A National Research Council panel urged the FDA and the National Institutes of Health to “make use of their extensive clinical trial database to carry out a program of research to identify common rates and causes of missing data” to inform future study designs and protocols.

The recommendation was part of a 150-page report from the Panel on Handling Missing Data in Clinical Trials that was released July 19. The FDA requested the panel because of concerns about the effect of missing data.

The report noted that “a substantial percentage of the measurements of the outcome or outcomes of interest is often missing. This ‘missingness’ reduces the benefit provided by the randomization and introduces potential biases in the comparison of the treatment groups.”
The panel concluded “a more principled approach to design and analysis in the presence of missing data is both needed and possible [and the] approach needs to focus on two critical elements: careful design and conduct to limit the amount and impact of missing data and analysis that makes full use of information on all randomized missing data underlying estimates of treatment effects.”

The group added statistical analysis tools “can reduce the potential bias arising from missing data by making principled use of auxiliary information available to nonrespondents.” Although the panel encouraged the increased use of these methods, it cautioned that “all of these methods ultimately rely on untestable assumptions concerning the factors leading to the missing values and how they relate to the study outcomes.  Therefore, the assumptions underlying these methods need to be clearly communicated to medical experts so that they can assess their validity.”

The group’s 20 recommendations covered trial objectives, reducing dropouts through trial design and conduct, treating missing data, and understanding the causes and degree of dropout in clinical trials.

More on the recommendations will be in the September issue of the Guide to Good Clinical Practice.