Benefit-risk evaluations of drugs have been conducted since the introduction of modern regulatory systems more than 50 years ago. Such judgments are typically made on the basis of qualitative or semiquantitative approaches, often without the aid of quantitative assessment methods, the latter having often been applied asymmetrically to place emphasis on benefit more so than harm. In an effort to preliminarily evaluate the utility of lives lost or saved, or quality-adjusted life-years (QALY) lost and gained as a means of quantitatively assessing the potential benefits and risks of a new chemical entity, we focused our attention on the unique scenario in which a drug was initially approved based on one set of data, but later withdrawn from the market based on a second set of data. In this analysis, a dimensionless risk to benefit ratio was calculated in each instance, based on the risk and benefit quantified in similar units. The results indicated that FDA decisions to approve the drug corresponded to risk to benefit ratios less than or equal to 0.136, and that decisions to withdraw the drug from the US market corresponded to risk to benefit ratios greater than or equal to 0.092. The probability of FDA approval was then estimated using logistic regression analysis. The results of this analysis indicated that there was a 50% probability of FDA approval if the risk to benefit ratio was 0.121, and that the probability approaches 100% for values much less than 0.121, and the probability approaches 0% for values much greater than 0.121. The large uncertainty in these estimates due to the small sample size and overlapping data may be addressed in the future by applying the methodology to other drugs.
The first vehicle safety rating systems were the US National Highway Traffic Safety Administration’s New Car Assessment Program (NCAP), started in 1979, and the Australasian NCAP, started in 1992. These systems were investigated in order to determine the methods used to develop them and the characteristics that make them scientifically valid. In addition, a proposed safety rating system for All-Terrain Vehicles (ATVs) and Side by Side Vehicles (SSVs) was compared to the automotive NCAP systems in order to determine its scientific validity. The literature related to the history and development of the original NCAP safety rating systems was reviewed. The proposed safety rating system for ATVs was also reviewed and comparisons with the original NCAP systems were made. The original NCAP systems have been based on correlations between the measured acceleration of the head and chest and actual injury outcome probabilities. These systems also were intentionally restricted to providing comparisons between vehicles of similar mass. Based on this premise, criteria for the establishment of a vehicle safety rating system have been developed with the aim to ensure that such a system has validity and provides ratings that are based on scientifically established correlations between objectively and repeatably measured values and desirable safety outcomes. The proposed safety rating system for ATVs and SSVs that was not developed following this method was found to have no basis in known relationships between the test outcomes and injury probabilities. Although the proposed safety rating system for ATVs and SSVs was found to be unacceptable, a methodology for developing a safety rating system that would meet the criteria is proposed. The methodology would involve collecting real-world injury and exposure data and correlations with measurable vehicle characteristics. This correlation could then lead to the development of scientifically valid safety rating systems for ATVs and SSVs.
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