Many of us have learned that large experiments with representative samples and random allocation of participants are vital to be able to generalise results back to the target population. Yet we must be careful in applying these results for individuals, for two reasons. Sometimes the individual may not represent the target population, and at other times, the individual may represent a sub-group within the target population for which the intervention was not beneficial or in fact, harmful.
A recent article explained this dilemma in relation to the benefits of taking certain drugs, and offered a short checklist to help make these recommendations. First of all, it is important to understand the pathophysiological explanation for how a particular drug works, in its target population. For many drugs, we have a good understanding of the way in which key chemicals and compounds are absorbed, distributed, metabolised and excreted. This is described as the normal mechanism of action.
Therefore, if the individual in question has the same normal mechanism of action, it is most likely that the chosen drug will have the same effect as it did on everyone else in the trial. However, if some aspect of the individual is different; they are much older, they have existing disease or they are overweight; then it is not so likely that the outcomes will be the same for that person. Some trials publish results for some of these key points of difference, but in many cases descriptions are limited.
Three key steps are offered as a way to better understand whether an individual may benefit from a specific research recommendation.
- is there a clear explanation of the mechanisms of how the intervention works? (is this supported by research evidence?)
- is the underlying mechanism of action for the target population, similar for the individual?
- are the contextual factors influencing whether relevant mechanisms are activated similar between the target population and individual?
The authors argue that judgement is always required in deciding to use research results for an individual. This article illustrates both how we do understand the mechanisms of actions for certain drugs and uses a black box to show where the mechanism of action is not well understood.
I wonder if this checklist of 3 important questions can also be applied to non-drug interventions, such as rehabilitation programmes, counselling or cognitive behaviour therapies? Instead of explaining the pathophysiological explanation for how a particular drug works, there will need to be a description of key components, and their associated materials, procedures, people, environments, and theoretical rationale. A new TIDieR checklist has been developed which emphasises the importance of describing the mechanisms of action for the active components of an intervention.