The Zero-Risk Illusion and Over-Finding — An Adult Relationship with Risk

"Let me note this just in case" — as these words accumulate, the correction request grows long, the other's defence grows deep, and even the findings that truly mattered become buried. This volume reads this phenomenon in the field of regulatory review through the concept of the zero-risk illusion. Bringing risk to zero is, in principle, impossible — yet we frequently try to approach zero, and in doing so generate another risk: over-finding. Sunstein, Slovic, Beck, Aristotle, the Buddha, and Taleb — six traditions on the practice of an adult relationship with risk.

01"Zero Risk" — a Contradiction in Terms

The expression "bring risk to zero" is commonly used, but on reflection it contains a contradiction. Risk is "the product of the probability and the impact of an undesirable event." To make both probability and impact strictly zero is impossible in principle in the real world. Yet we frequently move with zero risk as the goal. Why?

One reason is that human cognition of risk is not probabilistic but emotional. Even at small probability, an event that is easy to imagine and dreadful is overrated; even at large probability, an event that is everyday and familiar is underrated. When "findings just in case" multiply in the field of regulatory review, we are often pulled by the worst-case scenario that is easy to imagine. The first two of this volume — Sunstein and Slovic — illuminated this scientifically.

02Sunstein, "Laws of Fear" — Risk-Perception Bias and Over-Regulation

The American legal scholar Cass Sunstein (1954–), in Laws of Fear (2005), thoroughly analysed the cognitive biases around risk in individuals and society. His central proposition:

"The instinct to aim at zero risk (zero-risk bias) is deeply embedded in human cognition. But the pursuit of zero risk frequently generates other risks. The opportunity cost of risk reduction, the cost of over-regulation, secondary harms — these are overlooked." — paraphrase of Cass Sunstein, Laws of Fear (2005)

What Sunstein shows is the paradox that "lowering risk," which is in itself desirable, depending on context can on the whole increase risk. In approaching one risk toward zero, other risks (time, cost, trust, opportunity loss) grow. In the pharmaceutical field, multiplying "findings just in case" on one material generates other risks — important findings are buried, trust with the requester is damaged, the organisation's processing capacity is squeezed. Risk cannot be seen as a single number but only as the equilibrium relation among multiple risks.

03Slovic, "Dread and the Unknown" — Risks That Feel Frightening Are Overrated

The American psychologist Paul Slovic (1938–), from the 1980s, developed a two-dimensional model of human risk perception. The two axes: dread (the feeling of fear) and unknown.

"Subjective evaluation of risk is decided not only by objective probability and impact but varies greatly along the two axes of 'how dreadful it feels (dread)' and 'how unknown (unknown).' Between nuclear accidents and automobile accidents, both probability and fatality rate differ greatly, but people's evaluations line up differently from the objective data." — paraphrase of Paul Slovic, "Perception of Risk," Science (1987)

Slovic's finding has become the foundation of risk communication. When, in pharmaceutical material review, one imagines "if this were reported as a major pharmaceutical incident," that imagination amplifies dread and operates in the direction of overrating risk. As a safety-side bias it functions in itself, but when it operates excessively it generates the chain of over-finding and "just in case." The discipline of observing how strongly dread is operating within oneself supports the quality of risk judgement.

04Beck, "Risk Society" — Risk Is Not Individual Event but Social Structure

The German sociologist Ulrich Beck (1944–2015), in Risikogesellschaft (1986), diagnosed late-twentieth-century society as a risk society.

"The central problem of modern society has shifted from the distribution of wealth to the distribution of risk. Risk is not an individual event but is woven into the very structure of society. Therefore, the response to risk is not completed by the individual's judgement alone; it requires the design of social mechanisms." — paraphrase of Ulrich Beck, Risk Society (1986)

Applied to pharmaceuticals, Beck's implication is this: even by stuffing risk excessively into individual materials, the risk of society as a whole does not fall. Rather, by situating risk within the social mechanisms — the organisation's processing capacity, the industry's trust, the evolution of regulation, the communication of information to patients — the overall risk falls as a result.

This is not to say that individual findings may be sloppy. It demands the dual-layer perspective of being simultaneously conscious of the quality of individual findings and the design of social mechanisms.

05Aristotle's "Mean" — The Place of Virtue, Neither Excess nor Deficiency

The ancient Greek Aristotle, in Nicomachean Ethics, defined virtue as the mean (mesotēs).

"Virtue is the mean between excess and deficiency. Courage is the mean between recklessness and cowardice; temperance is the mean between licence and insensibility; liberality is the mean between profligacy and parsimony." — paraphrase of Aristotle, Nicomachean Ethics, Book II

Let us apply Aristotle's concept of the mean to risk judgement. The ideal response to risk is neither underestimation nor overestimation but the mean in that context. The continuing increase of "just in case" findings is excess (the bias of inhibition). To make light of important risks is deficiency (the bias of optimism). The mean is the judgement that discerns the "appropriate position" that differs by context.

In the pharmaceutical field, placing findings on every material with the same weight is not the mean. Changing the quantity and depth of findings according to context (the risk hierarchy of the product, the vulnerability of the patient population, the reach of the medium, the possibility of misunderstanding). This is the applied form of what Aristotle called phronesis (practical wisdom).

06The Buddha's "Middle Way" — The Eastern Response of Avoiding Both Extremes

From the Eastern lineage, the classical proposition most deeply applicable to risk judgement. The Middle Way (madhyamā pratipad), said to be taught by the Buddha (5th–6th c. BCE) in the first turning of the Dharma wheel after awakening.

Monks, the renunciant should avoid two extremes. One is to abandon oneself to the objects of desire. The other is to give oneself over to mortification. The Tathāgata has awakened to the Middle Way, which avoids both extremes.
— gist from the Dhammacakkappavattana Sutta (the Setting in Motion of the Wheel of the Dharma)

The Buddha's Middle Way, from a lineage different from Aristotle's mean, points to a strikingly similar place. The two extremes are often the same trap in disguise. The extreme of aiming for zero risk and the extreme of making light of risk — both are distortions of cognition. The Middle Way is not the midpoint between the two extremes but the very perspective from which both extremes can be surveyed.

In the field of regulatory review, when one hesitates whether to issue a correction, apply the Buddha's question. "Is the self that would issue this finding being pulled by the extreme of zero risk? Is the self that would not issue it being pulled by the extreme of making light?" The moment one becomes conscious of the two extremes, the position of the Middle Way comes into view.

07Taleb, "Fragile and Antifragile" — The Hidden Cost of Pursuing Zero Risk

The Lebanese-American probability researcher Nassim Nicholas Taleb (1960–), in Antifragile (2012), distinguished three responses to risk.

"The system that aims at zero risk often becomes the most fragile. It has no room to absorb variation, and a small shock generates a chain reaction. A healthy system becomes antifragile by experiencing moderate variation." — paraphrase of Nassim Taleb, Antifragile (2012)

Taleb's implication applies to pharmaceutical organisations as well. The organisation that continues over-finding in pursuit of zero risk becomes, ironically, the most fragile. The chain of findings expands the rules, the field's capacity for judgement thins, and the capacity to respond to truly important risks drops. Conversely, the organisation that accepts moderate risk and learns from small failures grows antifragile and stronger over the long term. The pursuit of zero risk itself generates great risk — Taleb formalised this paradox in the language of probability.

08The Hidden Costs of Over-Finding

Let us bring the abstract down to the hidden costs in the field. Over-finding is often justified as "for safety," but it actually generates several costs.

These costs often accumulate while invisible. Over-finding is not an investment in safety but an investment in another risk — this perspective is the core of the volume.

09An Adult Relationship with Risk in the Pharmaceutical Field

Let us bring it down to the field. How to apply the wisdom of this volume in the scene where a reviewer hesitates whether to issue one finding.

These are not practices for bringing risk to zero, but practices for handling risk maturely. What cannot be made zero is not to be forced toward zero but placed at the appropriate position. This is Aristotle's mean, the Buddha's Middle Way, and Taleb's antifragility.

10An Adult Relationship with Risk — Four Practices

To bring the same place to which the six traditions pointed down into daily practice, four practices are set here.

Zero risk does not exist. This is not an expression of weakness but a fact on which probability and cognitive science agree. Sunstein, Slovic, Beck, Aristotle, the Buddha, Taleb — six traditions pointed, in different words, to the same place. An adult relationship with risk is not bringing risk to zero but placing it at the appropriate position. Aristotle's mean, the Buddha's Middle Way, and Taleb's antifragility illuminate the same place from different angles.

"Let me note this just in case" — when you are about to write this, ask again. "Can I say one concrete adverse effect if this were not noted?" If yes, issue. If no, think one step further. That is the entry to an adult relationship with risk.