Patient-Level Meta-analysis: Effect of age of initiation, intensity and duration

患者层面的荟萃分析：起始年龄、强度和持续时间的影响

• 批准号: 8332700
• 负责人: Marilyn J Manco-Johnson
• 金额: $ 20万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-30 至 2014-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8332700
• 关键词: Patient; Level; Meta; analysis; Effect

Title: Patient-Level Meta-analysis: Effects of age of initiation, duration of therapy and intensity of treatment (dosing schedule) with factor VIII prophylaxis on prevention of hemophilic arthropathy using joint scoring via sensitive and specific magnetic resonance imaging (MRI) and sensitive physical joint examination to assess joint outcome. Abstract: This proposal will address the development of structural and functional joint disease in severe hemophilia A along with the benefits of prophylaxis in preventing or ameliorating joint damage. Chronic arthropathy in severe hemophilia is an important morbidity caused by microscopic or large hemorrhages into joints and results in pain that limits employment and social participation. Prophylaxis, or routine infusions of factor VIII to prevent bleeding, is the standard of care therapy to prevent joint and life-threatening bleeding events. However, while high-dose, frequent infusions begun before the age of two years (called primary prophylaxis) is effective in preventing chronic arthropathy, many questions remain regarding whether and to what degree delayed or less intensive prophylaxis prevents, limits or reverses joint damage. In addition, it is unknown whether and to what extent prophylaxis can help teens and adults with established joint disease (secondary prophylaxis). The aim of this proposal is to use existing data from three research studies that include joint imaging with sensitive and specific magnetic resonance imaging (MRI) in order to determine the natural history of hemophilic joint disease, the long-term outcome of primary prophylaxis and the impact of secondary prophylaxis. Two of the three studies include serial measurements over time and all of the studies include patients on prophylaxis in comparison to no prophylaxis. Two of the studies include patients who began prophylaxis by the age of two years, and all three studies include patients who began prophylaxis beyond the age of two years. In this proposal, individual patient data will be aggregated and analyzed as a single study. Analytic models are proposed to determine the time-trajectory of joint damage in patients on no-prophylaxis, and to determine the effects of prophylaxis on preventing, reversing or reducing the degree of joint damage. In addition, the study will address the impact of age of starting prophylaxis, FVIII dose and dose frequency on outcome of prophylaxis. Because the three studies incorporate a large number of subjects (at least 56 patients on no-prophylaxis, 60 patients on primary prophylaxis and 106 patients on secondary prophylaxis, and include four to six joint images for each MRI study, it is likely that the objectives of the proposed study will be met.

标题：患者水平荟萃分析：开始年龄、治疗持续时间和 因子VIII预防性治疗的强度（给药方案） 通过灵敏和特异性磁共振进行关节评分的血友病性关节病 磁共振成像（MRI）和敏感的物理关节检查，以评估关节 结果。 摘要： 这项建议将解决严重的结构性和功能性关节疾病的发展， A型血友病沿着预防或改善关节损伤的益处。 严重血友病的慢性关节病是一种重要的发病率， 关节的大肿块，并导致疼痛，限制就业和社会参与。 预防性治疗或常规输注凝血因子VIII以预防出血是标准治疗 治疗，以防止关节和危及生命的出血事件。然而，虽然高剂量， 在两岁之前开始的频繁输注（称为初级预防）对以下患者有效： 预防慢性关节病，许多问题仍然是关于是否和在多大程度上 延迟或强度较低的预防可预防、限制或逆转关节损伤。此外还 不知道预防是否以及在多大程度上可以帮助青少年和成年人建立 关节疾病（二级预防）。该提案的目的是利用现有数据， 三项研究，包括敏感和特异性磁共振关节成像 为了确定血友病性关节疾病的自然史， 一级预防的结果和二级预防的影响。其中两 研究包括随时间推移的系列测量，并且所有研究都包括 预防与不预防相比。其中两项研究包括那些开始 预防的年龄为2岁，所有三项研究都包括患者开始 预防超过2岁。在本提案中，将收集患者个人数据， 作为一项研究进行汇总和分析。提出了分析模型，以确定 无预防患者关节损伤的时间轨迹，并确定 预防、逆转或减轻关节损伤程度。此外该 研究将讨论开始预防的年龄、FVIII剂量和给药频率对 预防的结果。由于这三项研究纳入了大量的受试者（在 至少56例患者接受非预防治疗，60例患者接受一级预防治疗，106例患者接受 二级预防，并包括四到六个关节图像的每一个MRI研究，很可能， 拟议研究的目标将会达到。