Results of aquestionnaire survey inpatients with hemophilia
Hemophilia patient treatment status and awareness ofcoagulation factor products

Blood Product Subcommittee
Biologics Committee, EFPIA Japan

Introduction●European Federation of Pharmaceutical Industries and Associations, Japan(EFPIA Japan)
EFPIA Japan was established in 2002, and represents 24 R&D-based European pharmaceutical companies
operating in the Japanese market. We are the voice of the European innovative pharmaceutical industry in Japan.
Our mission is to contribute to the welfare of the Japanese population through the provision of innovative
pharmaceuticals and vaccines without delay.
EFPIA Japan has played active roles in reviewing, proposing and raising awareness to address various issues
related to the pharmaceutical industry. (Homepage: http://efpia.jp/)●Blood Product Subcommittee (BPSC)
The Blood Product Subcommittee (BPSC) is part of the Biologics Committee along with the Vaccine
Subcommittee and the Biological Products Subcommittee. BPSC aims to establish a stable supply process
for “Plasma Derived Products” manufactured from human blood and for essential products in medical care,and for any plasma related recombinant products that are manufactured with the world’s m~ost advanced
technology.

Objective and methods of the survey
In recent years, the safety against infectious diseases has been increasing with coagulation factor
preparation used for the treatment of hemophilia, and recombinant products together with plasmaderived preparations have been widely used. Routine prophylaxis with blood coagulation factor products, inaddition to on-demand treatment for bleeding episodes, has been widely used and increased the quality of life
(QoL) of patients.
As hemophilia treatment environment evolves, BPSC considered it worthwhile to investigate hemophilia
patient treatment status and awareness of coagulation factor products and the data for future activities.
As part of this effort, BPSC conducted this questionnaire survey in hemophilia patients.
The results of the questionnaire survey enable you to compare hemophilia treatment information andawareness that patients have among the patients participated in the survey. The results may provide
interesting information also to patients who did not participate in the survey. BPSC hopes that the survey
would serve as one of the useful sources for patient exchanges and meetings.
The questionnaire survey was conducted in the period between 1
August 2014 and 31 March 2015. At the beginning, the survey was
conducted online with the cooperation of the National Hemophilia
Network of Japan. In order to obtain more responses, a paper-based
survey was added in January 2015.
A request to participate in the survey both for the online survey andfor the paper-based survey, was distributed to patients via
healthcare professionals by three pharmaceutical companies
participated in BPSC.

Paper-based responses were sent directly to

the EFPIA Japan Office by the patient or their family members.
The survey was conducted anonymously and no personal identifiers
were collected.

2

Summary of the questionnaire survey
1) Responses were collected from 112 participants (82% with Hemophilia A and 17% with Hemophilia B).
2) 89% of the participants received home infusion therapy. The percentage of those who did not receive home
infusion was low in the Kyushu region (many were pediatric patients), and in the Tohoku region (many were
adult patients).
3) In the case of bleeding, 75% responded that they took injection as early as possible. On the other hand,
60% of the respondents did not necessarily observe instructions given by their doctors, and 20% tended tosave the drug consumption.
4) In general, appropriate dose was administered in the case of bleeding in joints.
5) While 87% received routine prophylaxis therapy, the dose and frequency fell below the levels recommended
by the guidelines in some respondents.
6) Both for genetically recombinant products and for plasma-derived products, the respondents were highlyinterested in safety and stable supply.
7) The respondents were more concerned about copayment in the future and increased medical expenses, thanabout the prices of coagulation factor products.

〈Details of the survey results〉
1. Attributes of the hemophiliac patients surveyed
A total of 112 respondents participated in the survey. Of these respondents, 66% were patients and 34% wereparents of patients.
82% of the 112 respondents were hemophilia A patients or parents, and 17% hemophilia B. One did not know
the type of his hemophilia (was not informed of the type by his doctor or did not remember). All the 112
participants were male.
As shown in Figure 1-1, responses were collected from patients from a wide range of age groups from smallchildren to aged adults (aged 0 to 69 years). Adults (aged 23 to 50 years), excluding students, accounted for
36%, the largest among all the age groups, followed by patients aged 51 years and above (24%).
Locations of residence of the patients were shown in Figure 1-2. While responses were collected from patientsand parents across the country, many responses were collected from the Kanto (37.5%) and Kinki (24.1%)
regions, which accounted for a majority (62%).

51 yearsor older24％

Hokkaido
0.9％
Shikoku
2.7％

0-6 years
14％

7-11 years
7％

12-22 years
19％
23-50 years
36％
n=112

Kyushu &Okinawa
12.5％

Tohoku6.3％

Chugoku
6.3％
Kanto
37.5％

Kinki
24.1％
Chubu
7.1％
Hokuriku
1.8％

Fig 1-1 Patient age distribution

Koshin'etsu
0.9％

n=112

Fig 1-2 Locations of residence of patients32. Home infusion therapy1) Implementation of home infusion therapy
The status of home infusion therapy is presented by age groups of the patients (Figure 2-1). The
implementation rate of home infusion therapy was 89%, and almost all the patients received home infusion
therapy at the age of seven and above. Seven out of 16 patients aged six years or younger did not receive
home infusion therapy, while all of the seven patents were aged three years or younger and had receiving
injections at home.
On home infusion therapy

Not on home infusion therapy

90-6 years

7

7-11 years

8

12-22 years

20

123-50 years

37

3

51 years or older

26

1

0%

n=112

40%

20%

60%

80%

100%

Fig 2-1 Implementation of home infusion therapy by age group
The status of home infusion therapy varied by the location of residence of patients (Fig 2-2). The
implementation rate of home infusion therapy was high in most of the regions, but four out of seven in the
Tohoku region and four out of 14 in the Kyushu including Okinawa did not receive home infusion therapy. For
the four patients in the Kyushu region, it was assumed that the age was the reason for not receiving injections
at home where they were younger than three years old. On the contrary, all of the 4 patients who did notreceive home infusion therapy in the Tohoku region were adults aged between 17 and 59 years. There may besome reasons, for example, long distance to medical institutions with haemophilia experts, or there may besome problems in access to such medical institutions.
On home infusion therapy
Hokkaido
TohokuNot on home infusion therapy
1

3

4

Koshin'etsu

1

Kanto

40

Chubu

8

Hokuriku

2

Kinki

26

Chugoku

6

Shikoku

3

2

1
1

10

Kyushu & Okinawa
20%

n=112

20%

40%

4

60%

80%

100%

Fig 2-2 Implementation of home infusion therapy by location of residence

4

The respondents selected precautions they took upon home infusion from multiple options (multiple-choicequestion). As a result, 75% of the patients with hemophilia A and 75% of those with hemophilia B selected "Takeinjection as early as possible when bleeding occurs", suggesting that patients and their family members were wellinformed by healthcare professionals about the importance of early treatment after bleeding. On the other hand, thepercentage of the respondents who selected "Adhere to the dose (units) and frequency of injections as instructed by
the doctor" fell below 40% both in hemophilia A and hemophilia B patients, which revealed that unexpectedly fewer
patients followed doctor's instructions about infusion. Approximately 20% of the respondents answered "Try tominimize the number of injections for hemostasis" or "Try to minimize the dose (units) of injections for hemostasis",
showing that the patients tended to reduce the drug consumption (frequency of injections or units) from that
instructed by the doctors (Fig 2-3).
(Multiple choice)
Hemophilia B (n=19)

Hemophilia A (n=92)
Take injection as early as
possible when bleeding occurs
Adhere to the dose (units) and frequency
of injections instructed by the doctor
Try to minimize the number of
injections for hemostasis
Try to minimize the dose (units) ofinjections for hemostasis
No particular precautions

0％

20％

40％

60％

80％

Fig 2-3 Precautions taken in home infusion

2）Doses in case of joint bleeds
The initial dose (units/kg) upon joint bleeds ranged from 10-20 IU/kg, 20-30 IU/kg, to 30-40 IU/kg in the
majority of the respondents with hemophilia A. The guidelines by Japan Society of Thrombosis and Hemostasis(JSTH) recommends 10-20 IU/kg for mild joint bleeds and 20-40 IU/kg for severe joint bleeds in hemophilia A.
The survey proved that the majority of the participants with hemophilia A received the appropriate dose inaccordance with the guidelines. Many respondents with hemophilia B also received the appropriate dose inaccordance with the guidelines (20-40 IU/kg for mild joint bleeds and 40-80 IU/kg for severe joint bleeds) (Fig20
15

Hemophilia A

The number of
respondents
n=92
25

15

Mild: 10-20 IU/kg
Severe: 20-40 IU/kg

10

<10IU
<20IU
<30IU
<40IU
<50IU
<60IU
<70IU
<80IU
<90IU
<100IU<100IU˜

Could not calculate

10

0

n=16

20

JSHT guideline：

5

Hemophilia B

JSHT guideline：
Mild: 20-40 IU/kg
Severe: 40-80 I/kg

5
0
/kg

Could not calculate

The number of
respondents
25

<10IU
<20IU
<30IU
<40IU
<50IU
<60IU
<70IU
<80IU
<90IU
<100IU<100IU˜

2-4).

/kg

Fig 2-4 The initial dose upon joint bleeds (per kg of body weight)

5

3. Routine prophylaxis therapy
While the report of the national survey on blood coagulation disorders conducted by the Ministry of Health,
Labor and Welfare in 2013 indicated that approximately 50% of hemophilic patients received routine
prophylaxis therapy, in this survey, the percentage of the patients who received routine prophylaxis
therapy exceeded 85% in all the age groups (Fig 3-1).
Yes

No

Do not know

n=112

15

0-6 years
7-11 years

1712-22 years

1
20

1

23-50 years

34

6

51 years or older

23

3

0％

20％

40％

60％

80％

1
100％

Response rate

Fig 3-1 Routine prophylaxis by age group

Reasons for not receiving routine prophylaxis were asked in 13 respondents (seven with hemophilia A, four withhemophilia B, and one with unknown type of hemophilia) who did not receive routine prophylaxis therapy (Fig3-2). Four patients with hemophilia A and three with hemophilia B answered "Because of infrequent bleeds".
Three (Two hemophilia A and one unknown) answered "Troublesome to receive routine prophylaxis", which isbased on the patient's own judgement. On another front, the survey revealed that two respondents
answered "My doctor did not recommend or explain about routine prophylaxis". While this is due to thedoctor's discretion, not the patient's, there should be some room for improvements in providing information topatients in more easily understandable ways.
(Multiple choice)
Hemophilia A (n=7)

Hemophilia B（n=4）

Do not know（n=1）

Infrequent bleeding
Troublesome to receive routine
prophylaxis
My doctor did not recommend or
explain about routine prophylaxis
Did not know the benefits or how
to take routine prophylaxis
Others

0

1

2

3

4

No. of responses5

Fig 3-2 Reasons for not receiving routine prophylaxis

6

The survey showed that many patients believed that "routine prophylaxis should be widely used to maintainjoint health". Also, a considerable number of the patients answered that "injections before physical activities(e.g., sport events, school excursions) should be more actively recommended", or "routine prophylaxis should
be proactively promoted to small children". No one answered that "routine prophylaxis is not desirable due toincreased consumption of drug products."
On another front, some respondents answered that "routine prophylaxis should be limited to patients withfrequent bleeds", which emphasized the need to look at communications between health care professionals
and patients (Fig 3-3).

(Multiple choice)

Hemophilia A (n=92)

Hemophilia B (n=19)

Do not know（n=1）

Routine prophylaxis should be widelyused to maintain joint health.
Routine prophylaxis is not desirable due to increased
consumption of drug products.
Injections before physical activities (e.g., sport events, school
excursions) should be more actively recommended.
Routine prophylaxis should be proactively
promoted to small children.
Routine prophylaxis should be limited to patientswith frequent bleeds.
I am not sure.
Others

0％

20％

40％

60％

80％

100％

No. of responses

Fig 3-3 Desirable status of routine prophylaxis

Dose in routine prophylaxis
The guidelines recommend 20-50 IU/kg for routine prophylaxis in hemophilia A and 40-80 IU/kg (of recombinant
products) in hemophilia B. In this survey, many patients with hemophilia A received routine prophylaxis within
the dose range recommended by the guidelines. However, 22 (26%) patients received lower doses than thelowest recommended dose. Among patients with hemophilia B in this survey, only two patients received lower
doses than the lowest dose recommended by the guidelines (Fig 3-4). The survey showed that the initial dosefor joint bleeds was in accordance with the guideline, but suggested that many patients received lower doses
than the recommended doses for routine prophylaxis. Further investigation should be made to understandwhether it comes from patients' intention to save the drug consumption or from instruction by doctors.
The number of
respondents
30

Hemophilia A
n=85

The number of
respondents
30

n=16

25

20

ガイドライン：
JSHT guideline：
20〜50単位/kg
Mild: 10-20 IU/kg

20

15

Severe: 20-40 I/kg

15
10

<10IU
<20IU
<30IU
<40IU
<50IU
<60IU
<70IU
<80IU
<90IU
<100IU<100IU˜

0

Mild: 20-40 IU/kg
Severe: 40-80 I/kg

5
0
/kg

<10IU
<20IU
<30IU
<40IU
<50IU
<60IU
<70IU
<80IU
<90IU
<100IU<100IU˜

5

Could not calculate

10

JSHT guideline：

Could not calculate

25

Hemophilia B/kg

Fig 3-4 Dose in routine prophylaxis (per kg of body weight)

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It was observed that injections for routine prophylaxis were given less frequently than recommended by theguidelines (three times a week, or every other day for hemophilia A, and twice weekly or every third day
for hemophilia B). The frequency of injection for routine prophylaxis was lower than twice weekly in 32
patients (35%) with hemophilia A and lower than once weekly in five (28%) with hemophilia B (Fig 3-5).
The number of
respondents

15

10

10

3

e

w

n

Tw

O

cc

O

rs

on

i
as

e
th

O

k

es

3

tim

Frequency of injections

a

ee

w

e

ce

0

r

w

ly
al

Tw
ic

e

Ev

e
ic

y

l
ek

ot
he

ry

a

tim

k
ee

y

es

h

ot

w

ly

er

d

er

ee

Ev

0

5

k

ay

al
ly

15

on

20

kl
y

20

as
i

25

cc

25

w
ee

30

O

30

kl
y

35

e

35

5

n=14

40

nc

40

Hemophilia B

w
ee

n=85

O

Hemophilia Aday

The number of
respondents

s

er

th

O

Frequency of injections＊"Others" includes lower frequencies.

Fig 3-5 Frequency of injections in routine prophylaxis

4. Products used by the patients
Approximately 78% of the patients in this survey used recombinant products. Recombinant products wereused in the majority of the patients both with hemophilia A and hemophilia B, but plasma derived products
were often used in the older age group. Eleven respondents (12%) did not know if the product they used
was recombinant or plasma derived. More attention should be paid to the way of information sharing - ifpatients were not interested in the products they used or they were not informed by their doctors (Fig 4-1).
Hemophilia A
Plasma derived products only
Recombinant products only
Both types
Unknown

10

0-6 years

1

Plasma derived products only
Both types

41

7-11 years2

12-22 years

23-50 years

21123-50 years

4

26

4

51 years or older

315

1 51 years or older

20％

40％

1

60％

80％

Response rate

1

0-6 years

12-22 years

0％

100％

0％

5
1

3

1

4
20％

4
40％

Fig 4-1 Drug products used by patients

8

n=19

Recombinant products only

7

7-11 years

Hemophilia B

n=92

60％

80％

Response rate100％

To the question asking respondents' view to the products they used, many patients both with hemophilia
A and hemophilia B chose the answers "Development of Japanese-made recombinant products isdesirable" and "Recombinant products should be used more commonly" (multiple-choice question),
which presented favorable opinions to recombinant products. Many also chose the answer "Multiple
products should be available in the both categories", reflecting their demand for stable supply of
coagulation factors and multiple treatment options (Fig 4-2).
Hemophilia A (n=92)

Hemophilia B (n=19)(Multiple choice)

Multiple products should be available in bothcategories.
Development of Japanese-made recombinant
products made in Japan is desirable.
Recombinant products should be used morecommonly.
Use of plasma derived products should becontinued in future.
OthersNo answer

0％

20％
40％
Response rate

60％

80％

100％

Fig 4-2 View to plasma derived and recombinant products

Many of 19 respondents (12 with hemophilia A and 7 with hemophilia B) who used plasma derived products
answered the reason for the product choice as "Using plasma derived products for many years without problems"and "Plasma derived products are derived from blood donation collected in Japan" (multiple-choice question), andfive answered it was because "Recommended by my doctor." (Fig 4-3).
Hemophilia A (n=12)

Hemophilia B (n=7)

Using plasma derived products for many years
without problems

46

Plasma derived products are derived from blood
donation collected in Japan
Recommended by my doctor
To secure production and supply system in Japan (crisis
management against over-dependence on imported products.

3

3

4

1

2

Prices seem to be lower.

1 1

Plasma derived products are made in Japan.

1 1

Do not find benefits of recombinant products.

1

No explanation about recombinant products
by my doctor.

0

Others1

40(Multiple choice)

1

5

10
No. of responses

15

Fig 4-3 Reasons for using plasma derived products9On another front, many respondents who used recombinant products stated the reasons for the
product choice as "Recommended by my doctor" (60%) and "Recombinant products seem to besafer than plasma derived products" (53%) (Fig 4-4).

45

Recommended by my doctor.
Recombinant products seem to be safer than plasma
derived products.
Using recombinant products for many years

7
10

36
15

without problems.
Do not find benefits of plasma derived products.

83

Recombinant products are used in many countries.

7

1

Easier to use than plasma derived products.

6

1

No explanation about plasma derived products(Multiple choice)

Hemophilia B (n=14)

Hemophilia A (n=72)

by my doctor.

2

Prices seem to be lower.

0

Others

1

5 2

0

20

40
No. of responses

60

Fig 4-4 Reasons for using recombinant products

The responders were asked to prioritize their expectations for recombinant products and plasma derived
products, respectively. Safety ("further enhancement of safety against infections" and "decrease in inhibitor
formation") and stable supply were highly prioritized over convenience ("development of more easily
reconstitutable products" and "extension of storage period at room temperature") and lower prices (Fig 4-5).

Priority rank： 1st

Recombinant products (n=112)

2nd

3rd

4th

5th

6th

Further enhancement of safety against infections
Stable supply
Decrease in inhibitor formation
Development of more easily reconstitutable products
Extension of storage period at room temperature
Lower prices

0

20

40

20

40

60

80

100

No. of responses

Plasma derived products (n=107)
Further enhancement of safety against infections
Stable supply
Decrease in inhibitor formation
Development of more easily reconstitutable products
Extension of storage period at room temperature
Lower prices

0

60

80

100

Fig 4-5 Priorities of expectations for recombinant and plasma derived products

10

No. of responses

5. Recognition about prices
As Fig 4-5 suggested that prices of products were prioritized relatively low by the respondents, and the sametendency was observed with the price related question. Being asked about a difference in prices between
recombinant products and plasma derived products, the majority (62%) of the respondents answered thatthey "do not know the price difference between the two categories (multiple-choice question) (Fig 5-1).
Hemophilia A (n=92)

Hemophilia B (n=19)

Do not know the price difference between the two categories.

(Multiple choice)62
29

Prices should be lowered for both categories.
High prices are acceptable for products withhigher level of efficacy, safety and convenience.

6

20
12

Prices of recombinant products seem to be higher than those ofplasma derived products.

7
7

4

7

Recombinant products should be priced lower than plasma derived products.

7

Prices seem to be the same level for both categories.

6 1

Prices of plasma derived products seem to be higher
than recombinant products.

4 2

Prices should be set the same for both categories.

22

Plasma derived products should be priced lower 11than recombinant products.

5

Others*"Prices" herein refer to prices ofdrug products patients used

0

20

40

60

80

No. of responses
Fig 5-1 Recognition about price differences between recombinant and plasma derived products

In addition, to the question about a view to prices, many chose the two answers "Worried that copayment
may be increased in the future" (77%) and "Concerned that high prices may lead to increase of medical
expenses in Japan" (59%) (multiple-choice question), suggesting that they were more concerned about
copayment in the future and increase in medical expenses, than prices of products (Fig 5-2).
Hemophilia A (n=92)

Hemophilia B (n=19)72

Worried about copayment may be increased in future.
Concerned that high prices may lead toincrease of medical expenses in Japan.

55

High prices may result in saving the
drug consumption.

14
10

17
12 3

Not interested in prices as I have no copayment.

8 2

Others*"Prices" herein refer to prices ofdrug products patients used

(Multiple choice)

0

20

40
60
80
No. of responses

100

Fig 5-2 View to prices

Blood Product Subcommittee in Biologics Committee of EFPIA Japan extends deep gratitude to thepatients and their family members for their participation in this survey.
BPSC will continue to make an effort to understand hemophilia patients and treatment through surveys
and awareness activities in collaboration with patient groups including National Hemophilia Network ofJapan, and hemophilia care professionals, ultimately to contribute to the improvement in the treatment
and QOL of hemophilia patients.

11

Blood Product Subcommittee,
Biologics Committee, EFPIA Japan〒100-8265 Marunouchi 1-6-5, Chiyoda-ku, Tokyo (Bayer Yakuhin, Ltd.)

info@efpia.jp