forecasting global arv demand - who

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


Regimen progression


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


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?


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


Methodology

- Background


- Product demand

- Upstream demand

Results


- Product demand

Agenda


Scale up

4.5MM

1.3MM


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


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


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)


Num

ber

of patients

on tre

atm

ent, e

nd y

ear

Number of patients on 1st line treatment


Number of patients on 1st line treatment

3TC

AZT

D4T

EFV

NVP

3TC

AZT

D4T

EFV

NVP

FTC

TDF

TDF


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


Num

ber

of patients

on tre

atm

ent, e

nd y

ear

Number of patients on 2nd line treatment


Number of patients on treatment, end year

Number of patients on 2nd line treatment

ABC

DDI

LPV/r

NFV

ABC

DDI

LPV/r

NFV


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


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


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*


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


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


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


Contact Details

CLINTON FOUNDATION HIV/AIDS INITIATIVE

225 Water Street

Quincy, MA 02169

USA

Email:

Anil Soni: [email protected]

Megan O’Brien [email protected]


Thank You!


BACKUP SLIDES


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


Model inputs – Failure Rates


Model inputs – Attrition Rate


Model inputs - contraindications


Model inputs – TB


Protocol database


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


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)


Patient Enrollment

On treatment

Enrolled

Died or lostto follow-up


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


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


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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