Saito Kazuyuki, Kodama Yasuo, Ono Shunsuke, Mutoh Mizue, Kawashima Susumu, Fujimura Akio
Division of Clinical Pharmacology, Department of Pharmacology, Jichi Medical School, Minamikawachi-machi, Tochigi, Japan.
Am J Ther. 2006 Mar-Apr;13(2):127-33. doi: 10.1097/00045391-200603000-00008.
To describe qualitatively recent changes in the Japanese clinical trial environments, we compared the results of the Good Clinical Practice (GCP) audits conducted from April 1997 to March 2000 (FY1997 to FY1999) with those from April 2002 to March 2003 (FY2002). In addition, the audit results were compared between the United States and Japan. The audit findings in the former period were based on the official audits by the Organization for Pharmaceutical Safety and Research (OPSR) that covered 331 hospitals and 775 trials. The audits by the OPSR in the latter period targeted 136 hospitals and 226 trials. The total number of deficiencies detected in the Good Clinical Practice audits in the former 3-year period (FY1997 to FY1999) was 1529, and the number in the single year (FY2002) was 1627. The total number of deficiencies detected and reported was about 3-fold on an annual basis between the periods. By category of deficiencies, there were 2 remarkable changes in the OPSR's audit findings between FY1997-FY1999 and FY2002. One was an increase in the proportion of protocol deviations from 14.7% (225/1529) in FY1997-FY1999 to 48.2% (785/1627) in FY2002, and the other was a decrease in the proportion of case report form-related deficiencies from 43.6% (666/1529) to 16.0% (260/1627). The high prevalence of protocol nonadherence and the relatively few findings of informed consent errors were important characteristics of Japanese trials inferred from the audit result reported by the OPSR in FY2002. In the United States, relatively high proportions of protocol nonadherence and informed consent errors were observed in the audit finding reported in 1997. Although the audit results for clinical trials between the United States and Japan are not strictly comparable, our results suggest that protocol deviations are a compelling issue for quality improvement in the conduct of clinical trials for the 2 regions.
为了定性描述日本临床试验环境最近的变化，我们比较了1997年4月至2000年3月（1997财年至1999财年）与2002年4月至2003年3月（2002财年）期间进行的药品临床试验规范（GCP）审核结果。此外，还比较了美国和日本的审核结果。前期的审核结果基于药品安全与研究组织（OPSR）的官方审核，涉及331家医院和775项试验。OPSR后期的审核针对136家医院和226项试验。前3年期间（1997财年至1999财年）GCP审核中发现的缺陷总数为1529个，而单一年度（2002财年）为1627个。两个时期之间，每年发现并报告的缺陷总数约为3倍。按缺陷类别划分，OPSR在1997财年至1999财年与2002财年的审核结果有两个显著变化。一是方案偏离的比例从1997财年至1999财年的14.7%（225/1529）增至2002财年的48.2%（785/1627），另一个是病例报告表相关缺陷的比例从43.6%（666/1529）降至16.0%（260/1627）。方案不依从的高发生率以及知情同意错误的相对较少发现是根据OPSR在2002财年报告的审核结果推断出的日本试验的重要特征。在美国，1997年报告的审核结果中观察到方案不依从和知情同意错误的比例相对较高。尽管美国和日本之间的临床试验审核结果并非严格可比，但我们的结果表明，方案偏离是这两个地区临床试验实施质量改进的一个紧迫问题。
