Exempt and Expedited Reviews Exempt and Expedited Reviews What Requires IRB and R&D What Requires IRB and R&D

ApprovalsApprovalsKimberly Summers, PharmDKimberly Summers, PharmD

Deputy ACOS for Research and DevelopmentDeputy ACOS for Research and DevelopmentSouth Texas Veterans Health Care SystemSouth Texas Veterans Health Care System

Research & Development ServiceResearch & Development Service

OverviewOverview

• Determining if a Protocol is Human Subjects Determining if a Protocol is Human Subjects ResearchResearch

• Types of Human Subjects Research ReviewsTypes of Human Subjects Research Reviews– ExemptExempt– ExpeditedExpedited– Convened BoardConvened Board

• What needs IRB Approval?What needs IRB Approval?• What needs R&D Approval?What needs R&D Approval?• SummarySummary

What is Human Subjects What is Human Subjects Research?Research?

• There are There are twotwo definitions of Human definitions of Human Research that must be considered. Research that must be considered. – An activity may meet either definitionAn activity may meet either definition– Definition from Department of Health and Definition from Department of Health and

Human Services (DHHS), orHuman Services (DHHS), or– Definition from the Food and Drug Definition from the Food and Drug

Administration (FDA)Administration (FDA)

DHHS Definition of ResearchDHHS Definition of Research• Is the activity research?Is the activity research?

– The distinction between practice and research is blurred, partly The distinction between practice and research is blurred, partly because they because they often occur togetheroften occur together, partly because , partly because departures departures from standard practice are called experimentalfrom standard practice are called experimental (not carefully (not carefully defined).defined).

– For the most part, the term "practice" refers to interventions that For the most part, the term "practice" refers to interventions that are designed are designed solely to enhance the well-being of an individualsolely to enhance the well-being of an individual patient or client and that have a reasonable expectation of patient or client and that have a reasonable expectation of success. success.

– Research designates an activity designed to test an hypothesis, Research designates an activity designed to test an hypothesis, permit conclusions to be drawn, and thereby to develop or permit conclusions to be drawn, and thereby to develop or contribute to generalizable knowledge (expressed, for example, contribute to generalizable knowledge (expressed, for example, in theories, principles, and statements of relationships).in theories, principles, and statements of relationships).

– Research is usually described in a Research is usually described in a formal protocolformal protocol that sets forth that sets forth an objective and a set of procedures designed to reach that an objective and a set of procedures designed to reach that objective. objective.

DHHS Definition of Human DHHS Definition of Human SubjectsSubjects

• Does the research involve human Does the research involve human subjects?subjects?– A human subject is:A human subject is:

• A living individual about whom an investigator A living individual about whom an investigator (whether professional or student) conducting (whether professional or student) conducting research obtains research obtains

– Data through Data through interventionintervention or or interactioninteraction with the with the individual, individual, oror

– Identifiable private informationIdentifiable private information

FDA Definition of ResearchFDA Definition of Research

• Is the activity a clinical investigation Is the activity a clinical investigation (research)?(research)?– If the activity involves an FDA regulated If the activity involves an FDA regulated test test

articlearticle • Use of a drug, other than the use of a marketed drug in the Use of a drug, other than the use of a marketed drug in the

course of medical practice; course of medical practice; oror• Use of a device to evaluate safety or effectiveness of that Use of a device to evaluate safety or effectiveness of that

device; device; oror• Data from the activity will be submitted to, or held for Data from the activity will be submitted to, or held for

inspection by, the FDA in support of a marketing or research inspection by, the FDA in support of a marketing or research application for an FDA-regulated productapplication for an FDA-regulated product

FDA Definition of Human ResearchFDA Definition of Human Research

Does the research involve human subjects?Does the research involve human subjects?– The test article will be used on one or more The test article will be used on one or more

humans; humans; oror– The data obtained from controls will be submitted The data obtained from controls will be submitted

to, or held for inspection by the FDA in support of a to, or held for inspection by the FDA in support of a marketing or research application for an FDA-marketing or research application for an FDA-regulated product; regulated product; oror

– The data obtained from use of a device on tissue The data obtained from use of a device on tissue specimens will be submitted to, or held for specimens will be submitted to, or held for inspection by, the FDA in support of a marketing inspection by, the FDA in support of a marketing application or research application for an FDA application or research application for an FDA regulated product.regulated product.

Definition of VA Research• Research sponsored by the VA• Research conducted using any property or facility of

STVHCS• Research conducted by or under the direction of any

salaried or without compensation (WOC) employee of the STVHCS during and in connection with her/his STVHCS responsibilities

• Funds for the research activities are managed by the STVHCS or Biomedical Research Foundation of South Texas

• Research which recruits subjects at the STVHCS or uses the STVHCS's nonpublic information to identify or contact human research subjects for research purposes

• Is the activity research?

• Does the activity involve human subjects?

• Is the activity VA research?

• Where does Quality Improvement (QI) fit?

HHS/OHRP Definition of QIHHS/OHRP Definition of QI

• Activities whose purposes are limited to:Activities whose purposes are limited to:– (a) implementing a practice to improve the (a) implementing a practice to improve the

quality of patient care, or quality of patient care, or – (b) collecting patient or provider data (b) collecting patient or provider data

regarding the implementation of the practice regarding the implementation of the practice for clinical, practical, or administrative for clinical, practical, or administrative purposespurposes

IRB Definition of QI• Systematic, data-guided activities designed to bring

about immediate, positive changes in the delivery of health care in particular settings

• QI involves deliberate actions to improve care, guided by data reflecting the effects (e.g., types of practical problem solving; an evidence-based management style; the application of science of how to bring about system change; review of aggregate data at the patient/provider/unit/ organizational level to identify a clinical or management change that can be expected to improve care).

• Not designed to contribute to generalizable knowledge.

QI or Research?QI or Research?

• A group of affiliated hospitals implements A group of affiliated hospitals implements a procedure known to reduce pharmacy a procedure known to reduce pharmacy prescription error rates, and collects prescription error rates, and collects prescription information from medical prescription information from medical charts to assess adherence to the charts to assess adherence to the procedure and determine whether procedure and determine whether medication error rates have decreased as medication error rates have decreased as expected. expected.

• Designed to test an hypothesis?Designed to test an hypothesis?• Designed to permit conclusions to be drawn?Designed to permit conclusions to be drawn?• Designed to develop or contribute to Designed to develop or contribute to

generalizable knowledge?generalizable knowledge?• Implementing a practice to improve the quality Implementing a practice to improve the quality

of patient care?of patient care?• Collecting patient or provider data regarding Collecting patient or provider data regarding

the implementation of the practice for clinical, the implementation of the practice for clinical, practical, or administrative purposespractical, or administrative purposes

QI or Research?• A clinic increasingly utilized by geriatric patients A clinic increasingly utilized by geriatric patients

implements a widely accepted capacity implements a widely accepted capacity assessment as part of routine standard of care in assessment as part of routine standard of care in order to identify patients requiring special services order to identify patients requiring special services and staff expertise. The clinic expects to audit and staff expertise. The clinic expects to audit patient charts in order to see if the assessments patient charts in order to see if the assessments are performed with appropriate patients, and will are performed with appropriate patients, and will implement additional in-service training of clinic implement additional in-service training of clinic staff regarding the use of the capacity assessment staff regarding the use of the capacity assessment in geriatric patients if it finds that the assessments in geriatric patients if it finds that the assessments are not being administered routinely. are not being administered routinely.

• An abstract of the data will be presented at a VA An abstract of the data will be presented at a VA National ConferenceNational Conference

• Does the activity represent a systematic investigation in which the person engaged in such activities intended to develop or contribute to generalizable knowledge?

QI and Publishing the Results• The intent to publish is an insufficient criterion

only for determining whether a quality improvement activity involves research

• Was the original intent to contribute to “generalizable knowledge”

• If the purpose of the activity changes as If the purpose of the activity changes as preliminary results are analyzed and the intent preliminary results are analyzed and the intent becomes to produce information that could be becomes to produce information that could be generalized it may be researchgeneralized it may be research

• Conversely, a quality improvement project may involve research even if there is no intent to publish the results

QI or Research?• A provider wants to review the records of transplant

patients that were using medication X in order to determine if the medication has had an effect on the stem cell collection.

• Patients will be identified by computer mediated search of medical records (CPRS) of transplant patients that were using medication X during the transplant procedure.

• All collected data will be de-identified after extraction from CPRS

• If an effect of recent medication use on stem cell collection efficacy is identified, then a clinical protocol will be developed for IRB submission to have a more complete look at the records of these patients to include all other aspects of their diagnosis, care, other medications etc.

• Designed to test an hypothesis?Designed to test an hypothesis?• Designed to permit conclusions to be drawn?Designed to permit conclusions to be drawn?• Designed to develop or contribute to Designed to develop or contribute to

generalizable knowledge?generalizable knowledge?• Implementing a practice to improve the quality Implementing a practice to improve the quality

of patient care?of patient care?• Collecting patient or provider data regarding Collecting patient or provider data regarding

the implementation of the practice for clinical, the implementation of the practice for clinical, practical, or administrative purposespractical, or administrative purposes

• Preparatory to Research?Preparatory to Research?

• Pilot Project?Pilot Project?

““Preparatory to Research”Preparatory to Research”

• Obtaining aggregate data or reviewing individually-identifiable Obtaining aggregate data or reviewing individually-identifiable information by a VA investigator to prepare a research protocol does information by a VA investigator to prepare a research protocol does not require IRB or R&D approvalnot require IRB or R&D approval– Examples: to generate a hypothesis, determine feasibility to Examples: to generate a hypothesis, determine feasibility to

conduct a study, determine the number of eligible patientsconduct a study, determine the number of eligible patients• In the VA, using individually-identifiable information to contact In the VA, using individually-identifiable information to contact

potential research subjects as part of recruitment into a research potential research subjects as part of recruitment into a research protocol is NOT considered “preparatory to research”protocol is NOT considered “preparatory to research” – VA regulations differ from those described in the HIPAA Privacy VA regulations differ from those described in the HIPAA Privacy

RuleRule– IRB and R&D Committee review and approval requiredIRB and R&D Committee review and approval required– IRB approved waiver of authorization and waiver of informed IRB approved waiver of authorization and waiver of informed

consent requiredconsent required

““Pilot Studies”Pilot Studies”

• An initial or preliminary investigation designed to An initial or preliminary investigation designed to test research hypotheses, gather data, and test research hypotheses, gather data, and validate the scientific approach and methodology validate the scientific approach and methodology for a particular area of research interestfor a particular area of research interest

• Pilot studies are NOT considered part of the Pilot studies are NOT considered part of the activities “preparatory to research”activities “preparatory to research”– IRB and R&D Committee review and approval IRB and R&D Committee review and approval

requiredrequired• Small exploratory study vs pilot studySmall exploratory study vs pilot study

Types of ReviewTypes of Review

• NotNot research research oror research not involving research not involving “human subjects”“human subjects”

• Human research eligible for Human research eligible for exemptionexemption• Human research (non-exempt) eligible for Human research (non-exempt) eligible for

expeditedexpedited IRB review IRB review• Human research (non-exempt) that is not Human research (non-exempt) that is not

eligible for expedited review and must be eligible for expedited review and must be reviewed by a reviewed by a convenedconvened meeting of the meeting of the IRBIRB

Exempt ReviewExempt Review

• Study does not extend beyond minimal Study does not extend beyond minimal risk, as defined by federal regulationsrisk, as defined by federal regulations

– ““The probability and magnitude of harm or The probability and magnitude of harm or discomfort anticipated in the research are not discomfort anticipated in the research are not greater in and of themselves than those greater in and of themselves than those ordinarily encountered in daily life or during the ordinarily encountered in daily life or during the performance of routine physical or performance of routine physical or psychological examinations or tests.”(45 CFR psychological examinations or tests.”(45 CFR 46.102(i))46.102(i))

Exempt ReviewExempt Review• Activities meet a category for exempt research in Activities meet a category for exempt research in

DHHS regulations for human subjects protectionsDHHS regulations for human subjects protections– Educational ResearchEducational Research– Research using surveys, interviews, educational testingResearch using surveys, interviews, educational testing– Research using surveys, interviews, educational testing Research using surveys, interviews, educational testing

involving elected/appointed public officials or where involving elected/appointed public officials or where confidentiality of data is protected by federal statueconfidentiality of data is protected by federal statue

– Research using existing specimens/dataResearch using existing specimens/data– Research or demonstration projects approved by Federal Research or demonstration projects approved by Federal

Department /Agency HeadDepartment /Agency Head– Taste and food quality evaluation or consumer acceptanceTaste and food quality evaluation or consumer acceptance

Exempt Research May NOT Exempt Research May NOT Involve…Involve…

• Prisoners as participantsPrisoners as participants• Test articles subject to FDA regulations Test articles subject to FDA regulations

except in accordance with 45 CFR 101(b)(6) except in accordance with 45 CFR 101(b)(6) Taste and food quality evaluation and Taste and food quality evaluation and consumer acceptance studiesconsumer acceptance studies

• Involve children under category 2(b) UNLESS Involve children under category 2(b) UNLESS research involves observations of public research involves observations of public behavior AND the investigators do not behavior AND the investigators do not participate in the activities being observedparticipate in the activities being observed

Research Using Existing Research Using Existing Specimens / DataSpecimens / Data

• An investigator will review CPRS records for all An investigator will review CPRS records for all subjects who have received a heart catherizationsubjects who have received a heart catherization

• The following elements will be extracted from the The following elements will be extracted from the medical record: risk factors, co-morbidities, medical record: risk factors, co-morbidities, demographic information, additional cardiac demographic information, additional cardiac procedures, number of hospitalizations, procedures, number of hospitalizations, concomitant medications, dates of concomitant medications, dates of hospitalizations, dates of deathhospitalizations, dates of death

• All extracted data elements will be de-identifiedAll extracted data elements will be de-identified

Exempt Research Involving Exempt Research Involving Existing DataExisting Data

• Does the research qualify for exempt status?Does the research qualify for exempt status?• Is a HIPAA Waiver of Authorization required?Is a HIPAA Waiver of Authorization required?• If the information collected is de-indentified If the information collected is de-indentified

can a code be maintained separate from the can a code be maintained separate from the research data?research data?

• Are amendments required for exempt Are amendments required for exempt research?research?

Individually-identifiable - Data HIPAA IdentifiersIndividually-identifiable - Data HIPAA Identifiers1. Names1. Names22. ALL. ALL geographic subdivisions geographic subdivisions smaller than the statesmaller than the state3. All elements of dates 3. All elements of dates smaller than a year smaller than a year and all ages over 89 and all ages over 894. Phone numbers4. Phone numbers5. Fax numbers 5. Fax numbers 6. E-mail addresses6. E-mail addresses7. Social Security numbers (SSN)7. Social Security numbers (SSN)8. Medical record number8. Medical record number9. Health plan beneficiary numbers9. Health plan beneficiary numbers10. Any other account numbers 10. Any other account numbers 11. Certificate/license numbers11. Certificate/license numbers12. Vehicle identifiers and license plate numbers12. Vehicle identifiers and license plate numbers13. Device identifiers and serial numbers13. Device identifiers and serial numbers14. WEB URL's14. WEB URL's15. Internet IP address numbers15. Internet IP address numbers16. Biometric identifiers (fingerprint, voice prints, retina scan, etc)16. Biometric identifiers (fingerprint, voice prints, retina scan, etc)17. Full face photographs or comparable images17. Full face photographs or comparable images18. Any other unique number, characteristic or code18. Any other unique number, characteristic or code

Common RuleCommon Rule

• Identity of the subject can not be readily Identity of the subject can not be readily ascertained by information remaining after ascertained by information remaining after removal of all 18 HIPAA identifiersremoval of all 18 HIPAA identifiers

• VA regulations require de-identification by VA regulations require de-identification by both HIPAA regulations and the Common both HIPAA regulations and the Common RuleRule

Expedited ReviewExpedited Review• Study does not extend beyond minimal risk, as Study does not extend beyond minimal risk, as

defined by federal regulationsdefined by federal regulations• Activities meet a category in DHHS guidance for Activities meet a category in DHHS guidance for

expedited reviewexpedited review• May not be used where identification of the May not be used where identification of the

subjects and/or their responses would reasonably subjects and/or their responses would reasonably place them at risk of criminal or civil liability or be place them at risk of criminal or civil liability or be damaging to the subjects’ financial standing, damaging to the subjects’ financial standing, employability, insurability, reputation, or employability, insurability, reputation, or stigmatizing, unless reasonable and appropriate stigmatizing, unless reasonable and appropriate protections will be implemented so that risks protections will be implemented so that risks related to invasion of privacy and breach of related to invasion of privacy and breach of confidentiality are no greater than minimalconfidentiality are no greater than minimal

Categories for Expedited Review• FDA regulated

– Approved drugs– In-vitro diagnostic testing– FDA approved devices being used in an approved manner– FDA approved device being used in an unapproved manner

• Collecting blood samples– In healthy, non-pregnant adults– From unhealthy adults, pregnant adults, or children

• Collecting biological specimens (non-invasive)• Non-invasive data collection• Clinical (non-research) materials• Recordings• Survey / Interview, program evaluation

Medical Record/Chart Review/Clinical Database Medical Record/Chart Review/Clinical Database Research StudiesResearch Studies

• May qualify for either Exempt or Expedited May qualify for either Exempt or Expedited reviewreview– Will you be maintaining identifying information? Will you be maintaining identifying information? – If retaining identifying information (name, medical record If retaining identifying information (name, medical record

number, etc.) for any amount of time, provisions must be in number, etc.) for any amount of time, provisions must be in place to maintain confidentiality of subject informationplace to maintain confidentiality of subject information

• The IRB reviewer of the research makes the The IRB reviewer of the research makes the final determination as to whether research is final determination as to whether research is exempt or expeditedexempt or expedited

What Needs IRB Approval?

• Answer: All Human Research must be reviewed and approved by the IRB before research is started

• What is Human Research?– Answer: There are two definitions of Human

Research that must be considered. If the activity meet either definition, it must be approved by the IRB

– Definition from Department of Health and Human Services (DHHS), or

– Definition from the Food and Drug Administration (FDA)

IRB GuidanceIRB Guidance

What Needs R&D Approval?

• Answer: All exempt, expedited, or convened IRB reviewed research protocols that meet the definition of “VA Research”

• R&D submission process and forms are the same for all types of research

VA R&D ApprovalVA R&D Approval

– Must have R&D approval letter prior to any of the following being conducted at the VA

• Recruitment • Obtaining informed consent

– Having an IRB approved VA consent form does NOT constitute R&D approval

• Enrollment• Providing patient follow up

– An IRB approval letter does NOT constitute R&D approval

ConclusionConclusion

• Human research and quality improvement are Human research and quality improvement are similar but different activitiessimilar but different activities– Distinction between practice and research is often Distinction between practice and research is often

times blurredtimes blurred – Questions about Quality Improvement activities Questions about Quality Improvement activities

should be directed to the IRBshould be directed to the IRB and the VA R&D office• IRB approval is required for all human subjects IRB approval is required for all human subjects

researchresearch• VA R&D approval is required for any research VA R&D approval is required for any research

meeting the definition of VA researchmeeting the definition of VA research

Questions?Questions?Kimberly Summers, PharmDKimberly Summers, PharmD

Office: (210) 617-5300 ext 15969Office: (210) 617-5300 ext 15969Email: kimberlyk.Summers@va.govEmail: kimberlyk.Summers@va.gov