EMACOLEX Budapest 12 and 13 May 2011

1. EMACOLEX Budapest 12 and 13 May 2011 QUESTIONNAIRE ON CLINICAL TRIALS Insurance matters

2. 1.      Who is responsible for insuring participants in clinical trials in your country? • Sponsor: Malta, Cyprus, Austria, Estonia, Bulgaria, Portugal, Italy, Slovakia, Netherlands, CzechRepublic, Germany, Latvia, Poland, Ireland, UK (and investigator), Belgium, Switzerland • Canadaremarks: There is noexpressregulatoryrequirementthatclinicaltrialsponsors hold insurance for thosethatparticipateinclinicaltrials. However...

3. -Are MA holders obliged to take insurances for those that participate in clinical trials? • Yes: France, Italy, Belgium • Yes, if the MA holder and the sponsor is the same legal person: Cyprus, Austria, Bulgaria, Latvia • Netherlands: Sponsor is by law obliged to insure participants (part of the protocol) • Malta: Ambiguous - trial cannot be approved without insurance.

4. -Is insurance coverage provided for by national law? • Yes: -France, Estonia, Bulgaria, Portugal, Italy, Slovakia, Latvia, Poland, Belgium -Cyprus: The relevant legislation is the Medicinal Products for Human Use (Good Clinical Practice) Regulations of 2004 that transpose the corresponding provisions of Directive 2001/20/EC as amended. -Austria:According to the Austrian Medicinal Product ACT an insurance for study participants is mandatory. However, the insurance sum is not further specified in the law – it is according to the potential risk. -Switzerland: According to art.7, par.1 and 2 of the Federal Ordinance on Clinical Trials of Therapeutic Products (OClin), the sponsor is liable for harm caused to a trial subject within the framework of a clinical trial and he must guarantee this responsibility.  Link: (German)http://www.admin.ch/ch/d/sr/8/812.214.2.de.pdf or (French)http://www.admin.ch/ch/f/rs/8/812.214.2.fr.pdf),

5. ...Is insurance coverage provided for by national law? …Yes: -Netherlands:According to the Dutch Law on Medicinal Scientific research with humans an insurance for participants is mandatory. -Czech Republic: Yes, insurance clinical trials is required by national law: Act 378/2007 Coll. on Pharmaceuticals, section 52 3) f) Quotes of the Act: Section 52 (3) A clinical trial may be undertaken only if: f) a liability insurance covering the investigator and the sponsor has been concluded prior to the commencement of the clinical trial, which shall cover also the damages in the event of the death of the trial subject or in the event of an injury to the health of the trial subject arising due to the conduct of the clinical trial; the sponsor shall be responsible for concluding such insurance. -Germany:German Drug Law stipulates that the insurance of trial subjects is mandatory. The coverage sum is fixed based on a potential risk evaluation; the sum of 500.000 Euro at least needs to be available in case of death or continuous occupation disability of a trial subject. -Ireland: Under Irish legislation, the conditions and principles which apply to all clinical trials include ‘Provision has been made for insurance or indemnity to cover the liability of the investigator and sponsor, which may arise in relation to the clinical trial’. Under the legislation ‘insurance or indemnity’ is defined as ‘includes a contract of insurance, a contract of indemnity, a guarantee, a surety, a warrant and a bond and which in any case shall be available to cover the liability of the sponsor and the investigator to provide for compensation in the event of any injury, loss or damage to, or the death, of any subject arising out of the arrangement for, or conduct of, the clinical trial and which the sponsor, or investigator, shall become liable to pay to such subject, or in respect of such subject [i.e. a participant in the clinical trial], by way of damages or costs’.

6. ...Is insurance coverage provided for by national law? • -UK: Yes, (A) Article 3(2)(f) of 2001/20/EC provides that a clinical trial may only be undertaken if "provision has been made for insurance or indemnity to cover the liability of the investigator and sponsor". -The UK's Medicines for Human Use (Clinical Trials) Regulations 2004 require insurance or indemnity cover to be in place to meet the potential liabilities of the sponsor (including any co-sponsors) and all investigators.  Those regulations do not specify the amounts of insurance required or how it should be provided. -Sponsors and investigators within the National Health Service are covered by a publicly funded indemnity scheme, the Clinical Negligence Scheme for Trusts (CNST).      -Investigators undertaking trials in private clinical practice are expected to have indemnity cover from medical defence societies. • No: Malta,

7. 2.      Who pays for insurances in clinical trials? • Sponsor: Malta, Austria, Estonia, Bulgaria, Portugal, Slovakia, Netherlands, CzechRepublic, Germany, Latvia, Poland, Belgium, Switzerland, (Canada). - -UK: The sponsor of the clinical trial is responsible for ensuring that insurance or indemnity is in place.  Different parties may have different insurance or indemnity arrangements, depending on the type of trial.   Commercial sponsors, and some non-commercial sponsors such as universities and charities, are expected to take out their own commercial insurance cover.  • A Government fund: none • Certainfundspaid for by MA holders: none • Theconcerned MA holder - ifthe MA holder and thesponsor is thesamelegalperson: Malta, Cyprus, France, Italy, Latvia

8. …Who pays for insurances in clinical trials? • Other: -Netherlands: Thesitewheretheresearch is donecansometimesbeliable. -Malta: Nolocallyfundedtrialsasyet – butcouldbe a Universityabroad. -Ireland: While the sponsor has responsibility the funding could be from the MA holder or others.

9. 3. How are participants in clinical trials insured? • Is theinsurancebasedonno-faultcompensation: Malta (usually), Austria, Estonia, Bulgaria, Portugal, Italy, Slovakia, Netherlands, Germany, Latvia, Poland, Ireland, Belgium, Switzerland • -UK: Insurance for commercial sponsors is based on no fault compensation, in line with guidelines issued by the Association of the British Pharmaceutical Industry (ABPI). The scope of the Clinical Negligence Scheme for Trusts is limited to compensation for negligence. Other sponsors, such as universities and charities, generally take out insurance for negligence only but may offer ex gratia payments. • Is theinsurancebasedonfaultcompensation: -France: Theinsurance is basedonallegedfaultcompensation. -Slovakia:Eachhealthcareprovidershouldhavethistype of insurance.

10. 4.      Are all insurance companies willing to provide for no-fault insurance for clinical trials? • No: -Portugal, Italy, Slovakia, CzechRepublic, -Switzerland: The extent and contractual element of the insurance policies are subject to private negotiations and have no effect on the sponsor's liabilities regarding the participants of the clinical trial. -UK: It's a specialist area so  in practice, clinical trials insurance is provided by a limited number of companies who specialise in this field.  These companies all provide policies on a no fault basis.   • Not known: Cyprus, France, Bulgaria, Latvia, Poland, Estonia: All submitted insurances are based on no-fault compensation, Germany: No information on refused insurances. • Other: -Malta:No Insurance companies in Malta have as yet provided insurance for trials. -Belgium: The insurance contract may set maximum amounts to compensate, as well limit the duration for coverage of the risk.

11. 5. Is National Health service staff insured for mal-practise with regard to participants in clinical trials? Yes: Austria, Netherlands, Poland -Malta: Indemnity of Health Care workers in Public Health Sector and private Insurance for Private Health Care Workers. -Bulgaria: The National Health service staff is compulsory insured for mal-practice in general by the Medicinal Centerin which they work. -Portugal: By the National Health system. -CzechRepublic: Most of them are insured for malpractice,  but some of them do not have insurance for research activities.  Medical facilities (hospitals) have insurance for its activities, but insurance does not have to cover research activities. -Germany: Yes, professional insurances; if applicable hospital insurance. -UK: Yes , negligence cover is provided under the Clinical Negligence Scheme for Trusts. Switzerland: Hospitals (which are generally part of the public sector) need an insurance policy of their own or are covered by the Cantonal (state) Liability Act of the concerned canton.

12. ...Is National Health service staff insured for mal-practise with regard to participants in clinical trials? • No: Estonia, Italy, -Latvia: Ingeneralno, butit is sometimesdonebyseveralhospitals. -Belgium: No, damage from mal practice where there is no causality with the trial, falls under the common medical contractual liability. • Not known: Cyprus, France, • Other: • -Slovakia:There is noNationalHealthServiceinSlovakia. • Canada: Doctors, nurses and hospitals and universitiesinvolvedinclinicaltrialsinsurethemselves. There is nocentralinsurancescheme (e.g. runbyeitherthefederalorprovincial/territorialgovernments).

13. 6.      What is the procedure for claiming compensation if a participant in a clinical trial suffers from AE/SAE? • Malta, Slovakia, CzechRepublic, Latvia:Participantcontactsinvestigatorwhoensurescontactwithsponsor and theinsurancecompany. • Austria, Netherlands: Approach at theinsurancecompanymaybesupportedbythepatientlawyer. • Estonia, Germany: Claims should be filed to the insurance company. (All disagreements between patient and insurance company will be settled by national courts – Estonia) • Bulgaria: The patient can either approach the insurance company, or in case of a dispute issue a claim in front of a national court. • Portugal: Nospecificprocedure is establishedinthenationallegislation for thispurpose. • Italy: By a legalrepresentative – no form is available. • Poland: Procedures set in insurance policies and insurance law. • UK: Each sponsor will have its own procedures for handling claims.  In the case of commercial sponsors, claims are referred to independent adjudication under the ABPI Guidelines.  • Switzerland: Deposit of theclaimbytheinvestigator. Shouldtheprocessthenresultin a litigation, thissecondstep is treatedby a civilcourtcompetent for thematter. • Belgium: Common insurance law: the participant can act directly against the sponsor. • Not known: Cyprus, France • Canada: Compensation for damages/ harm wouldbesoughtthroughthecourtsystem.

14. 7.    Which national authority is responsible for deciding whether insurance coverage in clinical trials is sufficient? • The National Ethics Committee: Cyprus, France, Austria, Estonia, Bulgaria, Portugal, Netherlands, Czech Republic, Germany, Latvia, Ireland, Belgium, Switzerland • The National Medicines Agency: Latvia, Poland • Other, who: -Local Ethics Committees: Italy, Slovakia, -UK: It will be the ethics committee that undertakes the ethical review of the trial concerned  which will make this assessment .   This could be any one of around 60 ethics committees with statutory recognition to review clinical trials in the UK.  • Netherlands: Can also be Central Committee on Research inv. Human subjects. • Malta: None - not assessed-but trials are funded by local bodies. • Canada: ResearchEthicsBoards (REBs) considerwhetheradequatearrangementsareinplacetocompensateclinicaltrialsubjectsintheevent of harm indecidingwhethertogivetheirapproval of it.

15. SummaryOutcome of answers • Sponsor is responsible for insuring participants (17)-Insurance coverage is provided for by national law (17) • Sponsor pays for insurances in clinical trials (14) • Insurance is normally based on no-fault compensation (15) • Not all insurance companies provide these insurances • According to answers –national health service staff is insured • Procedure for claiming compensation is most often: participant – investigator – sponsor – insurance company • The National Ethics Committee is most often responsible for determining if insurance coverage is sufficient (13) – in 2 countries it´s the Medicines Agency – or regional ethics committees.

16. ThesituationinIcelandwithregardtoinsurancemattersinclinicaltrialsThesituationinIcelandwithregardtoinsurancemattersinclinicaltrials • Sponsor is responsible for insuringparticipants. Softlawininsurances – butnoinsurancecoverageaccordingtolaw. • Sponsor pays for insurances • Insurance is basedonfault-compensation – ifinsuredbyanIcelandiccompany – not ifmulti-national • Icelandicinsurancecompaniesdo not sellno-faultcompensationinsurancesinclinicaltrials – foreign insurancestoocostly for sponsors • Nationalhealth-carestaff is not insured for mal-practisewithregardtoparticipantsinclinicaltrials • Procedure for claimingcompensation – sameasmostcountries • BoththeNationalEthicsCommittee and the Medicines Agencyareresponsible for determininginsurancecoverage – willbechanged Because of thissituation – insufficientinsurancecoverage for participants – Icelandis losingclinicaltrialsfromthecountry!