The US Food and Drug Administration (FDA) is reaching out to the private sector in a bid to help it improve the quality of the postmarketing surveillance data it receives regarding biologic drugs and products, saying new tools are needed to account for time-contingent variables.
The agency's market research notice, posted on 17 May 2013, calls for private-sector support for a problem now plaguing its Center for Biologics Evaluation and Research (CBER). That problem, it explains, is that post-marketing studies of products largely rely on observational studies, which are easier to influence relative to a premarket randomized and controlled clinical trial, which sets the standard for controlling the variables acting on patients.
A Question for Regulators
The question for FDA, then, is how these studies can be made better by isolating and controlling for undesirable variables.
FDA's notice points to something it calls quantitative bias analysis (QBA), a method of enhancing the validity of postmarketing safety surveillance studies, as its preferred method for accomplishing this task. And while those methods have been used for several years to stabilize data, FDA said that there are "several important challenges that the current QBA literature does not address," including the effects of variables that are dependent on time (known as time-varying confounders).
To cite an example put forth by FDA, the side effects of an influenza product will likely vary with the rates of influenza in the population, which depends on the cycle of a virus. There are two types of time-varying confounders, FDA notes: Type I, which are defined by calendar time, and Type II, which are random in respect to the calendar.
"The current QBA literature mostly focused on adjusting for time constant confounders," FDA argued. Therefore, it says it wants to gauge the capabilities of private-sector entities and whether they could develop new methods to address "specific bias problems" in postmarketing data, refine a software tool already built by FDA and train staff on how to apply QBA.
In addition, the proposal calls for a tool that can account for "multiple" sources of bias.
"The project would enhance the validity of biologic product safety surveillance studies," FDA added.
Read the proposal here.