The Big Picture

1

• The Big Picture
• Overview and Structure of the
• International Maternal Pediatric
• Adolescent AIDS Clinical Trials Group (IMPAACT)

2
Terms to be familiar with

• ACTG- AIDS Clinical Trials Group (formerly Adult
  AIDS Clinical Trials Group - AACTG)
• CCG- Community Constituency Group
• CCWG- Cross-CAB Working Group
• CP- Community Partners
• CRS- Clinical Research Site
• CTU- Clinical Trials Unit
• DAIDS- Division of AIDS
• DMC- Data Management Center (Frontier Science)
• HPTN- HIV Prevention Trials Network

3
Terms to be familiar with

• ICAB- IMPAACT Community Advisory Board
• IMPAACT- International Maternal Pediatric
  Adolescent AIDS Clinical Trials Group
• NCAB- Network Community Advisory Board
• NIAID- National Institute of Allergies and
  Infectious Diseases
• NICHD- National Institute of Child Health and
  Human Development
• OPs- Operations Center ( Social Scientific
  Systems)
• PACTG-Pediatric AIDS Clinical Trials Group
• PCCG- PACTG Community Constituency Group
• SDAC- Statistical and Data Analysis Center
  (Harvard School of Public Health)

4
Follow the Money
President / Congress
NIH
DHHS
AIDS
NIAID
OAR
DAIDS
IMPAACT
Operations Center
SDAC DMC
CTUs/CRSs
Site CABs
5
Department of Health and Human Services (DHHS)

• 1st Stop in a long line.
• Key departments for the IMPAACT
• Centers for Disease Control (CDC)
• Food and Drug Administration (FDA)
• Health Resources and Services Administration
  (HRSA)
• National Institutes of Health (NIH)

6
National Institutes of Health (NIH)

• Key Office within NIH for the IMPAACT
• Office of AIDS Research (OAR)
• Key Institutes with NIH for the IMPAACT
• National Institute of Allergy and Infectious
  Diseases (NIAID)
• National Institute of Child Health and Human
  Development (NICHD)
• Each institute receives funding contracts to
  operate within the IMPAACT.

7
Office of AIDS Research (OAR)

• Located within the Office of the Director of NIH
• Responsible for the scientific, budgetary,
  legislative, and policy elements of the NIH AIDS
  research program.
• Authority to plan, coordinate, evaluate and fund
  all NIH AIDS research.
• Responsible for developing annually, a
  comprehensive plan and budget for all NIH AIDS
  research.

8
National Institute of Allergies and Infectious
Diseases (NIAID)

• Many offices within the NIAID including
• AIDS Clinical Trials Group (ACTG)
• International Maternal Pediatric Adolescent AIDS
  Clinical Trials (IMPAACT)
• HIV Prevention Trials Network (HPTN)
• HIV Vaccine Trials Network (HVTN)
• are funded through the Division of AIDS (DAIDS).

9
Division of AIDS (DAIDS)

• DAIDS provides oversight and management of
• IMPAACT and other offices
• Operations Centers
• Statistical/Data Centers
• Clinical Trials Units/Clinical Research Sites

10
Where have we been?

• A Timeline......

11
1985-1986

• 1985 NIAID issued a Request for Proposals (RPF)
  to establish AIDS Treatment Evaluation Units
  (ATEU)
• 1986 14 institutions funded as ATEUs to do Phase
  I and Phase II clinical trials

12
1986

• AZT is shown to be effective, resulting in
  changes in research direction and a Congressional
  budget amendment to increase funding
• 5 additional ATEUs funded
• focused on pediatric and hemophilic populations
• established a Clinical Trials Coordinating Center

13
1987

• ACTG formed from ATEUs
• Statistical Center and Operations Office
  established
• RTI (data center) contracted with Harvard
• SSS (operations center)
• NIAID held first ACTG group meeting in Washington
  December 1987

14
1989

• ACT-UP New York attends an ACTG meeting uninvited
• 15 Pediatric ACTUs funded to join existing group
• SDAC became Statistical Data Center
• HSPH Statistical Office
• Frontier Science- Data Management Center (DMC)

15
1990

• Community representatives invited to 8th ACTG
  meeting
• Community Constituency Group (CCG) formed with 22
  members
• CCG members attend Executive Committee and
  Scientific Cores sessions at the 9th ACTG meeting
  as observers
• CCG members attend the 10th ACTG meeting as a
  formal part of the ACTG

16
19901991

• 1990 Westat sites (NICHD) participate in all
  pediatric studies
• 1991 9 additional Pediatric ACTUs funded in
  response to Congressional mandate
• recompetition of Adult ACTUs
• 35 sites funded

17
1993-1994

• NHF funded to enroll persons with hemophilia in
  ACTG
• separation of Adult (AACTG) and Pediatric (PACTG)
  research efforts
• competitive renewal of the original 15 Pediatric
  ACTUs
• Co-Chairs of the National Community Advisory
  Boards (NCABs) and Community Constituency Groups
  (CCGs) begin to meet annually

18
1995

• ACTG restructured and created true
• self-government with
• self-evaluation of sites
• priority setting scientific research
• discretionary spending

19
1996

• Recompetition and restructuring of the Adult ACTG
  (then called the AACTG)
• 30 sites funded
• DAIDS convenes an external review panel to
  identify the factors organizational,
  preocedural or other that could enhance the
  effectiveness of the NCABs/CCGs

20
1997

• 1997 recompetition and restructuring of the
  Pediatric ACTG (PACTG)
• 21 ACTUs funded (NIAID)
• 9 Westat sites (NICHD)
• 1997-2002 Trainings on topics such as Ethics in
  Research are collaboratively developed and
  provided at conferences and meetings

21
1998

• AACTG includes criteria for Community Advisory
  Boards (CAB) as part of site evaluation
• the Pediatric CCG (PCCG) ceased being a
  subcommittee of the Adult CCG (CCG) and became
  its own committee within the PACTG structure

22
1999-2005 Network Restructuring

• AACTG 19992004
• competitive renewal
• international initiative
• PACTG 20012005
• adolescent initiative
• international initiative
• AIDS epidemic becomes part of the Mission
  Statement of the ACTG and PACTG.

23
2002

• March PCCG Membership Expanded to include
  Adolescent Members
• May PCCG Presents Community Scientific Research
  Agenda Priorities to PACTG Leadership
• P1055 Direct Result of Priorities
• May PACTG Site Evaluation Subcommittee approves
  PCCG proposal giving sites scientific
  contribution points for community participation
• July PCCG joins discussions regarding forming a
  DAIDS cross-network community group

24
2002-2003

• January 2003 PCCG Members Join International
  Site Visit Teams
• 2003 First joint AACTG and PACTG regional
  training of site personnel.
• January 2003 First International PACTG CABs
• Feb. 2003 First cross-CAB group call is held.
  Results in formation of the Cross-CAB Working
  Group (CCWG)

25
2003-2004

• December 2003 First Organized CAB Retreat
  Sessions Developed by PCCG at PACTG Meetings
• August 2004 Adolescent CAB Members Attend PCCG
  CAB Retreat Sessions at PACTG Meetings
• Adolescent Specific Sessions Interactive Sessions
  with Investigators.
• December2004 First International PCCG Member

26
2004-2005

• December 2004 First International PCCG Member
  joins PCCG
• February 2005 PCCG Adolescent Initiated
  Web-Site Launched POSITIVE LIFE
  http//www.positivelife.net
• March 2005 PACTG Leadership Approves Funding at
  Operations Center for NIAID CAB Travel to PACTG
  Meetings

27
2005

• March Community Consultant Funded to Assist PCCG
  with Expanded PCCG, CAB and Adolescent
  Initiatives
• May PCCG Hosts Monthly Adolescent Calls
• May Members of the CCWG and DAIDS meet to
  discuss the role of the community in HIV/AIDS
  Research, resulting in Defining Best Practices
  for Community Representative Involvement in HIV
  Clinical Research Networks report.

28
2005

• April PCCG Develops Annual Work Plans
• April PCCG and CCG hold joint sessions at
  PACTG/AACTG meetings
• June/July International CAB members on FXB/PACTG
  Site Training Team
• July PCCG hosts stand-alone CAB retreat
• September PCCG Membership Self-Assessment

29
2005

• September First Publication of PCCG CAB
  Newsletter CAB-Share the Ride
• October PCCG presents interactive session at
  Fall PACTG Meetings
• December PACTG requires protocol teams to submit
  lay summaries with all PACTG-related manuscripts
• December PCCG Hosts Additional Adolescent Calls
  to Accommodate International Youth

30
2005 Network Restructuring

• May 2004 PCCG Provides Written Statement to
  DAIDS Regarding Network Restructuring
• August 2004 PCCG Dialogue with DAIDS Regarding
  Network Restructuring
• 2004 competitive renewal of AACTG, PACTG, and
  other DAIDS networks
• RFA to be issued Fall 2004
• 2005 application submitted in response to RFA
  for Network and sites
• Transition Planning in process
• PCCG leadership begin communications with HPTN
  community leaders

31
2005 Network Restructuring

• AACTG/PACTG restructuring and re-competition
• PACTG Responded to Request For Application (RFA)
  as IMPAACT Network
• International Maternal Pediatric Adolescent AIDS
  Clinical Trials Group
• Combination of PACTG and Perinatal Working Group
  of HPTN

32
2006

• February Full-time Operations Center Community
  Coordinator
• February Follow up meeting to develop specific
  guidelines on community involvement in HIV
  clinical trials. CCWG forms a working group to
  develop guidelines, now called the Community
  Recommendations Working Group.
• DAIDS/NIAID requires CAB/community evaluation as
  part of site and network/core evaluation as of
  2006
• September ICAB Leadership develops Roles
  Responsibilities of ICAB, RCAB and Site CABs
• October Meeting of CCWG and other Cross-Network
  Community working groups begin developing
  administrative and organizational guidelines for
  Community Partners (CP).

33
2006-2007

• 2006-2007 ICAB members on Francois-Xaiver
  Bagnoud Center (FXB) CAB Curriculum Advisory Team
• March 2007 FXB and ICAB Pilots CAB Curriculum at
  March IMPAACT Meetings
• April Full-time Operations Center Regional
  Community Coordinator
• May 2007 Africa RCAB Training in Kampala, Uganda

34
2007

• May Community Partners representative selections
  by each of the DAIDS-funded HIV Clinical Trials
  Networks are complete.
• June Community Partners convenes its first call.
  Interim CP representatives provide an
  introductory presentation at the HIV/AIDS Network
  Leadership Strategic Working Group meeting.
• July IMPAACT site CABs identify RCAB
  representatives and liaisons.

35
2007

• August IMPAACT RCABs elect officers
• August IMPAACT RCABs select ICAB members
• August Networks select CP Executive Committee
  Members
• September CP Executive Committee convenes its
  first call
• October New ICAB members meet for first time at
  IMPAACT Leadership Retreat

36
IMPAACT/PACTG

• Major scientific accomplishments

37
Accomplishments of the PACTG/IMPAACT

• IMPAACT P076
• Landmark trial, reducing mother to child
  transmission
• IMPAACT P152 / 300
• Definitive studies of pediatric regimens limited
  to NRTIs
• IMPAACT P331
• Established AZT dosing for pre-term babies
• IMPAACT P338 / 377
• efficacy of PIs in children
• IMPAACT P367
• Mother/Infant Chart chart study following
  pregnancy and outcomes of HIV moms
• Numerous scientific contributions defining
  pregnancy details outcomes of HIV women in the
  USA
• Final analysis underway
• Enrollment 4,761 Mother/infant pairs

38
Accomplishments of the PACTG/IMPAACT

• IMPAACT P382
• Provided data for FDA pediatric label of EFV
• IMPAACT P219/219C
• Twelve yrs into pediatric long term outcomes
  study
• Numerous publications providing data on
• Defining current antiretroviral treatment of
  children in the USA
• Severity of illness in HIV children in the USA
• Quality of Life in HIV children in the USA
• Enrollment 4689 children/adolescents

39
Accomplishments of the PACTG/IMPAACT

• IMPAACT P1005
• Established pediatric dosing for T-20
• IMPAACT P1025
• Established long term follow-up study on HIV
  positive mothers and their infants
• IMPAACT P1031A
• Acceptability of voluntary HIV counseling and
  rapid HIV testing in pregnant women who present
  in labor with undocumented HIV status
• Acceptability of administration of antiretroviral
  medication prior to delivery in women identified
  as HIV
• Enrollment 343 women/46 infants

40
Accomplishments of the PACTG/IMPAACT

• IMPAACT P1047
• Safety and tolerability of HPV vaccine in
  HIV-infected children
• Enrollment 130 children
• IMPAACT P1051
• Determine safety and tolerability of tipranavir
  formulations
• Enrollment 115 children (29 from PACTG sites)
• IMPAACT P1055
• Provided data on psychiatric issues in
  perinatally HIV-infected children and adolescents
• Enrollment 582 children/adolescents

41
Accomplishments of the PACTG/IMPAACT

• IMPAACT P1059
• Safety and tolerability of therapeutic HIV
  vaccines in HIV-1-infected young adults.
• Enrollment 20 young adults
• IMPAACT HPTN 027
• A Phase I Study to Evaluate the Safety and
  Immunogenicity of ALVAC-HIV vCP1521 in Infants
  Born to HIV-1 Infected Women in Uganda

42
IMPAACT

• Structure Organization

43
IMPAACT Network Mission

• To prevent and treat HIV in infants, children,
  adolescents and pregnant women domestically and
  internationally.

44
Operations Center Social Scientific Systems
(SSS) Network Community Coordinator
Network Executive Committee Group Chair Group
Vice Chairs S DMC PI Lab PI Ops Center
Director At-large members NIH Officers ICAB Reps

Statistical and Data Analysis Center (SDAC)
IMPAACT Community Advisory Board (ICAB)
Resource Committees
Scientific Oversight Committee Group Chair Group
Vice Chairs () SDMC PI Lab PI Scientific
Committee Chairs At-large members NIH
Officers ICAB Rep
Westat Coordinating Center for NICHD Clinical
Sites
Scientific Committees
Central Lab Steering Committee
Primary Therapy
Perinatal/Maternal
Laboratory Committee Virology Pharmacology Immunol
ogy Host Genetics Microbiology
Complications
Vaccine / IBT
ICAB Liaisons
Source François-Xavier Bagnoud Center at the
University of Medicine and Dentistry of New
Jersey (UMDNJ)
45
IMPAACT Leadership Committees

• Network Executive Committee (NEC)
• Responsible for the overall conduct of the
  IMPAACT
• And its eight Resource Committees
• Performance Evaluation
• Site Management/Clinical Care
• QA/QC
• Data Management
• Pharmacy
• Training/Education
• Policies and Procedures
• The IMPAACT Community Advisory Board (ICAB)

46
IMPAACT Community Participation
Other HIV Research Network CABs
Source François-Xavier Bagnoud Center at the
University of Medicine and Dentistry of New
Jersey (UMDNJ)
47
IMPAACT Leadership Committees

• Science Oversight Committee (SOC)
• Determines the scientific agenda and scientific
  priorities of the network, reviews and approves
  proposals for protocol development, and provides
  final scientific approval of studies. 
• The SOC has nine subcommittees
• Primary Therapy Scientific Committee
• Prevention of Mother to Child Transmission
  Scientific Committee
• Complications of HIV Scientific Committee
• Vaccine/Immune-Based Therapy Scientific Committee
  
• Laboratory Steering Committee
• Laboratory Committee
• Protocol Evaluation Committee
• Publications Committee
• Protocol Development and Study Monitoring
  Committee

48
IMPAACT Operations Center
Office of the Director Risë Phillips Director We
nde Levy Deputy Director
PERC, QA, Financial Disclosure Deline
Glover Executive Committees Coordinator. Erica
Eaton
Executive Group David Hughes Manager
Finance and Budget Group Brandy Price Manager
Clinical Group Elizabeth Hawkins Manager
Site Development Management Group Louis
Grue Manager
Laboratory Group Sue Sepelak Manager
MIS, Pubs, WEB Nathan Tryon Administrative
.Specialist LaShawn Campbell Meetings/Community
Stacey Holder-Clement
Clinical Project Specialist Jennifer Gardella
Clinical Trial Specialists Kimberly
Hudgens Joyce Kraimer Beth Sheeran Emily
Demske Quianna Douglas
Lab. Specialist Céline Husbands International
Lab Specialist Kim Banks
Budget Analyst Rafael Magana Janice Brown
Site Operations Research Analysts Joanne
Espanol Muthoni Njage Site Operations
Coordinators Olga Zografos
Network Community Coordinator Claire
Schuster Regional Community Coordinator Angela
Macharia
49
Operations CenterSocial Scientific Systems,
Inc. (SSS)

• Administers central grant
• Provides financial management
• Supports development and review of all IMPAACT
  protocols
• Provides coordination to all committees and sites
• Organizes and coordinates IMPAACT group meetings
  and leadership retreats
• Provides laboratory support in collaboration with
  IMPAACT Central Laboratory

50
Operations Center Contact

• http//impaact.s-3.com
• User Name impaact
• Password cure
• Find anyone in IMPAACT using Search Member
  Directory

51
Westat NICHD Coordinating Center

• Sub-contracts with NICHD clinical sites to
  conduct IMPAACT protocols
• Provides site monitoring, data management, and
  operational support for NICHD sites
• Performs site performance evaluations
• Conducts training sessions for NICHD IMPAACT Site
  staff

52
IMPAACT Where are we now?

• Some statistics

53
Currently in IMPAACT

• 39 NIAID Sites
• 13 Domestic Sites
• 26 International Sites
• NICHD Westat Sites to be announced, Fall 2007

54
IMPAACT Sites
Source François-Xavier Bagnoud Center at the
University of Medicine and Dentistry of New
Jersey (UMDNJ)
55
Domestic Clinical Trials Units - NIAID

• Baylor College of Medicine (Houston, TX)
• Bronx-Lebanon Hospital Center (New York, NY)
• Childrens Memorial Hospital (Chicago, IL)
• CHOP (Philadelphia, PA)
• Columbia University (New York, NY)
• Duke University MC (Durham, NC)
• University of Miami (Miami, FL)

56
Domestic Clinical Trials Units - NIAID

• St Jude Childrens Research Hospital (Memphis,
  TN)
• UCSD (San Diego, CA)
• UCLA (Los Angeles, CA)
• UMASS (Worcester, MA)
• UMDNJ (Newark, NJ)
• University of Puerto Rico (San Juan, PR)

57
International Sites - NIAID

• Brazil
• Porto Alegre
• Botswana
• Molepolole
• Gaborone
• India
• Pune
• Malawi
• Blantrye
• Lilongwe

58
International Sites - NIAID

• South Africa
• Johannesburg
• Durban
• Cape Town
• Tanzania
• Moshi
• Dar es Salaam

59
International Sites - NIAID

• Thailand
• Bangkok
• Chonburi
• Phayao
• Chiangrai
• Chantaburi
• Chang Mai
• Uganda
• Kampala

60
International Sites - NIAID

• Zambia
• Lusaka
• Zimbabwe
• Harare

61
IMPAACT Studies 2006 - 2008

• Year 1 June 2006 May 2007
• 7 new protocols opened (6 international and 1
  U.S.)
• Year 2 June 2007 May 2008
• 2 new protocols in U.S. (as of 9/2007)

62
Domestic protocols currently enrolling

• IMPAACT P394
• Evaluate single dose tenofovir DF alone or in
  combination with single dose emtricitabine in
  HIV-infected pregnant women and their infants
• IMPAACT P1025
• Long term follow-up study on HIV positive mothers
  and their infants
• IMPAACT P1026s
• Describe the pharmacokinetics (PK) during
  pregnancy of selected antiretroviral (ARV) drugs

63
Domestic protocols currently enrolling

• IMPAACT P1065
• Safety and immunogenicity of meningococcal
  vaccine in HIV-infected youth
• IMPAACT P1066
• First study to examine MK-0518 (a novel integrase
  inhibitor) in pediatric patients

64
International protocols currently enrolling

• IMPAACT P1032
• Address the problem of acquisition of NVP
  resistance mutations in the context of PMTCT
• IMPAACT P1041
• Determine the efficacy of INH to decrease TB
  disease in HIV-infected children and to decrease
  TB infection in HIV-exposed, uninfected children
• IMPAACT P1043/HPTN 040
• ARV regimens in newborns

65
International protocols currently enrolling

• IMPAACT P1054
• Babies born to infected women in P1060
• IMPAACT P1056
• Study a new generic FDC tablet (GPO-VIR S7) in
  Thailand
• IMPAACT P1060
• Compare treatment failure rates in NVP-exposed
  versus unexposed children on NVP-based versus
  LPV/r based treatment

66
International protocols currently enrolling

• IMPAACT HPTN 046
• Phase III Trial to Determine the Efficacy and
  Safety of an Extended Regimen of Nevirapine in
  Infants Born to HIV Infected Women to Prevent
  Vertical HIV Transmission During Breastfeeding
• Open to Accrual
• IMPAACT HPTN 057
• A Phase I Open Label Trial of the Safety and
  Pharmacokinetics of Tenofovir Disoproxil Fumarate
  in HIV-1 Infected Pregnant Women and their
  Infants

67
IMPAACT Community Structure and Input ICAB,
RCABs Site CABs
68
IMPAACT Community Participation
Other HIV Research Network CABs
Source François-Xavier Bagnoud Center at the
University of Medicine and Dentistry of New
Jersey (UMDNJ)
69
IMPAACT CAB

• The role of the IMPAACT Community Advisory Board
  Resource Committee (ICAB) is to
• Provide HIV/AIDS life-experience and expertise to
  positively impact the formulation and
  implementation of research by community
  representation on the IMPAACT Leadership
  Committee, Scientific Committees, Resource
  Committees and Protocol Teams.
• Provide guidelines for Regional and Site CABs.
• Evaluate value and effectiveness of community at
  network, regional and site levels.
• Network across the DAIDS research networks
  representation on the DAIDS Community Partners
  and collaborate with other community groups from
  NIH institutes and NGOs.
• Identify HIV/AIDS research needs and issues
  across networks and institutes and work toward
  effective resolution of these needs and issues.

70
ICAB Working Groups

• ICAB members serve on at least one working group
• Community Education Working Group
• Orientation and on-going education of ICAB
  members
• Global Adolescent Working Group
• Outreach to adolescents at sites conducting
  adolescent research
• Evaluation Working Group
• Assess the impact of community involvement in
  research within IMPAACT at the site, regional and
  network levels
• Scientific In-put Working Group
• Review capsules, concept sheets and protocols and
  provide feedback to researchers

71
Regional CABs

• Three Regions
• Africa
• Americas
• Asia
• The role of the Regional CABs are to
• Bring Site CAB members together within the
  regions for networking, training assessment and
  capacity building
• Assist as the conduit of information flow between
  voices of community at the sites and IMPAACT

72
Site CABs

• Purpose is community input into the sites
  research agenda and activities
• Each site shall have representative membership in
  a Regional Community Advisory Board (RCAB)
• Site CAB membership should reflect the diverse
  local community
• Direct and Indirect Stakeholders

73
Cross-Network Community

• To identify HIV/AIDS research needs and issues
  across networks and institutes and work toward
  effective resolution of these needs and issues
  the ICAB will
• Have representation on the DAIDS Community
  Partners group
• Collaborate with other community groups from NIH
  institutes and Non Governmental Organizations
  (NGOs)

74
Role of Community

• Communicate and share information as liaisons
  between
• Other ICAB members about scientific/resource
  committee and protocol team activities
• RCAB about ICAB and Network activities
• ICAB about RCAB, site CAB, and broader community
  activities and needs
• Researchers on the scientific/resource committees
  and protocol teams about community identified
  research needs and making research assessible to
  a diverse community
• Cross-network
• Read as much as you can to prepare yourself for
  conference calls, scientific committee and
  protocol team participation
• Ask questions if you do not understand
• Be willing to work as a volunteer along side
  other volunteers and professionals
• Respect confidentiality

75
Where do we go from here?

• More work, fewer dollars, work smarter
• Keep defining mission
• Shared resources
• Joint studies/Collaborations
• Perinatal longitudinal follow-up
• Adolescent/adult
• Mental health
• Adolescents
• International research

76
Getting Involved Why?

• New challenges and job satisfaction
• Global peer group
• Contribute to the larger group
• Personal fulfillment
• Your voice heard!

77
Getting Involved How?

• Attend open sessions at large group meetings
• Get to know Investigators
• Attend IMPAACT science and resource committees
  meetings
• Attend ICAB and ICAB working group meetings
• Attend RCAB meetings
• Recruit new members

78
And remember.....

• Knowledge IS
• power!

79
Acknowledgements

• Our sincere appreciation to
• Greg Ciupak
• Eva Janzen Powell
• Wende Levy, IMPAACT Operations Center
• François-Xavier Bagnoud Center at the University
  of Medicine and Dentistry of New Jersey (UMDNJ)
• For their help developing this presentation.