Delivering Benefits at Speed Through Real-World Repurposing of Off-Patent Drugs: The COVID-19 Pandemic as a Case in Point.
- 作者列表："Rogosnitzky M","Berkowitz E","Jadad AR
:Real-world drug repurposing-the immediate "off-label" prescribing of drugs to address urgent clinical needs-is a widely overlooked opportunity. Off-label prescribing (ie, for a nonapproved indication) is legal in most countries and tends to shift the burden of liability and cost to physicians and patients, respectively. Nevertheless, health crises may mean that real-world repurposing is the only realistic source for solutions. Optimal real-world repurposing requires a track record of safety, affordability, and access for drug candidates. Although thousands of such drugs are already available, there is no central repository of off-label uses to facilitate immediate identification and selection of potentially useful interventions during public health crises. Using the current coronavirus disease (COVID-19) pandemic as an example, we provide a glimpse of the extensive literature that supports the rationale behind six generic drugs, in four classes, all of which are affordable, supported by decades of safety data, and targeted toward the underlying pathophysiology that makes COVID-19 so deadly. This paper briefly summarizes why cimetidine or famotidine, dipyridamole, fenofibrate or bezafibrate, and sildenafil citrate are worth considering for patients with COVID-19. Clinical trials to assess efficacy are already underway for famotidine, dipyridamole, and sildenafil, and further trials of all these agents will be important in due course. These examples also reveal the unlimited opportunity to future-proof our health care systems by proactively mining, synthesizing, cataloging, and evaluating the off-label treatment opportunities of thousands of safe, well-established, and affordable generic drugs.
: 真实世界的药物再利用 -- 立即 “非标签” 处方药物来解决紧急的临床需求 -- 是一个被广泛忽视的机会。非标签处方 (即，对于未经批准的适应症) 在大多数国家是合法的，并且倾向于将责任和成本分别转移给医生和患者。然而，健康危机可能意味着现实世界的再利用是解决方案的唯一现实来源。最佳真实世界再利用需要安全性、可负担性和候选药物获取的跟踪记录。虽然已经有成千上万种这样的药物，但在公共卫生危机期间，没有一个超标签用途的中央储存库，以方便立即识别和选择潜在有用的干预措施。以目前的冠状病毒疾病 (新型冠状病毒肺炎) 大流行为例，我们提供了大量的文献，支持六种仿制药的基本原理，分为四类，所有这些都是负担得起的，由几十年的安全性数据支持，并针对使新型冠状病毒肺炎如此致命的潜在病理生理学。简要总结为什么西咪替丁或法莫替丁、双嘧达莫、非诺贝特或苯扎贝特、枸橼酸西地那非对新型冠状病毒肺炎患者值得考虑。评估法莫替丁、潘生丁和西地那非疗效的临床试验已经在进行中，所有这些药物的进一步试验在适当时候都很重要。这些例子还揭示了通过主动挖掘、综合、编目和评估成千上万安全、成熟的非标签治疗机会，为我们的医疗保健系统提供了无限的机会，以证明我们的未来，和负担得起的仿制药。
METHODS::Since mid-December of 2019, coronavirus disease 2019 (COVID-19) infection has been spreading from Wuhan, China. The confirmed COVID-19 patients in South Korea are those who came from or visited China. As secondary transmissions have occurred and the speed of transmission is accelerating, there are rising concerns about community infections. The 54-year old male is the third patient diagnosed with COVID-19 infection in Korea. He is a worker for a clothing business and had mild respiratory symptoms and intermittent fever in the beginning of hospitalization, and pneumonia symptoms on chest computerized tomography scan on day 6 of admission. This patient caused one case of secondary transmission and three cases of tertiary transmission. Hereby, we report the clinical findings of the index patient who was the first to cause tertiary transmission outside China. Interestingly, after lopinavir/ritonavir (Kaletra, AbbVie) was administered, β-coronavirus viral loads significantly decreased and no or little coronavirus titers were observed.
METHODS::In December 2019, a novel coronavirus (2019-nCoV) caused an outbreak in Wuhan, China, and soon spread to other parts of the world. It was believed that 2019-nCoV was transmitted through respiratory tract and then induced pneumonia, thus molecular diagnosis based on oral swabs was used for confirmation of this disease. Likewise, patient will be released upon two times of negative detection from oral swabs. However, many coronaviruses can also be transmitted through oral-fecal route by infecting intestines. Whether 2019-nCoV infected patients also carry virus in other organs like intestine need to be tested. We conducted investigation on patients in a local hospital who were infected with this virus. We found the presence of 2019-nCoV in anal swabs and blood as well, and more anal swab positives than oral swab positives in a later stage of infection, suggesting shedding and thereby transmitted through oral-fecal route. We also showed serology test can improve detection positive rate thus should be used in future epidemiology. Our report provides a cautionary warning that 2019-nCoV may be shed through multiple routes.
METHODS::There is a current worldwide outbreak of a new type of coronavirus (2019-nCoV), which originated from Wuhan in China and has now spread to 17 other countries. Governments are under increased pressure to stop the outbreak spiraling into a global health emergency. At this stage, preparedness, transparency, and sharing of information are crucial to risk assessments and beginning outbreak control activities. This information should include reports from outbreak sites and from laboratories supporting the investigation. This paper aggregates and consolidates the virology, epidemiology, clinical management strategies from both English and Chinese literature, official news channels, and other official government documents. In addition, by fitting the number of infections with a single-term exponential model, we report that the infection is spreading at an exponential rate, with a doubling period of 1.8 days.