RESUMO
This paper explores theories of motivation, including instinct theory, arousal theory, incentive theory, intrinsic theory, extrinsic theory, the ARCS model, self-determination theory, expectancy-value theory, and goal-orientation theory. Each theory is described in detail, along with its key concepts, assumptions, and implications for behavior. Intrinsic theory suggests that individuals are motivated by internal factors like enjoyment and satisfaction, while extrinsic theory suggests that external factors like rewards and social pressure drive behavior. Arousal theory says that to feel motivated, people try to keep an optimal level of activation or excitement. Incentive theory suggests that behavior is driven by the promise of rewards or the threat of punishment. The ARCS model, designed to motivate learners, incorporates elements of attention, relevance, confidence, and satisfaction. Self-determination theory proposes that individuals are motivated by their needs for autonomy, competence, and relatedness. The expectation-value theory suggests that behavior is influenced by individuals' beliefs about their ability to succeed and the value they place on the task. The goal-orientation theory suggests that individuals have different goals for engaging in a behavior. By understanding these different theories of motivation, educators, coaches, managers, and individuals may analyze what drives behavior and how to harness it to achieve their goals. In essence, a nuanced comprehension of these diverse motivation theories equips individuals across varied domains with a strategic toolkit to navigate the complex landscape of human behavior, fostering a more profound understanding of what propels actions and how to channel these insights toward the attainment of overarching goals.
Assuntos
Motivação , Autonomia Pessoal , Humanos , Recompensa , Punição , Comportamento SocialRESUMO
Teverelix drug product (DP) is a parenteral gonadotropin-releasing hormone (GnRH) antagonist that has been successfully tested in phase 2 trials for hormone-sensitive advanced prostate cancer (APC) and benign prostatic hyperplasia (BPH). In previous APC trials, teverelix DP was administered as intramuscular (IM) and subcutaneous (SC) injections, using a loading dose and (in a single trial) a maintenance dose. Our objective was to derive an optimal dosing regimen for phase 3 clinical development, using a pharmacometrics modeling approach. Data from 9 phase 2 studies (229 patients) was utilized to develop a population pharmacokinetic (PK) model that described the concentration profile accommodating both IM and SC routes of administration. A 2-compartment model with sequential first-order absorption (slow and fast) and lag times best described the PK profiles of teverelix following SC and IM administration. An indirect response model with inhibition of production rate was fit to describe testosterone (T) concentrations based on physiological relevance. The final population PK-pharmacodynamic model was used to conduct simulations of various candidate dosing regimens to select the optimal dosing regimen to achieve clinical castration (T < 0.5 ng/mL by day 28) and to sustain clinical castration for 26 weeks. Model simulation showed that a loading dose of 360 mg SC and 180 mg IM with a maintenance dose of 360 mg SC 6-weekly (Q6W) starting at day 28 can achieve a ≥95% castration rate up to 52 weeks. This dose regimen was selected for phase 3 clinical development, which includes cardiovascular safety assessment in comparison to a GnRH agonist.