Service des Maladies de l'Appareil Digestif, PU-PH, Hôpital Claude Huriez, 1er étage- Aile Est, Rue Michel Polonovski, 59037 Lille Cedex, France.
Digestive Diseases Division, Department of Surgery & Cancer, Imperial College, London W2 1NY, United Kingdom.
J Hepatol. 2019 Feb;70(2):314-318. doi: 10.1016/j.jhep.2018.11.005.
In some areas of medicine the clinical development pathway through phase II and III clinical trials has been well mapped out and refined through extensive experience. In contrast, a number of key questions remain unanswered in the development of novel therapeutics for alcoholic hepatitis. The use of mortality as an endpoint in phase II clinical trials will potentially restrict the appeal of this therapeutic area for pharmaceutical companies, as the number of patients required for adequately powered clinical trials becomes impractical. Herein, we discuss alternative endpoints and conclude that dynamic assessment of liver function is the most pragmatic option in early stage studies. Stratification based on disease severity should be applied to avoid uneven distribution of patients with substantially differing mortality risks. Consensus on early phase trial design would help to facilitate new therapeutic development in this area of high unmet medical need.
在医学的某些领域，通过 II 期和 III 期临床试验的临床开发途径已经通过丰富的经验得到了很好的规划和完善。相比之下，在治疗酒精性肝炎的新型疗法的开发中，仍有许多关键问题尚未得到解答。在 II 期临床试验中使用死亡率作为终点，可能会限制制药公司对这一治疗领域的兴趣，因为进行充分有力的临床试验所需的患者数量变得不切实际。在此，我们讨论了替代终点，并得出结论，在早期研究中，动态评估肝功能是最实用的选择。应根据疾病严重程度进行分层，以避免死亡率存在显著差异的患者分布不均。在早期试验设计方面达成共识将有助于促进这一高未满足医疗需求领域的新疗法开发。
