Guiding Principles for Evaluating Vaccines in Joint Health Technology Assessment in the European Union: Preparing for the European Union's Regulation on Health Technology Assessment for Vaccines.

OBJECTIVES: The appraisal of vaccines in the European Union (EU) currently involves many different decision-making bodies and processes. The objective of this study was to help inform the development of standardized methodology and vaccine-specific processes for use in the EU Regulation on health technology assessment (HTA). METHODS: Literature reviews and expert consultation were conducted to identify current practices and gaps related to vaccine appraisals and to develop guiding principles for the joint clinical assessment of vaccines. RESULTS: We found that significant variation exists across the EU member states in the decision-making processes when clinically evaluating vaccines. Three guiding principles consisting of 13 recommendations were developed to help inform the development of decision-making frameworks for the joint clinical assessment of vaccines in the EU: (1) support the creation of appropriate terminology and measurements for clinical appraisals of vaccines; (2) develop inclusive, timely, and transparent vaccine appraisal processes to support stronger evidence generation for vaccine decision making and appraisal; and (3) improve the collection and interoperability of real-world data, including robust surveillance, to foster evidence generation and support the standardization of vaccine clinical appraisals. CONCLUSIONS: Given the significance of vaccines for public health, there is an urgency to develop standardized and vaccine-specific methodologies and processes for use in the EU joint HTA framework. The proposed guiding principles could support the effective implementation of the EU Regulation on HTA for vaccines and have the potential to ensure consistent, transparent, and timely access to new vaccines in the EU.

Three-dimensional endomicroscopy of the human colon using optical coherence tomography.

Three-dimensional (3D) endomicroscopy imaging of the human gastrointestinal tract is demonstrated in vivo using a swept source optical coherence tomography (OCT) system. 3D datasets of normal and pathologic regions of the colon, rectum, and anal verge were obtained from seven volunteers undergoing diagnostic or therapeutic colonoscopy. 3D-OCT enables high resolution endomicroscopy examination through visualization of tissue architectural morphology using virtual cross-sectional images with arbitrary orientations as well as en face projection images. Axial image resolutions of 6 mum in tissue are obtained over a approximately 180 mm2 field with an imaging range of 1.6 mm. A Fourier domain mode locked (FDML) laser providing a tuning range of 180 nm at a sweep rate of 62 kHz is used as the system light source. This clinical pilot study demonstrates the potential of 3D-OCT for distinguishing normal from pathologic colorectal tissue, assessing endoscopic therapies and healing progression.

Coherence-gated Doppler: a fiber sensor for precise localization of blood flow.

Miniature optical sensors that can detect blood vessels in front of advancing instruments will significantly benefit many interventional procedures. Towards this end, we developed a thin and flexible coherence-gated Doppler (CGD) fiber probe (O.D. = 0.125 mm) that can be integrated with minimally-invasive tools to provide real-time audio feedback of blood flow at precise locations in front of the probe. Coherence-gated Doppler (CGD) is a hybrid technology with features of laser Doppler flowmetry (LDF) and Doppler optical coherence tomography (DOCT). Because of its confocal optical design and coherence-gating capabilities, CGD provides higher spatial resolution than LDF. And compared to DOCT imaging systems, CGD is simpler and less costly to produce. In vivo studies of rat femoral vessels using CGD demonstrate its ability to distinguish between artery, vein and bulk movement of the surrounding soft tissue. Finally, by placing the CGD probe inside a 30-gauge needle and advancing it into the brain of an anesthetized sheep, we demonstrate that it is capable of detecting vessels in front of advancing probes during simulated stereotactic neurosurgical procedures. Using simultaneous ultrasound (US) monitoring from the surface of the brain we show that CGD can detect at-risk blood vessels up to 3 mm in front of the advancing probe. The improved spatial resolution afforded by coherence gating combined with the simplicity, minute size and robustness of the CGD probe suggest it may benefit many minimally invasive procedures and enable it to be embedded into a variety of surgical instruments.

Influenza control in the 21st century: Optimizing protection of older adults.

Older adults (> or =65 years of age) are particularly vulnerable to influenza illness. This is due to a waning immune system that reduces their ability to respond to infection, which leads to more severe cases of disease. The majority ( approximately 90%) of influenza-related deaths occur in older adults and, in addition, catastrophic disability resulting from influenza-related hospitalization represents a significant burden in this vulnerable population. Current influenza vaccines provide benefits for older adults against influenza; however, vaccine effectiveness is lower than in younger adults. In addition, antigenic drift is also a concern, as it can impact on vaccine effectiveness due to a mismatch between the vaccine virus strain and the circulating virus strain. As such, vaccines that offer higher and broader protection against both homologous and heterologous virus strains are desirable. Approaches currently available in some countries to meet this medical need in older adults may include the use of adjuvanted vaccines. Future strategies under evaluation include the use of high-dose vaccines; novel or enhanced adjuvantation of current vaccines; use of live attenuated vaccines in combination with current vaccines; DNA vaccines; recombinant vaccines; as well as the use of different modes of delivery and alternative antigens. However, to truly evaluate the benefits that these solutions offer, further efficacy and effectiveness studies, and better correlates of protection, including a precise measurement of the T cell responses that are markers for protection, are needed. While it is clear that vaccines with greater immunogenicity are required for older adults, and that adjuvanted vaccines may offer a short-term solution, further research is required to exploit the many other new technologies.