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3 The Urgent Need for Regulatory Science
Pages 13-22

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From page 13...
... were being approved without certain essential safety measures and in noncompliance with the premarket safety steps mandated by the Safe Medical Devices Act of 1990.1 According to DeLauro, despite progress made at FDA since 2007 and the enactment of the Food and Drug Administration Amendments Act of 200, the ad hoc nature of the problems faced by the agency, such as continu ally emerging safety recalls, forces the agency to act reactively to issues as they arise instead of assuming a leadership role and proactively address 1 Safe Medical Devices Act of 1990, Public Law 101-629, 101st Cong. (November 28, 1990)
From page 14...
... At the same time, emerging technologies cannot meet the demand for new therapies without coordinated effort from regulatory bodies. The presentations summarized below focused on specific areas of emerging technology and the scientific gaps caused by the lack of strong regulatory science.
From page 15...
... Caviness Distin guished Professor of Medicine, University of North Carolina at Chapel Hill, and Director, Hamner Institute for Drug Safety Sciences. 3 The Serious Adverse Events Consortium, funded by pharmaceutical companies, exam ines gene banks of patients with common SAEs in an attempt to find genetic causes.
From page 16...
... Following its success with inbred mice panels, the Hamner Institute is now partnering with the pharmaceutical industry to study proprietary drugs that have shown success in animal safety and preclinical studies but failed at various stages of the drug's life cycle due to severe toxicities. According to Watkins, such studies utilize academia's existing resources and access patient populations not available to FDA.
From page 17...
... gene that was found to greatly increase precise prediction in the estimation of age of late-onset Alzheimer's Disease for carriers of the ε4 allele of the apolipoprotein E (APOE) gene, which is considered the most highly replicated genetic factor for risk and age of the disease (Roses et al., 2009)
From page 18...
... mutation are two examples of the successful use of regulatory science at FDA. In the case of influenza vaccines, phylogenetic mapping previously con ducted by academic laboratories had prepared FDA for the incoming data, and the agency was quickly able to acquire the necessary expertise to perform due diligence in an efficient regulatory support process.
From page 19...
... Unfortunately, noted Ellenberg, most statisticians -- including epidemiologists, computational biologists, and informaticians -- do not seek FDA reviewer positions. Ellenberg suggested further that, despite expectations for improved quantitative approaches, they will not eliminate the need for sufficiently large populations for safety assessment, adequate duration of follow-up for documentation of sustained efficacy and long-term safety, or long-term data to validate the use of surrogate endpoints.
From page 20...
... Ellenberg described the sponsor's frustration in being forced to "arbitrarily choose one outcome for submission to FDA." Because existing statistical methods, including global methods, 7 do not account for multiple comparisons, new regulatory methods that can cali brate the extent of correlation among the outcome variables are needed. Adaptive Designs The hope for adaptive designs is to telescope clinical trials into smaller, more efficient versions of themselves.
From page 21...
... Thus, Ellenberg believes, the involvement of regulatory scientists in studying and developing an optimal design for comparative effectiveness research is critical. Other Areas Ellenberg cited a number of other areas in emerging statistical technologies that warrant a standardized, science-based system of regulatory decision making: • developing regulatory pathways for biosimilars;8 • improving Phase I trial designs beyond cancer trials; • eveloping pediatric indications for drugs already studied in d adults; • developing therapies for rare diseases; • identifying optimal dosage levels in Phase II and III studies; and • dentifying safety signals during the translation phase from animal i to first-in-human studies.
From page 22...
... Therefore, some approaches recommended by research scientists in published journals go unnoticed by agency scientists. To make progress, said Ellenberg, two components are necessary: first, FDA statisticians who are adept at using newly developed approaches must be empowered to judge whether methods should be applied based on their appropriate scientific value; second, research statisticians must be knowledgeable about the regulatory environment so the advances created by their research will be relevant to, and take into account, issues faced by FDA.


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