Table 1

The Informed Consent and Assent Tool Kit—informed consent requirements for paediatric clinical trials in Europe

Consent/assent from child*Consent from parent(s)/guardian(s)General informed consent information
CountryLegal age of consent†Mandatory/suggested age ranges defined for assent (or consent if assent not used)‡Number of required signatoriesOfficial language requirementsConsent template(s)/guidelines/information sources
AustriaNot specified
Practice––14 years
8–13 years
EC may require younger assents
Both parentsGermanhttp://www.medunigraz.at/ethikkommission/Forum/index.htm
http://www.ethikkommissionen.at/
http://www.uibk.ac.at/strafrecht/scheil/scheil-einfuehrung-in-die-arzneimittelpruefung-bei-kindern-und-jugendlichen---kks--kids-ip.pdf
Belgium18 years4–11 years (some sites do not use under 12 years)
12–14 years
14–17 years
One parent at recruitment, but both parents at some point for signaturesDutch, French;
German at site request
http://www.fagg-afmps.be/en/human_use/medicines/medicines/research_development/ethic_committee/templates_informed_consent/
Do not have paediatric templates
Bulgaria18 years6–11 years
12–14 years
14–17 years—use own consent+parental signature also required
Both parentsBulgarianNo national EC websites available in English
Bulgarian Drug Agency -> clinical trials
http://en.bda.bg/index.php?option=com_content&view=category&layout=blog&id=14&Itemid=34
CroatiaNothing specifiedNothing specifiedNothing specifiedCroatianAgency for Medicinal Products and Medical Devices of Croatia -> Central Ethics Committee ->
http://www.almp.hr/?ln=en&w=o_SEPu
Information on clinical trials not available in English.
Czech Republic18 years7–11 years
12 years—own consent
12–14 years
15–17 years
Both parents. Only by one parent if the other parent is not listed in the child's birth certificate, has died or is younger than 18 years.Czech. Where the child's parents (or one of them) are foreign nationals, the information sheet shall be presented in bilingual format.State Institute for Drug Control -> Details of clinical trials / Guidelines and Forms / KLH-22 V.1:
http://www.sukl.eu/medicines/klh-22-version-1

Denmark18 years15–17 years––proxy consent

Both parents
Exception—no parents if aged 15–17 and non-interventional no-risk study (EC dispensation required)
DanishThe National Committee on Health Research Ethics -> Guidelines about notification
http://www.cvk.sum.dk/CVK/Home/English.aspx
http://cvk.sum.dk/English/guidelinesaboutnotification.aspx -> 4.4. Medicinal product trials and clinical investigations of medicinal devices involving legally incompetent subjects; 4.4.1 Trials with children and young people under the age of 18
http://cvk.sum.dk/English/guidelinesaboutnotification.aspx#Afsnit%205.0
Act on Research Ethics Review of Health Research Projects
Estonia18 years0–7 years
7–17 years––mandatory
Both parentsEstonianState Agency of Medicine -> Clinical trials -> Conditions and procedure for conducting clinical trials of medicinal products
http://www.ravimiamet.ee/en/clinical-trials-medicinal-products-estonia
Finland15 yearsWritten separate consent as soon as child is literate; under 15 years––own consent+parental consent;
15–17 years––own consent+parental notification if minor can understand the significance of research+direct health benefit is expected
Parent or legal guardian and the child, when they are literate, need to sign the consent. One parent by the law, but the other one can be informed (both can sign if they want).Finnish, SwedishMedicines Research Act 488/1999
Medical Research Decree 986/1999
Additional info:
FinPedMed guidelines; legal and ethical regulation—templates for age groups 6–17 and parents
Regulatory requirements for clinical trials in Finland
Picture cards to support IC process
France18 yearsBased on EC—usually two or three age groups
4–6 years
7–12 years
13–17 years
Picture ICFs for young children
Both parentsFrenchComité de Protection des Personnes Sud-Méditerranée II : http://www.cpp-sudmed2.fr/Information-et-autorisation-des?lang=fr
National Consultative Ethics Committee for Health and Life Sciences:
http://www.ccne-ethique.fr/en
Germany18 years7–11 years
12–16 years
17 years––own consent+parental consent required
Both parentsGermanGerman Ethics Council;
http://www.ethikrat.org/—no information for clinical trials
Landesärztekammer Brandenburg—information available ONLY in German.
https://www.laekb.de/
ICF Guidance
https://www.laekb.de/files/146A97FF999/AMG_Patienteninfo_Kinder_7bis11.pdf
Hungary18 yearsUnder 6 years
6–10 years
11–14 years
15–17 years
One parentHungarianNational Institute of Pharmacy and Nutrition -> Laws and regulations (only available in Hungarian) -> Miniszteri rendeletek
http://ogyei.gov.hu/search/index.php?searchPhrase=decree&from=10
http://www.ogyei.gov.hu/magyar_jogszabalyok/
-> Decree 35/2005 (VIII. 26.) of the Minister of Health on the clinical trial and application of correct clinical practices of investigational medicinal products intended for use in humans
7§ Clinical trials conducted on minors
http://net.jogtar.hu/jr/gen/getdoc.cgi?docid=A0500035.eum
Iceland18 yearsUnder 12 yearsOne parent—the EC can request both parents' signatures in some cases.Icelandic or English. The study objective in Icelandic. Materials in Icelandic.
(For studies involving groups of other ethnicity, an appropriate language is required.)
The National Bioethics Committee
(http://www.vsn.is/en/node/189)
The Parliament; http://www.althingi.is/english -> http://www.althingi.is/lagasafn/log-samthykkt-a-althingi/ ->
The Act of Law, No. 44/2014, on scientific research within the health sector defines the conditions for biomedical research and the role of the bioethics committees
http://www.althingi.is/lagas/nuna/2014044.html
Several laws and regulations on data protection, medicines, biobanks and health information collections (2014), etc
 Ireland16 years
(clinical trials)
18 years
(all other research)
7 years, or according to capacity of childOne parentEnglishList of Research Ethics Committees for clinical trials of IMP:
http://health.gov.ie/european-communities-clinical-trials-on-medicinal-products-for-human-use-regulations-2004/
Research Ethics Committee Standard Application Form:
http://www.molecularmedicineireland.ie/research_ethics
National Consent Policy: http://www.hse.ie/eng/about/Who/qualityandpatientsafety/National_Consent_Policy/consenttrainerresource/trainerfiles/NationalConsentPolicyDOC.html
Clinical Trial Regulation: S.I. No. 190/2004—European Communities (Clinical Trials on Medicinal Products For Human Use) Regulations, 2004
http://www.irishstatutebook.ie/2004/en/si/0190.html
Italy18 years6–10 years
11–14 years
15–17 years––with own signature
No official mandatory age(s) for assent. Different age-tailored assents are submitted voluntarily, and are evaluated by the ECs
Both parentsItalianThe Italian Medicines Agency http://www.agenziafarmaco.gov.it/en/content/clinical-trials
the Italian regulation on CTs include the following:
D.lgs 211/2003 http://www.agenziafarmaco.gov.it/sites/default/files/decreto_24062003_inglese.pdf
DM 21/12/07 https://www.agenziafarmaco.gov.it/ricclin/sites/default/files/files_wysiwyg/files/Normativa/MD_21_December_2007_CTAform_English.pdf
Latvia18 years0–7 years
7–17 years
One parent or legal representativeLatvianState Agency of Medicines of the Republic of Latvia -> Clinical trials and non-interventional trials -> legislation
http://www.zva.gov.lv/?setlang=en -> http://www.zva.gov.lv/?id=396&sa=396&top=386 ->
http://www.zva.gov.lv/index.php?id=381&sa=381&top=333&lang
http://www.zva.gov.lv/doc_upl/MK_not_289_English_02062010.pdf
Lithuania18 yearsNo set agesBoth parentsLithuanianThe Lithuanian Bioethics Committee -> Biomedical Research -> favourable opinion on clinical drug trial
http://bioetika.sam.lt/index.php?3202747546
Informed Consent
http://bioetika.sam.lt/index.php?3221858831 ->
http://bioetika.sam.lt/index.php?577320631—information available only in Lithuanian
http://bioetika.sam.lt/index.php?3202747546
Malta18 years6–17 yearsParents or legal representative
Practice—both parents
One of the official languages of Malta (eg, Maltese) or in a language
understandable to the clinical trial subject and/or his legal
representative.
Malta Health Ethics Committee
https://health.gov.mt/en/appbodies/hec/Pages/Links.aspx
Maltese Clinical Trials Regulations 2004 (LN490 of 2004) MEDICINES ACT, 2003 (ACT NO. III OF 2003); http://justiceservices.gov.mt/DownloadDocument.aspx?app=lp&itemid=16860&l=1
The Netherlands18 years12–17 yearsBoth parents.
If parents are divorced and they both have parental rights, they both have to sign. For a single parent, without another partner with parental rights, one signature is enough.
DutchCentral Committee on Research Involving Human Subjects (CCMO) -> Human Subject -> Informed Consent—information available only in Dutch.
http://www.ccmo.nl/en/ -> http://www.ccmo.nl/en/minors
Norway18 years16–17 years––with own signature
12–16 years––in special circumstances
Main rule: both parents sign the consent form if they have parental responsibility for the child.
Required for all children under 12 years old.
NorwegianThe Norwegian National Research Ethics Committees -> Clinical Trials -> Regulations
https://www.etikkom.no/en/ethical-guidelines-for-research/
http://www.legemiddelverket.no/English/Clinical_trials/Regulations/Documents/Norwegian%20regualtion%20for%20Clinical%20Trials.pdf
National database for Laws and Acts -> Lov om medisinsk og helsefaglig forskning (helseforskningsloven)—information available only in Norwegian.
https://lovdata.no/dokument/NL/lov/2008-06-20-44?q=helseforskning
Act on medical and health research (Helseforsknings-loven)
Guidance to Helseforsknings-loven (in Norwegian only) Additional info:
Norwegian Medicines Agency: Website on clinical trials.
Poland18 years6–11 years
12–15 years
16–17 years
One parent
Practice—both parents
Polishhttp://www.eurecnet.org/information/poland.html
No national EC websites available in English
Portugal18 years0–8 years
8–12 years
12–17 years
Both parentsPortuguesehttp://www.eurecnet.org/information/portugal.html
CEIC—National Ethics Committee for Clinical Research
http://www.infarmed.pt/portal/page/portal/CEIC/English
No national regulations/acts available in English
Romania18 yearsUnder 6 years
6–10 years
11–14 years
15–18 years
Both parentsRomanianNational Ethics Committee of Romania
http://www.adsm.ro/ro/comisia+nationala+de+bioetica+a+medicamentului+si+a+dispozitivelor+medicale#
No information available in English
Scotland (UK)16 years0–5 years
6–10 years
11–15 years
Consent with own signature under 16 years, if they are competent to do so
One parentEnglishNRES Guidance
http://www.hra-decisiontools.org.uk/consent/principles-children.html and
http://www.ukctg.nihr.ac.uk/default.aspx
Slovakian.a.n.a.n.a.SlovakianThe State Institute for Drug Control (SIDC) -> Clinical trials -> Instructions
http://www.sukl.sk/en?page_id=256 ->
http://www.sukl.sk/en/clinical-trials/instructions?page_id=2821
No national regulations/acts available in English
Slovenia18 years9 years—assent
15 years—with own signature
One parentSlovenianRepublic of Slovenia National Medical Ethics Committee ->
http://kme-nmec.si/—only front page
No additional information available.
Spain18 years0–11 years
12–17 years––with own signature
One parentSpanishThe Agencia Española de Medicamentos y Productos Sanitarios (AEMPS); A state agency within the Spanish Ministry of Health, Social Services and Equality -> Medicines for Human use—> Clinical research with medicines
http://www.aemps.gob.es/en/investigacionClinica/medicamentos/home.htm
The Ministry of Health, section about regulation of clinical trials:
http://www.aemps.gob.es/en/legislacion/espana/investigacionClinica/ensayos.htm
The Spanish Regulation about Clinical trials: the ROYAL DECREE 223/2004-section 7.3 (English version is available by request)
 Sweden18 yearsWritten separate consent as soon as child is literate
6–10 years
11–14 years
15–17 years––with own signature
Both parents and the child, when literate, need to sign the consentSwedishThe Central Ethical Review Board -> Documents -> Information for Research Participants
http://www.epn.se/en/start/the-organisation/ -> http://www.epn.se/en/start/central-ethical-review-board-documents/ -Etikprövningslagen 2008.
Regulatory requirement for clinical trials LVFS 2011:19
Läkemedelslagen—1992
Biobank law––2002
Personal Data Act 1998
National Medicines Agency -> Legislation -> Codes of Statutes -> 1996:17 Clinical trials of medicinal products
https://lakemedelsverket.se/english/ -> https://lakemedelsverket.se/english/overview/Legislation/Codes-of-statutes/
UK16 years0–5 years
6–10 years
11–15 years
One parentEnglishNRES Guidance;
http://www.hra-decisiontools.org.uk/consent/principles-children.html and
http://www.ukctg.nihr.ac.uk/default.aspx
  • © European Medicines Agency, 2015. Reproduced with permission

  • *Consent/assent from child: this information has been mainly collected via the normal daily work and notes of the CRO Company, PRA Health Sciences (UK), when preparing EC submissions for national authorities. Some of this information is not available in English, nor publicly available in regulatory authority’s web pages. In addition, some English-translated text versions may include inaccurate terms or explanations, which could give rise to different interpretations. Therefore, the authors cannot guarantee 100% accuracy for all national requirements. In addition, this table is a snapshot of the data gathered in 2014, which might have subsequently changed.

  • Legal age of consent: legal age of consent means the age from which a child is able to give and sign their own independent legally valid consent according to the national law/act/regulation. Children below this age limit are incapable of giving legal informed consent and need parental/legally authorised guardian's informed consent with a signature to participate in a clinical study. Parental/legally authorised guardian's informed consent may be obtained/sought in addition to the child’s own consent/assent, or when the child above the age limit is incapable to sign consent due to a difficult physical condition.

  • Mandatory/suggested age ranges defined for assent (or consent if assent not used): these mandatory or suggested age ranges are defined in national regulation/law/act, for a child below the legal age of consent and for own informed consent or assent (depending on the terminology used in legal texts). This consent or assent is obtained in addition to the legally valid parental/legally authorised guardian's signed informed consent. This type of child’s own assent/consent supports the child’s integrity and rights, creates the opportunity to hear their own opinion, supposed will and possible dissent, thus respecting the child’s autonomy in the informed consent process.