Quality of Japanese clinical trials estimated from good clinical practice audit findings.

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.