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: 8238087
• 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/8238087
• 关键词: Patient; Level; Meta; analysis; Effect

DESCRIPTION (provided by applicant): 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.

描述（由申请人提供）： 标题：患者水平荟萃分析：使用通过敏感和特异性磁共振成像 (MRI) 进行的关节评分以及敏感的物理关节检查来评估关节结果，使用因子 VIII 预防的起始年龄、治疗持续时间和治疗强度（给药方案）对预防血友病关节病的影响。摘要：该提案将解决严重甲型血友病中结构性和功能性关节疾病的发展，以及预防性治疗在预防或改善关节损伤方面的益处。严重血友病中的慢性关节病是一种重要的疾病，由关节内微小或大量出血引起，并导致限制就业和社会参与的疼痛。预防或常规输注因子 VIII 以预防出血是预防关节和危及生命的出血事件的标准护理治疗。然而，虽然两岁前开始高剂量、频繁输注（称为一级预防）可有效预防慢性关节病，但关于延迟或强度较低的预防是否以及在何种程度上预防、限制或逆转关节损伤，仍然存在许多问题。此外，尚不清楚预防是否以及在多大程度上可以帮助已患有关节疾病的青少年和成人（二级预防）。该提案的目的是利用三项研究的现有数据，包括敏感和特异性磁共振成像 (MRI) 联合成像，以确定血友病关节病的自然史、一级预防的长期结果以及二级预防的影响。三项研究中的两项包括随时间推移的连续测量，所有研究都包括接受预防的患者与未接受预防的患者的比较。其中两项研究纳入了两岁前开始预防的患者，所有三项研究均纳入了两岁以上开始预防的患者。在该提案中，个体患者数据将作为一项研究进行汇总和分析。提出分析模型来确定未进行预防的患者关节损伤的时间轨迹，并确定预防对预防、逆转或减轻关节损伤程度的效果。此外，该研究还将探讨开始预防的年龄、FVIII 剂量和剂量频率对预防结果的影响。由于这三项研究纳入了大量受试者（至少 56 例不进行预防的患者、60 例进行一级预防的患者和 106 例进行二级预防的患者，并且每项 MRI 研究均包含 4 至 6 个关节图像，因此拟议研究的目标很可能会得到满足。