CIRO Frequently Asked Questions

Q: Which regulatory guidance document should we use to make exempt determinations?

A: When the revised Army Regulation 70-25 is released (this regulation will replace both AR 40-38 and current 70-25 ) only those exemption categories outlined in the Common Rule, 32 CFR 219 will be allowable. The exempt categories listed in the current Army regulations predated the adoption of the Common Rule by the DOD in 1991. Restricting exempt determinations to the categories of human research allowed in the Common Rule decreases the potential for incorrect review determinations The categories of human research that are exempt from the requirements of the Common Rule (32 CFR 219) are the six categories of human research described in 32 CFR 219.101 (b). Note: All research involving prisoners and some research involving children may not be exempted from the requirement for human research protections regulatory oversight.

The 32 CFR 219.101 (b) exemption criteria are:

1. Research conducted in established or commonly accepted educational settings, involving normal educational practices, such as (i) research on regular and special education instructional strategies, or (ii) research on the effectiveness of or the comparison among instructional techniques, curricula, or classroom management methods.
2. Research involving the use of educational tests (cognitive, diagnostic, aptitude, achievement), survey procedures, interview procedures or observation of public behavior, unless: (i) information obtained is recorded in such a manner that human subjects can be identified, directly or through identifiers linked to the subjects; and (ii) any disclosure of the human subjects' responses outside the research could reasonably place the subjects at risk of criminal or civil liability or be damaging to the subjects' financial standing, employability, or reputation.
3. Research involving the use of educational tests (cognitive, diagnostic, aptitude, achievement), survey procedures, interview procedures, or observation of public behavior that is not exempt under paragraph (b)(2) of this section, if: (i) the human subjects are elected or appointed public officials or candidates for public office; or (ii) federal statute(s) require(s) without exception that the confidentiality of the personally identifiable information will be maintained throughout the research and thereafter.
4. Research involving the collection or study of existing data, documents, records, pathological specimens, or diagnostic specimens, if these sources are publicly available or if the information is recorded by the investigator in such a manner that subjects cannot be identified, directly or through identifiers linked to the subjects.
5. Research and demonstration projects which are conducted by or subject to the approval of department or agency heads, and which are designed to study, evaluate, or otherwise examine: (i) Public benefit or service programs; (ii) procedures for obtaining benefits or services under those programs; (iii) possible changes in or alternatives to those programs or procedures; or (iv) possible changes in methods or levels of payment for benefits or services under those programs.
6. Taste and food quality evaluation and consumer acceptance studies, (i) if wholesome foods without additives are consumed or (ii) if a food is consumed that contains a food ingredient at or below the level and for a use found to be safe, or agricultural chemical or environmental contaminant at or below the level found to be safe, by the Food and Drug Administration or approved by the Environmental Protection Agency or the Food Safety and Inspection Service of the U.S. Department of Agriculture.

Generally, exemptions 3,5 and 6 are never used at the MEDCENs. If you are classifying something as category 3, 5 or 6, please re-read the criteria.

Q: Do Headquarters-Level Review (e.g. Clinical Investigation Regulatory Office (CIRO) and Human Research Protection Office (HRPO)) stipulated changes to a protocol require review and approval by the local IRB?

A: All changes to an IRB approved protocol (including those required by an AMEDD HQ-level office as a condition of its approval of the protocol) must be reviewed and approved by the IRB. This includes all changes required by AMEDD HQ-level offices such as the CIRO and HRPO. These changes largely involve minimal risk amendments that are usually eligible for IRB approval using the expedited review process (per criteria referenced in 32 CFR 219.110).

Q: Can our DCI issue an approval letter before we receive feedback from CIRO?

A: There are only a limited number of categories of human research that require final approval from CIRO and thus a DCI must receive this written approval before issuing an approval letter. They are:

1. Investigational drug studies (IND) (except those involving schedule I substances in humans - restricted to TSG approval).
2. Investigational device studies (IDE) involving humans.
3. Studies involving vulnerable population studies: All studies involving pregnant women, fetuses, neonates, prisoners, and children.
4. Greater Than Minimal Risk (GTMR) studies requiring a Legally Authorized Representative (LAR).
5. Studies involving a Cooperative Research and Development Agreement (CRADA). If the study does not fall into category 1-4 but has a CRADA, the approval for the study may be granted by the local DCI however, no work related to the CRADA may begin until final approval of the CRADA is received from CIRO.

DCIs should NOT WAIT for CIRO feedback and should issue approval letters ASAP for all other categories of research.

Q: Can our human subjects protection regulatory office use the determination of "Research Not Involving Human Subjects."

A: Yes, this determination is allowable in the DOD

The Common Rule defines a human subject (32 CFR 219.102[f]) as follows:

• Human subject means a living individual about whom an investigator (whether professional or student) conducting research obtains:
  • data through intervention or interaction with the individual, or
  • identifiable private information.
• An activity is determined to be Research not Involving Human Subjects if it exclusively involves one or more of the following:
  • human cells obtained from a commercial provider
  • human cells about which the accompanying information is publicly available
  • unidentifiable specimens or information/data obtained from a commercial provider
  • unidentifiable specimens or information data obtained from a provider that is prohibited from releasing identifiers by established regulations or policies.
• Additionally the Research Not Involving Human Subjects determination is appropriate for studies where:
  • there is no interaction or intervention with living individuals, and
  • neither the provider nor recipient can link the specimens/data with identifiable individuals (living or dead)
    OR
  • the provider is not an investigator in the activity, and
  • the specimens/data have no code linking them with identifiable individuals, or it would be impossible for the recipient to use the code to identify someone.

Q: What is the Statement of Investigator, Form FDA 1572?

A: The Statement of Investigator, Form FDA 1572, is an agreement signed by the investigator to provide certain information to the study sponsor and assure that he/she will comply with FDA regulations related to the conduct of a clinical investigation of an investigational drug or biologic (IND). It does not apply to device studies. Once completed it should be filed with the local DCI and Study Sponsor.

Q: When does an investigator need to file a Form FDA 1572?

A: Only research that involves an investigational drug or biologic requires a Form FDA 1572. There is guidance on how to fill out the Form FDA 1572 on the FDA website. Co-investigators (co-PIs) are required to also file a Form FDA 1572.

Q: When does an investigator need to make changes to the Form FDA 1572?

A: Changes are required when there is a change in the investigator, or in the laboratory that is processing specimens, or a change in the IRB. All IND studies require that the investigator is on site at the study site (cannot be deployed and remain as PI/co-PI). Leave or TDY travel for more than 2 weeks is discouraged when serving as the PI. If leave or TDY is required, a change of PI and change to the Form FDA 1572 should be completed and filed with the local DCI and the study sponsor. Substitute PIs should be qualified to serve in that role.

Q: Please clarify some of the terms the FDA uses when talking about research studies: