Research Involving Pregnant Women, Human Fetuses and Neonates
18.3.1Definitions
Deadfetus-afetusthatexhibitsnoheartbeat,spontaneousrespiratoryactivity, spontaneousmovementofvoluntarymuscles,orpulsationoftheumbilicalcord.
Delivery-completeseparationofthefetusfromthewomanbyexpulsionorextractionor anyothermeans.
Fetus-theproductofconceptionfromimplantationuntildelivery.
Neonatemeansanewborn.A newbornis consideredaneonateupto30daysofage. Anewborn,31daysoldwillbeconsideredachildforresearchpurposes.
Nonviableneonate-aneonateafterdeliverythat,althoughliving,isnotviable.
Pregnancyencompassestheperiodoftimefromimplantationuntildelivery.Awoman isassumedtobepregnantifsheexhibitsanyofthepertinentpresumptivesignsof pregnancy,suchasmissedmenses,untiltheresultsofapregnancytestarenegativeor untildelivery.
Viable,asitpertainstotheneonate,meansbeingable,afterdelivery,tosurvive(given thebenefitofavailablemedicaltherapy)tothepointofindependentlymaintaining heartbeatandrespiration.
Stillborndeathorstillbirthmeansdeathpriortothecompleteexpulsionorextraction fromitsmotherofaproductofhumanconception,occurringafterthetwentieth weekof pregnancyanddoesnotinclude“inducedterminationofpregnancy.ColoradoRevised Statutes,§25-2-102(4.5).
Inducedterminationofpregnancymeansthepurposefulinterruptionofapregnancy withtheintentionotherthanproducingalive-borninfantorremovingadeadfetusthat doesnotresultinalivebirth.Coloradorevisedstatutes,§25-2-102(2.7).
18.3.2ResearchInvolvingPregnantWomenorFetuses
Researchthatinvolvespregnantwomenandfetusescanonlyoccurifallofthefollowing conditionsaremet(45CFR46.204):
Whenappropriate,preclinicalstudiesincludingstudiesonpregnantanimalsandclinical studies,includingstudiesonnon-pregnantwomen,havebeenconductedandprovidedata forassessingthepotentialriskstopregnantwomenandfetuses;
Therisktothefetusiscausedsolelybyinterventionsorproceduresthatholdout thepotentialofdirectbenefitforthewomanorthefetus,
or
Ifthereisnopotentialofbenefit,therisktothefetusmustbeminimal,and thepurposeoftheresearchisthedevelopmentofimportantbiomedical knowledgewhichcannotbeobtainedbyanyothermeans.
Anyriskistheleastpossibleforachievingtheobjectivesoftheresearch.No inducements,monetaryorotherwise,maybeofferedtoterminateapregnancy.
Researchersmaynottakepartindecisionsastothetiming,method,orprocedures usedtoterminateapregnancy.
Membersoftheresearchteammaynotdeterminetheviabilityofaneonate.
18.3.2.1WhoCanConsent
Themothermayconsentforthestudyif:
Theresearchholdsoutthepotentialofdirectbenefittothepregnantwoman,orboth thepregnantwomanandfetus,or;
Ifthereisnobenefitforthewomanorfetusandtherisktothefetus is minimal,and;Thepurposeoftheresearchisthedevelopmentofimportant biomedical knowledgethatcannotbeobtainedbyanyothermeans.
Themotherandfathermustconsentforthestudyif:
Theresearchholdsoutthepotentialofdirectbenefitsolelytothefetus,
Thefather’sconsentneednotbeobtainedifheisunabletoconsentbecauseof unavailability,incompetenceortemporaryincapacityorthepregnancyresulted fromrapeorincest.
COMIRBrequeststhatyoudocumentthereasonsfornotobtainingthefather’s consentin yourstudyrecords.
Eachindividualprovidingconsentmustbefullyinformedregardingthereasonably foreseeablerisksoftheresearchonthefetusorneonate.
Anyminorparentcangivepermissionfortheirchildtoparticipateinresearchbutthe parent/guardianoftheminorparentmustgivepermissionfortheminorparentto participateintheresearch.Parentalpermissionisnotrequirediftheminorparent
isemancipatedasdefinedbyColoradoStateLaw.
18.3.2.2VARegulations
Researchinwhichthesubjectisa fetus,in-uteroorex-utero(includinghuman fetaltissue)mustnotbeconductedbyVAinvestigatorswhileonofficialduty,or atVAfacilities,oratapprovedoff-sitefacilities.
ResearchrelatedtoinvitrofertilizationmustnotbeconductedbyVA investigatorswhileonofficialduty,oratVAfacilities,oratapprovedoff-site facilities.
18.3.3ResearchInvolvingNeonates
Neonatalresearchisdependentontheviabilitystatusoftheneonate(45CFR46.205). Aneonatethatisviablemayparticipateinresearchonlytotheextentoutlinedby45CFR
46subpartsAandD.
NeonateswhoseviabilityisnotcertainmayparticipateinresearchifCOMIRB
determinesthattheresearch:
Holdsouttheprospectofenhancingthesurvivaloftheneonatetothe pointofviabilityandtheriskisminimizedforachievingthatgoal,
or
Thedevelopmentofimportantbiomedicalknowledgewhichcannotbeobtained byothermeans,andtherecanbenoaddedrisktotheneonatefromthe research.
Inaddition:
Theappropriatepreclinicalandclinicalstudieshavebeencarriedoutthatallow foradequateriskassessment.
Aneonatologistorpediatriciannotassociatedwiththeresearchdeterminesthe viabilityoftheneonate.
Informedconsentofeitherparentoftheneonateisobtained
Ifneitherparentisabletoconsentbecauseofunavailability,incompetence,or temporaryincapacity,thelegallyauthorizedrepresentative[LAR]ofeitherparent mayprovideinformedconsent.COMIRBrequeststhatyoudocumentthe reasonsforwhyyouobtainedthelegallyauthorizedrepresentative’sconsent.
Theconsentofthefatherisnotneededifthepregnancyresultedfromrapeor incest.
Afterdelivery,nonviableneonatesmaybeinvolvedinresearchonlyif thefollowing conditionsaremet:
Thevitalfunctionsoftheneonatearenotartificiallymaintained
Theresearchwillnotterminatetheheartbeatorrespirationoftheneonate
Therearenoadditionalresearchriskstotheneonate
Thepurposeoftheresearchisthedevelopmentofimportantbiomedical knowledgethatcannotbeobtainedbyothermeans
Informedconsentofeitherparentoftheneonateisobtained
Ifneitherparentisabletoconsentbecauseofunavailability,incompetence,or temporaryincapacity,thelegallyauthorizedrepresentativeofeitherparentmay provide informedconsent.COMIRBrequeststhatyoudocumentthereasons whyyouobtainedthelegallyauthorizedrepresentative’sconsent.Theconsentof thefatherisnotneededifthepregnancyresultedfromrapeorincest
18.3.4ResearchInvolvingAfterDelivery:ThePlacenta,DeadFetusorFetalMaterial
Researchinvolvingtheplacentafollowingdelivery;thedeadfetus,maceratedfetal material;orcells,tissue,ororgansremovedfromthedeadfetusshallfollowthe appropriatefederal,stateorlocallawsandregulations(45CFR46.206).
Iftheabovetissue’sinformationisrecordedsothatlivingindividualscanbeidentified, thenthelivingindividualsareconsideredresearchsubjects.Informedconsentmustbe obtainedfromthelivingindividuals.
Nophysicianorinstitutionthatperformsproceduresfortheinducedterminationofpregnancyshall transfersuch tissueforvaluableconsiderationtoanyorganizationor personthatconductsresearchusingfetaltissueorthattransplantsfetaltissuefor therapeuticpurposes.(Coloradorevisedstatutes,§25-2-111.5).[Valuableconsideration meanssimplyanyprofitorgain.]
Foradditionalinformationaboutresearchusingfetalorembryonictissues,pleasesee section26.8.
18.3.5NeonatalResearchnotOtherwiseApprovable
ForresearchnotfundedbyDHHS,iftheCOMIRBfindsthattheresearchpresentsa reasonableopportunitytofurthertheunderstanding,prevention,oralleviationofa serious problemaffectingthehealthorwelfareofpregnantwomen,fetusesorneonates; andtheresearchisnotapprovableundertheaboveprovisions,thentheCOMIRBwill consultwithapanelofexpertsinpertinentdisciplines(forexample:science,medicine, ethics,law).Basedontherecommendationofthepanel,theCOMIRBmayapprovethe researchbasedoneither:
a. Thattheresearchinfactsatisfiestheconditionsabove,asapplicable;or b. Thefollowing:
oTheresearchpresentsareasonableopportunitytofurtherthe understanding,prevention,oralleviationofaseriousproblemaffectingthe healthorwelfareofpregnantwomen,fetusesorneonates;
oTheresearchwillbeconductedinaccordwithsoundethicalprinciples;and
oInformedconsentwillbeobtainedinaccordwiththeprovisionsfor informedconsentandotherapplicablesectionsofthismanual.
DHHS-fundedresearchthatfallsinthiscategorymustbeapprovedbytheSecretaryof HealthandHumanServices.IftheCOMIRBfindsthattheresearchpresentsa reasonableopportunitytofurthertheunderstanding,prevention,oralleviationofaserious problemaffectingthehealthorwelfareofpregnantwomen,fetusesorneonates;andthe researchisnotapprovableundertheaboveprovisions,thentheresearchwillbesentto OHRPforDHHSreview.
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