Helene Möller , (M.Pharm, PhD) UNICEF Supply Division, Copenhagen December 2004

Supply DivisionJuly 2005

ENSURING SECURE and RELIABLE

SUPPLY and DISTRIBUTION SYSTEMS in DEVELOPING

COUNTRIES, in the CONTEXT OF HIV/AIDS and PMTCT

Forecasting,

estimating requirements for

Procurement of HIV related supplies

Helene Möller , (M.Pharm, PhD)UNICEF Supply Division, CopenhagenDecember 2004


OVERVIEW OF PRESENTATIONChallenges in Forecasting supply needs in HIV Introduction: defining the context in

which the estimate is made

Managing supply and demand in scale up

Key issues in forecasting paediatric needs

Conclusion

Determine Quantities

needed

Reconcile needsand funds

Choose Procurementmethod

Locate and selectsuppliers

Specify contract termsMonitor

order status

Receive and Check Supplies

Make Payments

Distribute Supplies

Collect Consumption Information

Review Product Selection

THE PROCUREMENT CYCLEManaging Drug Supply; Second Edition


QUANTIFICATION Estimating requirements …

Screening tests

Confirmatory tests

Tie breakers

Consumables and waste management

VCT

Knowing one’s HIV status is

a key step in HIV

prevention and care Quality assurance


QUANTIFICATIONEstimating requirements …..

Cotrimoxazole

Isoniazid

Diagnosis, treatment of PCP

Diagnosis, treatment of TB

OI’s CPT/IPT

In high prevalence populations PCP is common, and

TB a leading cause of death

Diagnosis, treatment of OI’s


QUANTIFICATIONEstimating requirements …

Diagnostic tests

Pharmaceuticals forSyndromic management

Medical consumables(syringes, needles, waste)Condoms

STI

Regular STIscreening, prompt

treatment andcondom

distributionshould be part of

care of PLWHAInformation leaflets ?


QUANTIFICATIONEstimating requirements …

Palliative Care (relief of pain and distressing symptoms) Nutritional Support (nutritional assessment, dietary guidance, supplementary and therapeutic feeding) Universal precautions (clinical and home setting ) (Infection control, PEP)

OTHER …

More specialised … HAART, diagnosis and treatment of OI’s and HIV related cancers


ENSURING SECURE and RELIABLE SUPPLY and DISTRIBUTION SYSTEMS in DEVELOPING COUNTRIES, in the CONTEXT OF HIV/AIDS and PMTCT

ESTIMATING REQUIREMENTS challenges and hints

ANTI - RETROVIRALS


DEMAND : When to start ; What to start with ….

WHO Guidelines exist(http://www.who.int/hiv/pub/mtct/guidelines/en/)

• For Prevention of Mother to Child Transmission:– Guideline for mothers who qualify for initiation of treatment, who may become pregnant,

– Mothers on ART who become pregnant, and infants

– HIV infected pregnant women with or without indications for ART, and infants, etc

Zidovudine tablets, oral liq.

Nevirapine tablets, suspension

Lamivudine tablets, oral liq.

Zidovudine / lamivudine combination tablets

http://www.who.int/hiv/pub/mtct/guidelines/en/


DEMAND : When to start ; What to start with ….

WHO Guidelines exist(http://www.who.int/3by5/publications/documents/arv_guidelines/en/)

• For Treatment and Care: First Line– Adults (zdv or d4T) + 3TC + ( NVP or EFV )– Preferred option for children (zdv or d4T) + 3TC + NVP– Guideline for children on TB treatment regiments containing rifampicin,

substitute NVP for EFV

• For Treatment and Care: Second Line– Guidelines for adults, toxicity, treatment failure

– Guidelines for children with toxicity, treatment failure

http://www.who.int/3by5/publications/documents/arv_guidelines/en/


QUANTIFICATIONWhere to start ???

STEP 1: Postulate a patient profile at site(s) of service delivery

number of adults, pregnant women, children infants

what are their bodyweight ranges ? number of patients with TB co-infection potential to develop ADRs and/or treatment

failureFIRST LINE OPTIONS

d4T(30mg) + 3TC + NVP d4T(30mg) + 3TC + NVP

d4T(40mg) + 3TC + NVP d4T(40mg) + 3TC + NVP

d4T – ADRs ? NVP - TB or ADR ?

ZDV (100-200mg) + 3TC =NVP d4T(30mg) + 3TC + EFV

ZDV (300mg) + 3TC + NVP d4T(40mg) + 3TC + EFV


EXAMPLE OF MYANMARAssumptions for defining a patient profile

90% of all patients will weigh less than 60kg when enrolled

Stavudine will be the NRTI of choice

10% of cases may develop intolerance to d4T, switch to ZDV

Nevirapine is the NNRTI of choice.

Initial treatment with 200mg daily, for 2 weeks, is needed to reduce incidence of serious side-effects.

Regardless of this precaution, 20% of patients will develop intolerance to nevirapine. Switch to Efavirenz 600mg daily dose.

Not many patients on TB treatment to initiated on ARVs, allow for 5% of patients on rifampicin plus ART



STEP 2: Estimate the growth in numbers of patients on treatment

how many need treatment today ? what are the enrolment criteria ?, no. of trained health workers in the field to provide

care ? new enrolments, ability to screen and diagnose ?

HONESTLY, HOW MUCH MONEY WILL BE AVAILABLE THIS YEAR ?


0

50

100

150

200

250

Jan Feb March April May June

TOTAL on Rx

Nr enroled

Doctor on holiday

New doctor

arrives ( nurse trained to

Rx ?



STEP 3: Estimate the number of packs/kits needed to start, also to prevent stock outs

lead time for arrival of stocks decide on an ordering interval that will

minimise stock holding calculate a safety stock level, and a re-order

trigger calculate the number of packs needed per

recommended treatment regimen multiply the cumulative number of patients

with the numbers of treatment packs needed per regimen

MONITOR stock situation and re-order/redistribute until you have data on stock movement


MANAGING LEAD TIMES

0

100

200

300

400

500

600

TOTAL onRx

Nr enroled

Place order Place order

Supplies arrive Supplies arrive


? A PUBLIC HEALTH APPROACH

0

100

200

300

400

500

600

TOTAL onRx

Nr enroled

Place order Place order

Supplies arrive Supplies arrive

Re-order trigger

Month 3 x 2

1 2 3 4 5 6

Supplies arrive


WHAT ABOUT THE NEXT ORDER? When to place, how much ???

NEXT STEPS: Monitoring supply and demand continuously monitor lead time for arrival of

stocks continuously revise safety stocks and re-

order triggers continuously monitor expiry dates redistribute as needed to avert disaster

UNICEF Supply DivisionDec 2004


ENSURING SECURE and RELIABLE SUPPLY and DISTRIBUTION SYSTEMS in DEVELOPING COUNTRIES, in the CONTEXT OF HIV/AIDS and PMTCT

ESTIMATING REQUIREMENTS challenges and hints

ANTI – RETROVIRALSfor children, especially young infants


FORMULATIONS FOR PMTCT Key challenges in quantification ….

• Nevirapine suspension (10mg/ml):– Commercially available as 240ml– Donation programmes supply 20ml or 25ml– Large bottles adapted with fitted caps to facilitate dispensing– For PMTCT, need 0,6ml per day ?

– Dispensing syringe : BAXA Donation

• Zidovudine oral liquid (10mg/ml)– Commercially available as 100ml, 200ml, 240ml bottle– For PMTCT, need approximately 35ml for one week ?

• Lamivudine oral liquid (10mg/ml)– Commercially available as 100ml, 240ml– For PMTCT, need approximately 25ml for one week ?


CHILDREN ARE NOT LITTLE ADULTS Likelihood of developing AIDS within 12 Monthsfrom HPPMCS, Lancet 2003

49.0%

29.0%

20.0%16.0%

38.0%

20.0%

13.0%10.1%

27.0%

12.0%7.5% 5.7%14.0%

5.3% 3.1% 2.4%7.9%

2.5% 1.5% 1.2%

0%

20%

40%

60%

80%

100%

10 20 30 40

10 Yrs

5 Yrs

2 Yrs

1 Yr

6 Mos

CD4 Percent


CHILDREN ARE NOT LITTLE ADULTS• 510,000 children died of HIV in 2004 ; 1,400 per day

• Aggressive and bimodal presentation – 30% mortality at yr 1, – 50% at yr 2 and – 60% at yr 5

• Diagnosis for children below 18 months limited -PCR expensive; require sophisticated labs ad expertise

• Clinical staging difficult in infants

• Laboratory monitoring in children under 6 years difficult –CD4% required for children below 6 years

• Capacities and expertise on care and treatment limited, formulations limited


NUMBER OF INFECTED CHILDREN ALIVE AT SELECTED AGES (effect of COTRIMOXAZOLE [TMP-SMX] prophylaxis and/or ART for symptomatic)

300000

236,274210,881

196,736171,106

194,045

144,413119,596

74,6320

100000

200000

300000

BIRTH Age 1 Age 2 Age 5 Age 10

no TMP, no ARV

with ARV, no TMP

with TMP. No ARV

Marie-Louise Newell, Kirsty Little, Madeleine Bunders (Ghent-IAS Group on HIV infection in women and children)


NUMBER OF INFECTED CHILDREN ALIVE AND ELIGIBLE FOR ART AT SELECTED AGES

(effect of COTRIMOXAZOLE [TMP-SMX] prophylaxis and/or ART for symptomatic)

0

10,000

20,000

30,000

40,000

50,000

60,000

Age 1 Age 2 Age 5 Age 10

no TMP, no ARV

with ARV, no TMP

with TMP. No ARV



NUMBER OF INFECTED CHILDREN ALIVE AND ELIGIBLE FOR ART AT SELECTED AGES

effect of COTRIMOXAZOLE [TMP-SMX] prophylaxis and/or ART for symptomatic)

171106

56,265

050,000

100,000150,000200,000250,000300,000

Age 1 Age 2 Age 5 Age10

no TMP, no ARV

with ARV, no TMP

with TMP. No ARV

ALIVE 100% CTX



ESTIMATING THE NUMBER OF TREATMENTS NEEDED

STEP 1: Estimated number of births, existing death-rates, HIV prevalence in ANC settings

STEP 2: Estimated PMTCT coverage and transmission rates= estimated HIV positive infants born

STEP 3: What is the chance of survival ? Morbidity ? Mortality ?Coverage with cotrimoxazole prophylaxis

STEP 4: Estimated number of children at different ages eligible for treatment (assumptions around disease progression)

STEP 5: Reality check – who will enrol them into treatment, etc …


MSF PAPER: prices, availability of specific children formulations …• Cost of treatment drops when switching to adult

formulations:

Peak around 14kg bodyweight

• Using tablets for a child (20 kg) reduces the cost per treatment per year nearly 8 times:– (d4T / 3TC / NVP )

Best generic price/y $ 566 $224

Best innovator price/y $1,706 $631

• Managing the switch – increases complexities in resource poor settings


ARV REGIMENS COSTS …..(Ex manufacturer = excluding procurement and delivery costs)

Regimen Paediatric Cost / month Cost /month Total Generic Costs

original generic 1 yr 5 yrsZDV+3TC+NVP*

(<3yrs/10kg) 58.29 44.18 524.29 2,621

ZDV+3TC+NVP* (>3yrs/20kg) 90.46 68.93 817.97 4,090

d4T*+3TC+NVP* (<3yrs/10kg) 68.16 65.87 781.64 3,908

d4T*+3TC+NVP* (>3yrs/20kg) 134.89 130.67 1550.60 7,753

ZDV+3TC+EFV* (10kg - liq) 68.22 44.72 530.64 2,653

ZDV+3TC+EFV* (10kg - tab) 56.67 33.17 393.58 1,968

ZDV+3TC+EFV* (20kg - liq) 92.41 63.28 750.98 3,755

ZDV+3TC+EFV* (20kg - tab) 79.32 50.19 595.65 2,978

* No generic available


CONCLUSIONMaking demand forecasting simple …..Do an estimate as best as you can based on treatment targets

Consider the need for buffer stocks during scale up

Calculate the needs to fill up the pipeline

Look at lead times from industry and establish order intervals

Place order

ENSURE SECURE INVENTORY CONTROL MECHANISMS

Helene Möller , (M.Pharm, PhD) UNICEF Supply Division, Copenhagen December 2004

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Transcript of Helene Möller , (M.Pharm, PhD) UNICEF Supply Division, Copenhagen December 2004