Burlingame Center for Psychiatric Research and Education, The Institute of Living, Hartford Hospital, Hartford, Connecticut 06106, USA.
Pharmacotherapy. 2009 Dec;29(12):1408-16. doi: 10.1592/phco.29.12.1408.
To determine the prevalence, over 40 years, of using the last-observation-carried-forward (LOCF) imputation method in clinical trials, the association between use of LOCF and how the trials were conducted, and the extent of information about attrition and LOCF use in published reports.
Retrospective analysis of the reports of randomized antidepressant efficacy trials published over a 40-year period (1965-2004).
MEDLINE database, Cochrane reviews, reference- and bibliography-based manual search, and publication list services.
A total of 352 trials met the following criteria for analysis: antidepressant comparative efficacy trial, randomized design, patients with major depressive disorder, English-language article, published during 1965-2004, and first report of a trial. Design, attrition, and data analysis characteristics were recorded by investigators and trained assistants. Analyses included descriptive statistics of the trial size, duration, and number of patients who dropped out in LOCF versus non-LOCF studies, as well as the extent to which dropouts and the potential bias associated with attrition was discussed in the published report. The frequency of published antidepressant clinical trials increased from less than 1 trial/year (1965-1974) to 19 trials/year (1990-1994). Trials using the LOCF method were significantly larger than non-LOCF trials (p<0.01), and the proportion of subjects dropping out was significantly greater (p<0.05) in LOCF versus non-LOCF trials. The proportion of subjects dropping out remained relatively constant over time (approximately 30%) but was significantly greater among LOCF (30.9%) than non-LOCF (28.8%) trials (p<0.01). The LOCF study articles were more likely to report dropouts, but only 7% of these articles reported outcomes recorded for subjects before they dropped out. Less than 16% of articles discussed bias associated with dropouts, 6.8% discussed the direction of bias, and only about 2% suggested the magnitude of the bias.
The percentage of clinical antidepressant trials using the LOCF method and the percentage of study subjects' data imputed by using LOCF increased many-fold during 1965-2004. Published reports of trials provided little information to allow readers to assess possible bias introduced by use of the LOCF method.
确定在临床试验中使用末次观测值结转（LOCF）插补法的流行率，该方法的使用与试验设计之间的关联，以及已发表报告中有关数据缺失和 LOCF 使用的信息程度。
对 40 年间（1965-2004 年）发表的随机抗抑郁药疗效试验报告进行回顾性分析。
MEDLINE 数据库、Cochrane 评价、基于参考文献和书目手动搜索以及出版清单服务。
共有 352 项试验符合以下分析标准：抗抑郁药比较疗效试验、随机设计、患有重性抑郁症的患者、英文文章、发表于 1965-2004 年期间、且为首次报告试验。研究者和训练有素的助手记录了设计、失访和数据分析特征。分析包括失访率和潜在偏倚的描述性统计，LOCF 研究与非 LOCF 研究中脱落的患者比例，以及已发表报告中对脱落和与失访相关的潜在偏倚的讨论程度。发表的抗抑郁药临床试验的频率从每年少于 1 项（1965-1974 年）增加到每年 19 项（1990-1994 年）。使用 LOCF 方法的试验明显大于非 LOCF 试验（p<0.01），并且 LOCF 试验中脱落的患者比例明显更高（p<0.05）。随着时间的推移，脱落的患者比例相对稳定（约 30%），但 LOCF（30.9%）试验中的脱落患者比例明显高于非 LOCF（28.8%）试验（p<0.01）。LOCF 研究文章更有可能报告脱落，但只有 7%的文章报告了脱落前患者的结果。不到 16%的文章讨论了与脱落相关的偏倚，6.8%讨论了偏倚的方向，只有约 2%的文章提到了偏倚的大小。
在 1965-2004 年间，使用 LOCF 方法的临床抗抑郁药试验的百分比和使用 LOCF 插补的患者数据百分比呈数倍增长。试验报告很少提供信息，让读者能够评估使用 LOCF 方法引入的可能偏倚。
