Kaur Rimple Jeet, Singh Surjit, Sidhu Preeti, Sharma Pramod Kumar
Department of Pharmacology, Dr. S.N. Medical College, Jodhpur, India.
Department of Pharmacology, All India Institute of Medical Sciences, Jodhpur, India.
Rev Recent Clin Trials. 2018;13(4):252-256. doi: 10.2174/1574887113666180521093529.
Globally, there have been tremendous efforts by regulatory authorities to make clinical trials safer by making stringent clinical trial regulations. Despite this, we witnessed several tragic events. TGN1412 and BIA 10-2474 phase I trials are infamous trails in which healthy volunteers either succumbed to severe adverse effects or faced irreversible impairments of the test drug. Such afflictions in clinical trials are not only turbulent to the image of pharmaceutical industry but it also conveys dispiriting message for clinical trial participants.
To make clinical trials safer for participants, some regulatory changes are warranted.
Some stipulated measures to improve safety of clinical trial participants include inclusion of patients instead of healthy volunteers in phase I clinical trials, all compounds which are used for first time in humans should be considered as high risk compounds, amendments in first in human clinical trial design to N of 1 randomized control trial in place of 6+2 design with the sequential dosing of subjects both within and between cohorts and the individual patient pharmacokinetic and pharmacodynamic data should be used to calculate sequential dosing. Besides these, there should be appropriate process for systematic risk assessment involving the use of statistical techniques to select pertinent risk factors with high predictive values of studies or sites that may be procumbent to non-compliance.
Inclusion of above mentioned measures in clinical trials are bound to make them safer and may help in pacifying the insecurity that has emerged among humans to participate in clinical trials.
在全球范围内，监管机构为使临床试验更安全付出了巨大努力，制定了严格的临床试验法规。尽管如此，我们仍目睹了几起悲剧事件。TGN1412和BIA 10 - 2474的I期试验是臭名昭著的试验，在这些试验中，健康志愿者要么遭受严重不良反应，要么面临受试药物造成的不可逆损伤。临床试验中的此类痛苦不仅损害制药行业形象，也向临床试验参与者传达了令人沮丧的信息。
为使临床试验对参与者更安全，有必要进行一些监管变革。
一些规定的提高临床试验参与者安全性的措施包括：在I期临床试验中纳入患者而非健康志愿者；所有首次用于人体的化合物应被视为高风险化合物；将首次人体临床试验设计从6 + 2设计修改为N-of-1随机对照试验，对队列内和队列间的受试者进行序贯给药，应使用个体患者的药代动力学和药效学数据来计算序贯给药。除此之外，应有适当的系统风险评估流程，包括使用统计技术来选择具有高预测价值的相关风险因素，这些因素可用于研究或可能存在违规情况的试验点。
在临床试验中纳入上述措施必然会使其更安全，并可能有助于消除人们参与临床试验时出现的不安全感。
