Meier Niklaus, Ammann Daniel, Pletscher Mark, Probst Jano, Schwenkglenks Matthias
Institute of Pharmaceutical Medicine (ECPM), University of Basel, Basel, Switzerland.
Institute of Health Economics and Health Policy, Bern University of Applied Sciences, Bern, Switzerland.
J Med Econ. 2025 Dec;28(1):89-104. doi: 10.1080/13696998.2024.2444157. Epub 2025 Jan 3.
Haemophilia is a rare genetic disease that hinders blood clotting. We aimed to review model-based cost-effectiveness analyses (CEAs) of haemophilia treatments, describe the sources of clinical evidence used by these CEAs, summarize the reported cost-effectiveness of different treatment strategies, and assess the quality and risk of bias.
We conducted a systematic literature review of model-based CEAs of haemophilia treatments by searching databases, the Tufts Medical Center CEA registry, and grey literature. We summarized and qualitatively synthesized the approaches and results of the included CEAs, without a meta-analysis due the diversity of the studies.
32 eligible studies were performed in 12 countries and reported 53 pairwise comparisons. Most studies analysed patients with haemophilia A rather than haemophilia B. Comparisons of prophylactic versus on-demand treatment indicated that prophylaxis may not be cost-effective, but there was no clear consensus. Emicizumab was generally cost-effective compared with clotting factor treatments and was always dominant for patients with inhibitors. Immune tolerance induction following a Malmö protocol was found to be cost-effective compared to bypassing agents, while there was no consensus for the other protocols. Gene therapies as well as treatment with extended half-life coagulation factors were always cost-effective over their comparators. Studies were highly heterogenous regarding their time horizons, model structures, the inclusion of bleeding-related mortality and quality-of-life impacts. This heterogeneity limited the comparability of the studies. 19 of the 32 included studies received industry funding, which may have biased their results.
It was not possible to perform a quantitative synthesis of the results due to the heterogeneity of the underlying studies.
Differences in results between previous CEAs may have been driven by heterogeneity in modelling approaches, clinical input data, and potential funding biases. A more consistent evidence base and modelling approach would enhance the comparability between CEAs.
血友病是一种罕见的遗传性疾病，会阻碍血液凝固。我们旨在回顾基于模型的血友病治疗成本效益分析（CEA），描述这些CEA所使用的临床证据来源，总结不同治疗策略报告的成本效益，并评估质量和偏倚风险。
我们通过搜索数据库、塔夫茨医学中心CEA登记处和灰色文献，对基于模型的血友病治疗CEA进行了系统的文献综述。我们总结并定性综合了纳入的CEA的方法和结果，由于研究的多样性，未进行荟萃分析。
在12个国家进行了32项符合条件的研究，报告了53对比较。大多数研究分析的是A型血友病患者而非B型血友病患者。预防性治疗与按需治疗的比较表明，预防性治疗可能不具有成本效益，但没有明确的共识。与凝血因子治疗相比，艾美赛珠单抗总体上具有成本效益，并且对于有抑制剂的患者始终占主导地位。与旁路制剂相比，遵循马尔默方案的免疫耐受诱导被发现具有成本效益，而其他方案则没有共识。基因疗法以及延长半衰期凝血因子的治疗始终比其对照疗法更具成本效益。研究在时间范围、模型结构、出血相关死亡率的纳入以及生活质量影响方面存在高度异质性。这种异质性限制了研究的可比性。32项纳入研究中有19项获得了行业资助，这可能使其结果产生偏倚。
由于基础研究的异质性，无法对结果进行定量综合。
先前CEA结果的差异可能是由建模方法、临床输入数据和潜在资助偏倚的异质性驱动的。更一致的证据基础和建模方法将提高CEA之间的可比性。
