Nordic Trial Alliance

Nordic Cooperation in Clinical Research- Report January 2016

Project Leader Pierre Lafolie MD, PhD

Nordic Trial AllianceKarolinska Institutet

Nordic Trial Alliance- creating a Nordic clinical research infra-structure

Aimto strengthen clinical research

Objectiveto contribute to sustainable Nordic welfare

Facts§ An initiative from the Nordic Council

of Ministries

§ Part of

§ Three year pilot project: 2013 – 2016

§ Hosted by NordForsk

§ Funded by Nordic Council of Ministries and NordForsk

http://nta.nordforsk.org

SECRETARIAT

Project leader Pierre LafolieMD, PhD,Karolinska Institutet, SE

Project assistant Sandra ChesleyKarolinska Institutet, SE

Maria NilssonSenior adviser, NordForsk

NordForsk administration and economy

Eivind Sætre/Tor Martin NilsenCommunications advisers

Maria SkoogClinical trials CoordinatorThe Copenhagen Trial UnitCopenhagen University Hospital, DK

Christian GluudHead of DepartmentThe Copenhagen Trial UnitCopenhagen University Hospital, DK

Heli PehrmanResearch Funding DirectorFinnMedi Oy, FIN

Halla Sigrún ArnardóttirProject manager Clinical Research Center Landspitali University Hospital, IS

Sven M. CarlsenProfessorDepartment of Cancer Research and Molecular Medicine, NTNU, NO

Steinar AamdalProfessor II Department of OncologyUniversity of Oslo

WORK GROUPNordic Trial Alliance People BOARD

Lars KøberProfessor, CopenhagenRalf w. AckermannMedical Director, Novo Nordisk,Copenhagen Pauli PuolakkainenProfessor, HelsinkiMia BengtströmPharma Industry FinlandSalvör NordalNordic Committee on BioethicsIcelandKristjan Erlendsson, Special Advisor,Ministry of WelfareIcelandSameline GrimsgaardVice-Dean ResearchUniversity of TromsøOle Alexander OpdalsheiAss. Secretary GeneralNorwegian Cancer Society, OsloChristina ÅkermanPresident ICHO, Boston (Chair)Mef NilbertProfessor, Lund

Nordic Trial Alliance network and some stakeholders

Small & medium enterprises, global industry

Patients

Public

ResearchersHospitals

Iceland

NOS-M

The Context in which NTA startedEU GCP Directive 2001/20 implemented 2004

• Leading to drastic decline in clinical research in all Europeancountries

• Countries adapted – but differently

• Denmark launched early a national network of GCP-units and hubs for clinical research

• EU started ECRIN

• Slow progress in most Nordic countries

• 2010 Nordic Council of Ministers launched a paper proposing a Nordic Clinical Research Infra-structure

NTA primary targetsTo Create a Nordic Clinical Research Infra-structure

• Help researchers to identify tresholds and how to overcome them• Help companies to find researchers• Help Nordic patients to find on-going clinical research in their own country• Establish a web site connecting to Nordic national networks and research

sites• Present an overview of Nordic research ethical review systems• Present options for Nordic clinical research registries and transparency of

data• Identify Nordic barriers between academia and industry and propose how to

overcome them• Initiate, support and develop relevant Nordic Networks in clinical research• Not to repeat what was done elsewhere!

NTA Implementation Projects- Those we did

1. Ethics2. Monitoring of Clinical Research3. Transparency and Registration4. Collaboration between Industry and Academia5. Pediatrics (strategic area)

Implementation projects-Those we didn’t do

§ Initially eight projects opened for application

Other ideas were also issued by NTA for grant application, namely

Legislation for clinical research in Nordic countries (Competent authorities,CA)Patient safety and AE reportingDesign and statistical analysisEducation and trainingCollaboration academia/industry

- But for these project we received no applications!

NTA Pilot Projects

§ Five clinical research projects are onging, final reports will be prepared to Nordforsk whenprojects are ready

§ 16 miljon NOK in grant for Nordic Clinical Research

§ 20 applications arrived§ An international committee top-ranked 5 projects

§ Nordic Arthroplasty Register Association -an international quality register study of total joint arthroplasty of four nations

The aim of the register study is to analyze results of total hip arthroplasty and total knee arthroplasty in Nordic countries.

The aim is also to develop a universal joint replacement database to detect inferior implants as early as possible.

Project leader: Keijo Mäkälä, FinlandParticipating countries: Denmark, Finland, Norway, Sweden

§ CoNARTaS - Committee of Nordic ART and SafetyAssisted reproductive technology (ART) and safety in the Nordic countries

The project will use the CoNARTaS database to generate knowledge to optimise treatment programmes and create the best possible framework for all test-tube babies.

Project leader: Anja Pinborg, DenmarkParticipating countries: Denmark, Finland, Norway, Sweden

§ NordStar

The study aims to find out which is the most effective treatment strategy in early rheumatoid arthritis. As the first trial ever it will compare four different treatment modalities head-to-head.

Project leader: Merete Lund Hetland, DenmarkParticipating countries: Denmark, Finland, Iceland, Norway, Sweden

§ BMT (bone marrow transplantation) in elderly AML - a prospective, controlled, international study

Uses a novel study design allowing both HLA matched siblings and unrelated donors, and a strict scheme for registration, inclusion and allocation of patients to avoid selection biases. The trial has the potential to be the first to evaluate RIC* transplants in elderly AML (acute myeloid leukemia).

Project leader: Mats Brune, SwedenParticipating countries: Finland, Norway, Sweden (Australia, Canada, Estonia, Germany, Greece, New Zealand)

* Reduced Intensity Conditioning

§ Discontinuation of infliximab therapy in patients with Crohns' disease during sustained complete remission

A Nordic clinical trial that examines whether Remicade treatment can be stopped beneficially in patients in whom the disease is completely inactive, as determined by both a physicians assessment, examination of the intestines and blood tests.

Project leader: Mark Ainsworth, DenmarkParticipating countries: Denmark, Faroe Islands, Finland, Iceland, Norway

NTA WEB services

NTA WEB services

NTA WEB services

NTA WEB services

Listings of Nordic clinical trial units

Gap analysis

§ Nordic collaborative clinical research need a system for common Nordic research ethical review – would mean faster access and a large reduction in bureaucracy

§ Connecting Nordic Life Science clusters with Academia and University hospitals would support welfare sustainability by Tripod development

§ More similarities than differences between Nordic interventional and non-interventional clinical research

§ There is a LARGE need for funds for Nordic collaborative clinical research

§ Access of patients from one Nordic country to clinical studies ongoing in another Nordic country must be facilitated

Reflections and future work

The project ends March 2016There is a need for further development in terms of creatinga common Nordic Research Area- The fastest way would be focusing on the research ethical

review processThere is also a need for further focus on Nordic registry trials and other non-interventional studiesSmall funds available for some actions during 2016 (meetings)

@nordforskfacebook.com/NordForsk

For more information:www.nta.nordforsk.org

Contact:pierre.lafolie@ki.senta@nordforsk.org

NTA want to extend a greatTHANK YOU to all contributors and participants!!

SWOT2009fromNordicForumforInnovationinHealthCareandMedicineonChallengesforNordicCooperationinClinicalResearch

STRENGTHExcellentstandardofauthoritiesExcellentbiobanks andregistriesHighscientific standardofmedicalresearchHighstandardofclinicalresearchStudies performedrapidly andwithhighqualityHighcomplianceofpatientsEnglish-speaking professionalsNordiccooperationhasbeenorispresently beingestablishedwithincertaintherapeutic areas(e.g.cancer)

OPPORTUNITYLargerpool ofpatients(25million inhabitantsvs.5-9mill/country)- fasterrecruitmentorlargerstudiespossibleDifferentiation(biopharmaceuticals, patientgroups, therapeuticarea,clinicalphases etc.)Improved, standardised procedures, incl.legalapprovals (CompetentAuthorities, ethics)Nordicco-funding ofnon-commercial studiesUtilizeNordickeyopinion leadersAdvantageforpublic healthinNordiccountriesAdvantageforNordicmedicalresearchAdvantageforCROsandsponsors wantingtoperformstudies inNordiccountries

WEAKNESSSmallpopulations (andsmallmarkets)NationalapprovalsEthicscommitteesrequiretranslatedprotocolsStudies regardedexpensiveLowfunding forinvestigator-initiated studiesLimitedtimeandinterestinclinicalresearch

THREATLegalobstacles(notallowingNordicapproval)National,regionalandopinion leadercompetitionToofewnewcandidatedrugstokeepphaseIclinics inseveral/allNordiccountriesLackofinterestinNordiccooperation ifnationalfunding isnotestablishedPharmaandbiotechcompanies choosebig“preferredsuppliers”EvenfewerNordicoffices forCROsandbigpharmaceuticalcompanies(reduction isalreadyobvious)

REFERENCES

Nordiskt samarbete om kliniska multicenterstudier. Prof. Bengt Fellström, Uppsala universitetssjukhus, för arbetsgruppen. 2011

NOS-M, “Present Status and Future Potential for Medical Research in the Nordic Countries, Nordic White Paper on Medical Research”, Academy of Finland, 2011

OECD, “Facilitating International Cooperation in Non-Commercial Clinical Trials”. OECD Global Science Forum. October 2011

ECRIN = European Clinical Research Infrastructure Network

Stina Gestrelius, “Nordic Cooperation in Clinical Research- Opportunities and Challenges, Nordic Forum for Innovation in Health Care and Medicine, 2009-02-18

Norden ”A Study of Clinical Trials in a Nordic Arena”, Nordic Innovation Centre, 2010

What the NTA Implementation projects did- WP 1 Research Ethics

• Work Package on EthicsThe project will analyse and propose on best practices in order to achieve a

common research area with regard to ethical assessment of clinical Nordic clinical research.

Project leader: Mika Scheinin, FinlandParticipating countries: Denmark, Finland, Iceland, Norway, Sweden

ReportA booklet describing the ethical review systems in all Nordic countries

- an evaluation of possible ways for a common Nordic ethical reviewsystem- the booklet will be published on NTA web

A large summit held in Helsinki October 2014

WP 2 Nordic Monitoring Network

• Work Package on Monitoring of Clinical ResearchThe aim of the project is to strengthen the collaboration between the Nordic GCP-

units and to increase the quality of and facilitate the monitoring process of clinical research.

Project leader: Annette Jørgensen, DenmarkParticipating countries: Denmark, Finland, Norway, Sweden

ReportPrepared guideline for a coordinated GCP-monitoring of clinical trials in the Nordic countries

- A common Nordic SOPs (standard operating procedures) for monitoring and quality assurance in clinical research on NTA web

- http://nta.nordforsk.org/news/uideline-for-a-coordinated-gcp-monitoring-of-clinical-trials-in-the-nordic-countries-published

WP 3 Transparency and registries of clinical data

• Work Package on Transparency and RegistrationThe project aims to improve registration and reporting of clinical studies, interventional and non interventional, by raising the homogeneity and quality of what is registered and reported for all studies. Project leader: Christian Gluud, Head of Department, Copenhagen Trial Unit, Centre for Clinical Intervention Research. Participating countries: Denmark, Finland, Iceland, Norway, Sweden

Report- Prepared a booklet publiced by Nordforsk on registries of clinical data

and transparency- To be publiced at NTA web - Also available at the book-table today!

WP 4 Collaboration between industry and academia

• Work Package on Collaboration between Industry and AcademiaThis project is part of creating a fundament for attracting more industry-initiated clinical drug trials to the Nordic countries and increasing the academic clinical trials.

Project leader: Jussi Merikallio, FinlandParticipating countries: Denmark, Finland, Norway, Sweden

Report- Large meeting held in April 2015 in Helsinki- Report on NTA web

http://nta.nordforsk.org/news/nordic-collaboration-in-clinical-research

Strategic initiative on Nordic Pediatric Clinical Research Network, NordicPedMed

• Work Package on Collaboration for a Nordic Pediatric research networkThis project had initially gained interest in Norway and Finland. By a strategic grant it is now

adopted also in Sweden, Iceland and Denmark

Project leader: Kalle Hoppu and Pirkko Lepola, FinlandParticipating countries: Denmark, Finland, Norway, Sweden, Iceland

Report- Full report on NTA web- http://nta.nordforsk.org/files/NTANordicinvestigatorsnetworkforPediatricMedicinesIReport_D0

9_31.03.2015_FINAL.pdf

For industryHow to find Nordic Clinical Research Units

Site listingAny Nordic site is welcometo register!

OthersDirect link for industryLinks to national one-stop-shopHow to connect to ECRIN-ERIC resourcesList of useful linksCook-book for Nordic research

Webs not yet ready Jan 16