Considering the economic principles of pharmaceutical R&D

Importance of the field: Virtual screening (VS) coupled with structural biology is a significantly important approach to increase the number and enhance the success of projects in lead identification stage of drug discovery process. Recent advances and future directions in estrogen therapy have resulted in great demand for identifying the potential estrogen receptor (ER) modulators with more activity and selectivity.

Areas covered in this review: This review presents the current state of the art in VS and structure–activity relationship of ER modulators in recent discovery, and discusses the strengths and weaknesses of the technology.

What the reader will gain: Readers will gain an overview of the current platforms of in silico screening for discovery of ER modulators; they will learn which structural information is significantly correlated with the bioactivity of ER modulators and what novel strategies should be considered for the creation of more effective chemical structures.

Take home message: With the goal of reducing toxicity and/or improving efficacy, challenges to the successful modeling of endocrine agents are proposed, providing new paradigms for the design of ER inhibitors.     

我国基本药物遴选与替换原则研究

通过对WHO基本药物遴选原则与程序的研究,借鉴其在基本药物遴选方面的经验,进一步分析我国国家基本药物和各省增补目录药品遴选工作现状及存在的问题,为完善我国基本药物遴选替换原则和程序提供政策建议。     

Clinical and economic factors in the selection of low-osmolality contrast media

Both high- and low-osmolality contrast media are available for most radiographic procedures requiring iodinated contrast material. Newer low-osmolality contrast media cost much more than conventional high-osmolality formulations but cause fewer adverse reactions. However, most of these reactions are mild and easily treated, and do not affect the outcome of the procedure. Whether these additional clinical benefits justify the added cost is a crucial question which has not been answered. This review introduces some of the economic and clinical issues on which the choice of contrast media should be based. Low-osmolality contrast agents are not cost effective considering current pricing strategies and current inability to select patients at increased risk of an adverse event. Therefore, a better understanding of these adverse events and their mechanism takes on added importance.     

The design of pharmacokinetic studies to support drug discovery: the selection of the optimum number of animals for a study.

Using historic data from development and pre-development compounds, the variability in plasma concentration (including C(max)) and AUC that would be observed when only 1 or 2 animals per time point are used instead of the normal three has been studied. The results indicate that for pharmacokinetic studies carried out during the early discovery phase the number of animals per time point can be reduced to 2 without significantly affecting the quality of the data. Such an approach is not only more efficient, but it conserves valuable compound and reduces by one third the number of animals employed on the study.     

The optimum management of arthropathies

The aims in management of an arthropathy are to relieve symptoms, preserve function, and control the disease process. Drugs are an important, although not the only, part of any therapeutic regimen enabling us to achieve these aims. Although each individual requires a unique strategy, there is a logical progression from first-line agents to second-line agents. Third-line agents and experimental methods are reserved for aggressive or life-threatening disease. The choice of agent in each group is personal preference, but many agents have high adverse effect profiles, and close monitoring is essential.     

从WHO最新技术报告看WHO基本药物遴选调整进展

WHO的最新版基本药物目录在抗病毒药物部分调入了奥赛米韦,在心血管疾病药物部分将阿替洛尔替换为比索洛尔;提出了合理用药的下一步战略;WHO明确指出基本药物的调入申请应包含所有发表和未发表的证据。我国应借鉴WHO的经验,完善我国基本药物目录、基本药物的合理使用及基本药物的调入申请的评价。     

试验设计的三要素

试验研究中不可缺少的三项内容分别是试验因素、受试对象和试验效应,通常将他们称为试验设计的三要素。如何正确把握三要素是试验设计的关键问题之一。