Abstract
Treatment mechanisms (TM) reflect the steps or processes through which a treatment unfolds. However, TM research faces challenges due to inconsistent terminology and varying measurement approaches for each mechanism, which creates confusion and controversy among clinicians and scientists. In this paper, we: 1) define key terms associated with TM, 2) provide recommended categories of study that reflect intervention domains, and 3) present examples of measures of TM within the defined categories. Our recommended definitions differentiate associated TM (a finding that occurs following administration of a treatment that may or may not influence outcomes) from causal TM (which directly affects the clinical outcome). When measuring causal TM, we recommend that researchers consider three potential categories of interventional domains: a) anatomical, b) psychological/cognitive and c) behavioral. Lastly, we argue that within each interventional domain, TM can be measured across a spectrum that includes physiological (e.g., brain activity, nerve activity, biomarkers, etc.) and functional (e.g., range of motion, stiffness, cognition measures, etc.) mechanisms. Measuring both physiological and functional mechanisms improves the likelihood of understanding the complexity of clinical recovery. Harmonizing TM terminology, categories, and measurements across a spectrum, while providing examples of each, may reduce confusion and assist researchers and funding sources in targeting specific mechanistic-related questions.