Regulatory Requirements Of The Food And Drug Administration Would Preclude Product Claims Based On Observational Research

Abstract

As norms of comparative effectiveness research are sought within the biomedical and health care communities, and the science of conducting and interpreting this research develops, the Food and Drug Administration (FDA) must balance diverse interests. The agency's overarching interest is the development of high-quality comparative effectiveness information that contributes to improved patient care. To further this interest, the FDA can provide expertise in trial design and postmarketing surveillance. The FDA can also ensure that manufacturers of medical products use comparative effectiveness information in product promotion in a manner consistent with regulatory requirements. In this article we observe that these requirements would preclude the manufacturer's use in a promotional context of comparative effectiveness findings derived from an observational study. The FDA recognizes, however, that there are ongoing efforts to address the methodological problems inherent in observational approaches and to foster consensus on enhanced methods. The FDA must work to navigate challenges that relate to both the science of comparative effectiveness research and the agency's statutory responsibilities to the public health.

Content analysis of comparative claims in drug advertisements

“…equitable discussion of its risks and efficacy) (Baylor-Henry and Drezin, 1998). FDA allows comparative claims in prescription drug advertisements with restrictions: claims about drug efficacy or risks must be supported by substantial evidence, typically from two well-controlled head-to-head clinical trials (Griffin et al , 2012; Kesselheim and Avorn, 2012) to objectively demonstrate that the drug will have the claimed effect.…”

“…Efficacy- and risk-based comparative claims concentrate on a drug’s safety or effectiveness. Efficacy and risk comparisons in advertisements are generally based on head-to-head clinical trials (Griffin et al , 2012; Kesselheim and Avorn, 2012), per the restrictions on advertising put forth by the FDA.…”

The will of Congress? Permissive regulation and the strategic use of labeling for the anti-influenza drug Relenza

“…The FDA’s ‘gatekeeping’ power – its decisions to grant or withhold marketing approval for drugs – has enormous implications for public health and the broader healthcare system. Equally, the FDA’s oversight of the content and claims made in drug labels are important for public health and the broader healthcare system, since labels contain critical prescribing information for clinicians and determine the legal boundaries for companies’ marketing claims (Griffin et al, 2012). However, the label may also be used strategically to protect permissive, rather than precautionary, regulation, where regulators focus on communicating risks or uncertainty, rather than rejecting or withdrawing drugs on safety or efficacy grounds (Davis and Abraham, 2013).…”

Communicating and Promoting Comparative-Effectiveness Research Findings

“…[1][2][3] CER is intended to inform discussions about what works in health care. Much of the information comes from research using retrospective databases and quasi-experimental designs rather than randomized clinical trials.…”

“…The Food and Drug Administration (FDA) prohibits drug companies from using such information to promote pharmaceuticals, requiring that promotions be supported by "substantial evidence" of purported effects (which generally means evidence from two well-controlled trials, though one randomized, controlled trial is permitted in certain circumstances). 1,2 Pharmaceutical companies have complained about "asymmetry" between the strict rules for their industry and the absence of restrictions for other organizations -including public and private payers and agencies such as the new Patient-Centered Outcomes Research Institute (PCORI) -which are increasingly conducting CER and communicating its results. 3 The counterargument is that permitting drug companies to freely promote CER findings, including those that don't meet the substantial-evidence standard, opens the door for industry to mislead physicians and patients, potentially harming public health and safety.…”