Altria Client Services LLC, 601 E. Jackson Street, Richmond, VA, 23219, USA.
Harm Reduct J. 2024 Feb 8;21(1):35. doi: 10.1186/s12954-024-00953-8.
As part of its comprehensive plan to significantly reduce the harm from tobacco products, the US Food and Drug Administration is establishing a product standard to lower nicotine in conventional cigarettes to make them "minimally addictive or non-addictive". Many clinical studies have investigated the potential impact of such a standard on smoking behavior and exposure to cigarette constituents. These ambulatory studies required participants who smoke to switch to reduced nicotine study cigarettes. In contrast to clinical trials on pharmaceuticals or medical devices, participants had ready access to non-study conventional nicotine cigarettes and high rates of non-study cigarette use were consistently reported. The magnitude of non-compliance, which could impact the interpretation of the study results, was not adequately assessed in these trials.
We conducted a secondary analysis of data from a large, randomized trial of reduced nicotine cigarettes with 840 participants to estimate the magnitude of non-compliance, i.e., the average number of non-study cigarettes smoked per day by study participants assigned to reduced nicotine cigarettes. Individual participants' non-study cigarette use was estimated based on his/her urinary total nicotine equivalent level, the nicotine content of the study cigarette assigned and the self-reported number of cigarettes smoked, using a previously published method.
Our analysis showed that (1) there is a large variation in the number of non-study cigarettes smoked by participants within each group (coefficient of variation 90-232%); (2) participants in reduced nicotine cigarette groups underreported their mean number of non-study cigarettes smoked per day by 85-91%; and (3) the biochemical-based estimates indicate no reduction in the mean number of total cigarettes smoked per day for any group assigned to reduced nicotine cigarettes after accounting for non-study cigarettes.
High levels of non-compliance, in both the rate and magnitude of non-study cigarette use, are common in ambulatory reduced nicotine cigarette trials where participants have access to conventional nicotine non-study cigarettes. The potential impact of high non-compliance on study outcomes should be considered when interpreting the results from such ambulatory studies.
作为其大幅降低烟草制品危害综合计划的一部分，美国食品药品监督管理局正在制定一项产品标准，以降低传统香烟中的尼古丁含量，使其“低成瘾性或非成瘾性”。许多临床研究已经调查了这一标准对吸烟行为和接触香烟成分的潜在影响。这些非住院研究要求吸烟参与者改用降低尼古丁含量的研究香烟。与药品或医疗器械的临床试验不同，参与者可以随时获得非研究性常规尼古丁香烟，并且始终报告非研究性香烟使用率很高。这些试验没有充分评估不遵守规定的程度，这可能会影响对研究结果的解释。
我们对一项有 840 名参与者的降低尼古丁香烟的大型随机试验数据进行了二次分析，以估计不遵守规定的程度，即分配给降低尼古丁香烟的研究参与者平均每天吸食非研究性香烟的数量。根据参与者的尿总尼古丁当量水平、分配的研究香烟的尼古丁含量以及报告的吸烟数量，使用先前发表的方法估算每位参与者的非研究性香烟使用量。
我们的分析表明：（1）每个组内参与者吸食的非研究性香烟数量存在很大差异（变异系数为 90-232%）；（2）降低尼古丁香烟组的参与者每天平均少报告 85-91%的非研究性香烟使用量；（3）在考虑非研究性香烟后，任何分配到降低尼古丁香烟组的人的平均每天总吸烟量均无减少。
在参与者可以获得常规尼古丁非研究性香烟的非住院降低尼古丁香烟试验中，不遵守规定的程度很高，无论是在使用非研究性香烟的比率还是数量方面，均很常见。在解释这些非住院研究的结果时，应考虑高不遵守规定对研究结果的潜在影响。
