Trial Regulations
The aim of the Trials Network Committee is to facilitate academic clinical stroke research in Europe.
Austria
IRB / IEC
Forum of Austrian Ethics Committees; http://www.ethikkommissionen.at/ ; 27 local ECs & 7 lead ECs & 5 CTIS ECs
Legal Requirements / Regulations
–
Authorities (Government)
Bundesamt für Sicherheit im Gesundheitswesen BASG/ Federal Office for Safety in Health Care; Agentur für Gesundheit und Ernährungssicherheit AGES/ Austrian Medicines and Medical Devices Agency (https://www.ages.at/)
Registration Platform
Required according to declaration of Helsinki; no Austria specific Database; individual centers may require local study registration.
Requirements to Investigators
Physisican with right to practice (i.e. specialist or GP); CV dated and signed. New guidelines in preparation.
Protocol
not specified (MPG – ISO 14155; AMG – GCP guidelines)
PIIC Patient Information / Informed Consent Form
Text modules can be found on www.ethikkommissionen.at (-> Formulare -> Pat Info)
Only to be signed by patient or legal representative. Defered consent in emergency study situations. Oral consent with witness and documentation.
Safety Reporting
Serious adverse event and SURSAR to competent authority. No national standard reporting form. European standard SUSAR reporting form CIOMS-I recommended.
SAE, SURSAR, yearly safety report, final report to ethics committee. “Meldungsformular” (see download area of www.ethikkommissionen.at)
Contracts
Contact with local centers
Insurance
(Almost) always required, except if absolutly no danger to patient (e.g. questionnaire study). Confirmation template to be issued by insurance company – see download area of www.ethikkommissionen.at
Archive
25 years EU trials regulation, otherwise 15 years, MPG to be specified in study potocol (at least 10 years recomended)
Belgium
IRB / IEC
positive advice by Central Ethics Committee after having consulted Local EC’s if applicable, so submission needs to be done simultaneously to the CEC and LEC (not for EucraCT studies under CTR regulation – submission via CTIS)
Legal Requirements / Regulations
–
Authorities (Government)
FAMPH https://www.famhp.be/en
Registration Platform
FAMPH https://www.famhp.be/en
Requirements to Investigators
GCP / recent CV / training documentation & certificates / Site Site facilities
Protocol
Protocol
GDPR questionnaire ( Site specific document) ICF
No-fault liability insurance
Valid GCP certificate (<3 years) PI CV of PI ('s)
Clinical Trail application form
IB
PIIC Patient Information / Informed Consent Form
ICF template interventional non-EudraCT study
Safety Reporting
adverse events and serious adverse events
Contracts
Contract
Site specific application form for supporting departments
Insurance
No-fault liability insurance
Archive
Study documents archived for a minimum of 25 years; medical records need to be kept for a minimum of 30 years
Czech Republic
IRB / IEC
SÚKL ethic committee (submission via CTIS)
Low-intervention clinical trials (submission directly to EC)
Legal Requirements / Regulations
–
Authorities (Government)
State Institute for Drug Control (SÚKL)
Registration Platform
State Institute for Drug Control (SÚKL)
Requirements to Investigators
Actual CV (dated, signed)
GCP training not older than 2 years
Documentation on trial staff list (delegation log, training log, training certificates)
Protocol
Protocol content according to the legislation: ICH Topic E6 (R2) Guideline for GCP.
Namely general information, purpose of the trial, description of the trial, inclusion/exclusion criteria, treatment methods, evaluation of the efficacy and safety, statistical analysis, quality control and assurance, ethical aspects, data handling and record storage, funding, publication aktivity etc., for more information see the KHL-8
PIIC Patient Information / Informed Consent Form
PICF content according to the legislation: Regulation EU No. 536/2014 (chapter V), ICH Topic E6 (R2) Guideline for GCP.
PICF is in Czech language (or certified translation for foreigners)
Two versions for minors (for the age group 12-14 years and 15-17 years, younger minors may sign the PICF together with their parent)
Alternative ways of consent must be described in detail
When preparing PICF, It is recommended to follow KLH-22
Safety Reporting
Pharmacovigilance reporting according to the legislation: Act No. 378/2011 Coll., ICH Topic E6 Guideline for GCP.
Investigator is obliged to report SAE to the sponsor within 24 hours of finding out.
Sponsor is obliged to report:
SUSAR (grade A) – within 7 days to EVCTM and EC, within 15 days to investigators,
SUSAR (other grade) – within 15 days to EVCTM, EC, investigators,
DSUR – submission to SÚKL and EC annually,
Line listing – submition to MEC and investigators every 6 months.
For more info see KLH-21.
Contracts
Contracts with centres
Insurance
Insurance of the sponsor and investigators against harm to participants resulting from a clinical trial is required.
Insurance is not required in case of academic clinical trials where a registered medicinal products are used in accordance with SmPC or diagnostic a monitoring procedures do not pose a risk in compare to standard clinical practice.
(Act No. 387/2011 Coll.)
Archive
25 years (or longer if specified in the clinical trial agreement)
France
IRB / IEC
Comité de Protection des Personnes :
Compliance with French law concerning clinical trials and ethical considerations
Legal Requirements / Regulations
–
Authorities (Government)
ANSM
(National Agency for Medicines Safety)
Registration Platform
European Clinical Trials Database
Requirements to Investigators
GCP, CVs, training logs, training certificates…
Protocol
protocol according to GCP
PIIC Patient Information / Informed Consent Form
Patient information and consent form
Safety Reporting
adverse events and serious adverse events
Contracts
Contract with centers
Insurance
Insurance is always requested for new drugs/devices
Archive
15 years or 25 years depending on the studies.
Germany
IRB / IEC
52 Ethics committees (AKEK-Arbeitskreis
Medizinischer Ethik-Kommissionen; https://www.akek.de/ethik-kommissionen/#/cats_mitglieder/all/3/);
distinction between leading and associated ethics committees in case of multiple German centres
Deklaration of Helsinki
ICH-GCP-E6(R2)
Legal Requirements / Regulations
EU-clinical trials regulation 536/2014 (https://eur-lex.europa.eu/legal-content/EN/TXT/?uri=celex%3A32014R0536); Arzneimittelgesetz (AMG; https://www.gesetze-im-internet.de/amg_1976/ );
Medzinprodukterechtdurchführungsgesetz (MPDG; https://www.gesetze-im-internet.de/mpdg/)
Authorities (Government)
Bundesinstitut für Arzneimittel und Medizinprodukte BfArM (Humanarzneimittel; https://www.bfarm.de);
Paul-Ehrlich-Institut (PEI; https://www.pei.de) responsible for sera, vaccines, blood preparations, bone marrow preparations, tissue preparations, tissues, allergens, novel therapy medicinal products, xenogenic medicinal products and genetically engineered blood components. This also includes therapeutic monoclonal antibodies.
Federal authorities (https://www.zlg.de/arzneimittel/deutschland/laenderbehoerden)
Registration Platform
EudraCT number (https://eudract.ema.europa.eu);
CTIS (https://www.ema.europa.eu/en/documents/other/clinical-trial-information-system-ctis-sponsor-handbook_.pdf);
ClinicalTrials.gov (NCT-number; https://clinicaltrials.gov)
Requirements to Investigators
GCP certificate (provided by e.g.by CTU’s, TRREE (Training and Resources in Research Ethics Evaluation; https://elearning.trree.org)
CV, dated and signed
training logs, training certificates
documentation on trial staff list
Protocol
study protocol according to ICH-GCP chapter 6 and according to AMG/MPDG
PIIC Patient Information / Informed Consent Form
content differs according to local Ethics committee requirements
Safety Reporting
serious events
serious adverse events
see: https://www.ema.europa.eu/en/human-regulatory/research-development/clinical-trials/reporting-safety-information-clinical-trials;
https://www.bfarm.de/DE/Medizinprodukte/Antraege-und-Meldungen/SAE-melden/_node.html
annual safety report;more information about safety reporting and annual reports: https://www.bfarm.de/DE/Arzneimittel/Klinische-Pruefung/Genehmigungsverfahren/Mitteilungspflichten/_node.html
Contracts
individual contract requirements
Insurance
Mandatory insurance according to section 40, 1 Number 8 AMG (https://www.gesetze-im-internet.de/englisch_amg/englisch_amg.html#p1004)
Archive
according to § 58 EU-clinical trials regulation 536/2014 (https://eur-lex.europa.eu/legal-content/EN/TXT/?uri=celex%3A32014R0536): master file to be kept for 25 years (https://www.ema.europa.eu/en/documents/scientific-guideline/guideline-content-management-archiving-clinical-trial-master-file-paper/electronic_en.pdf)
Greece
IRB / IEC
A specific IRB/IEC for every hospital. A unique IRB/IEC may act as a reference IRB/IEC, but still approval for the specific IRB/IEC of every hospital is necessary
Legal Requirements / Regulations
–
Authorities (Government)
National Organization for Medicines (EOF)
Registration Platform
Clinical trials Information System (CTIS) – compulsory from 02/2023
Requirements to Investigators
GCP, CVs, training logs, training certificates, medical license
Protocol
table of content, what is necessary for a protocol (flow chart, inclusion-exclusion criteria, endpoints, methods, statistical evaluation, safety and more)
PIIC Patient Information / Informed Consent Form
Patient information and consent form
Safety Reporting
SAE, SUSAR, report to ethics committee bi-annually
Contracts
Contract with local centers
Insurance
all participants should be insured separately by the study sponsor regardless of their healthcare insurance status
Archive
15 years
Italy
IRB / IEC
Since January 2023 Italy has adhered to the Clinical Trial Information System (CTIS), which means that any trial, both those sponsored and those based on acdemic initiative, must be submitted to one Ethical Committee, which is not the EC of any of the participating centers, and to the Italian Agency for Drug Approval (AIFA). The centers must fill the feasibility questionnaire which is signed by the CEO of the Hospital. The approval by the unique EC is then communicated to the CEO of the Hospital and this is enough to start perticipating in the trial
Legal Requirements / Regulations
–
Authorities (Government)
AIFA (Agenzia Italiana del Farmaco)
Registration Platform
European Clinical Trials Database (#EUDRACT)
Requirements to Investigators
GCP, CVs, training logs, training certificates…
Protocol
table of content, what is necessary for a protocol (flow chart, inclusion-exclusion criteria, endpoints. Methods, statistical evaluation, safety and more)
PIIC Patient Information / Informed Consent Form
table of content, what is necessary for a protocol (flow chart, inclusion-exclusion criteria, endpoints. Methods, statistical evaluation, safety and more)
Safety Reporting
SAE, SUSAR, yearly safety report, final report to ethics committee
Contracts
Contract with Hospital and Contract with University Department
Insurance
Insurance is always requested for new drugs/devices
Archive
25 years
Scotland
IRB / IEC
There is a centralised service which provides a single approval for all UK sites. https://www.hra.nhs.uk/about-us/committees-and-services/res-and-recs/
Legal Requirements / Regulations
–
Authorities (Government)
UK Medicine and Healthcare products agency
Registration Platform
Applications are made via IRAS and automatically regsitered in ISRCTN
Requirements to Investigators
GCP training
Protocol
Protocol content according to the legislation: ICH Topic E6 (R2) Guideline for GCP.
PIIC Patient Information / Informed Consent Form
PICF content according to the legislation: Regulation EU No. 536/2014 (chapter V), ICH Topic E6 (R2) Guideline for GCP.
Safety Reporting
Annual DSUR submission to the regulator. SAE Line Listing to be provided, as well as SAR & SUSAR information
Contracts
Contracts with sites use a common template.
Insurance
Insurance is always requested for new drugs/devices
Archive
10-25 years depending on regulations governing study
Spain
IRB / IEC
A specific IRB/IEC for every hospital. A unique IRB/IEC may act as a reference IRB/IEC, but still approval for the specific IRB/IEC of every hospital is necessary
Legal Requirements / Regulations
–
Authorities (Government)
AEMPS (Agencia Española de Medicamentos y Productos Sanitarios) https://www.aemps.gob.es/
Registration Platform
European Clinical Trials Database
(#EudraCT) US Natiional Institutes of Health NIH (ClinicalTrials.gov, NCT-number)
Requirements to Investigators
GCP, CVs, training logs, training certificates…
Protocol
table of content, what is necessary for a protocol (flow chart, inclusion-exklusion criteria, endpoints. Methods, statistical evaluation, safety and more)
PIIC Patient Information / Informed Consent Form
Patient information and consent form. May require specific data protection consent form. Phone consent or deferred consent in emergency study situations.
Safety Reporting
adverse events and serious adverse events
Contracts
Contract with centers
Insurance
Insurance is always requested for new drugs/devices
Archive
25 years
Sweden
IRB / IEC
Submission to Swedish Ethics Committee (Etikprövningsmyndigheten)
Legal Requirements / Regulations
–
Authorities (Government)
anSM
(National Agency for Medicines Safety)
Registration Platform
European Clinical Trials Database (#EUDRACT)
Requirements to Investigators
CV signed & dated within last 2 years. GCP certificate. GCP to have been completed within last 2 years.
Protocol
Protocol content according to the legislation: ICH Topic E6 (R2) Guideline for GCP.
PIIC Patient Information / Informed Consent Form
PICF content according to the legislation: Regulation EU No. 536/2014 (chapter V), ICH Topic E6 (R2) Guideline for GCP.
Safety Reporting
Annual DSUR submission to the regulator. SAE Line Listing to be provided, as well as SAR & SUSAR information
Contracts
Contracts to be place with all participating hospitals, vendors, CROs etc
Insurance
Insurance is always requested for new drugs/devices
Archive
25 years EU Clinical Trials Regulation
Switzerland
IRB/IEC
7 EC’s (EKNZ, EKOS, CCER, CER-VD, KEKBern, EC Tessin, EC Zürich)
responsible for patient safety
Deklaration of Helsinki
ICH-GCP-E6(R2)
human rights:
CH Humanforschungsgsetz
CH Vklin
ethical consideration
Legal Requirements / Regulations
–
Autorities (Government)
Swissmedic Bern
IMP approval
Medical devices
Registration Platform
kofam – #SNCTP
swissethics: registry of all research projects (RAPS)
European Clinical Trials Database
(#EudraCT)
Europäische Studienregister (EU Clinical Trials Register)
US Natiional Institutes of Health NIH (ClinicalTrials.gov, NCT-number)
WHO: International Clinical Trials Platform (ICTRP)
Requirements to Investigators
GCP certificate (provided by CTU’s, SCTO, TRREE)
CV, dated and signed
training logs, training certificates
documentation on trial staff list
Protocol
Swissethics Vorlagen
table of content, what is necessary for a protocol (flow chart, inclusion-exklusion criteria, endpoints. Methods, statistical evaluation, safety and more)
PIIC Patient Information / Informed Consent Form
please check: homepage Swissethics, Vorlagen, Checklisten – Studieninfomationen- und Einwilligungen
patientinformation/informed consent form
patientinformation/informed consent form-nachtr
angehörige – patinfo/informed consent form
patientinformation/informed consent form-independent medical doctor
mandatory: content, what is necessary
Safety Reporting
see: https://www.swissethics.ch/templates/meldungen
serious events
serious adverse events
annual safety report
Contracts
please check: homepage Swissethics, Vorlagen, checklisten- Verträge
contract or service level agreements?
contract with centres
contract wit CROs
contract with service providers
contract with pharmacy regarding IMPs or Medical Devices
Insurance
please check: homepage Swissethics, Vorlagen, checklisten- Versicherungen
Archive
10 years according Swiss Law
check archiving regulations CH
The Netherlands
IRB / IEC
Submission to MREC or CCMO
Legal Requirements / Regulations
–
Authorities (Government)
Registration Platform
European Clinical Trials Database (#EUDRACT)
Requirements to Investigators
CV signed & dated within last 2 years. GCP certificate. GCP to have been completed within last 2 years.
Protocol
Protocol content according to the legislation: ICH Topic E6 (R2) Guideline for GCP.
PIIC Patient Information / Informed Consent Form
PICF content according to the legislation: Regulation EU No. 536/2014 (chapter V), ICH Topic E6 (R2) Guideline for GCP.
Safety Reporting
Annual DSUR submission to the regulator. SAE Line Listing to be provided, as well as SAR & SUSAR information
Contracts
Contracts with sites regulated by regional data protection agencies and local hospitals.
Insurance
Research subjects are covered by public insurance if research is performed in Denmark by authorized health personel.
Archive
5-25 years depending on type of clinical trial
Turkey
IRB / IEC
139 EC’s accross the country
sponsible for patient safety
Declaration of Helsinki, ICH-GCP-E6(R2), human rights and ethical consideration
Legal Requirements / Regulations
–
Authorities (Government)
Turkish Ministry of Health (TITCK-Turkish Pharmaceuticals and Medical Device Agency)
Separate pathways for IMP and medical devices
Registration Platform
TITCK application platform: https://ebs.titck.gov.tr/Login
US National Institutes of Health NIH (ClinicalTrials.gov, NCT-number) Not compulsory, however sponsors generally register to the NIH platform
Requirements to Investigators
GCP certificate
CV, dated and signed
Documentation on trial staff list
Protocol
Study objectives and end-points, flow chart, study design, Inclusion-exclusion criteria, study treatments, study duration, statistical evaluation, safety, administrative procedures, data management and monitoring, CRF’s, funding and sponsor information
PIIC Patient Information / Informed Consent Form
Patient informed consent forms
Next-of-kin informed consent forms for incapacitated persons
Minors=4 different age groups and mother+father together for parents
Safety Reporting
serious adverse events (reported within 24 hours to the ministry),reported to EC and TITCK at: https://ebs.titck.gov.tr/Login
adverse events (reports submitted to: https://ebs.titck.gov.tr/Login (annual submissions and DSUR submissions whenever applicable)
Contracts
contract with centres. All patient expenses, including the costs for comparative drugs should be covered by the study sponsor (not to be covered by the Social Security System of Turkey-SGK)
contract with CROs
Insurance
all participants should be insured separately by the study sponsor regardless of their healthcare insurance status
Archive
15 years
United Kingdom
IRB / IEC
Integrated Research Application System (IRAS), common gateway for ethics, R&D, MHRA, SSI and other research-related approval processes. https://www.myresearchproject.org.uk/Signin.aspx. The NIHR clinical trial toolkit is the best way to navigate the approvals process in the UK and get to all relevant sites and documents https://www.ct-toolkit.ac.uk/.
Also the HRA website has useful information on the ethics approval process: https://www.hra.nhs.uk/approvals-amendments/.
Legal Requirements / Regulations
–
Authorities (Government)
Health Research Authority (HRA) https://www.hra.nhs.uk/approvals-amendments/
UK Medicine and Healthcare products Regulatory Agency (MHRA), if applicable
Registration Platform
ISRCTN
Usually also register on Clinicaltrials.gov
(If multicenter with one site in the EU, need to register on EudraCT or EUDAMED)
Requirements to Investigators
CV: signed and dated, GCP, training logs, usually also confirm GMC registration
Protocol
Protocol content according to the legislation: ICH Topic E6 (R2) Guideline for GCP. Protocol templates are based on this, but differ in detail between hospitals/sponsors. contact Sponsor for their approved protocol template.
PIIC Patient Information / Informed Consent Form
Contact local Sponsor for their approved patient information and consent form template. Guidance available: http://www.hra-decisiontools.org.uk/consent/index.html
Safety Reporting
MHRA. Annual DSUR submission. HRA website also outline their requirement for safety reporting: https://www.hra.nhs.uk/approvals-amendments/managing-your-approval/safety-reporting/
Contracts
With the participating hospital/university. Can use NIHR Model site agreements (model contracts, standard research agreements) for studies carried out in the NHS.
Insurance
Via the NHS. Addtional clinical trials insurance required for industry sponsored trials.
Archive
10-25 years
Should you have any questions concerning regulations, please do not hesitate to contact us at esoinfo@eso-stroke.org
