bih mission and implementation - bihealth.org · 2020. 9. 15. · bih — mission and...

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BIH Mission and Implementation Working Draft, April 2020

BIH—MissionandImplementation Draft04/2020

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INDEX

Translation..............................................................................................................................................2

Medicalneed.......................................................................................................................................2

Challenges...........................................................................................................................................2

BIHApproach..........................................................................................................................................4

TheBIHTranslationalEcosystem........................................................................................................4

Cross-OrganSystemsMedicine...........................................................................................................5

Principles.............................................................................................................................................6

ImplementationattheBIH.....................................................................................................................7

InnovationEnablers............................................................................................................................7

TranslationsHubs................................................................................................................................9

FocusAreas.........................................................................................................................................9

SuccessCriteriaandExploitingthePotentialoftheBIH.......................................................................10

TABLE OF FIGURES Figure1:TheTranslationalValueChain..................................................................................................3

Figure2:ThetranslationalEcosystemofBIH..........................................................................................5

Figure3:ThecomponentsofBIH............................................................................................................7

Figure4:TheInnovationEnablersofBIH................................................................................................8

Figure5:TheRoleoftheInnovationEnablersinthetranslationalEcosystemofBIH............................8

Figure6:TheTranslationHubsofBIH.....................................................................................................9

Figure7:TheFocusAreasofBIH...........................................................................................................10


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Mission ThemissionoftheBIH(BerlinInstituteofHealth)istofacilitatethetranslationoffindings

from biomedical research into new approaches to diagnostics, personalized prediction,

prevention and therapy and, conversely, to utilize clinical findings to help researchers

developnovelapproaches.Theaimistodeliverrelevantmedicalbenefitsforpatients.

Translation

Medical need Health systems in Germany and around the world are facing major challenges. With agingpopulations leadingtomorepatients,andata timethat thereare fewernursesandcareworkers,medical research will be pivotal in providing us with fresh insights into new models of care andtreatment. Inaddition,whiledigitizationpromisestodeliveranetworkof informationfromawidevarietyofsourcesthatsupportresearch,themedicalworldmustbecomemoresuccessfulinbringingsolution-oriented observations and the questions raised by everyday clinical practice intotranslationalresearch.Thereverseprocess,thetransferofobservationsfromthelaboratorybacktoeverydayclinicalpractice,alsoneedstobeimprovedandaccelerated.With no long-term treatment options currently existing for many diseases, the hope of futuresuccesses in treatments fora rangeof conditionshingeson the rapid technologicalprogressbeingmade in basic research and information technology. Such a scenario makes it vital to combineinnovativetechnologiesandresearchactivitieswithclinicalexpertisethatisdrivenbymedicalneed,thusestablishingnewmedical,technicalanddigitalsolutionswithinareasonabletimeframe.ThisisoneofthecoretasksoftheBIH.BeingbasedinBerlin,theBIHsitsintheideallocationforfulfillingthismissionbyofferingeasy access tobiomedical research froma largenumberofuniversity andnon-universityworkinggroups.TheCharité,asEurope's largestuniversityclinic, isnotonlyable todeliverclinicalexcellenceinawiderangeofareas,butalsohasabroadspectrumofpatients-allthecomponentsneededforthesuccessfuldevelopmentofnewformsoftherapywithinthisbiomedical‘ecosystem.’Challenges Currently,thetranslationofinnovativeapproachesintoclinicalpracticerequiresmuchinthewayoftimeandresources,andunfortunatelyisoftennotassuccessfulasitcouldbe.Availabledatashowsthat thenumberofapproveddrugsperbillionUSD(adjusted for inflation) inresearch investmentshasonaveragehalvedeverynineyearssince1950.1Amajorreasonforthisdeclineisthecomplexityofthestepsrequiredalongthetranslationalvalue

chain, from innovative idea to real-world clinical application. In addition, a multitude ofinfrastructuresandtechnologies,aswellasprofessionalgroupswithdifferentskillsets,arerequiredtocontributetotheprocessandworktowardsacommongoal.

1DerekLowe,ScienceTranslationalMedicine,2012


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Figure1:TheTranslationalValueChain

However,anotherchallengeliesinthecombinationsofpeopleinvolvedinthesevariousstages,whooften have different priorities, speak different languages and work in different communities. Forscientists working in basic research, an understanding of new molecular mechanisms - andsubsequently publishing results in well-known journals - is crucial. Sitting opposite this, fortranslationalresearchtobesuccessfulindeliveringachievementfrompreclinicalandclinicalstudies,there is a need for all clinical partners and researchers involved in the process to share commongoalsandcooperatecloselyfromtheverybeginning.Greatercohesionisoftheutmostimportancehere - underlining the importance of those involved in both basic and translational research topossess the capabilities and skill sets needed to master the complex requirements for thepreparation and approval of clinical trials. These steps, however, require considerable time andresourcesandmaynotalwaysseemworthwhileinthebasicresearchenvironment.Suchhurdlesanddifficultiesexistatmanyinterfacesoftranslationalvaluecreationandcanleadtothedevelopmentofseparatedsilos,endangeringtheeffectivenessofthetranslationalprocess.Yet translation cannot, and should not, be divided into ‘basic scientific knowledge’ and‘implementationinclinicalpractice’.Onthecontrary,translation-orientedteamsandfacilitiesmustbothbeanchoredintheclinic,andinthelaboratory.Professionalsworkingindailyclinicalpracticeobserve medical need through contact with patients or through the help of innovative big dataprocesses,whilst pathophysiological research approaches and therapy concepts can be developedthroughinteractionwithscientistsinbasicresearchandreviewingthembasedonmedicalneed.Thenecessary‘mindset’fortranslationcanonlyarisewithinthiscontext.2

2Keyelementsfornourishingthetranslationalresearchenvironment.SciTranslMed.2015;Volk,Stevens,Mooney,Grainger,andDuda;DFGStellungnahmezurTranslationhttps://www.dfg.de/download/pdf/dfg_im_profil/reden_stellungnahmen/2019/190919_stellungnahme_empfehlung_ag_translation.pdf


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Another challenge for medical translation is the pathophysiological limits of traditional, organ-oriented, concepts in medicine and research. These promote a deep understanding of individualstructures,butdonottakesufficientaccountofthefactthatthedifferentfunctionsandstructureswithin an organism are closely linked; physiological and pathological mechanisms overlap, andgeneticsand theenvironmentaffectallorgansandsystemssimultaneously.Most chronicdiseasesoccurwhenprocessesthataffectthewholebodyfail.Theseincludethebody’simmunesystemandinflammatory processes, blood circulation or the regeneration of tissue lost through trauma ordegeneration.At the same time, fundamentally new opportunities are opening up for translational medicinethrough the digital revolution including new technologies such as: machine learning/artificialintelligence,biomimeticmaterials,3Dprinting,human-on-a-chip,pluripotentstemcells,organoids,genomeediting, thedramatically increasing levelofdetail and speedofmolecularanalysis (omics:genomics, proteomics, metabolomics), as well as new approaches in diagnostics and therapydevelopment at the cellular level. As an example, Novel Therapies (Advanced Therapy MedicinalProducts-ATMP)-anewclassofpersonalizedtherapeuticsatthecellularbasis(LivingMedicines)-offernewoptionsformoreeffectivetranslationintheareaofacademicresearch.

BIH Approach

The BIH is not a typical research institute. Its innovative approach is to utilize a novel concept ofclinically-anchored cross-organ systems medicine in a comprehensive translational ecosystem tosignificantlyincreasethespeedandeffectivenessofmedicaltranslation.OneofthemainreasonsforthesuccessitenjoysintranslationalresearchistheclinicalandscientificenvironmentattheCharitéandacrossBerlin,enablingahighdegreeof interactiondue to theproximityofdifferentpartners.The MDC (Max Delbrück Center for Molecular Medicine) is central to the development oftechnologiesandnewmechanisticapproaches.

The BIH Translational Ecosystem

Byestablishingcomprehensiveandcoordinatedstructuresinonelocation,theBIH

isabletosuccessfullyandefficientlyimplementitsmissionofmedicaltranslation.

Such an approach enables the various professional groups involved to use their

expertise to establish new preventive strategies, develop new diagnostics and

effective therapies, and to discover how these options can be effective for

patients.TogetherwithCharitéandMDC,theBIHhasestablishedacomprehensive

translationalvaluecreationsystem.

In order to transfer new concepts into clinical practice faster andmore effectively, it is importantthat the parties involved are networked in a translation-oriented environment - the translationalecosystem.TheBIHecosystembundlesavarietyofcompetenciesandinfrastructuresinthevicinityoftheCharitéclinicalfacilities,confirmingthefindingsthat:


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•translationalprocessesareusuallynotlinearandtargeted,assuggestedbytheconceptofthetranslationalvaluechain;and

•avarietyofskills,infrastructuresandsupportmechanismsareessentialforeffectivetranslationThisecosystemisuniquetotheBIH.Itencompassesthenecessarycriticalmassofallprofessionsandskills required, and provides the necessary structures and services for translation. As such, thisenvironment allows continuous optimization of ideas and solutions in one iterative ‘bench tobedside’ and ‘bedside to bench’ process. Crucial for the achievement of the BIH mission is thecontinuousdevelopmentof theecosystemasa learning system. Theexperiencegathered fromallprojects andprocesses, andnew ideas and concepts from the faculty andbenchmarks fromotherinstitutions,contributetothis.

Figure2:ThetranslationalEcosystemofBIH

Cross-Organ Systems Medicine

The BIH focuses on cross-cutting issues: for example, digital medicine, and cell-

based therapies as innovative drivers and enablers; and not organ-specific

approaches such as cardiology and cancer research. The BIH, thus, works across

systemsmedicine, examining processes that arise from the interaction of various

organsandsystemsinthebody.

The systems medicine translation approach at the BIH is therefore a necessary addition to thedisciplinarily oriented approach of the German Centers for Health Research, which uses adecentralizednetworkofexpertiseatseverallocations,witheachfocusingonwidespreaddiseases.


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Principles ThewaytheBIHworkscanbedescribedbythefollowingprinciples:FullCircle Together with the Charité and other stakeholders, the BIH is building a

comprehensive translational value creation system. Ideas from thelaboratory are transferred to the bedside and checked there (‘bench toclinical reality’). The observations in the clinic are carried back to thelaboratory(‘clinicalchallengestobench’)andstimulatethedevelopmentofnewideasandtechnologies.

One-Campus InterdisciplinarytranslationismadepossibleattheBIHasallparticipantsare

able to continuously exchange ideas. The essential prerequisites ofinnovation,theclinicandimplementation,areavailableonsiteandcanbeutilized without institutional barriers. This particularly applies to clinically-obtained data, which is made available to research, whilst ensuring thehighestlevelsofdataprotection.

Interdisciplinarity The BIH’s ‘translational scientific community’ includes medical

professionals, basic research scientists, innovators (i.e. scientists who givetheimpetusforclinicalapplicationwithoutcommercialinterestthemselves),engineers, digital experts and data scientists, business developers,entrepreneurs,marketanalysts,healthsystemexperts,aswellastheusers,andparticularly,patients.

Partnering Toensureexcellenceatallstagesofthetranslationprocessandtobeabletofundapplication-relatedphases, theBIHaddsto itsexpertiseandresourcesthroughcooperationwithprominentpartnersfromscienceandindustry.

Decide-Early TheBIHcontinuouslyanalyzesprojectsatalllevelsofthetranslationalvalue

chain in order to either specifically promote them, or where necessary, toterminate them early. This increases overall effectiveness and reduces theriskoffailureinthelater,cost-intensive,stages.

Value Research at the BIH must be reliable, robust and transparent. It must be

effective for science and of benefit to the wider society, and it must beproportionatetotherisksandburdenstaken.

Responsibility The BIH takes its responsibility towards patients and citizens extremely

seriously. This is reflected in their participation, and appropriaterepresentation, in the BIH processes and all within a gender and diversity-sensitiveorganizationalculturewithacontinuousfocusonrelevantmedicalneeds.


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Implementation at the BIH

To fulfill itsmission, the BIH’s translational ecosystem is based on three components: innovationenablers, translation hubs, and focus areas. These three components provide different supportmechanisms for the translational process and the implementation of specific projectswith a highlevel of innovation and translational potential. While the development of the translationalenvironment isacontinuoustaskthataffectstheentirefaculty,highly-relevantquestionsfromthevarious focusareas canbeaddressedbyexperts in the respective translational fields andadapteddynamicallytoscientificandclinicaldevelopment.

Figure3:ThecomponentsofBIH

Innovation Enablers

Thebasis of the ecosystem is the translation-orientedmindset of all stakeholders involved in theprocessandtheconstantsupportofthefacultyinallphasesoftranslation.Developingthisisthetaskof the BIH’s four innovation enablers: theBIHAcademy (BIA) continuously promotes doctors andscientists with translational skills and interests, designs specific further-education programs, andidentifiesgroup-specific careerpaths; theBIH-QUESTCenterhasdevelopedand implementednewapproachestoensurethequalityandsustainabilityofresearchthroughallphasesofthevaluechain;theBIH-Translation-Boosterdevelopsmechanismsandincentivestoovercomethehurdlesalongthechain; and BIH-Innovations promotes the early, and targeted, transfer of innovative ideas intoproductsandclinicalsolutionsatalllevelsoftranslation.


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Figure4:TheInnovationEnablersofBIH

Thesefourfunctionsareessentialinallareasofmedicaltranslation.However,astheydonotdirectlyaddressorgan-orientedmedicalquestions,theyarenotusuallythefocusoftranslationalinitiatives.Toaddressthis,andaddafurtherdimensiontotheeffectivenessoftranslation,theBIHhassetupthe innovation enablers to optimize conditions for the development and maintenance of thetranslational ‘mindset’ and ‘support’ over the long term. The incentive mechanisms of value,translation and innovation services complement the classic performance-oriented allocation offunds,whichrewardspublicationsandthird-partyfundraising.It is very important to avoid an oversimplified interpretation of the translational value chain. Thefocus of translational efforts in the academic environment is usually a question of whether newconceptsandideascanbeimplementedscientificallyandclinically(point1inFig.5).However,suchanarrowviewcanoftenleadtoprojectfailureinlaterphasesandtotheinefficientuseofresources.Reasonsforthiscanincludetheinadequatevalidityandrobustnessofdatafromtheearlierstages,oralackofforesightwhenexamininglegalandeconomicaspects.SuchdeficitsareavoidedintheBIH’stranslationalecosystemthroughBIH-InnovationsandtheBIH-Translation-Boosterexaminingideaswithhightranslationalpotentialattheearlystagewithscientificandtransferaspectsinmindandcontinuouslysupportingthepartiesinvolvedintheprocessasearlyaspossible.Inthisway,feasibilityintermsoftechnology,legal,financialandorganizationalaspects(points2and3)canbeclarifiedearlyoninordertolaunchlargernumbersofhighlyinnovativeandriskierprojects intothetranslationalecosystembasedonthis“decide-early”principle.Theservicesofferedby the innovationenablers are generally available to theentire scientific community, thushelpingtocontinuouslycreatethebestconditionsforconcretetranslationalapproaches.

Figure5:TheRoleoftheInnovationEnablersinthetranslationalEcosystemofBIH


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Translations Hubs

Eachtranslationalinstitutionmustselectwhichresearchanddevelopmentprioritiesitwantstofocusitsactivitiesandresourceson.ThistakesplaceattheBIHwithinthetranslationhubsandfocusareas.Inaccordancewiththestrategicdecisionforacross-organapproach,theBIHhasselectedtopicsthatcanmakefundamentalsystemsmedicinecontributionstotranslation.The translation hubs represent topics and technologies that will revolutionize medicine across

variousdisciplinesinthecomingyears:

•DigitalMedicine

•Multi-Omics

•OrganoidsandCellEngineering

•ClinicalTranslation

Figure6:TheTranslationHubsofBIH

In these areas in particular, highly relevant contributions can be made to the BIH’s translationalmissionandto improvingclinicaloptionsforpatients.ThetranslationhubDigitalMedicineenablestheextensiveuseofdata-basedapproaches;Multi-Omicsensuresphenotypingatthehighestlevel;andOrganoids and Cell Engineeringmake the targetedmodulation of cells and 3D organ culturesusable for innovative, precision-basedmedical approaches. The translation hubs support effectivetranslationalresearchthroughtheClinicalTranslationhubby:•Networkingexpertsandestablishingaresearchcommunity

•Developinginnovativetechnologiesandmethods

•Providingexcellenceinscientificservices(corefacilities)Focus Areas

The focus areas bring concrete translational research and development projects into thetranslationalecosystem.Thesefocusareasarecharacterizedby:•takingasystemsmedicineapproach

•havingahighpotentialforgroundbreakingsuccessintranslation

•successfulanddecisiveimplementationinthetranslationalecosystem


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Figure7:TheFocusAreasofBIH

ThreefocusareashavebeenestablishedattheBIH,eachusingdifferentelementsoftheBIH’stranslationalvaluechain(‘regenerativetherapies’,‘vascularbiomedicine’,and‘singlecell

approachesforpersonalizedmedicine’).Therelevanceofthese,aswellastheexcellenceachievedbythepartiesinvolved,isclearfromtheextraordinaryfactthatfromacrossallscientificfields,twoareas(‘regenerativetherapies’and‘singlecellapproachesforpersonalizedmedicine’)havemadeittothefinalselectionroundofthelastsix‘EuropeanFETFlagships’.Focusareasarefundamentallydynamicandarecontinuouslyadaptingtoscientific,technologicalandtranslationaldevelopments.Theintegrationofboththeavailableexpertisenecessaryforresearchprojectswiththatnotavailableon site,aswell as thepilotingof conceptsand technologiesparticularly relevant for translation, iscarried out via the dynamic ‘Excellence Fund’. High-risk projectswith high potential are given theopportunity to showevidence ofmedical added value through temporary funding and to connectwithexternalfundingagencies.

Success Criteria and Exploiting the Potential of the BIH As the BIH’s translational approach differs significantly from other basic research institutes, it isessentialtodevelopnewcriteriaforevaluatingthesuccessoftheBIHthatgowellbeyondtheusualindicators,suchasimpactfactorsorthird-partyfunding.Thesuccessoftranslationalresearchcannotbemeasured in termsof thenumberof individual publications and, as a rule, cannotbe assignedpurelytoindividuals.Bothspecificcriteriafortranslationalprojects(seebelow)andnewevaluationprinciplesforresearchersworkingintranslationalresearchmustthereforebedefined.Specific indicators must focus on the BIH mission, i.e. reflect the relevant medical benefits forpatients.Directparametersforthisgoalinclude:•Introductionofnewpreventive,diagnosticandtherapeuticproceduresintotheclinic

•Productsandlaunches

•Changestoguidelines,treatmentandtherapyguidelines

•Returnsfromsalesandlicensing

•Socialaddedvalue(virtualproceeds)

•PROMS(PatientReportedOutcomeMeasures)


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Thesedirect indicatorsonlyemergeat theendof the successful translationand, therefore,withaconsiderable delay in the important preparatory steps. However, these contributions areindispensable and can also be measured at short notice. They also need to be assessed andincentivized:•Proofofprinciplestudies

•Manufacturingpermits,etc.

•Firstinhuman-studiesandclinicalstudiesbasedonownconcepts(IIT)

•Ratio:fromnumberofpatentsorpatentapplicationstopatentsbeingused

•Licensing,spin-offsandcorrespondingcooperation

AlsorelevantfortheBIHstrategyareadditionalparametersthatassessqualityandsustainabilityatalllevelsoftranslation,suchas:•OpenAccesspublications

•OpenData/OpenScience

•Publicationofnegativeresults

•ConfirmatoryStudiesTheBIH-QUEST-CenterhaslaunchedimportantinitiativesforBIHandCharitéinrecentyearsinthisarea,whichhaveledtoasignificantincreaseinopendatapublicationsandhavebeenacknowledgedbothnationallyandinternationally.In order to further develop structures and mechanisms for translation, the BIH became the firstcontinental European partner to cooperatewith theWellcome Trust in 2019.Within this context,parametersformeasuringsuccessandmechanismstoincentivizethedifferentstepsoftranslation-and the different areas and individuals in the translational ecosystem -are being developed andcomparisonsmadewithotherinternationalmedicalresearchcenters,suchastheNationalInstitutesofHealth(NIH).Asystemisbeingdevisedinwhichevaluationwillmakeitpossibletocomparethedifferentsuccesscriteriaquantitatively.Structurally, the BIH is a new type of scientific institution and, when integrated into the Charité,becomesaprototypefordirectfederalfundingofhighereducationinstitutions.Theinvolvementinthe Charité enables the BIH to strive for new standards on a structural level. That ranges fromeducation – such as the promotion of young researchers into new translational career paths - toqualityassuranceandstructuralsupportintheprocessesofaresearchhospitalinprojectselection,recruitment,andentrepreneurialsupport.

bih mission and implementation - bihealth.org · 2020. 9. 15. · bih — mission and...

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