forecasting global arv demand - who
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Forecasting global ARV demand
Clinton Foundation HIV/AIDS Initiative
16 June 2006
Global ARV demand 2
Methodology
- Patients on treatment
- Product demand
- Upstream demand
Results
- Patient on treatment
- Product demand
Agenda
Global ARV demand 3
Goal
To develop a methodology for forecasting global ARV demandthat is:
• Clear and transparent
• Iterative
• Easily updated
• Sensitive to heterogeneity of epidemiology, protocols, and history oftreatment among countries
• Reflects the application of ‘best practices’
• Realistic—delineate data for planning from data for advocacy
Global ARV demand 4
Overview of approach
Product demand by patient type
e.g. 12,000 patients will be on first-line RX at the start of 2007
Point of service product demand
e.g. 4.3 million tablets of NVP 200 mg needed at the start of 2007
Upstream product demand
e.g. 6.7 million tablets of NVP 200 mg will be ordered in late 2006
Global ARV demand 5
Scope of the forecast
Countries included
Argentina** Mozambique*
Botswana Namibia**
Brazil** Nigeria
Cameroon** Rwanda*
China* South Africa**
Cote d’Ivoire** Tanzania*
Ethiopia* Thailand
India* Uganda**
Kenya* Zambia**
Malawi* Zimbabwe**
Mexico
• These 21 countries represent83% of global volume
• 8 of these countries (19% ofglobal volume) are countries inwhich CHAI has an office
• An additional 9 (48% of globalvolume) are members ofCHAI’s procurementconsortium
* CHAI partner countries **CHAI consortium countries
Global ARV demand 6
Scaling Up
There are several potential approaches to modeling howtreatment programs will grow:
• Increased growth towards higher coverage
• Growth to reach publicly stated country targets
• Continued growth at the same rate observed in the recent past
(WHO Data- Dec 04, June 05, Dec 05)
Will model growth to reach to reach targets that consider
resourcing and capacity
Global ARV demand 7
Demand by patient type
Patient Population
EPI Data
Enrollment Data
(scale-up curve)
Protocols
(past, current
and draft)
Patient
Demand
Global ARV demand 8
D4T/3TC/NVP(standard 1st line)
Peripheral neuropathy:start with AZT/3TC/NVP
TB: start withD4T/3TC/EFV
Children: startwith
AZT/3TC/NVP
Pretreated:start with
DDI/ABC/LPV/r
Example: Determining ARV needs
Global ARV demand 9
TIME
New patientenrollment
Treatment failure
Toxicity-relateddrug switch New pregnancy
Patient death
New casesof TB
Loss tofollow-up
Weightchange or
growthChange in
enrollment rate
Protocol change
Drug regimens over
timeDrug regimens over time
Global ARV demand 10
Recommended regimens are applied topatients as they progress on treatment
Global ARV demand 11
Regimen progression
Global ARV demand 12
Regimen progression
Global ARV demand 13
Regimen progression
Global ARV demand 14
Key Questions
Patient Population
EPI Data
Enrollment (?)
Protocols
Patient
Demand
Updated information needed overtime• New enrollment trends• New information on countrycapacity/ resources
• Few protocols have been updated to reflectpending revision of WHO guidelines
• Several patient profiles are not covered bycurrent protocols; for upwards of 10% ofpopulation there is at least one questionabout how patient demand converts toproduct
Global ARV demand 15
Moving upstream
Several questions have to be considered when estimatingupstream demand:
• How frequently do countries place orders, and how manydeliveries do they request?
• How much buffer stock do countries include in their orders?
• When do ARV manufacturers order the required API?
• How much API is ordered : is a buffer stock included in the order?is excess ordered to compensate for loss in production?
Global ARV demand 16
Assumptions impact quantity and productiontimeline for ARV & API manufacturers
- % buffer stock : 0%
- % lost in production :5%
- # deliveries requested:2 – 3
API is ordered justbefore ARVs are tobe produced,based onrequested deliveryschedule
Amount requiredto cover ARVorder + % bufferstock + % to coverloss in production
ARV
manufacturer
places order
with API
manufacturer
- Lead time: 2 – 15 mos
- buffer stock: 1 – 6 mos
- # months covered bytender: 1 – 4
Order is placedbased on country-specific lead time
Pills required fornumber of monthscovered by tender+ buffer stock
Country places
order with ARV
manufacturer
CHAI AssumptionsTimelineQuantityAction
Global ARV demand 17
Methodology
- Background
- Patients on treatment
- Product demand
- Upstream demand
Results
- Patients on treatment
- Product demand
Agenda
Global ARV demand 18
Scale up
4.5MM
1.3MM
Global ARV demand 19
Projected numbers of patients ontreatment at year-end
Region 2005 2006 2007 2008 2009 2010
Africa 814,000 1,296,000 1,795,000 2,295,000 2,791,000 3,279,000
Americas 318,000 344,000 377,000 409,000 440,000 472,000
Southeast Asia 141,000 206,000 263,000 320,000 376,000 432,000
Western Pacific 38,000 57,000 78,000 99,000 118,000 138,000
Global * 1,341,000 1,956,000 2,594,000 3,231,000 3,864,000 4,487,000
*EMRO and EURO regions account for 3% of global total and are not yet incl uded in forecast
Global ARV demand 20
Global ARV demand 21
2006 2007 2008 2009 2010
Adult
1st line 1,765,000 2,314,000 2,842,000 3,356,000 3,846,000
2nd line 105,000 166,000 245,000 337,000 442,000
Pediatric
1st line 81,000 107,000 133,000 156,000 180,000
2nd 4,000 7,000 11,000 15,000 19,000
Global 1,956,000 2,594,000 3,231,000 3,864,000 4,487,000
Global ARV demand 22
Cuts at Data
• AZT
• D4T
• 3TC
• FTC
• NVP
• EFV
• ABC
• TDF
• DDI
• LPV
• NFV
• IND
• SQV
• ATZ
Drug Market
•Region•Country•Generic Accessiblevs. Branded Only
Product Type
•API•Formulation•FDCs•Syrups•Tabs vs. Caps
Patient Groups
•1st Line Adult•2nd Line Adult•Pediatrics
Forecast Period
• Annually
• Quarterly
• Monthly
• Weekly (relevant
for clinical
planning)
Global ARV demand 23
Num
ber
of patients
on tre
atm
ent, e
nd y
ear
Number of patients on 1st line treatment
Global ARV demand 24
Number of patients on 1st line treatment
3TC
AZT
D4T
EFV
NVP
3TC
AZT
D4T
EFV
NVP
FTC
TDF
TDF
Global ARV demand 25
Key 1st Line Take Aways
• Overall ARV market growingat fast pace (4MM people on1st line treatment by 2010)
• High market potential for EFVvs. NVP relative to currentdemand
• AZT use is higher thanexpected because of use in1st line protocols in highvolume countries; potentialfor growth
Key Take Lessons Learned on
1st Line
• What will d4t market look likeover the next five years? Willcontinue to grow at paceanticipated?
• How will TDF be factored into1st line protocols?
• Given volume increases isthere adequate API capacity?
Key Questions
Global ARV demand 26
Num
ber
of patients
on tre
atm
ent, e
nd y
ear
Number of patients on 2nd line treatment
Global ARV demand 27
Number of patients on treatment, end year
Number of patients on 2nd line treatment
ABC
DDI
LPV/r
NFV
ABC
DDI
LPV/r
NFV
Global ARV demand 28
N % N %
Generic-Accessible Markets 50,264 44% 278,898 60%
15 countries in CHAI subset
Generic-Inaccessible Markets 44,502 39% 110,127 23%
6 countries in CHAI subset
Rest of the world 19,410 17% 79,680 17%
Total 114,176 468,705
Proportion of PIs in Generic Accessible Markets
2006 2010
Global ARV demand 29
Key 2nd Line Take Aways
• Aggregate volume growingsubstantially; based onconservative analysis will be atleast 500k on 2nd treatment by2010
• Certain drugs such as ABC havehigher than expected volumesbecause of contraindications(e.g. pregnant with TB and priorexposure to AZT, when protocolcalls for AZT-containingregimen)
• Any PIs countries choose willmatch need (storage and pricesrequirements)• SQF, NFV not real options
because of cost
Key Take Lessons Learned on
2nd Line
• Will countries use ATV/R takenas separate does if price is lessthan LPV/R?
• How will countries choosebetween DDI and TDF based onrelative cost profiles and toxicityrates?
Key Questions
Global ARV demand 30
Patient Volume vs. Spend
2010 Global ARV Demand Price vs. Volume
0%
20%
40%
60%
80%
100%
Patient Volume Total Cost
1st
Line
1st
Line
2nd
Line
2nd
Line• Market is price elastic
• Countries will use
forecasts to make
resource estimates
based on treatment
protocols
• And will use resource
estimates to adjust
protocols and
treatment targets
31
The average best price of these 12 possibilities is $1,320 today (with a range from$780 to $1,860). LPV/r is cheaper than SQV/r and will remain so. ATV/r pricing
has not yet been announced. Protease-inhibitors with ritonavir require cold-chain,but a heat-stable version of LPV/r will be available beginning in 2006.
ABC, ddI, LPV/r and TDF will be dominant. Countries should revise protocolsquickly to adjust demand forecasts. Also, the pace of registration of generic forms
of these products will be critical to realizing lower prices, when available.
TDF
- or -
ddI
ABC
- or -
AZT**
LPV/r
- or -
SQV/r
- or -
ATV/r
+ +
* These 12 possibilities are the most likely of 36 variations** AZT can be used + or – 3TC
Likely Revised 2nd LineRegimens*
Global ARV demand 32
Metric tons of API
2211NFV
2622177FTC
2518127RTV
96684427LPV
3524169DDI
66473018ABC
141196TDF
227190155118EFV
349299245188NVP
328278229180AZT
54463831D4T
3893302702173TC
2009200820072006
*Product volumes shifted forward 6 months for lead time on API
Global ARV demand 33
Refining the forecast
Through country contact
• Clarify ambiguities in country protocols, particularlyaround second line and peds protocols
• Check scale-up projection with countries
• Increase or decrease based on resourcecommitments
• Continue to gather country-specific epidemiologic inputs
• Cross check protocols against data on actual practice
Global ARV demand 34
CHAI Priorities
- Come to global agreement on key questions (e.g. use of
TDF vs. DDI) so that there is clarity in the market
- Revise current version of the model with missing inputs
- Continually update model with new input from countries
- Customize model outputs to meet needs of CHAI supply
partners
Global ARV demand 35
Contact Details
CLINTON FOUNDATION HIV/AIDS INITIATIVE
225 Water Street
Quincy, MA 02169
USA
Email:
Anil Soni: asoni@clintonfoundation.org
Megan O’Brien mobrien@clintonfoundation.org
Global ARV demand 36
Thank You!
Global ARV demand 37
BACKUP SLIDES
Global ARV demand 38
Model inputs
Patient demand by product type
Point of service product demandUpstream product demand
• Age of treatment program
• Number of people currently in treatment
• Growth of treatment program
• Degree of prior access to treatment
• Sex
• Age
• Weight
• Growth in children
• Anemia
• Active, diagnosed TB
• Pregnancy
• Severe peripheral neuropathy
• Toxicity-related drug switches
• Treatment failure leading to switch to second line
• Death/program drop-out
• National treatment protocol
• Fidelity of practice to protocol
• Consistent availability of product
• Expected changes to treatment protocol
• Order lead time
• Buffer stock protocol
• Financing constraints
• Tendering processes
• Forecasting/procurement planning within national program
• Conversion to API volumes
Global ARV demand 39
Model inputs – Failure Rates
Global ARV demand 40
Model inputs – Attrition Rate
Global ARV demand 41
Model inputs - contraindications
Global ARV demand 42
Model inputs – TB
Global ARV demand 43
Global ARV demand 44
Protocol database
Global ARV demand 45
Protocol gaps
Q codes:• Q1: Prior NVP exposure with incident pregnancy
• Q2: Prior EFV exposure with incident active TB
• Q3: Pregnant with TB and prior exposure to AZT, when protocol callsfor AZT-containing regimen
• Q4: Prior exposure to second line drug
PR: Pregnancy regimen
TB: Active TB regimen
Global ARV demand 46
CHAI subset Regional total
Proportion in
CHAI subset CHAI subset Regional total
Proportion in
CHAI subset
AFRO 15 46 33% 719,150 813,544 88%
AMRO 3 31 10% 234,751 317,879 74%
EMRO 0 15 0% 0 6,080 0%
EURO 0 27 0% 0 24,053 0%
SEARO 2 8 25% 133,046 140,866 94%
WPRO 2 9 22% 19,282 38,278 50%
Total 22 136 16% 1,106,229 1,340,700 83%
Number of people on treatment
Number of countries
(low- and middle-income)
Global ARV demand 47
Patient Enrollment
On treatment
Enrolled
Died or lostto follow-up
Global ARV demand 48
Demand by patient type
Epidemiologic profile for each country
• Sex and age
• Pregnancy and TB rates
• Prevalence of low body weight and contraindication
• Monthly probability of attrition, treatment failure or toxicity-driven switch
Enrollment data (scale-up curve)
Number of patients who:
• Start ARVs
• Are adults or children (by age inmonths)
• Are pregnant or possiblypregnant
• Have active TB
• Have contraindication to a drug
• Have toxicity necessitating adrug switch
• Fail first-line treatment
• Die
• Are lost to follow-up
INPUTS OUTPUTS
Discrete Event
Simulation
Global ARV demand 49
Patient types translated to products by usingnational treatment protocols
Protocols for each of the 21 countries collected into adatabase
• Protocols used in the past
• Current national protocol
• Drafts of protocols to be used in the future
Key findings• Few protocols have been updated to reflect pending revision of the
WHO guidelines
• Several patient profiles are not covered by current protocols
Global ARV demand 50
Point of service product demand
Country-specific treatment protocols
INPUTS OUTPUTS
Protocol
Application
Patient types from previous step
Regimen for each simulated patient
• Changes in regimen aspatients progressthrough history
Product Volume
• Quantity of drugsneeded to treat allpatients at any point intime
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