3.3.1. Overall IVD market

The impact of the broader economic backdrop on the diagnostic market is important to consider since diagnostics companies are more sensitive to changes in the macroeconomic cycle than other parts of the health care system. Around 20–25% of the sector’s revenue generation capability comes from exposure to industrial (as opposed to clinical) end markets such as food testing, which often carries greater macroeconomic sensitivity.¹⁷ Furthermore, cuts to government funding for scientific research are likely to have an impact on diagnostics companies. Illumina is an extreme example, with 80% of its sales to either government institutions, such as the National Institutes of Health (NIH), or academic organizations supported by government funding.¹⁸ Illumina is a dominant player in the gene-sequencing market, selling gene-sequencing platforms and assays to a primarily research-focused end market and, as such, is particularly exposed to changes in government funding. As with many diagnostic companies, they sell the capital equipment at low margins and make the bulk of their revenues from the sales of consumables. Although most companies in the sector generally have less than 25% exposure to government funding,¹⁹ cuts to, for example, the United States’ NIH budget and the move away from the use of Regional Development Funds in the United Kingdom may be an important concern for certain companies. The broader United States budgetary battles have had important ramifications for NIH spending, and while the approximately US$ 31 billion NIH budget is inconsequential to the overall fiscal picture in the United States, cuts have had a dramatic impact on public medical research funding encompassing the money which is allocated to diagnostics research. Anecdotal reports already suggest many NIH funding streams are on hold until there is further clarity regarding the cuts.²⁰ The triggered sequestration of 2013 resulted in a 5%, or US$ 1.55 billion, cut to the fiscal year 2013 NIH budget. This cut affected every area of medical research.²¹ In Europe, the European Research Council, which funds scientific and medical research, was allocated €13.1 billion for the period between 2014 and 2020 as part of the EU’s Horizon 2020 research programme.²² The global decline in R&D spending among pharmaceutical companies is also an important factor and, while absolute levels of R&D spending remain as high as they have ever been, recent trends (see Fig. 3.4) indicate that further growth may be anaemic at best.

Fig. 3.4

Global pharmaceutical R&D expenditure (Pharmaceutical Research and Manufacturers of America member firms).

Fiscal pressures not only impact publicly funded research budgets, but are also squeezing health budgets across key western markets. While in the medium-term this may be expected to drive rationalization of resource use, in which effective diagnostics may play a role, the short-term impact of budgetary constraints often leads to immediate cost control. This raises potential reimbursement challenges, particularly for more innovative and often higher priced diagnostics. A full analysis of reimbursement challenges is covered in section 10.2, but it would suffice to say here that reimbursement challenges are consistently flagged as an ongoing issue for diagnostic manufacturers.²⁴ Data from the European Diagnostic Manufacturers Association’s (EDMA) 2011 report on the IVD market in Europe document the impact that macro pressures are putting on the IVD market, noting particularly negative growth of the market size in both Greece (-9%) and Portugal (-10.5%) in 2010/2011.²⁵ Data from 2012 show that the European IVD market has continued to decrease, but that this decrease is not as drastic as had been forecast (-0.6% instead of a forecast -2.1%) (Fig. 3.5).²⁶ Continued budget constraints, measures such as reductions in the number of reimbursed tests, and moves to consolidate lab operations are among the drivers of this market decline.²⁷

Fig. 3.5

European IVD market revenues (€ million).

Sales of consumables, as opposed to capital equipment (the razorblade in the “razor/razorblade” business model), offer a degree of certainty even when the macro backdrop is challenging given the often long-term nature of the contracts entered into. Given the high cost of many diagnostic platforms, it is common for manufacturers to lease equipment instead of selling technology outright to end users with the lease tied to contracts to purchase associated reagents or assays for the equipment over the life of the contract. Indeed many diagnostic companies have in excess of 75% of sales from consumables such as assays and reagents. However, tying clinical facilities to long-term contracts for these consumables may be a double-edged sword. While they reward companies for innovative diagnostics that are taken up, when contracts are long-term the uptake of new technology may be hampered as end users are locked into existing agreements that prevent the upgrading or switching of technology from being cost–effective. Regarding technological progress more generally, there is a clear industry trend for greater automation that looks set to continue.²⁹ Technology that offers the potential to reduce other lab overheads, in particular labour, may present a compelling option for hospitals and labs looking to reduce costs in the face of budget cuts. For example, Guy’s and St Thomas’ clinical pathology unit recently part-funded trials of a gastro-intestinal infection diagnostic (Luminex’s xTAG GPP molecular platform) on the basis that it offered the potential for significant reductions in lab technician hours needed to process samples.³⁰

The shortage of both physical space and skilled staff faced by many labs may drive consolidation of testing onto a smaller number of platforms. There is an increasing demand for panel rather than single pathogen diagnostics given the flexibility they may offer labs and clinicians. There is some industry feedback indicating that panel diagnostics may be favoured by payers given the potential for economies of scope from the multi-function capabilities. Further, this creates a push incentive for industry consolidation on the diagnostics side and manufacturers are driven to divert resources to a smaller number of platforms to match this demand.³¹

3.3.2. POC diagnostics market

The global POC market is estimated to be worth in excess of US$ 15 billion annually (2011 data),³² with growth estimated at 7% per annum.³³ This is dominated by over-the-counter self-testing (US$ 9.6 billion), which is largely glucose testing and home pregnancy tests; professional POC testing is estimated to be worth in the region of US$ 5.6 billion annually, again dominated by glucose testing, with infectious disease testing comprising US$ 810 million annually. Estimates of the size of the professional POC market for infectious diseases vary: a 2011 report by Kalorama³⁴ put the global POC infectious disease testing market at US$ 810 million annual sales, whereas an industry overview from investment bank Morgan Stanley³⁵ estimated 37% of the US$ 3 billion professional POC market in the United States alone is dedicated to the area. Key players in the POC market are Roche, Siemens, Johnson & Johnson, Beckman Coulter/Danaher, and Abbott, although given the diversity of products on offer in this market segment there is no clear industry leader: particular sub-segments, however, tend to be dominated by a few companies.³⁶ The United States dominates the overall POC market (>50% global market share), and POC diagnostics are estimated to comprise 12% of the total IVD market in the United States.³⁷ This reflects more widespread use of POC devices in professional settings; self-testing uptake in the United States is lower than in some European countries. Delays in decisions by Medicare to reimburse self-testing products may explain this trend.³⁸ Adoption of POC diagnostics across Europe varies widely however: Germany, the Netherlands and Scandinavia are strong adopters, whereas uptake is low in France (where POC testing is not approved in physician setting), and the United Kingdom.³⁹ In general, there has been an increasing focus on near-patient testing across a number of settings, including physician offices and walk-in clinics or self-testing for chronic disease management; given the rise in chronic conditions such as diabetes, segments such as glucose testing are likely to remain an important part of the POC market. Already, the primary market for infectious disease POC testing is in non-hospital settings, with the industry leaders in this segment being Alere (35% market share), Beckman Coulter/Danaher (15%), Meridian and Quidel (c. 8% each).⁴⁰

Certain areas of infectious disease, such as influenza testing, already have well established POCTs, with almost 80% of flu testing performed at physician level in the United States. Competition in this POC market segment is already intense, leading to pricing pressure in the absence of meaningful developments in product differentiation.⁴¹ Concerns over sensitivity and specificity of rapid tests have led to a push towards the development of molecular assays, although these come at a significantly higher cost (>US$ 100 per patient, versus c. US$ 15 per patient for the rapid POCTs), which is likely to limit the volume growth of these tests outside of narrow patient populations (e.g. immuno-compromised) if consumable cost alone is accounted for.

While estimates of the growth potential for POC testing remain positive, POC devices may be particularly vulnerable to budgetary pressures, meaning achieving sales of devices is not a given. The burden is on the manufacturer to provide evidence of improved outcomes, but these outcomes can only be achieved through an improved care pathway. In many cases the realities of how patient care is managed may mean that, despite robust device design, inflexibility in the patient care pathway or poor understanding by diagnostics manufacturers of the clinical realities of managing patients may limit acceptance of POC devices.⁴² The developing world may provide a source of future growth for POC devices given the paucity of clinical pathology facilities in many countries, however reimbursement may be a challenge in these settings with limited purchasing power from fiscally squeezed health ministries; Cepheid’s TB platform, which was launched in India with funding from the Bill & Melinda Gates Foundation, exemplifies this issue, as the public–private partnership (PPP) agreement dictated that the device be made available to government facilities at cost, although the firm is free to sell to private facilities at market prices.⁴³ Furthermore, diagnostics devices used in a laboratory often need to be modified and/or miniaturized to be adapted to POC delivery – a difficult and expensive undertaking that can slow commercialization.

3.3.3. Molecular diagnostics market

To develop effective rapid diagnostics, developers are increasingly moving away from the classical methods requiring culture of the pathogens and turning to scientific advances from a range of fields. One of the fastest growing areas in infectious disease identification is molecular diagnostics (for an overview of the market see Fig. 3.6), which include techniques such as DNA (deoxyribonucleic acid) microarray analysis, mass spectrometry and nucleic acid amplification.^{44, 45}

Fig. 3.6

Molecular diagnostics market overview.

Estimates put the size of the molecular diagnostics (Mdevelopers) market at between US$ 3 and US$ 5 billion in annual global sales,^{46, 47} amounting to approximately 10% of the overall IVD market. With compounded annual growth estimated at 10–15% between 2012 and 2015,⁴⁸ molecular diagnostics is thought to be the fastest growing segment of the IVD market in the coming years.⁴⁹ Currently just over 50% of the molecular diagnostics market is focused on infectious disease testing. Fig. 3.7 demonstrates the dominance of this field in approved molecular devices in the United States to date. However, continuing development in other areas and the uptake of tests in the oncology field may drive future growth in the sector. Further, the demand for personalized medicine across other disease areas is also expected to expand, particularly as cost pressures and poor efficacy rates of therapies demand a more targeted approach to prescribing.

Fig. 3.7

Molecular tests approved in the United States by therapy area. Source: Datamonitor; adapted from Association of Molecular Pathology

Market leaders consist of a blend of diversified players such as Roche, Novartis, Abbott, Alere and Siemens, as well as niche companies that are more highly specialized in molecular diagnostics such as Qiagen, Gen-Probe, Cepheid and bioMerieux (see Fig. 3.8).⁵²

Fig. 3.8

Market overview of companies where molecular diagnostics are primary area of focus.

Given the growth profile of the molecular diagnostics market, it has been an area of focus for deals and consolidation. Many diagnostics firms that were under-represented in this area have sought partners or acquisitions to gain exposure, reflecting the growing interest in personalized medicine. Acquisitions by Qiagen (developersS) and LabCorp (Monogram Biosciences) are key examples of this trend.⁵⁴ This is a trend that may continue given the relatively favorable growth outlook and the potential for premium pricing, and given the role molecular diagnostics may play in improving the clinical decision-making process. This may be exemplified by the market for Clostridium difficile testing, in which molecular testing is growing in importance: about 2 million of the 5–7 million tests performed for C. difficile each year in the United States are now based on molecular diagnostics, a trend which is expected to continue given the superior accuracy and speed of available molecular tests on the market.⁵⁵ The fact that the product with the largest market share in this category, Cepheid, maintains a significant advantage, despite premium pricing relative to competitor products^a reflects the value users put on ease of use.

3.3.4. Consolidation

Consolidation at both the diagnostic manufacturer^{56, 57} and lab service^{58, 59} levels has been a prominent theme across a number of jurisdictions for the diagnostics industry. On the manufacturing side, while the number of deals in the sector remained relatively unchanged over the period 2008–2010, the IVD market has witnessed accelerating levels of consolidation in terms of deal values throughout 2010/11 (up 57% to US$ 4.7 billion in 2010 from US$ 3 billion in 2009), with particularly large deals by Danaher and Thermo Fisher making 2011 a strong year. A large number of these deals have been cross-border, highlighting the global nature of the industry.⁶⁰ Interested acquirers are a diverse range of entities, including private equity firms, clinical laboratories and life sciences firms. Pharmaceutical companies have been notably absent from major acquisitions of diagnostics companies, and have instead opted for partnerships with them (Novartis’ US$ 330 million acquisition of Genoptix being a notable exception). However, the number of partnership arrangements between pharmaceutical and diagnostic companies has tripled between 2008 and 2010,⁶¹ with these types of companion partnership arrangements addressed in more detail in Chapter 11. In terms of deal outlook, an industry report by PricewaterhouseCoopers (PwC) in 2011⁶² forecast a likely continuation of the positive trend for deals. This trend is supported by a number of factors, including new entrants to the IVD market, existing players aiming to cement their position, and potential ongoing interest from private equity in niche players in the most attractive segments of the IVD market such as molecular diagnostics. For example, Switzerland’s Biocartis raised US$ 44.5 million in 2012 from a range of investment partners to commercialize its molecular platform.⁶³ More recent reports, however, suggest venture capital early-stage interest in molecular diagnostics has cooled as firms become wary of regulatory and reimbursement risks in the sector, with interest instead shifting to “safer” fields of diagnostics such as imaging.⁶⁴ Finally, as the trend for drug–diagnostics co-development takes off, interest from large pharmaceutical companies may increase as acquiring diagnostics businesses may become more compelling for pharmaceutical firms when scale is applied to the trend for companion diagnostics. Note, however, that if large drug companies do become more actively involved in acquiring IVD companies rather than partnering, the most likely targets are niche players with specific capabilities which may enhance either the development or marketing of a particular drug rather than the large diverse diagnostic firms which may fit less well with the existing product suite or pipeline of the pharmaceutical firm. Larger, more diverse acquisitions are also likely to be more difficult to execute and integrate into existing pharmaceutical businesses.

The drive for panel diagnostics demand may be particularly acute in equipment-heavy segments of the market, such as molecular diagnostics, in part driven by pressure on both physical lab space and availability of skilled staff to execute the diagnostic tests. This may also drive consolidation on the manufacturer’s side, given the need to streamline the number of platforms marketed to end users, the route to which may involve integrating a number of technologies into a single platform. Consolidation has also been particularly prominent in the POCT market, with dominant market players continuing to make acquisitions in 2010.^a

The robust near-term outlook for further consolidation is driven by a number of factors, including recent entrants to the IVD market looking to grow their portfolios and established players responding to the changing competitive landscape by actively seeking acquisitions to cement market position and prevent growth of competition. Further consolidation will also be driven by continued interest from private equity firms (subject to capital market conditions) and the potential for major pharmaceutical firms to acquire IVD businesses (particularly molecular/tissue) as the trend for companion diagnostics takes off and the dynamic reaches a point where it makes more sense for pharmaceutical manufacturers to bring the diagnostic business in-house rather than manage the process through partnerships.

In many developed countries such as Australia, Scandinavia, the United Kingdom and the United States, there is a trend to try to keep patients out of hospital, bring care closer to home, and involve pharmacies and other retail outlets. In the United States, decentralization of the pathology market is an important theme; that is, the shift of certain types of testing from larger reference labs towards POC.⁶⁵ The extent to which this has happened varies by indication.⁶⁶ Given cost pressures throughout the health care system, many hospitals are aiming to consolidate either lab operations or volumes in order to exploit scale economies: to the extent that new diagnostics can bypass the need to use larger reference labs towards instead using hospital labs, they may be able to benefit from this consolidation trend.⁶⁷ From a pathology facility perspective, this same trend may squeeze smaller hospital labs as larger facilities attempt to exploit the scale economies and keep as much testing in-house as possible.

In the United Kingdom the prominent review of pathology services led by Lord Carter in 2006⁶⁸ highlighted the need for consolidation of pathology services across the United Kingdom in order to improve efficiencies across the service. This has led to the creation of a number of “pathology networks”, whereby groups of hospitals aim to more effectively share pathology services. The potential ramifications for diagnostics manufacturers are conflicting: the “arms race” for consolidation following the publication of the Carter review did lead to larger labs looking to cement their position and act as consolidators, by expanding equipment and capacity^{69, 70} However, the potential for larger pathology networks with greater purchasing power may mean pressure on diagnostic pricing. The full effects of changes in the United Kingdom pathology environment are as yet unclear, not least because the drive for consolidation has been beset by political issues at hospital/trust level,⁷¹ and the trend is yet to fully play out. Recent changes to commissioning in the United Kingdom have added further uncertainty to the sector and these issues are likely to present challenges for the diagnostics sector in the foreseeable future.

3.4.1. Xpert MTB/RIF test: a game-changer in global TB diagnosis

TB is a major global killer; in 2011, an estimated 1.4 million people died from the disease.⁷² Delays in diagnosis contribute significantly to unnecessary TB-related morbidity and mortality.⁷³ The traditional diagnostic gold standard, sputum culture, can take 6–8 weeks⁷⁴ and requires a biosafety infrastructure that limits its use to reference laboratories.⁷⁵ Smear microscopy can be used to achieve a faster diagnosis but this approach has lower sensitivity and needs to be undertaken by specially trained staff.⁷⁶

The Xpert MTB/RIF test (Cepheid), which became available in 2009,⁷⁷ is revolutionizing TB identification, bringing diagnosis closer to the point of care. The cartridge-based, fully automated nucleic acid amplification test (NAAT) can be used by a relatively unskilled health worker to simultaneously detect both the presence of the Mycobacterium tuberculosis pathogen and whether the strain harbours common rifampicin resistance related mutations in less than 2 hours.⁷⁸ The test was found to be highly sensitive and specific by a large multi-country study in 2008/2009: the test correctly identified 98.2% of smear-positive TB, 72.5% of smear-negative cases, and 99.2% of cases where the patient did not have TB.⁷⁹

In one recent study using the test at the point of care in a primary health care centre in South Africa, evidence suggested an increase in case detection, same-day treatment initiation in over 80% of new cases, and real-time contact identification when a patient was accompanied by a partner or relative.⁸⁰ Using data from implementation studies, researchers have estimated that the Xpert test will increase TB diagnosis by approximately 30% per year with up to 70% greater diagnosis of MDR strains.⁸¹ This improvement in diagnosis is expected to translate into better health outcomes. One study estimates that the technology could prevent over 4 million deaths between 2015 and 2050.⁸² With the support of the WHO,⁸³ over 1 million tests have been purchased by low- and middle-income countries since December 2010.⁸⁴

Xpert is not an ideal POCT;⁸⁵ it is expensive due to the large equipment investments required. But its development marks a key milestone on the journey towards a simple and reliable dipstick for community-based diagnosis.⁸⁶

A key benefit of the GeneXpert System that supports the Xpert MTB/RIF test is that, through interchangeable cartridges, the system can be used to detect a number of other pathogens. Health workers can load a sample to test for TB in one module while testing for another pathogen, such as MRSA or C. difficile, in another module.⁸⁷

3.4.2. Syphilis POC screening: helping cut unnecessary syphilis-attributable stillbirths and perinatal deaths

Each year, there are approximately 11 million new cases of syphilis worldwide.⁸⁸ When syphilis occurs in pregnancy, the consequences of the disease can be devastating. The WHO estimates that in 2007 syphilis contributed to 650 000 fetal and neonatal deaths worldwide,⁸⁹ deaths that could have been prevented if patients had been screened and treated for the disease.

A problem with traditional testing methods in low-income countries has been diagnostic delays. For example, in one study in Botswana in 2000, researchers found that the median time for women to present to antenatal services was 20 weeks into the pregnancy and there were delays of up to five weeks while blood samples were sent to a central laboratory to be tested.⁹⁰ Where there are delays, patients often don’t return for test results and treatment.⁹¹

POCTs are helping to cut deaths by providing rapid results. Generally easy to use, with results available in 15–20 minutes, more than 20 syphilis POCTs are now commercially available.⁹² In 2012, the results of a large multi-centre project funded by the Bill & Melinda Gates Foundation found that introducing POC devices can dramatically increase access to testing in some settings; in maternity hospitals in Lima and Callao, Peru, the percentage of sexually active individuals screened for syphilis increased from 51% to 95%, and in Kampala hospital and rural antenatal clinics in Uganda, testing increased from 1.7% to 90.3%.⁹³ In a recent systematic review of interventions to improve syphilis screening, Hawkes et al. also found that introducing POC testing and same-day treatment increased the frequency of testing and concluded that it could support decreasing the incidence of perinatal death and stillbirth.⁹⁴ The researchers estimated that interventions to improve the coverage and effectiveness of antenatal syphilis screening, such as introducing POC testing, could reduce syphilis-attributable stillbirths and perinatal deaths by up to 50%.⁹⁵

3.4.3. Syphilis: a modern approach to identifying an old disease in hard-to-reach patient groups

There is a range of barriers to patients seeking testing for syphilis at health clinics, including structural problems such as accessibility, clinic hours, financial barriers, patient knowledge of syphilis, and the silent nature of the infection.⁹⁶ POC testing is overcoming these barriers by enabling health workers to carry out rapid testing in the community on mobile and hard-to-reach at-risk groups.

In Edinburgh, Scotland, the ROAM (Resources, Outreach, Advice for Men) project, which is part of National Health Service (NHS) Lothian’s Harm Reduction Team, offers services for men who have sex with men in public sex environments. In a pilot project in October 2008, sexual health workers carried out POC testing at three of the city’s saunas. Of 63 patients tested, three were found to have undiagnosed syphilis, with almost half of the men being tested for the first time.⁹⁷

Using POCTs to support screening has also been found to improve treatment coverage in settings where there is a high risk of loss to follow up. For example, in a 2010 study funded by the Bill & Melinda Gates Foundation, female sex workers attending fixed and mobile sexually transmitted infection (STI) clinics in Bangalore, India, were more likely to accept a test where it could be performed rapidly on-site and individuals who had access to POCTs were found to have significantly higher treatment coverage.⁹⁸

3.4.4. Reducing unnecessary isolation bed days through rapid MRSA screening

MRSA is a leading cause of secondary infections that are acquired during hospital stays and in long-term nursing facilities.⁹⁹ One infection control approach is to place patients with suspected MRSA in isolation, but this can be costly for hospitals.

A large multi-centre study across the ICUs of 12 Dutch hospitals between 2005 and 2008 confirmed that the use of rapid MRSA screening tests has the potential to significantly reduce hospital costs by reducing the time patients were kept in isolation unnecessarily. Where testing was undertaken using traditional cultures, patients would typically spend 96 hours in isolation. This was reduced to 27.6 hours where patients were screened with the GeneOhm™ MRSA polymerase chain reaction (PCR) test (Beckman Coulter/Danaher) and 21.4 hours when staff used the GeneXpert MRSA/SA test (Cepheid).¹⁰⁰ Tests were undertaken by a central laboratory and the benefit to the hospitals concerned was between €121.76 and €136.04 per isolation day avoided.

The quicker results gained from using rapid tests have also been shown to improve the appropriateness of antibiotic prescribing. A study in northern Australia by Davies et al. found that performing the GeneXpert MRSA/SA test on 151 positive blood cultures with gram-positive cocci led to earlier appropriate prescription of vancomycin for 54% of patients with MRSA.¹⁰¹ This can translate into clinical benefits; in a 2010 study covering 167 patients with S. aureus bacteremia at the Ohio State University Medical Centre, researchers found that the adoption of the GeneXpert MRSA/SA test reduced the average length of stay (LOS) by 6.2 days compared to traditional blood culture, and decreased average hospital costs by US$ 21 387. The impact of the test in this study may have been enhanced by the close involvement of an infectious disease pharmacist in guiding prescribing.¹⁰²

While most studies to date have involved rapid tests being undertaken by a central laboratory, an additional advantage of the Xpert test is that it is sufficiently simple to use that testing could be undertaken by clinical staff at the point of care.¹⁰³ A recent feasibility study in a British hospital found that when testing was undertaken at the point of care, the results were available over 10 hours faster than from the lab. Testing at the point of care was particularly beneficial in the evenings and weekends when the lab was closed.¹⁰⁴

3.4.5. T2 Candida assay: using magnetic biosensor nanotechnology to diagnosis candidemia

The presence of the Candida pathogen in blood, a condition known as candidemia, is a major cause of morbidity and mortality in the inpatient care setting¹⁰⁵ and is associated with both prolonged hospital stays and high treatment costs.¹⁰⁶ Delays in treatment are associated with increased mortality.¹⁰⁷ Since clinical symptoms are non-specific¹⁰⁸and conventional diagnostic methods take 48 hours,¹⁰⁹ prescribers have had little option but to prescribe broad-spectrum antifungals empirically.¹¹⁰

In recent years, a range of new tests has been developed to improve the speed of candidemia diagnosis using technology such as PCR and molecular techniques.¹¹¹ The T2 Candida assay is a promising one that uses magnetic biosensor nanotechnology designed to enable detection of DNA, ribonucleic acid (RNA), protein, small molecules and other targets from a single blood sample in a one-step process that can be undertaken by non-specialist staff.^{112, 113} Although it is still early days in the clinical testing of the product, the manufacturer has reported that two independent research groups from Massachusetts General Hospital and University of Houston College of Pharmacy have confirmed that the test had equivalent sensitivity and specificity to blood cultures but provides results within 2 hours compared to 48.¹¹⁴ Formal clinical trials are planned¹¹⁵ to assess the assay’s potential benefits, which may include reduced mortality and lower health system costs.¹¹⁶

The device which supports the test, the T2developers, is versatile. Since it is capable of detecting a range of substances, including bacteria, cancer cells and viruses, and of processing almost any sample, including whole blood and urine, there is potential for it to be developed for a wide range of clinical uses.¹¹⁷

3.4.6. Speeding up the detection of respiratory pathogens with multiplex devices

There is a broad range of causative organisms responsible for respiratory tract infections, making them difficult to diagnose. This problem is compounded by the fact that conventional diagnostic techniques can take up to 72 hours.¹¹⁸ To overcome these challenges, there has been a recent trend towards the development of multiplex devices: devices designed specifically to rapidly detect a variety of bacterial, viral, or fungal pathogens in a single test.¹¹⁹

Techniques used in these devices include real-time PCR, PCR microarray technology and mass spectrometry.¹²⁰ While some techniques are better suited to high-throughput laboratory testing, others are designed to support near-patient diagnosis.¹²¹

One newly developed device is the Unyvero™ solution (Curetis AG), which has investigational device status in the United States and conforms to the CE-mark (Conformité Européenne) requirements in Europe.¹²² While the device is not necessarily “simple”, requiring the technician to perform multiple steps to prepare a sample, it supports a “sample to answer” approach to diagnosis. Patient samples are loaded directly into the device without prior preparation, the sample is then screened for a broad panel of pathogens with simultaneous detection of some antibiotic resistance determinants (overall predictive value of 60%), and results are presented on an integrated screen within 4 hours.¹²³ Unlike some molecular tests on the market, the device can be operated by staff without specialist training¹²⁴ and, when used in a decentralized setting, this can improve access to the technology, particularly at nights and weekends when central laboratories are often closed. The device currently supports the diagnosis of pathogens associated with pneumonia, with the company’s pipeline including panels for implant and tissue infections, bloodstream infections (sepsis) and TB.¹²⁵

Given the product’s novelty, there is still limited independent evidence of the benefits of the device (the sensitivity, which depends on bacterial species, ranges between 35% and 100%)¹²⁶ but it holds considerable promise. Studies of similar multiplex devices targeting respiratory infections have suggested that earlier detection of causative pathogens may improve the appropriateness of prescribing antibiotics, which in turn can help minimize antibiotic resistance.^{127, 128} An economic analysis undertaken by Curetis indicates that it may also help reduce overall health care costs and improve patient quality of life.¹²⁹ Oliver Schacht, PhD, Chief Executive of Curetis, reported that an additional multi-centre interventional trial is being planned to gather real-world evidence on the health economic benefits of the device.

3.4.7. Using a simple dipstick to improve diagnostic precision in suspected UTIs

A significant proportion of patients with suspected UTIs receive antibiotics unnecessarily.¹³⁰ One tool that can help improve appropriate prescribing is the simple urine dipstick test that has been used in clinical practice for over 30 years.¹³¹

Using clinical symptoms alone cannot accurately diagnose a UTI. In a 2003 prospective cohort study involving eight GPs in the United Kingdom, Fahey et al.¹³² investigated how a patient’s symptoms influenced the likelihood that GPs would opt for a dipstick test, urine culture or empirical antibiotic prescribing in the management of suspected UTIs. The study found that GPs were more likely to prescribe antibiotics as a clinical strategy when patients presented with a history of frequency and dysuria or a history of dysuria alone, yet less than 30% of cases that presented with these symptoms were later found to have a UTI. A dipstick test provides the physician with additional information on which to base their clinical decision. In a health technology assessment funded by the United Kingdom’s National Institute for Health Research (NIHR), Little et al. provided evidence that using a dipstick to test for the presence of either nitrite or a combination of blood and leucocytes modestly improved diagnostic accuracy.¹³³ This conclusion has been supported by a number of systematic reviews,^{134, 135} despite heterogeneity in the findings of individual studies.¹³⁶

Using a dipstick to target prescribing may also offer value for money. The study by Little et al. found that using a dipstick to target prescribing was cost–effective if the cost of a patient avoiding a day of moderately bad symptoms was valued at over £10.¹³⁷ However, other economic evaluations have provided conflicting results. In a study in 2000, Fenwick et al.¹³⁸ concluded that empirical antibiotic treatment was the most cost–effective strategy in managing suspected UTIs in general practice, however this did not take into consideration the long-term costs of increased antibiotic resistance – a factor that the researchers recognized could influence their study outcome.

A key weakness of dipstick tests is that, while they can aid prescribing decisions, they do not provide the gold standard of microbiological identification data and susceptibility information. Fortunately, it is likely to only be a matter of time before next-generation devices become available that can support rapid and definitive diagnosis at the point of care.^{139, 140}