Transcription
Global Drug DevelopmentGlobal Governance OfficeInvestigator Initiated Trials:a guide for prospectiveInvestigators
ContentsIntroduction2Requirements (feasibility) to conduct a clinical study3Overview of the submission/application process4Overview of the IIT process5Conducting the IIT5Safety reporting requirements6Study results and publications8Overview of key responsibilitiesof Novartis and the Investigator9Abbreviations10
Novartis believes inthe need to supportethical independentclinical researchIntroductionAs part of the commitment by Novartis to deliverinnovative therapies to patients worldwide, Novartisbelieves in the need to support ethical independentclinical research conducted by qualified third-partysponsors (Investigators). The value of this scientificresearch, together with Novartis-sponsored research,is fundamental to the understanding of the benefit/risk profile of Novartis therapies and the explorationof new opportunities to address unmet medicalneeds. This is why Novartis provides support to newInvestigator Initiated Trials/Studies (IITs) every year.An IIT is defined as a study with scientific and medicalmerit developed and sponsored by an independentInvestigator or academic sponsor. An IIT is a clinicalstudy conducted without the participation of Novartis,for which the IIT sponsor requests Novartis to provideeither funding, drug product or both.As an Investigator, if your IIT proposal is accepted,Novartis may provide you with financial support and/or Novartis product(s). However, you will retain fullresponsibility and control of the design, initiation,management, data analysis, monitoring, and reporting,as the sponsor of the study. Please note that for NonInterventional Studies, Novartis is only able to providefinancial support, not study drug.The purpose of this guide is to provide a cleardescription of each of the essential requirements thatmust be fulfilled before support will be considered byNovartis, and to highlight your obligations as the studysponsor when your IIT is being supported by Novartis.
3 INVESTIGATOR INITIATED TRIALS: A GUIDE FOR PROSPECTIVE INVESTIGATORSRequirements (feasibility)to conduct a clinical studyThe following are the key requirements that will needto be fulfilled in order for Novartis to evaluate andconsider supporting your study. Should you have anyquestions on these requirements, please contactyour Novartis Medical Science Liaison (MSL) or localMedical contact.All IIT submissions should be made to Novartis inGEMS, our cloud-based system which you can accessthrough www.novartis.com.Investigator qualificationsAll of the following documents must be provided: The Investigator’s curriculum vitae to ensure that theInvestigator is suitably qualified and able to conductthe required evaluation and analysis A current valid license to practice medicine* Recent clinical research experience within theprevious 3 years* Good clinical practice (GCP) training within theprevious 3 years**Only applicable for Interventional StudiesStudy CriteriaThe proposed study should be: For a legitimate research purpose– scientific merit, which complementsthe Novartis-generated research To better understand the risk/benefitprofile of the compound Address an unmet medical need Aligned with the Novartis compound scientific/development strategy as indicated onwww.novartis.com strategic areas of interest.ResourcesThe Investigator must have the appropriateinfrastructure in place and capability to conductthe study proposed.
4 INVESTIGATOR INITIATED TRIALS: A GUIDE FOR PROSPECTIVE INVESTIGATORSOverview of the submission/application processInvestigator creates profile on GEMS welcome pageand agrees to Novartis Privacy PolicyInvestigator is provided with access to the GEMS portal and asked for theinformation needed to meet the criteria required for the IITInvestigator submits concept with all necessary supporting documentation,including budget if required, proof of qualification and CVA study ID is assigned and Novartis evaluates the studyconcept and supporting documentationNovartis notifies Investigatorthat study concept is of interestNovartis notifies Investigator thatstudy concept is not of interestInvestigator submits full protocolInvestigator submits Itemized budget(if required)Review by NovartisNovartis carries out assessment inline with Fair Market Value (FMV)Investigator notified ofprotocol decline decisionInvestigator notified ofprotocol approval decisionInvestigator notifiedof acceptanceInvestigator notifiedof non-acceptanceNovartis prepares IIT agreementInvestigator/Investigator’s institution reviews agrees and signs agreementInvestigator submits proof of completion of all applicable regulatoryrequirements (e.g. local ethics approvals, registry in a public database)KeyInvestigatorNovartisDenotes actions where Investigators will be required to submit and uploadinformation and documentation associated with their IIT via the Novartis‘GEMS’ portal. This portal manages each stage of a Novartis IIT, from initialconcept submission through to final report and publication.
5 INVESTIGATOR INITIATED TRIALS: A GUIDE FOR PROSPECTIVE INVESTIGATORSOverview of the IIT processReceipt of funding/study drugIIT budgets submitted to Novartis will be subject toa Fair Market Value (FMV) assessment against anexternally benchmarked database prior to approval.The purpose of IIT funds are only to furtherthe scientific research and knowledge within aparticular therapeutic area. IIT funds cannot beprovided to just gain experience with a study drugor treatment protocol.It is also important to note that IIT support may notbe given to pay for the recipient’s ordinary operatingexpenses (i.e. expenses of activities that the recipientis already required to perform or customarilyperforms) or support research that has alreadyoccurred. Following the initiation of a study, fundingwill be released as key milestones are achieved, inaccordance with the payment schedule noted in theIIT Agreement. The mandatory key milestones include:MilestonePercentage offunding (%)Execution of IIT Agreement,Ethics Committee (EC)/Health Authority (HA)approval and First PatientFirst Visit (FPFV)*10%Provision of final ThirdParty Study Report (TPSR)to Novartis10%Submission for publicationor provision of publicationto Novartis10%*5% can be paid on execution of the IIT AgreementPlease note that all other payment milestones willdepend upon the study design and the schedule notedin the IIT Agreement and could include milestonesbased on recruitment.You will need to have the following items in place andprovided to Novartis prior to release of study drugand/or funding: Final protocol and informed consent form(as applicable) An institutional review board (IRB)/EC approval ofthe protocol and informed consent form HA approval (as applicable) Itemized study budget (subject to FMV assessment) Fully executed IIT Agreement with NovartisConducting the IITStudy status, reporting and registryin a public databaseAccording to the Novartis IIT Agreement,you should inform Novartis of any updates to thestatus of the IIT. For example:i. You must verify that all applicable regulatoryrequirements have been met which includesclinical trial registration in a public databasesuch as www.clinicaltrials.gov;ii. You should provide enrollment data, confirmingthat safety information is being transferred toNovartis as required;iii. As per the agreed frequency in the IITAgreement, you should complete AdverseEvent (AE) reconciliation and share thecompleted AE reconciliation summary formwith Novartis;iv. You should advise Novartis immediately ofany amendment to either the protocol orinformed consent form.
6 INVESTIGATOR INITIATED TRIALS: A GUIDE FOR PROSPECTIVE INVESTIGATORSSafety reporting requirementsOne of the most important requirements of an IITInvestigator is the responsibility to monitor and reportsafety data to the appropriate authorities, in a timelyand accurate manner.These requirements will vary depending on whetherthe study is of an interventional or non-interventionalnature, the type of data collection, as well as onwhether the study is focused or not on a Novartisproduct. These are outlined below:In addition to reporting safety data to all relevantauthorities, you will have the responsibility to reportthe following safety information to Novartis inaccordance with the IIT Agreement.For Interventional StudiesSafety reporting requirements for interventional studiesINVOLVING a Novartis investigational productTransfer to Novartis in an ongoing manner of Serious Adverse Events (SAEs), reports of drugexposure during pregnancy and reports of drug misuse or abuseTransfer to Novartis of any findings that might alter the current benefit-risk profile of the Novartisproduct or that would be sufficient to consider changes in the Novartis product administration orin the overall conduct of the studyProvision of the randomization codes (for blinded Interventional Studies)Provision of copies of Investigator notifications for suspected unexpected serious adversereactions (SUSAR) or provision of biannual SUSAR listing*Provision of copies of Development Safety Update Reports*Performing Adverse Event (AE) reconciliation periodically and at the end of the study*If the preparation and submission of such documents are required as per local regulationsSafety reporting requirements for interventional studiesNOT INVOLVING a Novartis investigational productNotification to Novartis of any Adverse Drug Reaction (ADR) (irrespective of seriousness) to a Novartisproduct that the Investigator becomes aware of as spontaneous reports
7 INVESTIGATOR INITIATED TRIALS: A GUIDE FOR PROSPECTIVE INVESTIGATORSFor Non-Interventional StudiesA Non-Interventional Study can involve: Primary data collection, for instance, prospectiveobservational studies and registries in which thedata collected derive from routine clinical care orscientific outcomes researchOR Secondary use of data, for instance, databaseresearch or review of records where all the eventsof interest have retrospectively occurred (e.g. casecontrol, cross-sectional and cohort studies)The timelines for providing this information to Novartismay differ depending on where the study is beingconducted according to local regulatory requirements.The timelines will be specified in the IIT Agreement.In turn, Novartis will ensure that any importantsafety findings or urgent safety measures for theNovartis product that is the focus of the IIT areshared with the investigator. Novartis will alsoprovide an output of the Novartis safety databasefor performing AE reconciliation, as required.The safety data requirements for each type ofNon-Interventional Study are shown below:1. Involving Primary data collection and WITH a Novartis product of focusTransfer to Novartis in an ongoing manner of SAEs, reports of drug exposure during pregnancy andreports of drug misuse or abuseTransfer to Novartis of non-serious AEs suspected to be causally related to the Novartis producti.e. Adverse Drug Reactions (ADRs)Transfer to Novartis of any findings that might alter the current benefit-risk profile of the Novartis productPerform AE reconciliation periodically and at the end of the study2. Involving Primary data collection but NO Novartis product of focusNotification to Novartis of any ADR (irrespective of seriousness) to a Novartis product that theInvestigator becomes aware of as spontaneous reports3. Involving Secondary use of dataTransfer to Novartis of any findings that might alter the current benefit-risk profile of the Novartis productNote: Individual AE reporting to Novartis is not required
8 INVESTIGATOR INITIATED TRIALS: A GUIDE FOR PROSPECTIVE INVESTIGATORSStudy results and publicationsNovartis requires the final Third-Party StudyReport (TPSR) to be provided within 13 monthsof the Last Patient Last Visit (LPLV) (or within 7months in the case of paediatric interventional trials).For TPSRs written in languages other than English,a full English translation is required for IITs that useda Novartis product.As part of Novartis’ commitment to publishingresearch, you are encouraged to publish the results ofIITs. As the Investigator, the content of any publicationis your responsibility, and Novartis will not be involvedin authorship selection or writing and should not beincluded as a co-author of IIT publications.You should submit any publications to Novartisfor review at least 15-30 days prior to submission,depending on the publication type.In order to receive the two final milestone payments,you must produce a TPSR within the specifiedtimelines and attempt to publish study data, e.g.submission of a manuscript, an abstract, or a posterto a congress or a journal for publication.
9 INVESTIGATOR INITIATED TRIALS: A GUIDE FOR PROSPECTIVE INVESTIGATORSOverview of key responsibilities of Novartis and the InvestigatorResponsibilitiesDevelopment of the Research ProtocolReview of the Research ProtocolDistribution of updated, approved product informationSubmission of dossier to IRB/EC at study start and annual renewalSubmission of dossier to local HARegistry of IIT in a public database, such as www.clinicaltrials.govImplementation and monitoring of clinical research(including data monitoring)Contracting with third-party vendors (clinical research organizations,medical writing, Pharmacokinetic (PK) or other analyses, patientinsurance, statistical, courier, etc.) and the management and oversight ofany other participating sites or contractorsConducting of research (patient inclusion, exams conduction, etc.)Ensure that the IRB/EC/local HA approved protocol is adequatelyfollowed (in accordance with GCP, applicable guidelines and localand international standards)Submission of protocol amendmentsReview of protocol amendmentsMaintaining clinical records of the study and assurance of the veracityof collected data and other attributions related to GCPReporting of safety data to the manufacturer of the study drug, asrequired, based on the study typePerforming of AE reconciliation, as required based on study typeReporting of safety data to HAs, as appropriateAnalysis of study data, preparation of interim and final study reports andforwarding them to NovartisSubmitting draft publications to Novartis prior to submission to ascientific congress or journalIndependently publishing the clinical trial resultsReporting study results to HAs, if required according to local regulationsNovartisInvestigator
10 INVESTIGATOR INITIATED TRIALS: A GUIDE FOR PROSPECTIVE INVESTIGATORSAbbreviationsADR Adverse Drug ReactionAE Adverse EventEC Ethics CommitteeFMV Fair Market ValueFPFV First Patient First VisitGCP Good Clinical PracticeGEMS Grants, External Studies, Managed Access SystemHA Health AuthorityIIT Investigator Initiated Trial/StudyIRB Institutional Review BoardLPLV Last Patient Last VisitMSL Medical Science LiaisonPK PharmacokineticSAE Serious Adverse EventSUSAR Suspected Unexpected Serious Adverse ReactionTPSR Third Party Study Report
In addition to the requirements set forth inthis guidance document, each request willbe assessed subject to applicable locallaws and regulationsPublished by:Novartis Pharma AG4002 Basel, Switzerland 2021All trademarks mentioned enjoy legal protection.www.novartis.com
Transfer to Novartis of non-serious AEs suspected to be causally related to the Novartis product i.e. Adverse Drug Reactions (ADRs) Transfer to Novartis of any findings that might alter the current benefit-risk profile of the Novartis product Perform AE reconciliation periodically and at the end of the study.
