer the study interventions being tested or evaluated under the protocol limited to a one-time or short-term basis;
4. provides patients with literature about a research study at another institution, including a copy of the informed consent document, and obtains permission from the patient to provide the patient's name and telephone number to the investigators;
5. access or utilize individually identifiable private information only while visiting an institution that is engaged in the research, provided their research activities are overseen by the IRB of the institution that is engaged in the research;
6. release to investigators at another institution identifiable private information or identifiable biological specimens pertaining to the subjects of the research. NOTE: the subjects would need to provide informed consent at the institution to which the data will be released.

Research involving food, dietary supplements, drugs and biologics, medical devices and/or electronic products (that emit radiation) must adhere to the FDA regulations governing human subject protection and the conduct of ethical research. 

Please visit our FDA Research page for more information and how to determine whether or not your research is FDA-regulated. 

Weill Cornell Medicine (WCM) and NewYork-Presbyterian Brooklyn Methodist Hospital (BMH) have entered into a Master Reliance Agreement for the WCM IRB to serve as the IRB of Record for oncology research.  For trials considered cooperative research, multi-site, or industry-sponsored, BMH may use a third party ("external IRB") for review. Please visit the Single IRB Reliance: Collaborative Oncology Research page for more information. 

It is our Institutional policy that only those with whom the organization has or intends to have an ongoing employment or contractual relationship may serve as Principal Investigator (PI) on research projects submitted to the WCM IRB.  In practice, this means: 

• the PI must be a faculty member with the rank of instructor or above; and
• the PI must be properly credentialed by the facility at which the research is approved to take place; and
• the PI must be employed (either full- or part-time) by WCM, and;
• if the research involves the administration of a drug or use of a device for research purposes, the PI must be a licensed physician;
• Voluntary faculty cannot serve as PIs, but may serve as co-investigators.

In addition, employees of New York Presbyterian Hospital/Weill Cornell Medicine (only pharmacists, nurses, dieticians) can serve as PIs on protocols, except clinical trials that include an intervention with human subjects. However, medical residents cannot serve as PIs, but may serve as co-investigators.

The PI assumes the responsibility of the whole of the research study, including any responsibility delegated to study coordinators and research teams.  The full scope of PI responsibilities is described in the Investigator Handbook.

All PIs and research team members must complete the required training described on the Research Team Training and Education page before they can be included on a protocol submitted to the WCM IRB, and before they can submit in WRG-HS.  

The full scope of the PI's responsibilities is outlined in a soon-to-be-published policy document, but can be summarized as follows:     

• Selection of qualified individuals for roles on study team.
• Complete knowledge of protocol, investigator's brochure(s), and consent form(s).
• Process for oversight of study team.
• Process for monitoring subject safety and data collection. 
• Understanding of reporting obligations to funding sources, FDA (if applicable), and IRB. 
• Understanding of scope of responsibility for multi-site studies, PI-initiated studies, federally funded studies. 
• Understanding of federal, IRB, and institutional policies and regulations applicable to the research. 

The research team plays an integral part in the administration of the research study.  It is therefore important that all members on a research team demonstrate:

• Understanding of federal, IRB, and institutional regulations and policies applicable to the research.
• Appropriate knowledge (according to role) of the study's purpose(s), activities, risks, and benefits.
• Thorough understanding of the individual's role on the study and its relation to regulations and policies.
• Understanding of reporting obligations to the PI, IRB, and institution.