Vaccines and the social amplification of risk.

In 2019, the World Health Organization (WHO) named "Vaccine Hesitancy" one of the top 10 threats to global health. Shortly afterward, the COVID-19 pandemic emerged as the world's predominant health concern. COVID-19 vaccines of several types have been developed, tested, and partially deployed with remarkable speed; vaccines are now the primary control measure and hope for a return to normalcy. However, hesitancy concerning these vaccines, along with resistance to masking and other control measures, remains a substantial obstacle. The previous waves of vaccine hesitancy that led to the WHO threat designation, together with recent COVID-19 experience, provide a window for viewing new forms of social amplification of risk (SAR). Not surprisingly, vaccines provide fertile ground for questions, anxieties, concerns, and rumors. These appear in new globalized hyperconnected communications landscapes and in the context of complex human (social, economic, and political) systems that exhibit evolving concerns about vaccines and authorities. We look at drivers, impacts, and implications for vaccine initiatives in several recent historical examples and in the current efforts with COVID-19 vaccination. Findings and insights were drawn from the Vaccine Confidence Project's decade long monitoring of media and social media and its related research efforts. The trends in vaccine confidence and resistance have implications for updating the social amplification of risk framework (SARF); in turn, SARF has practical implications for guiding efforts to alleviate vaccine hesitancy and to mitigate harms from intentional and unintentional vaccine scares.

Through a Glass Darkly: How Natural Science and Technical Communities Looked at Social Science Advances in Understanding Risk.

This article is one piece in a series of articles that reflect on advances in ideas about risk made by social science over the past 40 years and more. It differs from the other articles: its focus is not on specific advances themselves, but rather on how those advances were received and were encouraged or discouraged by the natural science and technical members of the risk community. Thus, the principal goal of this article is to provide some context for the other articlers in this series. Those articles describe work and intellectual developments that consider human responses to particular sorts of issues, concerns, and needs that relate to risk. The framing of this work was partly driven and shaped by natural science and engineering communities. It is illuminating to reflect on how these technical communities viewed the social science developments and on the perspectives they brought to the framing of issues and concerns. Their views are described in three minihistories of risk developments pertaining to nuclear accidents, high level radioactive waste disposal, and toxic chemicals. After considering common themes among the stories, the article considers characteristics of expert communities and their implications. It then concludes with discussions of its secondary goals, (i) a look at some opportunities for future social science studies relating to risk, (ii) a consideration of the extent to which risk analysis and broader considerations of risk can be considered a truly interdisciplinary field rather than a loose assemblage of perspectives.

Evaluation of child/adult pharmacokinetic differences from a database derived from the therapeutic drug literature.

Pharmacokinetics (PK) of xenobiotics can differ widely between children and adults due to physiological differences and the immaturity of enzyme systems and clearance mechanisms. This makes extrapolation of adult dosimetry estimates to children uncertain, especially at early postnatal ages. While there is very little PK data for environmental toxicants in children, there is a wealth of such data for therapeutic drugs. Using published literature, a Children's PK Database has been compiled which compares PK parameters between children and adults for 45 drugs. This has enabled comparison of child and adult PK function across a number of cytochrome P450 (CYP) pathways, as well as certain Phase II conjugation reactions and renal elimination. These comparisons indicate that premature and full-term neonates tend to have 3 to 9 times longer half-life than adults for the drugs included in the database. This difference disappears by 2-6 months of age. Beyond this age, half-life can be shorter than in adults for specific drugs and pathways. The range of neonate/adult half-life ratios exceeds the 3.16-fold factor commonly ascribed to interindividual PK variability. Thus, this uncertainty factor may not be adequate for certain chemicals in the early postnatal period. The current findings present a PK developmental profile that is relevant to environmental toxicants metabolized and cleared by the pathways represented in the current database. The manner in which this PK information can be applied to the risk assessment of children includes several different approaches: qualitative (e.g., enhanced discussion of uncertainties), semiquantitative (age group-specific adjustment factors), and quantitative (estimation of internal dosimetry in children via physiologically based PK modeling).

The history of uranium mining and the Navajo people.

From World War II until 1971, the government was the sole purchaser of uranium ore in the United States. Uranium mining occurred mostly in the southwestern United States and drew many Native Americans and others into work in the mines and mills. Despite a long and well-developed understanding, based on the European experience earlier in the century, that uranium mining led to high rates of lung cancer, few protections were provided for US miners before 1962 and their adoption after that time was slow and incomplete. The resulting high rates of illness among miners led in 1990 to passage of the Radiation Exposure Compensation Act.

The radiation exposure compensation act: what is fair?

In 1990 the U.S. Congress passed a law providing compensation to former uranium miners who became ill while the U.S. Government was the sole purchaser of uranium. Ten years later, in 2000, the law was amended to correct widely perceived problems. We reviewed the content of the Radiation Exposure Compensation Act (RECA) laws and regulations, cataloged complaints about the 1990 law, compared the law to the scientific knowledge base in 1990 and in the present, reviewed the 2000 amendments to RECA, and drew lessons about how such compensation programs might be better structured. We concur with popular sentiment that the 1990 law had numerous flaws, the central one being that it failed to compensate many miners who by most other standards would have been deemed deserving. This problem arose through setting exposure criteria very high (at six to 15 times elevated risk), with a disproportionate burden placed on miners who had smoked. The additional burden on smokers was exacerbated by a very stringent definition of smokers (one pack-year in a lifetime). Federal compensation laws should prioritize payment to deserving claimants rather than excluding un-deserving claimants. Thus, a doubling of risk should be an upper limit for setting an eligibility threshold and a lower "significant contributory effect" standard could be considered more appropriate. Uncertainties in exposure and in dose response should be considered and resolved with a bias toward compensation. Beyond setting appropriate criteria, an active effort is needed to inform potentially eligible people and to assist them in qualifying; the eligibility criteria and the requirements for documentation should be appropriate for Native Americans and other cultural groups. Built-in evaluation mechanisms are needed for all compensation programs to assess whether they are meeting their stated objectives.

Differences in pharmacokinetics between children and adults--II. Children's variability in drug elimination half-lives and in some parameters needed for physiologically-based pharmacokinetic modeling.

In earlier work we assembled a database of classical pharmacokinetic parameters (e.g., elimination half-lives; volumes of distribution) in children and adults. These data were then analyzed to define mean differences between adults and children of various age groups. In this article, we first analyze the variability in half-life observations where individual data exist. The major findings are as follows. The age groups defined in the earlier analysis of arithmetic mean data (0-1 week premature; 0-1 week full term; 1 week to 2 months; 2-6 months; 6 months to 2 years; 2-12 years; and 12-18 years) are reasonable for depicting child/adult pharmacokinetic differences, but data for some of the earliest age groups are highly variable. The fraction of individual children's half-lives observed to exceed the adult mean half-life by more than the 3.2-fold uncertainty factor commonly attributed to interindividual pharmacokinetic variability is 27% (16/59) for the 0-1 week age group, and 19% (5/26) in the 1 week to 2 month age group, compared to 0/87 for all the other age groups combined between 2 months and 18 years. Children within specific age groups appear to differ from adults with respect to the amount of variability and the form of the distribution of half-lives across the population. The data indicate departure from simple unimodal distributions, particularly in the 1 week to 2 month age group, suggesting that key developmental steps affecting drug removal tend to occur in that period. Finally, in preparation for age-dependent physiologically-based pharmacokinetic modeling, nationally representative NHANES III data are analyzed for distributions of body size and fat content. The data from about age 3 to age 10 reveal important departures from simple unimodal distributional forms-in the direction suggesting a subpopulation of children that are markedly heavier than those in the major mode. For risk assessment modeling, this means that analysts will need to consider "mixed" distributions (e.g., two or more normal or log-normal modes) in which the proportions of children falling within the major versus highweight/fat modes in the mixture changes as a function of age. Biologically, the most natural interpretation of this is that these subpopulations represent children who have or have not yet received particular signals for change in growth pattern. These apparently distinct subpopulations would be expected to exhibit different disposition of xenobiotics, particularly those that are highly lipophilic and poorly metabolized.