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Less serious or trivial

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, High requirements, important; low requirements, less important.

, High requirements, important; low requirements, less important.

sensitivity is less important [use of the marker would still be expected to result in fewer adverse reactions (ARs) than would otherwise be encountered; in indications where ARs are often viewed as necessary trade-offs].

On the other end of the spectrum, in more trivial indications where treatment is less urgent, the requirement for a safety marker would be very high sensitivity, as a false-negative test would result in the occurrence of an AR, which in this setting is much less acceptable than in a life-threatening illness. Specificity is less important, as "wrongful" withholding in a condition of modest severity is clearly less of an issue. Conversely, again, an efficacy marker would be expected to show high specificity: If the added cost of the test is to be acceptable in such a condition, it would presumably need to be justified more by cost-benefit considerations that would be set off by inappropriate inclusion in the treatment group of patients with false-positive test results.

One may view these considerations from the standpoint of that old medical principle: first, do no harm. In serious disease, the threat may come primarily from the illness, so harm would more likely result from inappropriate withholding of treatment based on a false test result. In contrast, in less serious disease, harm may, rather, come from inappropriate administration of a treatment, and one would perhaps be more aligned with the Hippocratic principle by avoiding noncritical treatments.

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