Determination of quality of life-related health utilities for surgical complications in ovarian cancer.

OBJECTIVE: To assess the health state utilities of ovarian cancer patients, clinicians, and non-cancer controls regarding surgical complications in ovarian cancer. METHODS: Utilities for 14 surgical complications were assessed from patients with recently diagnosed or recurrent ovarian cancer, clinicians, and non-cancer controls using the visual analog scale (VAS) and time trade-off (TTO) methods. Health state utilities were converted to a 0-to-1 scale, where 0 represents the least favorable outcome and 1 represents the most favorable outcome. RESULTS: Fifty patients, 50 clinicians, and 50 controls participated. Median VAS scores were lower than TTO scores across all groups (p < 0.01). Patients viewed 'bleeding requiring transfusion' most favorably (VAS utility 0.75), followed in order by less favorable utility scores for hernia, thromboembolism, pleural effusion, abscess, ileus/bowel obstruction, wound infection, bowel obstruction requiring surgery, anastomotic leak requiring drain, temporary ostomy, anastomotic leak requiring surgery, genito-urinary fistula, permanent ostomy, and genito-intestinal fistula (VAS utility 0.2). Overall, clinicians perceived complications more favorably than patients by VAS (overall utility score 0.49 vs 0.43, p < 0.01), but not by the TTO. There were no differences in overall utility scores between patients and controls. Patients who had not experienced certain surgical complications had less favorable scores than patients who did (utility score for ostomy = 0.2 for patients without ostomy vs. 0.7 for patients with ostomy, p = 0.02). CONCLUSIONS: This study establishes health state utilities for surgical complications associated with ovarian cancer. These utilities can be used in future cost-effectiveness evaluations to determine quality-adjusted outcomes and may help in counseling patients during the shared decision-making process.

Multiplexing of receptor occupancy measurements for pharmacodynamic biomarker assessment of biopharmaceuticals.

BACKGROUND: Receptor occupancy (RO) assays measure drug target engagement, and are used as pharmacodynamic (PD) biomarkers. RO assays are commonly performed by flow cytometry and often require multiplexing for assessment of multiple PD biomarkers when specimen volumes are limited. We present multiplexed RO assays for an IGF1R-EGFR bispecific antibody (Bs-Ab) and a CTLA4-Ig recombinant fusion protein to demonstrate key considerations for accurate RO assessment. METHODS: RO in cynomolgus monkeys was determined in whole blood using flow cytometry. Free and total receptors were measured using anti-receptor fluorescence-labeled detection reagents, competitive and noncompetitive to drug, respectively. RESULTS: RO of IGF1R was examined as PD for Bs-Ab, since IGF1R was expressed on blood cells. Multiplexed measurements of free and total IGF1R showed that IGF1R expression measured by total receptor was highly variable, impacting interpretation of free-IGF1R. Normalization of free-over-total IGF1R measurements compensated for variability of receptor expression allowing for accurate RO assessment. RO of CTLA4-Ig, a recombinant fusion protein targeting CD80 and CD86 receptors, was multiplexed to simultaneously measure target engagements for both receptors. Both RO methods demonstrated specificity of receptor measurements without cross-reactivity to each other in multiplexed formats. RO methods were used for evaluation of PD activity of Bs-Ab and CTLA4-Ig in cynomolgus monkeys. In both cases, RO results showed dose-dependent target engagement, corresponding well to the pharmacokinetics. CONCLUSIONS: Multiplexed RO methods allowed accurate assessment of PD activity for Bs-Ab and CTLA4-Ig, facilitating development of these biopharmaceuticals from preclinical to clinical stages.

Public perceptions and preferences for patient notification after an unsafe injection.

BACKGROUND: Unsafe injection practices in health-care settings often result in notification of potentially affected patients, to disclose the error and recommend blood-borne pathogens testing. Few studies have assessed public perceptions and preferences for patient notification. METHODS: Six focus groups were conducted during Fall 2009, with residents of Atlanta, GA, and New York City, NY. Questions focused on preferences for receiving health information, knowledge of safe injection practices, and responses to and preferences for a patient notification letter. A mixed-method analysis was performed for qualitative themes and descriptive statistics. RESULTS: A total of 53 individuals participated; only 2 had ever heard of the term safe injection practices. After identification of unsafe injection practices, participants preferred to be notified via telephone, letter/mailing, email, or face-to-face from the facility where the incident occurred. More than 25 different types of information were mentioned as elements to be placed in a patient notification letter including: corrective actions by the facility, course of action for the patient, assurance of medical coverage, and how it happened/reason for the incident. Participants preferred that the tone of the letter be empathetic; nearly all indicated it was "very likely" that they would seek testing if notified. CONCLUSIONS: Facilities and health departments should strive to assure the notification process is conducted swiftly, clearly guiding affected patients to the necessary course of action. Notification letters are not "one size fits all," and some preferences expressed by patients may not be feasible in all situations. Prevention efforts should be complemented by research on improving effective patient communications when unsafe injection practices necessitate patient notification.