Diabetes Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.
Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.
Daru. 2021 Jun;29(1):39-50. doi: 10.1007/s40199-020-00380-7. Epub 2021 Jan 2.
Type 2 diabetes mellitus (T2DM) is the subject of numerous randomized controlled trials (RCTs). The validity of RCTs may be threatened by attrition bias due to the discontinuation of the study. The aim of this systematic review is to evaluate the reasons of patient's withdrawal from these RCTs.
A systematic literature search on PubMed, Cochrane Library, Web of Science, and Scopus databases was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flow diagram. The aim was to obtain all relevant blinded RCTs published before January 2017 in which the effectiveness of synthetic drugs, vitamins/minerals were compared to that of placebo or active control in T2DM. The quality of RCTs was assessed using the Jadad score. The frequency of withdrawal reasons was presented based on treatments with placebo/active control, national/international level of the studies, and publication year. Meta-analysis was not performed due to the heterogeneity.
Overall, 1368 articles comprising of 640,780 subjects were included. In the majority of the RCTs (75.0%), the intervention and the placebo arms were compared. Most of the included studies (96%) were classified in the high-quality category (Jadad score≥3). The highest proportion of reported withdrawal cases was found in international studies, national RCTs conducted in Japan, and RCTs published in 2011. The withdrawal reasons were reported for 91,669 (63.75%) of the total 143,794 participants who had withdrawn from these studies. The main reported reasons were "adverse effects" (24.04%), "withdraw consent" (16.10%), and "missing data" (11.08%). Variations in the reported withdrawal reasons were based on the country or published year. RCTs with triple blinded design as well as those in which anti-hyperlipidemia and anti-obesity medications were applied, showed significantly higher probability of reported the withdrawal.
High proportion of reported discontinuation in blinded RCTs on patients with T2DM was related to drug adverse effects. Overall, the total number and reason of drop out were unsatisfactory.
2 型糖尿病（T2DM）是众多随机对照试验（RCT）的主题。由于研究的中断，损耗偏倚可能会对 RCT 的有效性造成威胁。本系统评价的目的是评估这些 RCT 中患者退出的原因。
根据系统评价和荟萃分析的首选报告项目（PRISMA）流程图，对 PubMed、Cochrane 图书馆、Web of Science 和 Scopus 数据库进行了系统文献检索。旨在获得所有相关的、发表于 2017 年 1 月之前的、以合成药物、维生素/矿物质与安慰剂或活性对照比较的、针对 T2DM 的有效性的、双盲 RCT 文献。使用 Jadad 评分评估 RCT 的质量。根据治疗方法（安慰剂/活性对照）、研究的国家/国际水平和发表年份，呈现退出原因的频率。由于存在异质性，因此未进行荟萃分析。
总共纳入了 1368 篇文章，包含 640780 名受试者。在大多数 RCT（75.0%）中，干预组和安慰剂组进行了比较。大多数纳入的研究（96%）被归类为高质量类别（Jadad 评分≥3）。报道退出病例比例最高的是国际研究、日本进行的国家 RCT 和 2011 年发表的 RCT。这些研究中有 91669 名（63.75%）参与者退出，报道了退出原因。主要报道的原因是“不良反应”（24.04%）、“撤回同意”（16.10%）和“数据缺失”（11.08%）。报告退出原因的差异基于国家或发表年份。采用三重盲法设计的 RCT 以及应用降脂和减肥药物的 RCT，报告退出的可能性显著更高。
T2DM 患者双盲 RCT 中报告的停药比例较高与药物不良反应有关。总体而言，脱落的总数和原因并不令人满意。
