Haemophilia (2017), 23, 89–97 DOI: 10.1111/hae.

13071

ORIGINAL ARTICLE Clinical haemophilia

The demographics, treatment characteristics and quality of

life of adult people with haemophilia in China – results
from the HERO study
J . S U N , * Y . Z H A O , † R . Y A N G , ‡ T . G U A N § and A . I O R I O ¶ O N B E H A L F O F T H E C H I N E S E H E R O
STUDY GROUP
*Nanfang Hospital, Southern Medical University, Guangzhou; †Peking Union Medical College Hospital, Beijing; ‡Institute of
Hematology and Blood Diseases Hospital, CAMS & PUMC, Tianjin; §Hemophilia Home of China, Beijing, China; and
¶Department of Clinical Epidemiology and Biostatistics, and Department of Medicine, McMaster University, Hamilton,
Ontario, Canada

Introduction: Haemophilia management in China needs to be further developed. To further improve the quality
of life (QoL) of people with haemophilia (PWH) in China, it is important to investigate the peculiarities of China
as compared to other countries. Aim: The primary objective of the Haemophilia Experiences, Results and
Opportunities (HERO) project was to quantify the impact of key psychosocial factors affecting PWH. This
article presents the demographics, treatment characteristics, and QoL of adult PWH in China as compared with
the results of the other nine countries participating in the HERO study. Methods: This was a web- (except in
Algeria) and questionnaire-based survey conducted in 10 countries. Results: A total of 110 adult PWH from
China and 565 from other countries completed the questionnaire. Compared with other countries, respondents in
China reported: lower rate of employment (45.6% vs. 63.1%); lower percentages of being treated by prophylaxis
(4.1% vs. 36.8%), being treated always at home (27.8% vs. 54.3%) and following treatment recommendation as
instructed (6.2% vs. 40.5%); greater difficulty in obtaining replacement factor products (97.3% vs. 29.6%) and
visiting their treatment centre (60.9% vs. 26.4%); more annual bleeds requiring treatment (mean: 29.4/year vs.
15.4/year); lower mean self-evaluated disease control score (5.5 vs. 7.7), EQ-5D index (0.71 vs. 0.75) and visual
analogue scale (7.1 vs. 7.5) scores. Employed PWH in China had a better self-reported generic QoL than those
unemployed. Conclusions: The study suggests that there is a major need for further improvement of both medical
care and ongoing psychosocial support for PWH in China.

Keywords: China, haemophilia, medical care, psychosocial, quality of life, treatment

disease management and in preventing haemophilic

Introduction
Haemophilia is an X-linked congenital bleeding disor-
der resulting from a deficiency of coagulation factor
VIII (haemophilia A) or factor IX (haemophilia B).
This disease is characterized by bleeding into the
joints, muscles and other tissues, which can cause sev-
ere pain, joint deformity and disability. Adequate and
timely replacement treatment plays a key role in
Correspondence: Jing Sun, Department of Hematology, Nanfang
Hospital, Southern Medical University, No. 1838 North
Guangzhou Avenue, Guangzhou 510515, China.
Tel.: +86-20-6164-1612; fax: +86-20-8728-0761;
e-mail: jingsun.cn@gmail.com
Chinese HERO study group details are given in Appendix.
Accepted after revision 15 July 2016
arthropathy and improving patients’ quality of life
(QoL) [1]. The bleeding episodes and the complica-
tions can have a negative impact on daily life and
social relationships of people with haemophilia
(PWH) [2]. Studies in PWH have shown that QoL is
reduced compared with healthy controls or normative
populations. The situation worsens if the clinical inter-
vention is insufficient due to more severe bleeding,
joint impairment, pain and activity limitations [3].
Besides medical care, QoL can also be assessed and
enhanced by psychological interventions [4].
It is acknowledged that PWH in developing coun-
tries are facing more barriers in acquiring optimal
treatment and given less healthcare resources than in
developed countries [5]. Nowadays, PWH born in a
developed nation can expect to lead a nearly normal

© 2016 John Wiley & Sons Ltd 89

90 J. SUN et al.
life. However, the majority of PWH are living in
developing countries, and they may receive little to no
treatment and rare psychosocial support. In China, a
developing country, there is an estimated haemophilia
population of 80 000–120 000. Although haemophilia
care in China has achieved significant progress since
the involvement of the World Federation of Hemophi-
lia (WFH) in 1993, both medical and non-medical
intervention are far from satisfactory, and only a small
proportion of PWH were officially registered [6,7].
PWH in China were also reported to have a signifi-
cantly lower health-related QoL compared with the
general male population, and more severe arthropa-
thies were observed in PWH in China than in western
countries mainly due to lack of treatment and care
[8]. Yet there is a lack of robust studies which com-
pare the status of PWH in China to other countries.
The Haemophilia, Experiences, Results and Oppor-
tunities (HERO) initiative was initiated in 2009 to
explore the unmet psychosocial needs of PWH and
those who care for them. Before the quantitative
study, in which the data of this article were collected,
a literature review [3] and a qualitative study were
conducted to provide the foundation of knowledge.
Ten countries including China contributed with partic-
ipants in the questionnaire-based quantitative study.
This manuscript aims to present the demographics,
treatment characteristics and QoL of adult PWH in
China by comparing the results with those of the
other nine countries.
Materials and methods
Study design and instruments
This quantitative study was a multinational, web-
based (face to face in Algeria) survey comprised of
two different questionnaires (one for adult PWH and
the other for parents of children with haemophilia)
developed and distributed as described in the previous
published article [9]. The questionnaires were designed
in English and translated by a specialised agency into
local languages for each of the participating countries,
and verified by at least one other independent profes-
sional translator. In this manuscript, only the results
from adult PWH (≥18 years) with haemophilia are
included. The respondents answered more than 100
questions to reflect their disease condition, treatment,
perceptions and well-being status. In this article, the
results of Chinese adult PWH were compared with
those of PWH from other nine countries. Major differ-
ences between Chinese PWH and PWH from other
countries were observed. As a consequence, the deci-
sion was made to compare Chinese outcomes with
those from Algeria, as both countries are relatively
similar with regards to gross domestic product (GDP)
per capita and gross national income per capita, thus
Haemophilia (2017), 23, 89--97
attempting to investigate if the economic strength
could explain the difference in outcomes. The Euro-
QoL 5 dimensions (EQ-5D) [10] was incorporated
into the questionnaire to assess the day by day QoL
of PWH. The EQ-5D evaluation carried two parts: the
EQ-5D Index ( 0.11 to 1.0 scale and the healthy sub-
ject score = 1.00), and the EQ-5D visual analogue
scale (VAS, 0–100 scale, where 100 is the best imagin-
able health state and 0 is the worst). The original VAS
score on the 0–100 scale was coded as an 11-point
categorical response in analyses, and the recoded VAS
score = (the original VAS score + 10)/10, e.g. an origi-
nal VAS score of 60 was recoded to be 7.0 in this
manuscript. As not all countries within this study had
the EQ-5D validated, the US formula for EQ-5D
Index calculation [11] was adopted as a standard.
The HERO study was registered on clinicaltrials.gov
(NCT01322620), and was conducted in accordance
with the relevant national guidelines and with the
Guidelines for Good Pharmacoepidemiology [12]. The
quantitative study was conducted in 10 countries:
Algeria, Argentina, Canada, China, France, Germany,
Italy, Spain, United Kingdom and United States of
America. Questionnaires and the translations were
first reviewed and approved by local patient associa-
tions and Institutional Review Board/independent
ethics committees. In China, ethics approval was not
required for this type of study, and the study was
approved by the Patient Association. Any survey-
related activities on each individual were not com-
menced until the informed consent was provided.
Patients
Adult PWH (hereafter referred to as ‘PWH’) in this
study were defined as males aged ≥18 years with hae-
mophilia A or B (with or without inhibitors). Respon-
dents were required to be currently receiving
treatment with replacement factor concentrate or a
bypassing agent, or had experienced at least one spon-
taneous bleed into one or more joints within the last
12 months. Participants had to have access to the
internet or be available to attend a face-to-face inter-
view (Algeria only). Only one eligible response was
allowed per household.
The study intended to enrol a total of 600 PWH
and the goal was an equal allocation to each country
[9]. The allocation was adjusted later as some coun-
tries with smaller haemophilia populations encoun-
tered difficulties in achieving the target. Additional
PWH were recruited from China and the US to com-
plete enrolment. Depending on the situation in each
participating country, eligible individuals were identi-
fied by one of three possible routes: membership
records held by National Haemophilia Organisations
(NHOs) or those linked electronically to those organi-
zations; patient records held by commercial
© 2016 John Wiley & Sons Ltd
 RESULTS OF THE CHINESE COHORT IN THE HERO STUDY 91

haemophilia health services providers; or patient
records held by haemophilia treatment centres
(HTCs). In China, the NHO source was chosen. Sur-
vey links were posted on the website of Hemophilia
Home of China and the portal was closed when the
number of respondent achieved the target number.
Statistical analysis
In order to conduct the descriptive comparative analy-
ses, countries were separated into two groups, of
which one included only China and the other con-
sisted of the remaining nine countries in the study.
reported Haemophilia A (HA), and percentage of
patients with inhibitors (PWI) was lower in China
(3.6%) than in other countries (15.4%) (Table 1).
PWH with no formal education rated 8.2% in China
and 0.5% in other countries. Overall, 40.0% of PWH
in China (vs. 60.0% in other countries) were married
or in a long-term relationship (Table 1). During this
survey, 45.6% of PWH in China (vs. 63.1% in other
countries) were currently employed (Table 1), and a
higher percentage of PWH in China than in other
Table 1. Demographics and current status of adult people with haemophi-
lia from China and other countries.

For some variables, China was further compared with China Other countries P value
Algeria separately. In addition, PWH were subgrouped N 110 565
by disease subtype or treatment regimen to perform Current age, years ≤0.0001
comparisons. Monte Carlo estimation of Pearson’s N 110 565
Mean (SD) 30.4 (7.8) 38.6 (12.4)
Chi-squared test or regular chi-square, if applicable, Median 29 37
was used to analyse two independent binary variables. Range 19–52 18–86
Pooled t-test (for equal variances) or Scattertwaite Diagnosis age, n (%*) 0.1172
≤2 years 59 (56.7) 350 (65.3)
t-test (for unequal variances) was used to analyse two >2 years 45 (43.3) 186 (34.7)
independent continuous variables. All percentages Haemophilia type, n (%*) 0.0042
were calculated with the number of respondents who Haemophilia A 90 (81.8) 408 (72.2)
completed the corresponding question or provided Haemophilia B 16 (14.5) 70 (12.4)
Haemophilia A or 4 (3.6) 87 (15.4)
valuable data as denominator. B with inhibitor
Exploratory analyses of potential factors influencing Patients experienced spontaneous bleed during past 12 months, n (%*)
EQ-5D Index/VAS score of PWH during the study Haemophilia A 86 (95.6) 291 (71.3) ≤0.0001
Haemophilia B 16 (100.0) 42 (60.0) 0.0098
were performed using ANOVA models. Age, diagnosis
Haemophilia A or 4 (100.0) 81 (93.1) 1.0000
age, treatment regimen, usage of replacement factor B with inhibitor
concentrates, bleed frequency were included as fixed Bleeds requiring treatment in the last year, times 0.0001
factors in the model. For the following variables: N 91 435
Mean (SD) 29.4 (32.5) 15.4 (31.1)
employment, work load, marriage status, psychologi- Median 20.0 6.0
cal treatment, responsible person, treatment location, Range 1–200 0–365
compliance to medical orders, visit to HTC, univariate Education, n (%*) ≤0.0001
analyses were performed first to examine their rela- No formal education 9 (8.2) 3 (0.5)
Still in full time 7 (6.4) 63 (11.2)
tionship with the EQ-5D index/VAS score, and only education
those with a P value <0.10 were incorporated into the Completed formal 89 (80.9) 485 (85.8)
multivariate ANOVA model. full education
Do not know/decline 5 (4.5) 14 (2.5)
to answer
Employment status, n (%*) 0.0014
Results Employed 47 (45.6) 317 (63.1)
Unemployed 56 (54.4) 185 (36.9)
Demographics Marriage status, n (%*) 0.0001
Married/in a long-term 44 (40.0) 339 (60.0)
Respondents were recruited from 3 June 2011 to 29 relationship
February 2012. A total of 675 adult PWH completed Other (single, widower, 66 (60.0) 226 (40.0)
decline to answer)
the questionnaire globally. Of the 110 PWH from
Haemophilia related concomitant disease, n (%)
China, 31.8% were living in large cities, 26.4% in Arthritis 84 (76.4) 241 (42.8) ≤0.0001
other urban areas, 13.6% in suburban areas and Anaemia 19 (17.3) 43 (7.6) 0.0023
28.2% in rural areas, showing a similar distribution Anxiety 18 (16.4) 79 (14.0) 0.5515
Chronic pain 34 (30.9) 221 (39.3) 0.1066
to the other nine countries (38.1%, 24.6%, 17.7%, Obesity 16 (14.5) 19 (3.4) ≤0.0001
19.6%; P = 0.1603). PWH from China were generally Depression 15 (13.6) 73 (12.9) 0.8761
younger than those from the other nine countries Stress 34 (30.9) 72 (12.8) ≤0.0001
(Table 1). Median diagnosis age was 2.0 years in HCV 24 (21.8) 265 (47.2) ≤0.0001
HIV 4 (3.6) 117 (20.9) ≤0.0001
China and 1.0 year in other countries. Percentage of
HCV, hepatitis C virus; HIV, human immunodeficiency virus; SD, stan-
PWH diagnosed ≤2 years old was 56.7% in China dard deviation.
and 65.3% in other countries (Table 1). The majority *Percentage of respondents who answered the corresponding question or
of PWH from both China and the other nine countries provided valuable data.

© 2016 John Wiley & Sons Ltd Haemophilia (2017), 23, 89--97
92 J. SUN et al.

countries were unemployed with short-term disability Visiting the HTC was rated as ‘very difficult’ by
(5.8% vs. 0.6%, P = 0.0011) or long-term disability 23.6% (vs. 5.7% in other countries, P ≤ 0.0001) and
(29.1% vs. 9.4%, P ≤ 0.0001). as ‘quite difficult’ by 37.3% (vs. 20.7%, P = 0.0002)
of PWH in China. The reasons why it was difficult to
visit the HTC/clinics were listed in Fig. 1d.
Treatment and access to care
As presented in Table 2, replacement factor concen-
Disease control
trates [factor VIII for HA and factor IX for haemophi-
lia B (HB)] infusion was the dominant treatment for PWH in China with HA or HB reported a higher
PWH without inhibitors both in China and other percentage of experiencing spontaneous bleeds in the
countries. But compared to other countries, in China past 12 months, and more bleeds requiring treatment
more PWH received other remedial treatments. Regu- in the last year than PWH from other countries
lar prophylaxis treatment was adopted only by 4.1% (Table 1). Haemophilia related arthritis, anaemia,
of PWH in China, and by 36.8% of PWH in other obesity and stress were reported to be more common
countries. Most PWH in China were treated only after in PWH from China than other countries; haemophi-
the onset of the bleeding episode (on-demand). More lia related HCV and HIV, however, were reported
than two-thirds of PWH in China reported to be trea- less in China. Although no differences were observed
ted always/mostly at home. However, the percentage between China and other countries, quite a relevant
of PWH treated always at home was lower in China proportion of PWH in China had experienced hae-
(27.8%) than other countries (54.3%, P ≤ 0.0001) mophilia related anxiety, depression and chronic pain
(Fig. 1a). In China, 28.2% of PWH reported that ‘I (Table 1). On the 10-point scale for disease control
have the main responsibility for my haemophilia care’, self-evaluation, the mean (SD) score was 5.5 (2.2)
and the corresponding percentage was as high as for PWH in China and 7.7 (1.8) for others
86.2% in other countries (P ≤ 0.0001). Only 7.3% of (P ≤ 0.0001).
PWH in China received psychological treatment in the
past 5 years (25.3% in other countries, P = 0.0002).
Comparisons between China and Algeria
Only 6.2% of PWH in China were using replace-
ment therapy exactly as instructed, far lower than the Among the other nine countries, Algeria was the only
corresponding percentage 40.5% in other countries one close to China in GDP per capita and gross
(P ≤ 0.0001). Besides, 48.5% in China reported to be national income per capita in 2011 and 2012 [13].
treated with clotting factor concentrates a little less or The distribution of different treatment regimen among
a lot less than instructed (Fig. 1b). Overall, 97.3% of the 50 Algerian PWH was similar to Chinese PWH
PWH in China reported difficulties in obtaining (on demand 78.0% vs. 72.2%, prophylaxis 0.0% vs.
replacement factor products in the past 5 years, higher 4.1%, on-demand + short-term prophylaxis 22.0% vs.
than 29.6% in other countries (P ≤ 0.0001). The 21.6%, P = 0.3903). There were 84.0% of Algerian
ranking of problems in obtaining replacement factor PWH (vs. 97.3% in China, P = 0.0043) reported diffi-
products reported in China was presented in Fig. 1c. culties in obtaining replacement factor products in the
last 5 years mainly due to supply issues. Nevertheless,
46.0% of PWH in Algeria (vs. 22.7% in China,
Table 2. Summary of treatment agents and strategy. P = 0.0054) could infuse replacement factor products
more than or exactly as prescribed. Compared with
Other
China countries P values China, a lower percentage of PWH without inhibitors
Treatment agents, n (%*)
from Algeria experienced spontaneous bleeds during
Haemophilia A the last year (74.5% vs. 96.2%, P ≤ 0.0001), and
Factor VIII 83 (92.2) 404 (99.0) 0.0008 PWH in Algeria reported lower annual bleeds requir-
Cryoprecipitate 58 (64.4) 45 (11.0) ≤0.0001 ing treatment [mean (SD) 12.5 (9.8) vs. 29.4 (32.5) in
Fresh frozen plasma 56 (62.2) 23 (5.6) ≤0.0001
Desmopressin 11 (12.2) 22 (5.4) 0.0233 China, P = 0.0012]. Haemophilia related arthritis was
Haemophilia B reported in only 10.0% of PWH in Algeria (vs.
Factor IX 13 (81.3) 69 (98.6) 0.0192 76.4% in China, P ≤ 0.0001). The mean (SD) score of
Fresh frozen plasma 10 (62.5) 12 (17.1) 0.0006
Haemophilia with inhibitor
disease control self-evaluation for them was 6.4 (1.9)
Specific products 1 (25.0) 78 (89.7) 0.0002 [vs. 5.5 (2.2) for China, P = 0.0191].
Treatment strategy, n (%*) ≤0.0001
On-demand 70 (72.2) 219 (39.7) ≤0.0001
Regular prophylaxis 4 (4.1) 203 (36.8) ≤0.0001 Quality of life and well-being
On demand + 21 (21.6) 125 (22.7) 0.8953
short-term prophylaxis Compared with other countries, PWH in China
*Percentage of respondents who answered the corresponding question or reported a slightly lower overall mean EQ-5D index
provided valuable data. score (0.71 vs. 0.75, P = 0.0696) (vs. 0.70 in Algeria,

Haemophilia (2017), 23, 89--97 © 2016 John Wiley & Sons Ltd
 RESULTS OF THE CHINESE COHORT IN THE HERO STUDY 93

(a) 27.8 (b) 7.2

Always at home** A lot more than instructed China
54.3 4.9
n = 97
9.3 Other countries
Mostly at home but sometimes 40.2 A little more than instructed
6.0 n = 551
at the clinic/hospital ** 22.9
6.2
Exactly as instructed**
Mostly at the clinic/hospital 16.5 40.5
but sometimes at home** 7.8
18.6
A little less than instructed
18.7
First dose at home and if needed 3.1 China
further doses at the clinic/hospital 2.4 n = 97 29.9
A lot less than instructed**
Other countries 6.5
12.4 n = 551
Always at the clinic/hospital Sometimes more, sometimes 24.7
12.0
less 16.5
0.0 10.0 20.0 30.0 40.0 50.0 60.0 0.0 20.0 40.0 60.0
Percentage of respondents (%) Percentage of respondents (%)

(c) (d)
86.0 74.6
Could not personally afford it** 12.6 It is a long way to travel
75.2
67.3 It takes a long time to get to 55.2
Difficulty with health insurance** 32.3 the centre/clinic 51.0
58.9 37.3
Lack of supply at the hospital* 44.3 The travel is expensive
38.3
Lack of supply throughout the 46.7 Sometimes there is no-one 16.4
country** 29.3
China available to take me 23.5
China
31.8 n = 107 The centre/clinic has limited n = 67
Unpredictability of supply 28.7
16.4
Other countries opening hours 21.5 Other countries
17.8 n = 167 n = 149
Physician reluctant to prescribe it 18.0
I am unable to take time off to 16.4
go there 22.1
0.0 20.0 40.0 60.0 80.0 100.0
0.0 20.0 40.0 60.0 80.0
Percentage of respondents (%) Percentage of respondents (%)

Fig. 1. Comparisons between adult people with haemophilia from China and other countries of (a) the percentage accepting infusion at home or at clinic/
hospital, (b) the percentage infusing replacement factor product/factor concentrate dosing more than, exactly as or less than instructed, (c) the percentage
meeting difficulties in obtaining replacement factor products, and (d) the percentage reporting varieties of difficulties in visiting the haemophilia treatment
centre/clinic. **P < 0.01, *P < 0.05 for China vs. Other countries.

P = 0.8684), and a lower mean score on the EQ-5D factors influencing EQ-5D score of PWH in China;
VAS (7.1 vs. 7.5, P = 0.0435) (vs. 7.4 in Algeria, employment was found to be associated with higher
P = 0.2635). The mean scores for all subgroups by EQ-5D index (the employed 0.75 vs. the unemployed
disease were slightly lower in China. When divided 0.66, P = 0.0435) but not with EQ-5D VAS (7.5 vs.
into subgroups by treatment regimen, PWH in China 6.8, P = 0.1639) (Fig. 2a,b).
treated with on-demand regimen reported a lower Correspondingly, among all topics in this survey,
mean score than those in other countries (index ‘education, employment and job issues’ was chosen by
score: 0.70 vs. 0.77, P = 0.0067; VAS score: 6.8 vs. the highest percentage of PWH (47.3%) in China as
7.5, P = 0.0089) (Table 3). Issues with mobility, self- being the most important one where improvements
care, usual activities and anxiety/depression were need to be made. Whereas, 68.2% of PWH in China
noted in higher percentages in China than those admitted that haemophilia had a very large negative
reported in other countries (Table 3). Although pain/ impact on their working life, while only 2.7% consid-
discomfort were reported by a lower percentage of ered haemophilia to have no negative impact on their
PWH in China than other countries by EQ-5D evalu- working life.
ation (Table 3), a greater percentage in China
thought that pain interfered ‘extremely’ (13.6% vs.
Discussion
7.4%, P = 0.0323) or ‘quite a lot’ (32.7% vs.
14.9%, P ≤ 0.0001) with their daily life in the past The HERO study is one of the largest multinational
4 weeks. studies focusing on psychosocial issues in haemophilia,
and provides new insights into the self-reported out-
comes of PWH from both developed and developing
Potential predictors of quality of life
countries. This study indicates that the lives of PWH
With the univariate analyses, only employment status are widely varied between countries [2,14]. This arti-
was incorporated into the multivariate analysis. In the cle compares patient perceptions about treatment, dis-
multivariate ANOVA model, age, diagnosis age, treat- ease control and self-reported generic QoL of adult
ment regimen, replacement factor usage and bleed fre- PWH in China with the other nine participating coun-
quency were not identified as statistically significant tries in the study. The data show that adult PWH in

© 2016 John Wiley & Sons Ltd Haemophilia (2017), 23, 89--97
94 J. SUN et al.

Table 3. EQ-5D index and VAS score and problems reported in EQ-5D China face more difficulties and barriers in obtaining
questions. adequate replacement factor products and medical
Other support, resulting in more issues in disease control
China countries P value and QoL management.
EQ-5D index score, mean (SD) People with haemophilia from China reported that
Overall 0.71 (0.20) 0.75 (0.19) 0.0696
28.2% of them were living in rural area. The overall
By disease
Haemophilia A 0.72 (0.20) 0.75 (0.19) 0.1884 percentage of rural residents in the total population of
Haemophilia B 0.68 (0.19) 0.76 (0.20) 0.1459 China was 50.3% in 2011 and 48.7% in 2012 [15].
Haemophilia with inhibitor 0.58 (0.19) 0.71 (0.17) 0.1305 This selection bias is mainly ascribed to the fact that
By treatment
On-demand 0.70 (0.19) 0.77 (0.19) 0.0067
this study was web-based in China, because the per-
Regular prophylaxis 0.87 (0.09) 0.74 (0.18) 0.1785 centage of rural internet users over the overall internet
On demand + 0.73 (0.19) 0.72 (0.20) 0.7676 users in China, which was 26.5% in 2011 and 27.6%
short-term prophylaxis
in 2012 [15], are comparable with the percentage of
Any reported problem*, n (%)
Mobility 79 (71.8) 319 (56.5) 0.0027 rural residents in this study. Meanwhile, the patients
Self-care 30 (27.3) 106 (18.8) 0.0417 could only get to the survey through the website of
Usual activity 64 (58.2) 251 (44.4) 0.0081 Hemophilia Home of China; those who were closely
Pain/discomfort 72 (65.5) 431 (76.3) 0.0171
Anxiety/depression 66 (60.0) 247 (43.7) 0.0017
engaged in the activities of this organization had
EQ-5D VAS score, mean (SD) higher chance to participate in this survey. As the
Overall 7.1 (2.1) 7.5 (1.9) 0.0435 PWH who have internet access and behave actively in
By disease social work probably have higher income and/or
Haemophilia A 7.2 (2.1) 7.6 (1.9) 0.1120
Haemophilia B 6.9 (1.6) 7.4 (2.1) 0.4544 access to better care than the overall population of
Haemophilia with inhibitor 4.8 (2.1) 7.2 (1.6) 0.0047 PWH, the results presented in this article are probably
By treatment better than the reality.
On-demand 6.8 (2.0) 7.5 (1.9) 0.0089
Adult PWH in China were generally younger than
Regular prophylaxis 8.8 (1.7) 7.5 (2.0) 0.2068
On demand + 7.7 (2.2) 7.5 (1.7) 0.5576 those from other countries. One report pointed out
short-term prophylaxis that a higher proportion of children with haemophi-
EQ-5D, Euro-QoL 5 dimensions; SD, standard deviation; VAS, visual lia compared with adults was anticipated in countries
analogue scale. with lower economic capacity [16]. The same situa-
*The EQ-5D questionnaire consisted of five questions with three answer
tion was identified in China years ago [7]. Younger
choices: ‘no impact’, ‘some impact’ and ‘severe impact’. ‘Any reported
problems’ include ‘some impact’ and ‘severe impact’. adult respondents from China could be interpreted as
a long-term effect of the late startup of haemophilia

(a) (b)
Factors N Estimates Factors N Estimates
Age group Age group
≤ 30 years 63 ≤ 30 years 63
31– 40 years 33 31– 40 years 33
≥ 41 years 14 ≥ 41 years 14
Diagnosis age Diagnosis age
≤ 2 years 59 ≤ 2 years 59
>2 years 45 > 2 years 45
Treatment regimen Treatment regimen
OD 70 OD 70
PPX 4 PPX 4
OD+S 21 OD+S 21
Usage of factor Usage of factor
More than 16 More than 16
Exactly as 6 Exactly as 6
Less than 47 Less than 47
Other 28 Other 28
Bleed frequency Bleed frequency
Mild 37 Mild 37
Moderate 16 Moderate 16
Severe 38 Severe 38
Employment* Employment
Employed 47 Employed 47
Unemployed 56 Unemployed 56

0.0 0.2 0.4 0.6 0.8 1.0 1.2 0 2 4 6 8 10 12 14

Mean EQ-5D index score Mean EQ-5D VAS score

Fig. 2. Potential factors influencing quality of life of adult people with haemophilia in China. In (a) forest plot of potential predictors of Euro-QoL 5 dimen-
sions (EQ-5D) index score and (b) forest plot of potential predictors of EQ-5D visual analogue scale (VAS) score. Variables including age, diagnosis age, treat-
ment regimen, usage of replacement factor concentrates, bleed frequency were mandatory in the ANOVA model. For the estimates, dots in the middle represent
Least Squares Means, and bars represent 95% confidence intervals. The ‘treatment regimen’ was classified as: OD, on demand; OD + S, on demand with situ-
ational prophylaxis; PPX, prophylaxis. The ‘bleed frequency’ was presented as mild ‘≤10 times per year’, moderate ‘>10 and ≤25 times per year’ and severe
‘>25 times per year’. The ‘usage of factor’ was classified by comparing with the prescribed dosing. *The effect of the factor is statistically significant,
P < 0.05.

Haemophilia (2017), 23, 89--97 © 2016 John Wiley & Sons Ltd
 RESULTS OF THE CHINESE COHORT IN THE HERO STUDY
management. A median diagnosis age of 2 years for
PWH in China is considered reasonable, albeit mod-
erately delayed compared with other countries. A far
lower incidence (3.6%) of inhibitor development
among PWH than other countries was reported in
China in the HERO study. This rate aligns with the
results of a cross-sectional study [17] in 1435 Chi-
nese patients with HA, in which the overall preva-
lence of inhibitors was 3.9%. This low incidence
might be partially ascribed to the fact that most Chi-
nese PWH experienced limited exposure days to clot-
ting factor concentrates and have favourable
genotypes [17]. Also, the lack of regular inhibitor
monitoring could have led to underestimation of the
inhibitors rate.
The results of treatment and access to care agree
with the status of PWH in China. Even for those liv-
ing in big cities, only approximately 1/3 of them
receive adequate replacement treatment after bleeding
[18], and the annual per capita consumption of coagu-
lation factor in China was reported to be only 0.03 IU
in 2008 [19]. Besides, the data reflect that other medi-
cal resources also could not cover the basic needs in
China, and more education and training on self-man-
agement should be delivered to PWH. Hence it was
not surprising that PWH in China reported worse dis-
ease control than those from the other nine countries.
To improve the situation in China, a low-dose sec-
ondary prophylaxis strategy is now on trial and has
produced a beneficial effect without increasing factors
consumption in children and adolescents with severe/
moderate HA [20].
Separately, we compared China to Algeria to confirm
that if economic level determines the healthcare of
PWH. Like China, a high percentage of PWH in Algeria
reported difficulties in obtaining replacement factor
products. But PWH in Algeria reported better compli-
ance to the prescription of coagulation factors, less
bleeds and haemophilic arthritis, and better self-evalu-
ated disease control score than those in China. Superior
to most countries with the similar level of gross national
income per capita, the mean per capita factor VIII and
IX use in 2013 for Algeria were 1.603 IU and 0.384 IU
[5]. The corresponding data of China was unavailable
in 2013, but is estimated to be much less than Algeria
according to relevant data [19,21]. This comparison
implies that factors other than economic condition, e.g.
medical insurance system and drug supply, could
impact on the haemophilia management of PWH at
national level.
The QoL of PWH in China has been proven to be
worse than in the general male population of China
[8]. The EQ-5D, which is one of the most frequently
used generic QoL instruments in adults PWH [22],
was used to reflect the self-reported QoL of PWH in
the HERO study. The results suggested that PWH in
China reported worse generic QoL compared with
© 2016 John Wiley & Sons Ltd
95
those from other countries. When divided by treat-
ment regimen, PWH in China treated with on-demand
regimen reported lower EQ-5D index and VAS
scores than those from other countries. PWH treated
on-demand usually relied more on support from gov-
ernment and society compared to those who could
afford prophylaxis treatment, and would be represen-
tative in China. In regard to each individual item of
EQ-5D index, PWH in China reported more issues
with mobility, self-care, usual activities and anxiety/
depression than those in other countries. The fact that
only 7.3% of PWH in China received psychological
treatment in the past 5 years indicates that the psy-
chosocial issues of PWH in China might need more
attention.
Employed PWH in China had a better self-reported
EQ-5D score than those unemployed. A job helps the
patient solve financial issues, gain better medical insur-
ance, build self-esteem and better relationships, conse-
quently allow them better access to coagulation factor
products and have fewer psychosocial problems. Some
other factors which were predicted to be closely associ-
ated with QoL [23] did not show influences on EQ-5D
score of PWH in China in this study. It should be
understood that to assess the determinants of QoL is
rather complicated, as QoL is culture-bound and
expectations of PWH and social environment vary
widely among regions. In addition, the results of these
ad hoc exploratory analyses should be interpreted with
caution.
Some overall limitations of the HERO study were
described by Forsyth et al. [9]. It is necessary to men-
tion that an on-line survey has its natural limitations in
sample selection, and in this article, there is a potential
bias towards PWH with higher income and accepting
more support and better care than the overall popula-
tion of PWH in China. And the HERO study was not
designed for pharmacoeconomic assessment and com-
parisons of outcomes among countries; a full phar-
maco-economic analysis was beyond the scope of this
paper, and would have required including GDP and
economic indexes for the countries involved in the
comparison. All data collected in this questionnaire-
based survey were self-reported independently by
PWH/parents, without any formal check of medical
records or direct patient evaluation. Hence some data,
e.g. the severity of haemophilia related disease may be
different than they would be if clinically assessed.
Despite medical terminologies were at the best avoided
to minimize misunderstanding, and the options for
each question were designed to make the intention as
clear as possible, participants from different countries
may have interpreted some expressions, e.g. haemophi-
lia care, in different ways. Besides, cross-cultural
equivalence could not be ensured completely while
translating the documents into local languages. In
addition, the EQ-5D index score was arbitrarily
Haemophilia (2017), 23, 89--97
96 J. SUN et al.

calculated according to US population data due to the of both medical care and ongoing psychosocial
absence of population data from China and some other support for PWH in China.
countries; this may impact the validity of the index
score.
Acknowledgements

Conclusions
The study highlights that the adult PWH in China
reported receiving poorer access to elements of hae-
mophilia care including clotting factors and healthcare
resources, worse disease control in regard to more
bleeds and haemophilia related concomitant diseases,
and more issues by the EQ-5D questionnaire with a
reflection of worse generic QoL than those from the
other nine countries. Employment was positively asso-
ciated with better generic QoL of adult PWH in
China, but negatively impacted by the disease in gen-
eral. Overall, this study provides new comparative
data suggesting a major need for further improvement
The authors would like to acknowledge the assistance of Kantar Health
(Surrey, UK) who managed the study and Hemophilia Home of China
who recruited participants in China under the direction of Novo Nordisk
and the HERO International Advisory Board (IAB) and with support
from Novo Nordisk A/S. The authors also acknowledge Maria D€ uring of
BioStata Aps for statistical analyses and Limin Zou of Novo Nordisk
(China) Pharmaceuticals Co., Ltd for writing assistance.
Disclosure
Professor Alfonso Iorio is a member of the HERO steering group, and
Chair of the HERO research grant committee. He has received research
funds and consultancy fees via McMaster from Novo Nordisk. The other
authors stated that they had no interests which might be perceived as pos-
ing a conflict or bias. No authors received compensation for any activity
related to the present manuscript.

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(Haematologist, Institute of Hematology and Blood Diseases Hospital,

Appendix
The members of HERO National Advisory Board (NAB) in China include
Professor Jing Sun (Haematologist, Nanfang Hospital, Southern Medical
University, Guangzhou), Professor Yongqiang Zhao (Haematologist, Pek-
ing Union Medical College Hospital, Beijing), Professor Renchi Yang
CAMS & PUMC, Tianjin), Professor Xuefeng Wang (Haematologist, Rui-
jin Hospital, Shanghai Jiao Tong University School of Medicine, Shang-
hai), Professor Jingsheng Wu (Haematologist, Anhui Province Hospital,
Hefei), Professor Xinsheng Zhang (Haematologist, Blood Center of Shan-
dong Province, Jinan), Bin Teng (Nurse, Blood Center of Shandong

Haemophilia (2017), 23, 89--97 © 2016 John Wiley & Sons Ltd
 RESULTS OF THE CHINESE COHORT IN THE HERO STUDY 97

Province, Jinan), Kuixing Li (Nurse, Peking Union Medical College Zikai Huang (PWH, Hemophilia Home of China, Guangzhou). Professor
Hospital, Beijing), Tao Guan (PWH, Hemophilia Home of China, Alfonso Iorio (Haematologist, McMaster University, Ontario, Cananda)
Beijing), Yuguang Chu (PWH, Hemophilia Home of China, Beijing) and is member of the HERO IAB.

© 2016 John Wiley & Sons Ltd Haemophilia (2017), 23, 89--97
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