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I.    Purpose

The Oklahoma State Department of Health (OSDH) is committed to providing an organizational structure in accordance with Title 45 of the Code of Federal Regulations (CFR) Part 46 (45 CFR Part 46) in order to establish and maintain an environment dedicated to the ethical principles for safeguarding the rights and welfare of the human beings recruited to participate in research activities. The OSDH Institutional Review Board (IRB) has been established to comply with federal regulations to protect the rights and welfare of human research participants. The OSDH IRB has the responsibility to assure that the risks of proposed research are justified by the potential benefits to the participants and to society, and that risks are minimized to the extent possible consistent with sound research design. The OSDH IRB must assure that the risks of research do not fall disproportionately on one group while the potential benefits accrue to another. The OSDH IRB oversees the consent process to assure voluntary and knowing consent to participate in research. Individuals who are particularly vulnerable or whose capacity to consent may be in doubt require additional protection during the consent process. The OSDH IRB must assure that the research is designed to respect individual privacy and preserve the confidentiality of private information. The OSDH IRB has the ongoing oversight responsibility of approved research to monitor the welfare of the participants and to determine that the risks and potential benefits remain unchanged. The OSDH IRB may approve, disapprove, or require modifications to research protocols. It may also suspend or terminate its approval of ongoing (previously approved) research.

Federally supported human subject research for which the OSDH IRB provides review and oversight will comply with 45 CFR Part 46. Except for research exempted or waived under 45 CFR § 46.101(b)&(i), all human subject research will be reviewed, prospectively approved, and subject to continuing oversight by the OSDH IRB. The OSDH IRB will have authority to approve, require modifications in, or disapprove the covered human subject research. This policy applies to all individuals at the OSDH engaged in or collaborating in research involving human subjects. The Commissioner of Health retains final authority to determine whether a particular activity is subject to this policy. This policy applies to any person paid by, under the control of, or affiliated with the OSDH, such as scientists, trainees, technicians and other staff members, students, fellows, guest researchers, or collaborators at OSDH. Research activities are exempt from this policy if they are determined by the OSDH IRB to meet criteria established in 45 CFR § 46.101.

II.    Operations

A. Board Composition [310:10-5-12 IRB Membership Requirements and 45 CFR § 46.107]

1.  The IRB shall have at least five members, with varying backgrounds to promote complete and adequate review of research activities commonly conducted by the entity. The IRB shall be sufficiently qualified through the experience and expertise of its members, and the diversity of the members, including consideration of race, gender, and cultural backgrounds and sensitivity to such issues as community attitudes, to promote respect for its advice and counsel in safeguarding the rights and welfare of human subjects.  In addition to possessing the professional competence necessary to review specific research activities, the IRB shall be able to ascertain the acceptability of proposed research in terms of institutional commitments and regulations, applicable law, and standards of professional conduct and practice.  The IRB shall therefore include persons knowledgeable in these areas.  If an IRB regularly reviews research that involves a vulnerable category of subjects, such as children, prisoners, pregnant women, or handicapped or mentally disabled persons, consideration shall be given to the inclusion of one of more individuals who are knowledgeable about and experienced in working with these subjects.

2.  Every effort will be made to ensure that no IRB consists entirely of men or entirely of women, including the institution's consideration of qualified persons of both sexes, so long as no selection is made to the IRB on the basis of gender.  No IRB may consist entirely of members of one profession.

3.  Each IRB shall include at least one member whose primary concerns are in scientific areas and at least one member whose primary concerns are in nonscientific areas.

4.  Each IRB shall include at least one member who is not otherwise affiliated with the institution and who is not part of the immediate family of a person who is affiliated with the institution.

5.  No IRB may have a member participate in the IRB's initial or continuing review of any project in which the member has a conflicting interest, except to provide information requested by the IRB.

6.  An IRB may, in its discretion, invite individuals with competence in special areas to assist in the review of issues that require expertise beyond or in addition to that available on the IRB.  These individuals may not vote with the IRB.  [19 Ok Reg 2046 eff 6-27-02]

7.  The IRB Administrator will be from within or outside the OSDH, fully capable of managing the IRB and the matters brought before it with fairness and impartiality.

8.  The Commissioner of Health will appoint the IRB Administrator.

B.  Meetings

1.  The IRB meets monthly, normally on the third Wednesday.

2.  The IRB may be called upon to meet on an emergency or otherwise as needed basis at times other than the regularly scheduled meetings.

C.  The Review Process

1.  The meeting agenda will be distributed to each IRB member one week prior to the meeting.  In addition to the meeting agenda, each member will receive the following information:

a.  Minutes of the most recent meeting of the IRB;

b.  Copy of the application form (which includes summary of protocol), consent form and other supporting documentation (advertisements, survey instruments, etc.) for all new submissions;

c.  Copy of the Protocol Modification Form and revised consent form (when applicable) for all requests for modification to a previously approved protocol;

d.  Copy of the Local Adverse Event Reporting Form and all supporting documentation (when applicable) for any serious adverse event (whether related or unrelated) occurring at this institution; and

e.  Copy of the Periodic Progress Report (PPR) Form, which includes a summary of the results since initial approval and current consent form for all requests for continuing approval.

2.  In addition to the above documents, a primary reviewer system is utilized for review of all agenda items.  One member is appointed as the primary reviewer for each new study, amendment, or continuing approval request.  The primary reviewer also receives the full protocol (which includes a completed copy of any applicable Federal grant application), the informed consent document and any other appropriate documentation. The primary reviewer will present the protocol at the IRB meeting.

3.  The IRB file (which includes the original and complete copy of all documents) for each agenda item is available at the meeting and in the office of the OSDH IRB Secretary prior to the meeting at the request of any member for review.

D.  Submission of New Protocols

1.  The IRB Secretary and IRB Administrator receive all new submissions and conduct pre-reviews to ascertain suitability (complete submission and adequate documentation) for IRB review.  An initial determination is made as to the type of review (full, expedited, exempt) required for the submission.  The IRB Chair or IRB Administrator provides additional input as needed during this part of the pre-review process.  The pre-review process is to assist in the complete submission of required documentation; it is not an official determination on behalf of the IRB.

2.  Based on the information gathered during the pre-review process, written feedback is provided to the Investigator so that appropriate revisions can be made to the documentation prior to review by the IRB.

3.  After receiving the feedback from the pre-review process, the Investigator makes a final submission to the IRB.  The submission is processed appropriately depending on whether it requires full Board or expedited review, or is exempt from IRB review.

4.  All items for consideration must be accompanied by an Institutional Review Board Application Form.  All forms are available as hard copies in the office of the OSDH IRB Secretary, as Word documents via e-mail request to the Institutional Review Board mailbox (IRB@health.ok.gov) or can be accessed from the OSDH IRB web page at http://www.health.ok.gov/irb/index.html.

5.  In addition to the application form as described above, each submission must also include the following supporting documentation:

a.  Complete protocol;

b.  Full grant application (all research described in the grant application or proposal must be entirely consistent with the protocol reviewed by the IRB.  Any discrepancies must be resolved prior to the involvement of human subjects); and

c.  All advertisements to be seen/heard by potential research subjects.

6.  Unless the study meets the criteria in either a. or b. below, a copy of the proposed informed consent document(s) must be included in all submissions.  The document(s) must contain all of the required elements of informed consent and must follow the OSDH standard format.  For National Institutes of Health (NIH) Supported Multicenter Clinical Trials, the IRB must also review a copy of the NIH approved sample informed consent document and the full NIH approved protocol.

a.  If the study meets the criteria for waiver of full or partial documentation of the informed consent process [see 45 CFR 46.116(c)] the proposed consent document (consent cover letter, telephone consent script, etc.) must be included.  This could be a telephone script, a cover letter for survey instruments or other consent tools, which may not include all the elements as designated above.  If the study meets the criteria for waiver of a portion of the informed consent process, this will be documented in the minutes, the IRB file, and the approval letter to the Investigator.

b.  The IRB may approve a consent procedure which does not include, or which alters, some or all of the elements of informed consent if the research involves no more than minimal risk to the subjects; the waiver or alteration will not adversely affect the rights and welfare of the subjects; the research could not practicably be carried out without the waiver or alteration; and whenever appropriate, the subjects will be provided with additional pertinent information after participation.  If the study meets the criteria for waiver of informed consent documentation [45 CFR 46.117(c)], the Board will address this specifically and document it in the minutes of the meeting, the IRB file, and in the approval letter to the Investigator.

c.  The IRB may waive the requirement for a signed consent document in accordance with 45 CFR 46.117(c) if:

(1) The only record linking the subject and the research would be the consent document and the principal risk would be potential harm resulting from a breach of confidentiality. Each subject will be asked whether the subject wants documentation linking the subject with the research, and the subject's wishes will govern or

(2) The research presents no more than minimal risk of harm to subjects and involves no procedures for which written consent is normally required outside of the research context. In cases in which the documentation requirement is waived, the IRB may require the Investigator to provide subjects with a written statement regarding the research.

E.  Criteria for IRB Approval

1.  In order to approve a research study, the IRB shall determine that all of the following requirements are satisfied:

a.  Risks to subjects are minimized by using procedures consistent with sound research design, which do not unnecessarily expose subjects to risk and whenever appropriate, by using procedures already being performed on the subjects for diagnostic or treatment purposes;

b.  Risks to subjects are reasonable in relation to anticipated benefits and the importance of the knowledge that may reasonably be expected to result;

c.  Selection of subjects is equitable, taking into account the purposes of the research and the setting in which the research will be conducted;

d.  Informed consent will be sought and obtained from each prospective subject or the subject's legally authorized representative or next of kin (where applicable);

e.  Informed consent will be appropriately documented;

f.  The research plan makes adequate provision for monitoring the data collected to ensure the safety of subjects;

g.  There are adequate provisions to protect the privacy of subjects and to maintain the confidentiality of data; and

h.  Appropriate additional safeguards have been included to protect the rights and welfare of particularly vulnerable subjects, such as persons with acute or severe physical or mental illness, persons who are economically or educationally disadvantaged, or persons who are likely to be vulnerable to coercion or undue influence.

2.  After review by the IRB, discussion and approval of the research, the IRB must also determine the appropriate length of the approval.  This specifically is the maximum number of days the IRB feels is appropriate for this study to continue without a full review of the research. Federal regulations do not allow for this approval period of time to exceed 365 days.

a.  If the IRB determines the risk to subjects is appropriate based on the procedures outlined in the protocol and the majority of potential risks are currently known, then approval will be granted for approximately one year.

b.  If the IRB determines the study involves a high degree of risk and/or the stage of the research is such that many of the potential risks are not yet known, then the approval will be granted for a shorter amount of time. The duration of approval will vary depending on the type of study, the projected enrollment, the study population, etc.  The duration of approval and reason for such determination will be noted in the IRB minutes.

c.  There will be projects, for which the IRB requires verification from sources other than the Investigator.  These types of studies could include (but are not limited to) studies not receiving additional outside review, studies including an extremely high level of risk or studies being conducted by an Investigator who has a history of research-related problems. In these circumstances, the IRB will work jointly with the appropriate OSDH officials to assure that appropriate monitoring procedures are in place prior to enrollment beginning in the study and will require reporting back to the IRB on a regular basis to monitor these studies.

F.  Voting

IRB Voting requirements include:

1.  A vote is only considered official when it has taken place with a majority of the IRB members including at least one member whose primary concerns are in nonscientific areas, and when investigational drug studies are to be reviewed, at least one physician member is present.

2.  No proxy votes are permitted.

3.  An IRB member may not vote on his/her own study or on any study where there is a potential conflict of interest.

4.  A simple majority of votes cast is needed for study approval.

5.  Any member who is determined to have a conflict of interest on a study will be excused from IRB discussion and will not vote on the study. A majority of the membership must remain intact when this member is excused, as they no longer are eligible to count towards this majority.

G.  Communication of IRB Decision

1.  The IRB shall notify the Investigator of its decision in writing, within two weeks of the decision.

a.  If the study is approved, the Investigator will be given an approval letter and a stamped copy of the approved informed consent document (where applicable).  The copy of the informed consent document will include an approval date and the date of approval expiration.  This stamped copy of the informed consent document is to be used by the Investigator to generate copies of the document to be signed by subjects.

b.  If the research activity is disapproved, a written statement of the reasons for its decision will be given and the Investigator will be given an opportunity to respond in person or in writing.

c.  If IRB approval is contingent upon minor and specific changes or modifications being made, the Investigator may make the recommended changes or modifications and return it to the office of the OSDH IRB Secretary.  The IRB Secretary will review the items to ensure the requested changes have been made in accordance with the original IRB request as reflected in the minutes from such meeting.  The changes will be forwarded to the IRB Chair or Administrator for verification that the specific changes requested by the IRB have been made.  Once verified, the Chair or Administrator will authorize approval on behalf of the IRB. An approval letter will be generated within 5 working days of such verification. This letter will be forwarded to the Investigator.  If the Investigator chooses not to make the recommended changes, the Investigator may respond in writing or in person at the next scheduled meeting of the IRB.

d.  If the IRB requires additional information of the Investigator to make an appropriate determination regarding appropriateness of the protocol, then the study is deferred or tabled for further review.  The Investigator is notified in writing of the reasons for deferral and is asked to present additional information to address these concerns.  This information can be presented in writing or in person at the next scheduled IRB meeting.

2.  Other OSDH offices may be responsible in accordance with State and Federal laws for further review and approval or disapproval of research that is approved by the IRB; for example, studies involving vital statistics, cancer registry, or other identifiable information require additional review and agreements.  The IRB will notify the appropriate office of the research; however, it is the Investigator's responsibility to comply with all State and Federal laws.  In accordance with HHS regulations at 45 CFR 46.112, no other institutional office or official may approve human subjects research that has not been approved by the IRB.

3.  In conjunction with IRB review, minutes are maintained, as well as agendas prepared, by the IRB Secretary.  The minutes include a recording of the vote that is documented in accordance with 45 CFR 46.115(a)(2).  The minutes document the discussion by the IRB and the determinations made for each protocol.  The minutes also include protocol specific information justifying the findings of the IRB in situations where regulations require such.

4.  The OSDH Commissioner of Health, as the signatory authority of the institution, will be notified of the IRB findings and actions on a monthly basis.  The notification will be accomplished in the form of a copy of the Board approved IRB meeting minutes.

H.  Appeal of IRB Decision

1.  A request for an appeal of an IRB decision must be made in writing within ten working days of notification of the original decision to the IRB and must be delivered to the office of the OSDH IRB Secretary.

2.  The appeal will be considered at the next regular meeting by the full IRB.  In addition to the written request for an appeal, the Investigator may respond in person at the meeting.

I.  Exempt from Further IRB Review

The IRB may exempt from full Board review and/or continuing review research activities in which the only involvement of human subjects will be in one or more of the following categories.  These categories are established by the federal regulations and require a pre-review by the OSDH IRB Administrator or Chair to determine appropriateness.  Note: Research involving prisoners, pregnant women, fetuses, human in vitro fertilization, and children is not exempt from the federal regulations because these classes of subjects are considered vulnerable.

1.  Certain types of research that do not fall within the purview of the review by the full IRB and meet all applicable criteria set forth by the federal regulations (45 CFR 46.101) and involve no greater than minimal risk may qualify for exemption.  This means that once the determination has been made by the designated OSDH official, the IRB will not routinely conduct subsequent reviews of the study.  Criteria for exempt status include:

a.  Research conducted in established or commonly accepted educational settings, involving normal educational practices, such as:

(1)  Research on regular and special education instructional strategies, or

(2) Research on the effectiveness of or the comparison among instructional techniques, curricula, or classroom management methods.

b.  Research involving the use of educational tests (cognitive, diagnostic, aptitude, achievement) survey procedures, interview procedures or observation of public behavior on subjects 18 years of age or older, unless:

(1)  Information obtained is recorded in such a manner that human subjects can be identified, directly or through identifiers linked to the subjects;

(2)  Any disclosure of the human subjects' response 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.

c.  Research involving the use of educational tests (cognitive, diagnostic, aptitude, achievement), survey procedures, interview procedures or observation of public behavior is not exempt under paragraph 2 (b) of this section, if:

(1)  The human subjects are elected or appointed officials or candidates for public office; or

(2) Federal statute(s) requires without except that the confidentiality of the personally identifiable information that will be maintained throughout the research and thereafter.

d.  Research involving the collection or study or existing (i.e., on the shelf, already collected and/or banked prior to the date the study is to start) 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.

e.  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:

(1)  Public benefit or service programs;

(2)  Procedures for obtaining benefits or services under those programs;

(3)  Possible changes in or alternatives to those programs or procedures; or

(4)  Possible changes in methods or levels of payment for benefits or services under those programs.

f.  Taste and food quality evaluation and consumer acceptable studies:

(1)  If wholesome foods without additives are consumed, or

(2)  If a food is consumed that contains a food ingredient 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 Food Safety and Inspection Service of the U.S. Department of Agriculture.

5.  The designated OSDH official who is authorized to make the determination that a study is exempt from further IRB review is the IRB Chair or IRB Administrator.

6.  Requests for exempt status must be submitted to the office of the OSDH IRB Secretary by the Investigator prior to initiating the research.  Once a determination has been made that this study is exempt from further review, a letter will be sent to the Investigator confirming this decision.  At that time, the research activities can begin.

7.  If the research does not meet the exemption criteria found in 45 CFR 46.101, the office of the OSDH IRB Secretary will proceed with the study review as either expedited or by the convened IRB.

J.  Expedited Review

Research activities that (1) present no more than minimal risk to human subjects, and (2) involve only procedures listed in one or more of the following categories, may be reviewed by the IRB through the expedited review procedure authorized by 45 CFR 46.110 and 21 CFR 56.110.

The categories in this list apply regardless of the age of subjects, except as noted.  The expedited review procedure may not be used where identification of the subjects and/or their responses would reasonably place them at risk of criminal or civil liability or be damaging to the subjects (i.e., financial standing, employability, insurability, reputation, or stigmatizing), unless reasonable and appropriate protections will be implemented so that risks related to invasion of privacy and breach of confidentiality are no greater than minimal. The standard requirements for informed consent (or its waiver, alteration, or exception) apply regardless of the type of review--expedited or full--utilized by the IRB.

1.  Clinical studies of drugs and medical devices only when one of the following conditions is met.

a.  Research on drugs for which an investigational new drug application (21 CFR Part 312) is not required.  (Note: Research on marketed drugs that significantly increases the risks or decreases the acceptability of the risks associated with the use of the product is not eligible for expedited review.)

b.  Research on medical devices for which (i) an investigations device exemption application (21 CFR Part 812) is not required; or (ii) the medical device is cleared/approved for marketing and the medical device is being used in accordance with its cleared/approved labeling.

2.  Collection of blood samples by finger stick, heel stick, ear stick, or venipuncture as follows:

a.  From healthy, non-pregnant adults who weight at least 110 pounds.  For these subjects, the amounts drawn may not exceed 550 ml in an 8-week period and collection may not occur more frequently than 2 times per week; or

b.  From other adults and children (defined as persons who have not attained the legal age for consent to treatments or procedures involved in the research, under the applicable law of the jurisdiction in which the research will be conducted), considering the age, weight, and health of the subjects, the collection procedure, the amount of blood to be collected, the frequency with which it will be collected.  For these subjects, the amount drawn may not exceed the lesser of 50 ml or 3 ml per kg in an 8-week period and collection may not occur more frequently than 2 times per week.

3.  Prospective collection of biological specimens for research purposes by noninvasive means.  Examples: (a) hair and nail clippings in a non-disfiguring manner; (b) deciduous teeth at time of exfoliation or if routine patient care indicates a need for extraction; (c) permanent teeth if routine patient care indicates a need for extraction; (d) excreta and external secretions (including sweat); (e) uncannulated saliva collected either in an unstimulated fashion or stimulated by chewing gumbase or wax or by applying a dilute citric solution to the tongue; (f) placenta removed at delivery; (g) amniotic fluid obtained at the time of rupture of the membrane prior to or during labor; (h) supra- and subgingival dental plaque and calculus, provided the collection procedure is not more invasive than routine prophylactic scaling of the teeth and the process is accomplished in accordance with accepted prophylactic techniques; (i) mucosal and skin cells collected by buccal scraping or swab, skin swab, or mouth washings; (j) sputum collection after saline mist nebulization.

4.  Collection of data through noninvasive procedures (not involving general anesthesia or sedation) routinely employed in clinical practice, excluding procedures involving x-rays or microwaves.  Where medical devices are employed, they must be cleared/approved for marketing.  (Studies intended to evaluate the safety and effectiveness of the medical device are not generally eligible for expedited review, including studies of cleared medical devices for new indications.)  Examples:  (a) physical sensors that are applied either to the surface of the body or at a distance and do not involve input of significant amounts of energy into the subject or an invasion of the subject's privacy; (b) weighing or testing sensory acuity; (c) magnetic resonance imaging; (d) electrocardiography, electroencephalography, thermography, detection of naturally occurring radioactivity, electroretinography, ultrasound, diagnostic infrared imaging, doppler blood flow, and echocardiography; (e) moderate exercise, muscular strength testing, body composition assessment, and flexibility testing where appropriate given the age, weight, and health of the individual.

5.  Research involving materials (data, documents, records, or specimens) that have been collected or will be collected solely for non-research purposes (such as medical treatment or diagnosis).

6.  Collection of data from voice, video, digital, or image recordings made for research purposes.

7.  Research on individual or group characteristics or behavior (including, but not limited to, research on perception, cognition, motivation, identity, language, communication, cultural beliefs or practices, and social behavior) or research employing survey, interview, oral history, focus group, program evaluation, human factors evaluation, or quality assurance methodologies.

III.   Inclusion of Genders and Minority Groups

All clinical research conducted at or sponsored by the Oklahoma State Department of Health or any institution covered under FWA00000183 must not exclude participants based on gender or minority status unless a clear and compelling rationale based on strong scientific or practical reasons justifies such exclusion and establishes to the satisfaction of the IRB that such exclusion is appropriate with respect to the health of the subjects or purpose of the research.  The IRB recognizes that certain research is gender specific and must include only one gender.  The IRB shall have discretion to determine the scientific merits of the grounds for exclusion and may require additional information from the sponsor.

When research is supposed by the NIH, each Investigator is responsible for following the NIH guidelines on the inclusion of women and members of minority groups and their subpopulations set forth in Vol. 59, Federal Register No. 59.  The Investigator must furnish the IRB with evidence of compliance before IRB approval may be given.

Research reviewed by the IRB shall not routinely exclude a gender, minorities, or any other subset of the population from participation in clinical research.  If a gender, minorities or any subset of the population are excluded from the research, the reason(s) must be so stated in accordance with this section.  Of note, exclusion of women of childbearing potential in clinical trials involving investigational drugs/devices is NOT allowed simply because of potential teratogenetic effects.  Women of childbearing potential can be required to use contraception while participating and must be fully informed of the known and potential side effects if they become pregnant, but they cannot be excluded entirely unless this can be scientifically justified.

IV.  Inclusion of Children in Research

By regulatory definition, children are persons who have not attained the legal age for consent to treatments or procedures involved in the research, under applicable law of the jurisdiction in which the research will be conducted.  Generally the law considers any person under 18 years old to be a child.

A.  Categories of Research Involving Children

The federal regulations permit four categories of research involving children.  The categories are determined by the degree of risk and prospect of benefit to the participating child-subject.  For any protocol involving children, the IRB, in consultation with the Principal Investigator (PI), is responsible for determining in which of the four categories of research the study belongs and for documenting in the minutes the rationale for its choice.  When an Investigator intends to use children as research subjects, he/she must address these issues directly in the protocol in a section entitled "The ethical and regulatory considerations concerning the involvement of children" in which he/she identifies which of the categories the study fits into and the rationale for this categorization.

1.  The four categories of research which may be approved by IRBs are:

a.  Category 1: research that does not involve greater than minimal risk to children.

b.  Category 2: research involving greater than minimal risk but presenting the prospect of direct benefit to the individual child-subject.

c.  Category 3: researching involving greater than minimal risk and no prospect of benefit to the individual child-subject.  In order to approve research in this category, the IRB must determine that the risk of the research represents no more than a minor increase over minimal risk; that the intervention or procedure presents experiences to the child-subjects that are reasonably commensurate with those inherent in their actual, or expected medical, dental, psychological, social, or educational situations; and the intervention or procedure is likely to yield generalizable knowledge about the subject's disorder or condition which is of vital importance for understanding or the amelioration of the disorder or condition.

d.  Category 4: research not otherwise approvable under one of the above categories but that the IRB determines presents a reasonable opportunity to further the understanding, prevention, or alleviation of a serious problem affecting the health or welfare of children.  In these cases, the IRB will forward the research for review by the Commissioner of Health, who may approve the research after consultation with a panel of experts.  The panel must determine that the research presents a reasonable opportunity to further the understanding, prevention, or alleviation of a serious problem affecting the health or welfare of children, and that the research will be conducted in accordance with sound ethical principles.

2.  Federal regulation prohibits the use of children as subjects in studies given exempt approval under the category 2 (anonymous surveys) of exempt criteria.

3.  NIH guidelines do require that children be included in all research studies unless there is a scientific or ethical justification for excluding them.  Each Investigator is responsible for complying with the specific guidelines as addressed in the "NIH Policy and Guidelines on the Inclusion of Children as Participants in Research Involving Research Subjects."

4.  Children who are wards of the state or any other agency, entity or institution, can be included in approved research only if such research is related to their status as wards or is conducted in schools, camps, hospitals, institutions, or similar settings in which the majority of children involved as subjects are not wards.

5.  A minor may consent to research if a lawfully recognized court of law has entered an order specifying the minor can consent to a specific research activity.  Additionally, a minor as defined in Title 63 O.S., §2602 who may consent to health services, may consent to research that is to preserve the child's life or the research has been approved by an IRB and relates to the management of reportable diseases.

6.  Assent of children is required unless:

a.  Minor subject is too immature/incapacitated to be consulted;

b.  The intervention/procedure involved in the research holds out a prospect of direct benefit that is important to the health or well-being of the children and is available only in the context of the research; or

c.  The IRB has approved a waiver (if the assent document would result in a confidentiality risk).

V.   Prisoners as Research Subjects

In accordance with our Federalwide Assurance, the OSDH IRB provides additional protection for prisoners inasmuch as prisoners may be under constraints because of their incarceration, which could affect their ability to make truly voluntary or uncoerced decisions regarding whether or not to participate as subjects in research.  For our purposes, prisoner means any individual involuntarily confined or detained in a penal institution.  This includes individuals sentence to such an institution under a criminal or civil statute, individuals detained in other facilities by virtue of statutes or commitment procedures, which provide alternatives to criminal prosecution in a penal institution, and individuals detained pending arraignment, trial, or sentencing.

A.  Principal Considerations

The principal considerations for including prisoners as research subjects are as follows:

1.  Any possible advantages accruing to the prisoner through his or her participation in the research, when compared to the general living conditions, medical care, quality of food, amenities, and opportunity for earnings in prison, are not of such a magnitude that his or her ability to weigh the risks of the research against the value of such advantages in the limited choice of the prisoner is impaired;

2.  The risks involved in the research are commensurate with risks that would be accepted by non-prisoner volunteers;

3.  Procedures for the selection of subjects within the prison are fair to all prisoners and immune from arbitrary intervention by prison authorities or prisoners;

4.  Adequate assurance exists that parole boards will not take into account a prisoner's participation in the research in making decisions regarding parole, and each prisoner is clearly informed in advance that participation in the research will have no effect on his or her parole;

5.  Where the IRB finds there may be need for follow-up examination or care of participants after the end of their participation, adequate provision has been made for such examination or care, taking into account the varying lengths of individual prisoner's sentences, and for informing participants of this fact.

6.  45 CFR 46.305-306 requires that any IRB reviewing studies involving prisoner subjects must include at least one member who is either a prisoner or a prisoner representative with appropriate background and experience to serve in that capacity.

VI.  Other Special Considerations

A.  Mentally Ill/Cognitively Impaired

1.  The primary ethical concern in research involving the mentally disabled is that their disability may compromise their capacity to understand the information presented and their ability to make a reasoned decision about participation.  For purposes of IRB review by the OSDH IRB, the following definitions are applicable.

a.  Mentally Ill/Cognitively Impaired - Having either a psychiatric disorder (e.g., organic and functional psychoses, neuroses, personality or behavioral disorders, senility) or a developmental disorder (e.g., mental retardation).  Others, including persons under the influence of or dependent on drugs or alcohol, those suffering from severe traumatic brain injury or degenerative diseases affecting the brain, terminally ill patients, and persons with severely disabling physical handicaps may also be compromised in their ability to make decisions in their best interest.

b.  Competence - As a description of mental status, means an ability to understand information presented, appreciate the consequences of acting (or not acting) on that information and express a choice.  As a description of legal status, competence or incompetence pertains to adjudication in court proceedings that a person's abilities are so diminished that his or her decisions or actions should have no legal effect (e.g., writing a will). Such adjudications are often determined by inability to manage business or monetary affairs and do not necessarily reflect a person's ability to function in their daily situation.

2.  As a general rule, all adults regardless of their diagnosis or conditions should be presumed competent to consent unless there is evidence of serious mental disability that would impair reasoning or judgment.  Even those who do have a diagnosed mental disorder may be perfectly able to understand the situation of being a research volunteer and quite capable of consenting or refusing.

3.  In the past, institutionalized individuals have been used as convenient research subjects in drug and vaccine tests, which were totally unrelated to their disorders or institutionalization.  This exploitation of the vulnerable and "voiceless" led the National Commission for the Protection of Human Subjects to recommend that, even in research on mental disabilities, subjects should be recruited from among the non-institutionalized whenever possible.  It is policy at this institution to support this position.

4.  Oklahoma law allows for surrogate consent for research.

5.  Oklahoma law forbids waiver of consent.

B.  Surrogate Consent for Research Subjects

1.  Oklahoma law allows for Family Member Consent in such cases where the potential subject is not capable of consenting on their own behalf.  Family member authority is in the following order: spouse, adult child, either parent, adult sibling, or a relative by blood or marriage.  There are some specific restrictions within this law and certain guidelines, which the IRB must follow to allow for such consent.  This law was essentially approved to allow research on such diseases as Alzheimer's, head trauma, sepsis, and psychiatric disorders.

a.  Surrogates cannot override the subject's previously expressed permission/prohibition.

2.  Family Member Consent is specifically addressed in the IRB approval process.  If requested by an Investigator, the IRB will specifically approve a separate consent form for the family member to sign and will reference this special approval in the response to the Investigator.

3.  Surrogate consent can be employed only if it has been approved by the IRB.  The IRB looks at a variety of issues when determining whether or not Family Member Consent is appropriate.  Some of these issues are:

a.  Will participating in the study directly benefit the potential subject?

b.  Are there alternate standard/approved treatments available for this subject?

c.  Could this study be done without allowing Family Member Consent?

4.  Based upon the answers found when addressing these questions, the Board will make a determination regarding the appropriateness of Family Member Consent.  The Investigator will be notified as to the approval/ denial of this process and the Board's reason for such. The Investigator may appeal this decision in writing to the Board and provide  documentation for such appeal.  Appeals will be brought back to the Board for consideration.

C.  Genetic Research

1.  Genetic testing in research studies is becoming more common and presents a variety of factors to be considered.  The IRB gives careful consideration to the use of genetic testing in research and evaluates each use on a case-by-case basis.  The following are OSDH policies for genetic testing.  Due to the potential for continual change in standards for genetic testing, any deviations to these standard policies will be limited to decisions made by the fully convened IRB.

a.  Unless primary IRB review is conducted at another site and includes IRB review, research involving genetic testing will not be approved under either the exempt or expedited process and must receive review and approval by the full Board prior to being started.

b.  If materials being prospectively collected are to be used or banked for future use in genetic research, the research subject(s) must be told specifically that their blood or tissue specimen will (or may) BE used for genetic testing.  They must give consent for this process to take place. They must be given all information available at the present time concerning the type of genetic research that will take place on their sample.  They must be told whether information regarding the results of these studies will be made available and why (or why not).

c.  In most cases, the Board feels that the results of the genetic testing should not be made available to the subjects.  The only acceptable time to allow the patient access to the results are situations where a positive result can be achieved by this information being released (i.e., treatment available to them because of this information or behavior modification recommendations that are appropriate for their medical care) and where an approved genetic counseling program is in place to help the patient deal with their access to this information.

d.  In all cases where genetic testing is being done, the potential risks (even those risks that are theoretical in nature) must be covered by the consent form.

D.  Non-English Speaking Subjects

1.  Regulations require that the informed consent information be presented (oral and written) in a language understandable to the subject.  In cases where the IRB and/or the Investigator feels there is a high likelihood that English will not be understood by most of the subjects, then the IRB will request that the Investigator submit a consent form written in the appropriate language.  In addition to the translated consent form, the IRB will require a notarized statement by the person who translates the consent that states that the translated consent form represents the same information as is written in the approved English consent form.  The Investigator may contact the office of the OSDH IRB Secretary for guidance or assistance in obtaining someone to translate this document.

2.  In cases where the Investigator may have a subject who does not speak English clearly enough to read, understand, and participate in the written/oral consent process, the IRB will require that the Investigator make provisions for their participation in the study.  The IRB will require a short form which explains the basics of the research process and that the subject has consented in a language different than English.  Someone outside of the study staff must witness this entire process and that person must attest to the fact that the study was explained and the subject understood the details of the study as listed in the full version consent.

E.  Fetal Research

1.  Research using fetal tissue is ILLEGAL under Oklahoma State Law.

VII.  Continuing IRB Review

A.  Continuing Review of Research Previously Approved

1.  Continuing review of research previously approved is as follows:

a.  Where (i) the research is permanently closed to the enrollment of new subjects; (ii) all subjects have completed all research-related interventions; and (iii) the research remains active only for long-term follow-up of subjects; or

b.  Where no subjects have been enrolled and no additional risks have been identified; or

c.  Where the remaining research activities are limited to data analysis.

2.  Continuing review of research, not conducted under an investigational new drug application or investigational device exemption where categories two (2) through (8) do not apply but the IRB has determined and documented at a convened meeting that the research involves no greater than minimal risk and no additional risks have been identified.

3.  In the expedited review process, the IRB Chair or IRB Administrator may exercise all of the authorities of the full IRB except disapproval of the research.  The office of the OSDH IRB Secretary will inform the Investigator of the expedited review decision.  All IRB members will be informed of the expedited review at the next regular meeting.  The meeting agenda will detail items approved under expedited review.  The chairperson will ask if there is any discussion on the expedited review items.  Discussion will be limited unless there are questions.  IRB files for all expedited projects are available in the office of the OSDH IRB Secretary at any time a member wishes to conduct their own review. Research approved as expedited will be reviewed annually by the IRB.

B.  Amendments to Previously Approved Protocols

1.  Investigators must promptly report any proposed changes or revisions in an approved research project to the IRB for review using the Protocol Modification Form (PMF).  Approval of such changes or revisions must be received before such changes or revisions are instituted.

2.  Types of modifications requiring submission of the PMF include:

a.  Change in procedure;

b.  Change in study personnel;

c.  Change in research site;

d.  Change in subject enrollment;

e.  Recruitment material/advertisement;

f.  Consent/assent/permission form changes; and,

g.  Other modifications.

3.  The Investigator will submit a copy of the revised protocol (complete new protocol which includes a summary attachment or the proposed revisions or where the revisions are clearly highlighted within the protocol), and a copy of the revised consent form (when applicable) to the office of the OSDH IRB Secretary.  All attachments, advertisements, and instruments that are effected in the modification must be submitted with changes highlighted.

4.  The IRB Secretary receives all requests for amendment approval from the Investigator. The IRB Secretary or Administrator pre-reviews them to ascertain suitability (complete submission and adequate documentation) for IRB review.  An initial determination is made as to the type of review (full or expedited) required for the submission.  The IRB Administrator provides additional input as needed during this part of the review process.  This part of the process is for educational purposes only to provide feedback to the Investigators and obtain additional documentation as necessary.  It is not an official determination on behalf of the IRB.

5.  Based upon the information gathered during the pre-review process, a written critique is provided to the Investigator so that appropriate revisions can be made to the protocol prior to final submission to the IRB.

6.  After receiving the feedback from the pre-review process, the Investigator makes a final submission to the IRB.  The submission is processed appropriately depending on whether it requires full Board, expedited, or exempt review.

7.  A primary reviewer system is utilized for review of protocol amendments.  This system follows the same procedures as referenced above for new protocol submissions.  The primary reviewer receives all documentation submitted for review and the remainder of the Board members receive the Protocol Modification Summary, amended Consent Form (when applicable), and any other instruments, which have been revised.

8.  A listing of changes and revisions will be provided on the IRB agenda.

9.  All changes and revisions will be reviewed, discussed, and voted on individually, with the vote indicated in the minutes in accordance with 45 CFR 46.115 (a)(2).

10.  All modifications previously approved under the expedited review process will be reported to membership on the meeting agenda and members will be invited to initiate discussion on any amendment for which they have questions or concerns.

11.  In the event an Investigator feels it is necessary to initiate the revisions immediately to eliminate apparent immediate hazards to the subject, the Investigator must immediately contact the office of the OSDH IRB Secretary.  The IRB Chair or Administrator will consider allowing initiation immediately, provided that additional information is furnished in writing and signed by the Principal Investigator plus a physician not involved in the study (if a physician is essential to the study).  This must include reasonable and compelling rationale for this immediate modification.  This must be reviewed and approved by the IRB Chair or IRB Administrator plus one additional group member prior to being implemented and must then be reported to the full Board at the next convened meeting.  The IRB expects that these instances will be rare and will make every effort to convene an emergency meeting to review these situations.

B.  Periodic Progress Reports

1.  At initial review the Board will approve each study for a specific period of time, not to exceed one year.  The IRB may require review more often than annually for high-risk protocols or protocols with a high risk to benefit ratio.  At six weeks prior to the date that this approval expires, the office of the OSDH IRB Secretary will send out a request for the Periodic Progress Report.  If no response is received, a second notice is sent about four weeks later.  This report requires an original signature by the Principal Investigator in ink and must be dated.  In the report, the Investigator must provide the IRB with adequate information to determine that the study is appropriate for continuation.  This progress report will include the following:

a.  Number of subjects enrolled, including demographic and gender-specific information;

b.  Number and types of adverse and unanticipated problems, both locally and at outside sites for multi-center trials;

c.  Number and types of complaints about the research, including any voluntary withdrawals of subjects;

d.  Summary of findings obtained thus far, amendments or modifications to the research since the last review, reports on multi-center trials, and all relevant information pertaining to risks associated with the research; and

e.  A copy of the most recently signed informed consent document (with identifying information blacked out) and a clean copy of the most recently approved consent document (for all studies open to new subject enrollment).

2.  The Period Progress Report must be reviewed and approved by the IRB Administrator or by the IRB before the expiration date of the approval for the study to be in compliance with federal regulations.  Federal regulations do not allow for any grace period for renewal.  For example, if a study is approved by the IRB on July 15, 2011, and the initial approval through July 14, 2012, a satisfactory progress report must be received, reviewed, and on the agenda for the IRB meeting prior to July 14, 2012.

3.  If the due date approaches and a PPR has not been received, a notice to inactivate the study with a final deadline is sent to the Investigator. Once the deadline passes with no response, the study is administratively inactivated and a letter of notification is mailed to the Investigator.

4.  Failure to complete the PPR in a timely manner will result in the study being closed as well as no further research being approved until such time as reports are completed.

5.  The due date of the PPR will not be the same as the expiration date of the approval.  The due date will reflect the time the IRB Administrator needs to receive the PPR in order to assure that the Board has time to review, meet, discuss, and approve continuation.

6.  If the progress report is incomplete or appears to be inaccurate, the IRB will telephone the Investigator and annotate changes.  If there is much missing information or no signature, the PPR will be sent back to the Investigator for completion.

7.  All IRB members will receive the summary of information listed above.  In addition, a primary reviewer system will be used for periodic reviews, with a copy of the most recently approved version of the protocol reviewed by a primary reviewer and available at the meeting for review by any member who requests it.

8.  The current informed consent document(s) is reviewed by the IRB to ensure the following:

a.  The currently approved or proposed consent document is still accurate and complete; and

b.  Any significant new findings that may relate to the subject's willingness to continue participation are provided to the subject in accordance with HHS regulations at 45 CFR 46.116(B)(5).

9.  Continuing review of research must be substantive and meaningful. HHS regulations describe at 45 CFR 46.111 (and at subparts B, C, and D of 45 CFR Part 46 when applicable) the criteria that must be satisfied in order for the IRB to approve research.  These criteria must be satisfied when the IRB conducts continuing review of research either at a convened meeting or under an expedited review procedure. These criteria include, among other things, determinations by the IRB regarding risks, potential benefits, informed consent, and additional safeguards for subjects likely to be vulnerable to coercion or undue influence.

10.  The IRB shall conduct continuing review of research where (i) there is active enrollment of subjects or pending enrollment of the first subject, (ii) the research is permanently closed to the enrollment of new subjects, and (iii) all subjects have completed all research-related interventions. Continuing review is required as long as the research remains active for long-term follow-up of subjects and continues to involve non-exempt human subjects research.  Furthermore, continuing IRB review of research is required where the remaining research activities are limited to data analysis of individually identifiable private information (see 63 Federal Regulations 60364-60367, category 8).

11.  Review of currently approved or newly proposed consent documents must occur during the scheduled continuing review of research by the IRB, but informed consent documents should be reviewed whenever new information becomes available that would require modification of information in the informed consent document.  Investigators must also report to the IRB planned changes in the conduct of the study, since these may affect the protection of human subjects.

12.  Once the PPR is reviewed by the IRB Administrator and approved by the Board, a letter giving approval, usually for one year, is mailed to the Principal Investigator within one week of the Board meeting.

C.  Final Closure Report

The completion of termination of a study is a change in activity and therefore must be reported to the IRB.  A notice of closure to the IRB is used by the IRB to close its files but more importantly to provide pertinent information to the IRB in its evaluation and approval of related studies. Completion or termination of a study is reported to the IRB on a Final Closure Report or can be terminated on the PPR if it is due within 30 days of termination of the study.

1.  A Final Closure Report will be submitted within thirty (30) days after completion or termination of the study.  The IRB Administrator or Chair will review all reports of study completion and, if needed, request further information from the Investigator to clarify any questions that may arise.

2.  The IRB Administrator will generate a final closure letter and will send the letter to the Investigator and file the final closure report and a copy of the final closure letter in the study file.

3.  The file will be stamped with the inactivated date on the front cover and filed in a separate area for inactivated study files.

4.  For exempt studies, once each year the IRB will send the Principal Investigator a Protocol Exempt Status letter.  The Investigator will indicate on the letter if the study is currently active or has been terminated and return the letter to the IRB.

a.  Upon receipt of the letter from the Investigator, the IRB will process the letter based upon the response given.  If the Investigator indicates the study is active, the letter is filed in the study file.

b.  If the Investigator indicates the study has been terminated, the letter will be presented to the Administrator for approval.  The termination will be recorded in the next appropriate agenda/minutes for reporting to the IRB.

D.  Serious, Unanticipated, and Other Adverse Events

Investigators must promptly report any unanticipated problems involving risks to subjects or others to the IRB.  There are two mechanisms for this reporting process.

1.  All serious adverse events occurring locally (i.e., at an institution under the jurisdiction of the OSDH IRB) must be reported by completing the Local Adverse Event Form.  This must be completed and furnished to the office of the IRB Secretary within 4 working days of the Investigator being made aware of the event.  A serious adverse event involves:

a.  The death of a subject (whether study-related or not).  Deaths must be reported no later than the next working day by phone or electronic mail to the IRB mailbox with the completed form to be submitted according to the above guidelines.

b.  Any experience that is immediately life threatening, permanently disabling, or requires (or prolongs) inpatient hospitalization; or

c.  A congenital anomaly or birth defect.

2.  The IRB Chair will make an immediate and preliminary determination regarding the degree of risk involved and notify the Investigator if she/he feels that the study should be immediately suspended.

3.  If the IRB Chair does not determine the event to require immediate suspension, then the completed report will be presented at the next scheduled IRB meeting for discussion by the full Board.

4.  Upon review by the Board, a determination will be made as to whether the event was related, possibly related, or unrelated to the study participation and whether or not it was expected or unexpected.  A vote will be taken regarding whether the Investigator can continue the study as approved, can continue the study with specific modifications required, or must discontinue the study.  This vote will be recorded in the minutes individually for each event in accordance with 45 CFR 46.115 (a)(2).

5.  Regarding serious adverse events occurring at outside sites (for multi-center trials), the Investigator may submit a copy of the report which was furnished from the sponsoring institution (or other Investigator as applicable).  This copy must include a minimum of the OSDH IRB number, the Principal Investigator at this institution, and his/her signature (assuring the IRB that Investigator is aware of this information).  These will receive administrative review by the IRB Chair and will be reported to the Board in summary form on the next meeting agenda.

6.  The IRB Administrator may implement a review process for outside serious adverse events in any situation where he/she feels that the situation warrants such process.

7.  Other adverse events to be reported include:

a.  Research subject's complaints that the researchers put undue pressure to participate;

b.  Research subject experienced extreme stress requiring medical treatment or follow-up as a result of research participation;

c.  A compromise of data confidentiality; and

d.  Other serious complaints lodged by subjects or potential subjects.

E.  Monitoring of Studies

1.  The IRB shall be empowered to monitor research activities by conducting random detailed reviews of patient charts and patient interviews, as it deems necessary for proper continuing review of research.

2.  The IRB Chair will appoint appropriate IRB members and staff to conduct such monitoring activities.

3.  Such monitoring will be conducted as often as deemed necessary.

4.  The Investigator(s) shall make all requested records available to the IRB.

5.  A report of findings will be sent to the Investigator(s) and the IRB at the conclusion of the review.

VIII.  Investigator Requirements

A.  Principal Investigator Responsibilities

1.  The Principal Investigator shall submit the IRB application form and all necessary documents at least one week prior to the monthly IRB meeting.

2.  The Principal Investigator shall certify that all Investigators will comply with all Office of Human Research Protections (OHRP), FDA, and IRB rules and regulations in conducting the research.

3.  The Principal Investigator shall see that all Investigators furnish to the IRB proof of compliance with the certificate of IRB training.

B.  Information to be Provided to the IRB by the Investigator

Information to be provided to the IRB by the Investigator includes:

1.  Title of the study;

2.  Purpose of the study, including the benefit obtained by doing the study;

3.  Sponsor of the study;

4.  Results of previous related research and appropriate background information;

5.  Subject selection and exclusion criteria, including justification for use of special subject populations, such as children of the mentally handicapped;

6.  Study design including as discussion of the appropriateness of research methods;

7.  Description of the procedures to be performed;

8.  Provisions for managing adverse reactions;

9.  Recruitment of subjects (see also advertising Section IX below); and

10.  Informed consent, which includes:

a.  A statement that the study involves research;

b.  An explanation of the purposes of the research and the expected duration of the subject's participation;

c.  A description of the procedures to be followed and identification of any procedures that are experimental;

d.  A description of any reasonably foreseeable risks or discomforts to subjects;

e.  A description of any benefits to the subject or to others that may reasonably be expected from the research;

f.  A disclosure of appropriate alternative procedures or courses of treatment that might be advantageous to the subject;

g.  A statement describing the extent of confidentiality of records identifying the subjects will be maintained and the possibility the IRB may inspect the records;

h.  An explanation of whether compensation or medical treatment is available if injury occurs and, if so, what it consists of, or where further information may be obtained;

i.  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.

C.  Additional Elements of Informed Consent Required (When Appropriate)

When appropriate, additional elements of informed consent may be required, including:

1.  A statement that the particular treatment or procedures 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;

7.  Documentation of informed consent shall also include;

a.  Use of a written consent form containing the above items and following the IRB standard consent form;

b.  Provision for a witness, as needed;

c.  Signature by the subject or subject's representative;

d.  Signature by the Investigator;

e.  Signature of the person obtaining the consent;

f.  Signature of a witness; and

g.  Verification the subject was given a copy of the consent form.

D.  Other Items the Investigator Shall Provide the IRB

The following items should be provided to the IRB (as applicable):

1.  A disclosure of any compensation provided to the subject for participation in the study;

2.  A disclosure of extra costs to the subject because of participation in the study;

3.  A disclosure of extra costs to third party payers because of subject's participation;

4.  Any changes in the study after initiation;

5.  A report of any unexpected serious adverse events or information regarding similar reports received from the sponsor as soon as possible and in no event later than four (4) working days after the Investigator discovers the information;

6.  An Investigator shall submit the proposed clinical investigation including the Investigator's brochure; the protocol of the investigation; a report of prior investigations; if using a medical device; and the materials to be used in obtaining the consent of human subjects to the IRB for review before any human subjects are allowed to participate in or requested formally to consent to participate in the investigation.

7.  Periodic Progress Reports as requested by the IRB, no less often than once per year, including the number of subjects withdrawing from the study and the reasons for each withdrawal; and

8.  A final report upon completion of the research.

IX.  Advertising for Research Subjects

A.  Advertising to General Public

When advertising to the general public is to be used, the IRB shall review the information contained in the advertisement and the mode of its communication to determine that the procedure for recruiting subjects provides adequate and accurate information.

1.  Advertisements to recruit subjects should be limited to:

a.  The individual name or specific office or department and the accurate address and telephone number of the clinical Investigator as well as the location of the research and the person to contact for further information;

b.  Wording that effectively communicates the purpose of the research, and in summary form, the eligibility criteria that will be used to admit subjects into the study; and

c.  A straightforward and truthful description of the benefits (e.g., payments or free treatment) to the subject for participation in the study and the duration of the study and treatment.

2.  Advertisements to recruit subjects should NOT:

a.  Mislead subjects;

b.  Claim, either explicitly or implicitly, that the drug or device is safe or effective for the purpose under investigation, or that the drug or device is in any way equivalent or superior to any other drug or device;

d.  Imply the researcher or Investigator has a unique or special skill, remedy, or treatment;

3.  Unless the research project is based within the Oklahoma State Department of Health, the name of the Oklahoma State Department of Health should not be stated other than to state the project meets the requirements of the IRB of the Oklahoma State Department of Health.

X.  Record Requirements

A.  Documentation

1.  Written procedures and guidelines will be maintained for IRB activities.

2.  A list of all IRB members and qualifications will be maintained.

3.  Minutes of each meeting will be maintained and recorded by the IRB secretary.  The IRB Administrator will sign the minutes.  The minutes shall include:

a.  The names of the members present;

b.  A record of discussion of controverted issues, including the basis for requiring changes in or disapproving research;

c.  A record of IRB discussions;

d.  A record of voting, including the number of members voting for, against, and abstaining;

e.  The name of the member making the motion and the name of the member seconding the motion shall be recorded in the minutes; and

f.  The period of time for which approval of the study is granted and the  frequency of IRB review which will be conducted.

B.  Retention

1.  Protocols and consent documents as submitted and as approved, shall be retained for not less than three years.

2.  Adverse reaction reports and IRB consideration of adverse reaction reports shall be retained for not less than three years.

3.  Period Progress Reports shall be retained for not less than three years.

4.  Statements of significant new findings provided to subjects shall be retained for not less than three years.

5.  Records of research involving minor subjects shall be maintained for 25 years.

6.  Budget and accounting records regarding acquisition and expenditure of resources shall be retained for not less than three years.

7.  All communications to and from the IRB shall be retained for not less than three years.

XI.  Research Integrity/Scientific Misconduct

The responsibility under 45 CFR Part 46 includes authority to suspend or terminate IRB approval of research that is not being conducted in accordance with the IRB's requirements or that has been associated with unexpected serious harm to subjects.  Any suspension or termination of approval shall include a statement of the reasons for the IRB's actions and shall be reported promptly to the Investigator, appropriate OSDH officials, and the Commissioner of Health.  Particular circumstances in an individual case may dictate variation from this procedure deemed in the best interests of the OSDH and U.S. Department of Health and Human Services (DHHS).  Any change from these procedures also must ensure fair treatment to the subject of the inquiry or investigation.  The Commissioner of Health should approve any significant variation in advance.

A.  Research Integrity Officer

The Commissioner of Health will appoint the Research Integrity Officer (RIO) in accordance with State Administrative Rule 310:10-7-3.  The RIO will have primary responsibility for implementation of these procedures in accordance with 310:10-7-1-20.

B.  Preliminary Assessment of Allegations

Upon receiving an allegation of scientific misconduct, the RIO will immediately assess the allegation to determine whether there is sufficient evidence to warrant an inquiry, whether DHHS support or DHHS applications for funding are involved, and whether the allegation falls under the DHHS definition of scientific misconduct.  If the RIO determines that the allegation provides sufficient information to allow specific follow-up, involves DHHS support, and is within the DHHS definition of scientific misconduct, he or she will immediately initiate the inquiry process.  In initiating the inquiry, the RIO should identify clearly the original allegation and any related issues that should be evaluated.  The purpose of the inquiry is to make a preliminary evaluation of the available evidence and testimony of the respondent, whistleblowers, and key witnesses to determine whether there is sufficient evidence of possible scientific misconduct to warrant an investigation.  The purpose of the inquiry is not to reach a final conclusion about whether misconduct definitely occurred or who was responsible.  The findings of the inquiry must be set forth in an inquiry report.

C.  Sequestration of the Research Records

After determining that an allegation falls within the definition of misconduct in science and involves DHHS Public Health Services funding [310:10-7-12], the RIO must ensure that all original research records and materials relevant to the allegation are immediately secured.  The RIO may consult with the Commissioner of Health for advice and assistance in this regard.

D.  Appointment of the Inquiry Committee

1.  The RIO, in consultation with other OSDH officials as appropriate, will appoint an inquiry committee and committee chair within 10 days of the initiation of the inquiry.  The inquiry committee shall consist of individuals who:

a.  Do not have real or apparent conflicts of interest in this case;

b.  Are unbiased; and

c.  Have the necessary expertise to evaluate the evidence and issues related to the allegation.  These may be scientists, subject matter experts, administrators, lawyers, or other qualified persons, and they may be from inside or outside the institution.

2.  The Inquiry Committee will interview the principal investigators and key witnesses, and conduct the inquiry.

3.  The RIO shall notify the respondent (investigators) of the proposed committee membership in 10 days.

4.  If the respondent submits a written objection to any appointed member of the inquiry committee or expert based on bias or conflict of interest within 5 days, the RIO shall determine whether to replace the challenged member or expert with a qualified substitute.

E.  Inquiry Process and Report

1.  The RIO will review the charge with the committee, discuss the allegations, any related issues, and the appropriate procedures for conducting the inquiry, assist the committee with organizing plans for the inquiry, and answer any questions raised by the committee.  The RIO and OSDH counsel will be present or available throughout the inquiry to advise the committee as needed.

2.  The Inquiry Committee will interview the whistleblower, the respondent, and key witnesses, as well as examine relevant research records and materials.  The Inquiry Committee will then evaluate the evidence and testimony obtained during the inquiry.  After consultation with the RIO and OSDH counsel, the committee members will decide whether there is sufficient evidence of possible scientific misconduct to recommend further investigation.  The scope of the inquiry does not include deciding whether misconduct occurred or conducting exhaustive interviews and analyses.

3.  A written inquiry report must be prepared that states:

a.  The name and title of the committee members and experts, if any;

b.  The allegations;

c.  The DHHS support;

d.  A summary of the inquiry process used;

e.  A list of the research records reviewed;

f.  Summaries of any interviews;

g.  A description of the evidence in sufficient detail to demonstrate whether an investigation is warranted or not; and

h.  The committee's determination as to whether an investigation is recommended and whether any other actions should be taken if an investigation is not recommended.  OSDH counsel will review the report for legal sufficiency.

4.  After first redacting the identity of the whistleblower, the RIO will provide the respondent with a copy of the redacted draft inquiry report for comment and rebuttal, and will provide the whistleblower, if he or she is identifiable, with portions of the draft inquiry report that address the whistleblower's role and opinions in the investigation.

5.  The RIO shall establish reasonable conditions for review to protect the confidentiality of the draft report.

6.  Within 14 calendar days of their receipt of the draft report, the whistleblower and respondent will provide their comments, if any, to the Inquiry Committee.  Any comments that the whistleblower or respondent submits on the draft report will become part of the final inquiry report and record.  Based on the comments, the Inquiry Committee may revise the report as appropriate.

7.  The RIO will transmit the final report and any comments to the Commissioner of Health, who will make the determination of whether findings from the inquiry provide sufficient evidence of possible scientific misconduct to justify conducting an investigation.  The inquiry is completed when the Commissioner of Health makes this determination, which will be made within 60 days of the first meeting of the Inquiry Committee.  Any extension of this period will be based on good cause and recorded in the inquiry file.

8. The RIO will notify both the respondent and the whistleblower in writing of the Commissioner of Health's decision of whether to proceed to an investigation and will remind them of their obligation to cooperate in the event an investigation is opened.  The RIO will also notify all appropriate institutional officials of the Commissioner of Health's decision.

9.  A decision recommending further investigation is confidential pursuant to 51 O.S. § 24A.12 and shall not be publicly disseminated.  The Commissioner of Health's determination, together with the Inquiry Committee's report, constitute the final investigation report for purposes of Office of Research Integrity (ORI) review.  When a final decision on the case has been reached, the Research Integrity Officer will notify both the respondent and the whistleblower in writing.  In addition, the Commissioner of Health will determine whether law enforcement agencies, professional societies, professional licensing boards, editors of journals in which falsified report may have been published, collaborators of the respondent in the work, or other relevant parties should be notified of the outcome of the case.  The Research Integrity Officer is responsible for ensuring compliance with all notification requirements of funding or sponsoring agencies.

11.  An investigation should ordinarily be completed within 120 days of its initiation, with the initiation being defined as the first meeting of the investigation committee.  This includes conducting the investigation, preparing the report of findings, making the draft report available to the subject of the investigation for comment, submitting the report to the Commissioner of Health for approval, and submitting the report to the ORI.

F.  Requirements for Reporting to the Office of Research Integrity

1.  Upon initiating an investigation, the OSDH shall send a report in writing to the Director, ORI, DHHS, on or before the date the investigation begins and will notify ORI of the final outcome of the investigation including a copy of the investigation report.  If the inquiry or investigation is terminated for any reason without completing all relevant requirements of the DHHS regulation, the Research Integrity Officer will submit a report of the planned termination to ORI, including a description of the reasons for the proposed termination.

2.  If the investigation will not be completed in 120 days, the Research Integrity Officer will submit to ORI a written request for an extension that explains the delay, reports on the progress to date, estimates the date of completion of the report, and describes other necessary steps to be taken.

3.  The Research Integrity Officer will contact ORI for consultation and advice when DHHS Public Health Services funding or applications for funding are involved and an admission of scientific misconduct is made.

4.  The Research Integrity Officer will notify ORI at any stage of the inquiry or investigation if:

a.  There is an immediate health hazard involved;

b.  There is an immediate need to protect Federal funds or equipment;

c.  There is an immediate need to protect the interests of the person(s) making the allegations or of the individual(s) who is the subject of the allegations as well as his/her Co-Investigators and associates, if any;

d.  It is probable that the alleged incident is going to be reported publicly;

e.  The allegation involves a public health sensitive issue (e.g., a clinical trial); or

f.  There is a reasonable indication of possible criminal violation.  In this instance, the institution must inform ORI within 24 hours of obtaining that information.

G.  Institutional Administrative Actions

1.  OSDH will take appropriate administrative actions against individuals when an allegation of misconduct has been substantiated.  If the Commissioner of Health determines that the alleged misconduct is substantiated by the findings, he or she will decide on the appropriate actions to be taken, after consultation with the Research Integrity Officer.  The actions may include:

a.  Withdrawal or correction of all pending or published abstracts and papers emanating from the research where scientific misconduct was found.

b.  Removal of the responsible person from the particular project, letter of reprimand, special monitoring of future work, probation, suspension, salary reduction, or initiation of steps leading to possible rank reduction or termination of employment.

c.  Restitution of funds as appropriate.

2.  The termination of the respondent's institutional employment, by resignation or otherwise, before or after an allegation of possible scientific misconduct has been reported, will preclude or terminate the misconduct procedures.  If the respondent, without admitting to the misconduct, elects to resign his or her position prior to the initiation of an inquiry or investigation, the inquiry or investigation will proceed.  If the respondent refuses to participate in the process after resignation, the committee will use its best efforts to reach a conclusion concerning the allegations, noting in its report the respondent's failure to cooperate and its effect on the committee's review of all the evidence.

3.  If the institution finds no misconduct and ORI concurs, after consulting with the respondent, the Research Integrity Officer will undertake reasonable efforts to restore the respondent's reputation if necessary.

4.  If relevant, the Commissioner of Health will determine whether the whistleblower's allegations of scientific misconduct were made in good faith.  If an allegation was not made in good faith, the Commissioner of Health will determine whether any administrative action should be taken against the whistleblower.

XII.  Additional Guidelines

Items not specifically addressed in these policies and procedures shall be governed by the Code of Federal Regulations, Title 45, Section 46, which covers the Protection of Human Subjects, and Oklahoma Administrative Code, Title 310, Oklahoma State Department of Health, Chapter 10, Human Subjects Protection.

XIII.  References

Code of Federal Regulations, Title 45, § 46

Federal Register, Volume 59

Title 63, O.S. § 2602

Oklahoma Administrative Rules, Title 310, Chapter 10

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