Table 1.

Different phases of mechanisms

	Examples of phase-specific mechanisms (or conditions, in the case of Phase I)
	Pharmacological therapy	Surgery (e.g. hip replacement)	Physiotherapy	‘Talking’ psychological therapies (e.g. CBT for depression)
Phase I – Set-up Conditions that must obtain in order to deliver the intervention	Correct diagnosis (implicit), availability of an appropriate formulation, etc.	Correct diagnosis (implicit), delivery of anaesthesia, clean instruments, etc.	Correct diagnosis (implicit), a comfortable environment in which the physiotherapeutic exercises can be performed, comfortable loose clothing, etc.	Correct diagnosis (implicit), establishing an appropriate (quiet, calm) environment, etc.
Phase II – Delivery The time after the ‘set-up’ and before the technology reaches the proximate site of action 1.1.1	Pharmaceutical and pharmacokinetic mechanisms (ADME)	(When the proximate site of action is accessed): skin, subcutaneous tissues, fat, muscle, blood vessels, etc.	(Such as when a preliminary strength exercise or stretch is performed): musculoskeletal system, nervous system, etc.	(The phase in which questions are asked, and problems are revealed): ‘mechanisms’ of speech, hearing, and understanding
Phase III – Action When the technology achieves proximate actions 1.1.2	Pharmacodynamic mechanisms	(When the problem is repaired): musculoskeletal mechanisms	(Such as a strength or flexibility exercise that improves neuromuscular functions): musculoskeletal, etc.	(When changes in understanding/ insight/ behaviour are achieved): cognitive mechanisms, etc.
Phase IV – Outcome The patient-relevant outcome that results from proximate actions and outcomes	Mechanisms involved in death (when the outcome is mortality); any other mechanisms involved in quality of life and other patient relevant outcomes; palliation, cure, prevention	Mechanisms involved in death (when the outcome is mortality); any other mechanisms involved in quality of life and other patient relevant outcomes, etc.	Mechanisms involved in death (when the outcome is mortality); any other mechanisms involved in quality of life and other patient relevant outcomes, etc.	Mechanisms involved in quality of life and other patient relevant outcomes

ADME = absorption, distribution, metabolism and excretion mechanisms