Final Report Summary - TEMPOTEST-QC (An Integrated Tool-Kit for the Clinical Evaluation of Microbial Detection and Antibiotic Susceptibility Point-of-Care Testing Technologies)
Executive Summary:
The TEMPOtest-QC project has completed its stated goal of creating and providing an “Integrated Tool Kit” that has (and will continue to) help diagnostic developers and manufacturers to evaluate and validate their Point-of-Care and rapid microbiological testing technologies. The project Tool Kit has been successfully utilized (and will continue to be utilized) to evaluate and validate existing and novel technologies that could revolutionize future developments in Point-of-Care and rapid microbiological testing. Further, the TEMPOtest-QC collection of resistant bacterial isolates and novel antimicrobial resistance genes currently contains more than 2000 isolates, including bacterial isolates and antimicrobial resistances obtained and characterised from a wide range of countries, many of these countries experiencing endemic problems associated with antimicrobial resistance. These isolates and genes could form the basis for future epidemic and endemic infectious disease outbreaks, and in this respect, the TEMPOtest-QC project has (and will continue) to help safeguard European citizens by helping provide SMEs and diagnosticians with access to rare and common bacterial isolates and antimicrobial resistances present in its archive.This means that at this moment in time European infectious disease diagnostic SMEs have the capability of gaining immediate access to bacterial isolates, novel antimicrobial resistance genes, and experienced resources that will ensure that they can compete, and better, business competitors in the rest of the world.Further the distribution of a European questionnaire has allowed TEMPOtest-QC to gather opinions from key target groups regarding the perceived hurdles and problems associated with the development, implementation and use of Point-of-Care and rapid microbiological testing in healthcare systems. These opinions have been collated and published in an open access article and have been added to the TEMPOtest-QC website. The publication includes a list of recommendations to help current and future developers and manufacturers of Point-of-Care and rapid microbiological testing to optimize their kit development, implementation and marketing strategies to key stakeholders in the European market. Importantly, this work has proceeded against a background of great financial insecurity that currently envelops Europe, and indeed the rest of the world. The knock-on effect is that many SMEs (including SMEs involved in the development of new diagnostic technologies) may not have survived, and it is impossible to predict how many SME’s would have required the services of the TEMPOtest-QC project had the financial crisis not occurred. Indeed, this crisis also affected one of the TEMPOtest-QC partners (C-it), who were declared bankrupt on 15th March 2013. However, all of the Deliverables of the project actually have still been achieved. Ultimately, the TEMPOtest-QC project has laid the foundations for future collaborations and projects that are designed to help businesses, SMEs (and indeed university research departments) to evaluate and validate their new microbiological testing technologies. The experience that the TEMPOtest-QC partners have gained working with SMEs and industry during the project period means that they are perfectly placed to offer their services to future microbiological diagnostic developers when requested. The TEMPOtest-QC project is just the beginning of what the partners hope will be a long and fruitful relationship with European diagnostic SMEs.
Project Context and Objectives:
Project Context:
In 2007, 2 EU expert groups recommended that more emphasis be placed on research into tackling antimicrobial resistance, largely due to the current lack of novel antibiotic drug development by pharmaceutical companies and the growing threat of antibacterial drug resistance. Their recommendations included preserving the older antibiotics currently in use, whilst developing strategies to improve surveillance, enable control measures, facilitate efforts to reduce over consumption, discourage inappropriate use, and to further develop the use of rapid diagnostic (point-of-care) testing methods for the detection of pathogenic bacteria and antibiotic resistance gene profiling. Further, a report from the American College of Microbiology titled "Clinical Microbiology in the 21st Century - keeping the pace”, stated that "translating research achievements into clinical microbiology laboratory practice is critically important" and that “forging relationships with industry colleagues in order to provide a meaningful feedback to manufacturers…will hasten this process”. This report emphasizes the advantages obtained when both industry and hospitals work together in validating translational research technologies.The hurdles to the implementation of novel diagnostic tests into health care systems may generally be split into two categories, those hurdles present at the national level (requiring governmental action), and those hurdles present at the clinical level. In essence, technical and regulatory issues are no longer problems relating to the implementation of point-of-care testing, leaving the following issues that currently affect the implementation of point-of-care diagnostic tests: 1) political issues (e.g. clinical microbiologists and clinical laboratories being unwilling to relinquish their power over clinical diagnostic testing), 2) maintenance of quality control at the point-of-care, 3) maintenance of equipment at the point-of-care, 4) providing support for the clinician in interpreting point-of-care tests, 5) financial issues (the way in which health care budgets are allocated and what is covered by health insurance) and 6) the entrenched positions of suppliers and established distribution chains. A
General hurdles:
• Lack of information regarding the national and international need for novel diagnostic tests in each clinical discipline
• Lack of cost-effectiveness (e.g. too low profit margins) for manufacturers
• No perceived (or proven) difference in patient benefit between novel diagnostic tests and current traditional testing methodologies with respect to time and/or cost per test procedure)
• Lack of information and public support for developing and using novel diagnostic tests within society - people would sooner that governments spend their tax revenue on crime and punishment, housing issues, job creation etc, rather than supporting the integration of novel diagnostic tests into the nosocomial and primary care settings
• Most technologies with potential application to point-of-care diagnostics currently require relatively large pieces of ancillary equipment (for example to wash microarrays, to detect labels etc). Progress in the miniaturization of these ancillary components e.g. via the use of microfluidics technology, needs to be translated through into point-of-care tests
• A requirement for test devices that are robust enough to withstand the challenges of use by differently skilled users in various environments (hospital, general practitioners surgery, at home, at different temperatures, varying humidities, low and high-level light extremes, in environments undergoing vibration etc)
• The development of easy-to-use test device interfaces suitable for use with individuals possessing various levels of experience and training
• The use of sub-optimal samples during evaluation test procedures and their influence of the accuracy of the point-of-care tests result. For example, the evaluation of clinical chemistry point-of-care tests using analytes in a buffer will not accurately reflect on the complexity of clinical (plasma or blood) specimens
• The recruitment of targeted patient populations representative of those that will be tested using the point-of-care methodology
• A lack of experience in large clinical hospitals in setting up management systems and quality testing systems for point-of-care testing manufacturers
• The incorporation of information from point-of-care tests into patient records (NB. the standardization of connecting point-of-care testing devices to hospital information systems has previously been addressed via the Connectivity Industry Consortium (25))
• The integration of patient information between various health environments, available for national access
• A lack of standardized feedback systems to inform point-of-care test manufacturers of possible problems and/or suggestions regarding their products
Specific hurdles:
• Lack of a European focal point (of clinical microbiology hospitals and laboratories) possessing relevant information and hands-on experience regarding the clinical evaluation of microbiology-related point-of-care testing
• Lack of a freely accessible standardized archive of bacterial pathogens available for initial evaluation testing (both pre-clinical and clinical )
• Lack of information regarding differences and similarities in the current national and European-wide demand for microbial point-of-care testing technologies within hospitals and the general practitioner environment (information is available from market trend sources, but these reports are not widely available (32)).
• Many different species and types of microorganisms may be associated with a disease state e.g. bacteria, viruses and fungi are all associated with respiratory infections. This variety of potential pathogens means that a “universal” point-of-care test for respiratory infections (and indeed most other disease states) is unlikely to be available in the near future. Moreover, though recent developments in PCR technology have decreased the time from specimen processing to detection (e.g. the Cepheid, GenExpert system), separate PCR mixes (modules) are required for each bacterial species or serogroup to be detected, and little information is provided regarding antimicrobial resistance profiles. Further, many different PCR thermocycling programs and modules may be required, dependant on the number of PCR primers (infectious agents) to be used.
• The ability of microorganisms to adapt and alter (surface expressed) protein sequences, or even to stop the expression of particular proteins (often proteins involved in the host immune response). This ability of microorganisms to mutate and undergo “phase variability” could be a problem for immunoassay based point-of-care technologies. Moreover, the effects of mutation and phase variability in microbial populations are very difficult to predict.
• Identical microorganisms may be found in many different specimen types e.g. blood and sputum. This specimen variability may have profound consequences on the ability of point-of-care technologies to detect these microorganisms. For example, point-of-care technologies relying on amplification techniques may have difficulty with respect to the removal of intrinsic amplification inhibitors present in some samples e.g. faeces and blood. The presence of PCR amplification inhibitors can result in false negative results, and if present may require additional (time-consuming) DNA purification steps. Amplificatoin inhibitors may also severely affect the sensitivity, reproducibility and reliability of test results.
It is in this context that the TEMPOtest-QC project was established.
Main Objectives:
The main objectives of the TEMPOtest-QC project was to address some of the major general and specific hurdles preventing the development and widespread application of infectious disease Point-Of-Care testing technologies in the clinical microbiological laboratory, hospital diagnostic, and the marketing environments.
In essence, the TEMPOtest-QC project addresses the need to “design integrated tools for closing the gap between microbiological point-of-care technologies and actual clinical need”. The project has performed this task by designing, developing and implementing a microbiological point-of-care “tool-kit”.
The objectives of this tool-kit are to provide:
i) accurate information on European attitudes to infectious disease point-of-care microbiological testing, so as to provide developers and manufacturers of infectious disease POC tests with invaluable, open access, information regarding the current attitudes and perceived hurdles of stakeholders to the development, implementation and marketing of infectious disease POC technologies and test kits. This information can then be used by POC developers and manufacturers to better design and target their POC technologies to the wishes of the medical community and general public, thereby greatly increasing the likelihood of a successful product launch and acceptance of the technology.
ii) an archive of freely available quality control/quality assured and characterized microbiological test samples for rapid initial evaluation of point-of-care microbiological testing technologies, as well as access to state-of-the-art microbiology testing facilities and expertise (in consultation with TEMPOtest-QC partners). Access to this archive by European infectious disease POC manufacturers provides such manufactures with immediate access to a wide range of common and rare bacterial isolates and antimicrobial resistances, reducing the time by which technological and product evaluation can occur.
iii) a freely available Comparison Tool comprising specimen archive/software tool to rapidly determine sensitivity, susceptibility, reproducibility microbiological technologies compared to current routine clinical microbiological protocols. The objective of the comparison tool is to provide infectious disease POC manufacturers with a single source of information relating to already available microbiological testing technologies, such that specificity and sensitivity results obtained from new microbiological technologies and test kits that are under development can be rapidly and easily compared with those results obtained using existing microbiological test kits. This information will allow microbiological POC test kit developers and manufacturers to determine the level at which new kits and technologies should be performing. This information will help ensure that new kits and technologies can at least compete with kits and technologies current ly available on the market.
iv) the further development of electronic nose and antimicrobial resistance gene microarrays as future tools for microbiological point-of-care testing. Electronic nose devices and microarrays represent two new technologies potential eventually developed as clinical laboratory, and even point of care, microbiological testing technologies. Therefore, the objective of the TEMPOtest-QC project was to further develop and help optimise these technologies as part of the developmental cycle for novel microbiological (POC) detection and testing technologies. Further, the inclusion of these new technologies in the project provided a template for collaboration between SME and university research departments, as well as invaluable experience with respect to evaluating new microbiological technologies using a blinded and quality control operating procedure.
v) the development of dedicated databases and an internet presence to promote the objectives and goals of the TEMPOtest-QC project is a fundamental step in helping disseminate the context and objectives of the TEMPOtest-QC project to stakeholders. The TEMPOtest-QC website has been a focal point for dissemination activities, providing a single website where all of the tools developed as part of the TEMPOtest-QC project can be rapidly and easily accessed by potential and existing microbiological POC developers and manufacturers.
Project Results:
Presented below is a summary of the main S & T results/foregrounds generated during the TEMPOtest-QC project. Further information is contained in the attached pdf file. Confidential data is not shown in this section of the report.
1) Questionnaire
An online questionnaire was established in order to determine the current hurdles and perceptions to the development and implementation of Point-Of-Care infectious disease testing technologies by relevant stakeholders, i.e. medical personnel, Point-Of-Care test kit manufacturers and the general public. The results are available at http://www.dovepress.com/perceptions-of-point-of-care-infectious-disease-testing-among-european
- peer-reviewed-article-PPA. and indicate that the general public tends to be much more enthusiastic about the introduction of Point-Of-Care test kits (particularly kits for use in the home environment) than medical personnel or Point-of-Care test kit manufacturers, This information has also been distributed to approximately 400 associated businesses.
2) Isolate Archive and Comparison Tool
The isolate archive comprises approximately >2000 clinical bacterial isolates. The collection of Gram–positive bacteria includes 11 different species including Clostridium spp. Staphylococcus spp. and Streptococcus spp. The isolates are representative of the major antimicrobial resistance mechanisms for Staphylococcus spp. (mecA, mecC, VanA, mupA, msrA etc) and for Streptococcus pyogenes (mefA and ermB), major capsular serotypes for Streptococcus pneumoniae, and virulence genes (tcdA, tcdB and CDT for Clostridium difficile ; speA, speC, speF and ssa for Streptococcus pyogenes; PVL for S. aureus). The collection of Gram-negative clinical isolates includes non-fermenters (Pseudomonas sp. and Acinetobacter sp.) and Enterobacteriaceae (Escherichia, Klebsiella, etc) originating from 20 different countries. Resistance mechanisms includes penicillinases (TEM, SHV or LEN, carbenicillinases), ESBLs (TEM, SHV, CTX-M), minor ESBLs (BEL, VEB, PER, GES), OXA-type ESBLs, plasmidic AmpC, metallo beta-lactamases (VIM, IMP, NDM) , class A carbapenemases (GES, KPC), class D carbapenemases (OXA-48, OXA-23, 24, 58 etc), Qnr conferring resistance to fluoroquinolones, and 16S RNA methylases conferring resistance to all clinically used aminoglycosides. In total, this represents a very large collection of well-characterized isolates that can be used for comparative testing or validation of various diagnostic methods.
3) Specimen Archive
The specimen archive contains >970 specimens that may be used for the evaluation of new technologies and Point-of-Care diagnostics for microbial infectious diseases. The majority of isolates are urines and feces (approximately 250 of each), followed by sputa, punctates, cerebrospinal fluids, bronchioalveloar lavages, pus and pleural fluids. The volume of each sample varies per samples type, but specimens may be “spiked” using different concentrations of test bacteria in a background of normal (or disease) bacterial flora.
The specimen archive also includes approximately 30 fecal samples and accompanying microbiome data (16S rRNA sequencing) for use in future quality control schemes, and as positive/negative controls for the evaluation of new diagnostic test kits designed ot investigate unculturable pathogenic bacteria associated with human disease.
4) Development of Electronic Nose Technology
Information regarding the development of the electronic nose is shown in the Confidential Section of this report.
5) Development of Antimicrobial Resistance Microarray
The development of the antimicrobial resistance microarray is explained in Deliverables 5.1 – 5.3. Progress has been made in optimizing and evaluating both the microarray itself, and the methodology to be used for processing the microarray (specially useful in the Point-of-Care setting). Attention was also paid to quality control issues as outlined below:
The process was split into 4 areas:
1) Pre-Shipment Requirements
• Pre-preparation & Project Documentation
• Material Shipment to QCMD
In order to support this activity QCMD organised a TEMPOtest-QC “Testing Study” process (See Appendix 1). The TEMPOtest-QC team selected antimicrobial samples that had been preliminary characterised as part of the TEMPtest project and defined an antimicrobial resistance panel specification that would be used as part of the quality assessment. The antimicrobial resistance samples were sent to QCMD.
2) TEMPOtest-QC Testing Panel Distribution
• Planning and Prep of Shipment
• Distribution of TEMPOtest-QC Panel to Partners
QCMD then prepared the material to the agreed specification under ISO17043 / ISO13485 and the samples were then assembled into a TEMPOtest-QC quality assessment panel. The quality assessment panel members were coded so the identity of the individual samples remained undisclosed for the duration of the assessment study. On request the panel was packed, labelled and shipped to the assessment laboratory.
3) TEMPOtest-QC Panel Testing phase
• Testing of Panel by Partners
The assessment laboratory then used the TEMPOtest-QC quality assessment panel to evaluate the performance of the antimicrobial resistance gene microarray assay (WP5).
4) Post-Testing data analysis & reporting
• Collation of Results & Data Analysis
• TEMPOtest-QC Report
On completion of testing, QCMD coordinated the reporting of results through the TEMPOtest-QC developed database and supported the data analysis phase. The results obtained were then used to provide information to support the evaluation of the novel antimicrobial resistance gene microarray technology.
Figure 1: TEMPOtest-QC “Testing Study” Process (Provided in Annex 1).
6) Internet and Database Management
A publicly accessible TEMPOtest-QC website was established at the beginning of the project (www.tempotest-QC.eu) and has been one of the key methods for disseminating TEMPOtest-QC information. The website was particularly important for the dissemination and collection of data relating to the perceived hurdles of clinicians, point-of-care manufacturers and the general public with respect to infectious disease Point-of-Care testing. The website also contains useful information and links for manufacturers of infectious disease Point-of-Care test kits, technologists and scientists active in this area.
Businesses Helped
The most important part of the project was to help businesses, SMEs and academic research institutions to develop and evaluate their infectious disease (Point-Of-Care) diagnostic technologies. After all, a toolbox is designed to be used! In this respect, a list of businesses, SMEs and academic research institutions that have utilized the expertise available within the TEMPOtest-QC is shown below:
1) CheckPoints B.V. (www.check-points.com)– Microarray
2) RiverD B.V. (www.riverd.com/raman.html) – Raman spectroscopy
3) Piext B.V. (http://patho-ngen-trace.eu/consortium/organisations/pbv/) – Optical Mapping
4) Academsich Centrum Tandheelkunde Amsterdam [Academic Centre for dentistry Amsterdam] (www.acta.nl/en/index.asp) – FRET probes and rapid diagnosis
5) Streeklab Haarlem [Regional Laboratory for Infection and Infection Prevention] (www.streeklabhaarlem.nl) – High-throughput MultiLocus sequence typing (HiMLST)
6) BioMérieux (www.biomerieux.com) – a) Pre-marketing evaluation of selective chromogenic culture media, discovery of the role of temocillin high-level resistance as a surrogate marker for the detection of OXA-48 carbapenemases; b) Sequencing of full genome of resistant Pseudomonas aeruginosa
7) Oxoid (www.oxoid.com/uk) - Pre-marketing evaluation of selective chromogenic culture media for the detection of ESBL and of CPE
8) Bruker (www.bruker.com) - Evaluation of Microflex Mass spectrometer
9) Qiagen (www.qiagen.com) - Certification according to ISO15189 fo End-Point PCR using Qiagen Master Mix and QiaXel capillary electrophoresis
10) Pfizer (www.pfizer.com) - Evaluation of the in vitro activity of tigecycline efficiency against ESBL producers
11) Siemens (www.siemens.com) – Evaluation of the Microscan WalkAway-96 from Siemens for its ability to identify Enterobacteriaceae and resistance to beta-lactams
12) Lifolchem (www.liofilchem.it) – MIC test strips
13) Alifax (www.alifaxgroup.com) – automated bacterial count and sensitivity analyzer
14) Becton Dickinson (www.bd.com) - PhoenixTM Automated Microbiology System
Technologies Evaluated / Validated:
Below is a list of novel / existing technologies that were used in evaluation/validation experiments by the TEMPOtest-QC consortium, including some example publications (not including manuscripts in preparation or submitted).
1) Novel Microbial Culture Media - doi: 10.1128/JCM.05247-11; doi:10.1128/JCM.06276-11
2) PCR and Sequencing – doi: 10.1128/JB.05786-11; doi: 10.1128/AAC.05583-11
3) Spectrophotmetry – doi:dx.doi.org/10.1016/j.diagmicrobio.2012.05.021
4) Microarray (CheckPoints and UNISI) – doi: 10.1128/AAC.00353-11; doi: 10.1128/JCM.02607-10
5) Electronic Nose (C-it)
6) Peptide-based Fret probes – doi: 10.1128/JCM.05313-11
7) Mass spectrometry
8) Raman spectroscopy - doi: 10.1128/JCM.02101-12
9) High-throughput MultiLocus sequence Typing (HiMLST)
10) Optical Mapping
11) MIC test strips
12) Automated Bacterial Count And Sensitivity Analyzer
13) Electronic Fingers
14) MicroScan WalkAway-96
15) Automated Microbiology System
16) Next Generation Sequencing
17) RNA Sequencing
These evaluated/validated technologies range from the more traditional techniques such as the development of new microbial growth media formulations, PCR and sequencing, spectrophotometry, MIC test strips, multi-locus sequence typing, automated bacterial count and sensitivity analyzer etc, to more “cutting edge” technologies that utilize molecular genetics or physical properties to detect microbiologically interesting diagnostic targets, e.g. microarrays, whole genome restriction fragment polymorphism analysis (Optical Mapping), mass spectrometry, Raman spectroscopy, electronic fingers, next generation sequencing etc. The evaluation and validation studies performed by the TEMPOtest-QC consortium, has shown the potential of these technologies as promising microbial diagnostic technologies of today, or of the near future, with each of these technologies having the capacity to become, an established and invaluable aid in the diagnosis of microbiological disease. Indeed, many of these technologies are already just starting to be used in diagnostic laboratories, simply waiting for advances in, for example miniaturization, in order to become more widely available to the majority of diagnostic applications, including Point-of-Care applications.
PROJECT DISSEMINATION
Website
The TEMPOtest-QC website (www.tempotest-qc.eu) has been successfully used to disseminate information regarding the goals and achievements of the TEMPOtest-QC consortium and toolkit. As well as providing access to the TEMPOtest-QC questionnaire and subsequent results.
Publications
The TEMPOtest-QC project has been particularly successful in discovering and describing new and geographically diverse antimicrobial resistance gene variants and bacterial isolates. To date more than110 publications have been published with help from TEMPOtest-QC project funding, with at least another 5 manuscripts currently being written or submitted to peer reviewed journals. All isolates and antimicrobial resistances described are available for use by European SMEs (via TEMPOtest-QC partners) to help them evaluate and validate future diagnostic testing technologies and kits. For further information, the list of TEMPOtest-QC publications has been submitted online via the EU Participant Portal.
National and International Conferences
The goals and results of the TEMPOtest-QC project have been disseminated via a range of national and international conferences, including conferences in Europe and the USA.
CONCLUSION
The TEMPOtest-QC body of work will help diagnostic microbiology stakeholders (laboratories, manufacturers, clinicians, the general public etc) gain confidence in the development and implementation of new Point-of-Care and rapid diagnostic detection technologies in all fields of diagnostic research and will allow the development of previously untapped European markets. Finally, the TEMPOtest-QC project results and knowledge gained is helping the EU promote and maintain its position as a world leader in (infectious disease) diagnostics.
Potential Impact:
In order to understand the societal impact of the TEMPOtest-QC project, it is first necessary to understand the environment in which the QC project has been operating in the previous 3 years.
It seems certain that society is currently experiencing the beginning of a revolution in Point-Of-Care and rapid testing in the field of medical health sciences, as both scientific and technology-based media (including social media) are increasingly publishing articles on the development of new technologies that are being adapted for use in the field of medical diagnostics. These articles include descriptions of such technological breakthroughs as miniaturisation; personal healthcare, e.g. via the use of "smartphone" technology; as well as (the collection and interrogation of data using) high-throughput bioinformatics analysis. However, many of the technological advances that can truly be named as rapid or Point-Of-Care technologies are still in their infancy, and though novel technologies are being developed to exploit the current "universal" use of smartphone technology, the successful development, evaluation, validation and exploitation of these (smartphone-based) technologies still lies some way in the future. In fact, at this moment in time, most novel diagnostic technologies are not yet ready for commercial exploitation.
Of all the medical disciplines, the development of point-of-care and rapid testing technologies in the field of medical microbiology (bacteria/fungi) has been perhaps the most sluggish, though surprisingly, developments in the field of medical virology are amongst the most advanced (not least due to the global repercussions of HIV disease and the need for rapid HIV diagnosis and treatment). However, in the last 5 years there has been a large increase in the number of new technologies being evaluated and validated for use as "rapid" medical microbiological diagnostics (as opposed to Point-Of-Care diagnostics i.e. testing technologies for use at the hospital bedside, at the general practitioner’s surgery, or at the patient's home). Further, these rapid and novel technologies are starting to be adopted within the actual routine microbiological diagnostic laboratory itself.
Of course, one of the biggest problems associated with the development of new technologies and novel kits for rapid diagnostics is their initial development costs, which when coupled to the global downturn and concomitant austerity measures of the last 5 years, makes the diagnostic kit development market very labile. Indeed, one of the SME partners within the TEMPOtest-QC project was itself a victim of current global circumstances, being declared bankrupt on March 13 2013. However, even so, partners are confident that the TEMPOtest-QC project will generate European and global impacts in the short, medium and long term. Though the number of TEMPOtest-QC toolkit users may have been temporarily reduced by economic circumstances, but the idea behind the toolkit, as well as the toolkit itself, remains intact and ready for use after EU funding has ended.
SHORT TERM:
The short term societal impact of the TEMPOtest-QC project are related to the evaluation and validation of “market-ready” kits and/or POC technologies currently being used in the clinical microbiology laboratory. In this respect, particularly important has been the evaluation/validation work performed on “market-ready” kits and/or POC technologies to detect a range of antibiotic resistances, not only the detection of extended spectrum beta-lactamase genes/enzymes, but also the detection of carbapenem genes/enzymes, which are steadily increasing in prevalence across the world and represent a serious threat to the effectiveness of current antibiotic therapy. Carbapenems are the last line of defence against antibiotic resistant organisms and their rapid detection is crucial in helping isolate affected patients. In the TEMPOtest-QC project, a range of simple (spectrophotometric, growth media-dependent) and more technically involved techniques and test kits (microarray, PCR) have been evaluated for the detection of carbapenem resistance. Armed with this knowledge and techniques, diagnosticians will possess a greater understanding of the mechanisms of carbapenem resistance, whilst having greater confidence in the tools available to rapidly diagnose such carbapenem resistance in clinical bacterial isolates.
MEDIUM TERM:
We are currently living in a “golden age” of new technological innovation with respect to the development of (infectious disease) diagnostics. Examples of the new technologies that are currently showing the most promise for infectious disease diagnostics being new techniques/methodologies based on molecular genetic analyses (custom polymerase chain reaction protocols, Optical Mapping, HiMLST, microarrays etc), and techniques/methodologies based on the molecular analysis of proteins (mass spectrometry e.g. MALDI-ToF, Raman spectroscopy etc). The TEMPOtest-QC project has been closely involved in the successful development and evaluation of many of these new technologies, providing a firm foundation on which the medium term success of these new technologies can be built. In this respect, the following medium term step for many of these evaluated technologies is the general acceptance of their usefulness and practicability in the routine infectious disease diagnostic laboratory, with the long term strategy being to further develop and eventually transfer these technologies to “true” Point-of-Care environments. Many of the techniques currently used in the routine infectious disease diagnostic laboratory are based on slow conventional culture techniques, although genetic and proteomic based methodologies are beginning to appear in laboratories across Europe. The results and publications of the TEMPOtest-QC project provide a strong justification for the adoption of these new technologies within a modern, efficient, routine infectious disease diagnostic laboratory,
LONG TERM:
The successful evaluation/validation of current experimental diagnostic infectious disease technologies (such as performed in the TEMPOtest-QC project) generates confidence for financial investment in these new technologies, for example via private investors and large pharmaceutical concerns, helping generate a long term developmental strategy for these technologies. Further, accompanying advances in mechanical and electrical engineering technologies, for example miniaturization, means that new infectious disease diagnostic technologies will result in an expansion of infectious disease diagnostic technologies into a “true” Point-Of-Care environment, devices / test kits available for sale from a local general practitioner, pharmacist or local supermarket, and available for direct use by the general public themselves. This scenario most likely involves the adaptation and application of smartphone-adapted devices that will provide information on a range of disease states and informed advice. The results and success of the TEMPOtest-QC project provides a model of a cooperative template between research institutions, SMEs and quality control institutes that can be successfully used to evaluate/validate the new technologies and technological applications that will be developed in the long term, even if this process itself does not involve the TEMPOtest-QC project partners per se.
SOCIO-ECONOMIC AND WIDER SOCIAL IMPLICATIONS
(IMPACT ON STAKEHOLDERS)
In order to assess the socio-economic and wider social implications of the TEMPOtest-QC project we must consider each of the relevant stakeholders that will benefit form the project results.
• Scientific Researchers - The TEMPOtest-QC project has provided a "template" for collaboration between researchers and manufacturers, a template that will help encourage future collaborations between researchers and manufacturers in the field of medical diagnostics. Further, the investigation of isolates for inclusion in the TEMPOtest-QC project archive has not only provided novel and varied geographical microbial isolates to be included in future evaluation/validation collaborations, but has also provided invaluable epidemiological information that will be useful to researchers in the field of microbiological epidemiology and in the field of health care planning. These aspects are likely to be the major cost expenditures with respect to limiting the global spread of (antimicrobial resistant) microbiological infections in the (near) future.
• POC Developers / Manufacturers - The TEMPOtest-QC project has successfully collaborated with national/international SMEs, academic research institutions and larger industrial concerns, to help them evaluate/validate their (novel) microbiological diagnostic technologies. The results obtained in these successful collaborations will provide POC developers/manufacturers with relevant information that will allow them to invest in their new technologies with extra "confidence", which should help result in the generation of new employment opportunities in this sector, or at least maintenance of the existing workforce (provided of course that extra finances are available in these times of economic uncertainty). The evaluation/validation of novel microbiological diagnostic technologies within academic research institutions, will encourage the establishment and development of new spin-off SMEs, also providing additional employment opportunities within this sector. The results from the TEMPOtest-QC questionnaire provide POC developers / manufacturers with invaluable information required for the optimized development of novel (or optimization of existing) microbiological diagnostic technologies. This will significantly impact on the success of these technologies and devices upon their introduction into the medical field, as well as greatly increasing their marketable value to the general public.
• Clinicians – The introduction of some (if not most) of the novel microbiological diagnostic technologies evaluated/validated during the TEMPOtest-QC project into the routine diagnostic microbiology laboratory is already being felt by clinicians. In particular, though not yet adapted for use as Point-Of-Care applications, novel technologies such as mass spectrometry, Optical Mapping, HiMLST and Raman spectroscopy are currently helping shape hospital diagnosis and infection control policies (albeit in a limited number of hospitals at the present moment in time). The TEMPOtest-QC project is helping establish these technologies as more sensitive, specific and rapid technologies that are able to replace existing “gold standard” culture-based techniques for microbiological detection and characterization.
• General Practitioners - The impact of the TEMPOtest-QC project on general practitioners is likely to be limited in the short-term, but may be substantial in the long-term. Certainly, not all general practitioners are enthusiastic about the introduction of rapid and Point-Of-Care diagnostics into the general practitioner’s surgery or at home, not least because of possible problems associated with result interpretation and a possible increase in general practitioner visits. However, the TEMPOtest-QC project puts forward the idea of an “Integrated Toolkit” that will allow extensive evaluation and validation of rapid and Point-Of-Care diagnostics before they reach the general practitioners surgery or home environments. The successful integration of this concept into the standard work practices of POC developers/manufacturers will help increase confidence in the value of these tests for general practitioners.
• General Public - As with the general practitioners, the impact of the TEMPOtest-QC project on the general public is likely to be limited in the short-term, not least due to the fact that the development of novel diagnostic technologies from inception to Point-Of-Care application can take many years. In fact, the market for such Point-Of-Care diagnostic products is available right now, and the general public are definitely willing to purchase this type of medical technology (as discovered and described in the TEMPOtest-QC questionnaire and accompanying publication). However, the Point-Of-Care microbiological diagnostic market is just beginning to evolve, currently being driven by the development of rapid home testing technologies for virus detection such as HIV. The work of, and idea behind, the TEMPOtest-QC project forms the basis for the future development of bacterial/fungal home testing technologies by POC developers and manufacturers, so that in the medium and long term, the general public of the future will be able to purchase microbiological diagnostic technologies with confidence.
• Society as a whole - The establishment of the TEMPOtest-QC consortium, and the achievement of its objectives, is a small, but significant, step towards generating a broad healthcare-related societal impact via the adoption of diagnostic POC technologies. This in turn helps fulfil the stated aim of the European Union to provide optimised healthcare to European citizens, for example, by reducing the ever increasing prevalence of antimicrobial resistance.
DISSEMINATION ACTIVITIES
Part of the important dissemination process of European-funded projects is to educate European citizens (including the general public, clinicians, researchers and manufacturers/developers of diagnostic testing technologies) regarding the efforts that the European Union is making in order to ensure that the stated aim of optimised healthcare for all EU citizens becomes a reality. In this respect, it is important that European-funded projects maintain good communications with a range of relevant stakeholder groups, and the TEMPOtest-QC consortium has made extensive endeavours to disseminate the objectives and results of the TEMPOtest-QC project to relevant stakeholder groups. These dissemination activities have included;
i) a dedicated project website (www.TEMPOtest-QC.eu)
ii) posters and presentations at leading international microbiological conferences (targeting researchers, diagnostic kit developers/manufacturers, and clinicians)
iii) advertisements in local and national newspapers (targeting the general public, researchers, diagnostic kit developers/manufacturers, and clinicians)
iv) a video (Youtube) and other postings (including postings to specialist groups on Linked-in advertising the TEMPOtest QC project) in the social media (targeting the general public, researchers, diagnostic kit developers/manufacturers, and clinicians);
v) an international press release (targeting the general public, researchers, diagnostic kit developers/manufacturers, and clinicians).
vi) articles in online and national newspaper forums
vii) scientific publications that describe and provide confidence in the use of novel technologies and test kits for microbiological diagnostics (targeting researchers, diagnostic kit developers/manufacturers, and clinicians).
Taken together, with Section 4.2 A1 and 4.2 A2, these dissemination activities have allowed the objectives and results of the TEMPOtest-QC project to be disseminated to all relevant stakeholder groups throughout Europe, stakeholders that will certainly be affected by (microbiological) POC diagnostics in the future, and should be aware of the current problems associated with microbiological diagnostics and the increasing threat of antimicrobial resistance.
EXPLOITATION OF RESULTS
The exploitation of results arising from the TEMPOtest-QC project lies mainly in the hands of the rapid and Point-Of-Care diagnostic developers/manufacturers who have used (and will continue to use) its services, and in the ability of these manufacturers to find sufficient funding to further develop and optimize their microbiological POC technologies and test kits. The TEMPOtest-QC partners remain committed to helping such companies achieve their goals, whilst at the same time helping generate confidence in the use of such kits by stakeholder groups such as clinicians, general practitioners and the general public.
CONCLUSION:
The TEMPOtest-QC project has helped, and is helping maintain, Europe as a global leader in the evaluation, validation and adoption of new technologies for rapid and Point-Of-Care microbiological diagnosis. The project has indirect and direct synergisms with several ongoing and completed European Union-funded projects, including the FP6 project DRESP2 and the FP7 TAILORED-Treatment project, and has even had an impact in the USA, where isolates from the TEMPOtest-QC archive have been requested by the State of Maine
Department of Health and Human Services. Further, the consortium provides a strong foundation upon which the future evaluation and validation of novel microbiological detection technologies can be built. Though just a first step in the long process of product development, the TEMPOtest-QC project has provided (and will continue to provide) support to European SMEs in the area of rapid and Point-Of-Care diagnostic microbiology and new technology innovation, and has provided a model for the development of similar "Toolkits" in other branches of medical science where POC diagnostics are being developed.
List of Websites:
http://www.tempotest-qc.eu/
Website Management -
John Hays
Room Na-903
Department of Medical Microbiology and Infectious Diseases
Erasmus MC
's Gravendijkwal 230
3015 CE
Rotterdam
The Netherlands
Tel: +31 (0) 10 7032177
Email: J. hays@erasmusmc.nl
