Epidemiology, Janssen Research & Development, LLC, Titusville, NJ, United States of America.
Global Medical Safety, Janssen Research & Development, LLC, Horsham, PA, United States of America.
PLoS One. 2018 Feb 28;13(2):e0193453. doi: 10.1371/journal.pone.0193453. eCollection 2018.
Observational studies of switching from branded to generic formulations of the same drug substance often lack appropriate comparators for the subjects who switched. Three generic formulations were deemed equivalent to Concerta: an authorized generic (AG) identical except for external packaging, and two other generics (EG).
Compare the incidence of a combined endpoint (switching back to Concerta, changing the use of immediate release methylphenidate (MPH), stopping all long-acting methylphenidate, or starting a new medication) among people switched from Concerta to the AG versus the EG.
Cohort study from the Truven CCAE database of people aged 6 to 65 diagnosed with ADHD, treated with Concerta, and switched to the EG or to the AG formulation.
In the EG arm 24.6% and in the AG arm 19.7% of subjects switched back to Concerta. The proportion of subjects meeting the combined endpoint was 39.5% in the EG arm, 32.9% in the AG arm, a crude risk ratio of 1.20 (95% CI 0.94, 1.54). After adjustment by propensity score stratification, the adjusted odds ratio (OR) was 1.23 (95% CI 0.90, 1.70). In an unplanned analysis using a different method of adjustment, the adjusted OR was 1.00 (95% CI 0.69, 1.44).
This study did not detect a difference between the proportion of people who met the study endpoint in the two study arms, i.e. between those who switched to a generic formulation that was identical to Concerta except for external packaging and those who switched to the comparison generics. The high incidence of the combined endpoint in the AG arm demonstrates the need for an appropriate comparator in studies of this type.
ClinicalTrials.gov NCT02730572.
从同一种药物活性成分的品牌药转换为仿制药的观察性研究通常缺乏对转换药物的受试者的合适对照。有三种仿制药被认为与Concerta 等效：一种除了外部包装之外与原研药完全相同的授权仿制药（AG），以及另外两种仿制药（EG）。
比较从 Concerta 转换为 AG 与 EG 的受试者中，联合终点（转回 Concerta、改变即刻释放型哌醋甲酯（MPH）的使用、停止所有长效 MPH 或开始新的药物治疗）的发生率。
从 Truven CCAE 数据库中进行一项队列研究，该数据库纳入了年龄在 6 至 65 岁之间、被诊断为 ADHD、接受 Concerta 治疗且转换为 EG 或 AG 制剂的患者。
在 EG 组中，有 24.6%的受试者转回 Concerta，在 AG 组中，有 19.7%的受试者转回 Concerta。在 EG 组中，符合联合终点的受试者比例为 39.5%，在 AG 组中为 32.9%，粗风险比为 1.20（95%置信区间 0.94，1.54）。经过倾向评分分层的调整后，调整后的比值比（OR）为 1.23（95%置信区间 0.90，1.70）。在使用不同调整方法的一项未计划分析中，调整后的 OR 为 1.00（95%置信区间 0.69，1.44）。
这项研究未发现两组之间达到研究终点的受试者比例存在差异，即与转换为除外部包装之外与 Concerta 完全相同的仿制药的受试者相比，与转换为比较仿制药的受试者相比。AG 组中联合终点的高发生率表明，在这类研究中需要使用适当的对照。
ClinicalTrials.gov NCT02730572。
