Chapter 7 - Research Activities

Title	Section
General	1-7.1
Definitions	1-7.2
Research	1-7.2A
Protection of Human Subjects	1-7.2B
Policy	1-7.3
Area Research Committee - Institutional Review Board	1-7.4
Institutional Review Board - General Duties	1-7.5
Institutional Review Board - Record Keeping Responsibilities	1-7.6
Institutional Review Board - Required Documents	1-7.7
Area Research Committee	1-7.8
Area Office Directors - Responsibilities	1-7.9
Indian Health Service Research Director	1-7.10

1-7.1  GENERAL

This chapter establishes policies, responsibilities, and procedures for the review, approval, and coordination of research activities affecting the Indian Health program and assessment of research findings in regard to possible further development and application to IHS program activities.

1-7.2  DEFINITIONS

1. Research

   Research is the use of systematic methods to evaluate concepts or practices to discover new knowledge.  It usually means an organized scientific investigation.  For the purpose of this chapter, the term "research" includes (1) basic and clinical research, (2) behavioral studies, (3) anthropological studies, (4) the development of clinical and public health methods and techniques for practical application to the Indian Health program, and (5) studies to determine the extent of special health problems, or solutions thereof.  Excluded from this broad definition are: peer review; quality assurance and medical audit activities; and retrospective, concurrent, or prospective medical chart review.  Also, excluded from a requirement for clearance by an Institutional Review Board (IRB) are studies which do not involve treatment of or risk to any individual or human subject which are conducted internally, and which are subject to the normal administrative management controls, policies, procedures, and review.  In addition, the following categories of research involving human subjects are exempt from IRB clearance,  (1) research involving surveys or interviews in which anonymity of subjects is assured; (2) research involving the collection or study of existing data, documents, pathological specimens, or diagnostic specimens, if these sources are publicly available or if the information is recorded so that the subjects can not be identified; (4) research conducted in established or commonly accepted educational settings, involving normal educational practices; and (5) research involving public behavior, if anonymity of subjects is assured.

   Studies conducted by external groups (non-PHS) are usually included within the definition, whether or not there are risks to human subjects, if IHS staff, records, facilities, etc., will be utilized or involved in such studies, unless specifically exempted by one of the conditions noted above.  The Area Chief Medical Officer will determine whether any proposed study or activity can be excluded or is subject to review as prescribed in this issuance.

2. Protection of Human Subjects

   For the purposes of this chapter, "Regulations Pertaining to the Protection of Human Subjects"; refers to The National Research Award Act, P.L. 93-348, July 12, 1974; DHHS Regulations 45 CFR Part 46, as amended, published in the Federal Register January 26, 1981 (46 FR 8366) and March 27, 1981 (46 FR 19195); "Fetuses, Pregnant Women and in Vitro Fertilization" 45 CFR Part 46 published in the Federal Register August 8, 1975 (40 FR 33526); "Medical Devices" 21 CFR 812.3 published in the Federal Register August 20, 1976 (41 FR 35281) and 21 CFR 812.3; "Research Involving Children" (43 FR 31786) July 21, 1978 and "Research Involving Those Institutionalized as Mentally Disabled" published in the Federal Register November 17, 1978 (43 FR 53950).

   "Human Subjects" 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) 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. "Private Information" includes information about behavior that occurs in a context in which an individual can reasonably expect that no observation or recording is taking place, and information which has been provided for specific purposes by an individual which the individual can reasonably expect will not be made public (for example, a medical record). Private information must be individually identifiable (i.e., the identity of the subject is or may readily be ascertained by the investigator or associated with the information) in order for obtaining the information to constitute research involving human subjects. Published January 26, 1981 (45 FR 8366).

1-7.3  POLICY

The Indian Health Service supports and encourages research efforts relating to improving the health status of Indians and Alaska Natives by its own staff or by outside groups, provided that:

1. The research is consistent with the goals and objectives of the Department of Health and Human Services, the Indian Health Service, and tribal groups involved.
2. The research does not significantly detract from or interfere with the provision of health services to American Indians or Alaska Natives.
3. The research has the full understanding, documented approval, and support of the Indian tribe(s) or Alaska village(s) involved.
4. The research is moral and ethical, does not endanger the health of individuals or communities, and involves the informed consent of all individuals, human subjects, or groups directly affected. In this regard, any research which is conducted must observe regulations pertaining to the protection of human subject.  In studies which include young children, informed consent must be obtained from the parent or guardian of each child prior to participation.
5. The research does not violate Federal Law or DHHS policy and complies with the provisions of the Privacy Act (P.L. 93-579) and its implementation published October 8, 1975 (40 FR 47406). 1/
6. The research is clinically relevant and technically, epidemiologically, and statistically sound.
7. The research to be conducted has been reviewed and approved in advance according to established procedure by the appropriate Indian Health Service Area Office Research Committee, the Indian Health Service Area Office Director involved, and the Health Service Research Director, or any committee or individual designated by the latter.
8. Investigational drugs and drugs not available in interstate commerce must have the approval of the Director, Indian Health Service, or his designee, for authority to procure and use in accordance with procedure outlined in the Indian Health Manual, Part 3, Chapter 7.14, Pharmacy Services, Investigational Drugs.

The Indian Health Service will offer technical review, assistance and advice to Indian tribes and Alaskan villages, at their request, in connection with proposed or ongoing research activities in which they may be involved.

The records for all IHS-connected research projects, together with copies of appropriate protocols, approval or disapproval notices, and progress and final reports will be maintained according to established procedures for those projects which are; (1) ongoing; (2) have been previously conducted, approved, or considered for approval; or (3) are pending approval.

It is further the policy of the IHS to inform Indian tribes, groups, and committees of IHS research needs, activities, and results.  (DHHS General Administration 13-40-180).

1-7.4  AREA RESEARCH COMMITTEE - INSTITUTIONAL REVIEW BOARD

Appointment and Composition

1. Each Area Director shall establish an Area Research Committee (ARC) which will serve concurrently as the Institutional Review Board (IRB) for that Area.  All research proposals will be submitted through the ARC which will review each in accordance with the IRB duties and responsibilities defined below. All manuscripts which are being submitted for publication will be reviewed by the ARC in accordance with the definitions provided as a part of this Chapter.
2. Each Area Director shall appoint all members of the ARC and all alternate members.  The members and alternate members of the ARC shall serve for an indefinite period at the discretion and pleasure of the Area Director.  The Area Director shall fill such vacancies as may occur within 30 calendar days of the vacancy occurring.  The ARC shall be chaired by the Area Chief Medical Officer or other health professional appointed by the Area Director.
3. The ARC must:
   1. be comprised of at least five individuals;
   2. include at least one physician;
   3. include both male and female members;
   4. have at least one member whose main concerns are in non-scientific areas (e.g., patient rights or tribal concerns); and
   5. have at least one member who is not affiliated with IHS and is not a part of the immediate family of a person who is affiliated with IHS.  (It is strongly encouraged that this member be from a Tribal Health Department or Tribal Health Board.)
4. If an Area Director, because of his/her staff size or for any other reason, does not consider compliance with sections 1-7.4A through C above feasible, he/she may arrange in writing for another ARC to perform the functions required.  However, the ARC which is to assume responsibility must agree in writing to this arrangement.
5. By 1 October of every year each Area Director shall report to the IHS Research Director the composition of the ARC for the forthcoming year.  In addition, the Area Director shall advise the IHS Research Director of any changes in the composition of the ARC within one month of the changes.
6. The ARC shall have its own procedures of which this document will be a part.  The ARC procedures will be maintained in a permanent file and include a current list of its members.  The members will be identified by name, earned degrees, and other identification necessary to describe each member's contribution to the ARC.  Each member shall be designated as having either scientific or non-scientific concerns for the protection of human subjects.

1-7.5  INSTITUTIONAL REVIEW BOARD

General Duties

1. The chairperson of the ARC may, in considering research protocols and projects, obtain consultants to assist the ARC in its deliberations.  These consultants shall not be voting members of the ARC.
2. No ARC member may participate in the initial or continuing review of any project in which he/she has a conflicting interest.
3. In order to conduct business, a majority of the ARC members (or alternate members) including a physician and a member whose primary concerns are in non-scientific areas must be present.
4. No research shall be undertaken, conducted, or started until the ARC has reviewed and approved the protocol and any other necessary documentation required by the law, regulations, or this chapter and forwarded the approved research study to the IHS Research Director.  No research shall be undertaken, conducted, or started until the IHS Research Director has reviewed and approved the protocol and any other necessary documentation required by the law, regulations, or this chapter.  A negative decision by an ARC may not be over ruled or reversed by other than that ARC itself.
5. The ARC shall, in its review process, determine and appraise the effect of research projects on the tribal organizations and Indian communities involved.  It shall also determine and appraise the effect of these research projects on the goals, objectives, programs, and activities of the Indian Health Service.  This responsibility and duty includes assessment of potential benefits of the proposal for elevating the health status of American Indians and Alaskan Natives and the potential impact of the program on resources primarily intended for the delivery of health services.
6. The ARC, in its review process, shall determine and assess each research proposal from the standpoint of clinical relevance, epidemiological soundness, technical completeness, and statistical appropriateness.
7. The ARC, in its review process, shall determine and assure that each research protocol and other ongoing research projects are consistent with federal policy governing the protection of human subjects, and with other moral, ethical and legal requirements.
8. An ARC may adopt any procedures to conduct its business as long as those procedures comply with the requirements of the human subject protection regulations of the Department of Health and Human Services and the Food and Drug Administration.  However, as a minimum, each IRB shall adopt and implement the following procedures which shall serve as meeting the requirements of the Department and the Food and Drug Administration.
   1. The ARC shall designate two categories of research projects:
      1. Projects which are wholly or partially funded by the IHS Research Program.
      2. Projects which do not require any IHS Research Program funds, i.e., wholly funded internally (i.e., within the Service Unit level of control), wholly funded externally by another agency and do not require any resources from the IHS, or are collaborative efforts which use resources from both an outside agency as well as from the IHS but do not use IHSRP funds.
   2. The principal investigator must submit the protocol in writing to the Chairperson, ARC.  Each ARC must determine the number of copies it requires of the principal investigator.  The IHS Research Director requires five (5) written copies be submitted to his office for further review and approval or disapproval if the research study proposed is to be funded wholly or partially with IHSRP funds.  If the proposed research does not require IHSRP funding, only one written copy is required by the IHS Research Director when the ARC has completed its review.  Each protocol received by the ARC will be date receipted.  In addition, each protocol received will be identified by an Area designator and number, as well as by title.  Numbers are to be assigned on a consecutive basis for each calendar year (e.g. the first research project for 1986 is designated by Area Name 86-1, the second Area Name 86-2, etc.).
   3. The ARC will review each protocol received at a convened meeting which shall take place no later than 45 calendar days from the date of receipt of the protocol.  The ARC will determine if the research proposed is desirable, appropriate and the degree of risk the research presents to the subjects of the research.
   4. When a project proposal is approved by a majority of the members present, the ARC will determine the interval at which it needs to receive a status report from the investigator for the purpose of determining continued approval for the study.  The initial approval may not exceed one year.  The ARC will notify the investigator in writing when the study has been approved.
   5. The ARC shall not approve a study until it determines the proposed informed consent document to be adequate.  Such notification of approval will not be sent until the ARC has received and documented that all requested modifications in the protocol have been met.  The notification will indicate:
      1. The study is approved and has been forwarded to the IHS Research Director for final approval or recommendation for funding (which ever is appropriate depending on the category of the research).
      2. The investigator will be required to provide status reports at the stated interval indicated in the letter.  The status report the investigator submits to the ARC shall be written and shall contain not less than the following:
         1. Status of the study
         2. Number of subjects entered in the study
         3. Number of subjects declining to enter the study
         4. Number of subjects withdrawing from the study
         5. Any adverse reactions that may be a result of the study
         6. Any conclusion drawn to date
         7. Request for approval to continue the study
         8. otice of termination of the study and reason for termination.
      3. The investigator must promptly report to the ARC any unanticipated problems or adverse reactions which may occur either in type or frequency.
      4. The investigator shall not initiate any changes in the approved research until the ARC has reviewed and approved the proposed changes, except where necessary to eliminate apparent immediate hazards to the subjects.
      5. If the investigator must make changes in the approved research to eliminate apparent immediate hazards to the subjects, the changes must be reported to the Chairperson, ARC within 5 calendar days of such changes.
      6. All manuscripts related to the research study must be reviewed and cleared by the ARC prior to their submission for publication.  Note:  Manuscripts received by the ARC are to be numbered in the same manner and as a part of the sequence noted for research protocols.
   6. The ARC may disapprove the research proposed for any reason it deems appropriate.  The ARC will notify the investigator in writing that the project has been disapproved and the reason for the disapproval.
   7. The ARC may take whatever action is necessary to assure that the research, once approved, is being conducted in accordance with the approved proposal.
   8. In order not to delay the review process, an ARC may grant provisional approval to an investigator if some of the required documentation was not included in the original submittal but is forthcoming.  However, both the Research Director and the investigator must be notified in writing of the deadlines that have been established by the ARC for receipt of the required documents.  The ARC shall determine and document for itself under which circumstances it will grant a provisional approval.
9. The ARC may use an expedited review procedure only to approve minor changes in a previously approved research project.  The Chairperson or the designated Alternate Chairperson may perform an expedited review and approve or disapprove the minor change requested.  Decisions (positive or negative) must be presented at the next meeting of the ARC or within 45 calendar days, which ever comes first, for concurrence or disapproval and will be recorded in the minutes of the ARC.

1-7.6  INSTITUTIONAL REVIEW BOARD

Record Keeping Responsibilities

1. The ARC shall maintain copies of all protocols, documents, correspondence, and other pertinent information relating to each proposed, approved and disapproved project or study it reviews.  The minutes of all ARC meetings as well as pertinent correspondence or other documents received and sent will be kept as part of the permanent files of the ARC for at least ten years after the document was received by the ARC or for at least three years after completion of project activity whichever is longer.
2. The minutes of the ARC shall contain and document in addition to the date, time and location of the meeting:
   1. The names of the ARC members present.
   2. Number of members voting to approve, disapprove or abstaining from each vote taken.
   3. Whether each protocol discussed was approved, disapproved or the decision postponed.
3. The ARC shall review, approve, disapprove, or recommend changes it required for approval of all submitted manuscripts that are related to previously approved research studies.  The ARC shall send forward to the appropriate IHS Headquarters office one copy of all ARC approved manuscripts for final IHS review and approval.  In addition, one copy of the ARC approved manuscript shall be sent to the IHS Research Director.
4. The ARC Chairperson shall have prepared and sent to the IHS Research Director a quarterly report of the activities of the IRB within 15 calendar days of the end of each quarter.  This report shall include the number and title of all protocols and manuscripts received and reviewed by the ARC as well as any other activities which were undertaken.  
   Proper minutes of all meetings conducted during the quarter will meet the requirement of submitting a quarterly report.  A report of no activity shall be prepared if appropriate.
5. In place of the fourth quarter report of activities, the ARC Chairperson shall have prepared and sent to the IHS Research Director an annual report concerning the activities of the ARC for the previous fiscal year.  This report shall be completed by 15 October of each year in the form and format provided by the IHS Research Director.

1-7.7  INSTITUTIONAL REVIEW BOARD

Required Documents

1. The ARC shall review written informed consent documents for all studies.  Those studies involving human subjects shall meet the requirements of Parts 50 and 56 of the FDA regulations (21 CFR Parts 50 and 56) for the purposes of assuring that each informed consent document contains adequate information to provide each subject regarding and describing:
   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 noting the possibility that the FDA may inspect the records.
   6. For research involving more than minimal risk, an explanation as to whether any compensation and any medical treatments are available if injury occurs and, if so, what they consist of, and whom to contact for further information.
   7. A notification of whom to contact for answers to pertinent questions about the research and research subjects' rights, and who to contact in the event of a research-related injury to the subject. Note: The individual to be contacted can be a member of the ARC but must be different from the person cited in (6) above.
   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.
2. The ARC shall not approve a study until it determines the proposed informed consent document to be adequate.
3. The informed consent document shall be in a language readily understood by the subject. In those cases where the subject does not readily understand the written document, the information in the document will be presented to the subject verbally.  The informed consent document must contain the signature of the subject, or if appropriate, the subject's legally authorized representative; the investigator, and a witness who can verify that the informed consent has been truly obtained.
4. As part of the written protocol submitted, the principal investigator must include a written statement that assures informed review and written approval or disapproval from the tribal communities or groups involved with or affected by the proposed research. No research can be undertaken without tribal approval of the research study.
5. As part of the written protocol submitted, the principal investigator must include a written statement that assures informed review and written approval or disapproval from the IHS Service Unit management involved with or affected by the proposed research.  No research can be undertaken without Service Unit management approval of the research study.
6. When and where appropriate, the ARC shall negotiate inter-IRB agreements whose purpose will be to establish and confirm the proposed (or ongoing) research project's authorized and responsible IRB.  These research projects can include those studies which are wholly funded externally from the IHS and those which are of collaborative or joint effort.  (Note: an sample inter-agency IRB form has been developed and is included.)
7. When and where necessary, the ARC shall negotiate agreements with the responsible parties associated with the research study that clarifies and designates responsibility for compensation and medical treatments and the liability that arises therefrom.

1-7.8  AREA RESEARCH COMMITTEE

In addition to the duties to be performed as an Institutional Review Board, the ARC shall:

1. Recommend to the Area Director the development of research projects and the application of research findings which may contribute to improving the health status of Indian people.
2. Assist in the coordination of research efforts of various agencies, public and private research organizations, and educational institutions, as they relate to the Indian Health Service.
3. Review all manuscripts submitted for publication irrespective of whether or not they are related to approved research projects.  Approve, disapprove or recommend changes required for approval of all submitted manuscripts.  Forward all approved manuscripts to the appropriate IHS Headquarters office for final agency approval.

1-7.9  AREA OFFICE DIRECTORS

Responsibilities.

1. The Area Office Director shall designate the Research Committee membership as outlined in Section 1-7.4 of this chapter.
2. The Area Office Director shall report by October 1, of each year, to the IHS Research Director the composition of its Area Office Research Committee for the forthcoming (new) fiscal year.
3. The Area Office Director shall forward to the IHS Research Director by October 15, of each year, a report of the committee's activities for the past fiscal year.
4. Consistent with the policies and considerations previously stated, the Area Office Director will provide final review and action regarding any research proposal approved by the Area Office Research Committee.  All approved and disapproved proposals will be forwarded by the Area Office Director to the IHS Research Director within 10 days of receipt from committee.
5. The Area Office Director shall request approval by the Director, IHS, or his designee, of the use of any investigational drug and drugs not available in interstate commerce which are proposed to be used in research activities.

1-7.10  INDIAN HEALTH SERVICE RESEARCH DIRECTOR

The Director, IHS shall designate the IHS Research Director who shall have final review and approval authority concerning any research proposal, as well as oversight responsibility regarding ongoing research activities.

At his/her discretion, the Research Director may utilize an alternate IHS Research Director, a standing and/or ad hoc committee or other mechanisms to assist in the review of research proposals and ongoing research activities. Such committees/mechanisms should reflect participation by appropriate clinical specialists and researchers as well as individuals familiar with research and epidemiological design, statistical methods, and requirements regarding informed consent, protection of human subjects, and other statutes, regulations, and policies governing research activities.  Procedures and guidelines governing such committees/mechanisms will be established by the Research Director.

With or without committee activity, the Research Director shall:

1. Upon receiving the research proposal, conduct final review and grant final approval or disapproval of any research proposal within three months.  Such review and approval or disapproval should be made in deference to the policies, responsibilities, procedures, and consideration previously outlined relevant to the Area Office research committees.  However, special consideration should be focused on:
   1. The clinical relevance, research design, and technical, epidemiological, and statistical soundness of the proposal.
   2. Compliance of the proposal with statutes, regulations, and policies regarding informed consent, protection of human subjects, the privacy act, and other appropriate research requirements.
   3. Ethical and moral responsibility of the proposal.
   4. Determination of the need for the proposed project in regard to consideration of other similar or related research which has been or is being conducted.
2. Be responsible for:
   1. Integrating and coordinating research activities conducted in connection with IHS field operations.
   2. Assisting in the coordination of research efforts of various agencies, public and private research organizations, and educational institutions, as they relate to the IHS.
   3. Assisting in coordinating and conducting negotiations on research projects between the IHS and other agencies, public or private research organizations, and educational institutions, especially those involving more than one IHS Area.
   4. Recommending to the Director, IHS the development of research projects and the application of research findings which may contribute to improving the health status of Indian people.
   5. Maintaining a listing of all research projects currently being conducted, pending approval, or approved or disapproved within the past 10 years, or three years after completion of the project, whichever is longer.  A copy of this listing shall be provided yearly, by December 31, to the Director, IHS along with the appropriate recommendations about IHS research matters, including a brief summary of ongoing projects, recently completed projects, and actual or possible application of findings.  Such listings should include for each project:
      1. Title.
      2. Location of research activities.
      3. Organization conducting research.
      4. Chief researcher(s).
      5. Date of Tribal, Area Committee/Area Director, and Research Director approval or disapproval.  If disapproved, brief reason for disapproval.
      6. Status of project (active, pending, completed), updated at least annually.
      7. If an active project, date of submission of last status or final report.
      8. If active, date expected to be completed.
   6. At his/her discretion, conducting an oversight function concerning ongoing or proposed IHS research activities.
   7. Establish further procedures and guidelines for the submission, review, approval, disapproval, coordination, and reporting requirement regarding research proposals and projects.
   8. Informing Indian tribes, communities, and groups as well as other interested parties of IHS research needs, activities, and results.

1/   The privacy act assures that personal information about individuals collected by IHS is limited to that legally authorized and necessary and is maintained in a manner which precludes unwarranted intrusions upon individual privacy.   An individual providing information to the government must be told what the IHS authority is for collecting the information; why it is being collected; whether he is required to provide the information; how IHS will use the information, including what disclosures will be made of the information without his/her consent as routine uses; and the effect refusal to provide the information will have on him/her.  Furthermore, the Act permits an individual to gain access to records pertaining to him/her, to have copies made of any or all such records, and to correct or amend a record pertaining to him/her.  IHS, employees, and contractors of IHS are subject to civil suit for any damages which occur as a result of willful or intentional action which violates any individual's rights under this Act.