Legal Authority 45 CFR Part 46 21 USC 321-392; 21 CFR, Parts 50 and 56 Coverage All research involving human subjects conducted, All clinical investigations regulated by the FDA, including supported or otherwise subject to regulation by any food and color additives, dietary supplements bearing a Federal Department or Agency*. This also includes nutrient/health claim, infant formula, drugs for human use, FDA. medical devices and biological products, etc. Impact on Other Laws Human Subject 45 CFR 46.101(a) and 46.102(e) Must comply with pertinent federal laws or regulations that provide more protection. 46.101(e) Does not override state or local laws or foreign laws/regulations that provide more protection. 46.101(f) A living individual about whom data is obtained through intervention or interaction with the individual or about whom individually identifiable private information is obtained. 21 CFR 50.1 [revised 4/24/01] Pertinent Federal, state or local laws and regulations are still applicable. 56.103(c) A patient or healthy individual who is or becomes a participant in research either as a recipient of the test article or as a control. Minimal risk Vulnerable Category of Subjects 46.102(f) 50.3(g) Probability and magnitude of harm or discomfort anticipated in the research are not greater in and of themselves than those ordinarily encountered in daily life or during the performance of routine physical or psychological examinations or tests. 46.102(i) and 50.3(k) and 56.101(i) [Has been interpreted to mean from the viewpoint of the human subject] Children Handicapped persons Prisoners Mentally disabled persons Pregnant Women Economically or educationally disadvantaged persons 46.107, 46.111(3); 56.107(a), & 56.111(3) 1
Emergency Use Not defined. However, they are not intended to limit the provision of emergency medical care. Use of a test article (drug, biological product or medical device, food additive, color additive, electronic product, etc.) on a human subject in a life-threatening situation in which no standard acceptable treatment is available, and in which there is not sufficient time to obtain IRB approval. Assurance IRB Written Procedures Filed with OHRP, NIH, DHHS. Must have written: Statement of principles governing the institution in the discharge of its responsibilities for protecting the rights and welfare of research human subjects conducted at or sponsored by the institution. 46.103(b)(1) Designation of 1 or more IRBs established, with provisions for meeting space and sufficient staff to support the IRB s review and record keeping duties. 46.103(b)(2) A list of IRB members identified by name, earned degrees; representative capacity, indications of experience such a board certifications, licenses, etc. 46.103(b)(3) Signed by individual authorized to act for the institution. 46.103(c) 56.101(d) None required. Written procedures are required for: Conducting initial and continuing review of research and for reporting its findings and actions to the investigator and the institution. 46.103(b)(4)(i), 48.108(a) and 56.108(a)(1) Determining which projects require review more often than annually and which projects need verification from sources other than the investigators that no material changes have occurred since previous IRB review. 46.103(b)(4)(ii), 46.108(a) and 56.108(a)(2) Ensuring prompt reporting to the IRB of proposed changes in a research activity. 46.103(b)(4)(iii), 46.108(a) and 56.108(a)(3) 2
IRB Written Procedures, cont'd. IRB Members IRB Quorum Requirements Ensuring that changes in an approved research activity may not be initiated without IRB review and approval except when necessary to eliminate apparent immediate hazards to the subject. 46.103(b)(4)(iii), 46.108(a) and 56.108(a)(4) Ensuring prompt reporting to the IRB, appropriate institutional officials and the Department or Agency head (or FDA under 56.108) of any: - Unanticipated problems involving risks to subjects or others or, - Any serious or continuing noncompliance with this policy or the requirements or determinations of the IRB - Suspension or termination of IRB approval. 46. 103(b)(5), 48.108(a) and 56.108(b) At least five members, with the following: Varying backgrounds Diversified as to race, gender, cultural background and sensitivity to community attitudes. Persons knowledgeable in the acceptability of proposed research in terms of institutional commitments and regulations, applicable law, and standards of professional conduct and practice. If regularly review research involving a vulnerable category, then the IRB should include 1 or more individuals knowledgeable about and experienced in working with these subjects. Includes both men and women. From separate professions. At least one scientist member. At least one non-scientist member. At least one member who is not affiliated with the institution, either directly or through an immediate family member. Any member with a conflicting interest shall not participate in the initial or continuing review of the project in which he/she has a conflicting interest. The IRB may invite consultants to assist in review, but who shall not vote. 46.107 and 56.107 Except for Expedited Review [and Exempt Activities], a majority of members must be present, including at least one non-scientist member. 46.108(b) and 56.108(c) Approval requires a majority vote of members present at a meeting. 46.108(b) and 56.108(c) 3
IRB Review Authority to approve, require modifications or disapprove research activities. 46.109(a) and 56.109(a) Require that informed consent meets the requirements of 46.116/ 50.25 respectively. 46.109(b) and 56.109(b) May require additional information be added to the informed consent that meaningfully adds to protection of rights & welfare of subjects. 46.109(b) and 56.109(b) Require documentation of informed consent or may waive it as allowed. 46.109(c) and 56.109(c) [FDA: if documentation requirement is waived, the IRB may require that subjects be provided with a written summary of the research 56.109(d)] Written notice to institution and investigators of its approval, modification or disapproval of proposed research activity. 46.109(d) and 56.109(e) If disapproved, provide reason for its decision and give the investigator an opportunity to respond in person or in writing. 46.109(d) and 56.109(e) Conduct continuing review of approved policies at intervals appropriate to the degree of risk, but not less than 1 year. 46.109(e) and 56.109(f) Authority to observe or have a third party observe the consent process and research. 46.109(e) and 56.109(f) FDA Only: Provide the sponsor a written copy of information publicly disclosed under 50.24(a)(7) when an exception to informed consent is granted. 56.109(g) Expedited Review IRB may conduct expedited review of the following: (Involves no more - List of categories published in Federal Register that the IRB finds involves no more than minimal risk (63 FR than minimal risk) 60353, attached) - Minor changes in approved research prior to date of continuing review. EXCLUDES classified research involving human subjects (March 27, 1997 Presidential memorandum) 46.110(b) and 56.110(b) Reviewed by the Chairperson or experienced IRB member(s) appointed by the chairperson. 46.110(b) and 56.110(b) Reviewers may exercise all authorities of the IRB, except the ability to disapprove. If unable to approve, must present to the full (quorum) IRB. 46.110(b) and 56.110(b) Advise IRB members of proposals approved by expedited review. 46.110(c) and 56.110(c) 4
IRB Approval Criteria Review by Institution after IRB Review IRB Federal Regulations Comparison Table 4/24/01 as updated through 10/31/01 Must determine the following: Risks to subjects minimized: - By using procedures consistent with sound research design that do not unnecessarily expose subjects to risk. - As appropriate, by using procedures already being performed on subjects for diagnostic or treatment purposes. 46.111(a)(1) and 56.111(a)(1) Risks of the research to subjects are reasonable in relation to anticipated benefits from the research, if any, to subjects and the importance of the knowledge that may reasonably be expected to result. 46.111(a)(2) and 56.111(a)(2) Equitable selection of subjects, being aware of special problems of research involving vulnerable category of subjects. 46.111(a)(3) and 56.111(a)(3) Informed consent obtained from each subject (or his/her legally authorized representative). 46.111(a)(4) and 56.111(a)(4) Informed consent documented unless waived by the IRB. 46.111(a)(5) and 56.111(a)(5) When appropriate, the research plan makes adequate provision for monitoring the data collected to ensure safety of the subjects. 46.111(a)(6) and 56.111(a)(6) When appropriate, adequate provisions are in place to protect the privacy of subjects and maintain the confidentiality of data. 46.111(a)(7) and 56.111(a)(7) Additional safeguards included to protect the rights and welfare of vulnerable subjects. 46.111(b) and 56.111(b) Institution Official(s) may further review and approve or disapprove the research, EXCEPT they may not approve a protocol disapproved by the IRB. 46.112 and 56.112 Suspension or Termination IRB Authority to suspend or terminate protocol when: - Protocol not conducted in accord with IRB s requirements - Unexpected serious harm to subjects. Includes a statement of reasons for IRB s action. Promptly notify: - Investigator(s) - Appropriate institutional officials - Department or Agency head 46.113 and 56.113 5
Government Upon a finding that the institution has materially failed to comply with the terms of the regulation. Various administrative actions are available, including suspension or termination of ongoing studies and disqualification of the IRB. Cooperate Research Change in IRB members IRB Records Retention of IRB Records 46.123 56.120-122 May enter into a joint review arrangement or rely upon the review of another qualified IRB or make similar arrangements to avoid duplication of effort if approved by the affected Department/Agency. 46.114 and 56.114 Must report to OHRP. 46.103(b)(3) Not addressed Must prepare and maintain the following: Copies of all research proposals reviewed, including any scientific evaluations, approved sample consent documents, investigator progress reports and reports of injuries to subjects. 46.115(a)(1) and 56.115(a)(1) IRB meeting minutes. They must show attendance, IRB actions taken, votes on actions, including those voting for, against and abstaining, the basis for requiring modifications or disapproving research and written summary of the discussion & resolution of controverted issues. 46.115(a)(2) and 56.115(a)(2) Records of continuing review activity. 46.115(a)(3) and 56.115(a)(3) Correspondence between IRB and investigators. 46.115(a)(4) and 56.115(a)(4) List of IRB members, identified by name, earned degrees, representative capacity, indications of experience sufficient to describe each member's chief anticipated contributions, and employment relationship (if any) with the institution. 46.115(a)(5) and 56.1159a)(5) Written IRB procedures as described above. 46.115(a)(6) and 56.115(a)(6) Statements of significant new findings provided to subjects, required by 46.116(b)(5). 46.115(a)(7) and 56.115(a)(7) DHHS Only: Administrative records required by 46.116(a) must be retained at least 3 years. Records relating to research must be retained for at least 3 years after completion of the research. Allow access to Agency for inspection and copying. 46.115(b) and 56.115(b) 6
Exempt Research Activity (Requires IRB determination of exempt status) In educational settings, involving normal educational Those listed under the Common Rule 46.101(b). practices. 46.101(b)(1) Emergency use of a test article, provided it is reported to Using educational tests, survey or interview the IRB within 5 working days. 56.104(c) [See procedures or observation of public behavior where additional requirements herein] recorded information does not identify the human subjects and disclosure of their responses outside the research will not place the subject at risk of criminal or civil liability or damage the subject s financial standing, employability or reputation. 46.101(b)(2) Excludes research with children unless the research involves observations of public behavior when the investigator(s) don t participate. 46.101(i) Using educational tests, survey or interview procedures or observation of public behavior not exempt under 46.101(b)(2) if the human subjects are elected or appointed public officials or candidates for public office or federal statutes require that the personally identifiable information will be maintained confidentially during and after the research. 46.101(b)(3) Involving the collection or study of publicly available or non-identifiable existing data, documents, records, pathological or diagnostic specimens. 46.101(b)(4) 7
Exempt Research Activity (Requires IRB determination of exempt status), cont'd. Informed Consent General Requirements Exception from General Requirements Emergency Use of Test Article Research & demonstration projects conducted by or subject to the approval of Department or Agency heads designed to study evaluate, or examine: - public benefit or service programs - procedures for obtaining benefits or services under such programs - possible changes in or alternatives to those programs/procedures, or - possible changes in methods or levels of payment for benefits or services under those programs. 46.101(b)(5) Taste and food quality evaluation & consumer acceptance studies if wholesome foods without additives are consumed or foods containing a food ingredient at or below the FDA acceptable level or approved by the EPA or USDA are consumed. 46.101(b)(6) 8 Taste and food quality evaluation & consumer acceptance studies if wholesome foods without additives are consumed or foods containing a food ingredient at or below the FDA acceptable level or approved by the EPA or USDA are consumed. 56.104(d) Except as provided elsewhere in the regulations, the Investigator must obtain legally effective informed consent of the subject or his/her legally authorized representative. 46.116 and 50.20 Cannot include any exculpatory language waiving or appearing to waive any of the subject s legal rights. 46.116 and 50.20 Cannot include any exculpatory language releasing or appearing to release the investigator, the sponsor, the institution or its agents from liability for negligence. 46.116 and 50.20 Not addressed other than to state that the regulations are not intended to interfere with a physician's judgment in treating a patient, including emergency care. Must certify in writing that: - The subject is confronted by a life-threatening situation necessitating the use of the test article. - Informed consent cannot be obtained from the subject due to an inability to communicate with, or obtain legally effective consent from the subject. - Insufficient time to obtain consent from the subject's legal representative. - No alternative method of approved or generally recognized therapy that provides an equal or greater
likelihood of saving the subject's life. 9
Exception from General Requirements Emergency Use of Test Article, cont'd. IRB Federal Regulations Comparison Table 4/24/01 as updated through 10/31/01 Certification must be made by: - The Investigator prior to use, and - A Physician not participating in the research either: (i) Prior to Use, OR (ii) Within 5 working days of use ONLY IF the Investigator determined prior to use that immediate use of the test article is required to preserve the subject's life, and time is not sufficient to obtain the independent determination from the non-participating physician 50.23(a) & (b) Documentation of either of the above shall be submitted to the IRB within 5 working days after use of the test article. 50.23(c) Basic Elements State that the study involves research, an explanation of the purposes of the research, expected duration of the subject s participation, description of the procedures to be followed and identification of experimental procedures. 46.116(a)(1) and 50.25(a)(1) Describe any reasonably foreseeable risks or discomforts to the subject. 46.116(a)(2) and 50.25(a)(2) Describe benefits to the subject or others reasonably expected from the research. 46.116(a)(3) and 50.25(a)(3) Disclose appropriate alternative procedures or courses of treatment, if any, that may be advantageous to the subject. 46.116(a)(4) and 50.25(a)(4) State the extent, if any, to which records identifying the subject will be maintained confidentially. For FDA research, must also state that FDA may inspect records. 46.116(a)(5) and 50.25(a)(5) If more than minimal risk involved, explain availability of compensation and any medical treatment if injury occurs, and if available what they consist of, or where further information may be obtained. 46.116(a)(6) and 50.25(a)(6) Explain whom to contact for answers to pertinent questions about the research and the subject s rights, and whom to contact in the event of a research-related injury to the subject. 46.116(a)(7) and 50.25(a)(7) State that participation is voluntary and refusal to participate will not result in penalty or loss of benefits to which the subject is otherwise entitled, and state the subject s right to withdraw at any time without penalty or loss of benefits to which the subject is otherwise entitled. 46.116(a)(8) and 50.25(a)(8) 10
Additional Elements IRB Federal Regulations Comparison Table 4/24/01 as updated through 10/31/01 When appropriate the following shall be included: State that the particular treatment or procedure may involve risks to subjects (or to embryo/fetus if the subject is or may become pregnant) that are currently unforeseeable. 46.116(b)(1) and 50.25(b)(1) Anticipated circumstances when the investigator may terminate the subject s participation without regard to the subject s consent. 46.116(b)(2) and 50.25(b)(2) Additional costs to the subject that may result from participation. 46.116(b)(3) and 50.25(b)(3) Consequences of a subject s decision to withdraw from the research and procedures for orderly termination of participation. 46.116(b)(4) and 50.25(b)(4) State that the subject will be informed of significant new findings developed during the course of the research that may relate to the subject s willingness to continue participation. 46.116(b)(5) and 50.25(b)(5) Approximate number of subjects involved. 46.116(b)(6) and 50.25(b)(6) Documentation Unless excepted ( 46.117(c) or 56.109(c)) the informed consent shall: - Be written - Approved by the IRB - Signed [and dated - FDA only] by the subject or his/her legally authorized representative at the time of the consent - A copy shall be given to the person signing the form. 46.117(a) and 50.27(a) TYPES OF DOCUMENTATION Long form written consent embodying the elements set forth in 46.116/ 5.025. - May be read to the subject - Must give subject (authorized legal representative) an opportunity to read 46.117(b)(1) and 50.27(b)(1) Short form written consent stating that the elements of 46.116/ 50.25 were presented orally to subject (authorized legal representative). - There must be a witness to the oral presentation - IRB must approve a written summary of the oral presentation - Subject (authorized legal representative) signs short form - Witness signs both the short form and copy of the summary - The person obtaining consent signs a copy of the summary. - A copy of the summary and short form is given to subject (authorized legal representative) 46.117(b)(2) and 50.27(b)(2) 11
Waiver of Written, Signed Informed Consent (Must still obtain Oral Consent) Informed Consent Requirements Modified or Waived IRB Federal Regulations Comparison Table 4/24/01 as updated through 10/31/01 IRB may waive the requirement for written, signed consent if: - The consent document is the only record linking the subject and the research and the principal risk would be potential harm resulting from breach of confidentiality. Subject is informed and his/her wishes govern. 46.117(c)(1) - The research presents no more than minimal risk of harm to subjects and involves no procedures for which written consent is normally required outside the research. 46.117(c)(2) IRB may require the investigator to provide a written statement regarding the research to subjects. 46.117 IRB finds and documents that the research or Not addressed demonstration project could not practicably be carried out without the waiver or change and is conducted by or subject to approval of state or local government officials and designed to study, evaluate, or examine: - public benefit or service programs - procedures for obtaining benefits or services under those programs - possible changes in or alternatives to those programs or procedures, or - possible changes in methods or levels of payment for benefits or services under those programs. 46.116(c) IRB finds and documents that the: - Research involves no more than minimal risk; - Waiver or change in consent will not adversely affect the subject s rights and welfare; - Research could not practicably be carried out without the waiver or change; and - When appropriate, the subjects will be provided additional pertinent information after participation. 46.116(d) 12 IRB may waive the requirement for signed consent if: - For some or all subjects if the requirements for exception from informed consent for emergency research ( 50.24) are met. - The research presents no more than minimal risk of harm to subjects and involves no procedures for which written consent is normally required outside the research. 56.109(c) IRB may require the investigator to provide a written statement regarding the research to subjects. 56.109(d)
13
IRB Exception from Prior Informed Consent for Emergency Research IRB Federal Regulations Comparison Table 4/24/01 as updated through 10/31/01 Not addressed other than to state that the regulations Only applies to protocols under a separate new IND or are not intended to interfere with a physician's IDE that clearly identifies it as possibly including judgment in treating a patient, including emergency subjects who are unable to consent. care. IRB may approve the research without requiring prior informed consent from the subject (with concurrence of a licensed physician not participating in the clinical investigation who is an IRB member or consultant to the IRB) for emergency research if it finds and documents ALL of the following: - Subjects are in a life-threatening situation, available treatments are unproven or unsatisfactory, and the collection of valid scientific evidence is necessary to determine the safety and effectiveness of particular interventions, and - Informed consent cannot be obtained because: (i) Subject's medical condition will not allow them to give their informed consent; (ii) Intervention under investigation must be administered before consent from the subjects' legally authorized representatives is feasible; and (iii) No reasonable way to identify prospectively the individuals likely to become eligible for participation, and - Participation holds out prospect of direct benefit to the subjects because: (i) Subjects are facing a life-threatening situation; and (ii) Animal and other pre-clinical studies conducted support the potential for the research to provide a direct benefit to subjects; and (iii) Risks are reasonable in relation to what is known about the medical condition, the risks and benefits of standard therapy, if any, and known risks and benefits of the proposed research, and 14
IRB Exception from Prior Informed Consent for Emergency Research, cont'd. - Could not practically carry out the clinical investigation without the waiver, and - The investigator has agreed to attempt to contact a legally authorized representative within the defined therapeutic window, and - The IRB has reviewed and approved informed consent document and procedures consistent with 50.25, and - Additional protections, including: (i) Consultation with community representatives where the research will be conducted and from which subjects will be drawn. (ii) Public disclosure of the research and its risks and expected benefits to the communities before initiation (iii) Public disclosure following completion of the research (iv) Establish an independent data monitoring oversight committee, and (v) If informed consent is not feasible from the subject or his/her authorized representative, the investigator will attempt to contact the subject's family member within the therapeutic window and provide written summarization of such efforts to be provided to IRB at continuing review. 50.24(a) IRB responsible for ensuring that procedures are in place to inform, at the earliest feasible opportunity, the subject, or if the subject remains incapacitated, the subject's legally authorized representative, or family member if legal authorized representative is not reasonably available of the following: - The subject's inclusion in the research 15
IRB Exception from Prior Informed Consent for Emergency Research, cont'd. Children Assent of Minor (NE - anyone under 19 who is not emancipated) Assent of Child Not Required - Details of the research and other information contained in the informed consent. - Right to discontinue subject's participation at any time without penalty or loss of benefits to which subject is otherwise entitled. 50.24(b) If IRB does not approve the research because it does not meet the criteria for exception from prior informed consent or due to other relevant ethical concerns, the IRB must document its findings and provide prompt written notice to the investigator and sponsor. 50.24(e) Documentation of IRB's approval or disapproval of the waiver must be retained for at least 3 years after completion of the research. 50.24(c) Defined as a child s affirmative agreement to participate in research. 46.402(b) and [ 50.3(n) as of 4/24/01; also includes that mere failure to object may not, absent affirmative agreement, be construed as consent.] The IRB must determine whether the children (individually or as a group) are capable of providing assent by taking into account: - Age - Maturity - Psychological state of children involved. 46.40(8)(a) and 50.55(a)&(b) as of 4/24/01 IRB determines that the: - Capability of some or all of the children is so limited that they cannot reasonably be consulted, or - Intervention or 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. 46.408(a) and 50.55(c) 16
IRB Waiver of Assent by Child Permission of Parent/Guardian Minimal risk involved Greater than minimal risk involved but presents the prospect of direct benefit to individual subjects Greater than minimal risk & no prospect of direct benefit to individual subjects, but likely to yield generalizable knowledge about the subject's disorder/condition. IRB Federal Regulations Comparison Table 4/24/01 as updated through 10/31/01 Even if IRB finds that the child can give provide assent, it may still waive assent if it finds and documents: - The clinical investigation involves no more than minimal risk to the subjects; - The waiver will not adversely affect the rights and welfare of the subjects; - The clinical investigation could not practicably be carried out without the waiver; and - Whenever appropriate the subjects will be provided with additional pertinent information after participation. 46.408(c) and 46.4116(d); 50.55(d) DHHS Only: If the protocol is designed for conditions or for a subject population for which parental/guardian permission is not a reasonable requirement to protect the subjects, IRB may waive consent (consistent with federal, state or local law) provided an appropriate mechanism for minor subjects is substituted. 46.408(c) The agreement of parent(s) or guardian to their child s/ward s participation in research is required. 46.402(c) and [ 50.3(r) as of 4/24/01] Must be documented in accordance as required by 50.27. 50.55(f) IRB must find [and document - FDA only] that adequate provisions are made for obtaining: - the assent of children capable of providing assent, and - the permission of the parent/guardian. 46.404 and 50.51 IRB may determine that permission of one parent is sufficient. 46.408(b) and 50.55(e)(1) The IRB must find [and document - FDA only] that: - the risk is justified by the anticipated benefit - the relation of the anticipated benefit to the risk is at least as favorable to the subjects as that presented by available alternative approaches; and - adequate provisions are made for obtaining assent and permission. 46.405 and [ 50.52 as of 4/24/01] IRB may determine that permission of one parent is sufficient. 46.408(b) and [ 50.55(e)(1) as of 4/24/01] IRB must find [and document - FDA only] that: - the risk represents a minor increase over minimal risk - the intervention/procedure presents experiences to subjects that are reasonably commensurate with those inherent in their actual or expected medical, dental, psychological, social, or education situations. - the intervention/procedure is likely to yield generalizable knowledge about the subject's disorder/condition of vital importance for the understanding or amelioration of the subject's disorder/condition; and - adequate provisions are made for obtaining assent and permission. 46.406 and [ 50.53 as of 4/24/01] Both parents must give consent, unless one parent is deceased, unknown, incompetent, or not reasonably available or only one parent has legal responsibility for the child. 46.408(b) and [ 50.55(e)(2) as of 4/24/01] 17
Research not otherwise approvable by the IRB that presents an opportunity to understand, prevent, or alleviate a serious problem affecting the health/welfare of children IRB Federal Regulations Comparison Table 4/24/01 as updated through 10/31/01 IRB finds [and documents - FDA only] that the research presents a reasonable opportunity to further the understanding, prevention, ore alleviation of a serious problem affecting the health and welfare of children, and The Secretary for DHHS or Commissioner for FDA research, after consultation with a panel of experts in pertinent disciplines and following opportunity for public review and comment determines either: - that the research satisfies the conditions which allow IRB approval by assent under 46.404, 46.405, 46.406, 50.51, 50.52 or 50.53, or - that the research satisfies the following conditions: (i) the research presents a reasonable opportunity to further the understanding, prevention or alleviation of a serious problem affecting the health or welfare of children. (ii) (iii) The research will be conducted in accordance with sound ethical principles; and Adequate provisions are made for soliciting the assent of children and the permission of their parents or guardians. 46.407; 50.54 Prisoners IRB At least one member shall be a prisoner or prisoner representative. Subpart C, 46.301 et. seq. Pregnant Women and Fetuses Pregnant Women or fetuses prior to delivery Where scientifically appropriate, pre-clinical studies, including studies on pregnant animals, and clinical studies, including studies on non-pregnant women, have been conducted and provide data for assessing potential risks to pregnant women and fetuses; Risk to the fetus is minimal, or any risk to the fetus which is greater than minimal is caused solely by interventions/procedures that hold out the prospect of direct benefit for the woman or the fetus; Any risk is the least possible for achieving the objectives of the research; Recommends that the IRB include an individual knowledgeable about and experienced in working with prisoners. 56.107(a) Not specifically addressed, therefore must follow the Common Rule 18
Woman's consent or the consent of her legally authorized representative is obtained in accord with the informed consent provisions unless altered or waived in accord with 46.101(i) or 46.116(c) or (d); Woman or her legally authorized representative is fully informed regarding the reasonably foreseeable impact of the research on the fetus or resultant child; For minors who are pregnant, assent and permission are obtained in accord with the provisions for assent of minors. No inducements, monetary or otherwise, will be offered to terminate a pregnancy; Individuals engaged in the research will have no part in - Any decisions as to the timing, method, or procedures used to terminate a pregnancy; and - Determining the viability of a fetus. 19
Research involving fetuses after delivery Where scientifically appropriate, pre-clinical and clinical studies have been conducted and provide data for assessing potential risks to fetuses. Individuals providing consent are fully informed regarding the reasonably foreseeable impact of the research on the fetus or resultant child. No inducements, monetary or otherwise, will be offered to terminate a pregnancy. Individuals engaged in the research will have no part in: - Any decisions as to the timing, method, or procedures used to terminate a pregnancy. - Determining the viability of a fetus. 46.205(a) Fetuses of Uncertain Viability: - The IRB must determine that: (i) the research holds out the prospect of enhancing the probability of survival of the particular fetus to the point of viability, and any risk is the least possible for achieving the objectives of the research; or (ii) The purpose of the research is the development of important biomedical knowledge which cannot be obtained by other means and there will be no risk to the fetus resulting from the research; and - Informed Consent of either parent or either parent's legally authorized representative is obtained, unless altered or waived in accord with 46.101(i) or 46.116(c) or (d), 46.205(b) 20
Research involving fetuses after delivery, cont'd. Research involving, after delivery, the placenta, the dead fetus, or fetal material Nonviable Fetuses: May be involved if the following criteria are met - Vital functions of the fetus will not be artificially maintained. - The research will not terminate the heartbeat or respiration of the fetus. - There will be no risk to the fetus resulting from the research, - The purpose of the research is the development of important biomedical knowledge that cannot be obtained by other means, and - Consent of both parents required unless one parent is unable to consent due to incompetence, etc, then the consent of one parent is sufficient. Cannot accept consent of legal representative. Cannot alter or waive consent. 46.205(c) Shall only be conducted in accord with any applicable Federal, State or local laws and regulations regarding such activities. [No known Federal, state or local laws for Nebraska] If information associated with the placenta, the dead fetus or fetal material is recorded for research purposes in a manner such that living individuals can be identified, then those individuals are research subjects and all pertinent consent and IRB approval requirements apply. 46.506 21
Research not otherwise approvable by the IRB which presents an opportunity to understand, prevent, or alleviate a serious problem affecting the health /welfare of pregnant women or fetuses. IRB finds that the research presents a reasonable opportunity to further the understanding, prevention, ore alleviation of a serious problem affecting the health and welfare of children, and The Secretary, after consultation with a panel of experts in pertinent disciplines and following opportunity for public review and comment determines either: - that the research satisfies the conditions which allow IRB approval by assent under 46.204, or - that the research satisfies the following conditions: (i) (ii) (iii) 46.207 the research presents a reasonable opportunity to further the understanding, prevention or alleviation of a serious problem affecting the health or welfare of pregnant women or fetuses. The research will be conducted in accordance with sound ethical principles; and Informed consent will be obtained unless altered or waived under 46.101(i) or 46.116(c) or (d). *Other Agencies: 7 CFR Part 1C (Department of Agriculture); 10 CFR Part 745 (Department of Energy); 14 CFR 1230 (NASA); 15 CFR Part 27 (Department of Commerce); 16 CFR Part 1028 (Consumer Product Safety Commission); 22 CFR 225 (Internal Development Cooperative Agency, Agency for International Development); 24 CFR Part 60 (HUD); 28 CFR Part 46 (DOJ); 32 CFR Part 219 (Department of Defense); 34 CFR Part 97 (Department of Education); 38 CFR Part 16 (Department of Veteran Affairs); 40 CFR Part 26 (EPA); 45 CFR Part 690 (National Science Foundation); 49 CFR Part 11 (Department of Transportation); 21 CFR Parts 50 and 56 (FDA) Mildred L. Johnson, J.D. 4/24/01 (Updated 10/31/01) No representations are made as to the accuracy of the information contained herein. You must go to the relevant statute/regulation to determine the applicability of any of this information to your institution or situation. 22