ABSTRACT
With the increasing cost of drug development and clinical trials, it is of great value to make full use of all kinds of data to improve the efficiency of drug development and to provide valid information for medication guidelines. Model-based meta-analysis (MBMA) combines mathematical models with meta-analysis to integrate information from multiple sources (preclinical and clinical data, etc.) and multiple dimensions (targets/mechanisms, pharmacokinetics/pharmacodynamics, diseases/indications, populations, regimens, biomarkers/efficacy/safety, etc.), which not only provides decision-making for all key points of drug development, but also provides effective information for rational drug use and cost-effectiveness analysis. The classical meta-analysis requires high homogeneity of the data, while MBMA can combine and analyze the heterogeneous data of different doses, different time courses, and different populations through modeling, so as to quantify the dose-effect relationship, time-effect relationship, and the relevant impact factors, and thus the efficacy or safety features at the level of dose, time and covariable that have not been involved in previous studies. Although the modeling and simulation methods of MBMA are similar to population pharmacokinetics/pharmacodynamics (Pop PK/PD), compared with Pop PK/PD, the advantage of MBMA is that it can make full use of literature data, which not only improves the strength of evidence, but also can answer the questions that have not been proved or can not be answered by a single study. At present, MBMA has become one of the important methods in the strategy of model-informed drug development (MIDD). This paper will focus on the application value, data analysis plan, data acquisition and processing, data analysis and reporting of MBMA, in order to provide reference for the application of MBMA in drug development and clinical practice.
ABSTRACT
<p><b>OBJECTIVE</b>To study responses of physiological ecology and quality evaluation of Rehmannia glutinosa in continuous cropping.</p><p><b>METHOD</b>The potted plant R. glutinosa which consists of first cropping, 1 year continuous cropping and 2 year continuous cropping were used as experimental materials. The photosynthetic activity, descending axis vitality, the protective enzymes system and MDA content were measured, the quality was evaluated by FTIR and HPLC.</p><p><b>RESULT</b>Continuous cropping reduced the content of chlorophyll in the non-first cropping R. glutinos, the photosynthetic activity and descending axis vitality were weakened. Because of the increase of the free radical in the R. glutinos due to the continuous cropping, the activity of protective enzymes including POD, SOD and CAT were enhanced and MDA content were increased, more importantly the medical potency declined . And along with the increasing years of the continuous cropping, this effect becomes even stronger.</p><p><b>CONCLUSION</b>Continuous cropping affects the descending axis ability of absorbing water and nutrition and photosynthesis are inhibited R. glutinosa, at the same time, it also causes the disorders of antioxidation systems in R. glutinos, resulting in continuous cropping obstacle and decline of the medicinal materials quality.</p>