Data and Safety Monitoring Board

DSMB, Data and Safety Monitoring Board IRB, Institutional Review Board NIH, National Institutes of Health. 

After a mean of 7 years of follow-up, the Data and Safety Monitoring Board also recommended stopping the oral estrogen-alone arm of the study. This arm consisted of 10,739 women who had undergone hysterectomy. Estrogen-only therapy had no effect on coronary heart disease risk and no increased breast cancer risk. ... 

V ftttes J, Barrett-Connor E, Braunwald E et al. 2004. Monitoring the randomized trials of the Women s Health Initiative The experience of the Data and Safety Monitoring Board. Clinical Trials 4 218-234. 

Cardiovascular In some cases tibolone prevents bone loss in elderly subjects, although after 40 years of use some questions regarding its clinical role remain unanswered. In a randomized study in the US, in which 4538 older women took either tibolone 1.25 mg/day or placebo, tibolone reduced the risk of vertebral fractures and of breast cancer. However, there was an increased risk of stroke (relative hazard = 2.19 95% Cl = 1.14, 4.23) the study was stopped after a mean treatment period of 34 months at the recommendation of the data and safety monitoring board [83. There were no significant differences between the two groups in the risks of either coronary heart disease or venous thromboembolism. 

The code will be broken and data will be analyzed when the 12-mo follow-up has been completed for all patients. At that time, DHA therapy will be offered to all patients who desire to receive it. Clinical and laboratory studies will be monitored by an independent data and safety monitoring committee. This committee will also perform an interim analysis when 30 patients have completed assessment and has permission to terminate the study if there are significant favorable findings or unanticipated adverse outcomes. A determination of statistical power indicates that this sample size is sufficient to detect a major effect (0.862 standard deviations). With a more modest effect of 25%, however, the statistical power diminishes to 60%. The study has been approved by the Institutional Review Board at the Johns Hopkins Medical Institutions and is supported by a research grant from the Office of Orphan Products Development at the Food and Drug Administration. Fifty-two patients are enrolled in the study at this time. The code has not yet been broken. No adverse effects attributable to the medication have been observed. 

Another potential use for these drugs was to prevent the formation of adenomatous polyps in patients with a history of colorectal adenomas. Rofecoxib and celecoxib were both tested in this disease. It was the results of this test that prompted Merck to withdraw their drug from the market since this study clearly established the increased risk of cardiovascular events when rofecoxib is used. The results were sufficiently strong to have the safety monitoring board reevaluate the data for a similar trial with celecoxib. On the basis of these data the study with celecoxib was also terminated. Interestingly, another study in which celecoxib was used to prevent polyp formation resulted in no increase in cardiovascular events. The only difference between the two studies was that in the latter case celecoxib was given once a day whereas in the prior study celecoxib was administered at the same dose but twice a day. How this difference in treatment schedules affected the toxic outcomes is unknown at the present time. 

However, just such a situation did arise on a trial I was involved in. This was the CARDS study (Colhoun et ah, 2004) of atorvastatin referred to in section 19.1. I was the statistician on the data-safety monitoring board and we called a halt to the... 

In 2002 FDA and Fiealth Canada asked the Institute of Medicine s Food and Nutrition Board (FNB) to formulate an expert committee to review and identify gaps in methods currently used to assess the safety of ingredients new to infant formulas. The committee was asked to identify tools to evaluate the safety of these ingredients under intended conditions of use in term infants. This charge included determining the data needed to demonstrate the safety of a component already present in human milk, that is, the effect of the matrix, and the utilization of preclinical and clinical studies and postmarket monitoring in the safety assessment process. FDA also asked the committee to apply its recommendations to the recent addition of LC-PUFAs as new ingredients in infant formulas, and others as appropriate. 

MEASURING PERFORMANCE 1. Safety committees will monitor their area s part in the overall plan 2. Incidents will be reviewed and key findings shared widely etc. Data from safety committees to be summarised for the board Safety department to monitor compliance... 

Inside the IXV spacecraft, the On-Board Software (OBSW) plays an important role. The OBSW manages the IXV elements that are necessary to perform all mission modes, including Launch, Orbital, Re-Entry and Descent-Flight, The IXV needs the OBSW to control the vehicle, perform experiments, monitor data, and provide data storage and telemetry, A number of constraints affect the OBSW it is embedded software, with hard real-time, dependability and safety constraints it must operate autonomously over extended periods of time it faces important hardware limitations and it has to cope with a hostile environment (radiation, large temperature changes). 

The computer system of the station control and data acquisition is a distributed micro processer based systems. A digital multiplexed control system takes the place of hard wired analogue control. This accounts for a significant reduction in cable usage. Built-in diagnostics and board level maintenance makes restoration of operability of any fault in the system a matter of replacement of printed circuit cards. Automatic control systems and procedures are deployed to simplify these procedures and power level manoeuvers. In case of unsafe conditions the reactor protection system (PMS) takes over and automatically scrams the reactor and actuates the relevant safety systems. Diverse methods are used to assure the shutdown of the reactor in hypothetical situations. The systems also provide for post-accident monitoring. 

As can be seen, in each case the lower limit of the two-sided 95 % confidence interval fell below unity (1.00) and the upper limit fell above unity, hence the nonsignificant result. The Data Monitoring Safety Board for the trial considered all interim analyses and recoimnended that the trial continue. 

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