Bench to bicycle

Wearables — small personal devices that monitor and transmit high volumes of personal physiological data — are now firmly seeded in the vernacular and promise improved understanding of patient and population disease levels. Blood pressure monitoring can be linked to applications determining optimal daily doses of antihypertensives, reducing unnecessary use of medication and maximising treatment efficacy. Wearables also offer regulators, clinicians and pharmaceutical companies’ transformative improvements in pharmacovigilance datasets, notably around patient adherence monitoring. This then helps reduce regulatory uncertainty and enables novel regulatory paths, including adaptive licensing and FDA breakthrough status, to become more accessible than ever before. Questions remain however, as to who is the most appropriate custodian of the collected data.

Presently, healthcare providers are the dominant collectors and custodians of patient level healthcare data, together with — to a lesser extent — healthcare insurers. The advent of wearables and virtual medical consultations places patients at the heart of data collection, and critical practical and ethical questions remain concerning the extent to which patients should be able to determine with whom collected data should be shared, and its permitted uses. Two independent groups identified as potential ‘data controllers’ are patient advocacy and disease-specific organisations. As demonstrated by the recent cases of Glybera¹ and Kalydeco², such organisations are evolving rapidly from being sources of information for patients to becoming active participants in regulatory and product development decision-making.

Wearable technologies offer potentially step-changing improvements in the ‘resolution of disease’ at an individual and population level. As illustrated by Jawbone users living through the recent northern California earthquake, where records of users awakened at 03:20am by the state’s biggest earthquake in 25 years correlated with seismic activity, they offer an opportunity to directly monitor our response to the external environment, and to immediate changes³.

Genomics

While recording the number of people awakened by an earthquake may seem to be little more than the nucleus of a transient news story, it illustrates the portent of an exciting chapter in modern medicine: epigenetics.

Describing the intricate interaction between an individual’s genome and their long-term exposure to environmental factors, epigenetics is simultaneously transforming our understanding of disease aetiology while also informing the most effective ways to treat it. For example, we are now beginning to elucidate the underlying genetic consequences of environmental factors such as smoking on underlying patient genetics through processes such as DNA methylation and histone modification⁴. Consequently, improved knowledge of biomolecular pathways is yielding druggable targets; for example, BRCA1 in breast cancer, the in vivo target for Herceptin (trastuzumab) — a monoclonal antibody for breast cancer — offered with combinational diagnostic Oncotype DX.

The data-rich 2030 healthcare system will also enable patient stratification and data mining at a population level, utilising pharmaceutical authentication tools intended to respond to commercial threats such as parallel importing — where pharmaceuticals purchased in lower price markets are illicitly sold in higher priced markets. Products such as AegateASSURE^TM and KODAK TRACELESS Anywhere^TM systems may be linked to patient records in order to tightly correlate medication with patient outcomes, thus yielding unforeseen pharmacological trends and applications for repurposing existing drugs. Where existing therapies are insufficiently efficacious, genomics also offers the opportunity for bespoke therapeutic approaches including gene editing techniques such as CRISPR. These are currently applied to add, disrupt or change the sequence of specific genes, in indications such as cystic fibrosis and haematological disorders including blood disorders such as sickle cell anaemia. The technique takes a subpopulation of cells in a bone marrow aspirate, namely mesenchymal stem cells (MSCs), then identifies and corrects errant genes to allow a population of gene corrected cells to be expanded ex vivo and administered back to a patient, permanently correcting the mutation and thus the disease. Therefore, it is apparent that by 2030, healthcare will be characterised by the convergence of e-health, genomics and applications of stem cells in regenerative medicine.

Routine application of regenerative medicines

Few areas of medical research have grasped public attention more than regenerative medicine, sustaining a cocktail of public hype, expectation and — in the case of embryonic stem cells (hESCs) — ethical concerns. However, as our understanding of the underpinning science and proof of efficacious patient outcomes grows⁵, the full ambit of regenerative medicine technologies — cell therapy, gene therapy, immunotherapy (iTx) and tissue engineering — is likely to become routine clinical practice in 2030. Perhaps most futuristically, this includes the alluring prospect of replacement engineered tissues and organs to address the shortages currently experienced.

Tissue engineering, and the broader descriptor of regenerative medicine, has its origins in transplantation medicine, pioneered by Christiaan Barnard (first heart transplant) and Donnall Thomas (first bone marrow transplantation). However, today tissue engineering — supported by advancements in transplant immunology and 3D printing — has demonstrated utility in the production of tracheas, bladders, kidneys, skin, vaginas, ears, livers, blood vessels and, somewhat esoterically, hamburgers. Availability of replacement organs to the many rather than the fortunate few will result in higher quality of life and productivity for society as a whole. Additionally, unlike conventional pharmaceuticals, regenerative medicines are likely to require multiple pharma business models, thereby supporting novel structures and growth areas. Current pharmaceuticals are dominated by a universal business model focused on allogeneic (non-patient specific) products — ‘pills in a box.’ Conversely, due to fundamental immunological challenges, including graft vs host disease (GvHD), regenerative medicines are likely to sustain both allogeneic and autologous (patient specific) products, following a transplant model. Therefore, the ‘product-plus’ offerings of 2014 are likely to grow in importance and breadth in the healthcare systems of 2030.

Conclusion

Accurately extrapolating the impact of healthcare trends decades into the future is challenging. However, there is little doubt that the technological triumvirate of e-health, genomics and regenerative medicines will have a profound and transformative effect on future patient outcomes, not least through the integration of these technologies into ‘product plus’ offerings.

In merely the last decade, genomic sequencing has been translated from human curiosity into tractable solutions at a pace that has far outstripped Moore’s Law. Concurrently, the expectations of patients and payers have changed, with people now wishing to be active for longer. Therefore, the pre-eminent mantra in healthcare translation — ‘(lab) bench to bedside’ — is under threat as healthcare in 2030 may best be described by the mantra ‘(lab) bench to bicycle’.

This article was taken from issue 7 of Insight magazine. Get your free copy of the latest issue here.

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References
1. Adherence to long-term therapies — Evidence for action, World Health Organisation (2003)
2. Horne, R., Concordance, adherence and compliance in medicine taking. Report for the National Coordinating Centre for NHS Service Delivery and Organisation R&D (NCCSDO), (2005)
3. Eichler, H.G. et al, EMA, Adaptive Licensing: Taking the Next Step in the Evolution of Drug Approval. Clinical Pharmacology & Therapeutics, 91 (3), 426–437 (2012)
4. The case for personalised medicine. Personalized Medicine Coalition, 4th Edition (2014)
5. Bingel, U. et al, The Effect of Treatment Expectation on Drug Efficacy: Imaging the Analgesic Benefit of the Opioid Remifentanil. Science Translational Medicine, 3 (70), (2011)

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About David
David Brindley is an international thought-leader in healthcare risk management.