Nahrwold M L, Roizen M F, Stanley T H, Thisted R A, Walawander C A, White P F, Apfelbaum J L, Grasela T H, Hug C C, McLeskey C H
Department of Anesthesia, Indiana University, Indianapolis.
Anesth Analg. 1993 Oct;77(4 Suppl):S34-43.
In 1989-1990, Stuart Pharmaceuticals conducted a Phase IV study of propofol on over 26,000 patients, later making the large data base available to a team of epidemiologists and anesthesiologists for analysis. We now describe the process of verifying the data to provide a sound basis for further analyses. Original data were collected by 1819 physicians at 1761 hospitals. In that study, anesthesia was induced by bolus injection of propofol and was maintained by inhaled drug and N2O-O2 (Step 1), or by propofol (either intermittent bolus injection [Step 2] or continuous infusion [Step 3]) and N2O-O2. Forty-six recorded variables described history, physical examination, course and quality of anesthesia and recovery, and adverse events. Data were scrutinized for inaccuracy or bias regarding adverse events, completeness of data, data entry, and violations of the study protocol. The initial data set pertained to 26,841 patients (10,698, Step 1; 8886, Step 2; and 7257, Step 3). Because we excluded data if 25% of the items were missing from the data set, 3.2% of the case reports were eliminated: the final data set used for subsequent analyses contained 25,981 patients (10,184, Step 1; 8672, Step 2; and 7125, Step 3). Inaccuracy of data entry was not excessive, and violations of study protocol were less frequent than in similar studies. The nature and frequency of adverse events were similar to those reported in Phase II and III clinical trials of propofol. Analysis showed that missing data occurred randomly and did not introduce obvious bias. We conclude that the data set was valid and most likely represents perioperative events occurring in similar patients; that Phase IV studies can be valuable because of the range of patients studied and the ability to detect even rare events; and that future Phase IV studies could be improved by more efficient design of data collection forms for both hypotheses to be tested and the entry of data onto forms.
1989年至1990年期间，斯图尔特制药公司对超过26000名患者进行了丙泊酚的IV期研究，随后将该大型数据库提供给一组流行病学家和麻醉学家进行分析。我们现在描述数据验证过程，以便为进一步分析提供可靠基础。原始数据由1761家医院的1819名医生收集。在该研究中，麻醉诱导采用丙泊酚静脉推注，维持麻醉采用吸入药物和N2O - O2（步骤1），或采用丙泊酚（间歇性静脉推注[步骤2]或持续输注[步骤3]）和N2O - O2。46个记录变量描述了病史、体格检查、麻醉及恢复过程和质量以及不良事件。对数据进行了审查，以检查不良事件方面的不准确或偏差、数据完整性、数据录入以及是否违反研究方案。初始数据集涉及26841名患者（步骤1为10698名；步骤2为8886名；步骤3为7257名）。由于如果数据集中25%的项目缺失，我们就会排除这些数据，因此3.2%的病例报告被剔除：用于后续分析的最终数据集包含25981名患者（步骤1为10184名；步骤2为8672名；步骤3为7125名）。数据录入的不准确情况并不严重，违反研究方案的情况比类似研究中更为少见。不良事件的性质和发生率与丙泊酚II期和III期临床试验中报告的情况相似。分析表明，缺失数据是随机出现的，并未引入明显偏差。我们得出结论，该数据集是有效的，很可能代表了类似患者围手术期发生的事件；IV期研究很有价值，因为研究的患者范围广，且有能力检测到即使是罕见的事件；未来的IV期研究可以通过更有效地设计用于待检验假设的数据收集表以及将数据录入表格的方式加以改进。
