1. Supply Division July 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, Copenhagen December 2004

2. Supply Division July 2005 OVERVIEW OF PRESENTATION Challenges 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

3. Determine Quantities needed Reconcile needs and funds Choose Procurement method Locate and select suppliers Specify contract terms Monitor order status Receive and Check Supplies Make Payments Distribute Supplies Collect Consumption Information Review Product Selection THE PROCUREMENT CYCLE Managing Drug Supply; Second Edition

4. Supply Division July 2005 QUANTIFICATION Estimating requirements …

5. Supply Division July 2005 QUANTIFICATION Estimating requirements …..

6. Supply Division July 2005 QUANTIFICATION Estimating requirements …

7. Supply Division July 2005 QUANTIFICATION Estimating requirements …

8. Supply Division July 2005 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

9. Supply Division July 2005 DEMAND : When to start ; What to start with …. WHO Guidelines exist (http://www.who.int/hiv/pub/mtct/guidelines/en/)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 Zidovudinetablets, oral liq. Nevirapinetablets, suspension Lamivudinetablets, oral liq. Zidovudine / lamivudine combination tablets

10. Supply Division July 2005 DEMAND : When to start ; What to start with …. WHO Guidelines exist (http://www.who.int/3by5/publications/documents/arv_guidelines/en/)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

11. Supply Division July 2005 QUANTIFICATION Where 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 failure FIRST LINE OPTIONS d4T(30mg) + 3TC + NVP d4T(40mg) + 3TC + NVP d4T – ADRs ?NVP - TB or ADR ? ZDV (100-200mg) + 3TC =NVPd4T(30mg) + 3TC + EFV ZDV (300mg) + 3TC + NVPd4T(40mg) + 3TC + EFV

12. Supply Division July 2005 EXAMPLE OF MYANMAR Assumptions 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

13. Supply Division July 2005 QUANTIFICATION Where to start ??? 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 ?

14. Supply Division July 2005 Doctor on holiday New doctor arrives ( nurse trained to Rx ?

15. Supply Division July 2005 QUANTIFICATION Where to start ??? 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

16. Supply Division July 2005 MANAGING LEAD TIMES Place order Supplies arrive

17. Supply Division July 2005 ? A PUBLIC HEALTH APPROACH Place order Supplies arrive Re-order trigger Month 3 x 2 123456 Supplies arrive

18. Supply Division July 2005 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 Division Dec 2004

19. Supply Division July 2005 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 for children, especially young infants

20. Supply Division July 2005 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 ?

21. Supply Division July 2005 CHILDREN ARE NOT LITTLE ADULTS Likelihood of developing AIDS within 12 Months from HPPMCS, Lancet 2003 CD4 Percent

22. Supply Division July 2005 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

23. Supply Division July 2005 NUMBER OF INFECTED CHILDREN ALIVE AT SELECTED AGES (effect of COTRIMOXAZOLE [TMP-SMX] prophylaxis and/or ART for symptomatic) Marie-Louise Newell, Kirsty Little, Madeleine Bunders (Ghent-IAS Group on HIV infection in women and children)

24. Supply Division July 2005 NUMBER OF INFECTED CHILDREN ALIVE AND ELIGIBLE FOR ART AT SELECTED AGES (effect of COTRIMOXAZOLE [TMP-SMX] prophylaxis and/or ART for symptomatic) Marie-Louise Newell, Kirsty Little, Madeleine Bunders (Ghent-IAS Group on HIV infection in women and children)

25. Supply Division July 2005 NUMBER OF INFECTED CHILDREN ALIVE AND ELIGIBLE FOR ART AT SELECTED AGES effect of COTRIMOXAZOLE [TMP-SMX] prophylaxis and/or ART for symptomatic) Marie-Louise Newell, Kirsty Little, Madeleine Bunders (Ghent-IAS Group on HIV infection in women and children)

26. Supply Division July 2005 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 …

27. Supply Division July 2005 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

28. Supply Division July 2005 ARV REGIMENS COSTS ….. (Ex manufacturer = excluding procurement and delivery costs) Regimen PaediatricCost / month Total Generic Costs originalgeneric1 yr5 yrs ZDV+3TC+NVP* (<3yrs/10kg)58.2944.18524.29 2,621 ZDV+3TC+NVP* (>3yrs/20kg)90.4668.93817.97 4,090 d4T*+3TC+NVP* (<3yrs/10kg)68.1665.87781.64 3,908 d4T*+3TC+NVP* (>3yrs/20kg)134.89130.671550.60 7,753 ZDV+3TC+EFV* (10kg - liq)68.2244.72530.64 2,653 ZDV+3TC+EFV* (10kg - tab)56.6733.17393.58 1,968 ZDV+3TC+EFV* (20kg - liq)92.4163.28750.98 3,755 ZDV+3TC+EFV* (20kg - tab)79.3250.19595.65 2,978 * No generic available

29. Supply Division July 2005 CONCLUSION Making 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