Voretigene Neparvovec for Treating Inherited Retinal Dystrophies Caused by RPE65 Gene Mutations: An Evidence Review Group Perspective of a NICE Highly Specialised Technology Appraisal

The UK National Institute for Health and Care Excellence (NICE) considered evidence for voretigene neparvovec (VN; Luxturna®) for the treatment of RPE65-mediated inherited retinal dystrophies (IRD) within its highly specialised technology programme. This paper summarises the evidence provided by the company; the appraisal of the evidence by the Peninsula Technology Appraisal Group, who were commissioned to act as the independent evidence review group (ERG); and the development of the NICE guidance by the appraisal committee. The evidence presented by the company highlighted the significant lifelong burden of IRD for patients and carers. Evidence to support the effectiveness of VN was lacking, but the available evidence showed a modest, sustained improvement across a variety of vision-related outcomes. While patients would remain visually impaired, the committee considered that VN would prevent further deterioration in vision. The modelling approach used by the company had a number of limitations and relied heavily upon a large volume of clinical expert input to produce cost-effectiveness estimates with large uncertainty around long-term effectiveness. The ERG’s main concerns revolved around these long-term outcomes and the plausibility of utility values. The NICE committee were convinced that the clinical benefits of VN were important and an appropriate use of national health service resources within a specialised service. The committee concluded that a high unmet need existed in patients with RPE65-mediated IRD and that VN represents a step change in the management of this condition

Chirped pulse Raman amplification in warm plasma: towards controlling saturation

Stimulated Raman backscattering in plasma is potentially an efficient method of amplifying laser pulses to reach exawatt powers because plasma is fully broken down and withstands extremely high electric fields. Plasma also has unique nonlinear optical properties that allow simultaneous compression of optical pulses to ultra-short durations. However, current measured efficiencies are limited to several percent. Here we investigate Raman amplification of short duration seed pulses with different chirp rates using a chirped pump pulse in a preformed plasma waveguide. We identify electron trapping and wavebreaking as the main saturation mechanisms, which lead to spectral broadening and gain saturation when the seed reaches several millijoules for durations of 10's - 100's fs for 250 ps, 800 nm chirped pump pulses. We show that this prevents access to the nonlinear regime and limits the efficiency, and interpret the experimental results using slowly-varying-amplitude, current-averaged particle-in-cell simulations. We also propose methods for achieving higher efficiencies.close0

Early access schemes for innovative health technologies: the views of international stakeholders

This is the final version. Available on open access from Cambridge University Press via the DOI in this recordOBJECTIVES: Early access schemes (EASs) are approaches used by payers to balance and facilitate earlier patient access to innovative health technologies while evidence generation is ongoing. Schemes require investment from payers and are associated with significant risk since not all technologies will be routinely reimbursed. The purpose of this study was to gain the perspectives of policy experts about the key challenges for EASs and potential solutions for their optimal design and implementation. METHODS: Two virtual workshops were convened including (i) UK-based policy experts (England, Wales, and Scotland) and (ii) representatives from multiple healthcare systems (England, France, Sweden, Canada, Poland, and Norway). Participants were encouraged to share their experiences with EASs in their healthcare system and highlight key challenges for policy makers. Discussions were transcribed and analyzed using framework analysis. RESULTS: Participants agreed that EASs have value when targeted toward innovative technologies with the potential for significant clinical benefit in an area of high unmet need. Participants discussed potential solutions to the challenges faced by payers implementing EASs, including defining eligibility criteria, supporting evidence generation, and approaches to reimbursement. CONCLUSIONS: Participants agreed that EASs are one possible solution for their healthcare systems and have the potential to deliver significant clinical value to patients. However, widespread adoption of EASs is limited due to concerns about the risks for patients and healthcare budgets, further solutions are needed to deliver EASs for targeted therapies.NHS Englan

An evaluation of managed access agreements in England based on stakeholder experience

This is the final version. Available on open access from Cambridge University Press via the DOI in this recordOBJECTIVES: The objective of this research was to evaluate managed access policy in England, drawing upon the expertise of a range of stakeholders involved in its implementation. METHODS: Seven focus groups were conducted with payer and health technology assessment representatives, clinicians, and representatives from industry and patient/carer organizations within England. Transcripts were analyzed using framework analysis to identify stakeholders' views on the successes and challenges of managed access policy. RESULTS: Stakeholders discussed the many aims of managed access within the National Health Service in England, and how competing aims had affected decision making. While stakeholders highlighted a number of priorities within eligibility criteria for managed access agreements (MAAs), stakeholders agreed that strict eligibility criteria would be challenging to implement due to the highly variable nature of innovative technologies and their indications. Participants highlighted challenges faced with implementing MAAs, including evidence generation, supporting patients during and after the end of MAAs, and agreeing and reinforcing contractual agreements with industry. CONCLUSIONS: Managed access is one strategy that can be used by payers to resolve uncertainty for innovative technologies that present challenges for reimbursement and can also deliver earlier access to promising technologies for patients. However, participants cautioned that managed access is not a "silver bullet," and there is a need for greater clarity about the aims of managed access and how these should be prioritized in decision making. Discussions between key stakeholders involved in managed access identified challenges with implementing MAAs and these experiences should be used to inform future managed access policy.NHS Englan

An ultra-high gain and efficient amplifier based on Raman amplification in plasma

Raman amplification arising from the excitation of a density echelon in plasma could lead to amplifiers that significantly exceed current power limits of conventional laser media. Here we show that 1-100 J pump pulses can amplify picojoule seed pulses to nearly joule level. The extremely high gain also leads to significant amplification of backscattered radiation from "noise", arising from stochastic plasma fluctuations that competes with externally injected seed pulses, which are amplified to similar levels at the highest pump energies. The pump energy is scattered into the seed at an oblique angle with 14 J sr(-1), and net gains of more than eight orders of magnitude. The maximum gain coefficient, of 180 cm(-1), exceeds high-power solid-state amplifying media by orders of magnitude. The observation of a minimum of 640 J sr(-1) directly backscattered from noise, corresponding to approximate to 10% of the pump energy in the observation solid angle, implies potential overall efficiencies greater than 10%

Exploring the Activities and Target Audiences of School-Based Violence Prevention Programs: Systematic Review and Intervention Component Analysis.

Adolescents are at an increased risk for experiencing dating and relationship violence (DRV) and gender-based violence (GBV). School-based interventions remain an important and frequently used method for DRV/GBV prevention. A clear understanding and description of the different components of school-based interventions specific to DRV/GBV is needed to organize and advance the array of prevention efforts being utilized in school settings. We conducted an intervention component analysis to create a taxonomy for school-based interventions addressing DRV and GBV. We searched 21 databases in July 2020 and updated searches in June 2021, alongside extensive supplementary search methods. We included randomized controlled trials (RCTs) in adolescents of compulsory school-age that were implemented within the school setting which partially or wholly focused on DRV and GBV topics. Our analysis included 68 studies describing 76 different school-based interventions. Through an iterative coding process we identified 40 intervention components organized within 13 activity categories, including both student-directed components and non-student-directed components such as activities for school personnel and family members of students. We also identified components addressing higher levels of the social-ecological model including structural-social and structural-environmental aspects of DRV/GBV which prior reviews have not considered. This taxonomy of components and synthesis of intervention efficacy for DRV/GBV school-based interventions provides a framework for comparing past intervention evaluations and constructing new interventions to address these issues at multiple levels within a community

Self-reported data: a major tool to assess compliance with anti-malarial combination therapy among children in Senegal

Background: Although there are many methods available for measuring compliance, there is no formal gold standard. Different techniques used to measure compliance were compared among children treated by the anti-malarial amodiaquine/sulphadoxine-pyrimethamine (AQ/SP) combination therapy, in use in Senegal between 2004 and 2006. Methods: The study was carried out in 2004, in five health centres located in the Thies region (Senegal). Children who had AQ/SP prescribed for three and one day respectively at the health centre were recruited. The day following the theoretical last intake of AQ, venous blood, and urine samples were collected for anti-malarial drugs dosage. Caregivers and children above five years were interviewed concerning children's drug intake. Results: Among the children, 64.7% adhered to 80% of the prescribed dose and only 37.7% were strict full adherent to the prescription. There was 72.7% agreement between self-reported data and blood drug dosage for amodiaquine treatment. Concerning SP, results found that blood dosages were 91.4% concordant with urine tests and 90% with self-reported data based on questionnaires. Conclusion: Self-reported data could provide useful quantitative information on drug intake and administration. Under strict methodological conditions this method, easy to implement, can be used to describe patients' behaviors and their use of new anti-malarial treatment. Self-reported data is a major tool for assessing compliance in resource poor countries. Blood and urine drug dosages provide qualitative results that confirm any drug intake. Urine assays for SP could be useful to obtain public health data, for example on chemoprophylaxis among pregnant women

Comparing online campaigning: The evolution of interactive campaigning from Royal to Obama to Hollande

© 2016 Macmillan Publishers Ltd.Studies of election campaigning from a comparative perspective have a long history; this study approaches the topic through a most-similar regime perspective to explore the ebb and flow of innovations in digital campaigning between presidential campaigns in France and the United States. The hype surrounding the 2008 Obama campaign overshadowed innovations in France the previous year, while the 2011 contest gained little serious academic attention. Using a well-established content analysis methodology the research explains the strategic design of the digital dimension of the campaigns of the leading candidates (Sarkozy and Royal in 2007, Obama and McCain in 2008, Hollande and Sarkozy in 2011, and Obama and Romney in 2012). The research then assesses the strategic contribution of each feature using schematics for understanding the flow of communication, as well as the strategy employed by each candidate. The key findings are that the campaigns are becoming more interactive, with the citizens increasingly more able to enter into conversations with the campaign teams, however interactivity when it happens is carefully controlled. Largely, however, there is a strong similarity masked by the sophistication of US contests. Despite the advances in communication technology and the social trends they have instigated, campaign communication remains top-down and digital technologies are used to gather data and push supporters towards activism than creating an inclusive space for the co-creation that cyberoptimists argued would revitalise the structures of democracy