a network model for early clinical development · 2019-08-30 · anactionplan figure 2: the site...
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A NETWORK MODEL FOR EARLY CLINICAL DEVELOPMENTAuthor: Alexandre Templier, Lead Human data science.
Table of contentsIntroduction 3
Relationships with sites 3
Challenges in pre market study 4
Selecting the right commercial site for an early phase trial 4
A rigorous site qualification process 5
Ensuring high quality study delivery 5
Key features of a successful network model 6
Why ECLEVAR? 7
Conclusion 7
About the author 9
2 | A network model for early clinical development
INTRODUCTION
This paper examines the benefits of a proven network model in pre market clinical trial, for all medicaldevices, including Class III and active implantable devices. The authors examine lessons learned basedon ECLEVAR’s experience with a vast number of pre market clinical trial studies across the Asia-Pacificregion, Europe and the United States, involving patients. Solutions to challenges relating to capacity,timelines and quality are also described. The paper considers the importance of site selection,relationships with sites and strong governance, and describes ECLEVAR’s proven processes for sitequalification and for ensuring high quality study delivery. The authors conclude that the pre marketclinical trial network model provides flexibility, speed, quality and cost-effectiveness, delivering thebest solution to fit biopharma companies’ needs, rather than fitting existing capabilities to theirchallenges.
RELATIONSHIPS WITH SITES
Pre market clinical trials are a critical phase inmedical devices development, requiring a highlevel of confidentiality, fast decisions and rapidstart-up. This “fast-track” approach requireslean processes, standardized contracting, anda thorough knowledge of the regulatoryenvironments of various countries, and howthese can be used to advantage whileprotecting patient safety and data integrity.
Pre market clinical trials sites are typicallycommercial ventures, based on a differentfinancial model than academic teachinghospitals. A CRO’s relationships with thesesites should be based on true partnerships,with learnings quickly communicated withinthe network. This is key to differentiating thequality of service from that of loose, first-come,first-served relationships.
Addition of key academic centers withexperienced researchers and access tomultiple patient populations strengthens theability to operationalize the pre market clinicaltrials.
Strong governance is essential to ensure a highlevel of patient safety, that all ethicalconsiderations are taken into account, and thatthe site can meet all regulatory requirements,optimize clinical conduct and recruitment,deliver quality data, and deliver according tocontracted timelines. All sites should gothrough a multi-step qualification process, withsite performance – including safety, qualityand delivery aspects – monitored via audits,medical safety assessments.
The network model (Figure 1) allows forflexibility to focus on the development needsof medical devices, including selecting themost appropriate region, country and sites fora particular trial design, based onconsiderations such as the sites’ experience,expertise, access to patients, historicaltimelines and costs. This model also providesaccess to specialized capabilities, such as theability to perform a bridging study with aJapanese population. The network model hasbeen particularly successful in accelerating thedevelopment of medical devices, enablingrapid completion of pre market clinical andexpedited start-up of PMCF trials in parallel.
3 | A network model for early clinical development
SERVICES PROVIDEDü Project managementü Medical servicesü Clinical monitoringü Feasibilityü Regulatory & start up
ü Life cycle safetyü Data managementü Biostatisticsü Medical Writing
Figure 1: A global pre market clinical trials network delivery model
KEY ADVANTAGE FOR SPONSOR• One core dedicated team: Same process, safety oversight, efficiencies, ease ofplanning and execution, speed, better patient solutions• Single partner: Capable to perform pre market clinical and PMCF studies• Bring best in class: ECLEVAR pre market clinical and PMCF experience & resources
IntegratedServices
Sponsor
Partner Site Network
PortfolioTeam lead
Creating solutionsFor you to drive
Healthcare forward
CHALLENGES IN PRE MARKET STUDYIn operationalizing global earlydevelopment studies, there are threemain challenges:
Capacity: There is strong competitionfor major studies. Hence, strongrelationships with sites are essential tosuccess. With a network of carefullychosen sites, ECLEVAR is able toleverage our experience and alliancewith these sites to obtain priorityplacement of study. They assessfeasibility quickly and are part of theearly engagement process.A customized approach is provided foreach protocol, whether the customerneeds hundreds of healthy volunteersor a smaller group of patients, or acombination of both.
Timelines: Timelines are key in drugdevelopment. Startup timelines areshortened by utilization of a simplified,fit-for-purpose process for start-up ofearly development sites, andstandardizing templates for sponsorand site materials and documents. Useof master independent contractoragreements accelerates the study-specific contracting process.
Quality: Collaborative relationshipsbetween sites and CROs, with apredefined and agreed quality matrix,can yield optimal quality. Usingpremarket studies experienced, trainedand dedicated Project Managers andClinical Research Associates (CRAs) co-located with sites facilitates monitoringthat is close to real time. Externalnetwork sites are held to the samerigorous quality metrics as theECLEVAR internal pre market studyunit.
4 | A network model for early clinical development
SELECTING THE RIGHT COMMERCIAL SITEFOR AN EARLY PHASE TRIAL
Site selection is a key decision. Priorexperience with a site may play a major role ina sponsor’s decision, or a study award may bebased on a proposal document plus follow-onmeetings. The widest possible portfolio of sitesshould be examined, and the following criteriaconsidered:
• The medical safety judgment of the site’smedical team
• Education and experience of the site’smedical and clinical teams
• The physical infrastructure and training ofsite staff to conduct the study and requiredprocedures
• The ability of the site to recruit the patientsneeded for the study, and the speed andquality of similar prior studies
• Site per patient cost
• Confirmation of detailed standardoperating procedures (SOPs) that meet orexceed expectations regarding training,processes, quality measures and patientsafety, and regulatory and ethicalrequirements.
An appropriate biopharmaceutical servicespartner can help with this process. Recent highprofile incidents in pre market clinical trialshave again highlighted the critical importanceof an in-depth assessment of a site’s medicaljudgment.
An appropriate biopharmaceutical servicespartner can help with the site selectionprocess. Recent high profile incidents in premarket clinical trials have again highlightedthe critical importance of an in-depthassessment of a site’s medical judgment.
A RIGOROUS SITE QUALIFICATIONPROCESS
ECLEVAR follows a stringent vetting approachfor early phase trial sites (Figure 2). This isbased on long-term relationships with a widenetwork of sites around the world. An analysisof the sites’ scientific, therapeutic, regulatory,site management, and project managementexperience and expertise helps identifystrengths and weaknesses. Each site on theshort-list completes a detailed questionnaireabout its capabilities and experience. A premarket clinical team, including clinicaloperations representatives, physicians andscientific experts, then conducts an on-sitequalification visit. Evaluation is repeated everytwo years, unless significant changes or qualityissues arise.
ENSURING HIGH QUALITY STUDY DELIVERY
This approach to vendor and site qualityoversight and governance ensures high qualitystudy delivery (Figure 3) through stepsincluding:
Rigorous site qualification/vendor approvalprocess
Accelerated start-up timelines
» Negotiation of an initial MasterIndependent Contractor Agreement(MICA), which enables the use ofabbreviated, three-page study specifictask orders
Comprehensive project planning
» Integrated project managementplan including vendor management,clinical operations, communications,risk management, and qualitymanagement plans
» Site expectation meeting andplanning meetings with vendors
Initial and ongoing project team training
» Detailed training during site initiation
» Ongoing study specific training forany new staff or new protocolrequirements
• Close CPM oversight during study conduct
» Regular interaction with the CRA,sites and vendors to ensure thatdeliverables are on track, to identifyand manage risks or issues and toensure all stakeholders are up to datewith project status
» ECLEVAR pre market clinical trial QAleadership on issue investigationand CAPAs
• Pre market clinical trial Site:maintain a close relationship with network sitesand provide additional oversight ofperformance through regular governancemeetings.
• Proactive QA oversight: Pre market clinicaltrial team conducts site/unit audits on selectedstudies based on an anticipated risk matrix.
• Lessons learned: Work with the CRA, siteand vendors on completion of a study toreview performance, agree processimprovements and implement an action plan.
Work with the CRA, site and vendors oncompletion of a study to review performance,agree process improvements and implementan action plan
Figure 2: The site qualification process
Identify site for
assessment
Send site a detailed pre
market clinical study specific questionnaire
Arrange an on-site audit ISO 14155
and medical safety assessment
Post successful qualification site will be added to approved vendor
list
Evaluation every 2 years, unless
significant changes/quality
issues
5 | A network model for early clinical development
KEY FEATURES OF A SUCCESSFUL NETWORK MODEL
All network sites receive a full ECLEVAR Quality Assurance (QA) Audit and Medical Safety Assessment tofacilitate the sites meeting the ethical, regulatory, medical and quality standards.
• Assessment provides clear guidance on the trial designs that may be conducted and the types of drugcandidates and medical devices that may be investigated at each site.
Maximum flexibility to customize site and delivery location to suit the needs of the customer.
• The project team can be co-located either with the sponsor or the site region.
• The network is seasonally independent with sites in the Northern and Southern Hemispheres.
• This enables the best site to be offered per protocol for on time delivery.
Hand selected, experienced sites ensure not only high quality, on-time delivery, but also a unique, easy- to-access pool of therapeutic and procedure specialties.
Any region can work with any site, ensuring the best site globally is proposed for the study.
Globalized processes and team structures allows for seamless delivery, quality and consistency regardless oftrial design or indication.
Global access to internal and site pre market clinical trial and therapeutic experts to ensure best in classstudy design.
Pre market clinical trial is a small and nimble team that is able to pull in knowledge, therapeutic expertiseand data from the broader ECLEVAR organization.
Immediate change
needed for QA
Hosting customer audits and regulatory inspections of
ECLEVAR services
Qualifying sites and other
ECLEVAR vendors
Management of quality issues
Risk-based audit strategy for trial related audits at investigator sites
and inhouse
Internal process audit programe.g. Project management activities, monitoring, medical oversight etc.
Support process changes &
improvements
Contracted audits
e.g. eTMF, investigator site,
CSR audits
QA representation on the ECLEVAR pre market
clinical trial Medical and Scientific Safety Review
Group and Management Team
Figure 3: Quality assurance: strategy overview
All these elements come together in early phase therapeutic focused network (figure 4 and 5).
6 | A network model for early clinical development
Figure 4: Early phase therapeutic focused networks
Key Requirements Communication
SPONSOR THERAPEUTIC AREA OF FOCUS
Early Engagement with Sponsor
Input & oversight
ECLEVAR Center of Excellence
ECLEVAR Site Feasibility & Experience
Pre market clinical trial ExpertiseMedical Safety Review Group, Scientific & Operational Input
Leadership
NetworkElements
ECO Therapeutic Strategy
Commercial affiliate sites KOLs & academic sites
ECLEVAR Prime & Partner Site Network Biomarker/device providers
Customized Delivery Solutions
CONCLUSION
The pre market clinical trial site networkprovides flexibility, speed and quality within acost-effective model, and includes initial sitequalification, and proactive and ongoingoversight during study conduct. This approachdelivers the best solution to fit a biopharmacompany’s needs, rather than fitting existingcapabilities to their challenges. The modeloperates over a wide range of geographies,providing contracting and pricing benefits tosponsors. Benefits accrue to all partiesinvolved with the network model:
• Biopharma customers have a single point ofcontact (ECLEVAR), without the need to dealwith multiple vendors
• Sites receive a regular flow of business andalso have a single point of contact (ECLEVAR)to address any issues that need to beovercome to complete the study on time andon budget
• ECLEVAR is able to meet customers’ needsby offering solutions from first in man to proofof concept studies across various patientpopulations, using a harmonized approachacross multiple global markets, and providingan effective solution in terms of costs andtimelines.
WHY ECLEVAR?
ECLEVAR offers a full range of pre marketclinical trial services, with:
•One core dedicated team: Globallyharmonized processes, rigorous safetyoversight, efficiencies, ease of planning andexecution, speed, better patient solutions
•Single partner: Capable of performingpatient first in human to proof of conceptstudies
•Best in class expertise, including ECLEVARTherapeutic Centers of Excellence and premarket clinical trial expertise, experienceand resources
•Ability to address a diverse range oftherapeutic areas
•Established relationships with experiencedsites across the globe within the network
•Ease burden of contracting with sites
•Negotiation of site budgets
•Dedicated site across the globe, to be thevoice at partnersites for the customer,project manager and ECLEVAR.
7 | A network model for early clinical development
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Figure 5: Aligned and expanded pre market clinical trial site network with dedicated sites
NORTH AMERICA
• >400 bed capacity
• Partner Sites across U.S. (Cluster of 8 Sites)
• TAs: specialized in Psychiatry & Neurology, Pain
Management, Endocrinology, Immunology, Respiratory,
Cardiovascular, Dermatology, Special Population
CENTRAL EUROPE
• >160 bed capacity (Cluster of 4 sites)
• HVN Partner Sites in Poland, Czech Republic • HVN
studies, Naive subject population
WESTERN EUROPE
• >400 bed capacity (Cluster of 6 sites)
• Patients Partner Sites in UK, Netherlands, Germany
• TAs: Sickle Cell, Respiratory, Endocrinology/ Metabolic,
Immunology, Neurology & Psychiatry, Internal Medicine
ASIA PACIFIC
• >200 bed capacity (Cluster of 20 sites) • Various TAs: Respiratory, Endocrinology, Neurology, Immunology,
Nephrology • Access to appropriate populations for Western biosimilar drug and
medical devices development
Clinical sites
8 | A network model for early clinical development
ABOUT THE AUTHOR
Alexandre Templier has worked in the field of Life Sciences for over 20years. Passionate about information technology and optimizing decision-making in complex environments, Alexandre has spent most of his careermaking engineering sciences work for the benefit of the medical world.Co-founder and CEO of QUINTEN since it was founded, he takes particularresponsibility for development and academic partnerships in the field ofHealth. Alexander holds a doctorate in biomechanics from the EcoleNationale Supérieure d'Arts & Métiers Paris Tech, and an MBA from theInstitut d'Administration des Entreprises in Paris; he was associate lecturerat the Ecole Nationale Supérieure d'Arts & Métiers - Paris Tech from 2001to 2013.
Alexandre Templier, Lead Human data science, ECLEVAR
9 | A network model for early clinical development
