Dose-Response Relationship

A Dose-Response Relationship is a stimulus response function that describes the response of an organism to a medical dose over a time period.

• Context:
  • It can be described by a Dose-Response Curve.
• Example(s):
  • a Dose Exposure-Response Relationship,
  • a Dose Concentration-Response Relationship,
  • …
• Counter-Example(s):
  • Plasma Exposure-Response Relationship,
  • Plasma Concentration-Response Relationship,
  • Arndt-Schulz Rule,
  • Drug-Dependent Effect,
  • Drug-Limiting Effect.
• See: Dose-Response Study, Sensory Receptor, Drug Delivery, Biochemistry, Stimulus, Stressor, Ceiling Effect, Pharmacodynamics, Spatial Epidemiology, Weber-Fechner Law, Dose Fractionation, Adverse Effect, Schild Snalysis, Agonist-Antagonist Opioids, Pain Ladder.

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References

2021

• (Wikipedia, 2021) ⇒ https://en.wikipedia.org/wiki/Dose–response_relationship Retrieved:2021-12-12.
  • The dose–response relationship, or exposure–response relationship, describes the magnitude of the response of an organism, as a function of exposure (or doses) to a stimulus or stressor (usually a chemical) after a certain exposure time. Dose–response relationships can be described by dose–response curves. This is explained further in the following sections. A stimulus response function or stimulus response curve is defined more broadly as the response from any type of stimulus, not limited to chemicals.

2003

• (FDA, 2003) ⇒ U.S. Department of Health and Human Services Food and Drug Administration (FDA), Center for Drug Evaluation and Research (CDER), and Center for Biologics Evaluation and Research (CBER) (2003). "Guidance for Industry: Exposure-Response Relationships — Study Design, Data Analysis, and Regulatory Applications".
  • QUOTE: Exposure-response information can support the primary evidence of safety and/or efficacy. In some circumstances, exposure-response information can provide important insights that can allow a better understanding of the clinical trial data (e.g., in explaining a marginal result on the basis of knowledge of systemic concentration-response relationships and achieved concentrations). Ideally, in such cases the explanation would be further tested, but in some cases this information could support approval. Even when the clinical efficacy data are convincing, there may be a safety concern that exposure-response data can resolve. For example, it might be reassuring to observe that even patients with increased plasma concentrations (e.g., metabolic outliers or patients on other drugs in a study) do not have increased toxicity in general or with respect to a particular concern (e.g., QT prolongation). Exposure-response data thus can add to the weight of evidence of an acceptable risk/benefit relationship and support approval. The exposure-response data might also be used to understand or support evidence of subgroup differences suggested in clinical trials, and to establish covariate relationships that explain, and enhance the plausibility of, observed subgroup differences in response.

1981

• (Altshuler, 1981) ⇒ Bernard Altshuler (1981). "Modeling of dose-response relationships". In: Environmental health perspectives, 42, 23-27.
  • QUOTE: The focus of this paper is on chronic toxicity with irreversible components and in particular on cancer. It presents the more important dose-response functions, which are of two kinds: dichotomous response and timed response.

    In dichotomous response, the outcome of a single animal trial is either "yes, with cancer" or "no, without cancer;" the animal is either a responder or a non-responder. Response of an experimental group of animals is the fraction of responders.

     Timed response refers to the measurement of the experimental life of the animal which is terminated by the occurrence of cancer or the occurrence of some non-cancer event and are described by time-to-occurrence models.

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