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  • Repurposing use of approved drugs for

    2019-05-21

    Repurposing (use of approved drugs for new indications) or repositioning (use of drugs whose development was not continued for new indications) of existing drugs has been put forward as a method to overcome some of these issues. Indeed, drug repositioning and repurposing could lead to higher rates of success, with lower costs of development, in a faster timeframe than de novo discovery approaches. However, these potential advantages are far from certain. Furthermore, drug repurposing/repositioning in and of itself does not remove the need for certain preclinical studies and clinical trials. Drugs still need to be validated and studied in the indications for which they cox 2 inhibitor are proposed. In silico approaches might hold a key to overcoming some of these obstacles. Use of bioinformatics-based high-end computing to simulate drug–disease biological processes provides the ability to bypass time-consuming and costly in vitro and in vivo studies and increase the probability of success of clinical trials. For Ebola treatments, in silico approaches might offer two specific means to improve the current process and help address some of the critical preclinical and clinical concerns raised at the WHO meeting of international experts to discuss Ebola therapeutics on Sept 5. First, the number of preclinical compounds already containing clinical data for other therapeutic indications could be considerably increased. Although traditional repositioning methods using in vitro screening have led to initial discoveries for Ebola, computational screening could provide the needed efficiency to identify candidates more rapidly and accurately than de novo discovery methods. Second, virtual clinical trials could alleviate some of the logistical and ethical issues surrounding the clinical use of unregistered Ebola treatments, including the balance between generating safety data and the need to introduce treatments as soon as possible. This method would permit non-interventional assessments of pharmacokinetic-pharmacodynamic parameters and allow precise and efficient clinical trial design (the latter being particularly important because the epidemiology and infrequent emergence of Ebola often provides a narrow window of opportunity and limited population size to assess an intervention). There is at least one caveat, though. In silico approaches are dependent on drug and disease process data. Therapeutic Ebola research is heavily funded by the US government under the auspices of threats to national security, and international activities are limited to a few research groups. To allow for greater participation of researchers globally, real-time accessibility of crucial data is necessary.
    We read with interest the WHO systematic analysis of global causes of maternal death (June issue) and the WHO maternal mortality trends report and press release. However, we urge caution regarding calls for policymakers, funding bodies, and health actors to give greater importance to indirect than direct causes of maternal mortality. With the exception of HIV infection, the systematic analysis does not provide insight into the main indirect causes of maternal mortality, nor into how these causes vary according to region or lifetime risk of pregnancy-related death. Putative causal relations between indirect causes of maternal mortality and pregnancy, and the relative surplus risk that they present, are also not discussed.
    Comprehensive analyses of the causes of maternal mortality have been published by WHO and the Institute for Health Metrics and Evaluation. These analyses strikingly show the increasing importance of indirect causes of maternal death. Say and colleagues noted that 27·5% of all maternal deaths result from these indirect causes, with the highest proportion of such deaths in south Asia and sub-Saharan Africa. Kassebaum and colleagues similarly show the growing direct and indirect effects of non-communicable diseases on maternal mortality. The authors conclude that indirect causes of maternal deaths cannot be ignored and that efforts should be focused on their reduction.