Basic Institutional Review Board (IRB) Regulations and Review Process

Introduction

The purpose of this module is to provide a basic understanding of the human subject protection regulations that gove the participation of human volunteers in research in the United States Learning Objectives B! end of the module !ou should be able to" #escribe the role$ authorit!$ and composition of the IRB %ist the IRB re&uirements for conducting research involving human subjects #escribe the t!pes of IRB review #escribe the process of wor'ing with the IRB

Identif! other regulations and regulator! groups that re&uire compliance based on the t!pe of research bei conducted

IRB Role, Authority, and Composition

The Role of the IRB

(n Institutional Review Board (IRB) is a review committee established to help protect the rights and welfare human research subjects Regulations re&uire IRB review and approval for research involving human subjects if i funded or regulated b! the federal government )ost research institutions$ professional organi*ations$ and schola journals appl! the same re&uirements to all human research (lthough federal regulations refer to IRBs$ an instituti ma! have chosen a different name for this committee To clarif! when IRB review is re&uired$ let+s define some terms"

Research ,ederal regulations define research as" -a s!stematic investigation designed to develop or contrib to generali*able 'nowledge - ./0 1,R /2 345(d)6 If an investigator is unclear about whether a planned activit! research$ the investigator should contact his7her IRB office

!uman "ubjects The #epartment of 8ealth and 8uman Services (#88S) regulations define a human subject -a living individual about whom an investigator (whether professional or student) conducting research obtains" #ata 9r Identifiable through private intervention or interaction ./0 with 1,R the /2 345

individu

information -

#ote Some state laws include deceased individuals and fetal materials as -human subjects - 1hec' with the local IR about the definition of a human subject that applies in the state where the research will be conducted

$rivate Information includes"

Information about behavior that occurs in a setting in which the individual can reasonabl! e:pect that no observati or recording is ta'ing place

Information that has been provided for specific purposes , other than research, where the individual can reasonab e:pect that it will not be made public (such as a medical record ) ./0 1,R /2 345(f)6

Coded $rivate Information or Biological "pecime #88S 9ffice of 8uman Research Protection (98RP) polic! considers private information or specimens to individuall! identifiable when the! can be lin'ed to specific individuals either directl! or indirectl! through codi s!stems #88S 98RP guidance recommends that onl! a 'nowledgeable person or entit! be authori*ed to determi if coded specimen or data constitute research 98RP recommends that investigators not be given authorit! to ma'e independent determination that research involving coded private information or specimens does not involve hum subjects .98RP #88S ;uidance on Research Involving 1oded Private Information or Biological Specime 9ctober 544< 6

Clinical Investigation" The ,ood and #rug (dministration (,#() defines clinical investigation as -a e:periment that involves a test article and one or more human subjects and that either must meet the re&uirements prior submission to the ,ood and #rug (dministration or need not meet the re&uirements for prior submission to t ,ood and #rug (dministration but the results of which are intended to be later submitted to$ or held for inspecti b!$ the ,ood and #rug (dministration as part of an application for a research or mar'eting permit - .53 1, 02 345(c)6

The Authority of the IRB

,ederal regulations stipulate that an IRB can" (pprove research #isapprove research )odif! research 1onduct continuing reviews 9bserve 7 verif! changes Suspend or terminate approval 9bserve the consent process and the research procedures

The Composition of the IRB

,ederal regulations dictate that the IRB membership will include" (t least five members )ember of both se:es )embers that come from varied professions (t least one member whose primar! concerns are in nonscientific areas

(t least one member whose primar! concerns are in scientific area (t least one member who is not otherwise affiliated with the institution

The regulations also stipulate that the IRB membership will include"

Reviewers with e:perience and e:pertise in all of the areas of research being reviewed (t its discretion$ an IR ma! invite individuals with competence in special areas to assist in the review of issues which re&uire e:pert be!ond or in addition to that available on the IRB #iversit! of bac'grounds$ including racial and cultural diversit! Sensitivit! to communit! attitudes

=nowledge of institutional commitments and regulations$ applicable laws$ and standards of professional cond and practice =nowledge and e:perience with vulnerable populations

#ote If an IRB reviews research that involves vulnerable subjects$ the IRB must consider the inclusion of individual who has 'nowledge of$ and e:perience with$ these vulnerable subjects The regulations ma! also re&uir voting IRB member who has relevant research e:pertise (for e:ample$ research involving prisoners) IRBs ma! c e:perts to help with problematic reviews$ but those persons ma! not vote on the disposition of the application If IRB member has a conflict of interest$ that member cannot be present for the review of that project e:cept to provi the IRB with information as re&uested and ma! not vote on that project

IRB Re&uirements for !uman "ubjects Research

IRB Re&uirements

Institutions and IRBs var! in the practices that assure the! meet the federal regulations and in the details of standards the! appl! >hat follows are the minimum federal re&uirements Institutions and7or IRBs ma! a additional protections or procedures to these minimum re&uirements IRB applications usuall! contain$ at a minimum$ information that allows IRB members to assess" Ris' ( anticipated benefit analysis Identification and assessment of ris's and anticipated benefits #etermination that ris's are minimi*ed #etermination that ris's are reasonable in relation to potential benefits Informed consent Informed consent process and documentation Assent The affirmative agreement of a minor or decisionall! impaired individual to participate in research

(ssent process and documentation

"election of subjects ?&uitable selection in terms of gender$ race$ ethnicit! Benefits are distributed fairl! among the communit!+s populations (dditional safeguards are provided for vulnerable populations susceptible to pressure to participate "afeguards

?nsure that subject recruitment does not invade individuals+ privac! and that procedures are in place to assure th the confidentialit! of the information$ collected during the research$ is monitored Research plan for collection, storage, and analysis of data

1linical research studies often include data safet! monitoring plans and7or data safet! monitoring boards (#S)B IRBs will review the plans to ensure the! are ade&uate to protect human subjects Research design ( methods (re appropriate$ scientificall! valid and therefore$ justif! e:posing subjects to research ris's Additional information (bout identification$ recruitment and safeguards if the research involves special populations In addition, the IRB must revie) The &ualifications of the principal investigator (PI) and scientific collaborators ( complete description of the proposed research Provisions for the ade&uate protection of rights and welfare of subjects 1ompliance with pertinent federal and state laws7regulations and institutional polic!

#88S funding proposals (other funding agencies ma! also have similar re&uirements7e:pectations) 1linical Brochures7Investigator Protocols (for ,#(@regulated research)

Responsibilities of the $rincipal Investigators and Research "taff

Principal investigators and research staff have specific responsibilities The! are re&uired to" Protect the rights and welfare of human subjects who participate in research Understand the ethical standards and regulator! re&uirements governing research activities with human subjects Personall! conduct or supervise the research

?nsure that all staff$ collaborators$ and colleagues assisting in the conduct of the stud! are informed about stud!$ the regulations governing research$ and the institutional policies

?nsure that all research activities have IRB approval and other approvals re&uired b! the institution before hum subjects are involved Implement the research activit! as it was approved b! the IRB

9btain the informed consent of subjects before the subject is involved in the research and document consent approved b! the IRB

)aintain written records of IRB reviews and decisions and obtain and 'eep documented evidence of inform consent of the subjects or their legall! authori*ed representatives 9btain IRB approval for an! proposed change to the research protocol prior to its implementation

1ompl! with the IRB re&uirements for timel! reporting of unanticipated problems involving ris's to subjects others including adverse events$ safet! reports received from the sponsor$ or data safet! and monitoring summa reports 9btain continuation approval from the IRB on the schedule prescribed b! the IRB )a'e provisions for the secured retention of complete research records and all research materials ?nsure the confidentialit! and securit! of all information obtained from and about human subjects

Aerif! that IRB approval has been obtained from all participating institutions in collaborative activities with oth institutions

Botif! the IRB regarding the emergenc! use of an investigational drug or device within 0 wor'ing da!s$ or soon if re&uired b! the IRBCs policies$ of the administration of the test article

*hen IRB regulations are not follo)ed, conse&uences could include

Suspension of research project Suspension of all of a PI+s research projects

Inabilit! to use data or publish results Botification of sponsors$ regulator! agencies$ and funding agencies of noncompliance #ebarment b! ,#( from using investigational products Inabilit! to receive funding from federal grants (dditional monitoring and oversight b! the IRB and7or third part! monitoring of research activities Termination of emplo!ment %oss of licenses Immediate shut@down of (%% research at an organi*ation

These are not theoretical conse&uences% "ome or all of these conse&uences have occurred at sites )he human subjects research )as conducted improperly or )ithout IRB approval%

The Types of IRB Revie)

1ontact the IRB office for the guidelines for submitting a stud! for IRB review Under federal regulations$ th are three possible IRB review procedures" +ull(Convened Committee Revie)

,-pedited Revie) Revie) for ,-emption "tatus

+ull(Convened Committee Revie)

,ull committee review or review b! the convened IRB is the standard t!pe of review described in the ,ede regulations It must be used for the initial review of all studies that are not eligible for e:pedited review or e:empti status The procedures and conditions for full committee revie) re&uire that" The review must be conducted at a convened meeting of the IRB ( majorit! of IRB members (a &uorum) must present at the meeting (t least one member whose primar! concerns are in nonscientific areas must be present at the meeting addition$ ,#( polic! recommends that a ph!sician be present)

In order to approve research$ the IRB must determine that all of the re&uirements specified in /0 1,R /2 333 (a if applicable$ 53 1,R 02 333) are satisfi See" http"77answers hhs gov7ohrp7categories73025 and www fda gov7oc7ohrt7irbs7appendi:c html

( majorit! of the members present at the meeting must approve the research

IRB members who have a conflict of interest in a research project ma! provide information to the IRB$ but cann participate in the review of the protocol or be present for voting )embers with a conflict do not count toward t &uorum for the review of that stud!

 The IRB must notif! investigators and the institution in writing of its decision to approve$ modif! or disappro the research IRBs must 'eep detailed documentation of meeting activities including attendance$ voting on actions$ the basis the actions$ and a written summar! of the IRB discussion of controverted issues and their resolution

(lthough not specificall! addressed in the regulations$ IRBs ma! emplo! a -primar! reviewer s!stem- In such s!stem$ all IRB members receive basic information about the research application$ but a -primar! reviewer- w e:perience and7or e:pertise in the stud! area is assigned to conduct a thorough review of the IRB application and a accompan!ing documentation (for e:ample$ an Investigator+s Brochure or grant application) The -primar! review will then report his7her findings for discussion at a convened meeting of the full board (t some institutions review ma! contact the investigator with &uestions or suggestions prior to the meeting (t some institutions the IRB ma! a that investigators attend the IRB meeting or be available b! phone to answer &uestions that ma! arise at the meeting

,-pedited Revie)

,ederal Regulations establish nine categories that IRBs ma! use to invo'e the e:pedited review process Institutio ma! adopt some or all of the categories when determining if a research activit! can be appropriatel! reviewed b! e:pedited review process 1ategories 3 through D pertain to both the initial and to the continuing IRB revie 1ategories < and E pertain onl! to continuing review The E categories are listed below ,ollow the h!perlin's more details about each categor! 8!perlin's will open in a new browser window 1lose the new window to retu here The ,ederal Regulations establish two main criteria for an e:pedited review There are" The research ma! not involve more than -minimal ris'-

-)inimal ris'- means that -the probabilit! and magnitude of harm or discomfort anticipated in the research are n greater in and of themselves than those ordinaril! encountered in dail! life or during the performance of routi ph!sical or ps!chological e:aminations or tests - (./0 1,R /2 345(i)6 and .53 1,R Part 02 345(i)6)

The entire research project must be consistent with one or more of the following federall! defined categor (&uoted from the 98RP$ the IRB oversight agenc!$ guidance document on ?:pedited Reviews )

Some institutions7IRBs have additional re&uirements 1hec' with !our IRB office for more information about h e:pedited review is handled b! !our IRB

Research Categories that .ualify for ,-pedited Revie)

The following are the nine categories that IRBs ma! use to invo'e the e:pedited review process Category /

1linical studies on drugs or medical devices for which an investigational new drug (IB#) or an investigational dev e:emption (I#?) application is B9T re&uired Similarl!$ a stud! with a cleared7approved medical device that is bei used in accordance with its cleared7approved labeling )ore details Category 0 1ollection of blood samples b! finger stic'$ heel stic'$ ear stic'$ or venipuncture )ore details Category 1

Prospective collection of biological specimens for research purposes b! noninvasive means )ore details Category 2 1ollection of data through noninvasive procedures routinel! emplo!ed in clinical practice provided that"

The noninvasive procedure must not involve general anesthesia or sedation routinel! emplo!ed in clinical pract or procedures involving :@ra!s or microwaves

>here medical devices are emplo!ed$ the! must be cleared7approved for mar'eting (Studies intended to evalu the safet! and effectiveness of the medical device are not generall! eligible for e:pedited review$ including studies cleared medical devices for new indications ) ?:amples of noninvasive procedures are" Ph!sical sensors that are applied either to the surface of the bod! or at a distance and do not involve input significant amounts of energ! into the subject or an invasion of the subject+s privac! >eighing or testing sensor! acuit! )agnetic resonance imaging

?lectrocardiograph!$ electroencephalograph!$ thermograph!$ detection of naturall! occurring radioactivi electroretinograph!$ ultrasound$ diagnostic infrared imaging$ doppler blood flow$ and echocardiograph!

)oderate e:ercise$ muscular strength testing$ bod! composition assessment$ and fle:ibilit! testing where appropri given the age$ weight$ and health of the individual )ore details Category 3 Research involving data$ documents$ records$ or specimens that" 8ave or been

collect

>ill be collected solel! for non@research purposes (such as for medical treatment or diagnosis)

#ote Some research in this categor! ma! be e:empt from the #88S regulations for the protection of human subjec /0 1,R /2 343(b)(/) This listing refers onl! to research that is not e:empt )ore details Category 4 1ollection of data from voice$ video$ digital$ or image recordings made for research purposes )ore details Category 5 Research on individual or group characteristics or behavior )ore details Category 6 1ontinuing review of research previousl! approved b! the convened IRB where"

The research is permanentl! closed to the enrollment of new subjectsF all subjects have completed all researc related interventionsF and, the research remains active onl! for long@term follow@up of subjec

Or where:

Bo

subjects

have

been

enrolled

and

no

additional

ris's

have

been

identifi

Or where:

The remaining research activities are limited to data anal!sis )ore details

Category 7

1ontinuing review of research not conducted under an investigational new drug (IB#) application or investigatio device e:emption (I#?) and where categories two (5) through eight (<) do not appl! )ore details ,-pedited Revie) $rocess

The IRB chairperson or one or more e:perienced IRB members$ designated b! the 1hair$ can conduct an e:pedi review IRB members with a conflict of interest cannot be designated to serve as an e:pedited reviewer In conducti the review$ a determination must be made that the research meets the conditions for e:pedited review procedures

The reviewer conducting the e:pedited review ma! e:ercise all of the authorities of the IRB with one importa e:ception$ the reviewer ma! not disapprove research To approve a research activit!$ the reviewer must ma'e t determination that all of the re&uirements specified in ,ederal regulations (/0 1,R /2 333 and 53 1,R 02 333) a satisfied The reviewer (s) ma! either approve the research$ re&uire modifications (to secure approval) or refer research to a convened IRB meeting for review in accordance with the -full committee review- procedures describ in section 5 above$ and set forth in #88S regulations at /0 1,R /2 34<(b) and 53 1,R 02 34<(c)

?:pedited procedures can also be used to review minor modifications of previousl! approved research ./0 1 /2 334(b) and 53 1,R 02 334(b)6

Revie) for ,-emption "tatus

,ederal regulations specificall! define 2 categories of human subjects research that are exempt from the oth provisions of the regulations ,ederal guidance indicates that determinations of e:empt status should be made individuals independent of the research who are well@ac&uainted with interpretation of the regulations governing conduct of human subjects research )an! institutions grant the authorit! to ma'e determinations of e:empt status the IRB 1hec' with the IRB office to find out who has been granted authorit! to ma'e the e:emption determinatio Note: the determination must be made prior to initiation of research or of the activity; it cannot be ma retroactively.

Research that is ,-empt

The regulations found in /0 1,R /2 have determined that the following si: categories of research are eligible e:emption status$ ./0 1,R /2 343(b)6" See the h!perlin'ed material for the regulator! details and conditio

associated with each categor! The lin's will open in a new browser window 1lose the new browser window to retu here

Research conducted in established or commonl! accepted educational settings$ involving normal educatio practices )ore #etails

Research involving the use of educational tests (cognitive$ diagnostic$ aptitude$ achievement)$ surve! procedur interview procedures$ or observation of public behavior Some studies that emplo! observation$ surve!$ or intervi procedures do not &ualif! for e:emption )ore #etails Research not e:empt under -5- above$ ma! still &ualif! for an e:emption if the human subjects are elected appointed public officials or candidates for public office )ore #etails

Research involving the collection or stud! of freel! available de@identified e:isting data$ documents$ recor pathological specimens$ or diagnostic specimens )ore #etails

Research and demonstration projects conducted b! heads of government departments or agencies which are design to evaluate public programs )ore #etails Taste and food &ualit! evaluation and consumer acceptance studies )ore #etails

*hen Revie) of ,-emption "tatus is #ot Appropriate

(ccording to the #88S regulations /0 1,R /2$ research involving the following are not appropriate for e:emption" Prisoner Surve!ing or interviewing of children

9bservations of public behavior of children when the investigator(s) participates in the activities being observed

Additional !I$AA Re&uirements That Indirectly Impact The Revie) Of ,-emption "tatus

The Privac! Rule is a ,ederal regulation under the 8ealth Insurance Portabilit! and (ccountabilit! (ct (8IP(() 3EE2 ./0 1,R 324 and 32/6 If an IRB has been given the responsibilit! to consider 8IP(( in research issues and the research potentiall! falls under the purview of 8IP(($ an IRB will be appl!ing not onl! the /0 1,R /2 e:empti categories but also determining if 8IP(( applies In some cases$ 8IP(( applicabilit! re&uirements are mo stringent than #88S e:emption re&uirements and in other cases less stringent ( research project that is e:empt fro the human research subject IRB re&uirements ma! not be e:empt from 8IP(( provisions (lso$ a project that is n e:empt from IRB might be e:empt from 8IP(( See the #88S 98RP Guidance on Research Involving Cod Private Information or iological !pecimens$ and the BI8 and guidance entitled Institutional Revie" oards a #IP$$ Privacy Rule

$rocess of *or'ing )ith the IRB

Criteria for IRB Approval

,ederal polic! lists Basic Criteria that the IRB must appl! ./0 1,R Part /2 333 and 53 1,R Part 02 3336 wh reviewing research involving human subjects To approve a research project$ the IRB must determine that"

The ris's to subjects are minimi*ed

The ris's are reasonable in relation to an! anticipated benefits to the subject$ and to the advancement 'nowledge The selection of subjects is e&uitable Informed consent will be sought Informed consent will be documented

>here appropriate$ the research plan ma'es ade&uate provisions for monitoring the data collected to ensure saf of subjects There are ade&uate provisions to protect the privac! of subjects and to maintain the confidentialit! of data

>here an! of the subjects are li'el! to be vulnerable to coercion or undue influence$ additional safeguards ha been included in the stud! to protect subjects

In addition$ there are specific re&uirements regarding the informed consent process These will be detailed in Inform Consent module

The IRB must determine that these conditions e:ist at the time of initial review and at each subse&uent revi conducted b! the IRB

Types of IRB "ubmissions

Application for initial revie) The first re&uest for approval of a specific project is the application for initial review

Application for continuing revie) The IRB must re@review studies at a minimum of once ever! G20 da!s (n IR ma! re&uire review more fre&uentl! depending on the IRB+s assessment of the stud!+s ris'7benefit ratio The revi ma! be a full or e:pedited review

Amendments or modifications 1hanges can not be made to approved studies$ including the informed cons document$ without prior IRB review and approval The review ma! be full or e:pedited$ depending on the magnitu of the change and the effect of the change on the ris's 7 benefit ratio Reports The IRB ma! re&uire a report for" (dverse events or unanticipated problems involving ris's to subjects or others Incidents of noncompliance #eviations from an approved stud! protocol and violations of the terms of approval #ata Safet! and )onitoring Report summaries Application for Initial Revie)

The initial review ma! be either a -1onvened7,ull 1ommittee- or -?:pedited- review depending on the t!pe of stud the subjects and the level of ris' Application for Continuing Revie)

The IRB must do substantive continuing review and must consider the same issues as during initial revie Specificall!"

>hen conducting a continuation review$ the IRB uses -,ull 1ommittee Review- procedures unless the resear meets the e:pedited review criteria

To approve research$ the IRB must determine that all the re&uirements for initial approval (specified in /0 1 /2 333 and 53 1,R 02 333) continue to be satisfied IRB should review$ at a minimum$ the protocol and an! amendments as well as a status report including" The number of subjects accrued

( description of adverse events$ unanticipated problems$ withdrawal of subjects$ complaints$ summar! of releva new information ( cop! of current informed consent document

,ollow the lin' to view the latest Guidance on IR Continuing Revie" of Research

1ontinuing review must occur$ at a minimum$ once per !ear (within G20 da!s) of previous approval )ore fre&ue review is at the discretion of the IRB$ and ma! be the result of considering the ris's associated with the stud! or t proposed population It is an investigator+s responsibilit! to 'now when IRB approval will e:pire 8owever$ m institutions7IRBs$ as a courtes! to their investigators$ send out reminders that IRB approval is about to e:pi Sometime prior to the e:piration of IRB approval$ investigators will receive a re&uest to complete a progress report continuing review b! the IRB It is an investigator+s responsibilit! to complete the continuing review re&uest$ submi bac' to the IRB in a timel! manner prior to the end of the current IRB approval period

If a protocol+s approval e:pires before the IRB completes its review$ the investigator must stop all resear procedures >hen stopping the research could place subjects at ris'$ the investigator should contact the IR immediatel! to obtain approval to continue treating subjects on that stud! Amendments and 8odifications

(ll amendments and modifications to a stud! need IRB approval before the! are implemented If the investiga wants to change anything in the research that would impact the subjects$ such as recruitment procedures$ ' personnel$ inclusion7e:clusion criteria$ research procedures$ the informed consent document 7 process$ or d elements collected$ the investigator must obtain IRB review and approval prior to implementation of the changes T onl! e:ceptions are changes necessar! to immediatel! protect subjects+ safet!$ as noted in 53 1,R 02 34<(a)(/) a 02 330(a)(3) If an investigator is unsure about reporting changes to the IRB$ he7she should call the IRB office and a for guidance The IRB office can also provide investigators with instructions for submitting a re&uest to modif! IRB@approved research Reports of 9nanticipated $roblems ( Adverse ,vents ( #oncompliance to the IRB

,ederal reporting re&uirements for IRBs$ investigators$ and funding sponsors are confusing 1onse&uentl!$ IRBs te to develop their own idios!ncratic reporting re&uirements$ based upon their interpretation of both ,#( and 98R guidance This poses some difficult! for investigators because if the project is funded$ the sponsor ma! have reporti re&uirements that differ from the IRB polic! and procedures At a minimum, to ensure compliance, the investigator is responsible for

3 #etermining the IRB re&uirements for reporting with respect to what needs to be reported$ when it should reported$ and the procedure for submitting the report 5 Setting up s!stems to ensure that reportable events are identified and submitted to the IRB in a timel! manner ?:amples of the t!pe of events that ma! be reportable include"

(n unanticipated problem$ which ma! be defined as an! une:pected event that affects rights$ safet! or welfare subjects The event could be ph!sical such as an adverse drug e:perience or adverse device effect The event cou also involve some harm or ris' (i e breach in confidentialit! or harm to a subject+s reputation)

Serious adverse event$ which ma! be defined as a death$ life@threatening adverse drug or device e:perien inpatient hospitali*ation or prolongation of e:isting hospitali*ation$ a persistent disabilit!7incapacit!$ or a congeni anomal!7birth defect

Protocol e:ception$ which ma! be defined as enrollment of a research subject that fails to meet proto inclusion7e:clusion criteria

Protocol deviation$ which ma! be defined as a departure from the protocol as approved b! the IRB for a sin subject #ata and Safet! )onitoring Plan or Board summar! reports

1omplaints concerning subject rights submitted b! subjects or concerned parties$ famil! members$ or stu personnel

The IRB will use the reports to assess whether the ris's7benefit ratio is still reasonable$ whether changes in informed consent document or stud! procedures are needed$ or whether re@consent is necessar! IRB re&uirements reporting var! regarding what should be reported$ when the reports should be submitted$ and the format of the repor 1hec' with !our IRB to determine its specific re&uirements

Basic IRB Regulations and Revie) $rocess

Additional Reporting Re&uirements

Besides the IRB$ the Principal Investigator (PI) has a variet! of entities to which he7she is responsible for reportin )inimum reporting re&uirements for each entit! are" ,ntit y Rese arch "ubje ct $I Reporting Re&uirements >hile it might not be considered reporting in the strictest sense$ the informed consent process is a report to the potential subject about the research$ both before the research begins and on an ongoing basis throughout the stud! (lso$ if new information becomes available during the research that might impact the subject+s willingness to participate$ an investigator is obligated to provide the subject with that information This information will also need to be reported to the IRB The IRB office can provide guidance on how additional information should be reported Instit )ost institutions have reporting lines set up so that the investigator ution ma'es reports to the IRB and it falls upon the IRB to 'eep the institution informed 8owever$ chec' with the applicable IRB to ma'e sure that the investigator does not have direct responsibilit! for reporting incidents to the institution "pon sor (dverse events should be reported immediatel! to the sponsor Investigators should also chec' the sponsor proposed changes that might be made to the stud!$ base on the adverse event that has occurred or preliminar! findings The sponsor also should be told about serious or ongoing noncompliance in a stud! (dverse events7Unanticipated problems should be reported directl! to ,#( if the research is PI@initiated (without e:ternal sponsorship) and falls under the ,#(+s purview 9ther reporting re&uirements related to ,#(@regulated research ma! appl! If !our project has a #ata Safet! and )onitoring Board$ chec' !our #S)B plan for reporting re&uirements

+:A

:"8 B

Record ;eeping

The signed informed consent document is one of the most critical research records the investigator needs to obtain a 'eep It provides verification that the research was e:plained to the subject and that the subject understood a voluntaril! agreed to participate in the research stud! Investigators are responsible for retaining signed cons documents$ IRB correspondences$ and research records for at least three (G) !ears after the completion of the resear activit! (/0 1,R /2 330) 8owever$ local institutional polic! or sponsoring agenc! re&uirements ma! dictate th records be 'ept longer 1hec' with the sponsor and IRB office to ma'e sure that the minimum G !ears retenti re&uirement meets their needs

The ,#( regulations specif! uni&ue document retention re&uirements for ,#( regulated studies .see 53 1,R G35

(c)6 These re&uirements must be met for ,#(@regulated studies

Other Regulations and Regulatory <roups

+unding and Regulatory Agencies
#epending upon the nature of !our research and the agenc! that funds !our research there are a number regulations$ policies and procedures that ma! need to be considered Below is a brief description of regulations$ regulator! bodies$ and funding agencies that ma! oversee !our research ,unding agencies and local IRB offices can also provide guidance on whether an! additional re&uirements appl! to a research 8!perlin's will open in a new browser window 1lose the new browser window to return here +unding Agency ( Regulatory Agencies #88S <eneral Regulations

of oth selec 7or !o activi

The #88S /0 1ode of ,ederal Regulations (1,R) Part /2 applies to The #epartment of 8ealth and all human research submitted to or 8uman Services (#88S) is funded b! #epartment of 8ealth and responsible for one group of human 8uman Services and is applied to all subjects federal regulations human research b! most large institutions Subparts include"

"ubpart A Basic ,ederal Polic! for the Protection of 8uman Subjects "ubpart B (dditional Protections for Pregnant >omen$ 8uman ,etuses and Beonates Involved in Research "ubpart C (dditional Protections for Prisoners "ubpart : (dditional Protections for 1hildren "ubpart , Registration of institutional Review Boards

BI8 The Bational Institutes of 8ealth include funding agencies that provide federal funding for biomedical research BI8 re&uires grantees conducting certain t!pes of clinical research studies to have either data safet! monitoring plans

(3) BI8 Polic! for #ata and Safet! )onitoring (5) Polic! for the Bational 1ancer Institute for #ata and Safet! )onitoring of 1linical Trials (G) ?ssential ?lements of a #ata and Safet! )onitoring Plan for

and7or data safet! and monitoring boards In general BI8 polic! re&uires that a #ata and Safet! )onitoring Board be established for all phase III randomi*ed clinical trials 98RP The 9ffice for 8uman Research Protections is the #88S oversight bod! that provides guidance to IRBs and investigators conducting human subject research

1linical Trials ,unded b! the Bational 1ancer Institute (/) ,urther ;uidance on #ata and Safet! )onitoring for Phase I and Phase II Trials 98RP Polic! and (ssurances guidelines$ regulations$ ethical principles$ IRB ;uide Boo'$ 98RP79PRR Reports$ ,(Hs$ and other materials relevant to the protection of human research subjects are available from the 9ffice for 8uman Research Protections >ebsite 98RP+s most current compilation of international standards ma! be found here

,#(

The ,ood and #rug (dministration (,#() has numerous regulations The ,ood and #rug (dministration directl! impacting informed consent oversees the use of all drugs$ See ;uidance documents$ information devices$ biologics$ etc including sheets and regulations indirectl! their use in research with human impacting IRBs and investigators subjects 8uman subject research that is conducted in international settings ma! have additional re&uirements that must be met such as$ International 1onference on 8armonisation 7 ;ood 1linical Practices Research that is funded b! the ,ederal #epartment of ?ducation ma! have additional re&uirements that must be met Research involving human subjects recruited from or conducted in a Aeterans (ffairs facilit! must also meet the re&uirements as set forth b! the A( The A( 9ffice of Research 9versight provides a number of publications related to research on its web site ?ach federal agenc! ma! have

I187;1P International 1onference on 8armonisation 7 ;ood 1linical Practices

#epartment of ?ducation

#epartment of Aeterans (ffairs

9ther ,ederal (gencies

additional policies$ procedures$ re&uirements$ etc that must be applied to research involving human subjects ?:amples are the #epartment of #efense$ #epartment of ?nerg!$ and Bational Science ,oundation

Assurance Re&uirements

#88S human subject protection regulations and policies re&uire that an! institution engaged in non@e:empt hum subjects research conducted or supported b! 88S must submit a written assurance of compliance to 98RP T ,ederalwide (ssurance (,>() is the onl! t!pe of new assurance accepted and approved b! 98RP ,>(s also approved b! the 98RP for federalwide use$ which means that other federal departments and agencies that ha adopted the ,ederal Polic! for the Protection of 8uman Subjects (also 'nown as the 1ommon Rule) ma! rel! on ,>( for the research that the! conduct or support Institutions engaging in research conducted or supported b! no #88S federal departments or agencies should consult with the sponsoring department or agenc! for guidan regarding whether the ,>( is appropriate for the research in &uestion

(n assurance of compliance is a written document submitted b! an institution (not an Institutional Review Board) th is engaged in non@e:empt human subjects research conducted or supported b! 88S Through the assurance$ institution commits to 88S that it will compl! with the re&uirements set forth in the regulations for the protection human subjects at /0 1,R part /2

IRB Registration
Both the +:A and :!!" re&uire IRB registration%

?ach IRB that is designated b! an institution under an assurance of compliance approved for federalwide use 98RP under I/2 34G(a) and that reviews research involving human subjects conducted or supported b! the #88 must be registered with 88S (dditionall!$ an! IRB in the U S that reviews research that is regulated b! the ,#( must be registered (ll IRB registrations are completed through 98RP+s website