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How much work can the diagnostic device itself do? This question was at the heart of a workshop on ‘Diagnostics, Disease & Development’ that was hosted at the University of Edinburgh on 30th January 2014. The workshop brought together stakeholders from academia, civil society activism, private industry and non-profit product development partnerships to address the opportunities and challenges afforded by the rapid development, proliferation and roll-out of new diagnostics for development.

The rationale behind the experimental format was simple. While the social scientists and civil society activists who participated in the event wanted to learn more about the specificities of the “partnership” based product development approach that increasingly dominates this sector and the constraints imposed by the institutional contexts, funding structures and regulatory environments in which those designing, developing and implementing new devices must operate; representatives from industry were keen to find out more about the health systems and care environments in which their devices will ultimately need to work. The focus on new diagnostics as the solution to problems of diagnosis has seen extraordinary progress in the development of affordable technologies. But these technologies have been accompanied by unanticipated challenges, obstacles and complications: in the global regulation of rapidly expanding markets, the integration of new diagnostics with existing health system infrastructures, and the unforeseen technological glitches that occur in difficult environments. These emerging challenges highlight the urgent need for cross-sector dialogue about the wider implications of and opportunities for new diagnostics in fragile health systems.

Partnership

The opening panel on “innovation networks and institutional configurations” highlighted the significance of partnership as both a buzzword and an actual constellation of relationships. Marcus Lovell Smith from Diagnostics for All highlighted some of the challenges accompanying the ‘non-profit’ partnership model for technology development. Non-profits avoid the major bias affecting Big Pharma, as they are not required to make product choices based on profit margins. But he pointed to the constant pressure on non-profit organisations to raise capital. All but 1 of the 5 speakers depended on “soft funding” for their product development work. As Roger Peck pointed out in the case of PATH – this means they have to find $300 million dollars in “partnership” funding every year to ensure the stable employment of 1200 people employed across projects in 70 countries. Meanwhile Chris Lowe, whose hi-tech personalised diagnostics, such as smartphone biomedical sensors for blood glucose, have resulted in several spin-off companies, pointed to the current dearth of alternatives to soft funding when he suggested that his devices were unlikely to be extended to low-income countries because the returns for investors in such contexts were too low. Meanwhile, the presentation by Peter Jeffries from GALVmed, an organisation that focuses on improving poor livelihoods through protecting livestock health, highlighted the very different opportunities for market-driven development afforded by the human-animal interface. Livelihood dependence on livestock presents a clear link, for both local farmers and international investors, between diagnostics and economic development that is often missing in the human health dimension and that enables GALVmed to operate according to what Jeffries calls a ‘sustainable economic framework’.

Many of the PDPs share funding streams, with the key funders - Gates Foundation, DFID and NIH – emphasising the development of ‘novel’ products that reduce complexity and enable implementation in low resource settings. A common language of ‘transformative innovations’ (Roger Peck) and ‘transformational improvement’ (Peter Jeffries) across the PDP presentations pointed to the weight of expectation currently being placed on new diagnostic devices, and also perhaps to certain biases within that funding environment. Nonetheless presentations on the everyday activities of product development revealed a multiplicity of relationships and institutional arrangements, and challenged the social scientists present to produce more fine-grained analyses of what partnership means in practice. Joseph Ndung’u of FIND described how it tended to concentrate its efforts towards the start of the pipeline, on the creation and evaluation of new diagnostic prototypes, with decreasing engagement as the pipeline progressed; while Roger Peck suggested that PATH’s greatest contribution was to the middle of the pipeline - development, approval and implementation – which required them to maintain a much greater infrastructure and laboratory footprint. They have their own Seattle based R&D infrastructure, with a biosafety level 2 isolation facility and environmental testing lab.

Is product development driven by “technology” or “needs”? Who defines such needs emerged as a key question for the day. This was highlighted when Roger Peck pointed out that PDPs often struggle to treat their end users as clients while their funding comes from elsewhere, when Chris Lowe argued that needs are easy to identify but private-sector funding less so, and when Peter Jeffries suggested that the relationship between needs and technology is best conceived as an on-going process of negotiation and adaptation where a ‘best fit’ might ultimately emerge.

What and who, Caroline Jones asked, are diagnostic devices actually for? She noted the shifting goals for malaria diagnosis, whereby an earlier clinical goal – to identify infected persons for treatment – has become a mere add-on to a larger public health goal - evaluating the implementation and impact of malaria control programmes, in line with global control and elimination targets. This prescient question grew in significance as the day went on. Joseph Ndung’u described the perceived need to monitor impact of public health programs to be a driving force behind the development of new diagnostics for Neglected Tropical Diseases. A presentation from Annie Wilkinson described the biosecurity concerns that have framed diagnosis interventions for lassa fever in Sierra Leone. Chris Lowe explained that the mHealthcare phone applications his team were designing target the ‘worried well’ in a bid to identify illnesses sooner and bring down mounting health costs, raising questions about the ways in which new diagnostic devices might both create as well as respond to perceived needs. The expanding remit for diagnostic technologies is likely to have important consequences for national health systems as they attempt to integrate new testing regimes and data streams without complementary increases in budgetary support.

Jennifer Cohn from Medecins Sans Frontieres argued that the significant variability in the price that ministries of health pay for diagnostic devices indicates considerable leeway in device pricing. For example the cost of an HIV viral load test in Kenya is £11.50, in Thailand the same test costs $44.07. Diagnostics, Cohn argued, have a long way to go in terms of access by comparison with pharmaceuticals. Rather than demanding more regulation MSF’s agenda is to provide greater transparency, with the goal of assisting governments in negotiating down pricing. This provoked strong disagreement from Chris Lowe, who felt that the substantial R&D costs involved in diagnostics were being played down. Cohn’s key point was that access to information could prevent market failure in contexts of greatest need. Where the devices supported by PDPs fall on MSF’s pricing spectrum was unclear, and it is significant that this moral debate about the role of business in public health involved the representatives from civil society and commercial industry rather than public-private partnerships.

Indeed the tension between collaboration and competition emerged as a major theme that was crystallised in a discussion about whether we should design single or multiplex devices. On the one hand multiplex devices afford opportunities for cross-subsidy. Joseph Ndung’u underscored FIND’s approach to diagnostic development which seeks out ‘technology platforms’ applicable to more than one disease. In this way products developed for profitable diseases like malaria or TB have their applications explored for non-commercial diseases. Here he cited two examples of cross over products – the iLED microscope and the LAMP test – which, while initially devised for TB - are now being used to diagnose the neglected tropical disease Human African Trypanosomiasis. Establishing a good relationship with the manufacturer is a key component of this FIND strategy. On the other hand it was noted that while the Bill and Melinda Gates Foundation would ideally like to see the development of universal do-it-all diagnostic device there is in fact no appetite for this kind of device from industry quarters as it would kill off competition in the market.

The Point of Care

The question of single versus multiplex surfaced again in the session on “point of care challenges”. Clare Chandler’s extensive field research on rapid diagnostic tests for malaria in Tanzania suggests that they have had very little impact on treatment practices, partly because a negative result for malaria still effectively leaves the patient undiagnosed. For many of the participants from industry this example pointed to the importance of the multiplex test that would enable health workers to diagnose for multiple common diseases at the same time. It also points to the potential proliferation of infrastructure around supposedly self-contained diagnostic devices, as the ability to diagnose for one disease necessitates the diagnosis of further diseases.

Caroline Jones suggested that presuming the need to diagnose at all costs was problematic and would take us to a place where ‘if we can’t diagnose it, it doesn’t exist’. In her opinion this stance would risk pitting technology against a clinician’s skill, and a holistic approach to healthcare against the simplistic imperative to administer drugs. Caroline Jones also reminded us that it was only in 1993 that the WHO took the decision to treat all fevers as ‘malaria’ and that this regimen of presumptive treatment often replaced nuanced local distinctions between types of fevers. Behaviour change can be successful, she suggested, but by the time it has been achieved it might no longer be desirable.

Where the celebration of new diagnostic devices has focused on their ability to obviate the need for diagnostic infrastructure and technical expertise in remote settings, the presentations by Clare Chandler and Christina Acup highlighted the continuing importance of the health worker in the diagnostic process. Clare Chandler argued that training that reduces the healthworker’s role to the blanket following of test results rather than using clinical judgement can lead to deskilling. Meanwhile Alice Street pointed out that extensive training programs were required to accompany the roll out of malaria RDTs in Papua New Guinea. The point of care operational problems that followed a system-wide change in the device supplier suggest that significantly more “skill” is involved in the administering of such tests than commonly recognised. Christina Acup from Edinburgh University highlighted the continued importance of microscopy to diagnose Human African Trypanosomiasis in highly-endemic areas of Uganda, and suggested that investment in staff training was perhaps the best way to ensure cases would be picked up at point of care in that setting.

Crucial here are issues of trust, both in relationships between patient and clinician and clinician and test. Diagnostic tests are only useful in case management if they are acted on and this depends on the health worker trusting the result. Joseph Ndung’u and Lars Gredsted of the Wellcome Trust both suggested that the reliability of health devices (in this instance HAT RDTs and DDT bed nets) could be double-checked with supplementary tests. Indeed FIND are currently involved in the development of positive control wells that will enable health workers to test the accuracy of devices on site. But might this safeguard potentially undermine rather than strengthen user trust in the original device?

Meanwhile it is often assumed that the people administering point of care diagnostics are trained health workers. But David Mabey’s, Nora Engel’s and Annie Wilkinson’s presentations all drew attention to the increasing role of informal providers as a point of access to diagnostics. Here the issue is often the lack of trust that policy makers have in the informal sector. Annie Wilkinson pointed out that informal providers need to be recognised as an increasingly important part of future health systems rather than simply as an obstacle to quality care. Meanwhile Nora Engel extended the diagnostic encounter to include the patient as well as the caregiver. In India’s highly privatised and decentralised health system the onus is on the individual patient to navigate the system. By following the patient in such settings it becomes apparent that diagnosis is better conceptualised as a process or cycle rather than a product.

Regulatory Environments

The issue of trust emerged again in relation to global regulatory frameworks. David Mabey pointed out that the WHO simply cannot keep up with the current pace of diagnostic development. Where in the pharmaceutical industry only four or five new drugs require pre-qualification in a given year hundreds of new diagnostic devices are coming onto the market annually. This has the potential to both reduce the quality of devices and trust in those devices by health workers. David Mabey discussed a new International Centre for Diagnostics set up at LSHTM by Professor Rosanna Peeling with mission to facilitate the development, evaluation and implementation of accessible, quality assured in-vitro diagnostics for global health through information sharing and advocacy. The Centre is working with a variety of other organisations, such as the Global Harmonisation Task Force, the Asian Harmonisation Working Party and the African Society for Laboratory Medicine to try to harmonise the regulation of diagnostic tests globally. This raises important questions about the future role of the WHO in the diagnostics field, and what kinds of institutional networks and partnerships will enable effective regulation in a rapidly growing market.

Equally important is the fact that medical equipment does not usually need to undergo the same levels of testing and qualification to meet country level requirements as pharmaceuticals. This means that either country level guidelines/laws need to change or governments are even more dependent on global regulation and pre-qualification systems. Joseph Ndung’u pointed out that FIND’s approach to project management is ISO certified. Does this represent an effort to begin to introduce standards into a largely unregulated field? Determining the correct role for WHO and other bodies in providing regulatory oversight over emerging diagnostics is paramount given the pace at which new diagnostic devices are coming onto market. But arming bodies with the capacity to enforce their authority will be challenging. At a regulatory level the varying capacity of national and regional authorities to operationalise effective safeguards reminds us of the broader system requirements needed to support new point of care diagnostics.

Hidden Infrastructures

‘Health systems integration’ was the theme of the third and last panel. Ian Harper described the roll out of cartridge-based Gene Xpert machines for the diagnosis of multi-drug resistant tuberculosis in Nepal. Intended to improve the accuracy and speed of diagnosis, the $25,000 machines encountered numerous operational challenges in the field. Breakdowns were common and frequent power outages added to diagnosis times. The machines generated an increase in positively diagnosed TB cases - cases which had not been budgeted for in the national treatment budget; and there was no room in the national database for categorising the additional cases picked up by the machines.

Interestingly, while GeneXpert is feted as a point of care TB diagnostic, the presentations by Ian Harper and Jennifer Cohn drew attention to the substantial infrastructure demands the machines place on existing laboratories – the machines require a dependable electricity supply, a working computer, careful infection control and a skilled operator. Indeed the discrepancy between the skillsets of existing lab techs and the lab techs needed to operate the machines has seen the introduction of financial incentives for technicians to conduct the tests in Nepal, raising further questions about the overall cost-burden of such devices and their post-donor sustainability.

The limitations of GeneXpert brought the discussion full circle to the implications of potential multi-platform monopolies for health system capacity. Cepheid, the company that manufactures GeneXpert is currently planning the development of cartridges to test for multiple diseases. The need to integrate new tests into existing infrastructure or to create new supportive infrastructure for new diagnostic tests marks them out as uniquely different to pharmaceuticals, which can be switched in and out of health systems. Instead, having built the required infrastructure for diagnostics, it is much less likely that a diagnostic device will be easily superseded by an improved or cheaper device. The infrastructure foundations give the test a semi-permanence, which may have cost and efficacy repercussions for the national health system later down the line.

In Harper’s study GeneXpert worked as an ethnographic probe, bringing into focus infrastructural capacities and constraints that are otherwise difficult to discern. This raises more general questions about the relationship between diagnostic devices and health system infrastructures. Several of the papers discussed the problems of temperature stability, both in terms of the development of devices which remain stable at high temperatures and in terms of keeping those devices at the correct temperature when in transit or in storage. In other words, what happens to these devices between the point of manufacture and point of care is just as important as what happens to them in their moment of use. Temperature control is one of the clearest indications of the necessity of health system integration. Do ‘cool chains’ need to be created alongside the roll-out of point of care devices?

The case studies of new diagnostic devices discussed at the workshop suggest that point of care devices do not substitute for laboratory infrastructure or negate the need for it. Instead they might actually require entirely new types of infrastructure being built up around new, potentially ‘infrastructure-lite’ tests: solar, cool chain, mobile technologies to geospatially capture diagnoses. In this scenario new tests are not removing the need for infrastructure but may in fact be replacing it with more platform-less physical infrastructures that require more sophisticated technological platforms.

Concluding remarks: Product Profiles

Can diagnosis be contained in a single device? Where a policy and investment focus has increasingly narrowed diagnosis down to diagnostics, this workshop drew attention to the infrastructures, institutions, and practices that make up the diagnostic process.

Taking Nora Engel’s concept of the diagnostic process as a starting point we suggest that this process might be expanded backwards from the point of care to include a focus on the funding structures, regulatory environments, partnership agreements and lab bench collaborations that enable and direct the flow of product development; and outwards to the health system infrastructures, logistics and complexity of point of care interactions that new devices must necessarily entangle with.

One very practical way to think through the implications of expanding the parameters of diagnosis in such a way is to focus on the role of Target Product Profiles. Target product profiles are a central part of the early product development cycle across the medical device industry. At present TPPs focus on technical specifications and are usually written with assistance from a variety of technical and scientific experts, which rarely resonate directly with ‘end users’: people seeking treatment. More than anything it is the TPP that defines the parameters of the device and the responsibility of the developers, often cutting the network at the sidelines of scientific evidence and capacity. This workshop highlighted the impossibility of divorcing technology from context: perfectly functional technologies are rendered useless if they are not trusted, test results are renegotiated, new devices necessitate new infrastructures, regulatory frameworks struggle to keep up with product development. What if these insights, often garnered from social science research, were used to expand the remit of the target product profile in ways that afforded improved health system integration? What might a socio-technical product profile that tracks needs, limitations and opportunities through institutional arrangements, point of care processes and health system infrastructures look like?