Monitoring the quality of conduct of clinical trials: a survey of current practices.

BACKGROUND: There is a little empirical evidence to determine which, if any, monitoring practices best achieve the goals of trial monitoring set forth in ICH E6 under the variable circumstances of different clinical trial settings. PURPOSE: The purpose of this project was to describe current methods of monitoring clinical trials and to explore the rationale for the use of those methods. METHODS: An electronic survey of known monitoring practices was developed and sent to over 200 organizations involved in conducting clinical research. The survey collected information on institutional demographics, methods of overall study oversight, use of risk-based monitoring and factors that influence assessments of risk, and details on quality assurance and monitoring practices. RESULTS: Seventy-nine organizations completed the survey; our analysis included the 65 organizations that indicated they perform clinical trials. Data from the survey indicate that a wide variety of monitoring practices are currently being employed. Eighty-three percent of respondents use centrally available data to evaluate site performance, but only 12% of respondents always or frequently used centralized monitoring to replace on-site visits. Eighty-seven percent of respondents indicated that they always performed on-site visits. This varied by type of organization, with 31% of academic coordinating centers/cooperative groups/government organizations always performing on-site monitoring visits versus 84% of other organizations. The rationale for using a specific monitoring approach does not appear to be based on empirical evidence. Fifty-four percent of respondents stated that 'usual practice' determined the frequency with which they conducted on-site monitoring visits. LIMITATIONS: The overall response rate to our survey was only 30%; thus, we may not have captured the full variance of current monitoring practices, and our responding sample may not be representative. CONCLUSION: These findings underscore the necessity of research to provide an evidence base for monitoring practice.

Serum leptin levels, hormone levels, and hot flashes in midlife women.

OBJECTIVE: To examine the associations between serum leptin levels, sex steroid hormone levels, and hot flashes in normal weight and obese midlife women. DESIGN: Cross-sectional study. SETTING: University clinic. PATIENT(S): 201 Caucasian, nonsmoking women aged 45 to 54 years with a body mass index of <25 kg/m2 or >or=30 kg/m2. INTERVENTION(S): Questionnaire, fasting blood samples. MAIN OUTCOME MEASURE(S): Serum leptin and sex steroid hormone levels. RESULT(S): Correlation and regression models were performed to examine associations between leptin levels, hormone levels, and hot flashes. Leptin levels were associated with BMI, with "ever experiencing hot flashes" (questionnaire), with hot flashes within the last 30 days, and with duration of hot flashes (>1 year, P=.03). Leptin was positively correlated with testosterone, free testosterone index, and free estrogen index and inversely associated with levels of sex hormone-binding globulin. In women with a body mass index>or=30 kg/m2, leptin levels no longer correlated with testosterone levels. CONCLUSION(S): Serum leptin levels are associated with the occurrence and duration of hot flashes in midlife women; however, no correlation was found between leptin and serum estradiol.

Cigarette smoking, androgen levels, and hot flushes in midlife women.

OBJECTIVE: To test the hypothesis that cigarette smoking is associated with hot flushes through a mechanism involving androgen levels, progesterone levels, sex hormone-binding globulin levels, or the ratio of androgens to estrogens. METHODS: Women with and without hot flushes were recruited from Baltimore, Maryland, and the surrounding counties. Women were between 45 and 54 years of age, with at least three menstrual periods in the previous 12 months, and were not postmenopausal. Study participants completed a questionnaire and gave a blood sample for hormone measurements. RESULTS: Current smokers had significantly higher androstenedione levels and a higher androgen-to-estrogen ratio than never smokers. Current smokers had significantly lower progesterone levels compared with never smokers. Former and current cigarette smokers had increased odds of experiencing hot flushes compared with never smokers (former: odds ratio [OR] 1.41, 95% confidence interval [CI] 0.99-2.01; current: OR 2.43, 95% CI 1.28-4.62). This association, however, was not attenuated by the addition of hormones to the smoking and hot-flush model. CONCLUSION: Cigarette smoking is associated with hot flushes through a mechanism that may not involve alterations in hormone levels or their ratios. LEVEL OF EVIDENCE: II.