The present invention provides method for longitudinal monitoring of disease changes and/or drug response. At multiple time points, a composition is introduced into a body of a subject (the composition includes an activity sensor comprising a plurality of reporters liberated through enzymatic cleavage, which occurs in a tissue of the body when enzymes associated with known activity of a therapeutic intervention are present in the body) and reporters are detected to determine activity levels of disease-associated enzymes in the subject, which is correlated to changes in disease state and/or drug response. A report or therapeutic response profile may further be used to support a clinical trial and for longitudinal monitoring of disease progression or regression in a subject. A prospective or active clinical trial participant, or patient undergoing treatment, may be qualified, stratified or staged based on the determined activity levels.