Clinical Interaction
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A Clinical Interaction is a Statistical Interaction that evaluates the joint effects of 2 or more medical interventions or/and exposures.
- AKA: Clinical Interaction Effect.
- Context:
- It can range from being a Quantitative Clinical Interaction to being a Qualitative Clinical Interaction.
- It can range from being an Additive Clinical Interaction to being a Multiplicative Clinical Interaction.
- It can range from being a Pharmacodynamic Interaction to being a Pharmacokinetic Interaction.
- It can range from being a Synergistic Interaction to being a Antagonistic Interaction.
- Example(s):
- a Drug-Drug Interaction such as:
- joint interaction effect of low-dose aspirin and warfarin for the prevention of ischemic heart disease;
- a Drug-Disease Interaction such as:
- interaction between stroke severity and the efficacy of a drug on patient survival;
- interaction between smoking and inhaling asbestos fibres;
- …
- a Drug-Drug Interaction such as:
- Counter-Example(s):
- See: Synergism, Antagonism, Mediation Analysis, Statistics, Additive Map, Regression Analysis, Factorial Experiments, Exposure-Outcome Relationship, Cause-Effect Relationship, Disease-Disease Association.
References
2022a
- (Wikipedia, 2022) ⇒ https://en.wikipedia.org/wiki/Interaction#Medicine_and_pharmacology Retrieved:2022-3-20.
- In medicine, most medications can be safely used with other medicines, but particular combinations of medicines need to be monitored for interactions, often by the pharmacist. Interactions between medications fall generally into one of two main categories:
- pharmacodynamic: Involving the actions of the two interacting drugs.
- pharmacokinetic: Involving the absorption, distribution, metabolism, and excretion of one or both of the interacting drugs upon the other.
- In medicine, most medications can be safely used with other medicines, but particular combinations of medicines need to be monitored for interactions, often by the pharmacist. Interactions between medications fall generally into one of two main categories:
- In terms of efficacy, there can be three types of interactions between medications: additive, synergistic, and antagonistic.
- Additive interaction means the effect of two chemicals is equal to the sum of the effect of the two chemicals taken separately. This is usually due to the two chemicals acting on the body via same or similar mechanism. Examples are aspirin and motrin, alcohol and depressant, tranquilizer and painkiller.
- Synergistic interaction means that the effect of two chemicals taken together is greater than the sum of their separate effect at the same doses. An example is pesticide and fertilizer.
- Antagonistic interaction means that the effect of two chemicals is actually less than the sum of the effect of the two drugs taken independently of each other. This is because the second chemical increases the excretion of the first, or even directly blocks its toxic actions. Antagonism forms the basis for antidotes of poisonings.
- In terms of efficacy, there can be three types of interactions between medications: additive, synergistic, and antagonistic.
2022b
- (Wikipedia, 2022) ⇒ https://en.wikipedia.org/wiki/Glossary_of_clinical_research#I Retrieved:2022-3-20.
- QUOTE: Interaction (Qualitative & Quantitative)
- The situation in which a treatment contrast (e.g. difference between investigational product and control) is dependent on another factor (e.g. centre). A quantitative interaction refers to the case where the magnitude of the contrast differs at the different levels of the factor, whereas for a qualitative interaction the direction of the contrast differs for at least one level of the factor. (ICH E9)
- QUOTE: Interaction (Qualitative & Quantitative)
2021
- (Bours, 2021) ⇒ Martijn J.L.Bours (2021). "Tutorial: A nontechnical explanation of the counterfactual definition of effect modification and interaction". In: Journal of clinical epidemiology, 134, 113-124.
- QUOTE: In other words, to study for whom and in which situation(s) causal effects occur. Studying the combined influence of two (or more) exposures on some outcome constitutes a more elaborate and refined type of causal question that refers to the concepts of effect modification and interaction(...). What's more, effect modification and interaction may sometimes be confused with the concept of confounding. Confounding is concerned with separating causal from noncausal effects that cloud inferences about exposure-outcome relations (...). Unlike confounding though, effect modification and interaction are not unwanted biases to be eliminated, but are part of causal reality to be elucidated (...).
Effect modification and interaction have been defined as follows within the field of epidemiology (...):
- Effect modification: Variation in the selected effect measure for the factor under study across levels of another factor.
- Interaction: The interdependent, reciprocal, or mutual operation, action, or effect of two or more factors to produce, prevent, control, mediate, or otherwise influence the occurrence of an event.
- QUOTE: In other words, to study for whom and in which situation(s) causal effects occur. Studying the combined influence of two (or more) exposures on some outcome constitutes a more elaborate and refined type of causal question that refers to the concepts of effect modification and interaction(...). What's more, effect modification and interaction may sometimes be confused with the concept of confounding. Confounding is concerned with separating causal from noncausal effects that cloud inferences about exposure-outcome relations (...). Unlike confounding though, effect modification and interaction are not unwanted biases to be eliminated, but are part of causal reality to be elucidated (...).
2017
- (Corraini et al., 2017) ⇒ Priscila Corraini, Morten Olsen, Lars Pedersen, Olaf M. Dekkers, and Jan P. Vandenbroucke (2017). "Effect modification, interaction and mediation: an overview of theoretical insights for clinical investigators". In: Clinical epidemiology, 9, 331.
- QUOTE: The notions of effect modification, interaction and mediation represent conceptually different, although potentially interdependent notions. These subtle different notions address different research aims, which are related to different aspects of an exposure–outcome relationship (Box 1).
| Type of assessment | Aim of the assessment |
|---|---|
| Effect modification | Separate exposure effects according to another variable (...) |
| Interaction | Evaluate individual and joint effects of exposures (...) |
| Mediation | Evaluate direct and indirect effects of exposures (...) |
- The clinical motivation behind the assessment of effect modification is to identify whether the effect of a treatment (or exposure) is different in groups of patients with different characteristics. If the effects are the same, the treatment (or exposure) effect is called homogeneous; if the effects are different, they are called heterogeneous(...).
Assessing effect modification may also help to identify a subset of patients who would not benefit from an intervention at all(...).
Interaction is of interest when researchers want to obtain the joint effect of two (or more) exposures on a disease or outcome.[1] To be considered a synergistic interaction, the joint effect has to be higher than the effect expected by the sum of their individual effects. Conversely, there is an antagonistic interaction between exposures, when the joint effect is less than the sum of their individual effects. This is in contrast to effect modification, where the effect of an exposure on an outcome is assessed in different strata of a third variable, but a joint effect is not assessed.
From a clinical perspective, to assess interaction is particularly important when a disease can be treated by a combination of two or more treatments.
- The clinical motivation behind the assessment of effect modification is to identify whether the effect of a treatment (or exposure) is different in groups of patients with different characteristics. If the effects are the same, the treatment (or exposure) effect is called homogeneous; if the effects are different, they are called heterogeneous(...).
- ↑ Rothman KJ. Synergy and antagonism in cause-effect relationships. Am J Epidemiol. 1974;99(6):385–388.
2012
- (Knol & VanderWeele,2012) ⇒ Mirjam J. Knol, and Tyler J. VanderWeele (2012). "Recommendations for presenting analyses of effect modification and interaction". In: International Journal of Epidemiology, 41(2), 514-520.
- QUOTE: Suppose now instead we study the interaction between A and B (the two exposures of interest) on D (the outcome), where A, B and D are dichotomous. We propose the following four steps in presenting the results of this analysis which will allow a reader to obtain the information needed to assess interaction (...): Note that Steps 1 and 3 are exactly the same for studying interaction or effect modification. Step 2 for studying interaction, however, requires presenting the effects in strata of B and strata of A, whereas Step 2 for studying effect modification only includes presenting the effects in strata of X (the effect modifier). Step 4 for studying interaction requires that confounders for both the relation between A and D and between B and D are reported, whereas Step 4 for studying effect modification only includes listing the confounders for the relation between A and D.
2009b
- (VanderWeele, 2009) ⇒ Tyler J. VanderWeele (2009). "On the Distinction Between Interaction and Effect Modification". In: Epidemiology, 20(6), 863-871.
- QUOTE: Interaction is defined in terms of the effects of 2 interventions whereas effect modification is defined in terms of the effect of one intervention varying across strata of a second variable. Effect modification can be present with no interaction; interaction can be present with no effect modification.