Abstract：
Decision-making in clinical medicine ideally is based upon evidence from randomized, placebo-controlled trials (RCTs) and subsequent systematic reviews and meta-analyses. However, for orphan diseases, the expectation of having one or multiple RCTs that inform clinical guidelines or justify specific treatments can be unrealistic and subsequent therapeutic nihilism can be detrimental to patients. This article discusses the benefits of therapeutic decision-making in the context of orphan diseases, focusing on primary sclerosing cholangitis (PSC) as an example of an orphan disease with poor clinical outcomes. PSC is a rare disorder characterized by inflammation and progressive fibrosis of the bile ducts. It carries a high risk of liver failure, malignancies, and debilitating symptoms that impair quality of life. Liver transplantation is currently the only life-prolonging intervention for PSC, but it is not a curative option. The article highlights the potential benefits of treating PSC patients with oral vancomycin (OV), which has shown significant clinical responses and improved quality of life in some cases. However, access to OV therapy is limited due to the lack of RCTs supporting its use. The standard requirement of having evidence from RCTs may result in withholding potentially life-altering and/or life-saving treatments for patients with orphan diseases. Conducting RCTs is challenging in these patient populations due to difficulties in recruiting the required patient cohorts and limited commercial returns. A standardized \'adaptive treatment strategy\' is proposed to address this. This approach leverages the best available evidence for specific treatments, considers individual clinical responses, and adjusts treatment over time.
摘要：
临床医学的决策理想情况下是基于随机的证据，安慰剂对照试验(RCT)和随后的系统评价和荟萃分析。然而,孤儿病，期望有一个或多个RCT为临床指南提供信息或证明特定治疗是不现实的,随后的治疗虚无主义可能对患者有害.本文讨论了孤儿疾病背景下治疗决策的好处，重点关注原发性硬化性胆管炎（PSC），作为临床预后不良的孤儿疾病的一个例子。PSC是一种罕见的疾病，其特征是胆管的炎症和进行性纤维化。它有很高的肝功能衰竭风险，恶性肿瘤,和损害生活质量的衰弱症状。肝移植是目前唯一延长PSC寿命的干预措施，但这不是治愈性的选择。文章强调了口服万古霉素（OV）治疗PSC患者的潜在益处，在某些情况下，已显示出明显的临床反应并改善了生活质量。然而,由于缺乏支持其使用的RCTs,OV治疗的获得受到限制.从随机对照试验中获得证据的标准要求可能会导致对孤儿疾病患者隐瞒潜在的改变生命和/或挽救生命的治疗。由于难以招募所需的患者队列和有限的商业回报，因此在这些患者人群中进行RCT具有挑战性。提出了一种标准化的“适应性治疗策略”来解决这个问题。这种方法利用了特定治疗方法的最佳可用证据，考虑个体临床反应，并随着时间的推移调整治疗。
