Investigator Resources

The Basic Ethical Principles of Conducting Research with Human Participants

When we talk about conducting research ethically and having ethics, what does "ethics” mean? In the simplest terms, ethics are the norms for conduct that distinguish between acceptable and unacceptable behavior. So, when we talk about conducting research ethically, we are talking about the normal conduct that is acceptable when conducting research.There are numerous resources that guide us in understanding these norms of conduct, including, The Belmont Report, Good Clinical Practice Guidelines and even the Federal regulations. This section provides resources on these norms for conduct that guide research with human participants.

The Belmont Report

The Belmont Report is a report created by the National Commission for the Protection of Human Subjects of Biomedical andBehavioral Research. The purpose is to protect participants in clinical trials and research studies. The Belmont Report highlights 3 principles imperative to conducting ethical research which are justice, beneficence and respect for persons.

Researchers should minimize risks to study participants by utilizing procedures that are consistent with sound study design. Studies should be designed to ensure the research will likely develop or contribute to generalizable knowledge. In addition, researchers should document in their IRB application and support materials how the potential risks of participation are reasonable in relation to anticipated benefit and that the expected results of the research justify proceeding.

The Belmont Report Educational Video – Office for Human Research Protections (OHRP)

Office for HumanResearch Protections Educational Videos including:
Research Use of Human Biological Specimens and Other Private Information
Reviewing and Reporting Unanticipated Problems and Adverse Events
General informed Consent Requirements
Institutional Review Board (IRB) Membership
Complex Issues with Research Involving Vulnerable Populations
IRB Records (Parts One and Two)

Additional References

The Basics of Informed Consent
The Basics of Informed Consent fornon-English Speaking Individuals
Human Subject Protection Training at UH (CRECProgram)
Protecting HumanSubjects Training (HRSA)

Fundamentals of Conducting Clinical Research: Good Clinical Practice
Federal Guidelines for Research Involving Human Subjects

All research conducted at University Hospitals Health System, and its affiliates, is governed by Federal and state regulations pertaining to human research protections, as well as other guidance and local policies and procedures.

The UH IRB regulates human subject research under the following U.S. Code of Federal Regulations: 21 CFR Parts 50 and56, 45 CFR Part 46, Subpart A (The Common Rule) and 45 CFR 160 and 164 (HIPAA Privacy Rule). Regulations that govern investigational new drugs (INDs) are found in 21 CFR Part 312; biologics are found in 21 CFR Part 600 and devices are found in 21 CFR Part 812.

A FederalwideAssurance (FWA) is an institution or organization's assurance to the Federal government that human subject research conducted at that site is in compliance with Federal regulations pertaining to the protection of human subjects.

The UH IRB’s FWA is FWA00003937.

The Assurance states that all research involving human subjects that is conducted by UH staff or by researchers who fall under the purview of UH, or on UH premises or under its sponsorship, whether supported by Federal funds or not, must be reviewed and approved by the UH Cleveland Medical Center IRB. This policy also applies to protocols sponsored by UH staff conducting research at other hospitals, institutions, or community groups. In order to approve human subject research in accordance with Federal regulations the UH IRB must determine that all of the following requirements are satisfied:

  1. Risks to subjects are minimized.
  2. Risks to subjects are reasonable in relation to anticipated benefits, if any, to subjects, and the importance of the knowledge that may reasonably be expected to result.
  3. Selection of subjects is equitable.
  4. Informed consent will be sought from each prospective subject or the subject’s legally authorized representative.
  5. Informed consent will be appropriately documented.
  6. When appropriate, the research plan makes adequate provision for monitoring the data collected to ensure the safety of participants.
  7. When appropriate, there are adequate provisions to protect the privacy of participants and to maintain the confidentiality of data.
UH Research Policies and Procedures
Conducting FDA Regulated Studies – FDA Guidance Documents

The following list of the USFood and Drug Administration (FDA) Guidance documents represents the Agency's current thinking on good clinical practice (GCP) and the conduct of clinical trials. For a complete list of all available FDAGuidance documents click here.

General Information Sheet Guidance
Drugs and Biologics Information Sheet Guidance
Medical Devices Information Sheet Guidance
General Guidance Documents
Institutional Review Boards (IRBs) and Informed Consent Guidance Documents
Responsibilities of a Principal Investigator
Investigational New Drug Applications (IND) – What you should know

An IND is required for a clinical study if it is intended to support a:

  • New indication.
  • Change in the approved route of administration or dosage level.
  • Change in the approved patient population (e.g. pediatric) or a population at greater or increased risk (elderly, HIV positive, immunocompromised).
  • Significant change in the promotion of an approved drug.

Initiating an Investigational New Drug Application

There are three IND types:

  • An Investigator IND is submitted by a physician who both initiates and conducts an investigation, and under whose immediate direction the investigational drug is administered or dispensed. A physician might submit a research IND to propose studying an unapproved drug, or an approved product for a new indication or in a new patient population.
  • Emergency Use IND2 allows the FDA to authorize use of an experimental drug in an emergency situation that does not allow time for submission of an IND in accordance with 21CFR , Sec. 312.233 or Sec. 312.34.4 It is also used for patients who do not meet the criteria of an existing study protocol, or if an approved study protocol does not exist.
  • Treatment IND5 is submitted for experimental drugs showing promise in clinical testing for serious or immediately life-threatening conditions while the final clinical work is conducted and the FDA review takes place.

The IND application must contain information in three broad areas:

  • Animal Pharmacology and Toxicology Studies – Preclinical data to permit an assessment as to whether the product is reasonably safe for initial testing in humans. Also included are any previous experience with the drug in humans (often foreign use).
  • Manufacturing Information – Information pertaining to the composition, manufacturer, stability, and controls used for manufacturing the drug substance and the drug product. This information is assessed to ensure that the company can adequately produce and supply consistent batches of the drug.
  • Clinical Protocols and Investigator Information – Detailed protocols for proposed clinical studies to assess whether the initial-phase trials will expose subjects to unnecessary risks. Also, information on the qualifications of clinical investigators--professionals (generally physicians) who oversee the administration of the experimental compound--to assess whether they are qualified to fulfill their clinical trial duties. Finally, commitments to obtain informed consent from the research subjects, to obtain review of the study by an institutional review board (IRB), and to adhere to the investigational new drug regulations.

Responsibilities of an Investigator Who is also the Holder of the IND

Investigators who are IND holders are responsible for (this is a list of general responsibilities, and shouldnot be considered all inclusive):

  • Preparing and submitting an annual renewal to the FDA.
  • Understanding when a protocol amendment should be filed with the FDA.
  • Filing FDA Safety Reports: when required, how to complete and where to send them.
  • Responding to FDA protocol inquiries.
  • Understanding Forms FDA 1571, 3455 and 1572 and how and when to update them.
  • Understanding FDA Guidance documents.
Additional References

Investigational New Drug (IND) Application– Information from the FDA
Presentation Archive: How Do You KnowWhen and IND is Required? (4/2012)
Presentation Archive: Maintaining yourIND with the FDA: Keys for Success (7/2012)
UH Investigator Initiated ResearchChecklist – Good Clinical Practice (GCP) Guidance

Investigational Device Exemptions (IDE) – What you should know
Conducting Your Study at Multiple Sites Locally – The Multi-Institutional FacilitatedInstitutional Review Board (IRB) Process

The online, electronic Facilitated Review Hub is a collaborative effort within the Cleveland Clinical and Translational Science Collaborative (CTSC) to provide a centralized review and approval process for human subject research involving two or more CTSC affiliated institutions and its participating medical research facilities. Investigators at Case Western Reserve School of Medicine (CWRU), Cincinnati Children’s Hospital Medical Center (CCHMC), Cleveland Clinic (CC), Nationwide Children’s Hospital (NCH),The MetroHealth System (MHS), The Ohio State University (OSU), University Hospitals Cleveland Medical Center (UHCMC), and University of Cincinnati (UC) are eligible to utilize the ‘Hub’. Once a protocol is approved at one CTSC institutional review board (IRB of Record), it can be submitted to the Hub for a Facilitated review by the other participating institutions (Named IRBs).

Researchers can register to access the IRB hub at

Submitting to the Institutional Review Board (IRB)
Important Definitions Relating to Human Subject Research

Clinical Investigation (FDA) : Any experiment that involves a test article and one or more human subjects. The terms research, clinical research, clinical study, study, and clinical investigation are deemed to be synonymous.

Human Subject (DHHS) : A living individual about whom an investigator (whether professional or student) conducting research obtains (1) data through intervention or interaction with the individual or (2) identifiable private information.

Human Subject (FDA) : An individual who is or becomes a participant in research either as a recipient of the test article or on whose specimen a test article is used or as a control. A subject may be a healthy individual or a patient.

Research (DHHS) : A systematic investigation, including research development, testing, and evaluation, designed to develop or contribute to generalizable knowledge.

Protected Health Information – PHI is individually identifiable health information, including demographic data that is collected from an individual, and:

  1. is created or received by a health care provider, health plan, public health authority, employer, life insurer, school /university, or health care clearing house; AND
  2. relates to past, present or future physical or mental health or condition of the individual; or the provision of health care to an individual; or the past, present, or future payment for the provision of health care to an individual; AND
  3. identifies the individual or where there is a reasonable basis to believe the information can be used to identify the individual; AND
  4. is transmitted or maintained in any form or medium, whether electronic, paper or oral.

(UH Policy R-3 – Uses and Disclosures of PHI for Research Purposes)

Subject Identifiers under HIPAA include: (1) Names (including the patient’s name and names of other individuals connected to the patient); (2) Geographic subdivisions smaller than a state (zip-code, street address, etc); (3) All elements of a date (except year) including birth date, admission date, discharge date, date of death, and all ages over 89); (4) Telephone numbers; (5) Fax numbers; (6) E-mail address; (7) Social security number; (8)Medical record number; (9) Health plan beneficiary numbers; (10)Account numbers; (11) Certificate/license numbers; (12) Vehicle identifiers and serial numbers including license plates; (13) Device identifiers and serial numbers; (14) Web universal resource locators (URLs); (15) Internet protocol (IP) address numbers, (16) Biometric identifiers including fingerprints and voice prints; (17) Full face photographic (or comparable) images; (18) Any other unique identifying number, characteristic, or code unless otherwise permitted by the Privacy Rule for re-identification (UH Policy R-3 – Uses and Disclosures of PHI for Research Purposes)

Test Article (FDA): Any drug for human use, biological product for human use, medical device for human use, human food additive, color additive, electronic product, or any other article for human use.

Professional Research Organizations

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