What You Can Do To Facilitate Efficient IRB Review
Institutional Review Board
1) Definition of Human Subjects Research
2) Tips to facilitate efficient IRB review
3) IRB Terminology Related to Data Collection
4) Criteria for IRB Approval
5) Categories of Exempt Research
6) Categories of Expedited Review
7) Criteria for Waiver of the Elements of Informed Consent
8) Criteria for Waiver of the Written Documentation of Informed Consent
If you have questions about IRB review or procedures, contact the IRB office at (212) 870-3481.
If you have technical questions, contact the RASCAL help line at (212) 870-3480.
accordance with the terms of the Federalwide
Assurance (FWA) that
Research is defined as a systematic investigation, including research development, testing and evaluation, designed to develop or contribute to generalizable knowledge. Activities, which meet this definition, constitute research for purposes of this policy, whether or not they are conducted or supported under a program, which is considered research for other purposes. For example, some demonstration and service programs may include research activities.
Human subject is defined as a living individual about whom an investigator (whether professional or student) conducting research obtains:
through intervention or interaction with the individual, or
(2) identifiable private information.
Federal regulations permit exemption from IRB review for research with human subjects that involve only procedures in one or more of six specific categories (http://ohrp.osophs.dhhs.gov/humansubjects/guidance/45cfr46.htm#46.101). While review of such proposals by the convened IRB is not required, in accordance with the FWA the determination of eligibility for exemption must be made by the IRB. Therefore, all requests for exemption must be submitted via RASCAL for the appropriate determinations.
Proposals for all investigative activities that involve the use of humans or human specimens should be submitted to the IRB via RASCAL, even if the definitions of “research” and/or “human subject” may not appear to be met. In some cases, a determination of “not human subjects research” will be made; funding agencies and/or research sites may require documentation from the IRB of such a determination. A designation of “not human subjects research” does not imply that other institutional or agency approvals are not required, or that methods routinely employed in the ethical conduct of human subjects research should not be utilized.
The IRB encourages investigators, faculty, and staff to call the IRB office for consultation regarding whether or not an activity requires IRB review.
Tips To Facilitate Efficient Protocol Review
Resubmission (in response to Correspondence)
1. Respond via correspondence; be sure to address all questions and concerns.
2. Revise the protocol, consent forms, or other documents as necessary.
3. Reattach all consent forms built in RASCAL that were detached for editing.
4. Archive any superceded attached documents.
5. Remember to approve and resubmit the protocol in addition to answering correspondence.
1. Submit a modification request if there will be any change to an approved protocol. A request via correspondence does not change the protocol.
2. Explain why the modification is requested.
3. Modify relevant fields and documents.
4. Attach new documents.
5. Review personnel section to ensure that the list is still current.
1. Validate far enough in advance to avoid expiration. Expired protocols cannot be reactivated; a new protocol, with a new number, must be submitted if the study is to continue.
2. The IRB can assist with scanning of documents if necessary. Allot enough time for documents to be scanned and returned.
3. Attach the latest versions of all relevant material, e.g., funding proposal (grant or contract), the complete protocol, study instruments [i.e., questionnaire(s) or survey(s)], and non-CU site approvals (e.g., permission to conduct the study).
4. Be aware that a pending modification may impede the submission of a renewal request. Withdraw pending modifications if submitting a renewal and incorporate the changes in the study description. Be sure to explain the changes, either in the study description, or in a cover letter.
5. Submit the renewal sufficiently in advance of the expiration date to allow processing time. If the renewal is submitted, the protocol will not expire.
6. Understand the validation process and the “history” entry.
Renewal of a RASCAL Protocol
Submissions to the IRB are often returned to the investigator for clarification of the nature of data collection. The IRB must be able to determine whether the data are:
a) Anonymous – the identity of the respondent cannot be determined; no links exist between the data and the individual about whom the data are recorded;
b) De-identified – identifiers have been removed from the dataset under consideration; links between the data and the individual about whom the data are recorded exist but are not readily accessible to the researcher at CU;
c) Coded – identifiers have been removed from the dataset under consideration but can readily be replaced through the use of a master list that is accessible to the investigator;
d) Identifiable or non-coded – the identity of the subject is documented, linked or associated with the data.
The manner in which data are recorded and maintained influence the decisions of the IRB, particularly determination of risk level and type of review required. To avoid delay in the review process, investigators should clearly state whether data are anonymous, de-identified, coded, or identifiable. A description of the data to be recorded is particularly helpful.
All protocols involving identifiable or coded data should include mechanisms to ensure confidentiality is maintained.
Criteria for IRB Approval of Research (45 CFR 46.111)
(a) In order to approve research covered by this policy the IRB shall determine that all of the following requirements are satisfied:
(1) Risks to subjects are minimized: (i) by using procedures which are consistent with sound research design and which do not unnecessarily expose subjects to risk, and (ii) whenever appropriate, by using procedures already being performed on the subjects for diagnostic or treatment purposes.
(2) Risks to subjects are reasonable in relation to anticipated benefits, if any, to subjects, and the importance of the knowledge that may reasonably be expected to result. In evaluating risks and benefits, the IRB should consider only those risks and benefits that may result from the research (as distinguished from risks and benefits of therapies subjects would receive even if not participating in the research). The IRB should not consider possible long-range effects of applying knowledge gained in the research (for example, the possible effects of the research on public policy) as among those research risks that fall within the purview of its responsibility.
(3) Selection of subjects is equitable. In making this assessment the IRB should take into account the purposes of the research and the setting in which the research will be conducted and should be particularly cognizant of the special problems of research involving vulnerable populations, such as children, prisoners, pregnant women, mentally disable persons, or economically or educationally disadvantaged persons.
(4) Informed consent will be sought from each prospective subject or the subject's legally authorized representative, in accordance with, and to the extent required by §46.116.
(5) Informed consent will be appropriately documented, in accordance with, and to the extent required by §46.117.
(6) When appropriate, the research plan makes adequate provision for monitoring the data collected to ensure the safety of subjects.
(7) When appropriate, there are adequate provisions to protect the privacy of subjects and to maintain the confidentiality of data.
(b) When some or all of the subjects are likely to be vulnerable to coercion or undue influence, such as children, prisoners, pregnant women, mentally disabled persons, or economically or educationally disadvantaged persons, additional safeguards have been included in the study to protect the rights and welfare of these subjects.
Categories of Exempt Research (45 CFR 46.101(b))
(b) Unless otherwise required by Department or Agency heads, research activities in which the only involvement of human subjects will be in one or more of the following categories are exempt from this policy:1
(1) Research conducted in established or commonly accepted educational settings, involving normal educational practices, such as (i) research on regular and special education instructional strategies, or (ii) research on the effectiveness of or the comparison among instructional techniques, curricula, or classroom management methods.
(2) Research involving the use of educational tests (cognitive, diagnostic, aptitude, achievement), survey procedures, interview procedures or observation of public behavior, unless:
(i) information obtained is recorded in such a manner that human subjects can be identified, directly or through identifiers linked to the subjects; and
(ii) any disclosure of the human subjects' responses outside the research could reasonably place the subjects at risk of criminal or civil liability or be damaging to the subjects' financial standing, employability, or reputation.
Research involving the use of educational tests (cognitive, diagnostic,
aptitude, achievement), survey procedures, interview procedures, or observation
of public behavior that is not exempt under paragraph (b)(2) of this section,
(i) the human subjects are elected or appointed public officials or candidates for public office; or
(ii) Federal statute(s) require(s) without exception that the confidentiality of the personally identifiable information will be maintained throughout the research and thereafter.
(4) Research involving the collection or study of existing data, documents, records, pathological specimens, or diagnostic specimens, if these
sources are publicly available or if the information is recorded by the investigator in such a manner that subjects cannot be identified, directly or through identifiers linked to the subjects.
(5) Research and demonstration projects which are conducted by or subject to the approval of Department or Agency heads, and which are
designed to study, evaluate, or otherwise examine:
(i) Public benefit or service programs;
(ii) procedures for obtaining benefits or services under those programs;
(iii) possible changes in or alternatives to those programs or procedures; or
(iv) possible changes in methods or levels of payment for benefits or services under those programs.
(6) Taste and food quality evaluation and consumer acceptance studies, (i) if wholesome foods without additives are consumed or (ii) if a food is consumed that contains a food ingredient at or below the level and for a use found to be safe, or agricultural chemical or environmental contaminant at or below the level found to be safe, by the Food and Drug Administration or approved by the Environmental Protection Agency or the Food Safety and Inspection Service of the U.S. Department of Agriculture.
Categories of Research That May Be Reviewed by the
Institutional Review Board (IRB) through an
Expedited Review Procedure1
(A) 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 activities listed should not be deemed to be of minimal risk simply because they are included on this list. Inclusion on this list merely means that the activity is eligible for review through the expedited review procedure when the specific circumstances of the proposed research involve no more than minimal risk to human subjects.
(B) The categories in this list apply regardless of the age of subjects, except as noted.
(C) 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= financial standing, employability, insurability, reputation, or be 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.
(D) The expedited review procedure may not be used for classified research involving human subjects.
(E) IRBs are reminded that the standard requirements for informed consent (or its waiver, alteration, or exception) apply regardless of the type of review--expedited or convened--utilized by the IRB.
(F) Categories one (1) through seven (7) pertain to both initial and continuing IRB review.
(1) Clinical studies of drugs and medical devices only when condition (a) or (b) 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 investigational 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, nonpregnant adults who weigh 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 children2, considering the age, weight, and health of the subjects, the collection procedure, the amount of blood to be collected, and 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 nondisfiguring 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 collected 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 nonresearch purposes (such as medical treatment or diagnosis). (NOTE: Some research in this category may be exempt from the HHS regulations for the protection of human subjects. 45 CFR 46.101(b)(4). This listing refers only to research that is not exempt.)
(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. (NOTE: Some research in this category may be exempt from the HHS regulations for the protection of human subjects. 45 CFR 46.101(b)(2) and (b)(3). This listing refers only to research that is not exempt.)
(8) Continuing review of research previously approved by the convened IRB 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.
(9) Continuing review of research, not conducted under an investigational new drug application or investigational device exemption where categories two (2) through eight (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.
1 An expedited review procedure consists of a review of research involving human subjects by the IRB chairperson or by one or more experienced reviewers designated by the chairperson from among members of the IRB in accordance with the requirements set forth in 45 CFR 46.110.
2 Children are defined in the HHS regulations 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." 45 CFR 46.402(a).
Waiver of Elements of Informed Consent (45 CFR 46.116)
(c) An IRB may approve a consent procedure which does not include, or which alters, some or all of the elements of informed consent set forth above, or waive the requirement to obtain informed consent provided the IRB finds and documents that:
(1) the research or demonstration project is to be conducted by or subject to the approval of state or local government officials and is designed to study, evaluate, or otherwise examine: (i) public benefit or service programs; (ii) procedures for obtaining benefits or services under those programs; (iii) possible changes in or alternatives to those programs or procedures; or (iv) possible changes in methods or levels of payment for benefits or services under those programs; and
(2) the research could not practicably be carried out without the waiver or alteration.
(d) An IRB may approve a consent procedure which does not include, or which alters, some or all of the elements of informed consent set forth in this section, or waive the requirements to obtain informed consent provided the IRB finds and documents that:
(1) the research involves no more than minimal risk to the subjects;
(2) the waiver or alteration will not adversely affect the rights and welfare of the subjects;
(3) the research could not practicably be carried out without the waiver or alteration; and
(4) whenever appropriate, the subjects will be provided with additional pertinent information after participation.
Waiver of Written Documentation of Informed Consent (45 CFR 46.117)
(c) An IRB may waive the requirement for the investigator to obtain a signed consent form for some or all subjects if it finds either:
(1) That 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) That 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.