In o med consen o paedia ic clinical ials
in Eu ope
Pi kko Lepola,
1,2
Allison Needham,
3
Jo Mendum,
4
Pe e Sallabank,
5
Da id Neubaue ,
6
Saskia de Wild
7
1
Finnish In es iga o s Ne wo k
o Pedia ic Medicines, Clinical
Resea ch Ins i u e Helsinki
Uni e si y Cen al Hospi al L d,
Helsinki, Finland
2
Tampe e Cen e o Child
Heal h Resea ch, 33014
Uni e si y o Tampe e,
Tampe e, Finland
3
The Hospi al o Sick Child en
Resea ch Ins i u e, To on o,
Canada
4
PRA Heal h Sciences,
Reading, UK
5
RegulinX, Su bi on, UK
6
Depa men o Child,
Adolescen and De elopmen al
Neu ology, Uni e si y
Child en’s Hospi al/Uni e si y
Medical Cen e Ljubljana,
Ljubljana, Slo enia
7
Depa men o Pha macology
and Toxicology, Radboud
Uni e si y, Nijmegen,
The Ne he lands
Co espondence o
M s Pi kko Lepola, Finnish
In es iga o s Ne wo k o
Pedia ic Medicines, Clinical
Resea ch Ins i u e Helsinki
Uni e si y Cen al Hospi al,
00290, Helsinki, Finland;
pi kko.lepola@u a.fi
Recei ed 23 Decembe 2015
Re ised 4 May 2016
Accep ed 9 May 2016
Published Online Fi s
25 May 2016
To ci e: Lepola P,
Needham A, Mendum J,
e al.A ch Dis Child
2016;101:1017–1025.
ABSTRACT
Objec i e Paedia ic clinical ials a e o en conduc ed
as mul ina ional ials. In o med consen o assen is pa
o he e hics commi ee app o al o clinical ials. The
consen equi emen s a y be ween coun ies due o
na ional laws and egula ions, which a e no ha monised
in Eu ope. These disc epancies can p esen challenges
o paedia ic clinical ials. The aim o his s udy was o
assemble hese consen and assen equi emen s ac oss
he Eu opean Economic A ea. The colla ed na ional
equi emen s ha e no been publicly a ailable be o e,
despi e a eal need o his da a.
Me hods Na ional consen and assen equi emen s o
paedia ic clinical ials we e analysed and colla ed o
25 Eu opean Union Membe S a es and 2 Eu opean F ee
T ade Associa ion coun ies un il he end o 2014. The
da a we e e ie ed om exis ing da abases and h ough
communica ion wi h he compe en au ho i ies and
selec ed e hics commi ees. Resul s om a li e a u e
sea ch o in e na ional o na ional guidelines,
decla a ions and con en ions and academic socie ies’
publica ions se ed as compa ison ma e ial.
Resul s Consen and assen equi emen s a e
he e ogeneous ac oss hese coun ies. We compiled ou
findings in ‘The In o med Consen and Assen Tool Ki ’,
a able including 27 na ional consen and assen
equi emen s lis ed by indi idual coun y.
Conclusions Wide a ia ion in paedia ic consen s and
assen s p esen s challenges o mul ina ional paedia ic
ials in Eu ope. The oolki is a ailable o all hose
in ol ed in paedia ic clinical ials and e hics
commi ees, p o iding a new pla o m o p oac i e
eedback on in o med consen equi emen s, and may
finally lead o a needed ha monisa ion p ocess, including
uni o m s anda ds accep ed ac oss Eu ope.
INTRODUCTION
Clinical ials (CTs) in child en a e o en conduc ed
as mul ina ional, mul icen e ials, necessi a ed by
small pa ien popula ions, a i y o disease and
limi ed specialis acili ies. As CTs need a sepa a e
compe en au ho i y (CA) and e hics commi ee
(EC) app o al in each pa icipa ing coun y, he
pha maceu ical indus y and in es iga o s spend
much ime and esou ces p epa ing documen a ion
and co espondence o hese submissions.
In Janua y 2007, he Eu opean Union (EU)
Paedia ic Regula ion ((Eu opean Commission) No
1901/2006)
1
came in o o ce equi ing he conduc
o mo e paedia ic CTs o acili a e he de elop-
men and accessibili y o medicinal p oduc s o
child en. A u he EU CT Regula ion will come
in o o ce a e 28 May 2016,
2
bu while his
ha monises he clinical ial applica ion (CTA)
p ocess, i does no add ess he di e si y in e iew
and conduc o EC app o als a each si e.
The p ocess o ob aining EC app o al (wi h
consen o assen equi emen s o child en) is no
ha monised in he EU. Despi e in e na ionally
accep ed e hical p inciples
3–11
and se e al EU-le el
guidelines,
12–16
his a ea p esen s a majo challenge
o paedia ic CTs ac oss he EU. Al hough he doc-
ine o consen is an e hical co ne s one o
medical esea ch conduc ed in humans, special p o-
isions o child en a y be ween and, in some
cases, wi hin coun ies due o di e ences in
na ional laws and p ac ices.
Wi hin he Eu opean Economic A ea (EEA),
h ee egula o y amewo ks go e n he conduc o
paedia ic esea ch: he Con en ion on Human
Righ s and Biomedicine ( he O iedo
Con en ion);
12
Di ec i e 2001/20/EC (Eu opean
Wha is al eady known on his opic?
▸The e a e no iceable di e ences be ween
na ional consen and assen equi emen s o
paedia ic clinical ials in Eu ope due o
na ional laws and egula ions.
▸The in e na ional and he e hics socie ies’
guidelines a e no based on uni o m s anda ds
and a ely p o ide de ailed consen o assen
ecommenda ions o child en.
▸A single sou ce o comp ehensi e mul ina ional
da a on in o med consen and assen
equi emen s o paedia ic clinical ials ac oss
Eu ope is no publicly a ailable.
Wha his s udy adds?
▸The ‘In o med Consen and Assen Tool Ki ’is a
publicly a ailable esou ce o s akeholde s
in ol ed in he unning o paedia ic clinical
ials in Eu ope.
▸These da a p o ide a new pla o m o
p oac i e eedback om s akeholde s o
main ain a common esou ce and app oach o
consen and assen equi emen s in Eu ope.
▸These da a hope o p omo e discussion o
long- e m decisions and p ac ical changes
leading o uni o m e hics commi ee p ocedu es
ac oss he Eu opean Economic A ea.
Lepola P, e al.A ch Dis Child 2016;101:1017–1025. doi:10.1136/a chdischild-2015-310001 1017
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Commission Di ec i e)
14
and he Paedia ic Regula ion
((Eu opean Commission) No 1901/2006).
1
Disc epancies exis
be ween hese h ee amewo ks. Fo example, he e o powe
o a child o pa icipa e in esea ch is no co e ed in he
Paedia ic Regula ion, while he O iedo Con en ion allows a
mo e ex ensi e decision-making capaci y by he child han he
Eu opean Commission Di ec i e, which elies on in es iga o ’s
conside a ion o he explici wish o a child. The aim o his
wo k is o desc ibe he he e ogenei y in consen and assen
equi emen s o paedia ic CTs and o p o ide a abula ed
summa y o hese equi emen s by coun y as a ool o s ake-
holde s p epa ing paedia ic CT submissions in he EEA.
METHODS
The wo king g oup (WG) o he Eu opean Ne wo k o
Paedia ic Resea ch a he Eu opean Medicines Agency
(Enp -EMA) collec ed specific legal equi emen s o consen and
assen o child en and adolescen s om he na ional legisla ions
o 25 EU membe s a es and 2 Eu opean F ee T ade Associa ion
(EFTA) coun ies (No way and Iceland) du ing 2014. The
p ima y da a sou ce was a eposi o y o EC submissions om
na ional au ho i ies p o ided by he Con ac Resea ch
O ganiza ion (CRO), PRA Heal h Sciences (PRAHS).
17
Seconda y sou ces we e publicly a ailable da a ound on
na ional websi es o egula o y au ho i ies, such as Medicines
Agencies and Na ional E hics Commi ees. Addi ional da a came
h ough Regulinx,
18
a UK-based company specialised in consul -
ing on egula o y a ai s, and om he Finnish In es iga o s
Ne wo k o Pedia ic Medicines (FinPedMed).
19
Table 1 p o ides a snapsho o he in o ma ion colla ed in
2014. The da a a e a anged by coun y unde h ee main head-
ings. The fi s heading, ‘Consen /Assen om child’, includes
da a on he legal age o consen and manda o y o sugges ed
age anges defined o assen (o consen i assen is no used).
The second heading, ‘Consen om pa en (s)/gua dian(s)’,
includes legal equi emen s o he numbe o equi ed signa o -
ies. The hi d heading, ‘Gene al in o med consen in o ma ion’
includes o ficial language equi emen s and consen empla e(s),
guidelines o addi ional na ional in o ma ion wi h exis ing web
links.
In addi ion, he WG sys ema ically sea ched online sou ces o
iden i y subjec - ela ed a icles, lea ned socie ies’ ecommenda-
ions and e hical guidelines, con en ions and ecommenda ions.
The sea ch was conduc ed in he PubMed (US Na ional Lib a y
o Medicine, Na ional Ins i u es o Heal h) da abase, EU
Commission websi e, na ional compe en au ho i ies’websi es
and Google sou ces using he keywo ds: e hics, guideline, egu-
la ions, paedia ic, mino s, child en, biomedical esea ch, clin-
ical ials, human igh s and child en’s igh s. The sea ch
esul ed in 28 ele an documen s ela ed o medical esea ch
e hics on humans and, mo e specifically, on child en. Ten had a
wo ldwide scope, nine a con inen al o na ional scope, and nine
we e publica ions om academic socie ies.
2–14 20–34
These docu-
men s we e compa ed wi h he cu en o ficial and legal ecom-
menda ions by e i ying he consen - ela ed and assen - ela ed
ex s o hese documen s.
Finally, pe sonal expe iences o he WG membe s (ie, in he
conduc ed mul icen e ials and communica ion wi h ECs)
we e used o supplemen a y compa ison. Once all he da a
sou ces o consen and assen equi emen s in he EEA had
been colla ed, he WG compa ed and analysed he sou ces o
disc epancy in p ac ice ac oss he ju isdic ions. This e ealed
se e al disc epancies, which a e add essed in he discussion
sec ion.
RESULTS
Assen and consen : di e ences in use and defini ions
Bo h he e m ‘consen ’and ‘assen ’a e in e p e ed di e en ly
in legal ex s be ween EEA coun ies. Gene ally, each coun y’s
na ional legisla ion includes legal age anges and equi emen s
o ei he consen o assen om a child, in addi ion o any
legal (pa en al o gua dian) signa u es. The defini ion o hese
wo e ms es s on he need o hese signa u es: ei he gi en by
he ial subjec alone, o in conjunc ion wi h he pa en s/gua -
dians. Usually, consen is defined acco ding o he legal age limi
o majo i y, which di e s be ween coun ies. This is no he
case in all coun ies, like he Ne he lands whe e in an in o med
consen is needed, in addi ion o pa en al consen in child en
be ween 12 and 17 yea s o age. Assen is a non-legal ag ee-
men , and an addi ional pa en al/gua dian signa u e (consen ) is
always equi ed be o e he pa icipa ion o he child in a ial is
legally accep ed.
Di e ences in consen and assen age limi s and legal
signa u es
In mos o he EEA coun ies, 18 yea s is he legal age o inde-
penden consen , bu he ollowing excep ions should be no ed:
14 yea s in Aus ia, 15 yea s in Finland and Denma k and
16 yea s in he UK. These excep ions come wi h ce ain limi a-
ions and wi h he obliga ion o no i y pa en s/legal gua dians.
Howe e , ac oss all he EEA coun ies, 32 di e en age g oup-
ings o he legal age exis o ecommended addi ional assen o
consen needed om he child pa icipa ing in he CT. These
g oupings include, o example, 4–11 yea s, 12–14 yea s and
14–17 yea s. Only h ee coun ies (C oa ia, Li huania and
Slo akia) ha e no specified age g oups o assen o consen .
Di e ences a e also seen in he equi emen o signa u es
om pa en s o legal gua dians. Se en een coun ies (63%)
equi e signa u es o bo h pa en s in addi ion o he child’sown
assen o consen . Specific guidelines wi h consen o m em-
pla es and addi ional aid ma e ial (eg, pic u es) o child en in
paedia ic CTs ha e been gene ally accep ed by some EU
membe s a es (eg, Finland and UK).
DISCUSSION
The Uni ed Na ions Con en ion on he Righ s o he Child
defines a child as e e yone unde 18, unless, ‘unde he law
applicable o he child, majo i y is a ained ea lie ’.
3
Fo chil-
d en below ha age, he e a e no iceable di e ences be ween
na ional and o ganisa ional egula ions on e hical consen in
paedia ic CTs. These conce n specifically non-uni o m age
limi s and age anges, di e en defini ions o legal consen and
he equi emen o pa en al o legal gua dian signa u es.
I appea s ha hese c i e ia, o unknown easons, a e no
uni o mly defined in Eu opean guidelines o ecommenda ions.
We also ound ha he in e na ional and he e hics socie ies’
guidelines and ecommenda ions a ely de ail consen o assen
p ocedu es o child en,
71327–31
bu o en e y gene ic ins uc-
ions wi hou specificdefini ions.
2–68–12 20–26 32–34
Fo he
g ea e pa , hese c i e ia do no seem o be based on he de el-
opmen al s age o he child and his/he compe ency le el o
in o med consen o assen . Compe ency, in addi ion o heal h
condi ion, is impo an o de e mining u he ac ions i ial
subjec s each he age o majo i y du ing he s udy and need o
gi e hei own (legal) consen o con inue.
2
The e ms ‘consen ’and ‘assen ’a e also no defined in
gene al guidelines and a e no ha monised ac oss he EEA.
Some Eu opean coun ies use he e m consen o bo h mino s
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Table 1 The In o med Consen and Assen Tool Ki —in o med consen equi emen s o paedia ic clinical ials in Eu ope
Consen /assen om child* Consen om pa en (s)/gua dian(s) Gene al in o med consen in o ma ion
Coun y
Legal age
o consen †
Manda o y/sugges ed age
anges de ined o assen
(o consen i assen no
used)‡Numbe o equi ed signa o ies
O icial language
equi emen s Consen empla e(s)/guidelines/in o ma ion sou ces
Aus ia No
speci ied
P ac ice––
14 yea s
8–13 yea s
EC may equi e younge
assen s
Bo h pa en s Ge man h p://www.medunig az.a /e hikkommission/Fo um/index.h m
h p://www.e hikkommissionen.a /
h p://www.uibk.ac.a /s a ech /scheil/
scheil-ein ueh ung-in-die-a zneimi elp ue ung-bei-kinde n-und-jugendlichen---kks--kids-ip.pd
Belgium 18 yea s 4–11 yea s (some si es do no
use unde 12 yea s)
12–14 yea s
14–17 yea s
One pa en a ec ui men , bu bo h
pa en s a some poin o signa u es
Du ch, F ench;
Ge man a si e eques
h p://www. agg-a mps.be/en/human_use/medicines/medicines/ esea ch_de elopmen /e hic_
commi ee/ empla es_in o med_consen /
Do no ha e paedia ic empla es
Bulga ia 18 yea s 6–11 yea s
12–14 yea s
14–17 yea s—use own
consen +pa en al signa u e
also equi ed
Bo h pa en s Bulga ian No na ional EC websi es a ailable in English
Bulga ian D ug Agency -> clinical ials
h p://en.bda.bg/index.php?op ion=com_
con en & iew=ca ego y&layou =blog&id=14&I emid=34
C oa ia No hing
speci ied
No hing speci ied No hing speci ied C oa ian Agency o Medicinal P oduc s and Medical De ices o C oa ia -> Cen al E hics Commi ee ->
h p://www.almp.h /?ln=en&w=o_SEPu
In o ma ion on clinical ials no a ailable in English.
Czech
Republic
18 yea s 7–11 yea s
12 yea s—own consen
12–14 yea s
15–17 yea s
Bo h pa en s. Only by one pa en i
he o he pa en is no lis ed in he
child’s bi h ce i ica e, has died o is
younge han 18 yea s.
Czech. Whe e he child’s pa en s
(o one o hem) a e o eign
na ionals, he in o ma ion shee
shall be p esen ed in bilingual
o ma .
S a e Ins i u e o D ug Con ol -> De ails o clinical ials / Guidelines and Fo ms / KLH-22 V.1:
h p://www.sukl.eu/medicines/klh-22- e sion-1
Denma k 18 yea s 15–17 yea s––p oxy consen Bo h pa en s
Excep ion—no pa en s i aged 15–17
and non-in e en ional no- isk s udy
(EC dispensa ion equi ed)
Danish The Na ional Commi ee on Heal h Resea ch E hics -> Guidelines abou no i ica ion
h p://www.c k.sum.dk/CVK/Home/English.aspx
h p://c k.sum.dk/English/guidelinesabou no i ica ion.aspx -> 4.4. Medicinal p oduc ials and
clinical in es iga ions o medicinal de ices in ol ing legally incompe en subjec s; 4.4.1 T ials
wi h child en and young people unde he age o 18
h p://c k.sum.dk/English/guidelinesabou no i ica ion.aspx#A sni %205.0
Ac on Resea ch E hics Re iew o Heal h Resea ch P ojec s
Es onia 18 yea s 0–7 yea s
7–17 yea s––manda o y
Bo h pa en s Es onian S a e Agency o Medicine -> Clinical ials -> Condi ions and p ocedu e o conduc ing clinical
ials o medicinal p oduc s
h p://www. a imiame .ee/en/clinical- ials-medicinal-p oduc s-es onia
Finland 15 yea s W i en sepa a e consen as
soon as child is li e a e; unde
15 yea s––own consen
+pa en al consen ;
15–17 yea s––own consen
+pa en al no i ica ion i mino
can unde s and he
signi icance o esea ch+di ec
heal h bene i is expec ed
Pa en o legal gua dian and he
child, when hey a e li e a e, need o
sign he consen . One pa en by he
law, bu he o he one can be
in o med (bo h can sign i hey wan ).
Finnish, Swedish Medicines Resea ch Ac 488/1999
Medical Resea ch Dec ee 986/1999
Addi ional in o:
FinPedMed guidelines; legal and e hical egula ion— empla es o age g oups 6–17 and
pa en s
Regula o y equi emen s o clinical ials in Finland
Pic u e ca ds o suppo IC p ocess
Con inued
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Table 1 Con inued
Consen /assen om child* Consen om pa en (s)/gua dian(s) Gene al in o med consen in o ma ion
Coun y
Legal age
o consen †
Manda o y/sugges ed age
anges de ined o assen
(o consen i assen no
used)‡Numbe o equi ed signa o ies
O icial language
equi emen s Consen empla e(s)/guidelines/in o ma ion sou ces
F ance 18 yea s Based on EC—usually wo o
h ee age g oups
4–6 yea s
7–12 yea s
13–17 yea s
Pic u e ICFs o young child en
Bo h pa en s F ench Comi é de P o ec ion des Pe sonnes Sud-Médi e anée II : h p://www.cpp-sudmed2. /
In o ma ion-e -au o isa ion-des?lang=
Na ional Consul a i e E hics Commi ee o Heal h and Li e Sciences:
h p://www.ccne-e hique. /en
Ge many 18 yea s 7–11 yea s
12–16 yea s
17 yea s––own consen
+pa en al consen equi ed
Bo h pa en s Ge man Ge man E hics Council;
h p://www.e hik a .o g/—no in o ma ion o clinical ials
Landesä z ekamme B andenbu g—in o ma ion a ailable ONLY in Ge man.
h ps://www.laekb.de/
ICF Guidance
h ps://www.laekb.de/ iles/146A97FF999/AMG_Pa ien enin o_Kinde _7bis11.pd
Hunga y 18 yea s Unde 6 yea s
6–10 yea s
11–14 yea s
15–17 yea s
One pa en Hunga ian Na ional Ins i u e o Pha macy and Nu i ion -> Laws and egula ions (only a ailable in
Hunga ian) -> Minisz e i endele ek
h p://ogyei.go .hu/sea ch/index.php?sea chPh ase=dec ee& om=10
h p://www.ogyei.go .hu/magya _jogszabalyok/
-> Dec ee 35/2005 (VIII. 26.) o he Minis e o Heal h on he clinical ial and applica ion o
co ec clinical p ac ices o in es iga ional medicinal p oduc s in ended o use in humans
7§ Clinical ials conduc ed on mino s
h p://ne .jog a .hu/j /gen/ge doc.cgi?docid=A0500035.eum
Iceland 18 yea s Unde 12 yea s One pa en — he EC can eques bo h
pa en s’signa u es in some cases.
Icelandic o English. The s udy
objec i e in Icelandic. Ma e ials
in Icelandic.
(Fo s udies in ol ing g oups o
o he e hnici y, an app op ia e
language is equi ed.)
The Na ional Bioe hics Commi ee
(h p://www. sn.is/en/node/189)
The Pa liamen ; h p://www.al hingi.is/english -> h p://www.al hingi.is/lagasa n/
log-sam hykk -a-al hingi/ ->
The Ac o Law, No. 44/2014, on scien i ic esea ch wi hin he heal h sec o de ines he
condi ions o biomedical esea ch and he ole o he bioe hics commi ees
h p://www.al hingi.is/lagas/nuna/2014044.h ml
Se e al laws and egula ions on da a p o ec ion, medicines, biobanks and heal h in o ma ion
collec ions (2014), e c
I eland 16 yea s
(clinical
ials)
18 yea s
(all o he
esea ch)
7 yea s, o acco ding o
capaci y o child
One pa en English Lis o Resea ch E hics Commi ees o clinical ials o IMP:
h p://heal h.go .ie/
eu opean-communi ies-clinical- ials-on-medicinal-p oduc s- o -human-use- egula ions-2004/
Resea ch E hics Commi ee S anda d Applica ion Fo m:
h p://www.molecula medicinei eland.ie/ esea ch_e hics
Na ional Consen Policy: h p://www.hse.ie/eng/abou /Who/quali yandpa ien sa e y/Na ional_
Consen _Policy/consen aine esou ce/ aine iles/Na ionalConsen PolicyDOC.h ml
Clinical T ial Regula ion: S.I. No. 190/2004—Eu opean Communi ies (Clinical T ials on Medicinal
P oduc s Fo Human Use) Regula ions, 2004
h p://www.i ishs a u ebook.ie/2004/en/si/0190.h ml
Con inued
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Table 1 Con inued
Consen /assen om child* Consen om pa en (s)/gua dian(s) Gene al in o med consen in o ma ion
Coun y
Legal age
o consen †
Manda o y/sugges ed age
anges de ined o assen
(o consen i assen no
used)‡Numbe o equi ed signa o ies
O icial language
equi emen s Consen empla e(s)/guidelines/in o ma ion sou ces
I aly 18 yea s 6–10 yea s
11–14 yea s
15–17 yea s––wi h own
signa u e
No o icial manda o y age(s)
o assen . Di e en
age- ailo ed assen s a e
submi ed olun a ily, and a e
e alua ed by he ECs
Bo h pa en s I alian The I alian Medicines Agency h p://www.agenzia a maco.go .i /en/con en /clinical- ials
he I alian egula ion on CTs include he ollowing:
D.lgs 211/2003 h p://www.agenzia a maco.go .i /si es/de aul / iles/dec e o_24062003_inglese.
pd
DM 21/12/07 h ps://www.agenzia a maco.go .i / icclin/si es/de aul / iles/ iles_wysiwyg/ iles/
No ma i a/MD_21_Decembe _2007_CTA o m_English.pd
La ia 18 yea s 0–7 yea s
7–17 yea s
One pa en o legal ep esen a i e La ian S a e Agency o Medicines o he Republic o La ia -> Clinical ials and non-in e en ional
ials -> legisla ion
h p://www.z a.go .l /?se lang=en -> h p://www.z a.go .l /?id=396&sa=396& op=386 ->
h p://www.z a.go .l /index.php?id=381&sa=381& op=333&lang
h p://www.z a.go .l /doc_upl/MK_no _289_English_02062010.pd
Li huania 18 yea s No se ages Bo h pa en s Li huanian The Li huanian Bioe hics Commi ee -> Biomedical Resea ch -> a ou able opinion on clinical
d ug ial
h p://bioe ika.sam.l /index.php?3202747546
In o med Consen
h p://bioe ika.sam.l /index.php?3221858831 ->
h p://bioe ika.sam.l /index.php?577320631—in o ma ion a ailable only in Li huanian
h p://bioe ika.sam.l /index.php?3202747546
Mal a 18 yea s 6–17 yea s Pa en s o legal ep esen a i e
P ac ice—bo h pa en s
One o he o icial languages o
Mal a (eg, Mal ese) o in a
language
unde s andable o he clinical
ial subjec and/o his legal
ep esen a i e.
Mal a Heal h E hics Commi ee
h ps://heal h.go .m /en/appbodies/hec/Pages/Links.aspx
Mal ese Clinical T ials Regula ions 2004 (LN490 o 2004) MEDICINES ACT, 2003 (ACT NO. III OF
2003); h p://jus icese ices.go .m /DownloadDocumen .aspx?app=lp&i emid=16860&l=1
The
Ne he lands
18 yea s 12–17 yea s Bo h pa en s.
I pa en s a e di o ced and hey bo h
ha e pa en al igh s, hey bo h ha e
o sign. Fo a single pa en , wi hou
ano he pa ne wi h pa en al igh s,
one signa u e is enough.
Du ch Cen al Commi ee on Resea ch In ol ing Human Subjec s (CCMO) -> Human Subjec ->
In o med Consen —in o ma ion a ailable only in Du ch.
h p://www.ccmo.nl/en/ -> h p://www.ccmo.nl/en/mino s
Con inued
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Table 1 Con inued
Consen /assen om child* Consen om pa en (s)/gua dian(s) Gene al in o med consen in o ma ion
Coun y
Legal age
o consen †
Manda o y/sugges ed age
anges de ined o assen
(o consen i assen no
used)‡Numbe o equi ed signa o ies
O icial language
equi emen s Consen empla e(s)/guidelines/in o ma ion sou ces
No way 18 yea s 16–17 yea s––wi h own
signa u e
12–16 yea s––in special
ci cums ances
Main ule: bo h pa en s sign he
consen o m i hey ha e pa en al
esponsibili y o he child.
Requi ed o all child en unde
12 yea s old.
No wegian The No wegian Na ional Resea ch E hics Commi ees -> Clinical T ials -> Regula ions
h ps://www.e ikkom.no/en/e hical-guidelines- o - esea ch/
h p://www.legemiddel e ke .no/English/Clinical_ ials/Regula ions/Documen s/No wegian%
20 egual ion%20 o %20Clinical%20T ials.pd
Na ional da abase o Laws and Ac s -> Lo om medisinsk og helse aglig o skning
(helse o skningslo en)—in o ma ion a ailable only in No wegian.
h ps://lo da a.no/dokumen /NL/lo /2008-06-20-44?q=helse o skning
Ac on medical and heal h esea ch (Helse o sknings-lo en)
Guidance o Helse o sknings-lo en (in No wegian only) Addi ional in o:
No wegian Medicines Agency: Websi e on clinical ials.
Poland 18 yea s 6–11 yea s
12–15 yea s
16–17 yea s
One pa en
P ac ice—bo h pa en s
Polish h p://www.eu ecne .o g/in o ma ion/poland.h ml
No na ional EC websi es a ailable in English
Po ugal 18 yea s 0–8 yea s
8–12 yea s
12–17 yea s
Bo h pa en s Po uguese h p://www.eu ecne .o g/in o ma ion/po ugal.h ml
CEIC—Na ional E hics Commi ee o Clinical Resea ch
h p://www.in a med.p /po al/page/po al/CEIC/English
No na ional egula ions/ac s a ailable in English
Romania 18 yea s Unde 6 yea s
6–10 yea s
11–14 yea s
15–18 yea s
Bo h pa en s Romanian Na ional E hics Commi ee o Romania
h p://www.adsm. o/ o/comisia+na ionala+de+bioe ica+a+medicamen ului+si+a+dispozi i elo
+medicale#
No in o ma ion a ailable in English
Sco land
(UK)
16 yea s 0–5 yea s
6–10 yea s
11–15 yea s
Consen wi h own signa u e
unde 16 yea s, i hey a e
compe en o do so
One pa en English NRES Guidance
h p://www.h a-decision ools.o g.uk/consen /p inciples-child en.h ml and
h p://www.ukc g.nih .ac.uk/de aul .aspx
Slo akia n.a. n.a. n.a. Slo akian The S a e Ins i u e o D ug Con ol (SIDC) -> Clinical ials -> Ins uc ions
h p://www.sukl.sk/en?page_id=256 ->
h p://www.sukl.sk/en/clinical- ials/ins uc ions?page_id=2821
No na ional egula ions/ac s a ailable in English
Slo enia 18 yea s 9 yea s—assen
15 yea s—wi h own signa u e
One pa en Slo enian Republic o Slo enia Na ional Medical E hics Commi ee ->
h p://kme-nmec.si/—only on page
No addi ional in o ma ion a ailable.
Spain 18 yea s 0–11 yea s
12–17 yea s––wi h own
signa u e
One pa en Spanish The Agencia Española de Medicamen os y P oduc os Sani a ios (AEMPS); A s a e agency wi hin
he Spanish Minis y o Heal h, Social Se ices and Equali y -> Medicines o Human use—>
Clinical esea ch wi h medicines
h p://www.aemps.gob.es/en/in es igacionClinica/medicamen os/home.h m
The Minis y o Heal h, sec ion abou egula ion o clinical ials:
h p://www.aemps.gob.es/en/legislacion/espana/in es igacionClinica/ensayos.h m
The Spanish Regula ion abou Clinical ials: he ROYAL DECREE 223/2004-sec ion 7.3 (English
e sion is a ailable by eques )
Con inued
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Table 1 Con inued
Consen /assen om child* Consen om pa en (s)/gua dian(s) Gene al in o med consen in o ma ion
Coun y
Legal age
o consen †
Manda o y/sugges ed age
anges de ined o assen
(o consen i assen no
used)‡Numbe o equi ed signa o ies
O icial language
equi emen s Consen empla e(s)/guidelines/in o ma ion sou ces
Sweden 18 yea s W i en sepa a e consen as
soon as child is li e a e
6–10 yea s
11–14 yea s
15–17 yea s––wi h own
signa u e
Bo h pa en s and he child, when
li e a e, need o sign he consen
Swedish The Cen al E hical Re iew Boa d -> Documen s -> In o ma ion o Resea ch Pa icipan s
h p://www.epn.se/en/s a / he-o ganisa ion/ -> h p://www.epn.se/en/s a /
cen al-e hical- e iew-boa d-documen s/ -E ikp ö ningslagen 2008.
Regula o y equi emen o clinical ials LVFS 2011:19
Läkemedelslagen—1992
Biobank law––2002
Pe sonal Da a Ac 1998
Na ional Medicines Agency -> Legisla ion -> Codes o S a u es -> 1996:17 Clinical ials o
medicinal p oduc s
h ps://lakemedels e ke .se/english/ -> h ps://lakemedels e ke .se/english/o e iew/Legisla ion/
Codes-o -s a u es/
UK 16 yea s 0–5 yea s
6–10 yea s
11–15 yea s
One pa en English NRES Guidance;
h p://www.h a-decision ools.o g.uk/consen /p inciples-child en.h ml and
h p://www.ukc g.nih .ac.uk/de aul .aspx
© Eu opean Medicines Agency, 2015. Rep oduced wi h pe mission
*Consen /assen om child: his in o ma ion has been mainly collec ed ia he no mal daily wo k and no es o he CRO Company, PRA Heal h Sciences (UK), when p epa ing EC submissions o na ional au ho i ies. Some o his in o ma ion is no a ailable
in English, no publicly a ailable in egula o y au ho i y’s web pages. In addi ion, some English- ansla ed ex e sions may include inaccu a e e ms o explana ions, which could gi e ise o di e en in e p e a ions. The e o e, he au ho s canno
gua an ee 100% accu acy o all na ional equi emen s. In addi ion, his able is a snapsho o he da a ga he ed in 2014, which migh ha e subsequen ly changed.
†Legal age o consen : legal age o consen means he age om which a child is able o gi e and sign hei own independen legally alid consen acco ding o he na ional law/ac / egula ion. Child en below his age limi a e incapable o gi ing legal
in o med consen and need pa en al/legally au ho ised gua dian’s in o med consen wi h a signa u e o pa icipa e in a clinical s udy. Pa en al/legally au ho ised gua dian’s in o med consen may be ob ained/sough in addi ion o he child’s own consen /
assen , o when he child abo e he age limi is incapable o sign consen due o a di icul physical condi ion.
‡Manda o y/sugges ed age anges de ined o assen (o consen i assen no used): hese manda o y o sugges ed age anges a e de ined in na ional egula ion/law/ac , o a child below he legal age o consen and o own in o med consen o assen
(depending on he e minology used in legal ex s). This consen o assen is ob ained in addi ion o he legally alid pa en al/legally au ho ised gua dian’s signed in o med consen . This ype o child’s own assen /consen suppo s he child’s in eg i y and
igh s, c ea es he oppo uni y o hea hei own opinion, supposed will and possible dissen , hus espec ing he child’s au onomy in he in o med consen p ocess.
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(olde child en below legal adul age) and pa en s (legal gua -
dians). Usually, he e m assen e e s o a child’s o mino ’s
ag eemen o he ial (no legally alid on i s own), while
consen is documen ed h ough legal signa u e(s) by he pa en s
(gua dians) o he child, when he child is abo e he legal age.
The e a e mo e han 1000 ECs in Eu ope,
35
which esul in
subs an ial a iabili y o EC composi ions and p ac ices,
36–38
wi h consequen ly a ce ain deg ee o inconsis ency in he
equi ed consen and assen documen a ion o mul ina ional
and mul icen e ials. Mo eo e , much ime and esou ces may
be needed o ob ain app o als. To manage hese inconsis encies
and o educe he duplica i e wo kload, sponso s a e ecom-
mended o pe o m an i e a i e o sequen ial e iew a each pa -
icipa ing ins i u ion o coun y.
The Eu opean Medicines Agency (EMA) has e alua ed he
impac o he Paedia ic Regula ion a e i s fi s 5 yea s o being
in o ce.
39
So a , he egula ion has no ye led o mo e paedia -
ic CTs in Eu ope, al hough he e a e plans o conduc CTs wi h
en olmen o mo e child en.
39
S ill, he ini ia ion o new CTs
may be hampe ed by he p ac ical obs acles o complex EC
p ocesses.
Cu en ly, i is no possible o seek Eu opean-wide legisla i e
changes o EC p ac ice ha monisa ion, as he p ac ice o one
EC will no necessa ily wo k o ano he wi hou conce ed
e o o achie e ha mony. Howe e , an expe g oup has
designed model consen and assen o ms o di e en paedia -
ic age g oups,
40
which could be applied ac oss Eu ope.
Fu he mo e, be e defini ions o he concep s o ‘unde s and-
ing’,‘capabili y’,‘capaci y o au onomous decisions’and
‘mo al unde s anding o al uism’could g ea ly suppo a ha -
monisa ion p ocess.
To sol e hese p oblems, we sugges he ollowing measu es:
▸Uni o m, commonly accep ed s anda ds and guidance ac oss
Eu ope/EEA
▸Defini ion o he lowes age limi o consen and assen
equi ing own signa u es in addi ion o pa en al (legal)
consen un il he legal age o majo i y pe mi s independen
consen
▸Fundamen al discussion o c ea e mo e de ailed defini ions
o assen and consen and o decide whe he hese e ms
could be ha monised and used wi h simila p inciples o
paedia ic popula ion
▸S anda dised s uc u e and eading le el equi emen s o
consen and assen documen s, including ecommenda ions
o legal gua dian’s (pa en al) signa u es
▸A mas e consen /assen empla e in all na ional languages
being publicly and eadily a ailable.
‘The In o med Consen and Assen Tool Ki ’was upda ed
mainly un il he end o 2014. As na ional-le el egula ions and
laws may change o e di e en in e als, he accu acy o he
da a and linked documen s a e dependen upon egula e iew.
The Enp -EMA’s cen al aim is o enhance and p omo e he
conduc o paedia ic CTs in Eu ope. This oolki being publicly
a ailable ee o cos on he Enp -EMA websi e mee s his aim.
Please go o: h p://www.ema.eu opa.eu/Pa ne s&Ne wo ks/
Ne wo ks/Enp -EMA/Enp -EMA ac i i ies, o di ec ly a : h p://
inyu l.com/h2x l . Wi h his oolki , we hope ha all s ake-
holde s will p oac i ely p o ide eedback ia he Enp -EMA, o
keep his oolki up o da e and os e ing discussion on ha mon-
isa ion o EC p ocedu es needed o paedia ic ials ac oss
Eu ope.
Acknowledgemen s Special hanks go ou o o he pa ne s o ou o iginal
wo king g oup, I ana Sil a (EMA), D Richa d T ompe e (GOSH/IPTA, UK) and
D Alan Boddy (p e iously Newcas le Uni e si y/cu en ly, he Uni e si y o Sydney)
o hei help in p epa ing he ini ial epo o Enp -EMA.
Con ibu o s Li e a u e sea ch was done by PL, AN, JM, PS and DN; da a
collec ion and figu es we e done by PL, JM, PS and AN; Da a in e p e a ion, w i ing
and app o al o final e sion we e done by all au ho s.
Funding This esea ch has ecei ed unding om he Eu opean Union’s Se en h
F amewo k P og amme o esea ch, echnological de elopmen and demons a ion
unde g an ag eemen no. 261060 (Global Resea ch in Paedia ics—GRiP ne wo k
o excellence).
Compe ing in e es s None decla ed.
P o enance and pee e iew Commissioned; ex e nally pee e iewed.
Open Access This is an Open Access a icle dis ibu ed in acco dance wi h he
C ea i e Commons A ibu ion Non Comme cial (CC BY-NC 4.0) license, which
pe mi s o he s o dis ibu e, emix, adap , build upon his wo k non-comme cially,
and license hei de i a i e wo ks on di e en e ms, p o ided he o iginal wo k is
p ope ly ci ed and he use is non-comme cial. See: h p://c ea i ecommons.o g/
licenses/by-nc/4.0/
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