linicians and patients need to know if new medical interventions improve survival, patient function, or symptoms. Optimally, clinical trials would directly evaluate these outcomes, consistent with regulatory agencies moving toward more patient-focused drug development. 1 However, many clinical trials evaluate new medicines on the basis of indirect (also called surrogate) outcomes, which a US Food and Drug Administration (FDA) and National Institutes of Health (NIH) working group defined as trial end points that "substitute for a direct measure of how a patient feels, functions, or survives." 2(p48) Indirect measures include physical signs, biomarkers, and other laboratory-based measures.The FDA and NIH further categorize indirect outcomes based on the level of evidence that they reflect direct patient benefit. 2 Validated surrogates are supported by a clear mechanistic rationale and clinical data that provide strong evidence that an effect on the sur-rogate predicts clinical benefit. Reasonably likely surrogates are supported by mechanistic or epidemiologic rationales, but there are not sufficient data showing that they predict clinical benefits. Candidate surrogates are under evaluation, but there is not yet sufficient rationale or evidence to be classified as either validated or reasonably likely surrogates.Almost half of recent FDA drug approvals are based on pivotal trials that use surrogate outcomes as the primary trial end points. 3 The FDA has released a list of surrogate outcomes (with various levels of supporting evidence) that have been used as primary end points in pivotal clinical trials 4 and the 21st Century Cures Act of 2016 encourages the FDA to make even greater use of surrogate outcomes as the basis for new drug approvals. 5 The FDA can grant a new product accelerated approval based on a reasonably likely surrogate, or standard approval on the basis of a surrogate shown by clini-IMPORTANCE Regulatory and scientific guidelines stipulate that indirect, surrogate measures of patient benefit, such as a change in microbial culture status, should be used as primary end points only in pivotal trials of chronic conditions that are serious or life threatening and when the experimental therapy is expected to offer substantial benefit compared with available therapy. However, many recent US Food and Drug Administration (FDA) anti-infective drug approvals for acute and/or non-life-threatening diseases have been based on pivotal trials using surrogate measures as primary end points rather than clinical outcomes, such as symptom resolution or survival.OBJECTIVES To review FDA recommendations for primary end points in pivotal trials of new anti-infective drugs and assess the concordance of those recommendations with the regulatory and scientific conditions for the appropriate use of surrogate measures as primary trial outcomes.EVIDENCE REVIEW All guidance documents for antimicrobial drug development hosted on the FDA website were searched in November 2017; the search was updated in June 2018. For each docume...
Cyberspace odyssey (CSO) is a novel serious game supporting computer networking education by engaging students in a race to successfully perform various cybersecurity tasks in order to collect clues and solve a puzzle in virtual near-Earth threedimensional space. Each team interacts with the game server through a dedicated client presenting a multimodal interface, using a game controller for navigation and various desktop computer networking tools of the trade for cybersecurity tasks on the game's physical network. Specifically, teams connect to wireless access points, use packet monitors to intercept network traffic, decrypt and reverse engineer that traffic, craft well-formed and meaningful responses, and transmit those responses. Successful completion of these physical network actions to solve a sequence of increasingly complex problems is necessary to progress through the virtual story-driven adventure. Use of the networking tools reinforces networking theory and offers hands-on practical training requisite for today's cyber operators. This article presents the learning outcomes targeted by a classroom intervention based on CSO, the design and implementation of the game, a pedagogical overview of the overall intervention, and four years of quantitative and qualitative data assessing its effectiveness.
Background: Surgical site infections (SSI) are major problem in general surgery. Aim of this study is to know the role of subcutaneous conrrugated drain in class III and IV laparotomy wounds. Methods: Comparative study was done in 100 patients of emergency laparotomy in civil hospital, Gandhinagar from January 2014 to December 2016. Results: Incidence of surgical site infections were significantly lower (16%) in patients with subcutaneous drain, compared to 40% in patients without drain (p value 0.01). Conclusions: Corrugated subcutaneous drain is cost effective way of reducing surgical site infections and subsequent morbidities in class III and IV laparotomy wound.
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