IS THIS RESEARCH? EXEMPT? EXPEDITED?

Vivienne Carrasco, MPH, CIP

Senior IRB Regulatory Analyst

Social & Behavioral Sciences IRB

Human Subject Research Office

ASSURANCE AND REGULATIONS

• The University of Miami requires review and approval by an IRB of all research involving human subjects, if any UM faculty, staff, or students are engaged as key personnel in that research (FWA Policy 2.4, Revised May 10, 2011)… conducted in accordance with its FWA (binding agreement with DHHS, OHRP and FDA, when applicable).– FWA authorizes review of research regardless of funding

source.• DHHS Code of Federal Regulations 45 CFR 46 (“the

Common Rule”) and its subparts B, C and D. – Additional FDA regulations found in 21 CFR 50, 54, 56,

312, 600, and 812.ALL HUMAN SUBJECT RESEARCH AT UM= IRB APPROVAL

IS IT RESEARCH?

• Is the activity a systematic investigation designed to develop or contribute to generalizable knowledge?– Including research development, testing, and evaluation.– Systemic design generally utilizing a scientific approach or protocol. – Research can encompass studies that are experimental or

observational, surveys, tests and recordings whether or not they are conducted or supported under a program which is considered research for other purposes.

– Clear intent to contribute to generalized knowledge with a scientific protocol.

– Research may or may not include public health monitoring activities.

IS IT HUMAN SUBJECT?• A living individual about whom an investigator

conducting research obtains:– 1. Data through intervention or interaction with the

individual, or– 2. Identifiable private information.

• FDA: Participates in an investigation, either as an individual on whom or on whose specimen a test article is used or as a control.

• Are these human subject?– Decedent information?– Secondary Subjects?– Product Information?

INTERACTIONS AND INTERVENTIONS?

• Interactions– Communication– Interpersonal Contact– Online

• Interventions– Physical procedures– Manipulations of the participant– Manipulations of the participant’s environment

IDENTIFIABLE INFORMATION

• Identifiable– Individual’s identity is or may readily be ascertained by the

investigator or associated with the information.• Contains one or more data elements that can be combined with other

reasonably available information to identify an individual. • Judgment of HSRO/ IRB Member• HIPAA Standards

– “Obtaining” of identifiable private information or identifiable specimens for research purposes constitutes human subject research.

– Research is not considered to involve human subjects when such research involves only coded private information or specimens if both of the following conditions are met: (1) not collected specifically for the currently proposed AND (2) investigator(s) cannot readily ascertain the identity of the individual(s).

PRIVATE INFORMATION

• Private– About behavior that occurs in a context in which an individual

can reasonably expect that no observation or recording is taking place, OR

– Provided for specific purposes by an individual and the individual can reasonably expect will not be made public.

• Medical records, student records?

WHAT ABOUT QA ACTIVITIES AND PROGRAM EVALUATIONS?• QA activities that are designed solely for internal

program evaluation purposes, with no external application or generalization, usually do not constitute human subject research and usually do not require IRB review.

• QA activities constitute human subject research and require IRB review, when they are designed or intended, at least in part, to develop or contribute to generalizable knowledge.

• Program evaluations are generally not considered human subject research because the intent is to implement a program and evaluate its effectiveness.

CASE STUDY #1• Analyze de-identified survey data that was

already collected (retrospectively) to assess knowledge among Haitian women about cervical cancer screening, HPV, HPV vaccine and compare two different regions in Haiti.– Activity is designed to develop or contribute to

generlizable knowledge.– Data cannot be tracked back to the individual (records

anonymized).

CASE STUDY #2• This study will determine whether alterations in

the levels of enzymes that control gene expression without directly altering DNA sequences are associated with a history of child abuse. Specimens are obtained from postmortem human brain tissue.– Intended for generalizable knowledge.– Is it a living individual about whom?

CASE STUDY #3• This study will assess the nature of social support and the

quality of life (QOL) of cancer patients and their family caregivers who use the American Cancer Society sponsored, free, temporary housing facility, Hope Lodge. ACS will provide the PI with a de-identified data set for analysis. Documentation has been provided from ACS that the key to unlock the identifiers will not be released.• Intended for generalizable knowledge.• Coded data- documentation from ACS that link will not be

provided.

CASE STUDY #4• This study intends to show that there needs to be more

emphasis on pedestrian and bicycle safety in drivers education classes. This research can be used as the basis to make changes in the Florida Drivers Handbook and ideally, ultimately change the Florida state drivers exam policies. This study will involve a survey that has no identifiable information. The survey asks questions solely about the Florida Driver’s Manual.• Intended for generalizable knowledge• Is this a human subject “about whom?”

CASE STUDY #5• The goal of this study is to provide technical and scientific

support to the governments of Colombia, Peru, Panama and Guatemala and to generate knowledge required to strengthen their current malaria control measures. Another goal of this project is to facilitate malaria elimination programs in the region. The roles of the UM PIs are limited to coordinating the project, analyzing de-identified data and providing statistical data that is de-identified.– Intended for generalizable knowledge.– Is there intervention/ interaction?– Is there private identifiable data?

CASE STUDY #6UM PI will collaborate with University X by providing expertise, aiding in the creation of study materials (protocol, guidelines, informed consents etc.), aid in recruitment by providing expertise (not physically doing recruitment), and collaborate in writing journal articles. NO activities in the field will be conducted by the University of Miami. – Intended for generalizable knowledge.– Is there intervention/ interaction?– Is there private identifiable data? – The questionnaire contained personal questions to be asked of the

daughter about her father and other family members, covering topics such as abnormal genitalia, mental illness, and substance abuse.

CASE STUDY #7The questionnaire study asks personal questions to of a daughter about her father and other family members, covering topics such as abnormal genitalia, mental illness, and substance abuse. – Intended for generalizable knowledge.– Intervention/ interaction.– Private information.– Who is the “about whom?”

HOW CAN IRB REVIEW BE DONE AFTER DATA HAVE BEEN

COLLECTED?• IRB approval for the research use of

previously collected identifiable data collected for non-research purposes, or

• Verification from the IRB that the research use of non-identifiable data is exempt or does not involve human subjects

WILL I NEED APPROVAL FOR A MEDICAL CASE REPORT?

• It is a description of medical observations or an interesting medical condition, innovative treatment, presentation, disease progression or outcome

• It relates to three or fewer patients• The patients must be those treated by the clinician

preparing the report• The report describes observations and is not

presented as a systematic investigation designed to contribute to generalizable knowledge

• The report usually contains no data analysis or testing of a hypothesis

IS IT “EXEMPT”?

EXEMPT FROM WHAT?• Under Federal regulations, certain categories of activity

are considered research, but can be declared exempt from further review by the IRB. This determination is made by the IRB itself, not the researcher. While the IRB might decide under these rules that a particular project is exempt from further review, it is still considered research and a complete application must be submitted in order for the research to be granted the exemption.– [Exemptions b(1-6)] [45 CFR 46.101(b)]– Exemption categories 1-5 are not applicable to research

governed by FDA regulations (21 CFR 50.20)

CATEGORIES OF EXEMPT RESEARCH

1. Research conducted in established educational settings, involving normal educational practices

2. Research involving the use of educational tests, survey procedures, interview procedures, or observation of public behavior

3. Same as # 2, but covers elected officials

4. Research involving use of existing data

5. Research and demonstration projects by approval of agency heads

6. Taste and food quality

• IRB Chair or an IRB member designated by the Chair

• Exemption documented in the IRB records (including category)

• Decision communicated in writing to investigator

IRB DETERMINATIONS OF EXEMPTION

WELL THEN, CAN MY STUDY BE EXPEDITED?

• No more than Minimal Risk. • Must fit one or more of the categories on the

Expedited Review Categories List [Authority: 45 CFR 46.110 and 21 CFR 56.110]

• Minor changes in previously approved research during the period for which the approval is authorized

WHAT RESEARCH ACTIVITIES ARE ELIGIBLE FOR EXPEDITED

REVIEW?

MINIMAL RISK

…means that the 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 tests. (45 CFR 46.102(i))

EXPEDITED CATEGORIES(NEW OR CONTINUING)

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; OR

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 children, 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.

EXPEDITED CATEGORIES (CONT)

(NEW OR CONTINUING)3. Prospective collection of biological specimens or other biological information for research purposes by noninvasive means. Examples include but are not limited to:

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.

k) Vaginal swabs that do not go beyond the cervical os

l) Rectal swabs that do not go beyond the rectum

m) Nasal swabs that do not go beyond the nares

EXPEDITED CATEGORIES (CONT)

(NEW OR CONTINUING)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. 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 subjects or an invasion of the subjects’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

EXPEDITED CATEGORIES (CONT)

(NEW OR CONTINUING)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: This category includes research involving materials that were previously collected (retrospective/existing) for either non-research or research purposes, provided that any materials collected for research were not collected for the currently proposed project.

– NOTE: This category permits research on materials collected prospectively but only if such materials are collected solely for non-research purposes.

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

7. Research on individual or group characteristics or behavior or research employing survey, interview, oral history, focus group, program evaluation, human factors evaluation, or quality assurance methodologies.

EXPEDITED CATEGORIES (CONT)

(CONTINUING ONLY)8. Continuing review of research previously approved by the convened IRB as follows:

a) Wherei. 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.

CASE #8:

• This study proposes to collect data on 5,000 UMHC patients with ICU admissions from 2003-2004 to compare statistical models of risk adjustment and mortality prediction. There is no direct patient contact and scrambled patient identifiers are used to link data from various sources.

CASE #9

• An investigator proposes a medical record review of 200 charts. No identifiers will be recorded. The data will be collected during the upcoming year as new patients join the Endocrinology clinic. Does the study qualify for exemption under 45 CFR 16.101(b)(4)?

IRB EXPEDITED DETERMINATIONS

• IRB Chair or one or more experienced reviewers designated by the Chair from among members of the IRB

• Notification of IRB members & PI• Subject to continuing review based on IRB

approval date

SO THEN, WHAT IS IP3R?

INNOVATIVE PRACTICES FOR THE PROTECTION OF

PARTICIPANTS IN RESEARCH

“to facilitate applicable research, streamline processes, promote efficiency, reduce bureaucracy and minimize administrative burdens to investigators and reviewers while assuring that institutional human protection resources are allocated to areas where such resources are most needed”

MULTI-YEAR APPROVALS• Not applicable for studies when they:

– are under federal jurisdiction pursuant to 45 CFR 46 because support for the study or for training purposes related to the study is derived from federal sources

– are under FDA jurisdiction pursuant to 21 CFR 50 because the study includes FDA regulated components (drugs, devices or biologics)

– are under state or local regulations that relate to the ethical standards of research involving human subjects

– are in receipt of NIH-issued Certificates of Confidentiality– are under federally related obligations or contractual restrictions– pose more than minimal risk to participants as determined by

the IRB

PROCESS FOR GRANTING MULTI-YEAR APPROVALS

tudy receives Expedited Review

Approval Letter is sent to the study team

The reviewer recommends to the convened IRB

By majority vote, the IRB grants 3-year approval

Revised Approval Letter is sent to the study team

THE PI AFFIRMATION(YEARS 1 & 2)

• The study protocol is unchanged from that granted multi-year approval by the IRB

• The risk to subjects is unchanged• No study-related, serious adverse events

occurred