Califf: Current evidence generation system in clinical research needs an overhaul

Regulatory NewsRegulatory News | 24 January 2023 |  By 

Clinical research in the US needs an overhaul to better optimize health outcomes in a way that matches advances in biomedical science, according to a recent perspective authored by US Food and Drug Administration Commissioner Robert M. Califf, published in Clinical Trials journal.
“Biomedical science and technology are undergoing a remarkable period of discovery and development, one driven in large part by the innovations of US scientists and engineers. Unfortunately, these advances are not resulting in superior health outcomes for US patients and consumers,” Califf wrote in the paper. “However, if supported by effective policies and investment, the intersection of discovery in biomedical science, technology, and communication has the potential to usher in a new era of better health for the United States and the world.”
The contrast between health outcomes in the US and other countries is stark and "not uniformly distributed," with disparities in health outcomes across race, ethnicity, sex, and gender, Califf wrote. Social determinants of health such as socioeconomic status, housing, geography, and employment status also contribute to adverse health outcomes. As a result, life expectancy can vary across the country by as much as 20 years or more, he noted.
Compounding these issues is the failure rate of medical products, which can fail due to “off-target effects, failure to effectively engage the therapeutic target, or insufficient health effects despite target engagement” as well as design or engineering issues. While the current premarket system keeps most failed products from reaching the market, the process is expensive, Califf explained. “The high failure rate of the products themselves suggests that we need a more efficient system to enable more ‘shots on goal’ to develop effective new products.”
Califf outlined several areas where a new evidence generation system could improve these problems. Specific areas for improvement include better integration of high-quality data from clinical trials, electronic health records, and wearable devices/sensors; focusing clinical research operations to involve patients and clinicians on the front line; and creating a system of responsible data sharing with ethical constructs.
A common information base, rather than a disaggregated system, could lead to an increase in the value of evidence generation and result in better outcomes for patients. “Closing the enormous gap between what we need to know for evidence-based practice and what we actually know has the potential to enable major improvements in health status,” Califf wrote.
Further, FDA can collaborate with market stakeholders to achieve reforms in areas where it has authority, according to Califf, although he did not elaborate on how this might be accomplished.
"Given the tremendous shortfall in evidence needed to guide optimal health interventions, coupled with systemic inefficiencies and rising costs, the need for structural change and realignment is obvious,” he wrote. “The large gaps in the postmarket space, where the FDA generally has less direct influence on evidence generation, will require collaboration across multiple sectors.”
In the postmarket phase, FDA may be able to assist in creating an evidence generation system where components of its mission statement to includes “ensuring the safety, efficacy, and security of human and veterinary drugs, biological products, and medical devices” and “helping the public get the accurate, science-based information they need to use medical products and foods to maintain and improve their health” apply, Califf noted.
“[T]he FDA has a stake in a better evidence generation system that goes well beyond the premarket phase,” he wrote. “Developing such a system will require coordinated action across the clinical research enterprise."
Perspective article


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