Perkins Kenneth A
University of Pittsburgh School of Medicine, Western Psychiatric Institute and Clinic , 3811 O'Hara Street, Pittsburgh, PA 15213 , USA +1 412 246 5395 ; +1 412 246 5390 ;
Expert Opin Drug Discov. 2014 Nov;9(11):1259-64. doi: 10.1517/17460441.2014.951632. Epub 2014 Aug 20.
One obstacle to rapid development of new smoking cessation medications is the inefficient early clinical evaluation of the efficacy of novel drugs, which inform us as to whether or not to proceed with the greater expense and time of more formal clinical trials. The vast majority of novel drugs fail to show efficacy for cessation only after substantial resources have been spent and, thus, are largely wasted.
The author reviews the general limitations in the current typical procedures for initial tests of cessation efficacy in novel drugs. Small, randomized clinical trials often have good validity but may have practical limitations in achieving adequate statistical power to test novel versus placebo treatment conditions. Lab tests of acute drug effects on abstinence symptoms, during brief enforced cessation periods, are practical but have limited clinical predictive validity.
Initial efficacy testing may be more efficient if done using innovative crossover designs that evaluate brief 'practice' quit periods for both active and placebo treatments within the same smokers, recruiting those high in quit motivation. Because this approach would require far fewer subjects and a shorter duration of testing, results could be obtained more rapidly and inexpensively to indicate that a novel drug may, or may not, be sufficiently efficacious as to warrant the greater costs and time of formal randomized clinical trials.
新型戒烟药物快速研发的一个障碍是新药疗效的早期临床评估效率低下，而这种评估能让我们知晓是否要继续进行更正式的临床试验，这类试验成本更高且耗时更长。绝大多数新药在投入大量资源后才被证明没有戒烟疗效，因此大量资源被浪费了。
作者回顾了当前新药戒烟疗效初始测试典型程序中的普遍局限性。小型随机临床试验通常具有良好的效度，但在获得足够的统计效力以测试新药与安慰剂治疗条件方面可能存在实际限制。在短暂强制戒烟期间对药物对戒断症状的急性影响进行实验室测试是可行的，但临床预测效度有限。
如果采用创新的交叉设计进行初始疗效测试，可能会更有效。这种设计在同一吸烟者中评估活性药物和安慰剂治疗的短暂“练习”戒烟期，并招募戒烟动机高的人。由于这种方法所需的受试者少得多，测试持续时间也更短，因此可以更快、更廉价地获得结果，以表明一种新药可能有效，也可能不足以有效到值得进行更昂贵、耗时更长的正式随机临床试验。
