Simulate SubQ: The Methods and the Media.

For decades, there has been a growing interest in injectable subcutaneous formulations to improve the absorption of drugs into the systemic circulation and to prolong their release over a longer period. However, fluctuations in the blood plasma levels together with bioavailability issues often limit their clinical success. This warrants a closer look at the performance of long-acting depots, for example, and their dependence on the complex interplay between the dosage form and the physiological microenvironment. For this, biopredictive performance testing is used for a thorough understanding of the biophysical processes affecting the absorption of compounds from the injection site in vivo and their simulation in vitro. In the present work, we discuss in vitro methodologies including methods and media developed for the subcutaneous route of administration on the background of the most relevant absorption mechanisms. Also, we highlight some important knowledge gaps and shortcomings of the existing methodologies to provide the reader with a better understanding of the scientific evidence underlying these models.

A cultural adaptation and validation study of a self-report measure of the extent of and reasons for medication nonadherence among patients with diabetes in Singapore.

BACKGROUND: This self-report measure is a new instrument to measure the extent of and reasons for medication adherence separately. However, few studies have assessed its psychometric properties in diabetic patients and also in Asian populations. OBJECTIVES: To validate this self-report measure in diabetic patients in Singapore. METHODS: We collected data prospectively using a questionnaire among 393 diabetic patients from hospitals in Singapore from July 2018 to January 2019. Using the COnsensus-based Standards for the selection of health Measurement INstruments framework, we assessed face validity, internal consistency, test-retest reliability, structural validity, and measurement error. We tested four a priori hypotheses on correlation of extent score with patient-reported outcome measures to assess construct validity. We examined cross-cultural validity via measurement invariance across gender, age groups, and languages. RESULTS: We performed cognitive interviews with 30 consenting English-literate, Chinese-literate, and Malay-literate (10 patients per language) diabetic patients (age range 48-76 years, 53% male, disease duration range 1-30 years) and face validity was supported. Among 393 patients (mean age: 59.4±12.2 years, 50.9% female, 52.4% Chinese), we showed moderate internal consistency (Cronbach's alpha =0.67) and test-retest reliability (intra-class coefficient=0.56 [95% CI 0.37-0.70]). We calculated smallest detectable change as 0.80. We established construct validity by meeting all four hypotheses. We showed structural validity as confirmatory factor analysis confirmed a one-factor model, with excellent fit statistics (Comparative Fit Index=1.0; Tucker-Lewis Index=1.0; Root Mean Square Error of Approximation<0.001; Standardized Root Mean Residuals<0.001). Analysis of cross-cultural validity supported configural invariance model but not metric invariance and scalar invariance model. Caution must be taken against directly comparing extent scores across gender, age groups, and languages. CONCLUSION: This self-report measure is valid and reliable in measuring medication adherence in diabetic patients in Singapore.