Selumetinib 75 mg did not cause any QT/QTc interval prolongation in these healthy subjects, and selumetinib is not expected to have a clinically relevant effect on cardiac repolarization in patients at the anticipated therapeutic dose of 75 mg. The model also demonstrated the low potential for any QTc effects of selumetinib at doses higher than the standard therapeutic dose.

<div>Abstract<p>Despite some notable successes, there are still relatively few agents approved for cancer prevention. Here we review progress thus far in the development of medicines for cancer prevention, and we outline some key concepts that could further enable or accelerate drug development for cancer prevention in the future. These are summarized under six key themes: (i) unmet clinical need, (ii) patient identification, (iii) risk stratification, (iv) pharmacological intervention, (v) clinical trials, and (vi) health care policy. These concepts, if successfully realized, may help to increase the number of medicines available for cancer prevention.</p>Significance:<p>The huge potential public health benefits of preventing cancer, combined with recent advances in the availability of novel early detection technologies and new treatment modalities, has caused us to revisit the opportunities and challenges associated with developing medicines to prevent cancer. Here we review progress in the field of developing medicines to prevent cancer to date, and we present a series of ideas that might help in the development of more medicines to prevent cancer in the future.</p></div>

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Robust and transparent formal benefit-risk (BR) analyses for medicinal products represent a means to better understand the appropriate use of medicinal products, and to maximize their value to prescribers and patients. Despite regulatory and social imperatives to conduct structured BR (sBR) assessments, and the availability of a plethora of methodological tools, there exists large variability in the uptake and execution of sBR assessments among pharmaceutical companies. As such, in this paper we present an sBR assessment framework developed and implemented within a large global pharmaceutical company that aims to guide the systematic assessment of BR across the continuum of drug development activities, from first-time-in-human studies through to regulatory submission. We define and emphasize the concepts of Key Clinical Benefits and Key Safety Risks as the foundation for BR analysis. Furthermore, we define and foundationally employ the concepts of sBR and a Core Company BR position as the key elements for our BR framework. We outline 3 simple stages for how to perform the fundamentals of an sBR analysis, along with an emphasis on the weighting of Key Clinical Benefits and Key Safety Risks, and a focus on any surrounding uncertainties. Additionally, we clarify existing definitions to differentiate descriptive, semi-quantitative, and fully quantitative BR methodologies. By presenting our framework, we wish to stimulate productive conversation between industry peers and health authorities regarding best practice in the BR field. This paper may also help facilitate the pragmatic implementation of sBR methodologies for organizations without an established framework for such assessments.

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