Clinical research or human experimentation poses potential significant liability risks to all involved—the individual researcher, the facility where the research is conducted, the facility’s Institutional Review Board (IRB), and the pharmaceutical or medical device manufacturer sponsoring the research.  Protection of the individuals participating in your research study by strict adherence to applicable ethical standards and laws and regulations is crucial for limiting your liability risk.    

Recent high-profile cases involving clinical drug trials by pharmaceutical companies and the growing number of clinical trials being conducted is expected to result in increasing numbers of lawsuits filed by research subjects.  Allegations frequently include:  subjects were not adequately informed about the risks involved; conflicts of interest existed; and the responsible IRB was negligent in performing its duties.          

The best protection against and defense to a research-related lawsuit is a program solidly grounded in ethics with the safety of its research subjects paramount. 

Ethical Principles  

Ethical guidelines for protecting human research subjects are set forth in three major documents: 1) the Nuremburg Code developed in 1946 as a response to the Nazi war crimes involving human research, which lists ten principles for human research, including the “absolutely essential”  voluntary consent of the human subject;  2) the Declaration of Helsinki adopted by the World Medical Association in 1964, and later revised, which sets forth principles for biomedical research; and 3) the Belmont Report from the United States in 1979 which sets forth three basic ethical principles: respect for persons, beneficence, and justice.

The Belmont Report principles are defined in part as follows:

• Respect for persons—acknowledge each individual’s autonomy and protect those with diminished autonomy due to circumstances such as immaturity, impaired capacity to deliberate, and confinement to an institution
• Beneficence—make efforts to secure the well-being of human subjects by accepting the obligations to do no harm and to maximize possible benefits and minimize possible harms
• Justice—consider who is to benefit from research and who is to bear the risks, and treat all persons equally

The Belmont Report also lists three specific applications of its general principles to the requirements for the conduct of human research:

1.  Informed consent—elements of information, comprehension, and voluntariness

2.  Risks/Benefits assessment—careful gathering and examination of information about the proposed research including, when applicable, alternate ways of securing the benefits sought in the research

3.  Selection of subjects—fair procedures and outcomes in the selection of subjects

The Belmont Report principles were adopted by the United States in 1981 in the “Federal Policy for the Protection of Human Subjects” which is known as the Common Rule.  The Common Rule controls all federally funded research and has been adopted by 14 federal agencies including the Department of Justice, the EPA, and the Consumer Products Safety Commission.  The Common Rule addresses matters such as the composition and role of the IRB, informed consent, record management, and handling adverse events.

Regulation of Research 

Research on human subjects is regulated by the U.S. Department of Health and Human Services (DHHS) and the Federal Drug Administration (FDA). 

The FDA rules apply to research involving products that it regulates—drugs, devices, and biologics such as vaccines.  FDA approval is required before human testing may begin.  

The DHHS regulations apply to federal agencies and departments and any research facility that receives federal funding.  The Office for Human Research Protections (OHRP) is charged with providing compliance oversight and guidance to protect persons who volunteer as subjects in research conducted or supported by DHHS.   The OHRP’s Division of Compliance Oversight (DCO) reviews institutional compliance with DHHS regulations.  OHRP also requires written assurance from the agencies and facilities that it oversees stating that they will comply with the federal regulations found in the Code of Federal Regulations at 45 CFR part 46 (available on the internet at www.hhs.gov/ohrp) requiring them to protect their human subjects. 

Research funded by the Public Health Services Act is monitored by the Office of Research Integrity. 

It is imperative that you know and comply with all federal and any state regulations that are applicable to your research facility. 

The OHRP may be contacted for guidance and resource materials by toll-free telephone at (866) 447-4777, and by e-mail at ohrp@osophs.dhhs.gov. 

The Role of the IRB 

A facility that conducts clinical research subject to federal regulations must have an IRB.  The FDA defines an IRB as “any board, committee, or other group formally designated by an institution to review, to approve the initiation of, and to conduct periodic review of, biomedical research involving human subjects.  The primary purpose of such review is to assure the protection of the rights and welfare of the human subjects.”   The federal regulations specify criteria for the size and composition of an IRB. 

The specific functions and operations of an IRB for review of research are:

1.      Review and approve or disapprove research activities, and give written notice of its decision to the investigators and institution

2.      Require that the specified information for an informed consent is given to subjects and that the informed consent is appropriately documented

3.      Conduct continuing review of research at “intervals appropriate to the degree of risk,” but not less than once per year.

An IRB also must determine that risks to subjects are minimized.  In addition, it is charged with the responsibilities of reviewing a study design for safety and performing a risk-benefit analysis of the potential risks and the anticipated benefits.  The IRB must be satisfied that the selection process for subjects was fair and free of undue influence, with special consideration given to vulnerable groups such as pregnant women, minors, and prisoners. 

All activities of the IRB must be properly documented.  Written policies and procedures covering IRB functions and activities are also required.    

A self-evaluation checklist for IRBs is available from the FDA and may be accessed online at www.fda.gov/oc/oha.  A guidance document from the FDA that is also available includes important FDA contacts, the Belmont Report, the Declaration of Helsinki, informed consent regulations, and links to related websites.

Informed Consent for Clinical Research 

The basic elements of informed consent for clinical research include: 

• A statement that the study involves research, and an explanation of the purposes, duration, and procedures to be followed, with identification of any procedures that are experimental
• A description of any reasonably foreseeable risks or discomforts and benefits
• Alternative procedures or treatment that might be advantageous to the subject
• The extent to which the confidentiality of the subject’s records will be maintained
• Whether there is compensation and medical treatment for a research-related injury
• Who to contact with questions or to report a research-related injury
• A statement that participation is voluntary, refusal to participate is without penalty, and the subject may discontinue participation at anytime without penalty

Other elements for informed consent are also required when appropriate: 

• A statement that there may be currently unforeseeable risks to the subject or the embryo or fetus if the subject is or becomes pregnant
• Circumstances under which a subject may be terminated from the study
• Any expected costs to the subject
• The number of subjects in the study
• The consequences of the subject’s decision to withdraw from the study and procedures for orderly termination of his/her participation
• A statement that significant new findings developed during the course of the study which may relate to the subject’s willingness to continue will be provided 

Risk Management Strategies 

ü       Keep abreast of all applicable laws and regulations covering research studies in your facility, including the HIPAA Privacy Rule

ü       Appoint qualified, unbiased IRB members who are committed to honoring their ethical obligations

ü       Credential all clinical trials investigators

ü       Educate all responsible individuals about their duties and obligations related to research, and the potential implications of noncompliance

ü       Make sure that all research subjects are being given the information that they need and are required by law to receive for informed consent

ü       Adopt and implement written policies and procedures for the conduct of research studies in your facility, and update it on a regular basis

ü       Develop a written compliance plan with assistance of qualified legal counsel or other experts

ü       Monitor on an ongoing basis significant areas of potential risk including: the informed consent process and documentation, conflicts of interest, solicitation and selection of research subjects, and reporting an injury sustained by a subject

ü       Secure necessary insurance coverage for the study, including professional liability, directors and officers, and errors and omissions coverage