1 / 19

HIV Vaccine Research: Ethical and Regulatory Issues NIH (DAIDS) Experience

HIV Vaccine Research: Ethical and Regulatory Issues NIH (DAIDS) Experience. Alan Fix, MD, MS Chief, Vaccine Clinical Research Branch (VCRB) Vaccine Research Program (VRP) Division of AIDS (DAIDS) National Institute of Allergy & Infectious Diseases (NIAID)

tanith
Download Presentation

HIV Vaccine Research: Ethical and Regulatory Issues NIH (DAIDS) Experience

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript


  1. HIV Vaccine Research: Ethical and Regulatory Issues NIH (DAIDS) Experience Alan Fix, MD, MS Chief, Vaccine Clinical Research Branch (VCRB) Vaccine Research Program (VRP) Division of AIDS (DAIDS) National Institute of Allergy & Infectious Diseases (NIAID) US National Institutes of Health (NIH)

  2. Division of AIDS (DAIDS) Mission To help end the HIV/AIDS epidemic by: • increasing basic knowledge of the pathogenesis and transmission of HIV, • the development of therapies for HIV infection and its complications, and • the development of vaccines and other prevention strategies.

  3. NIAID Supported HIV Vaccine Trials • >24,000 volunteers • 14 countries • 17 international trials • 97 preventive HIV vaccine trials • 83 phase I • 12 phase II • 1 phase IIB • 1 phase III • 36 products, 14 adjuvants • 10 different routes/methods of administration • Excellent safety experience

  4. Vaccine Safety • Safety data published for Phase I/II trials (1988 – 2001)* • 3,189 volunteers followed for 12,340 person years: • 2,458 in 49 phase I trials • 731 in 2 phase II trials • Similar safety patterns in over 2,000 additional volunteers enrolled in the last 5 years • No increased incidence in grade 3 or 4 adverse events between vaccine and placebo for any local or systemic toxicity except for one study using IFA • No evidence of autoimmunity, cancer, vaccine allergy, death or disability *Gilbert, et al. (2003). Vaccine 21: 2933-47.

  5. DAIDS Global HIV Vaccine Trial Activity Americas • Caribbean • Dominican Republic, Haiti, Jamaica, Puerto Rico • North America • United States (continental) • South America • Brazil, Peru • Africa • Southern Africa • Botswana, Malawi, South Africa • Eastern Africa • Kenya, Rwanda, Tanzania, Uganda • Asia • Thailand

  6. Trials Supported by DAIDS (2006/07)

  7. HVTN: A Global Network

  8. DAIDS Protocol Review(general steps) • DAIDS Prevention Sciences Review Committee (PSRC) • DAIDS regulatory review • FDA • Host country regulatory reviews • EC/IRBs • IBCs

  9. Regulatory ComplianceDAIDS’ Requirements • Compliance with host country regulations • Compliance with U.S. regulations • Approval by local IRB/EC & IBC • Approval by local required bodies (government, scientists, ethical) • Site initiation by DAIDS, Network • Rigorous adherence to protocol • Timely reporting of Adverse Events • Security of files, product • Availability for audits

  10. US Requirements • Regulation/Law • FDA - 1572 • OHRP (Office of Human Research Protections) – FWA & IRB registration • State • Required review per US regulation • FDA • Local IRB/EC • NIH requirements • OBA (Office of Biotechnology Activities) • “NIH Guidelines for Research Involving Recombinant DNA Molecules” • RAC (Recombinant DNA Advisory Committee) • Local IBC (Institutional Biosafety Committee) • Equivalence

  11. Non-US Host Country Requirements • National ethical and/or scientific review(s) • Pharmacy Boards (or equivalent) • Biosafety review • Local review

  12. Sources of Delay • Lack of understanding of requirements (including initial failure to identify all review requirements) • Incomplete submissions and responses to review • Infrequent/missed meetings of regulatory bodies • Reorganization of review bodies • Relatively new agencies

  13. Rochester, NY Baltimore, MD Boston, MA Providence, RI Nashville, TN Kampala, Uganda Birmingham, AL Nairobi, Kenya Kingston, Jamaica Port-au-Prince, Haiti Kericho, Kenya Kigali, Rwanda Sao Paulo, Brazil Mbeya, Tanzania Rio de Janeiro, Brazil Soweto, South Africa KOSH*, South Africa Capetown, South Africa * Klerksdorp, Orkney, Stiflontein, Hartbeesfontein Multi-Network Phase I/II Trials of VRC HIV Vaccine HIV Vaccine Trials Network (HVTN) US Military HIV Research Program (USMHRP) International AIDS Vaccine Initiative (IAVI)

  14. Partnership for AIDS Vaccine Evaluation(PAVE) • A voluntary consortium of USG agencies and key USG-funded organizations involved in the conduct of HIV vaccine clinical trials • NIH/NIAID, including • DAIDS • Dale and Betty Bumpers Vaccine Research Center (VRC) • HIV Vaccine Trials Network (HVTN) • AIDS Vaccine Research Working Group (AVRWG) • Centers for Disease Control and Prevention (CDC) • U.S. Military Program for HIV Research Program (USMHRP) • U.S. Agency for International Development (USAID) • International AIDS Vaccine Initiative (IAVI) • Initiated January 2003

  15. PAVE 100 • DAIDS-sponsored, multi-network Phase IIB trial of VRC DNA/rAd5 (if supported by results of current Phase II Triad) • CDC • HVTN • IAVI • USMHRP • Three regions • Americas – HVTN • East Africa – CDC, IAVI, & USMHRP • South Africa – HVTN, IAVI

  16. Global HIV/AIDS Vaccine Enterprise • Meeting in Airlie, Virginia – August 19, 2003 • “The Airlie group agreed that the Global HIV/AIDS Vaccine Enterprise should be developed as an alliance of independent organizations committed to: • accelerating the development of a preventive vaccine for HIV/AIDS through implementation of a shared scientific strategic plan, • mobilization of additional resources, and • greater collaboration among HIV vaccine researchers worldwide.” The Global HIV/AIDS Vaccine Enterprise: Scientic strategic plan. 2005. PLoS Med 2(2): e25.

  17. A Global Vaccine EnterprisePotential Benefits • Accelerated rate of vaccine candidate development • Expanded clinical trials capacity • Assured availability of manufacturing capacity • Harmonized regulatory approaches • Provision of a forum and mechanisms for multiple stakeholders to collaborate more closely

  18. Enterprise Regulatory Action Priorities • Harmonize and exchange information needed by regulatory bodies within the differing legal frameworks of different countries • Facilitate regulatory decision making, possibly using regional approaches for reviews & recommendations • Build regulatory capacity • Perform risk/benefit evaluations in the context of differing epidemic dynamics and country needs and resources • Identify and remove potential scientific impediments to rapid regulatory decision making • Address ethical issues that interface with regulatory decision making The Global HIV/AIDS Vaccine Enterprise: Scientic strategic plan. 2005. PLoS Med 2(2): e25.

  19. Challenges • Multiple EC/IRB & national agency review and potential for multiple directives for modification • Communication among agencies • Insurance and other mechanisms to cover expense of care of study related injury • Maturing agencies (fledgling) – “learning curve” • Mutual understanding of regulations, requirements, and areas of harmony, e.g., • Recommended vs. required • Terminology: e.g., Compensation, Indemnification

More Related