Regulatory Operations and Other Trial Considerations

Transcription

1 Reguatory Operations and Other Tria Considerations Trini Ajazi, MM Aiance Chief Administrative Officer New Investigators Course, Aiance Group Meeting May 11, 2017

2 Presentation Agenda Pharmaceutica Affairs, Reguatory, Protoco and Project Management Resources Confict of Interest Investigationa New Drug (IND) New Drug Appication/Registration Trias Internationa Coaborations

3 Staff Resources Lesie Keey, Reguatory Compiance Manager (COI) Ligi Matthews, Pharmaceutica Affairs Manager (IND/IDE) Aimee Farre, Senior Project Manager (Registration Trias) Stacy Reeves, Senior Project Manager (Internationa Coaborations) Michae Key, Director Protoco Operations Morgen Aexander-Young, Associate Director Protoco Operations

4 Confict of Interest/Financia Discosure Discosure of financia interest required for those who directy or significanty affect design, conduct, anaysis or reporting of the cinica research. This confict coud incude any investigator with a significant interest in a drug or medica device, techniques or technoogy or proprietary arrangements which may impact research being done at the Aiance. Aiance COI Committee reviews a COI discosures and makes recommendations to Group Chair and Executive Committee

5 Discosure requirements and management > $5,000/year incuding trave, honoraria, private stock, pubic stock, ownership interest, inteectua property, unrestricted research grants > $5,000 < $25,000 ($50,000 pubic stock) requires management pan incuding study oversight by study co-chair and study statistician

6 Financia Confict Threshod An investigator with financia reationships >$25,000/year in a privatey hed business, equity interest in a pubicy traded company sponsor that exceeds $50,000/year, or >5% ownership interest (incuding common stock) in either a privatey hed or pubicy traded business, wi generay be prohibited from assuming chairmanship of a study.

7 If Confict Investigator retains rights of authorship on pubications derived from the study in accordance with the requirements for discosure of conficts of interest estabished by the reevant pubishing authorities. Any individuas with a significant confict of interest such that they are ineigibe for a study chair or co-chair roe cannot serve as either first, corresponding, or senior (ast) author of an Aiance pubication. Financia conficts of interest must be discosed in each pubic presentation of research resuts.

8 Investigationa New Drug (IND) An appication to the FDA to test a new drug or a new use of a marketed drug in humans, in a cinica investigation. When do you need to request an IND? When testing a new drug that currenty is not used in the US. When you are using new indication of a drug that is currenty marketed in the US. Generay a study with invoving no significant change in the abeing use of the drug may be IND EXEMPT however you sti must submit an appication to the FDA to confirm exemption.

9 Investigator-Initiated IND Aiance submits Sponsor/Investigator IND appications Aiance is sponsor Monica Bertagnoi, MD is principa investigator Aows Aiance to manage and hod a INDs for Aiance trias CTEP may aso hod IND

10 IND Appication FDA Investigationa New Drug Appication Investigator s CV incuding copy of your medica icense FDA 1572-an agreement between an investigator and the FDA to compy with a FDA reguations whie conducting a cinica tria. FDA 3674-Certificate of Compiance-an agreement to compy with CinicaTrias.gov reguations A copy of the protoco, protoco and ICF Investigator Brochure/Package Insert Cross Reference Letter provided by the drug manufacturer giving the FDA permission to reference another IND regarding this investigationa drug.

11 Now What? The FDA has 30 days from receipt of the appication to request carification or additiona documents. After 30 days...exhae! the IND appication has been accepted. Shorty afterwards you wi receive officia notification. Each year a progress report needs to be submitted as ong as the IND is active. This report shoud incude any protoco updates, changes in safety methods and accura information.

12 What is a Investigationa Device Exemption (IDE) An appication to the FDA to test the effectiveness and/or safety of a device in a cinica study. This type of appication covers both devices and bio assays. There are 2 types of cassifications for these devices: Significant Risk (SR)-poses a potentia risk to heath or safety of the subject. An exampe woud be impantabe devices Non-significant Risk (NSR)

13 Registration Trias New Drug Appication (NDA) for marketing of an investigationa new drug Retrospective Pharmaceutica company decides to fie NDA after Aiance study resuts are reeased; e.g., suppementa NDA for abe extension of drug approved for another indication Prospective Pharmaceutica company requests deveopment of tria with registration intent NDA fied by pharmaceutica company for approva by US Food and Drug Administration (FDA)

14 NDA (New Drug Appication) It is the process by which the sponsor formay request the reguatory body (FDA) to grant approva to market and se a new drug. (The data gathered during the anima studies and human cinica trias of an Investigationa New Drug (IND) become part of the NDA) The goas of the NDA are to provide enough information to permit FDA reviewer to reach the foowing key decisions: Whether the drug is safe and effective in its proposed use(s), and whether the benefits of the drug outweigh the risks. Whether the drug's proposed abeing (package insert) is appropriate, and what it shoud contain. Whether the methods used in manufacturing the drug and the contros used to maintain the drug's quaity are adequate to preserve the drug's identity, strength, quaity, and purity.

15 Key Issues for IND/NDA Studies Sponsor Oversight Investigator Oversight Study Monitoring Data Integrity Pharmacovigiance Inspection Readiness Reguatory Documentation Overa Compiance with FDA reguations and ICH Good Cinica Practice

16 Investigator Responsibiities Scientific contribution to study design Participation in meetings with FDA Assist with pharmaceutica coaboration Study monitoring in cose conjunction with statistica, data center and operations staff Case evauations of eigibiity and disease outcomes/primary endpoints rea time, ongoing is best Protoco deviations Safety reviews Site inquiries

17 Reated Initiatives: Centra Monitoring Centra Data Monitoring Source documents upoaded in Rave Source data review and verification Key eigibiity, disease outcomes/primary endpoints, treatment, AE, patient termination Conducted by centra monitor at data center Appies to investigationa new drug (IND) studies, even if not panned for NDA/registration

18 Reated Initiatives for IND/NDA Audits with documented targeted source data verification (TSDV) in Rave Deegation of Task Log (DTL) Registration and Credentia Repository (RCR) Training documentation (GCP, protoco-specific) Financia discosure Investigator registration CTEP-AERS/Rave integration

19 Aiance Internationa Coaborations Internationa coaborations provide unique opportunities to enhance research in areas such as study design, anaysis, and accrua. The Aiance Internationa Coaborations oversees the operationa activities of internationa sites that participate in Aiance trias; this incudes fu member and non-member coaborators. Non North American sites participate on Aiance trias as Members or Non Member Coaborators (NMCs). NMCs are institutions or networks that participate on Cinica Therapy Evauation Program (CTEP) and Division of Cancer Prevention (DCP) sponsored protocos but are not fu member institutions of the ead protoco organization or a participating organization.

20 Criteria and Issues Considered for Internationa Coaborations Accrua and Accrua Duration Rare Tumors NCI reviews proposa with foowing in mind necessity of contribution of the coaborating organization/sites past experience with the coaborating organization/sites potentia contributory accrua of the coaborating organization/sites country of the coaborating organization/sites

21 Considerations per NCI pan for auditing/monitoring of coaborating organization/sites can be impemented abiity to execute necessary MOU/agreement abiity for coaborating organization/sites to compy with appicabe reguatory requirements and NIH grant requirements (e.g., FWA and State Dept. cearance) whether the tria is conducted under an IND or not, and if so, who is the IND sponsor IND agent suppier, distributor and company coaborator approva, if appicabe cost impications

22 Reguatory Fiings in other countries European Union Cinica Trias Appication- The CTA is submitted to the Competent Authority (CA) of each EU member state participating in the cinica tria in the member state s officia anguage. The preparation, submission and verification of CA approva shoud be handed by the EU member state coaborating institution. European Cinica Trias Database (EudraCT) Austraia Austraian New Zeaand Cinica Tria Registry (ANZCTR)

23 Aiance Internationa Coaborators Fu Members Swiss Group for Cinica Cancer Research (SAKK) N Phase II/III Tria of Neoadjuvant FOLFOX, with Seective Use of Combined Modaity Chemoradiation Versus Preoperative Combined Modaity Chemoradiation for Locay Advanced Recta Cancer Patients Undergoing Low Anterior Resection with Tota Mesorecta Excision Non-Member Coaborators European Organization for Research and Treatment of Cancer (EORTC) A A Randomized Phase III Tria Comparing Conventiona-Dose Chemotherapy Using Pacitaxe, Ifosfamide, and Cispatin (TIP) with High-Dose Chemotherapy Using Mobiizing Pacitaxe Pus Ifosfamide Foowed by High-Dose Carbopatin and Etoposide (TI-CE) as First Savage Treatment in Reapsed or Refractory Germ Ce Tumors N N0577 (CODEL): Phase III Intergroup Study of Radiotherapy with Concomitant and Adjuvant Temozoomide versus Radiotherapy with Adjuvant PCV Chemotherapy in Patients with 1p/19q Co-deeted Anapastic Gioma or Low Grade Gioma Austraian and New Zeaand Urogenita and Prostrate Cancer Trias Group (ANZUP) Recenty approved to participate on A031102

24 Requirements for Internationa Coaboration Approva Aiance Internationa Feasibiity Assessment Aiance Executive Committee Review NCI review and approva Request for Internationa Site Participation in CTEP Studies (form submitted at the time of LOI/concept submission) Request to Amend Ongoing Study for Internationa Site Participation The CTEP Internationa Site Coordinating Group (ISCG) wi review the request. A fina decision wi be sent approximatey 4-6 weeks from submission

25 Logistica Considerations Reguatory Registration and Credentiaing (Investigators, Research site staff in the future) CTEP-ID/CTEP-IAM Account (Investigator and Research site staff) Human Research Subjects training GCP training documentation for investigators and site staff. Submission of this information to the NCI wi change with impementation of the NCI Registration and Credentia Repository (RCR). Ethics Approva Federa Wide Assurance (FWA) State Department Cearance Execution of Memorandum of Understanding (MOU) Drug Access and Distribution Audit & Monitoring Pan AE and Expedited AE Reporting Transationa Research and specimen submissions System Access and Training (OPEN, Rave, BioMS, CTSU, CTEP-AERs)

26 Reguatory Registration and Credentiaing Investigator Prior to participation in NCI sponsored cinica trias investigators must register with the Pharmaceutica Management Branch (PMB) of the Cancer Tria Evauation Program (CTEP). FDA Form 1572, Suppementa Investigator Data Form (IDF), Financia Discosure Form (FDF), Current Curricuum Vitae (CV) After PMB registration investigators must register with CTEP IAM; an active user account and password wi be provided. Research staff or associates (non-investigator cinica site staff) Must obtain CTEP IAM user account. Registration with the NCI wi aso be required for a research staff once the RCR is impemented. FWA - A NMCs must have an active FWA ( )

27 Reguatory State Department Cearance (SDC) Advance cearance from the US Department of State is needed for each non-us component Aiance wi submit the information to NCI, and the NCI wi submit to the State Department. Approva is received in approximatey 3-6 months. Information needed for the Internationa partner: CTEP Site code for institution Address of institution Name, phone, and emai of Principa Investigator CTEP ID of PI (Required for SDC submission) FWA# (Required for SDC submission)

28 Group Specific Appendix The GSA must be incuded as an appendix to the protoco, per NCI poicy. The document serves as a reference for Internationa participants and identifies processes that may be country specific, incuding: Tria organization Investigator and site registration procedures Patient registration and randomization procedures Study procedures Safety reporting Drug Access and Distribution Audit & Monitoring Pan Administrative contacts

29 Chaenges Timeine for activating internationa sites (approximatey 6-8 months) Navigating oca and internationa reguations NCI Guidance for Internationa Coaborations-2007 revised NCI guidance to be reeased Non North American reguations QA/QC and equivaency of quaity between countries Funding (drug shipment, correatives) Lapse in NCI Registration Investigator Site Staff (with new RCR) Each protoco is unique with varying requirements

30 Aiance Internationa Team Trini Ajazi, Chief Administrative Officer Michae Key, Director Protoco Operations Morgen Aexander-Young, Associate Director Protoco Operations Yujia Wen, Director Transationa Research Marcia Key Administrative/Membership Manager Stacy Reeves, Sr. Project Manager

31 Questions