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Authors’ Reply: “The Need for a Bleed Type–Specific Annual Bleeding Rate in Hemophilia Studies”

Authors’ Reply: “The Need for a Bleed Type–Specific Annual Bleeding Rate in Hemophilia Studies”

Authors’ Reply: “The Need for a Bleed Type–Specific Annual Bleeding Rate in Hemophilia Studies”

Letter to the Editor

1Centre for Health Management and Policy Research, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan, China

2NHC Key Laboratory of Health Economics and Policy Research, Shandong University, Jinan, China

3Centre for Health Preference Research, Shandong University, Jinan, China

4School of Public Health, Fudan University, Shanghai, China

5NHC Key Laboratory of Health Technology Assessment, Fudan University, Shanghai, China

6Macquarie University Centre for the Health Economy, Macquarie Business School and Australian Institute of Health Innovation, Macquarie University, Sydney, Australia

7Shandong Hemophilia Treatment Center, Shandong Blood Center, Jinan, China

Corresponding Author:

Shunping Li, PhD

Centre for Health Management and Policy Research

School of Public Health, Cheeloo College of Medicine

Shandong University

44 Wenhuaxi Road

Jinan, 250014


Phone: 86 13188934998

Fax:86 053188380161


We appreciate Huang’s [1] thoughtful consideration of our article [2]. Their suggestion to refine the attribute of “annual bleeding rate” in our discrete choice experiment (DCE) by distinguishing between spontaneous versus injury-induced bleeding, and further categorizing bleeds as joint or mild, is acknowledged with appreciation. In the formulation of our DCE questionnaire, considerable attention was devoted to addressing this aspect. However, the integration of a comprehensive spectrum of bleed types into the DCE was met with challenges, particularly within the context of the current hemophilia A scenario in China and the specific focus of our investigation.

Our study focused on adult patients with hemophilia. With the notable increase in the adoption of low-dose prophylactic treatment and advancements in diagnostic and therapeutic capabilities, there has been a significant rise in pediatric patients benefiting from prophylaxis with coagulation factor [3]. However, it is important to highlight that the current percentage of adult patients undergoing prophylaxis with coagulation factor remains relatively low [4]. In our DCE, the number of annual bleeds attribute was operationalized as spontaneous bleeding events. The decision not to delve into further details of bleeding types in the DCE was primarily influenced by the reasons listed below.

First, patients have limited ability to assess their own bleeding, and misrecording or missing records often occur [5]. Unlike during a clinical trial, it is challenging for them to obtain detailed descriptions of all types of bleeds per year via questionnaire. Second, while adult patients with hemophilia in developed countries engage in physical activities at rates comparable to the general population, the situation in China is markedly different [6]. With age, patients often exhibit varying degrees of joint damage or deformities, particularly in the knees, ankles, and elbows, resulting in a generally reduced activity level [7]. Consequently, the incidence of activity- or injury-induced bleeding is relatively low. Moreover, a significant portion of adult patients in China may already be experiencing joint deformities or at a stage requiring joint replacement [4], rendering the notion of “target joints” less relevant.

In the DCE context, it is crucial that the chosen attribute and levels align with practical conditions, ensuring ease of investigation and data collection from the participants. Therefore, for this study, we selected the number of annual bleeds (spontaneous bleeding) as the attribute. Our DCE design, particularly in determining attributes and levels, entailed multiple rounds of consultations and interviews with clinical experts, including hemophilia specialists from the Shandong Hemophilia Treatment Center (the core center of the Hemophilia Treatment Center Collaborative Network of China and the World Federation of Hemophilia). These consultations were instrumental in providing valuable professional guidance.

We believe that these additional details provide a comprehensive background of our DCE design. Furthermore, our aspiration is to enhance access to prophylaxis with coagulation factor for adult patients in China, accompanied by a commitment to maintain precise bleeding records. This commitment would not only benefit our study but also pave the way for future research to refine the measurement of annual bleeding frequency by incorporating additional indicators like bleeding types.

Conflicts of Interest

None declared.

  1. Huang K. The Need for a Bleed Type–Specific Annual Bleeding Rate in Hemophilia Studies. JMIR Public Health Surveill. 2024. [CrossRef]
  2. Wang L, Liu S, Jiang S, Li C, Lu L, Fang Y, et al. Quantifying benefit-risk trade-offs toward prophylactic treatment among adult patients with hemophilia A in China: discrete choice experiment study. JMIR Public Health Surveill. Jul 26, 2023;9:e45747. [FREE Full text] [CrossRef] [Medline]
  3. Wu R, Luke KH, Poon MC, Wu X, Zhang N, Zhao L, et al. Low dose secondary prophylaxis reduces joint bleeding in severe and moderate haemophilic children: a pilot study in China. Haemophilia. Jan 29, 2011;17(1):70-74. [CrossRef] [Medline]
  4. Song X, Zhong J, Xue F, Chen L, Li H, Yuan D, et al. An overview of patients with haemophilia A in China: epidemiology, disease severity and treatment strategies. Haemophilia. Jan 27, 2021;27(1):e51-e59. [CrossRef] [Medline]
  5. Keipert C, Müller-Olling M, Gauly F, Arras-Reiter C, Hilger A. Annual bleeding rates: pitfalls of clinical trial outcomes in hemophilia patients. Clin Transl Sci. Nov 30, 2020;13(6):1127-1136. [FREE Full text] [CrossRef] [Medline]
  6. Sun J, Zhao Y, Yang R, Guan T, Iorio A, Chinese HERO study group. The demographics, treatment characteristics and quality of life of adult people with haemophilia in China - results from the HERO study. Haemophilia. Jan 2017;23(1):89-97. [CrossRef] [Medline]
  7. Liu S, Zhou R, Jin Z, Wu M, Zhang P. Age-related severity and distribution of haemophilic arthropathy of the knee, ankle and elbow among Chinese patients with haemophilia. Haemophilia. Jan 2020;26(1):129-135. [CrossRef] [Medline]

DCE: discrete choice experiment

Edited by T Leung; This is a non–peer-reviewed article. submitted 20.11.23; accepted 29.12.23; published 13.03.24.


©Limin Wang, Shimeng Liu, Shan Jiang, Chaofan Li, Liyong Lu, Yunhai Fang, Shunping Li. Originally published in JMIR Public Health and Surveillance (, 13.03.2024.

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