REGULATORY APPROVAL OF NEW MEDICAL DEVICES: A CROSS SECTIONAL STUDY

Objective To investigate the regulatory approval of new medical devices. Design Cross sectional study of new medical devices reported in the biomedical literature. Data sources PubMed was searched between 1 January 2000 and 31 December 2004 to identify clinical studies of new medical devices. The search was carried out during this period to allow time for regulatory approval. Eligibility criteria for study selection Articles were included if they reported a clinical study of a new medical device and there was no evidence of a previous clinical study in the literature. We defined a medical device according to the US Food and Drug Administration as an “instrument, apparatus, implement, machine, contrivance, implant, in vitro reagent, or other similar or related article.” Main outcome measures Type of device, target specialty, and involvement of academia or of industry for each clinical study. The FDA medical databases were then searched for clearance or approval relevant to the device. Results 5574 titles and abstracts were screened, 493 full text articles assessed for eligibility, and 218 clinical studies of new medical devices included. In all, 99/218 (45%) of the devices described in clinical studies ultimately received regulatory clearance or approval. These included 510(k) clearance for devices determined to be “substantially equivalent” to another legally marketed device (78/99; 79%), premarket approval for high risk devices (17/99; 17%), and others (4/99; 4%). Of these, 43 devices (43/99; 43%) were actually cleared or approved before a clinical study was published. Conclusions We identified a multitude of new medical devices in clinical studies, almost half of which received regulatory clearance or approval. The 510(k) pathway was most commonly used, and clearance often preceded the first published clinical study

Optimisation of two-dimensional ion trap arrays for quantum simulation

The optimisation of two-dimensional (2D) lattice ion trap geometries for trapped ion quantum simulation is investigated. The geometry is optimised for the highest ratio of ion-ion interaction rate to decoherence rate. To calculate the electric field of such array geometries a numerical simulation based on a "Biot-Savart like law" method is used. In this article we will focus on square, hexagonal and centre rectangular lattices for optimisation. A method for maximising the homogeneity of trapping site properties over an array is presented for arrays of a range of sizes. We show how both the polygon radii and separations scale to optimise the ratio between the interaction and decoherence rate. The optimal polygon radius and separation for a 2D lattice is found to be a function of the ratio between rf voltage and drive frequency applied to the array. We then provide a case study for 171Yb+ ions to show how a two-dimensional quantum simulator array could be designed

Versatile ytterbium ion trap experiment for operation of scalable ion-trap chips with motional heating and transition-frequency measurements

We present the design and operation of an ytterbium ion trap experiment with a setup offering versatile optical access and 90 electrical interconnects that can host advanced surface and multilayer ion trap chips mounted on chip carriers. We operate a macroscopic ion trap compatible with this chip carrier design and characterize its performance, demonstrating secular frequencies >1 MHz, and trap and cool nearly all of the stable isotopes, including 171Yb+ ions, as well as ion crystals. For this particular trap we measure the motional heating rate 〈ṅ〉 and observe an 〈ṅ〉∝1/ω2 behavior for different secular frequencies ω. We also determine a spectral noise density SE(1 MHz)=3.6(9)×10-11 V2 m-2 Hz-1 at an ion electrode spacing of 310(10) μm. We describe the experimental setup for trapping and cooling Yb+ ions and provide frequency measurements of the 2S1/2↔2P1/2 and 2D3/2↔3D[3/2]1/2 transitions for the stable 170Yb+, 171Yb+, 172Yb+, 174Yb+, and 176Yb+ isotopes which are more precise than previously published work

Discovery of active proteins directly from combinatorial randomized protein libraries without display, purification or sequencing:identification of novel zinc finger proteins.

We have successfully linked protein library screening directly with the identification of active proteins, without the need for individual purification, display technologies or physical linkage between the protein and its encoding sequence. By using 'MAX' randomization we have rapidly constructed 60 overlapping gene libraries that encode zinc finger proteins, randomized variously at the three principal DNA-contacting residues. Expression and screening of the libraries against five possible target DNA sequences generated data points covering a potential 40,000 individual interactions. Comparative analysis of the resulting data enabled direct identification of active proteins. Accuracy of this library analysis methodology was confirmed by both in vitro and in vivo analyses of identified proteins to yield novel zinc finger proteins that bind to their target sequences with high affinity, as indicated by low nanomolar apparent dissociation constants

Fluorescent microplate-based analysis of protein-DNA interactions II:immobilized DNA

A simple protein-DNA interaction analysis has been developed using both a high-affinity/high-specificity zinc finger protein and a low-specificity zinc finger protein with nonspecific DNA binding capability. The latter protein is designed to mimic background binding by proteins generated in randomized or shuffled gene libraries. In essence, DNA is immobilized onto the surface of microplate wells via streptavidin capture, and green fluorescent protein (GFP)-labeled protein is added in solution as part of a crude cell lysate or protein mixture. After incubation and washing, bound protein is detected in a standard microplate reader. The minimum sensitivity of the assay is approximately 0.4 nM protein. The assay format is ideally suited to investigate the interactions of DNA binding proteins from within crude cell extracts and/or mixtures of proteins that may be encountered in protein libraries generated by codon randomization or gene shuffling

EDC-mediated oligonucleotide immobilization on a long period grating optical biosensor

We present the development and simplification of label-free fiber optic biosensors based on immobilization of oligonucleotides on dual-peak long period gratings (dLPGs). This improvement is the result of a simplification of biofunctionalization methodology. A one-step 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC)-mediated reaction has been developed for the straightforward immobilization of unmodified oligonucleotides on the glass fiber surface along the grating region, leading to covalent attachment of a 5´-phosphorylated probe oligonucleotide to the amino-derivatized fiber grating surface. Immobilization is achieved via a 5´phosphate-specific linkage, leaving the remainder of the oligonucleotide accessible for binding reactions. The dLPG has been tested in different external media to demonstrate its inherent ultrahigh sensitivity to the surrounding-medium refractive index (RI) achieving 50- fold improvement in RI sensitivity over the previously-published LPG sensor in media with RI’s relevant to biological assays. After functionalization, the dLPG biosensor was used to monitor the hybridization of complementary oligonucleotides showing a detectable oligonucleotide concentration of 4 nM. The proposed one-step EDC reaction approach can be further extended to develop fiber optic biosensors for disease analysis and medical diagnosis with the advances of label-free, real-time, multiplex, high sensitivity and specificity

Making the leap: the translation of innovative surgical devices from the laboratory to the operating room

MINI-ABSTRACT: A decade from publication, approximately one in ten surgical devices described in the literature made the leap from the laboratory to a first-in-human study. Clinical involvement was a significant predictor of translation; devices developed with clinical collaboration were over six times more likely to be translated than those without. STRUCTURED ABSTRACT: OBJECTIVE: To determine the rate and extent of translation of innovative surgical devices from the laboratory to first-in-human studies, and to evaluate the factors influencing such translation. SUMMARY BACKGROUND DATA: Innovative surgical devices have preceded many of the major advances in surgical practice. However, the process by which devices arising from academia find their way to translation remains poorly understood. METHODS: All biomedical engineering journals, and the five basic science journals with the highest impact factor, were searched between January 1993 and January 2000 using the Boolean search term “surgery OR surgeon OR surgical”. Articles were included if they described the development of a new device and a surgical application was described. A recursive search of all citations to the article was performed using the Web of Science (Thompson-Reuters, New York, USA) to identify any associated first-in-human studies published by January 2015. Kaplan-Meier curves were constructed for the time first-in-human studies. Factors influencing translation were evaluated using Log Rank and Cox proportional hazards models. RESULTS: 8,297 articles were screened, and 205 publications describing unique devices identified. The probability of a first-in-human at 10 years was 9.8%. Clinical involvement was a significant predictor of a first-in-human study (p = 0.02); devices developed with early clinical collaboration were over six times more likely to be translated than those without (RR 6.5 [95% CI 0.9 - 48]). CONCLUSIONS: These findings support initiatives to increase clinical translation through improved interactions between basic, translational, and clinical researchers

Real-time detection of DNA interactions with long-period fiber-grating-based biosensor

Using an optical biosensor based on a dual-peak long-period fiber grating, we have demonstrated the detection of interactions between biomolecules in real time. Silanization of the grating surface was successfully realized for the covalent immobilization of probe DNA, which was subsequently hybridized with the complementary target DNA sequence. It is interesting to note that the DNA biosensor was reusable after being stripped off the hybridized target DNA from the grating surface, demonstrating a function of multiple usability. © 2007 Optical Society of America

Regulatory approval of new medical devices: cross sectional study

OBJECTIVE:  To investigate the regulatory approval of new medical devices. DESIGN:  Cross sectional study of new medical devices reported in the biomedical literature. DATA SOURCES:  PubMed was searched between 1 January 2000 and 31 December 2004 to identify clinical studies of new medical devices. The search was carried out during this period to allow time for regulatory approval. ELIGIBILITY CRITERIA FOR STUDY SELECTION:  Articles were included if they reported a clinical study of a new medical device and there was no evidence of a previous clinical study in the literature. We defined a medical device according to the US Food and Drug Administration as an "instrument, apparatus, implement, machine, contrivance, implant, in vitro reagent, or other similar or related article." MAIN OUTCOME MEASURES:  Type of device, target specialty, and involvement of academia or of industry for each clinical study. The FDA medical databases were then searched for clearance or approval relevant to the device. RESULTS:  5574 titles and abstracts were screened, 493 full text articles assessed for eligibility, and 218 clinical studies of new medical devices included. In all, 99/218 (45%) of the devices described in clinical studies ultimately received regulatory clearance or approval. These included 510(k) clearance for devices determined to be "substantially equivalent" to another legally marketed device (78/99; 79%), premarket approval for high risk devices (17/99; 17%), and others (4/99; 4%). Of these, 43 devices (43/99; 43%) were actually cleared or approved before a clinical study was published. CONCLUSIONS:  We identified a multitude of new medical devices in clinical studies, almost half of which received regulatory clearance or approval. The 510(k) pathway was most commonly used, and clearance often preceded the first published clinical study

Associations Between Left Ventricular Dysfunction and Brain Structure and Function: Findings From the SABRE (Southall and Brent Revisited) Study

Background Subclinical left ventricular (LV) dysfunction has been inconsistently associated with early cognitive impairment, and mechanistic pathways have been poorly considered. We investigated the cross‐sectional relationship between LV dysfunction and structural/functional measures of the brain and explored the role of potential mechanisms. Method and Results A total of 1338 individuals (69±6 years) from the Southall and Brent Revisited study underwent echocardiography for systolic (tissue Doppler imaging peak systolic wave) and diastolic (left atrial diameter) assessment. Cognitive function was assessed and total and hippocampal brain volumes were measured by magnetic resonance imaging. Global LV function was assessed by circulating N‐terminal pro–brain natriuretic peptide. The role of potential mechanistic pathways of arterial stiffness, atherosclerosis, microvascular disease, and inflammation were explored. After adjusting for age, sex, and ethnicity, lower systolic function was associated with lower total brain (beta±standard error, 14.9±3.2 cm3; P<0.0001) and hippocampal volumes (0.05±0.02 cm3, P=0.01). Reduced diastolic function was associated with poorer working memory (−0.21±0.07, P=0.004) and fluency scores (−0.18±0.08, P=0.02). Reduced global LV function was associated with smaller hippocampal volume (−0.10±0.03 cm3, P=0.004) and adverse visual memory (−0.076±0.03, P=0.02) and processing speed (0.063±0.02, P=0.006) scores. Separate adjustment for concomitant cardiovascular risk factors attenuated associations with hippocampal volume and fluency only. Further adjustment for the alternative pathways of microvascular disease or arterial stiffness attenuated the relationship between global LV function and visual memory. Conclusions In a community‐based sample of older people, measures of LV function were associated with structural/functional measures of the brain. These associations were not wholly explained by concomitant risk factors or potential mechanistic pathways