6.0 Preparing for IRB Review

6.1 Protocol Preparation Requirements
6.2 Special Research Issues
        6.2.1 Use of Protected Health Information for Research
        6.2.2 Gender Differences in Clinical Evaluation of Drugs
        6.2.3 Genetic Research
        6.2.4 Studies Involving Investigational New Drugs
        6.2.5 Use of Biohazardous Materials
        6.2.6 Use of Radioisotopes, Radiation, and Radioactive Drugs
        6.2.7 Studies Involving Investigational New Devices

6.1 PROTOCOL PREPARATION REQUIREMENTS
 Research investigators shall prepare a protocol giving a complete description of the proposed research involving human subjects.  All protocols shall contain provisions for the adequate protection and rights and welfare of prospective research subjects and for ensuring that pertinent laws and regulations are observed.

The protocol shall be detailed and include the following information:

  • Describe the characteristics of the subject population, such as their anticipated number, age ranges, sex, ethnic background and/or health status.  Identify the criteria for inclusion or exclusion.
  • Explain the rationale for the use of special classes of subjects, such as children, pregnant women and fetuses, institutionalized mentally disabled persons, prisoners or others who are likely to be vulnerable.  (See Section 9.0, Vulnerable Research Populations)
  • Describe the purpose of the study, the results of previous related research, study design, the procedures to be performed and, if appropriate, the identity of the sponsor
  • Describe plans for the recruitment of subjects and the consent procedures to be followed, including the circumstances under which consent will be sought and obtained, who will seek it, the nature of the information to be provided to prospective subjects and the method of documenting consent.  (See Section 7.0, Informed Consent)  State if the IRB has authorized a modification or waiver of consent or of the requirement for documentation of consent.
  • Describe any potential risks (physical, psychological, social, legal or other) and assess their likelihood, seriousness and management. 
  • Describe the procedures for protecting against or minimizing any potential risks, including risks to confidentiality and assess their likely effectiveness.  Where appropriate, discuss provisions for insuring professional intervention in the case of adverse effects to the subjects and for monitoring the data collected to ensure the welfare of the subjects.
  • Discuss why the risks to subjects are reasonable in relation to the anticipated benefits to subjects and in relation to the importance of the knowledge that may reasonable be expected to result.
  • Identify the costs to research subjects and/or any third party payers. Where applicable, describe the compensation or benefit (i.e. extra credit for students) to be provided to research subjects for participation.
  • Describe the timeline and procedure for disposing of or destroying any easily identifiable information received from research subjects.

6.2 SPECIAL RESEARCH ISSUES
 This section presents an overview of research issues that require special consideration and must be addressed prior to IRB review.

                 6.2.1 Use of Protected Health Information for Research
  The Health Insurance Portability and Accountability Act (HIPAA) of 1996 (“Privacy Rule”) establishes the conditions under which protected health information (PHI) may be used or disclosed by covered entities or their “business associates” for research purposes. 

The Privacy Rule defines the means by which human research subjects are informed of how medical information (written, electronic or verbal) about them will be used or disclosed and their rights with regard to gaining access to information about themselves when such information is held by entities.  Where research is concerned, the Privacy Rule protects the privacy of individually identifiable health information, while at the same time, ensuring that researchers continue to have access to medical information necessary to conduct research.  Research information protected by the Privacy Rule includes:

  • All research, regardless of funding source, involving/associated with treatment (because PHI is created)
  • Medical records review
  • Medical registry review
  • Research of identifiable or coded data (i.e., research involving data that has been coded where researcher does the coding)

Although a research investigator who holds a Ph.D. as a general rule is not subject to HIPAA (not health care providers) there are exceptions (possible exception:  a Ph.D. working out of lab who provides feedback to subjects regarding testing).  Because of the ambiguity of such exceptions, the research investigator must in addition to receiving informed consent from the human subject participants provide written documentation to the IRB that:

  • Use or disclosure is sought solely to review PHI as necessary to prepare a research protocol or for similar purposes preparatory to research
  • No PHI is to be removed from the entity or the custody of the research investigator in the course of the review
  • The PHI for which use or access is sought is necessary for research purposes

The Office for Civil Rights (DHHS) is charged with enforcement of HIPAA  and the review of all PHI compliance.

            6.2.2 Gender Differences in Clinical Evaluation of Drugs
 On July 22, 1993, FDA published in the Federal Register “Guideline for the Study and Evaluation of Gender Differences in Clinical Evaluation of Drugs.” (58 FR 39406, July 22, 1993)  This guideline presented two major changes in FDA regulations.  First the guideline lifts the restriction on the participation of women of childbearing potential in early clinical trials, including clinical pharmacology studies and early therapeutic studies.  Second, the guideline states that sponsors should collect gender-related data during research and development and should analyze the data for gender effects in addition to other variables such as age and race.  In response to this guideline and to ensure adequate protection of women in research studies or early clinical trials, the IRB will consider the following in its review of both drug/biologic product and device protocols:

  • Women of Childbearing PotentialWomen of childbearing potential may enter research studies or limited clinical trials.  Clinical trial protocols should include provisions for testing for pregnancy as well as to medically acceptable methods of birth control.
  • Pharmacokinetic Issues Three specific pharmacokinetic issues that should be considered in such a protocol are:

    --Effect of menstrual status on the drug's pharmacokinetics, including both comparisons of pre-menopausal and postmenopausal subjects and continuation of within cycle changes
    --Effect of exogenous hormonal therapy including oral contraception
    --Effect of the test article on the pharmacokinetics of oral contraceptives

When preclinical teratology and reproductive toxicology studies have not been completed prior to initial human studies, subjects should be informed of this incomplete data in the informed consent document as well as the potential effects of the test article on conception and fetal development.  Any new pertinent information arising from preclinical studies as well as any new clinical data that emerge regarding general safety and effectiveness (including gender differences) should be provided to subjects and the informed consent document should be updated, when appropriate. 

            6.2.3 Genetic Research
 Because of the specific ethical, regulatory and public relations concerns associated with research with genetic material, research investigators should review and be familiar with all applicable regulations prior to submitting to the IRB any project involving genetic research, including the collection and/or use of samples for DNA analysis or establishment of cell lines, with or without long-term storage.

            6.2.4 Studies Involving Investigational New Drugs
 If the research study involves an investigational new drug, or a marketed drug that is being used for an indication not in the approved labeling, the research investigator must follow the requirements of FDA’s Investigational New Drug Application (IND) regulation (21CFR312).  The IRB will not review any protocol involving an investigational new drug without authorization from FDA.

            6.2.5 Use of Biohazardous Materials
 Although not presently active at Drake University, any research involving the use of biohazardous materials (recombinant DNA and/or infectious biological agents) and human subjects must be reviewed and approved by the University Biosafety Officer, Environmental Health and Safety Officer and/or Provost prior to review by the IRB.  A copy of any approval or exemption must be provided to the IRB before any review can begin.

            6.2.6 Use of Radioisotopes, Radiation, and Radioactive Drugs
 Although not presently active at Drake University, any research involving the use of radioisotopes, radiation and radioactive drugs and human subjects must be reviewed and approved by the University Radiation Officer, Environmental Health and Safety Officer and/or Provost prior to review by the IRB.  A copy of any approval or exemption must be provided to the IRB before any review can begin.

            6.2.7 Studies Involving Investigational New Devices
 Although not presently active at Drake University, any research involving an investigational new device, or a marketed device that is being used for an indication not in the approved labeling, and human subjects must follow the requirements of FDA's Investigational Exemption (IDE) regulation (21CFR812). The IDE regulation applies to all clinical investigations of devices to determine safety and effectiveness.  The research must be reviewed and approved by the University Environmental Health and Safety Officer and/or Provost prior to review by the IRB.  A copy of any approval or exemption must be provided to the IRB before any review can begin.

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