walker canadianandinternationalstandards

8/18/2019 Walker CanadianandInternationalStandards

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International and CanadianStandards:

Ethics and Regulatory

Melanie Walker, PhD Candidate


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Learning Objectives

Understand:

1. Clinical trial regulations and guidelines inCanada

2. International regulations and how theydiffer from Canada (USA, EuroeanUnion!

". In#estigator resonsi$ilities forcomliance with regulations andguidelines


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Not a learning objective…


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Canada


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Ethics / Regulatory Approvals o

Clinical !rials in Canada

Ethics Aro#al

% Conducted $y &esearchEthics 'oards:

institutional (local! or

central $oard or $oth % )andated $y any*all:

institution

funding source*agency

+ealth Canadaregulations

&egulatory Aro#al % Conducted $y o#-t

regulatory agencies:

+ealth roducts and

/ood 'ranch of +ealthCanada

% )andated $y:

Clinical 0rial&egulations for rugs

)edical e#ices&egulations

atural +ealthroducts &egulations


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Current Ethics "uidelines/

Regulations Applicable to Clinical

!rials in Canada

3ary $y trial

In#o4ed*re5uired $y: % use of human su$6ects

% source of funding

% inter#ention $eing studied % local*institutional re5uirements


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Applicable "uidelines/Regulations

Any )edical&esearch in#ol#inghumans

urem$erg Code

eclaration of+elsin4i

7ocal*Secific

re5uirements (i.e.&E', hosital,uni#ersity, industryor other sonsor!


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#cont$d%

+uman &esearchfunded $y Canadianfederal grantingagencies (CI+&,SE&C, SS+&C!

+uman &esearch

funded $y US federalfunds (i.e. ationalInstitutes of +ealth(I+!!

0ri8council olicyStatement

US /ederal

&egulations re:+uman Su$6ectsrotections

I+ uidelines


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#cont$d%

Clinical 0rialsIn#ol#ing rugs

Canada: +ealthCanada /ood andrug Act &egulationsre: Clinical 0rials

US: /A&egulations

IC+ 8 ood Clinicalractice uidelines(IC+8C!


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#cont$d%

Clinical 0rialsIn#ol#ing atural+ealth roducts

Clinical 0rialsIn#ol#ing )edicale#ices

atural +ealthroducts&egulations

(+ealth Canada!

)edical e#ices

&egulations(+ealth Canada!


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&ure'berg Code

19 standards hysicians must conform towhen carrying out eeriments on humans

i.e.

% Informed Consent 88 articiation voluntary

% &esearch must $e necessary ; $ased on rioranimal eerimentation

% &is4 roortionate to imortance % o unnecessary hysical*mental suffering

% /reedom to withdraw articiation at any time


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(eclaration o )elsin*i

)edical rogress $ased on research< research imro#estreatments and understanding of disease $ut in#ol#es ris4s and$urdens< must $e su$6ect to ethical standards

Content of rotocol

Comliance with eclaration

Indeendent &E' must gi#e continuing aro#al

=ell8$eing of su$6ect o#errides interests of science* society

3oluntary and informed articiation

rotect ri#acy and confidentiality of su$6ects Informed consent re5uirements

u$lication re5uirements


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RE+ "uidelines/Re,uire'ents

Address

% &e5uirement for S>s

% )em$ershi

% 0yes of aro#al

% =hat information must $e ro#ided to the&E'

% =hat must $e aro#ed $y the &E'(rotocol, informed consent, atientinformation, ad#ertisements etc!


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!C.S: Content

&E' mem$ershi

% um$er

% Comosition

&E' rocedures forre#iewing research

% ocuments*E#ents

% 7e#el of re#iew

% )eeting rocedures % &ecord ?eeing

/ree and InformedConsent % E#idenced in writing

% ecessary consentelements listed

ri#acy andconfidentiality

Conflicts of Interest

Clinical 0rials +uman enetic&esearch

+uman 0issue


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S 0ederal Regulations

US Code of Federal Regulations

Title 45, Part 46, Protection of Human Subjects

Includes research funded $y the US ational

Institutes of +ealth (I+! or it-s agencies (i.e.ational Cancer Institute or CI US!

% Ethics education re5uirement for researchers wor4ing onI+ funded ro6ects

% I+ collect C3s, / and 1@2-s annually % in#estigator B

>+& (US >ffice for +uman Su$6ects rotection!ensures comliance with this olicy

% Assurance re5uired for each articiating site


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S C0R !itle 123 .art 14

&E' mem$ershi and function

7e#el of re#iew (eedited*full $oard!

Informed consent re5uirements &E' and Institutional Assurances

must $e o$tained

ocumentation of +IAA comliance(atient authoriation!


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Canada 0ood 5 (rug Act

Regulations

art C, i#ision @:Drugs for Clinical 0rials In#ol#ing +uman Su$6ects

Aly to clinical trials in#ol#ing:

% In#estigational drugs (i.e. drugs that are not mar4eted,aro#ed for use, in Canada!

or

% )ar4eted drugs $eing used outside of their aro#ed use in

Canada i.e. clinical use, dose*formulation, route of administration or target

atient oulation


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Clinical !rials Regulations

&e5uire the su$mission of a FClinical 0rials Alication- (C0A!, formerly called anIn#estigational ew rug Alication (I!

% rotocol, consent, drug information, in#estigator$rochure

C0A Su$mitted to +ealth Canada % "9 day

re#iew eriod % o o$6ection letter issued


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Clinical !rials Regulations Re,uire…

Aro#ed Clinical 0rials Alication (C0A! Comliance with IC+8ood Clinical racticeuidelines

Su$mission and aro#al of changes to the rotocol(i.e. amendments, re#isions!

rug la$eled secifically for the trial

In#estigator signature on FGualified In#estigatorUnderta4ing /orm- which indicates agreement toerform trial in accordance with C

otification of re8mature discontinuation of the trial

&eorting serious ad#erse reactions

+ealth Canada may insect (audit! sonsors and*or

sites articiating on trials


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Clinical !rials Regulations -

Ethics Re,uire'ents

rotocols and any changes to rotocols(including informed consent! must $earo#ed $y an &E'

&E' comosition defined in regulations

(similar to 0ri8Council comosition H Cdncomonent!

&E' chair must sign an attestation (agrees tofollow +ealth Canada regulations, IC+8C!

&E' refusals to aro#e a rotocol or changesto a rotocol must $e reorted to +ealthCanada


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S 0ood and (rug Ad'inistration

#0(A% Regulations

Alica$le to studies conducted in Canada whereStudy is $eing done directly under a US I

US Is re5uired when:

% rug (s! is not mar4eted >r

% rug is mar4eted $ut one of the following conditionseist:

% intention to su$mit trial to /A as a well8controlled study % intention to change la$eling as a result of study results

% indication*dose etc. in#ol#es a significant increase in ris4


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S 0ood and (rug Ad'inistration

#0(A% Regulations

&egulations: % Code of /ederal &egulations, 0itle 21, Section

"12

% &e5uire the su$mission of an In#estigationalew rug Su$mission (I!

% &e5uirements for la$eling, safety reorting,in#estigators, &E' re#iew etc. secified in regs

In ractical terms % /A 1@2 re5uired

% /A /inancial disclosure re5uired


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IC) "ood Clinical .ractice

"uideline #"C.%

International ethical and scientific 5ualitystandard for trials in#ol#ing humans. Itaddresses:

% esign< conduct< recording< reorting

/ollow when conducting a trial:

Intended for su$mission to a regulatoryagency in an IC+ region

Any trial $eing conducted under a Clinical0rials Alication in Canada


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IC)-"C.

C: 'asic Structure % 1. lossary

% 2. rinciles

% ". &E' resonsi$ilities

% . In#estigator resonsi$ilities

% @. Sonsor resonsi$ilities

% J. rotocol and amendments % . In#estigator 'rochure

% K. Essential ocuments


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"C.: .rinciples

1. ethical rinciles

2. $enefits*ris4

". rights*safety of

su$6ects mostimortant

. drug info suorts trial

@. trial scientificallysound, rotocol

J. rotocol &E'aro#ed

. medical care $y a5ualified hysician

K. 5ualified indi#idualsconduct trials

L. free informed consent

19 data accurate etc.

11. confidentiality

12. drugs: )*rotocol

1". 5uality assurance


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"C.: Research Ethics +oard

#RE+% Responsibilities

Comosition, function and rocedures

ocuments to o$tain ; re#iew

&ecords


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"C.: Investigator

Responsibilities

Gualifications ; resources

Care of su$6ects

Communication with &E' rug

atient consent rocess

&ecords*reorts

Safety reorting


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"C.: Sponsor

Responsibilities

Guality assurance and5uality control

0rial management, datahandling and record

4eeing In#estigator selection

&egulatorysu$missions

Confirmation of &E're#iew

rug

Informed consentre5uirements

Serious Ad#erse E#ent&eorting

)onitoring ; Auditing % atients rights*well8$eing

rotected

% data is accurate,comlete, #erifia$le

Conduct o trial byeveryone is "C.co'pliant


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Su''ary o Applicable Regulations and

"uidelines by !rial !ype

RE+ "C.

(O)

!C.S )C

C!A

O)R.

&I)

0(A

All human trials M M M

H ew indication M M M M

US o#t funding * drug M M M N M N

Under US I M M M N M


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Su''ary o Investigator

Re,uire'ents

Aroriately 5ualified $y education and training

Gualifications (curriculum #itae! on file

Comlete*file re5uired forms (i.e. +ealth Canada

Gualified In#estigator form! eclare financial conflicts of interest (i.e. own a

comany! to &E', sonsor, su$6ects % in some cases, should not conduct trial

0raining on trial rotocol

I+ ethics education certificate (if alica$le!


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International Standards


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+ac*ground

&egulations that aly to trialsconducted in Canada are descri$ed inre#ious section

E#en if Canadian centres are notsu$6ect to international regulations,may $e of interest*rele#ance when

articiating in international trials 8may imact on o#erall rotocolconduct * logistics


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SA: 0ood and (rug Agency

#0(A% 7argest mar4et. harmaceutical comanies are

US8dri#en in their registration * de#elomentlans

% 0rials may $e conducted under a US I )ay recei#e comments from the /A re5uiringrotocol amendments e#en after aro#ed $y+ealth Canada

% E#en if not conducted under a US I, rotocolmay $e su$mitted for Secial rotocol Assessmentif A lanned

)ay ha#e to amend rotocol $ased on /A

comments


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SA 0(A

I is drug secific. >nce an I is inlace, any new trials are Ffiled- to theI. 0he /A ha#e "9 days tocomment, $ut no formal aro#al is

gi#en (no news is good news!: 'U0 theymay issue a FClinical +old-

In Canada, each trial has a uni5ue C0A; >7. 0he rug is filed under a rug)aster /ile, and each C0A su$mittedmust cross reference that )/.


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0(A

Unless the trial is conducted under a USI, /A1@2 and financial disclosuresare not needed % e#en if later /A Ais lanned.

If the trial is conducted under an I

% )ust conform to US regulations including&E' and informed consent regulations

% Essentially O +C*C re5uirements H 1@2* / forms


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European nion

Eu8C0 issued in 2991 (2991*29*EC!

)em$er states imlemented

thereafter Essentially addresses C

imlementation in clinical trials


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Eu(-C!

0rials re5uire regulatoryaro#al (h I eemt! andha#e EU&AC0 num$er

In#estigational )edicinalroduct

% )anufactured to ) 8authoriation needed

0rial harmacy*)may ac4 * la$el forthe trial

% 0rial medications sulied

to atient free of charge All trials conducted to C

&egulatory authorityenforcement

Safety sur#eillance % SUSA&s

&eort to &As andin#estigators for

sonsors trials &eort to EU

centralharmaco#igilancedata$ase

% SSA&s Annual listing to &A

and &E's forsonsors trial


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Chec*lists

6eeping !rac* o Your Responsibilities…77


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.rior to Opening !rial

=hat regulations alyPCan your &E' comly (i.e. >+&!P

In#estigator 5ualifications, C3, conflicts, trial training

reare ethics and regulatory $inders

Su$mit a C0A if re5uired< letter for cross8filing to)/< drug la$els '

Ensure 0CS, C, +C comliance

Informed consent % include all re5uired elements andris4s

Initial full $oard &E' aro#al % su$mit all re5uiredinformation*documents


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(uring the !rial

Informed consent rior to trial secificrocedures

Comly with the rotocol, document*reort if not

Source documents

)aintain essential documents (C!)aintain confidentiality

Ensure drug reconciliation * comliance with regs

>ngoing annual aro#al (full $oard if >+&!&E' ; +C aro#al for amendments*changes(may $e ost8hoc if immediate safety haard!


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End o the !rial

Inform &E' and +C when trial closes

Su$mit /inal reort to &E'

)onitor long term safety : inform atients and&E' as needed&etain records (included source documents andradiology! according to regulations (2@ years for

C0A trial! Audits*insections may occur during trial or afterfinal analysis


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