A quantitative approach for cardiovascular safety evaluation of a generic drug

In generic drug development, comparative pharmacokinetic (PK) studies are conducted to assess equivalence in pharmacokinetics and safety profiles between test and reference formulations. However, there is no established quantitative approach available for safety assessment. This study aimed to propose a method for drug safety evaluation in generic drug development, as assessed by drug influence on blood pressure and heart rate change. Data were taken from a randomized, open label, 2-way cross-over comparative PK study for megestrol conducted in 39 healthy male volunteers. Vital signs of systolic blood pressure (SBP), diastolic blood pressure (DBP) and heart rate (HR) were measured at 0 (pre-dose), 4, 8, 12, 24, 48, 72, 96 and 120 hours after the dose. Safety parameters used in the analysis were area under vital sign change versus time curve to the last measured time (AUVlast) and maximum vital sign change (Vmax). Considering highly variable nature of vital signs, the scaled bioequivalence approach developed by US FDA was adopted as a decision rule for safety evaluation between formulations. With the FDA scaled approach, 90% confidence intervals of geometric mean ratio for DBP, 0.7969~1.0377 for Vmax and 0.7304~1.0660 for AUVlast, were both included in the equivalence ranges of 0.7694~1.2997 and 0.6815~1.4674, respectively, and similarly, those for HR were included in their respective scaled equivalence limits, while SBP satisfied the conventional equivalence criterion of 0.8-1.25. These results illustrate the feasibility of applying the suggested approach in cardiovascular safety evaluation in a generic drug.

Application and analysis of mixed scientific methods in life experience of older persons with depression in Macau / 中国实用护理杂志

Objective To analyze and discuss the appropriate use of mixed methods using both qualitative and quantitative approaches to research older persons with depression in Macau in combination with Chinese characteristic of Macau.Methods A mixed methods research design,using both quantitative and qualitative approaches,was employed to interpret the lived experiences of these older persons.Using a purposive sampling approach,the final study involved 31 older persons with depression.A range of standardized,validated scales including the MSQ,GDS-15,BI,Lawton IADL,LSNS,SF- 36QOL were adopted.Results These lived experiences clustered into four broad dominant categories: negative thinking,physical limitations and complaints,poor living conditions and social support,and the tragic experience.Negative emotion included useless,hopeless,pessimistic and helpless.Physical limitations included poor activity,dependence,arthralgia,insomnia,poor appetite and memory,too many medicine.Poor living conditions and social support included poverty,illiterate,unfair,etc.Tragic experience included strenuous labor,passing away of father,failure of marriage,etc.Conclusions Mixed methods can be successfully used in discussing life experience of older persons with depression,combination of quantitative and qualitative approaches can explain this research phenomenon more comprehensively and deeply.