How the post trial acess issue has progressedthroughout the world in recent years
Fanny Nascimento Moura Viana
Sanitary point of view on post-trial access
DEVELOPMENT OF A NEW MEDICINEDEVELOPMENT OF A NEW MEDICINE
DRUG DISCOVERY
PRE-CLINICAL
Synthesis Identification of targets
In vitro testing
Pharmaco dynamics
Pharmaco kinetics
Toxicology
DEVELOPMENT OF A NEW MEDICINEDEVELOPMENT OF A NEW MEDICINE
Pharmaco techniques Clinical Trials
Approval/ registration Postmarketing
Formulation Phase I Phase IIIPhase IIApproval/
registration Phase IV
USE OF MEDICINES IN BRAZILUSE OF MEDICINES IN BRAZIL
In In BrazilBrazil, , productionproduction, marketing , marketing andand use use ofof medicines medicines cancan onlyonly bebe mademade afterafter grantinggranting sanitarysanitary registrationregistration byby thethe MinistryMinistry ofof HealthHealth..
SituationsSituations wherewhere unprovenunproven medical medical therapiestherapies is is permittedpermitted::
ClinicalClinical TrialsTrials
CompassionateCompassionate UseUse
ExpandedExpanded Access Access
PostPost trialtrial AccessAccess
CLINICAL TRIALSCLINICAL TRIALS
INSTANCE FOR APPROVAL OF CLINICAL TRIALS IN BRAZILINSTANCE FOR APPROVAL OF CLINICAL TRIALS IN BRAZIL
ETHICSETHICS
CEPsCEPs/CONEP/CONEP
HEALTH HEALTH SURVEILLANCESURVEILLANCE
LEGISLATION FOR REGULATORY LEGISLATION FOR REGULATORY CLINICAL TRIAL IN HUMANSCLINICAL TRIAL IN HUMANS
Law 6360/76 Law 6360/76 –– HEALTH SURVEILLANCEHEALTH SURVEILLANCE
RDC 39/2008Clinical Trials
R CNS 196/1996Humans
R CNS 292/1999Foreign cooperation
R CNS 301/2000Placebo
RDC 305/2002TSEs/ BSE
RDC 68/2003TSEs/ BSE
R CNS 346/2005CEP-CONEP
R CNS 251/1997Thematic area: new drugs
R CNS 340/2004Human Genetics
RDC 81/2008Import
R CNS 370/2007CEP-CONEP
IN 04/2009GCP
RDC 17/2010GMP
APPROVAL OF CLINICAL TRIALS IN BRAZILAPPROVAL OF CLINICAL TRIALS IN BRAZIL
-- SponsorSponsor-- CRO/ORPCCRO/ORPC
DOSSIERDOSSIER CEP(IRB)CEP(IRB)
JUDGEMENTJUDGEMENT
DOSSIER + IRB JUDGEMENTDOSSIER + IRB JUDGEMENT
EXPANDED ACCESSEXPANDED ACCESS
WithWith thethe adventadvent ofof thethe AIDS AIDS epidemicepidemic, , AIDS AIDS activistsactivists demandeddemanded whatwhat theythey calledcalled
““expandedexpanded accessaccess,,”” arguingarguing thatthat AIDS AIDS patientspatients whowho werewere notnot enrolledenrolled in a in a clinicalclinical trialtrial shouldshould
bebe allowedallowed to to taketake experimental experimental drugsdrugs underunder thethe supervisionsupervision ofof theirtheir personalpersonal physiciansphysicians..
(GROOPMAN, J., 2006)(GROOPMAN, J., 2006)
In In BrazilBrazil, , thethe conceptconcept ofof ExpandedExpanded Access Access waswas defineddefined in 1999:in 1999:RDC 26RDC 26 ((decemberdecember 17)17)
EXPANDED ACCESSEXPANDED ACCESS
ConceptConcept
SponsoredSponsored processprocess ofof providingproviding newnew productproduct, , promisingpromising, , notnot yetyet approvedapproved in in thethe NationalNational HealthHealth
SurveillanceSurveillance AgencyAgency, , whichwhich is inis in phasephase III III developmentdevelopment in in BrazilBrazil oror in in thethe country country ofof originorigin, for , for patientspatients withwith seriousserious
illnessesillnesses andand lifelife threateningthreatening, in , in thethe absenceabsence ofof satisfactorysatisfactory therapeutictherapeutic alternativesalternatives availableavailable in in thethe country, country, withoutwithout
additionaladditional costcost to to thethe patientpatient..
RDC No. 26, December 17, 1999
COMPASSIONATE USECOMPASSIONATE USE
In cases In cases ofof researchresearch involvinginvolving situationssituations for for whichwhich therethere is no is no establishedestablished treatmenttreatment ("("HumanitarianHumanitarian use" use" oror
""compassionatecompassionate") ") couldcould bebe authorizedauthorized to release to release thethe productproduct in in anan emergencyemergency,, provided there has been approval by the provided there has been approval by the
CEP, CONEP and ratified by the SVS / MS.CEP, CONEP and ratified by the SVS / MS.
ResolutionResolution ofof NationalNational HealthHealth CouncilCouncil (CNS) (CNS) No. 251, August 7, 1997.No. 251, August 7, 1997.
COMPASSIONATE USECOMPASSIONATE USE
TheThe compassionatecompassionate use is use is alsoalso characterizedcharacterized
byby thethe use use ofof unprovedunproved medical medical therapiestherapies outsideoutside thethe
contextcontext ofof clinicalclinical trialtrial to to patientspatients withwith seriousserious illnessesillnesses andand
lifelife threateningthreatening thatthat havehave no no therapeutictherapeutic alternativealternative
registeredregistered in in thethe country, country, butbut thethe authorizationauthorization is for is for eacheach
individual individual patientpatient differentlydifferently expandedexpanded accessaccess programsprograms..
POST TRIAL ACCESSPOST TRIAL ACCESS
ContinuedContinued use use byby participantsparticipants in a in a surveysurvey afterafter thethe conclusionconclusion ofof clinicalclinical trialstrials..
DECLARATION OF HELSINKI DECLARATION OF HELSINKI
“The protocol should describe arrangements for post-study access by study subjects to interventions identified as beneficial in the study or access to other appropriate care or benefits”.
COUNCIL FOR INTERNATIONAL ORGANIZATIONS OF MEDICAL COUNCIL FOR INTERNATIONAL ORGANIZATIONS OF MEDICAL SCIENCES (CIOMS)SCIENCES (CIOMS)“Additionally, if an investigational drug has been shown to be beneficial, the sponsor should continue to provide it to the subjects after the conclusion of the study, and pending its approval by a drug regulatory authority. ”
POST TRIAL ACCESSPOST TRIAL ACCESS
ContinuedContinued use use byby participantsparticipants in a in a surveysurvey afterafter thethe conclusionconclusion ofof clinicalclinical trialstrials..
RESOLUTION NO. 196/1996 (CNS)RESOLUTION NO. 196/1996 (CNS)The search should guarantee the return of benefits gained through research to the people and the communities where they are held.
RESOLUTION NO. 251/1997 (CNS)RESOLUTION NO. 251/1997 (CNS)The sponsor should ensure access for the drug under investigation for patients who have benefited from using.
POST TRIAL ACCESSPOST TRIAL ACCESS
BENEFITS OF RESEARCHBENEFITS OF RESEARCH
SeveralSeveral benefitsbenefits to to thethe communitycommunity::
Training Training ofof healthhealth workersworkers,,
ImprovementsImprovements in in thethe infrastructure,infrastructure,
ProvisionProvision ofof standard standard treatmenttreatment availableavailable,,
ProvisionProvision ofof publicpublic healthhealth measuresmeasures, , amongamong othersothers..
TheThe benefitbenefit ofof researchresearch notnot onlyonly directlydirectly relatedrelated to to thethe researchresearch subjectssubjects whowho participatedparticipated in in thethe studystudy..
DAINESI, S. M., 2006DAINESI, S. M., 2006
POST TRIAL ACCESSPOST TRIAL ACCESS
BENEFITS OF RESEARCHBENEFITS OF RESEARCH
The subjects in the study benefited clinically have the right toThe subjects in the study benefited clinically have the right to continue receiving free medication that brought a good for your continue receiving free medication that brought a good for your health, health, beyondbeyond the benefits that the study has brought to the the benefits that the study has brought to the community.community.
JÚNIOR, B. R. S., 2007
POST TRIAL ACCESSPOST TRIAL ACCESS
TheThe responsibilitiesresponsibilities ofof thethe sponsorssponsors do do notnot endend withwith thethe
completioncompletion ofof thethe studystudy, as , as theythey shouldshould provideprovide conditionsconditions ofof
securitysecurity andand monitoringmonitoring thethe use use ofof thethe drugdrug as as longlong as as
necessarynecessary whilewhile thethe researchresearch subjectsubject is is benefitingbenefiting fromfrom thethe
experimental experimental treatmenttreatment..
JÚNIOR, B. R. S., 2007
POST TRIAL ACCESSPOST TRIAL ACCESS
RISK MANAGEMENTRISK MANAGEMENT
-- Was the safety properly evaluated in studies in the early stagesWas the safety properly evaluated in studies in the early stages??
TheThe effectseffects ofof thethe drugdrug are are monitoredmonitored for short for short periodsperiods andand safetysafety assessmentassessment is is relatedrelated to to thethe studystudy periodperiod andand does does notnot extendextend thethe closedclosed..
GOLDIM, J. R., 2008GOLDIM, J. R., 2008
POST TRIAL ACCESSPOST TRIAL ACCESS
TOP QUESTIONSTOP QUESTIONS
-- HowHow longlong shouldshould suchsuch accessaccess postpost--studystudy??
-- Who is Who is responsibleresponsible for for providingproviding andand storingstoring thethe productproduct in in researchresearch??
-- HowHow to monitor to monitor andand reportreport adverseadverse eventsevents outsideoutside thethe contextcontext ofof a a controlledcontrolled clinicalclinical trialtrial??
-- Does a Does a singlesingle studystudy prove prove thethe efficiencyefficiency ofof a particular a particular interventionintervention??
-- Does the individual benefits correspond to the results obtained Does the individual benefits correspond to the results obtained in the study in the study as a whole?as a whole?
TheThe superioritysuperiority ofof a a newnew drugdrug mustmust bebe provenproven throughthrough a a statisticalstatistical analysisanalysis ofof surveysurvey data data andand notnot fromfrom thethe clinicalclinical evaluationevaluation ofof a a singlesingle patientpatient..
DAINESI, S. M., 2006 / 2009DAINESI, S. M., 2006 / 2009
• For cases where there is patient benefiting from the drug under investigation,
• Best alternative therapy,• The protocol does not provide an extension of the study
DONATION OF THE DRUG
SANITARY POINT OF VIEW ON POST-TRIAL ACCESS
www.anvisa.gov.br
Criteria and procedures:– Quantitative;– Final study report;– Letter explaining the need to execute the decision
recommended by the Resolution CNS 251/97;– Medical report;– Notification CEP;– Declaration by the sponsor :
• supply of study medication and safety evaluation.
DONATION OF THE INVESTIGATIONAL PRODUCT
www.anvisa.gov.br
194177
237
197
250
213
289
229
281
221
366
243
291
220
0
50
100
150
200
250
300
350
400
2003 2004 2005 2006 2007 2008 2009
Aprovação de Estudos Clínicos ANVISA
Estudos Submetidos à ANVISA para AprovaçãoEstudos Aprovados pela ANVISA
PROFILE OF REQUESTS
0
50
100
150
200
250
300
350
No.
of p
atie
nts
incl
uded
No. of patients included 73 316 109
EXPANDED ACCESS COMPASSIONATE USE POST TRIAL ACCESS
Requests approved by ANVISA to use unregistered drugs outside the context of clinical trial in the period from January 2008 to July 2010.
EXPANDED ACCESSEXPANDED ACCESS
ANTIRETROVIRAL82%
ANTINEOPLASTIC18%
Therapeutic class of expanded access programs authorized by ANVISA from January 2008 to July 2010.
COMPASSIONATE USECOMPASSIONATE USE
68%
28%
1%
1%
2%
0,31%
ANTINEOPLASTIC
ENZYME FOR REPLACEMENT
ANTIRETROVIRAL
ANTIVIRAL DRUGS
OTHER DRUGS ACTING ON THEVISION
Therapeutic class of compassionate use authorized by ANVISA from January 2008 to July 2010.
EXPANDED ACCESSEXPANDED ACCESS and COMPASSIONATE USECOMPASSIONATE USE
Status of registration of medicinal products authorized by ANVISA for use in programs of expanded access and compassionate use from January 2008 to July 2010.
Unregistered drugs in ANVISA15 (65%)
Registered drugs in ANVISA8 (35%)
POST TRIAL ACCESSPOST TRIAL ACCESS
- The donation of non-approved drugs may have been under-reported or under-counted,-The donation post-study can is covered in a program extension, which is nothing more than an extension of the research with the same subjects recruited.
NOTIFICATION OF THE EXTENSION STUDYNOTIFICATION OF THE EXTENSION STUDY
CHALLENGESCHALLENGES
- Review of RDC No. 26, December 17, 1999 (EXPANDED ACCESSEXPANDED ACCESS) include compassionate use and donation after study;
- Procedural donation after study;
- Medical Medical reportreport;;
-- Final Final studystudy reportreport;;
-- QuantitativeQuantitative;;
-- NotificationNotification IRB;IRB;
-- SponsorSponsor: : supplysupply ofof medicationmedication, , safetysafety evaluationevaluation, , monitoringmonitoring..
SANITARY POINT OF VIEW ON POST-TRIAL ACCESS
FANNY NASCIMENTO MOURA VIANA
THANK YOU!
WWW.ANVISA.GOV.BR