Horizon 2020 SME-Instrument topic: clinical research for the validation of biomarkers and/or diagnostic medical devices.

The European Commission released €130 million over 2014, 2015 and 2017 under the EU Framework Program for Research and Innovation, Horizon 2020, to support innovative small and medium-sized enterprises in the diagnostic area. The call topic focused on 'Clinical research for the validation of biomarkers and/or diagnostic medical devices'. It attracted 1194 applicants from all over Europe. The quality of the proposals was high and a large proportion of them were eligible for funding. In the majority, proposals were about in vitro diagnostics and tackled both clinical validation of new biomarkers and device optimization. The proposals dealt with various advanced technologies. One third of the proposers gave priority to the new and promising field of personalized medicine.

Point-Counterpoint: Meningitis/Encephalitis Syndromic Testing in the Clinical Laboratory.

INTRODUCTIONSyndromic panels were first FDA cleared for detection of respiratory pathogens in 2008. Since then, other panels have been approved by the FDA, and most recently, the FilmArray meningitis/encephalitis panel (BioFire, Salt Lake City, UT) has become available. This assay detects 14 targets within 1 h and includes pathogens that typically cause different manifestations of infection, although they infect the same organ system. Several studies have reported both false-positive and false-negative results with this test, and all agree that the cost is significant. As with other panels, health care systems have adopted different strategies for offering this assay. Some have implemented strategies to limit the use of the test to certain patient populations, others have elected not to offer the test, and others have elected not to offer the test and instead request that providers order specific PCRs for the pathogens that best fit the patient's symptoms. In this Point-Counterpoint, Jennifer Dien Bard of the Department of Pathology and Laboratory Medicine, Children's Hospital Los Angeles, and of the Keck School of Medicine at the University of Southern California explains why laboratories should offer these assays without restriction. Kevin Alby of the University of Pennsylvania explains the concerns about the use of these assays as first-line tests and why some limitations on their use might be appropriate.

Point-of-care coagulation monitoring: first clinical experience using a paper-based lateral flow diagnostic device.

Vitamin K antagonists such as warfarin are the most widely used class of oral anticoagulants. Due to a narrow therapeutic window, patients on warfarin require regular monitoring. Self-testing using point-of-care (POC) diagnostic devices is available, but cost makes this monitoring method beyond reach for many. The main objective of this research was to assess the clinical utility of a low-cost, paper-based lateral flow POC diagnostic device developed for anticoagulation monitoring without the need for a separate electronic reader. Custom-fabricated lateral flow assay (LFA) test strips comprised of a glass fiber sample pad, a nitrocellulose analytical membrane, a cellulose wicking pad, and a plastic backing card were assembled in a plastic cassette. Healthy volunteers and patients on warfarin therapy were recruited for this prospective study. For each participant, a whole blood sample was collected via fingerstick to determine: (1) international normalized ratio (INR) using the CoaguChek® XS coagulometer, (2) hematocrit by centrifugation, and (3) red blood cell (RBC) travel distance on the experimental LFA device after 240 s using digital image analysis. RBC travel distance measured on the LFA device using blood samples obtained from warfarin patients positively correlated with increasing INR value and the LFA device had the capability to statistically distinguish between healthy volunteer INR values and those for patients groups with INR ≥ 2.6. From these data, it is predicted that this low-cost, paper-based LFA device can have clinical utility for identifying anticoagulated patients taking vitamin K antagonists who are outside of the desired therapeutic efficacy window.

Ultrasound-Guided Core-Needle Versus Vacuum-Assisted Breast Biopsy: A Cost Analysis Based on the American Society of Breast Surgeons' Mastery of Breast Surgery Registry.

PURPOSE: To evaluate the cost-efficacy of vacuum-assisted ultrasound-guided breast biopsy instruments compared to ultrasound-guided 14-gauge spring-loaded core-needle biopsy. METHODS: The American Society of Breast Surgeons' Mastery of Breast Surgery Registry was reviewed. Biopsy findings, any rebiopsy, and the instrument used were abstracted for 31,451 ultrasound-guided biopsy procedures performed between 2001 and July 2014. Rates of cancer diagnosis and rebiopsy were calculated for each instrument. A linear mathematical model was developed to calculate total cost per cancer diagnosis, including procedural costs and the costs of any additional surgical rebiopsy procedures. Mean cost per cancer diagnosis with confidence limits was then determined for 14-gauge spring-loaded core-needle biopsy and 14 different vacuum-assisted instruments. For 14-gauge spring-loaded core-needle biopsy, mean cost per cancer diagnosis was $4346 (4327-$4366). For the vacuum-assisted instruments, mean cost per cancer diagnosis ranged from a low of $3742 ($3732-$3752) to a high of $4779 ($4750-$4809). RESULTS: Vacuum-assisted instruments overall were more cost-effective than core with a mean cost per cancer diagnosis of $4052 ($4038-$4067) (p < 0.05). Tethered vacuum-assisted instruments performed best with a mean cost per cancer diagnosis of $3978 ($3964-$3991) (p < 0.05). Nontethered devices had a mean cost per cancer diagnosis of $4369 ($4350-$4388), a result no better than core (p < 0.05). CONCLUSIONS: Ultrasound-guided vacuum-assisted breast biopsy had a lower mean cost per cancer diagnosis than 14-gauge spring-loaded core-needle biopsy. This advantage was only seen in tethered vacuum-assisted instruments. Within device families, larger instruments tended to outperform smaller instruments.

Novel cost-effective quality control approach for the Cepheid Xpert CT/NG assay for the detection of Chlamydia Trachomatis and Neisseria Gonorrhoeae.

The Xpert CT/NG is a rapid assay for detection of Neisseria gonorrhoeae and Chlamydia trachomatis. QC materials must be formulated to emulate human specimens, and are prohibitively expensive. A creative, cost-effective QC approach is proposed. The acceptable sample types for the Xpert CT/NG assay were extended to include eye swabs.

Defining the diagnostic divide: an analysis of registered radiological equipment resources in a low-income African country.

INTRODUCTION: Diagnostic radiology is recognised as a key component of modern healthcare. However there is marked inequality in global access to imaging. Rural populations of low- and middle-income countries (LMICs) have the greatest need. Carefully coordinated healthcare planning is required to meet the ever increasing global demand for imaging and to ensure equitable access to services. However, meaningful planning requires robust data. Currently, there are no comprehensive published data on radiological equipment resources in low-income countries. The aim of this study was to conduct the first detailed analysis of registered diagnostic radiology equipment resources in a low-income African country and compare findings with recently published South African data. METHODS: The study was conducted in Tanzania in September 2014, in collaboration with the Tanzanian Atomic Energy Commission (TAEC), which maintains a comprehensive database of the country's registered diagnostic imaging equipment. All TAEC equipment data were quantified as units per million people by imaging modality, geographical zone and healthcare sector. RESULTS: There are 5.7 general radiography units per million people in the public sector with a relatively homogeneous geographical distribution. When compared with the South African public sector, Tanzanian resources are 3-, 21- and 6-times lower in general radiography, computed tomography and magnetic resonance imaging, respectively. CONCLUSION: The homogeneous Tanzanian distribution of basic public-sector radiological services reflects central government's commitment to equitable distribution of essential resources. However, the 5.7 general radiography units per million people is lower than the 20 units per million people recommended by the World Health Organization.

Optimizing tuberculosis case detection through a novel diagnostic device placement model: the case of Uganda.

BACKGROUND: Xpert MTB/RIF (Xpert) is being widely adopted in high TB burden countries. Analysis is needed to guide the placement of devices within health systems to optimize the tuberculosis (TB) case detection rate (CDR). METHODS: We used epidemiological and operational data from Uganda (139 sites serving 87,600 individuals tested for TB) to perform a model-based comparison of the following placement strategies for Xpert devices: 1) Health center level (sites ranked by size from national referral hospitals to health care level III centers), 2) Smear volume (sites ranked from highest to lowest volume of smear microscopy testing), 3) Antiretroviral therapy (ART) volume (sites ranked from greatest to least patients on ART), 4) External equality assessment (EQA) performance (sites ranked from worst to best smear microscopy performance) and 5) TB prevalence (sites ranked from highest to lowest). We compared two clinical algorithms, one where Xpert was used only for smear microscopy negative samples versus another replacing smear microscopy. The primary outcome was TB CDR; secondary outcomes were detection of multi-drug resistant TB, number of sites requiring device placement to achieve specified rollout coverage, and cost. RESULTS: Placement strategies that prioritized sites with higher TB prevalence maximized CDR, with an incremental rate of 6.2-12.6% compared to status quo (microscopy alone). Diagnosis of MDR-TB was greatest in the TB Prevalence strategy when Xpert was used in place of smear microscopy. While initial implementation costs were lowest in the Smear Volume strategy, cost per additional TB case detected was lowest in the TB prevalence strategy. CONCLUSION: In Uganda, placement of Xpert devices in sites with high TB prevalence yielded the highest TB CDR at the lowest cost per additional case diagnosed. These results represent novel use of program level data to inform the optimal placement of new technology in resource-constrained settings.

Determining the utility and durability of medical equipment donated to a rural clinic in a low-income country.

BACKGROUND: Health centers in low-income countries often depend on donations to provide appropriate diagnostic equipment. However, donations are sometimes made without an understanding of the recipient's needs, practical constraints or sustainability of supplies. METHODS: We donated a set of physical diagnostic equipment, non-invasive instrument tests and laboratory supplies to a rural health center in the Democratic Republic of Congo. We collected information on the usage and durability of equipment and supplies for each patient encounter over a 1-year period. RESULTS: We recorded 913 patient encounters. The most commonly used physical diagnostic equipment were the stethoscope (98.9%; 903/913), thermometer (81.7%; 746/913), adult scale (81.4%; 744/913), stop watch (62.6%; 572/913), adult sphygmomanometer (55.8%; 510/913), infant scale (24.9%; 228/913), measuring tape (24.3%; 222/913) and fetoscope (23.8%; 218/913). The most commonly used laboratory tests were the blood smear for malaria (53.7%; 491/913), hematocrit (23.5%; 215/913), urinalysis (20.1%; 184/913) and sputum stain for TB (13.3%; 122/913). With the exception of a penlight and solar lantern, all equipment remained functional. CONCLUSIONS: This study adds valuable information about the utility and durability of equipment supplied to a health center in the Democratic Republic of Congo. Our results might aid in determining the appropriateness of donated medical equipment in similar settings. The selection of donated goods should be made with knowledge of the context in which it will be used, and utilization should be monitored.

The hidden costs of installing Xpert machines in a tuberculosis high-burden country: experiences from Nigeria.

INTRODUCTION: Since the endorsement of GeneXpert MTB/RIF by the WHO, many countries have embarked on implementing this technology. OBJECTIVE: We outline the cost of installing GeneXpert in district hospitals in Abuja, Nigeria. METHODS: We prospectively documented costs related to the installation of GeneXpert at five sites. Costs were collected from receipts received from suppliers and normalized to USD 2012 values. RESULTS: Costs were often identified after initiating installation for many reasons. Installation varied widely between sites with sufficient space and power supply; sites with insufficient space or power supply and costs not directly associated with site installation. The basic cost for installation was USD 2,621.98 per machine. Sites that required additional space cost close to USD 7,000.00. CONCLUSION: Space and power requirements have a significant effect on installation costs. Countries need to carefully consider the placement of Xpert machines based on the quality and size of the available infrastructure.

Transitioning to a national (New Zealand) sole supply scheme for glucose meters: lessons learned, problems yet to be solved.

This case study describes the clinical impact of moving to a single brand of glucose test strips. In 2013 the New Zealand public health system completed a move to procure test strips at a significant discount. The associated direct savings is estimated at around 40% of the total glucose strip budget. Half the local diabetes population undertake glucose monitoring using government-funded diabetes supplies. These patients no longer have a choice of brand of meters and strips. Although the majority of patients adapted well to this change, a small percentage did not. Also, some consumers expressed concerns about analytical performance of the new strips, when used in everyday life. A pragmatic postmarketing surveillance system, designed with consumer input, may help address these residual concerns.

Use of prehospital ultrasound in North America: a survey of emergency medical services medical directors.

BACKGROUND: Advances in ultrasound imaging technology have made it more accessible to prehospital providers. Little is known about how ultrasound is being used in the prehospital environment and we suspect that it is not widely used in North America at this time. We believe that EMS system characteristics such as provider training, system size, population served, and type of transport will be associated with use or non-use of ultrasound. Our study objective was to describe the current use of prehospital ultrasound in North America. METHODS: This study was a cross-sectional survey distributed to EMS directors on the National Association of EMS Physicians (NAEMSP) mailing list. Respondents had the option to complete a paper or electronic survey. RESULTS: Of the 755 deliverable surveys we received 255 responses from across Canada and the United states for an overall response rate of 30%. Of respondents, 4.1% of EMS systems (95% CI 1.9, 6.3) reported currently using ultrasound and an additional 21.7% (95% CI 17, 26.4) are considering implementing ultrasound. EMS services using ultrasound have a higher proportion of physicians (p < 0.001) as their highest trained prehospital providers when compared to the survey group as a whole. The most commonly cited current and projected applications are Focused Abdominal Sonography for Trauma (FAST) and assessment of pulseless electrical activity (PEA) arrest. The cost of equipment and training are the most significant barriers to implementation of ultrasound. Most medical directors want evidence that prehospital ultrasound improves patient outcomes prior to implementation. CONCLUSIONS: Prehospital ultrasound is infrequently used in North America and there are a number of barriers to its implementation, including costs of equipment and training and limited evidence demonstrating improved outcomes. A research agenda for prehospital ultrasound should focus on patient-important outcomes such as morbidity and mortality. Two commonly used indications that could be a focus of standardized training programs are the FAST exam, and assessment of PEA arrest.

Case studies of innovative medical device companies from India: barriers and enablers to development.

BACKGROUND: Over 75% of the medical devices used in India are imported. Often, they are costly and maladapted to low-resource settings. We have prepared case studies of six firms in Bangalore that could contribute to solving this problem. They have developed (or are developing) innovative health care products and therefore are pioneers in the Indian health care sector, better known for its reverse engineering skills. We have sought to understand what enablers and barriers they encountered. METHODS: Information for the case studies was collected through semi-structured interviews. Initially, over 40 stakeholders of the diagnostics sector in India were interviewed to understand the sector. However the focus here is on the six featured companies. Further information was obtained from company material and other published resources. RESULTS: In all cases, product innovation has been enabled by close interaction with local medical practitioners, links to global science and technology and global regulatory requirements. The major challenges were the lack of guidance on product specifications from the national regulatory agency, paucity of institutionalized health care payers and lack of transparency and formalized Health Technology Assessment in coverage decision-making. The absence of national evidence-based guidelines and of compulsory continuous education for medical practitioners were key obstacles in accessing the poorly regulated and fragmented private market. CONCLUSIONS: Innovative Indian companies would benefit from a strengthened capacity and interdisciplinary work culture of the national device regulatory body, institutionalized health care payers and medical councils and associations. Continuous medical education and national medical guidelines for medical practitioners would facilitate market access for innovative products.

New diagnostic aids for melanoma.

Detection of melanoma at an early stage is crucial to improving survival rates in melanoma. Accurate diagnosis by current techniques including dermatoscopy remains difficult, and new tools are needed to improve our diagnostic abilities. This article discusses recent advances in diagnostic techniques including confocal scanning laser microscopy, MelaFind, SIAscopy, and noninvasive genomic detection, as well as other future possibilities to aid in diagnosing melanoma. Advantages and barriers to implementation of the various technologies are also discussed.

Scaling up Xpert MTB/RIF technology: the costs of laboratory- vs. clinic-based roll-out in South Africa.

OBJECTIVE: The World Health Organization recommends using Xpert MTB/RIF for diagnosis of pulmonary tuberculosis (PTB), but there is little evidence on the optimal placement of Xpert instruments in public health systems. We used recent South African data to compare the cost of placing Xpert at points of TB treatment (all primary clinics and hospitals) with the cost of placement at sub-district laboratories. METHODS: We estimated Xpert's cost/test in a primary clinic pilot and in the pilot phase of the national Xpert roll-out to smear microscopy laboratories; the expected future volumes for each of 223 laboratories or 3799 points of treatment; the number and cost of Xpert instruments required and the national cost of using Xpert for PTB diagnosis for each placement scenario in 2014. RESULTS: In 2014, South Africa will test 2.6 million TB suspects. Laboratory placement requires 274 Xpert instruments, while point-of-treatment placement requires 4020 instruments. With an Xpert cartridge price of $14.00, the cost/test is $26.54 for laboratory placement and $38.91 for point-of-treatment placement. Low test volumes and a high number of sites are the major contributors to higher point-of-treatment costs. National placement of Xpert at laboratories would cost $71 million/year; point-of-treatment placement would cost $107 million/year, 51% more. CONCLUSION: Placing Xpert technology at points of treatment is substantially more expensive than placing the instruments in smear microscopy laboratories. The incremental benefits of point-of-treatment placement, in terms of better patient outcomes, will have to be equally substantial to justify the additional cost to the national health budget.

Quality of medical devices and in vitro diagnostics in resource-limited settings.

The phenomenon of poor-quality medicines in resource-limited settings is well documented, and field observations reveal similar problems with medical devices (MDs) and in vitro diagnostics (IVDs). In scientific literature, however, there are only scarce reports and documents providing evidence of quality problems of MDs or IVDs in resource-limited settings. This discrepancy may be ascribed to (i) the poor regulatory oversight of MDs/IVDs in resource-limited settings, (ii) a general lack of awareness of the problem of poor-quality MDs/IVDs amongst the scientific community and decision-makers, and (iii) poor quality assurance in diagnostic laboratories in resource-poor settings, precluding tracing quality problems of IVDs from the other potential causes of diagnostic inaccuracy. The problem of poor-quality MDs/IVDs in resource-limited settings is a complex one to address. Firstly, operational definitions for substandard and counterfeit MDs/IVDs are required, as well as ad hoc field surveys, to ensure proper appraisal of the real extent of the problem. Investments are needed to reinforce the national regulatory oversights on MDs/IVDs in resource-limited settings, and to encourage a proactive and transparent exchange of information between Northern and Southern regulatory authorities. Industrialized countries can play a role by expanding and strengthening their regulatory oversight and quality labels to those MDs/IVDs that are frequently used in resource-poor settings. Hopefully, the combination of these measures will result in better protection of patients in resource-poor countries from the effects of being exposed to poor-quality MDs and IVDs.

Portable CT imaging of acute stroke patients in the emergency department.

A study was performed to determine whether the use of a portable CT scanner dedicated for ED patients would reduce the time elapsed from the physician's request for CT imaging until the start time of the study. The portable scanner allowsfor more rapid assessment of stroke patients and does not require additional facilities or personnel. In addition, when not in use in the ED, the scanner couldbe transported elsewhere in the hospital, for example the ICU, and be available for alternative clinical applications. For most hospitals, it is not neccessary to invest in an additional CT scanner dedicated for stroke imaging in the ED unless demand for the scanner exceeds 60 patients per day or, alternatively, the prevalence of stroke in the community served by the hospital is approximately 4-5 times the national average.