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Conducting Clinical Trials

  • Updated: 06/03/2013

Appendices 1 - 2

Appendix 1: Definition of Terms
Appendix 2: Code of Federal Regulations for the Protection of Human Subjects in Research

Appendix 1: Definition of Terms

Research means a systematic investigation designed to develop or contribute to generalizable knowledge; e.g., to discover new information or to revise conventional wisdom. Such investigations may include development of new therapeutic interventions, their evaluation, and subsequent application.

Human Subject means 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.

Intervention includes both physical procedures by which data are gathered (for example, 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.

Clinical Trial, for the purpose of these recommendations, is a research activity that involves administration of a test intervention (e.g., a drug, surgical procedure, diagnostic test, or medical device) to humans in order to evaluate the intervention. In some cases it may refer to the first use of a new intervention in humans without any control treatment. In other cases it may refer to a rigorously designed and executed experiment involving a test and control intervention and randomization.

Appendix 2: Code of Federal Regulations for the Protection of Human Subjects in Research

DEPARTMENT OF HEALTH AND HUMAN SERVICES (45 CFR 46. 116)

General Requirements for Informed Consent

Except as provided elsewhere in this policy, no investigator may involve a human being as a subject in research covered by this policy unless the investigator has obtained the legally effective informed consent of the subject or the subject's legally authorized representative. An investigator shall seek such consent only under circumstances that provide the prospective subject or the representative sufficient opportunity to consider whether or not to participate and that minimize the possibility of coercion or undue influence. The information that is given to the subject or the representative shall be in language understandable to the subject or the representative. No informed consent, whether oral or written, may include any exculpatory language through which the subject or the representative is made to waive or appear to waive any of the subject's legal rights, or releases or appears to release the investigator, the sponsor, the institution, or its agents from liability for negligence.

(a) Basic elements of informed consent. Except as provided in paragraph (c) or (d) of this section, in seeking informed consent the following information shall be provided to each subject:*

  1. A statement that the study involves research, an explanation of the purposes of the research and the expected duration of the subject's participation, a description of the procedures to be followed, and identification of any procedures which are experimental;
  2. A description of any reasonably foreseeable risks or discomforts to the subject;
  3. A description of any benefits to the subject or to others which may reasonably be expected from the research;
  4. A disclosure of appropriate alternative procedures or courses of treatment, if any, that might be advantageous to the subject;
  5. A statement describing the extent, if any, to which confidentiality of records identifying the subject will be maintained;
  6. For research involving more than minimal risk, an explanation as to whether any compensation and an explanation as to whether any medical treatments are available if injury occurs and, if so, what they consist of, or where further information may be obtained;
  7. An explanation of whom to contact for answers to pertinent questions about the research and research subjects' rights, and whom to contact in the event of a research-related injury to the subject; and
  8. A statement that participation is voluntary, refusal to participate will involve no penalty or loss of benefits to which the subject is otherwise entitled, and the subject may discontinue participation at any time without penalty or loss of benefits to which the subject is otherwise entitled.

(b) Additional elements of informed consent. When appropriate, one or more of the following elements of information shall also be provided to each subject:

  1. A statement that the particular treatment or procedure may involve risks to the subject (or to the embryo or fetus, if the subject is or may become pregnant) which are currently unforeseeable;
  2. Anticipated circumstances under which the subject's participation may be terminated by the investigator without regard to the subject's consent;
  3. Any additional costs to the subject that may result from participation in the research;
  4. The consequences of a subject's decision to withdraw from the research and procedures for orderly termination of participation by the subject;
  5. A statement that significant new findings developed during the course of the research which may relate to the subject's willingness to continue participation will be provided to the subject; and
  6. The approximate number of subjects involved in the study.

* Paragraphs (c) and (d) refer to Informed Consent waivers and have not been included in this document.

FDA CONSENT REQUIREMENTS (21 CFR 50. 20-27)

Basic Elements of Informed Consent

(a) In seeking informed consent the following information shall be provided to each subject:

  1. A statement that the study involves research, an explanation of the purposes of the research and the expected duration of the subject's participation, a description of the procedures to be followed, and identification of any procedures which arexperimental.
  2. A description of any reasonably foreseeable risks or discomforts to the subject.
  3. A description of any benefits to the subject or to others which may reasonably be expected from the research.
  4. A disclosure of appropriate alternative procedures or courses of treatment, if any, that might be advantageous to the subject.
  5. A statement describing the extent, if any, to which confidentiality of records identifying the subject will be maintained and that notes the possibility that the Food and Drug Administration may inspect the records.
  6. For research involving more than minimal risk, an explanation as to whether any compensation and an explanation as to whether any medical treatments are available if injury occurs and, if so, what they consist of, or where further information may be obtained.
  7. An explanation of whom to contact for answers to pertinent questions about the research and research subjects' rights, and whom to contact in the event of a research-related injury to the subject.
  8. A statement that participation is voluntary, that refusal to participate will involve no penalty or loss of benefits to which the subject is otherwise entitled, and that the subject may discontinue participation at any time without penalty or loss of benefits to which the subject is otherwise entitled.

(b) Additional elements of informed consent. When appropriate, one or more of the following elements of information shall also be provided to each subject:

  1. A statement that the particular treatment or procedure may involve risks to the subject (or to the embryo or fetus, if the subject is or may become pregnant) which are currently unforeseeable.
  2. Anticipated circumstances under which the subject's participation may be terminated by the investigator without regard to the subject's consent.
  3. Any additional costs to the subject that may result from participation in the research.
  4. The consequences of a subject's decision to withdraw from the research and procedures for orderly termination of participation by the subject.
  5. A statement that significant new findings developed during the course of the research which may relate to the subject's willingness to continue participation will be provided to the subject.
  6. The approximate number of subjects involved in the study.

(c) The informed consent requirements in these regulations are not intended to preempt any applicable Federal, State, or local laws which require additional information to be disclosed for informed consent to be legally effective.

(d) Nothing in these regulations is intended to limit the authority of a physician to provide emergency medical care to the extent the physician is permitted to do so under applicable Federal, State, or local law.

Sec. 50. 27 Documentation of Informed Consent

(a) Except as provided in Sec. 56. 109(c), informed consent shall be documented by the use of a written consent form approved by the IRB and signed and dated by the subject or the subject's legally authorized representative at the time of the consent. A copy shall be given to the person signing the form.

(b) Except as provided in Sec. 56. 109(c), the consent form may be either of the following:

  1. A written consent document that embodies the elements of informed consent required by Sec. 50. 25. This form may be read to the subject or the subject's legally authorized representative, but, in any event, the investigator shall give either the subject or the representative adequate opportunity to read it before it is signed.
  2. A short form written consent document stating that the elements of informed consent required by Sec. 50. 25 have been presented orally to the subject or the subject's legally authorized representative. When this method is used, there shall be a witness to the oral presentation. Also, the IRB shall approve a written summary of what is to be said to the subject or the representative. Only the short form itself is to be signed by the subject or the representative. However, the witness shall sign both the short form and a copy of the summary, and the person actually obtaining the consent shall sign a copy of the summary. A copy of the summary shall be given to the subject or the representative in addition to a copy of the short form.