主要胆道胆炎药物评估和监管部门的批准:我们从这里走向何方?
David E J Jones1, Ulrich Beuers2, Alan Bonder3
1Faculty of Medical Sciences, Newcastle University, Newcastle, UK.
Hepatology (Baltimore, Md.)
|March 20, 2024
概括
原发性胆道胆道炎 (PBC) 的新疗法面临监管障碍. 现实世界的数据收集对于证明PBC等罕见肝病的长期结果至关重要.
科学领域:
- 肝病学 肝病学是一种肝病学.
- 药理学 药理学是指药理学的学科.
- 监管科学 监管科学
背景情况:
- 初级胆道胆炎 (PBC) 是一种慢性胆固醇性肝病.
- 乌尔苏多氧胆酸 (UDCA) 是一线治疗,但高达40%的患者表现出不充分的反应.
- 肥酸 (OCA) 提供了二线选择,但高风险患者仍然存在未满足的需求.
研究的目的:
- 分析EMA反思论文对新PBC疗法的监管途径的影响.
- 以现有治疗方法探索对罕见疾病进行安慰剂受控结局试验的挑战.
- 提出实用解决方案,使用现实世界的数据来证明PBC的长期疗效.
主要方法:
- 审查关于监管审批流程的EMA反思文件.
- 分析招募和留住PBC疗法的确认试验中患者的挑战 (例如,COBALT研究).
- 讨论现实世界数据 (RWD) 对罕见疾病证据生成的有用性.
主要成果:
- 基于替代终点的有条件营销许可对随后的确认试验造成了困难.
- 当有效的治疗方法在商业上可用时,在安慰剂对照试验中保留患者是具有挑战性的.
- 欧洲药物管理局的论文虽然提供了指导,但可能没有完全解决RWD对罕见疾病的价值.
结论:
- 目前的监管模式对批准新的PBC疗法提出了重大挑战.
- 现实世界数据收集对于产生关于PBC长期结果的强有力的证据至关重要.
- 需要整合RWD的务实方法来导航监管途径,并改善罕见肝病患者的治疗结果.
更多相关视频
08:42Using Multi-fluorinated Bile Acids and In Vivo Magnetic Resonance Imaging to Measure Bile Acid Transport
Published on: November 27, 2016
11.2K
11:34A Competent Hepatocyte Model Examining Hepatitis B Virus Entry through Sodium Taurocholate Cotransporting Polypeptide as a Therapeutic Target
Published on: May 10, 2022
2.2K
相关概念视频
01:16Hepatic Drug Excretion: Influencing Factors
128
The biliary system of the liver, crucial for bile secretion and drug excretion, comprises intrahepatic bile ducts that merge to form the common hepatic duct. This duct, carrying hepatic bile, combines with the cystic duct, draining the gallbladder and forming the common bile duct, which empties into the duodenum. Bile, produced by hepatic cells lining the bile canaliculi, is composed primarily of water, bile salts, pigments, electrolytes, and lesser amounts of cholesterol and fatty acids. Bile...
128
01:24Drugs for Treatment of Crohn's Disease in IBD Using Biologic Agents: Anti-TNF
137
Tumor Necrosis Factor (TNF), a proinflammatory cytokine, contributes significantly to the inflammation seen in Crohn's disease. It exists as soluble TNF and membrane-bound TNF, with actions mediated through TNF receptors (TNFR). TNFR activation leads to the release of proinflammatory cytokines, T-cell activation, collagen production, and leukocyte migration, all contributing to inflammation in Crohn's disease. Anti-TNF monoclonal antibodies, namely infliximab (Remicade), adalimumab...
137
01:29Chronic Pancreatitis II: Collaborative Care
86
The management of chronic pancreatitis is multifaceted, involving a comprehensive approach that includes thorough assessment, diagnostic testing, and a variety of management strategies.
Assessment:
Assessment:
86
01:29Drugs for Treatment of Crohn's Disease in IBD Using Immunomodulatory Agents
163
Crohn's disease is an inflammatory bowel disorder marked by chronic inflammation of the GI tract. Various treatment strategies for Crohn's disease are employed, such as immunomodulatory agents, glucocorticoids, and biologics or anti-TNF therapy. Azathioprine (Imuran), a commonly used immunomodulatory drug for Crohn's disease, is converted in the body to mercaptopurine, which inhibits purine biosynthesis and cell proliferation. Both are utilized in severe cases of Inflammatory Bowel...
163
01:14Hepatic Drug Clearance: Role of Transporters
56
In the liver and bile canaliculi, influx and efflux transporters modification can influence intrinsic clearance. Transporters play a significant role in moving drugs within liver cells. Elaborate models, such as the Biopharmaceutical Classification System (BCS), are essential to relate transporters to drug disposition. This system categorizes drugs into four classes based on solubility and permeability, providing insights into elimination routes and the effects of transporters following oral...
56
01:11Clinical Trials: Overview
2.9K
Clinical development focuses on how the drug will interact with the human body and encompasses four key phases of clinical trials, each serving a specific purpose in assessing the safety and effectiveness of new drugs. These phases overlap and build upon one another. Phase I involves a small group of healthy volunteers (typically 20-80 individuals) or, in cases where significant toxicity is expected, patients with the targeted disease, such as cancer or AIDS. The volunteers are tested for...
2.9K