The Importance of the Public Health Approach in Development of Standard Treatment Guidelines and Pro

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The Importance of the Public Health Approach in
Development of Standard Treatment
Guidelines and Product Selection Peter Graaff,
Technical Officer WHO, AIDS Medicines and
Diagnostics Service
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Outline of Presentation

• The public health approach, what and why
• Simplification and standardization of therapy
  through standard treatment guidelines
• Ensuring access to quality products through
  prequalification

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The Public Health Approach

• What and Why?

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What is a Public Health Approach?

• A population-based approach, which seeks the
  greatest public health impact given the resources
• The approach for scaling up access to
  antiretroviral therapy (ART) emphasizes
• Simplification and standardization of therapy
• Decentralization and integration of service
  delivery

Goal in the case of antiretroviral therapy (ART)
maximizing survival at the population level
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Why the Public Health Approach?

• Specialist physician management of individual
  patients, with sophisticated laboratory
  monitoring, cannot be scaled up to meet demands
  for treatment in resource-constrained settings
• Physicians are scarce (1 per 12,500 in Uganda)
• Laboratory infrastructure is inadequate (1
  microscope per 100,000 in central Malawi)
• Procurement and supply chain management is
  fragile (and quantities of commodities set to
  increase exponentially)

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Why the Public Health Approach? "The market in
2008 will be between 3 and 6 million clients"
Patients on ART (millions)
6.6
5.2
4.1
3.1
2.3
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The Public Health Approach building on earlier
experiences.
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The Public Health Approach

• Simplification and Standardization of Therapy
  through
• Standard Treatment Guidelines

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The Public Health Approach1st Line ARV Drugs in
Adults and Adolescents (proposed revised WHO
guidelines)
d4T or AZT
Triple NRTI alternative
EFV
3TC or FTC
NVP
ABC or TDF
Classical NRTI/NNRTI approach
Triple NRTI should be considered as a
simplification strategy for 1st line as suggested
above, mainly for situations where NNRTIs options
provide additional complications ( e.g.,
pregnancy, viral hepatitis co-infection, TB
confection, women who wish to fall pregnant or
who have CD4 gt 250 NVP or EFV grade 4 SAE HIV-2
or HIV-0 adolescents).
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NRTI Backbone in Resource Limited Settings
(criteria for selection)
Low Moderate (or ---) High
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The Public Health ApproachSimplification and
standardization of antiretroviral therapy..

• Simplifies clinical decision making (4S approach)
• Start
• Substitution (for toxicity)
• Switch (for failure)
• Stop (or Salvage)
• Reserves 2nd line treatment options with new
  classes of medicines
• Facilitates training (and task-shifting)
• Encourages production of suitable products and
  formulations
• 4 two drug FDCs, 4 three drug FDCs and 4
  co-packaged combinations available
• Drives down prices
• 37-53 between 2003 and 2005
• Limits the number of products moving through the
  supply chain

Clinical Staging Immunological (CD4) monitoring

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NRTI Backbone in Resource Limited Settings
(country adoption / adaptation)
Most countries that entered a programme of rapid
scale-up of ART followed / adapted WHO treatment
guidelines thereby reducing the number of
treatment combinations used

• Process can be improved by more systematically
• Considering the locally applicable criteria
• Cost and Availability
• Involving
• Non clinicians, e.g. procurement and supply
  management experts and health economists
• Key stakeholders such as PLWHAs, NGOs, private
  sector, donors, technical partners

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The Public Health Approach Basic laboratory
support requirements, more than testing for HIV
status.
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The Public Health Approach

• Ensuring access to quality products through
  prequalification

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Why prequalification is needed

• Problems
• Lack of experience in procurement of these new
  products
• Weak/absent QA systems of medicines supply chain
• Risks
• Procurement and supply of substandard and
  counterfeit products in different countries
• Treatment failure, resistance

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Prequalification results in

• List of products and manufacturers approved for
  UN procurement
• Meeting international norms and standards on
  quality, safety, and efficacy
• Better access to treatment
• Fair procurement mechanisms
• Harmonization
• DRAs, WHO treatment programs, NGOs, procurement
  organizations
• Capacity building
• DRA's life-time learning experience in
  assessment and inspection
• Manufacturers free feed-back on performance and
  advice how to improve
• Added benefits at country or programme level
• Simplified product source selection
• Better understanding of the importance of quality
  issues

gt100 HIV related medicines prequalified to date
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http//mednet3.who.int/prequal/
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Thank youe-mail graaffp_at_who.int
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Additional Slides(back-up for questions)
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Pediatric patients are expected to comprise 10
of total people on treatment by 2008
Number of patients (000s), select CHAI Consortium
Countries
Children
Adults
Includes Angola, Bahamas, Brazil, Cambodia,
China, DR, Ethiopia, Haiti, India, Jamaica,
Kenya, Lesotho, Mozambique, OECS, Rwanda,
Tanzania, Zambia
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1st Line ARV Drugs in Infants and Children
d4T or AZT
Triple NRTI alternative1
EFV2
3TC or FTC
NVP
ABC
Classical NRTI/NNRTI approach
(1) Triple NRTI should be considered as a
simplification strategy for 1st line as
suggested above, mainly for situations where
NNRTIs options provide additional complications
(e.g. TB confection, NVP or EFV grade 4 SAE
HIV-2 or HIV-0, children lt 3 years old who cannot
take NVP). (2) EFV is not currently recommended
for children lt 3 years-old or lt 10 kg. (3) TDF
is not currently recommended for children.
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2nd Line ARV Drugs in Adults and Adolescents
TDF or ddI
PI/r
EFV or NVP
NRTI sparing option if simplified triple NRTI
approach were used in 1st line
ABC or AZT 3TC
Standard 2nd line option if classical NRTI/NNRTI
approach were used in 1st line
Ritonavir boosted PIs are considered as the key
component in 2nd line regimens and its use should
be reserved for this situation. LPV/r has been
recommended as the preferred RTV-boosted PI as
it is available as a FDC and a new formulation
that doesn't need refrigeration was recently
launched, but other boosted PIs (ATV/r, SQV/r,
fosAPV/r and IDV/r) can be substituted based on
individual program priorities. In the absence of
a cold chain and where the new LPV/r formulation
is not available, unboosted ATV or NFV can be
employed as the PI component but it is considered
less potent than a RTV-boosted PI. ZDV 3TC
are listed here for strategic use as resistance
to both drugs is predicted to be present
following failure on the respective first-line
regimen listed. ZDV may prevent or delay the
emergence of the K65R mutation 3TC will maintain
the M184V mutation which may decrease viral
replicate capacity as well as induce some degree
of viral desensitization to ZDV. It must be
stressed that the clinical efficacy of this
strategy in this situation has not been proven.
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2nd Line ARV Drugs in Infants and Children
Standard 2nd line option if classical NRTI/NNRTI
approach were used in 1st line
2nd line option if simplified triple NRTI
approach were used in 1st line
ddI4
NVP or EFV2
PI/r1
ABC or AZT 3TC3
(1) Ritonavir boosted PIs are considered as the
key component in 2nd line regimens and its use
should be reserved for this situation. Currently
only LPV/r and SQV/r are available for children.
In the absence of a cold chain a NFV can be
employed as the PI component but it is considered
less potent than a RTV-boosted PI. (2) ZDV 3TC
are listed here for strategic use as resistance
to both drugs is predicted to be present
following failure on the respective first-line
regimen listed. ZDV may prevent or delay the
emergence of the K65R mutation 3TC will maintain
the M184V mutation which may decrease viral
replicate capacity as well as induce some degree
of viral desensitization to ZDV. It must be
stressed that the clinical efficacy of this
strategy in this situation has not been
proven. (3) EFV is not currently recommended for
children lt 3 years-old or lt 10 kg. (4) TDF is
not currently recommended in children.
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Status per September 2005

• Started with HIV/AIDS products in 2001 malaria
  and TB products later
• Prequalified products (Sept 2005) Dossiers
  arrived (July 2005)
• 98 HIV related medicines - 289 (Feb-05) 316 (Aug
  -05)
• 8 anti-tuberculosis medicines - 153 156
• 2 anti-malarial medicines - 46 48
• 108 488 520
• Ongoing assessments and follow-up
• Products
• Manufacturing sites
• CROs
• Drug quality control laboratories