Clinical evaluation of medicinal products for acceleration of fracture healing in patients with osteoporosis
Clinical evaluation of medicinal products for acceleration of fracture healing in patients with osteoporosis
复制标题
DOI：
10.1016/j.bone.2008.04.017
复制
发表时间：
2008-08-01
期刊：
影响因子：
4.1
通讯作者：
Reginster, Jean-Yves
中科院分区：
文献类型：
--
作者：
Goldhahn, Joerg;Scheele, Wim H.;Reginster, Jean-Yves
临床前研究表明，药物可以增强骨折愈合。如果这些药理学方法可以转化为临床效益，并提供给骨质疏松症患者或有其他骨折愈合受损风险的患者（例如，大缺损或并发症发生率高的开放性骨折），它们可以为骨折治疗提供重要的辅助手段。然而，广泛接受的指导方针对于鼓励开展评估生物活性物质、药物和新制剂的研究是很重要的，这些物质、药物和新制剂可能促进骨折愈合并随后恢复正常功能。一个共识的过程被启动，为临床评估潜在的治疗方法提供建议，以增加骨折修复的患者与中骺端骨折。根据骨折愈合和固定的特点，临床研究的以下研究目标可能是合适的：a)加速骨折愈合，b)加速恢复正常功能，c)减少骨折愈合并发症。预期目标应决定后续的研究方法。虽然加速恢复正常功能或减少骨折愈合并发症本身可能是3期关键研究的主要研究终点，但仅加速骨折愈合并不足够。x线评估可以在愈合过程中的多个时间点进行，目的是测量达到定义状态所需的时间（例如，三个皮质桥接或骨折线消失），如果患者预期达到共同的临床里程碑（例如，在负重骨折病例中无疼痛完全负重），则可以在单个预先确定的时间点获得of。经过验证的患者报告结果（PRO’s）措施需要支持恢复正常功能的共同主要终点。如果降低并发症发生率（如骨不连）是主要目标，则必须在研究方案中明确预期的并发症，以及它们与特定骨折类型和固定装置的可能关联。研究设计应随机、平行、双盲和安慰剂对照，所有骨折受试者应接受标准化的骨折固定方法，定义为标准护理。(C) 2008爱思唯尔公司版权所有。
Pre-clinical studies indicate that pharmacologic agents can augment fracture union. If these pharmacologic approaches could be translated into clinical benefit and offered to patients with osteoporosis or patients with other risks for impaired fracture union (e.g. in subjects with large defects or open fractures with high complication rate), they could provide an important adjunct to the treatment of fractures. However, widely accepted guidelines are important to encourage the conduct of studies to evaluate bioactive substances, drugs, and new agents that may promote fracture union and subsequent return to normal function.A consensus process was initiated to provide recommendations for the clinical evaluation of potential therapies to augment fracture repair in patients with meta- and diaphyseal fractures. Based on the characteristics of fracture healing and fixation, the following study objectives of a clinical study may be appropriate: a) acceleration of fracture union, b) acceleration of return to normal function and c) reduction of fracture healing complications. The intended goal(s) should determine subsequent study methodology. While an acceleration of return to normal function or a reduction of fracture healing complications in and of themselves may be sufficient primary study endpoints for a phase 3 pivotal study, acceleration of fracture union alone is not. Radiographic evaluation may either occur at multiple time points during the healing process with the aim of measuring the time taken to reach a defined status (e.g. Cortical bridging of three cortices or disappearance of fracture lines), OF could be obtained at a single pre-determined timepoint, were patients are Expected to reach a common clinical milestone (i.e. pain free full weight-bearing in weight-bearing fracture cases). Validated Patient Reported Outcomes (PRO's) measures will need to support the return to normal function co-primary endpoints. If reduction of complication rate (e.g. non-union) is the primary objective, the anticipated complications must be defined in the study protocol, along with their possible associations with the specified fracture type and fixation device.The study design should be randomized, parallel, double-blind, and placebo-controlled, and all fracture subjects should receive a standardized method of fracture fixation, defined as Standard of Care. (C) 2008 Elsevier Inc. All rights reserved.