Protect participants (ethical and regulatory compliance)

Some of the protections are explained below.


General oversight

Researchers follow the general ethical guidelines, some of which are listed below, proposed by various regulatory and oversight organizations.

• Belmont Principles. Established in 1979, the Belmont principles outline three key principles for ethical research involving human subjects.
  • First is respect for persons and recognition of their autonomy; those with diminished autonomy should be accorded protection.
  • Second is beneficence, including doing no harm, minimizing potential risks, and maximizing benefits.
  • Finally, a sense of justice in who bears the burden of the research and who benefits from it.
• International Conference on Harmonization (ICH) of Technical Requirements for Registration of Pharmaceuticals for Human Use Good Clinical Practice –E-6. The ICH guidelines were developed in 1996 to facilitate the sharing of research between the European Union, Japan and the US. In addition to the technical standards recommended for research, the ICH also provides guidance on maintaining independence among the IRB and monitoring committee. The US Food and Drug Administration (FDA) has published its implementation of this policy in the Federal Register.
• Council for International Organizations of Medical Sciences (CIOMS). The CIOMS was established by the World Health Organization and United Nations Educational, Scientific and Cultural Organization (UNESCO) to maintain long-term programs in discussing and establishing guidelines for bioethics and human values in research, particularly international research.
• Declaration of Helsinki. Drafted by the World Medical Association in 1964 and last updated in 2004, the Declaration presents another perspective on ethical principles for research involving human subjects.

All federally-supported research is governed by Federal regulations that are overseen by the Office of Human Research Protections (OHRP). Participation in studies is specifically regulated by Title 45 CFR 46.

Research that involve products that are regulated by the FDA follow Title 21, CFR 50


NIH standards for clinical research

The NIH has several sets of guidelines, including some that incorporate the provisions above, for those who conduct and support clinical research funded by the NIH. Information about some of these guidelines is included below:

• Standards for clinical research within the NIH Intramural Program
  • Clinical Informatics, Data Management, and Protocol Tracking
  • Biostatistics Support
  • Quality Assurance and Quality Control
  • Protocol Review
  • Human Resources and Physical Plant
  • Training and Education
• Guidelines for the conduct of clinical research within the NIH Intramural Program
• NIH Office of Extramural Research Ethical Guidelines and Regulations
• NIH Office of Extramural Research Guidelines for Research Involving Vulnerable Populations

• Study protocols. A study protocol is a document that describes in detail the plan for conducting a clinical study.
  • Federal regulations define study protocol contents, particularly if the study involves investigational (unlicensed) products.
  • Clinical studies are designed so that only people with a particular disease or condition that justifies accepting the risks are enrolled. A study protocol will include a listing of the characteristics that allow a person to participate called the eligibility criteria.
  • Studies also schedule relevant procedures and evaluations for participants often enough so that potential risks can be detected and addressed in a timely manner.
  • Study participants also have specific contact information so that they can contact someone related to the study for any reason at any time.
• Study participation consent process. One of the primary safeguards for study participants is that they are informed about the potential risks, benefits, alternatives, and responsibilities of the clinical trial before they agree to participate. When a potential study participant understands the risks, alternatives, and responsibilities, he or she formalizes the decision to participate by communicating with the study investigator or representative and by documenting the agreement in writing. The interactive process of receiving information, asking questions, and indicating agreement is known as the consent process.
• Institutional Review Boards (IRBs). The IRB reviews the study protocol at length. At the federal level, the Office for Human Research Protection (OHRP) regulates IRBs and ensures that they meet criteria outlined in the Code of Federal Regulations (CFR) Title 45, Part 46.
  • The IRB is responsible for ensuring that the study is scientifically sound as well as ethical to carry out. The IRB will also approve the consent form given to participants outlining the procedure and possible risks and benefits.
  • If a study protocol uses a product regulated by the Food and Drug Administration (FDA), then the FDA may also review the protocol and has the option to request changes before the study can proceed. In some cases the FDA may waive the requirement for an IRB to approve a study. IRBs that review FDA-regulated research must follow Title 21, Part 50 of the CFR.
• Data and Safety Monitoring Committee. Some studies rely on this independent committee to monitor the study results and its conduct while the trial is underway. The functions and oversight of such committees are distinct and independent from IRB activities and approvals.
• Certificates of Confidentiality. In general, confidentiality of study participants is covered under the Health Insurance Portability and Accountability Act. In addition, if the release of study data could have negative consequences if linked to a certain participant, either by design or due to the nature of the disease or condition, the study can receive a Certificate of Confidentiality. A Certificate of Confidentiality protects investigators and institutions from being compelled to reveal information that would identify research participants.
• Good Clinical Practices.
  • International policies. International ethical and scientific quality documents, such as the Good Clinical Practices, created by the International Conference on Harmonization (ICH) of Technical Requirements for Registration of Pharmaceuticals for Human Use, provide further protection for those who take part in clinical studies. Such standards are agreed to by regulatory agencies in the United States, Europe, Japan, and other countries to provide general guidance for assuring that participants in clinical research are respected and protected.
  • FDA Good Clinical Practice Guidelines. The Food and Drug Administration (FDA) has developed guidelines related to good clinical practices. Guidances, Information Sheets, and Important Notices on Good Clinical Practice

Protections related to an Investigational New Drug (IND) or Investigational Device Exemption (IDE)
If a study involves an IND or IDE, the FDA must approve a study beforehand to exempt the study from FDA licensing requirements, which allows a study to proceed. The sponsor for the study needs to apply for this exemption. The IND or IDE application must include: exact chemical or biological makeup of the therapy and the mechanisms by which it is thought to be effective; results from animal studies; results from clinical trials; how the drug or therapy is manufactured, processed, and packaged; quality control standards; and information about drug or intervention samples of the product in the form(s) in which it is to be administered.

• The FDA outlines its Requirements for an IND and its requirements for IND Content and Format.
• The FDA Center for Devices and Radiological Health issues guidelines on medical devices, available in the Device Advice section of the FDA Web site.

Resources for protecting participants

Study consent process

• Cornell Medical College: Guidance on the Informed Consent Process (Word File)
• National Cancer Institute (NCI): Children’s Assent to Clinical Trial Participation
• National Library of Medicine: Current Bibliographies in Medicine—Ethical Issues in Research Involving Human Subjects (Journal Articles)
• University of California, Irvine: Informed Consent Process
• Albert Einstein College of Medicine: Informed Consent Guidelines

IRB resources

• NIH researcher computer based training
• NIH information for IRB members
• FDA Guidance for IRBs, Clinical Investigators, and Sponsors
• FDA Regulations for IRBs
• OHRP Policy Guidance
• OHRP IRB Guidebook

Data Safety and Monitoring Committees

• FDA Guidance on Data Monitoring Committees
• NIH Clinical Research Policy Analysis and Coordination: Clinical Trials Monitoring

Certificate of Confidentiality

• Apply for a Certificate of Confidentiality

IND resources

• Instructions for submitting an IND application
• Pre-IND contacts at the FDA

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