Prepared for the Sixth WFH Global Forum on the Safety and Supply of Treatment Products for Bleeding

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Global Factor Usage and Projected Trends in
Supply and Demand
Prepared for the Sixth WFH Global Forum on the
Safety and Supply of Treatment Products for
Bleeding Disorders
Jeffrey S. Stonebraker, PhD Assistant
Professor Supply Chain Management
September 24, 2009
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AGENDA
Introduction Methods Results Discussion
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The primary aims of this research were to study
the reported FVIII use on a country-by-country
basis and determine whether FVIII use varied
across national economies.
Introduction
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We defined FVIII use as IUs per capita and IUs
per PWHA to explore implications for national
healthcare planning and industry production
planning.
Methods
FVIII use (IUs per capita) divide the reported
number of IUs of FVIII used for a country by its
total population FVIII use (IUs per person with
haemophilia A PWHA ) divide the reported
number of IUs of FVIII used for a country by its
reported number of PWHA
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We used the World Bank to classify the national
economies of the 104 countries in our study.
Methods
OECD Organisation for Economic Co-operation and
Development
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We obtained time-series data on the reported
number of IUs of FVIII use from Market Research
Bureau, Inc. (MRB) and the World Federation of
Hemophilia (WFH).
Methods

• Market Research Bureau, Inc. (MRB)
• Market research firm
• Obtains data through industry and government
  interviews
• Does not collect data annually for each country
• World Federation of Hemophilia (WFH)
• Non-profit organization
• Sends survey questionnaire annually to national
  member organizations (NMOs)
• Countries do not provide data each year

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We analyzed the time-series data for each
country, consisting of 11 possible FVIII use
observations (1996-2006).
Methods

• Descriptive statistics (11 possible observations)
• Mean
• Standard Deviation (SD)
• Coefficient of Variation (CV)
• Regression analysis
• Correlation coefficient (R)
• Slope of regression line (annual growth)
• ANOVA compared the means of FVIII use between
  economic classifications
• H0 m1 m2
• H1 m1 ? m2

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FVIII use data (IUs) were obtained from MRB and
WFH for 104 countries (1996-2006).
Results
Countries Annual observations
MRB
MRB
WFH
WFH
17
30
57
175
245
64
N 104
n 484

• Of the countries reporting FVIII use data to both
  MRB and WFH, there were differences in what was
  reported annually
• 64 comparisons
• 35 instances where MRB gt WFH, with average
  difference of 44
• 29 instances where WFH gt MRB, with average
  difference of 29
• Means were not statistically different

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FVIII use (IUs) data have not been available each
year but the number of countries responding has
increased in recent years.
Results
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Most (67 out of 104) countries are consuming less
than 1 IU/capita.
Results
FVIII use lt 1 IU/capita
FVIII use gt 1 IU/capita
Mean is the average annual FVIII use
(IUs/capita) from 1996-2006, inclusive
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The use of FVIII in treating hemophilia A varies
by national economies with most countries
consuming less than 1 IU/capita.
Results
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FVIII use (IUs per capita) increased over time
with 90 of countries have positive sloping
regression lines.
Results
Econ Average Slope 1 0.1543 2
0.0556 3 0.1141 4
0.0299 5 0.0182
0.1560 gt 1 IU per capita 0.0474 lt 1 IU per
capita
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Some countries had unusually high FVIII use (IUs
per capita) when compared to the countries within
their economic classification.
Results
Iceland
Slovenia
Hungary Slovak Republic
Iran
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The FVIII use (IUs per capita) was significantly
different for all economic classification.
Results
P compares the mean FVIII use (IUs per capita)
between economic classifications using an ANOVA
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To analyze FVIII use IUs per PWHA (person with
hemophilia A), we needed estimates of prevalence.
Results
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More than half of the countries (47 out of 88)
are consuming less than 20,000 IUs/PWHA (person
with hemophilia A).
Results
FVIII use lt 20,000 IUs/PWHA
FVIII use gt 20,000 IUs/PWHA
Mean is the average annual FVIII use (IUs/PWHA)
from 1998-2006, inclusive
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The use of FVIII in treating hemophilia A varies
by national economies with most countries
consuming less than 20,000 IUs/PWHA (person with
hemophilia A).
Results
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FVIII use (IUs per PWHA person with hemophilia
A) increased over time with 74 of countries have
positive sloping regression lines.
Results
Econ Average Slope 1 2,906 2
2,198 3 1,184 4 -213
5 271
2,233 gt 20K IU per PWHA 503 lt 20K IU per
PWHA
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Some countries had unusually high FVIII use (IUs
per PWHA person with hemophilia A) when
compared to the countries within their economic
classification.
Results
Saudi Arabia
Germany
United States
Guatemala
Eritrea
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The FVIII use (IUs per PWHA person with
hemophilia A) was significantly different for all
economic classification except for the high
income countries.
Results
N n
P compares the mean FVIII use( IUs per PWHA
person with hemophilia A) between economic
classifications using an ANOVA
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Reported FVIII use varies significantly across
national economies.
Discussion

• Reported FVIII use is significantly different
  across national economies
• Trends suggest that FVIII use increases with
  increasing economic capacity
• Trends suggest that FVIII consumption has been
  increasing at a faster rate for countries
  consuming more than 1 IU/capita or 20,000
  IUs/PWHA
• Higher FVIII use (IUs per PWHA) may indicate
• better care is being delivered
• over-treatment
• over-reporting of use due to under-reporting of
  PWHA
• Policy making implications Need to understand
  treatment modalities of a country

0.1560 gt 1 IU per capita 0.0474 lt 1 IU per
capita
2,233 gt 20K IU per PWHA 503 lt 20K IU per
PWHA
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In Sweden we have sufficient amounts of factor
VIII and factor IX concentrates available, and
for the Haemophilic Centres there are no
restrictions on the use of such treatment. (p.
515)
Discussion
Number of units used during 1974 3.25 million
IUs 1974 0.40 IUs per capita 2005 6.89 IUs per
capita
17-fold increase (10 growth per year)

• Has Sweden reached a steady-state of FVIII use?
• Will countries currently consuming at Swedens
  1974 FVIII use levels grow at the same rate over
  the next 30 years?
• Is there a target level of demand for FVIII use
  for each country?
• How could this impact national healthcare
  planning?
• How could this impact industry production
  planning?

Nilsson IM. Management of Haemophilia in Sweden.
Thrombosis Haemostasis 1976 35 510-521.
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To estimate the target level of demand for FVIII
use for each country, we must first recognize
that demand is not the same as supply.
Discussion

• Past sales (historical supply) does NOT equal
  demand
• Why invest hundreds of millions of dollars in RD
  and capital expenditures when it appears that
  suppliers could already meet FVIII demand?
• The demand for factor VIII is difficult to
  estimate due to a lack of a therapeutic standard
  and uncertainty surrounding the epidemiology of
  hemophilia A
• No consensus on therapy (prophylaxis, episodic
  therapy, and immune tolerance induction therapy)
  resulting in variability in treatment modalities
• Reported prevalence of hemophilia A varies
  considerably in the developed world and even more
  so in the developing world

Stonebraker, J.S., R.E. Amand, M.V. Bauman, A.J.
Nagle, and P.J. Larson, Modelling haemophilia
epidemiology and treatment modalities to estimate
unconstrained factor VIII demand, Haemophilia,
Vol. 10, pp. 18-26, 2004. Stonebraker, J.S. and
D.L. Keefer, Modeling potential demand for
supply-constrained drugs A new hemophilia drug
at Bayer Biological Products, Operations
Research, Vol. 57, pp. 19-31, 2009.
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Modeling demand for hemophilia A is important to
Discussion

• allow manufacturers to better estimate needed
  production levels of FVIII
• allow benefits of more effective treatment
  regimens to be realized for hemophiliacs without
  worrying about supply constraints
• allow for better planning and allocation of
  national health care resources to treat
  hemophilia
• understand the needs of the global hemophilia
  community and better respond to those needs