Overcoming Adoption Challenges in Healthcare for Societal Benefit

BIN@Sheffield2017 Meeting Report

The Business Innovation Network (or BIN) is holding its annual meeting in Sheffield this week. This is an unusual event in that it seeks to stimulate economic growth and wider societal benefits by harnessing the specific-but-often-disparate strengths of a city and region, in particular the academic base. I had the privilege of attending a morning dedicated to medical, dental and social challenges, and chaired the session on overcoming barriers to adoption in healthcare. My experienced speakers - who kindly  also formed a panel for a lengthy Q&A session - were Keith Jackson (CEO of 8-Q and former MD of JRI Ltd.), Jason Brannan (Communications Director for Y&H Medilink), and Fernando Monteiro (Professor of Biomedical Engineering, University of Porto).  While some of the more obvious issues were raised and discussed, there were also some points that were less predictable and therefore worth capturing on this blog.  Those that struck me included:

• Regulations are essential for patient protection and a cornerstone of responsible innovation. While the new medical devices regulations were undoubtedly going to stress our industry (with a heightened risk of losing businesses that manufacture excellent products), there were also some benefits beyond increased patient safety. Firstly, innovation would need to make a demonstrable difference before it could be placed on the market. Secondly, the new regulations also presented new business opportunities. My previous two blog posts deal with the new regulations and responsible innovation.

• One good example of an emerging business opportunity is the translation of in silico modelling for use as a real tool for validating medical devices or drugs as a part of a comprehensive pre-clinical screening and testing programme. Tremendous academic progress has been demonstrated by groups such as Insigneo in Sheffield, but the attractiveness to industry of this work will be increased by the inclusion of modelling in the new medical devices directives (and parallel developments at the FDA).  The development of sound, validated modelling tools will therefore assist both the development of healthcare technologies and their passage to the market.

• The final point made by the panel was that it was possible that some contemporary healthcare solutions were potentially over-engineered (and therefore costly). New approaches were needed to determine which solutions were “good enough” in terms of delivering a satisfactory and cost-effective result without compromising quality of life. The innovation community is already complex, but there is a case for bringing together even more multi-skilled teams to tackle challenges that have reached new levels of complexity.

Wider changes and the huge scale of the healthcare challenge suggests that societies will need to find new ways of covering the costs (and risks) of translating from the laboratory to the clinic.  Multi-disciplinary partnerships with private and public sector entities will be increasingly attractive as a means of sharing risks and costs, with some degree of government engagement and involvement. These could be all the more successful if city and regional councils can work together to strengthen the environment or “place” where innovation is developed and tested.  We will perhaps see the rise of new not-for-profit entities to act as umbrella organisations that address the more complex healthcare challenges. City regions that best understand and support these changes will benefit from the high value jobs and economic growth that the healthcare industry will deliver.

The UCL Special Inquiry into Regenerative Medicine Research

University College London (UCL) has published the findings of a Special Inquiry into Regenerative Medicine Research, a lengthy document that seeks to understand the role of one of the UKs foremost research institutions in the rise and subsequent fall of Paolo Macchiarini. By way of brief background, Macchiarini was considered to be a leading researcher and pioneering surgeon in the field of regenerative medicine for tracheal and airway "tissue engineering" until a series of troubling revelations - associated with several tragic deaths - culminated in his public exposure in 2016.  Many aspects of the story, especially the role and personality of Macchiarini himself, have been covered by the media (including social media), and it is clearly a complex scenario. Macchiarini could not though have achieved his notoriety alone, indeed he became an internationally respected figure in the wider tissue engineering community, and the UCL report provides a substantial insight into how senior academics and hospital clinicians became associated with him personally and professionally.  The report is especially compelling as it has been written by some of the UK's leading academics and clinicians with an international reputation for excellence and probity including in the broad field of tissue engineering and regenerative medicine (TERM), and who have had access to at least some key documents and people. This makes it a more reliable document than some previous media reports, as well as essential reading for all researchers in the TERM field (as well as bioethicists, lawyers, and clinicians more generally). Inevitably though while resolving a number of issues, it also raises questions where more information is needed, and perhaps some of these unanswered questions could only be resolved in a legally empowered inquiry. Before considering these though, it is important to bear in mind the following:

• TERM is a broad field that is largely concerned with the development of therapies that promote the successful healing of human tissues in situations where this would not otherwise occur naturally.  While more research is needed, it is a field that offers potential solutions where current clinical interventions are either limited or do not exist.  Many thousands of scientists, engineers and clinicians are engaged in sound and responsible research all over the world (including at UCL), and in parallel other experts including regulators and industries are working equally hard to reduce risks while bringing benefits to patients.  The Macchiarini story is not a reason to curtail this activity, but it is essential that it informs practice, especially proper governance in responsible translation to the clinic.
• The clinical cases covered by this inquiry involved sometimes subtly different interventions, and this diversity is greater when considering all of the surgical procedures where Macchiarini was involved outside of the UK. When patients die, this is always a tragedy for them and the families left behind. Even if interventions were classed as palliative, this does not negate questions related to the governance of an experimental medical procedure and informed consent (questions that lay largely outside of the scope of this inquiry, but questions that should arguably be now addressed using a robust instrument).

While UCL's report on the special inquiry is both detailed and insightful, it also recognises the scale and complexity of investigating experimental clinical interventions involving more than one organisation (and therefore the limits to this type of investigation). The subject of the inquiry was the primarily the role of UCL staff in forming a relationship with Paulo Macchiarini (including the award of an honorary chair), and the role of the institution in a series of operations that sought to apply experimental TERM-like technologies in human tracheal/large airway surgery. In places the inquiry also considered interactions between academic and clinical staff, and aspects of local compliance with legal, regulatory and governance requirements.  In my experience of working in a mixed clinical-basic science environment, senior staff understand very clearly which organisation they work for (it is printed on their payslip), and also to whom they are responsible to when working (which could be an NHS Trust), irrespective of the honorary contracts they hold. In simple terms, if a clinician is treating a patient, they are responsible to the relevant NHS Trust irrespective of which organisation is printed on their personal payslip. Likewise it is the NHS organisation governance that applies when treating patients, irrespective whether the intervention is established or experimental.

Outside of the remit of this report lie a number of as yet unanswered questions. For example is the current legal, regulatory and ethical framework fit for purpose, and if "yes" then were established legal/governance processes and procedures accidentally or deliberately bypassed in some clinical cases covered by this inquiry (and indeed others around the world)? While my experiences suggest that our existing legal and regulatory framework is both robust and fit for purpose, this is a question that can only be addressed fully by a wider pool of experts (including in law, ethics and regulatory affairs). It is also a question that is arguably more pertinent to the hospitals concerned rather than their associated universities, and it seems therefore likely that this UCL report is only a first step towards gaining a better understanding of these events in the UK and beyond.

New European Medical Devices Regulations: Implications for Innovation, Brexit and i4

The Medical Devices Directives are European laws that essentially govern the manufacture and sale of all medical devices - ranging from dental fillings to hip replacements and pacemakers - in the European Economic Area.  These have recently been overhauled for a variety of reasons, including better harmonisation with the regulatory environment for pharmaceuticals as well as in response to a number of disasters I have written about before (such as metal-on-metal hip replacements and the PIP breast implant scandal). No blog could be sufficiently long and detailed to cover the details of the new rules, but some key features of note are:

• The regulations are more comprehensive and demanding in almost every way, meaning more details are recorded (from the supply chain, placement in the patient, and at the point of failure). The level of detail is greater, and the depth and rigour of the quality assurance processes being applied has been increased substantially.
• With resect to traceability, the vast majority of medical devices will now have a unique identifier so that they can be followed on a supply chain "time line" from manufacturer to patient to failure.  Some devices will most likely be exempt, for example dental materials, but for the first time so-called cosmetic devices (such as breast implants) will be captured by the new regulations.
• Patients will benefit from an "implant card" that describes their new device, the risks, and alternatives, all in theory written in lay terms.
• Post-market surveillance will be strengthened substantially, and communication between different European countries will be greatly improved.
• Manufacturers will need to employ and identify a named competent person to oversee and take personal responsibility for the quality assurance of their products and compliance with the Medical Devices regulations.

While many campaigners will see these changes as good and probably long overdue, there will inevitably be some more negative consequences.  Most obviously, tougher regulations will introduce new costs into the manufacturing process and the healthcare system, and these costs will ultimately need to be covered (with the most simple mechanism being a price rise that we will all pay for in one way or another).  There are, however, a number of impacts that are more difficult to predict.  For example, the scale and complexity of the regulations means that smaller companies might struggle to comply - especially with innovative products - and instead it is likely the new regulations will on balance favour the larger multinationals who have the critical mass and expertise to manage these changes internally.  This may not appear as a "negative" to the casual reader, but there is evidence that a proportion of innovation that is destined to be valuable for patients (in terms of reduced pain or enhanced quality of life) takes place in smaller companies (so-called SMEs).  I am therefore concerned that some aspects of the new regulations could work against the product innovations we all need, and patients will suffer and/or have shortened lives as a result. This may though be a price worth paying for more responsible innovation, especially in sectors such as regenerative medicine where there is an emerging narrative suggesting that experimentation on patients without proper informed consent may have occurred.

There are countless examples of unmet clinical needs. Just one increasing challenge is device-associated deep bone infection.  The costs associated with this problem are huge, the pain and misery for the patients is very real, and the consequences for society are serious.  There are many promising solutions that could address this challenge being worked on throughout Europe (including in my laboratories), and the most promising technologies are already being passed to companies for commercial assessment. There is a real risk that, at the time of greatest clinical need, we will raise the regulatory barrier so high that their development ceases to be clinically or commercially viable.

Not all aspects of the new regulations are negative; indeed I agree that the system needed a major overhaul, and the majority of changes are affordable and in the public interest. The possibility of small businesses failing and innovation being curtailed is a risk rather than a certainty, but one we should be aware of.  Of the many positive aspects, the most exciting is arguably the traceability of medical devices throughout the supply chain to the patient. Coupled to "i4"(the 4th industrial revolution where the level of detail and control of the manufacturing processes is being transformed),  there is an opportunity here to gain unparalleled insights into the factors that determine success (or failure) of almost every medical device placed in a person.

There is though one final dark cloud looming ... Brexit!  In my opinion, access to the European market for UK medical devices manufacturers is essential and non-negotiable. My reasoning is based primarily the huge value of this sector to the UK economy, and the specific value of European exports to most of our businesses. This will mean full UK compliance with the new regulations, but without a seat at the table to discuss their modification or improvement during this long but critical implementation phase.  Some Brexit supporters seem unable to grasp the potential social and economic costs of a failure to negotiate a sound departure from the EU, and their first instinct is to be pleased to shake off the shackles of European laws, even laws designed to promote trade while protecting citizens. The changes to the Medical Devices Directives will have a real impact that should include safer materials and technologies for patients, but could include the loss of businesses and jobs in the UK if we do not manage their implementation carefully.