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开发|什么是监测生物标志物?

2022-3-11 11:19| 编辑: 归去来兮| 查看: 1659| 评论: 0|来源: 诊断科学 | 作者:认真的刘博

摘要: 01定义需要反复测量的生物标志物,用于评估疾病或医疗状况的状况,或用于证明接触某种医疗产品或环境制剂(或其影响)。02示例➤ 在评估慢性丙型肝炎患者的治疗反应时,丙型肝炎病毒核糖核酸(HCV-RNA)水平 ...


01

定义


需要反复测量的生物标志物,用于评估疾病或医疗状况的状况,或用于证明接触某种医疗产品或环境制剂(或其影响)。


02

示例


➤  在评估慢性丙型肝炎患者的治疗反应时,丙型肝炎病毒核糖核酸(HCV-RNA)水平可作为监测生物标志物[2, 3];

➤  国际正常化比率(INR)或凝血酶原时间(PT)可作为监测生物标志物,用于评估使用华法林的患者是否达到了预期的抗凝效果[12];

➤  血液中的单克隆蛋白(M蛋白)水平可作为监测生物标志物,以评估被诊断为意义不明的单克隆性腺病(MGUS)的个体是否有进展为其他疾病的迹象,包括可能需要治疗的某些类型的血癌[15];

➤   在评估前列腺癌患者的疾病状态或负担时,可将前列腺特异性抗原(PSA)作为监测生物标志物[8];

➤  在评估卵巢癌患者治疗期间和治疗后的疾病状态或负担时,可将癌抗原125(CA125)用作监测生物标志物[9];

➤   HIV-RNA可作为监测生物标志物,用于衡量和指导抗逆转录病毒疗法(ART)的治疗[1];

➤   B型钠尿肽(BNP)或N端原BNP(NT-proBNP)可作为随访期间的监测生物标志物,以补充儿科肺动脉高压患者的临床决策[14];

➤   一种成瘾药物的血液浓度可作为药物成瘾预防和治疗试验中的监测生物标志物,以衡量戒断和依从性[4];

➤   怀孕期间连续测量骨骺线高度可用于产前筛查,以检测胎儿生长障碍[17];

➤  尿液中烟草特定亚硝胺(TSNAs)的浓度(如。总N-亚硝基烟碱(NNN)和总4-(甲基亚硝胺)-1-(3-吡啶基)-1-丁醇(总NNAL)可作为评估烟草和烟草烟雾暴露的监测生物标志物[25]。


03

详解


在一段时间内被反复评估的生物标志物被称为监测生物标志物,可用于评估:


➤  疾病进展,包括新的疾病影响的发生,以前存在的异常的恶化,或疾病严重程度或特定异常的变化;

➤  疾病或病症对治疗的反应,无论是有利的还是不利的。


该范围包括各种类别的生物标志物(如安全性生物标志物、药效/反应性生物标志物、预后性生物标志物)。


当人们不仅对生物标志物的测量值感兴趣,而且对其随时间变化的速度、变化的幅度、变化与个体或病人(如基因型或人口统计学)或疾病相关特征(如疾病严重程度、疾病持续时间和特定疾病)的关系感兴趣时,通常会反复评估生物标志物。


在临床护理环境中或在临床试验的背景下,监测生物标志物可以在病人临床过程的一个或多个时期进行测量。例如,在疾病或病症诊断后和干预前(例如,建立基线特征,评估治疗前的进展率),在提供干预的时期,或在提供干预完成后。


当反复评估时,生物标志物的测量有时可以发现疾病或病情恶化的迹象,这可能表明预后恶化或需要干预。


干预过程中的生物标记物监测可以达到几个目的,包括通过监测药物浓度确定药物在病人体内的代谢情况,在治疗过程中或治疗后检测治疗效果或疾病进展,或检测毒性。


这些用途的例子包括测量PT和部分凝血活酶时间(PTT)值,以保持接受抗凝治疗的病人的华法林或肝素水平在治疗范围内,以及监测HCV-RNA水平,以评估是否存在将受益于治疗的丙型肝炎感染以及对治疗的反应或不反应的证据。


对接受来氟米特和甲氨蝶呤治疗类风湿性关节炎的患者,通过定期测量肝酶来评估肝脏毒性的证据。连续的影像学研究被常规用于监测实体瘤患者的疾病状态,以检测治疗期间或治疗后的退缩或进展,或检测初始治疗达到无病状态后的复发情况。


监测生物标志物也被用于整个医疗产品的开发,例如,在新药、生物制品或设备的治疗或预防试验中。


在治疗过程中或治疗后观察到的生物标志物测量的变化可以提供药效或早期治疗反应的支持证据。在早期临床试验中反复测量的安全生物标志物可以是一种监测器官毒性的生物标志物。


此外,生物标志物有时被用于治疗或预防试验,以评估参与者对指定干预的依从性。例如,生物标志物可能是给药的血液水平,也可能是血清中的可替宁水平(使用烟草制品的指标),作为旨在预防吸烟的干预性试验的一部分。因此,除了指导临床护理外,监测生物标志物可能有助于促进干预性研究的可解释性和可信性。


监测生物标志物可用于个人或人群层面的监测,以了解是否存在疾病或医疗状况或发展风险。


被监测的个人可能没有临床上明显的医疗条件或疾病,或者他们可能有一些医疗条件或以前的暴露,使他们容易发展成一些新的条件或疾病。


接受年度体检的健康成年人被例行监测血清胆固醇、血糖和尿肌酐等生物标志物的水平,以评估高胆固醇血症、糖尿病和肾功能受损等医疗状况的风险并检测其出现情况。


向上滑动阅览


参考文献

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