Transcript Weight Distribution Assumptions

A Demand Forecasting Tool
for Pediatric Antiretroviral
Medications
November 3, 2004
Acknowledgements
This talk was developed by:
Alex Hurd
Lynn Margherio
Kate Condliffe
Stephen Nicholas
Special thanks to:
Mark Klein, Elaine Abrams, Consuelo Beck-Sague
Clinton HIV/AIDS Initiative Overview
Mission
To bring high-quality medical care and treatment to people living with
HIV/AIDS, and to improve healthcare systems in resource-poor
countries
Philosophy
To be effective, programs must:
•combine prevention, care, and treatment
•be integrated into public health infrastructure
•have strong in-country political and policy support
•be viewed as an emergency, not as business as usual
Value-Add
1) Mobilize political will (donor and host governments)
2) Combine business and clinical expertise in operational planning and
ongoing implementation support
3) Change economics of care and treatment
4) Strategic partnerships with other international HIV/AIDS organizations
Goals
Access to high quality, low-cost ARVs and diagnostic testing
Aim: 2 million people on ARVs by the end of 2008 in partner countries
Clinton HIV/AIDS Initiative Overview (cont.)
At the invitation of government leaders, the Clinton HIV/AIDS Initiative is
currently working in the following countries:
Africa
Caribbean
Asia/Pacific
Lesotho
Bahamas
China
Mozambique
Dominican Republic
India
Rwanda
Haiti
South Africa
Jamaica
Tanzania
Organization of Eastern
Caribbean States
33% of cases in Africa
90% of cases in Caribbean
85% of cases in Asia
Cost of Antiretroviral drugs
Characteristics of early ARV market
• ARV market was fragmented and characterized by small
orders, resulting in sub-optimal production
• Lack of harmonization of treatment guidelines
• Lack of dependable demand forecasts
• Weak supply management systems
•Price reductions were achieved through generic competition,
fixed-dose drug production, and better organization of market,
driving predictable and sustainable cost reductions
•The effect of increased volume of production has also begun
to lower the cost of ARVs
History of Antiretroviral Pricing
The introduction of generic competition into the ARV market resulted in a
substantial reduction in the price of adult formulations
ARV Price History - WHO recommended first line drug regimens
Note: Benchmark pricing is lowest global price; prices outside of selected African countries are substantially higher
Source: Médecins Sans Frontières, Untangling the Web of Price Reductions, April 2004
High Cost of Pediatric Formulations
Adult
# of generic suppliers w/WHO approval
for at least 1 product
Lowest available WHO pre-qualified
price (d4T+3TC+NVP)
Price reduction since October 2000**
Pediatric
5
1*
$132-140
$1,000-1,150
93%
62%
* Cipla is currently the only generic supplier with pediatric formulations approved by the WHO
**Source for price comparison: “Selected drugs used in the care of people living with HIV,” MSF, October 2000
ARV procurement for children
living with HIV/AIDS
Challenges to Procurement of Pediatric ARVs
Challenges to HIV/AIDS
procurement for
pediatrics
• High cost of pediatric
formulations of ARVs
• Pediatric AIDS low priority
for pharmaceutical
companies, governments
• Lack of universal
international treatment
guidelines for children
living with HIV/AIDS
• Complicated dosing
scheme based on weight
or surface area and age
• Issues of palatability,
storage, adherence, et al.
Effective procurement for pediatric
ARVs is based on the following
principles:
• Standardization of international treatment
guidelines for pediatric patients living with
HIV/AIDS, with simplification where possible
• Advocacy for the inclusion of pediatric HIV
care and ARV treatment in every national
operational and procurement plan
• Training and monitoring to ensure clinician
awareness and compliance with national
guidelines
• Development of global demand forecasts
based on agreed guidelines and proper
dosing to spur production of high quality-low
cost generic pediatric ARVs
International Treatment Guidelines
The following guidelines for treatment of children living with
HIV/AIDS have been developed:
• Scaling Up ARV Therapy in Resource-Limited Settings,
WHO 3 by 5 Initiative; (2003)
• HIV Drug Dose Ranges, Harvard AIDS Institute, MSF,
ACHAP; (May 2003)
• Pediatric ARV & Cotrimoxazole Dosing, CDC, Baylor,
Columbia; (March 2004)
Slight variations between guidelines remain
Forecasting will be more exact once agreement on universal guide is
reached
National planning activities
• National operational plan for treatment, including:
•
•
•
Pediatric ARV treatment protocols (1st and 2nd line)
Regimen change assumptions due to toxicity & treatment failure
Projection of pediatric patients on treatment (“patient targets”)
• National drug ordering, storage, distribution and tracking
system operational
• Forecasting tool completion and drug ordering:
•
Dosage, formulations
•
Weight distribution
•
Security stock
Implementation activities
• Clinician training:
• International pediatric HIV treatment guidelines
• National protocol with standardization, simplification
• Monitoring:
•
•
•
•
•
Efficiency of national drug distribution system
Physician prescribing practices
Patient adherence
Drug consumption data
National viral resistance monitoring
• Ongoing projection updates, revision of toxicity, treatment
failure assumptions if necessary
• Regular ordering to improve supply management and
reduce risk of stock-outs and drug wastage through
expiration
A Demand Forecasting Tool for Pediatric
Antiretroviral Medications
Demand Forecast Model: Steps
• Identify appropriate dosage and formulation for each weight class
• Include following assumptions from National Plan:
• First and second line regimens
• Regimen sequencing
• Single drug toxicity
• Treatment failure rate
• Patient targets per month
• Weight distribution of patients coming onto treatment
• Security stock
Demand Forecast Model: Dosage & Formulation
• Dosage assumptions for the ARV forecasting
model are based on the following sources :
 HIV Drug Dose Ranges, Harvard AIDS Institute, MSF,
ACHAP; (May 2003)
 Pediatric ARV & Cotrimoxazole Dosing, CDC, Baylor,
Columbia; (March 2004)
Demand Forecast: Dosage & Formulation (cont.)
From: Pediatric Antiretroviral and Cotrimoxazole Dosing guide,
CDC, Baylor, Columbia; March 2004
Weight
KG
Abacavir
(Ziagen®)
Stavudine
(Zerit®,
d4T)
Lamivudine
(Epivir®, 3TC)
Zidovudine
(Retrovir®, ZDV,
AZT)
8 mg/KG
twice daily
1 mg/KG
twice daily
4 mg/KG
twice daily
240 mg/m2
twice daily
Liquid
20 mg/ml
5 – 6. 9
2 ml
7 – 9. 9
3 ml
10 – 11. 9
Tablet
300 mg
Capsules
15, 20, 30 mg
Liquid
10 mg/ml
Tablet
150 mg
Liquid
10 mg/
ml
Didanosine
(Videx®, DDI)
120 mg/m2
twice daily
Capsule
100 mg
Chewable tablets
25, 50, 100 mg
2 ml
7 ml
15 mg
3 ml
9 ml
1 cap
25mg + 25mg
4 ml
15 mg
or
(20 mg1)
4 ml
12 ml
1 cap
25mg + 25mg
12 – 14. 9
5 ml
15 mg
or
(20 mg1)
5 ml
14 ml
1 cap
50mg + 25mg
15 - 16. 9
6 ml
15 mg
or
(20 mg1)
6 ml
½ tab
15 ml
2 caps
50mg + 25mg
17 – 19 .9
7 ml
20 mg
7 ml
½ tab
17 ml
2 caps
50mg + 50mg
½ tab
Demand Forecast: Dosage & Formulation (cont.)

Liquid formulation vs. caps/tabs assumptions:
Weight
Liquid
Tabs/Caps
3-5 kg
100%
0%
5-10 kg
100%
0%
10-15 kg
100%
0%
15 - 20 kg
100%
0%
20 - 25 kg
50%
50%
25 - 30 kg
50%
50%
30 - 40 kg
50%
50%
Demand Forecast: National Protocol
Clinical Assumptions
ILLUSTRATION
Protocols and regimen sequencing
assumptions may need to be
adjusted overtime
Regimen
Initial regimen used for treatment naïve patients
AZT + 3TC + NVP
Regimen
Sequencing
100%
At end of year 1, Clinical assumptions project following
regimen sequencing
First Line
Initial Regimen
AZT + 3TC + NVP
80%
Toxicity to NVP
AZT + 3TC + EFV
10%
Toxicity to AZT
d4T +3TC + NVP
4%
Toxicity to AZT & NVP
d4T + 3TC + EFV
4%
ABC + ddI + Lop/rit
2%
Second Line
After treatment failure
Demand Forecast: Patient Targets
ILLUSTRATION
Patient Target Assumptions
Project accrual of patients receiving treatment per month
# of
pediatric
patients
Jan
Feb
Mar
Apr
May
Jun
Jul
Aug
Sep
Oct
Nov
Dec
275
550
825
1,100
1,375
1,650
1,925
2,200
2,475
2,750
3,025
3,300
Assumptions:
3300 pediatric patients are projected to be on treatment by the end of year 1
Demand Forecast: Weight Distribution
ILLUSTRATION
Weight Distribution Assumptions
Project the amount of patients per weight class and calculation of weight
distribution percentages
Weight
% of patients
3-5 kg
6%
5-10 kg
8%
10-15 kg
17%
15 - 20 kg
25%
20 - 25 kg
23%
25 - 30 kg
12%
30 - 40 kg
9%
Assumptions:
Weight distribution provided by country in this example. When weight distribution is unknown, each
weight class receives an even weight distribution (14.3%).
Demand Forecast: Security Stock
Security stock Assumptions
ILLUSTRATION
Establish security stock as additional number of months of treatment.
Security Stock/Buffer (Number of months):
3
Assumptions:
Example: Country orders once per quarter. 3 month additional security stock added to each quarterly
order.
Demand Forecast: Calculations
Outputs of model:
•
# of patients/month/ weight
class/formulation
•
# of units (ml, caps, tabs) per month
•
# of units/quarter (with security
stock)
•
# of boxes/quarter (with security
stock)
•
Cost per quarter
Sample page
Patients Per Month Taking Drug
Drug
Jan
Suspension
D4T
Feb
Mar
Apr
May
Jun
Jul
Aug
Sep
Oct
Nov
Dec
3-5 kg
5-10 kg
10-15 kg
15 - 20 kg
20 - 25 kg
25 - 30 kg
30 - 40 kg
15
1
2
4
6
3
-
30
3
4
7
11
5
-
45
4
5
11
17
8
-
59
5
7
15
22
10
-
74
7
9
19
28
13
-
89
8
11
22
33
15
-
104
9
12
26
39
18
-
119
11
14
30
44
20
-
134
12
16
34
50
23
-
149
13
18
37
55
25
-
163
15
19
41
61
28
-
178
16
21
45
66
30
-
3TC
210
420
631
841
1,051
1,261
1,471
1,682
1,892
2,102
2,312
2,523
NVP
180
360
541
721
901
1,081
1,261
1,441
1,622
1,802
1,982
2,162
AZT
193
386
579
772
965
1,158
1,351
1,544
1,737
1,931
2,124
2,317
DDI
4
8
12
16
20
24
28
32
36
40
44
49
Lop/Rit
4
9
13
17
21
26
30
34
39
43
47
51
ABC
4
9
13
17
21
26
30
34
39
43
47
51
NFV
-
-
-
-
-
-
-
-
-
-
-
-
Capsules
D4T (15mg)
-
-
-
-
-
-
-
-
-
-
-
-
D4T (20mg)
3
5
8
10
13
15
18
20
23
25
28
30
D4T (30mg)
7
14
21
29
36
43
50
57
64
72
79
86
Sample page (cont.)
Drug
Units Needed Per Month
Formulation
Jan
Suspension
D4T
Feb
Mar
Apr
May
Jun
Jul
Aug
Sep
Oct
Nov
Dec
ml
8
15
25
35
45
13,286
321
803
2,844
5,855
3,463
-
26,573
642
1,606
5,688
11,710
6,926
-
39,859
964
2,409
8,532
17,566
10,389
-
53,145
1,285
3,212
11,376
23,421
13,852
-
66,432
1,606
4,015
14,220
29,276
17,315
-
79,718
1,927
4,818
17,064
35,131
20,778
-
93,004
2,248
5,621
19,908
40,986
24,241
-
106,290
2,570
6,424
22,752
46,842
27,704
-
119,577
2,891
7,227
25,596
52,697
31,166
-
132,863
3,212
8,030
28,440
58,552
34,629
-
146,149
3,533
8,833
31,284
64,407
38,092
-
159,436
3,854
9,636
34,128
70,263
41,555
-
3TC
ml
85,883
171,766
257,649
343,532
429,415
515,298
601,181
687,064
772,947
858,830
944,713
1,030,596
NVP
ml
122,316
244,633
366,949
489,266
611,582
733,899
856,215
978,532
1,100,848
1,223,165
1,345,481
1,467,798
AZT
ml
181,082
362,163
543,245
724,326
905,408
1,086,489
1,267,571
1,448,652
1,629,734
1,810,815
1,991,897
2,172,978
DDI
ml
1,849
3,699
5,548
7,397
9,247
11,096
12,945
14,795
16,644
18,493
20,343
22,192
Lop/Rit
ml
570
1,140
1,710
2,281
2,851
3,421
3,991
4,561
5,131
5,701
6,271
6,842
ABC
ml
1,753
3,505
5,258
7,011
8,764
10,516
12,269
14,022
15,774
17,527
19,280
21,033
NFV
mg
-
-
-
-
-
-
-
-
-
-
-
-
Capsules
D4T (15mg)
Caps
-
-
-
-
-
-
-
-
-
-
D4T (20mg)
Caps
154
308
462
616
770
923
1,077
1,231
1,385
1,539
1,693
1,847
D4T (30mg)
Caps
281
562
843
1,124
1,405
1,686
1,967
2,248
2,529
2,811
3,092
3,373
3-5 kg
5-10 kg
10-15 kg
15 - 20 kg
20 - 25 kg
25 - 30 kg
30 - 40 kg
Sample page (cont.)
3 month security stock per
quarter = 25% additional
stock
Security Stock/Buffer (Number of months)
Drug
3
Cost Per Import Duties
Units per
Box/Bottle and Freight
Bottle/Box
(MSF)
Costs
Suspension
D4T
200
3TC
240
NVP
Total Boxes/Bottles per Quarter
(includes Security Stock)
Total units per quarter (includes Security Stock)
Q1
(US$)
Prices and box sizes must be verified with suppliers
before placing order
Q2
Q3
Q4
Q1
Q2
Q3
Total Cost Per Quarter (includes Security Stock)
Q4
Q1
Q2
(US$)
9.500
Q3
Q4
(US $)
10.93
99,647
249,118
398,589
548,060
498
1,246
1,993
2,740
5,443
13,608
21,773
29,938
6.73
8.75
644,123
1,610,307
2,576,491
3,542,675
2,684
6,710
10,735
14,761
23,481
58,702
93,924
129,145
240
17.50
20.13
917,374
2,293,434
3,669,494
5,045,555
3,822
9,556
15,290
21,023
76,926
192,314
307,702
423,091
AZT
100
1.53
1.99
1,358,111
3,395,278
5,432,446
7,469,613
13,581
33,953
54,324
74,696
27,013
67,532
108,051
148,571
DDI
200
14.74
16.95
13,870
34,675
55,480
76,285
69
173
277
381
1,176
2,939
4,702
6,466
Lop/Rit
200
14.74
16.95
4,276
10,690
17,104
23,518
21
53
86
118
362
906
1,450
1,993
ABC
240
34.80
40.02
13,145
32,863
52,581
72,299
55
137
219
301
2,192
5,480
8,768
12,056
NFV
7,200
35.37
40.68
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
Capsules
D4T (15mg)
56
5.25
6.04
-
-
-
-
D4T (20mg)
56
5.25
6.04
1,154
2,886
4,617
6,349
21
52
82
113
124
311
498
684
D4T (30mg)
60
3.7
4.81
2,108
5,270
8,432
11,593
35
88
141
193
169
422
676
929
Total Cost for 1 year (4 quarterly orders): $US 2,058,715
Summary
Challenges
•
National drug distribution system inefficiencies may render
this model less effective
•
Physician practices may not be consistent with national
plans, thereby rendering model less effective
•
Regular communication between program management and
implementing physicians is crucial
•
Strength of model depends on validity of data – regular
reporting of updates allows for more accurate projections
Benefits Forecasting Tools
•
The development and use of demand forecasting tools will
spur production of lower cost – high quality ARV pediatric
formulations
•
Ordering guided by model output will make stock-outs and
drug wastage less likely by making national drug distribution
programs operate more smoothly
•
Physician prescribing practices, regimen sequencing, and
treatment costs can be tracked
•
Model becomes more accurate over time with introduction
of updated information and will provide important national
program overview data