Applying the Bradford Hill Criteria for Causation to Repetitive Head Impacts and Chronic Traumatic Encephalopathy.

Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease associated with a history of repetitive head impacts (RHI). CTE was described in boxers as early as the 1920s and by the 1950s it was widely accepted that hits to the head caused some boxers to become "punch drunk." However, the recent discovery of CTE in American and Australian-rules football, soccer, rugby, ice hockey, and other sports has resulted in renewed debate on whether the relationship between RHI and CTE is causal. Identifying the strength of the evidential relationship between CTE and RHI has implications for public health and medico-legal issues. From a public health perspective, environmentally caused diseases can be mitigated or prevented. Medico-legally, millions of children are exposed to RHI through sports participation; this demographic is too young to legally consent to any potential long-term risks associated with this exposure. To better understand the strength of evidence underlying the possible causal relationship between RHI and CTE, we examined the medical literature through the Bradford Hill criteria for causation. The Bradford Hill criteria, first proposed in 1965 by Sir Austin Bradford Hill, provide a framework to determine if one can justifiably move from an observed association to a verdict of causation. The Bradford Hill criteria include nine viewpoints by which to evaluate human epidemiologic evidence to determine if causation can be deduced: strength, consistency, specificity, temporality, biological gradient, plausibility, coherence, experiment, and analogy. We explored the question of causation by evaluating studies on CTE as it relates to RHI exposure. Through this lens, we found convincing evidence of a causal relationship between RHI and CTE, as well as an absence of evidence-based alternative explanations. By organizing the CTE literature through this framework, we hope to advance the global conversation on CTE mitigation efforts.

Information effects on lay tradeoffs between national regulatory costs and benefits.

A novel stated-preference "macro-risk" approach introduced to estimate the life-prolonging benefits of proposed environmental, health, and safety regulations may answer questions unasked or wrongly answered by conventional revealed-preference (e.g., "wage premiums" for high occupational risks) and stated-preference methods (e.g., willingness to pay for tiny reductions in one's own premature death risk). This new approach asks laypeople to appraise directly their preferred tradeoffs between national regulatory costs and lives prolonged nationwide (regulatory benefits). However, this method may suffer from incomplete lay understanding of national-scale consequences (e.g., billions of dollars in regulatory costs; hundreds of lives prolonged) or tradeoffs (e.g., what are lives prolonged worth?). Here we (1) tested effects of numerical contextual examples to ground each hypothetical regulatory tradeoff, and (2) explored why some people implicitly offer "implausible" values (< $10,000 or > $1 billion) for the social benefit of prolonging one life. In Study 1 (n = 356), after testing their separate effects, we combined three contextual-information aids: (1) comparing hypothetical regulatory costs and benefits to real-life higher and lower values; (2) reframing large numbers into smaller, more familiar terms; and (3) framing regulatory costs as having diffuse versus concentrated impacts. Information increased social benefits values on average (from $4.5 million to $13.8 million). Study 2 (n = 402) found that the most common explanations for "implausible" values included inattention, strong attitudes about regulation, and problems translating values into responses. We discuss implications for this novel stated-preferences method, and for comparing it to micro-risk methods.

Toward Complete, Candid, and Unbiased International Consensus Statements on Concussion in Sport.

Five international consensus statements on concussion in sports have been published. This commentary argues that there is a strong need for a new approach to them that foregrounds public health expertise and patient-centered guidance. Doing so will help players, parents and practitioners keep perspective about these potentially life-altering injuries especially when they recur.

The Pebble Remains in the Master's Hand: Two Careers Spent Learning (Still) from John Evans.

In this article, we discuss four vexing problems in risk-based decision making that John Evans has addressed over the last nearly 40 years and has perennially challenged the two of us and others to think about. We tackle the role in decision making of potential thresholds in dose-response functions, how the lack of health reference values for many chemicals may distort risk management, the challenge of model uncertainty for risk characterization, and the yet-untapped potential for value-of-information analysis to enhance public health decision making. Our theme is that work remains to be done on each of these, but that some of that work would merely involve listening to ideas that John has already offered.

A Decision-Analytic Approach to Addressing the Evidence About Football and Chronic Traumatic Encephalopathy.

Doubts can be raised about almost any assertion that a particular exposure can lead to an increase in a given adverse health effect. Even some of the most well-accepted causal associations in public health, such as that linking cigarette smoking to increased lung cancer risk, have intriguing research questions remaining to be answered. The inquiry whether an exposure causes a disease is never wholly a yes/no question but ought to follow from an appraisal of the weight of evidence supporting the positive conclusion in light of any coherent theories casting doubt on this evidence and the data supporting these. More importantly, such an appraisal cannot be made sensibly without considering the relative consequences to public health and economic welfare of specific actions based on unwarranted credulity (false positives) versus unwarranted skepticism (false negatives). Here we appraise the weight of evidence for the premise that repeated head impacts (RHIs) in professional football can increase the incidence of chronic traumatic encephalopathy (CTE) and, in turn, cause a variety of cognitive and behavioral symptoms. We first dismiss four logical fallacies that should not affect the appraisal of the weight of evidence. We then examine four alternative hypotheses in which RHI is not associated with CTE or symptoms (or both), and we conclude that the chances are small that the RHI→ CTE→ symptoms link is coincidental or artifactual. In particular, we observe that there are many specific interventions for which, even under a skeptical appraisal of the weight of evidence, the costs of a false positive are smaller than the false negative costs of refusing to intervene.

Demystifying Evidence-Based Policy Analysis by Revealing Hidden Value-Laden Constraints.

Consider any choice that affects some social policy. A decision that considers evidence will, at its heart, contain some kind of explicit or implicit "because" statement: "We are doing X because the evidence says Y." But can evidence ever truly speak for itself, in the sense of being reducible to objective utterances that are either correct or in need of correction? Before answering, consider what you'd prefer. Would you rather receive evidence that was free of any value judgments imposed by human actors, that was laden with value judgments that you agree with, or laden with value judgments that you disagree with? The central assertion of this essay is that, throughout policy analysis but especially in assessments of the costs and benefits of regulating versus encouraging new technologies (cost-benefit analysis, or CBA), the first possibility above is a mirage, and the second and third are self-contradictory. Instead, we are overwhelmingly confronted with a fourth possibility: we receive evidence that appears to be (or is deliberately touted as) value neutral but is suffused with hidden value judgments. In the second part of this essay, entitled "A Guided Tour through Inevitable Value Judgments," I identify in a systematic way approximately sixty-five value judgments that are routinely (in some cases, invariably) made in CBA, but that are kept hidden. For each judgment, I discuss its genesis as it is most commonly invoked in CBA, explain how it is hidden in plain sight, and offer one or more value judgments that could be made instead of or in addition to the conventional one. The alternative judgments highlight the width of the spectrum of reasonable conclusions an analyst could reach merely by substituting other judgments for the ones currently embedded. Bringing hidden value judgments to light is doubly valuable. First, it allows discussion to ensue on a level playing field; instead of conclusory statements about what the evidence says, transparency permits statements taking the form of "when channeled through these value judgments, the evidence says this." Perhaps more importantly, transparency about value judgments permits participants in the discussions to offer interpretations of evidence contingent on there being different value judgments chosen at one or more points in the analysis, interpretations that may suggest that alternative course(s) of action are preferable to the one being championed.

Public Perceptions of Regulatory Costs, Their Uncertainty and Interindividual Distribution.

Public perceptions of both risks and regulatory costs shape rational regulatory choices. Despite decades of risk perception studies, this article is the first on regulatory cost perceptions. A survey of 744 U.S. residents probed: (1) How knowledgeable are laypeople about regulatory costs incurred to reduce risks? (2) Do laypeople see official estimates of cost and benefit (lives saved) as accurate? (3) (How) do preferences for hypothetical regulations change when mean-preserving spreads of uncertainty replace certain cost or benefit? and (4) (How) do preferences change when unequal interindividual distributions of hypothetical regulatory costs replace equal distributions? Respondents overestimated costs of regulatory compliance, while assuming agencies underestimate costs. Most assumed agency estimates of benefits are accurate; a third believed both cost and benefit estimates are accurate. Cost and benefit estimates presented without uncertainty were slightly preferred to those surrounded by "narrow uncertainty" (a range of costs or lives entirely within a personally-calibrated zone without clear acceptance or rejection of tradeoffs). Certain estimates were more preferred than "wide uncertainty" (a range of agency estimates extending beyond these personal bounds, thus posing a gamble between favored and unacceptable tradeoffs), particularly for costs as opposed to benefits (but even for costs a quarter of respondents preferred wide uncertainty to certainty). Agency-acknowledged uncertainty in general elicited mixed judgments of honesty and trustworthiness. People preferred egalitarian distributions of regulatory costs, despite skewed actual cost distributions, and preferred progressive cost distributions (the rich pay a greater than proportional share) to regressive ones. Efficient and socially responsive regulations require disclosure of much more information about regulatory costs and risks.

EPA underestimates, oversimplifies, miscommunicates, and mismanages cancer risks by ignoring human susceptibility.

If exposed to an identical concentration of a carcinogen, every human being would face a different level of risk, determined by his or her genetic, environmental, medical, and other uniquely individual characteristics. Various lines of evidence indicate that this susceptibility variable is distributed rather broadly in the human population, with perhaps a factor of 25- to 50-fold between the center of this distribution and either of its tails, but cancer risk assessment at the EPA and elsewhere has always treated every (adult) human as identically susceptible. The National Academy of Sciences "Silver Book" concluded that EPA and the other agencies should fundamentally correct their mis-computation of carcinogenic risk in two ways: (1) adjust individual risk estimates upward to provide information about the upper tail; and (2) adjust population risk estimates upward (by about sevenfold) to correct an underestimation due to a mathematical property of the interindividual distribution of human susceptibility, in which the susceptibility averaged over the entire (right-skewed) population exceeds the median value for the typical human. In this issue of Risk Analysis, Kenneth Bogen disputes the second adjustment and endorses the first, though he also relegates the problem of underestimated individual risks to the realm of "equity concerns" that he says should have little if any bearing on risk management policy. In this article, I show why the basis for the population risk adjustment that the NAS recommended is correct-that current population cancer risk estimates, whether they are derived from animal bioassays or from human epidemiologic studies, likely provide estimates of the median with respect to human variation, which in turn must be an underestimate of the mean. If cancer risk estimates have larger "conservative" biases embedded in them, a premise I have disputed in many previous writings, such a defect would not excuse ignoring this additional bias in the direction of underestimation. I also demonstrate that sensible, legally appropriate, and ethical risk policy must not only inform the public when the tail of the individual risk distribution extends into the "high-risk" range, but must alter benefit-cost balancing to account for the need to try to reduce these tail risks preferentially.

Perceiving others' perceptions of risk: still a task for Sisyphus.

The recent literature providing insights from neuroscience and evolutionary biology into how individuals perceive risky choice situations represents a "second wave" of findings that recapitulates as well as challenges the risk perception research begun in the 1980s, which relied on psychometric survey research. Gleaning insights from the first wave of research that could improve the communication and control of environmental risks has yielded disappointing results. This is a result, in part, of the eagerness of scholars and pundits to posit a chasm between the "rational" and "objective" perceptions of experts, on the one hand, and a lay public that is seen as lurching between "paranoia and neglect" and as insensitive to the magnitude of risks. Interpretations of the psychometric research have suffered from inattention to uncertainty and interindividual variability in risk, to expert biases, and to important aspects of risky choice that were not explored in the first wave of research. Initial signs indicate that neuroscience and evolutionary biology research may fall prey to similar misinterpretations. This article summarizes some of the most intriguing findings of the "second wave" of risk perception research and advances four themes that may help make the new findings less divisive and more useful for improving risk communication and risk management. Continued research into risk perception should perhaps be embedded in a more general theory of public choice in the face of uncertain and variable costs and benefits and with a respect for distributive justice as an important goal in risk management.