Development and validation of the irritable bowel syndrome satisfaction with care scale.

BACKGROUND & AIMS: Satisfaction with care is an important measure of quality, from the patients' perspective, and could also affect outcomes. However, there is no standard measure of patient satisfaction for irritable bowel syndrome (IBS) care; a multi-item, condition-specific instrument is needed. METHODS: Using standard qualitative methods, we conducted focus groups to identify items that patients associated with satisfaction in their care for IBS. These and additional items identified by experts were placed into a preliminary questionnaire, which was refined through pilot testing and cognitive debriefing by additional patients, as well as standard statistical methods. The resulting instrument and several external validation measures were administered to 300 adult US patients with IBS. Factor analysis was performed to identify clinically relevant subscales and then psychometric properties were assessed. RESULTS: We developed an IBS satisfaction with care scale (IBS-SAT) that has 38 items from 5 clinically relevant subscales (connection with provider, education, benefits of visit, office attributes, and access to care). This IBS-SAT had a high level of internal consistency (Crohnbach's α = .96). Convergent validity was established by correlations between the IBS-SAT and a single, global satisfaction with care question (r = 0.68; P < .001), and a generic, multi-item satisfaction scale (physician satisfaction questionnaire-18) (r = 0.75, P < .001). Discriminant validity (among known groups) was established across groups that were stratified based on IBS-quality of life (r = 0.34; P < .0001), IBS severity (functional bowel disorders severity index) (r = -0.21; P < .001), and number of unmet expectations (r = -0.38; P < .0001). CONCLUSIONS: The IBS-SAT is a validated measure of patient satisfaction with IBS care. As a new, condition-specific instrument, it is likely to be a useful tool for quality measurement, health services research, and clinical trials.

Pharmacokinetic-pharmacodynamic correlation from mouse to human with pazopanib, a multikinase angiogenesis inhibitor with potent antitumor and antiangiogenic activity.

With the development of targeted therapeutics, especially for small-molecule inhibitors, it is important to understand whether the observed in vivo efficacy correlates with the modulation of desired/intended target in vivo. We have developed a small-molecule inhibitor of all three vascular endothelial growth factor (VEGF) receptors (VEGFR), platelet-derived growth factor receptor, and c-Kit tyrosine kinases, pazopanib (GW786034), which selectively inhibits VEGF-induced endothelial cell proliferation. It has good oral exposure and inhibits angiogenesis and tumor growth in mice. Because bolus administration of the compound results in large differences in C(max) and C(trough), we investigated the effect of continuous infusion of a VEGFR inhibitor on tumor growth and angiogenesis. GW771806, which has similar enzyme and cellular profiles to GW786034, was used for these studies due to higher solubility requirements for infusion studies. Comparing the pharmacokinetics by two different routes of administration (bolus p.o. dosing and continuous infusion), we showed that the antitumor and antiangiogenic activity of VEGFR inhibitors is dependent on steady-state concentration of the compound above a threshold. The steady-state concentration required for these effects is consistent with the concentration required for the inhibition of VEGF-induced VEGFR2 phosphorylation in mouse lungs. Furthermore, the steady-state concentration of pazopanib determined from preclinical activity showed a strong correlation with the pharmacodynamic effects and antitumor activity in the phase I clinical trial.