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Medicines personalised for Tom, Dick and Harry

Dorothy may have finally got home to Kansas, but are we doomed to keep following the Yellow Brick Road?

If the Wicked Witch of the East’s ruby slippers had been several sizes smaller, would Dorothy have been destined to remain in the Land of Oz? Just as one shoe doesn’t fit all, a particular drug will not necessarily provide the same benefit to everyone. We spend our lives wanting to be treated as individuals and not mere statistics, and yet the one time where it is beneficial to be considered part of the crowd is when we lie smack in the middle of the efficacy bell curve, basking in the warmth of statistical significance with no sign of a stopping rule on the horizon. However, as we wander about the curve plateau, we peak over the edge and dimly are able to make out those outliers ahead of us near the bottom of the steep gradient in whom the treatment has exhibited phenomenal efficacy, and we wonder why that can’t be us, never mind those who have not been able to climb the curve in the first place.

And so enters the concept of personalised medicine with the aim of providing treatments to ever-shrinking populations of high responders. We have been meandering about in the foothills of personalised medicine for years; individual dosing regimens, use of alternatives or combinations through a process of elimination, etcetera. The ideal is to tailor-make a treatment regimen specific to the physiological requirements of each patient. Perhaps, however, we ought to flip the concept of personalised medicine on its head and consider instead the personality of the disease with the spectrum of its variance being affected by the genetic makeup and resultant physiology of its host. Diseases are mindless, they don’t care how they’ve been defined or characterised by clinicians. There is still a basic lack of understanding as to the causes of most human diseases; lots of smoking guns but little in the way of identifying the actual perpetrators. One can’t help but wonder if so many clinical trials fail because the targeted molecular mechanisms do not in the end contribute directly to disease aetiology or, if they do, the redundancy built into our cellular processes can somehow compensate. Did some undetected chaos-inducing molecular hiccup occur 17 years ago that resulted in the storm that only reveals its effects now? Studies are currently being conducted on our genomes, our transcriptomes, our proteomes, our metabolomes and any other ‘omes’ you can think of to try and answer such questions.

Even when we finally understand the causes of human disease, how are we going to pay for the treatment that satisfies an individual’s or small sub-group’s requirements? Are the current development costs for rare diseases and cancer any higher than those for other therapy areas or are the typically high costs of such medications more concerned with offsetting the diminished returns from small patient populations, with the gamble that reimbursement will be sanctioned due to reduced concerns of budget impact? However, if personalised medicine is to be fully realised, patient volume and resolving unmet need in those with rare conditions may become indistinguishable from the small subgroups of patients diagnosed with previously defined common disease.
There is an increasingly frenetic tug of war over costs between the pharmaceutical industry and healthcare providers. Perhaps more radical ideas need to be considered to deliver personalised medicine that is both equitable and sustainable to all parties. With a greater understanding of underlying disease mechanisms, clinical trials should perhaps have a much greater focus on patient-level data where patient responses are subdivided into clinically meaningful efficacy grades so that only the top grade therapeutic performers qualify for exclusivity for best in-class treatments. In such cases, perhaps patent protection should be extended to permit adequate reimbursement to allow pharma to recoup costs. Furthermore, replacement of best in-class exclusivity with pipeline products could no longer be derived from placebo-controlled trials but reflect head-to-head comparisons relevant to the target population, a continuous game of efficacy leap-frog. Reimbursement could then depend on the true cost of development with additional modifiers based on efficacy grades, and with the costs spread over more extended exclusivity periods. The healthcare systems would also have a role to play ensuring mandatory uptake of new products and actively promoting information dissemination to healthcare professionals and patients. This would free pharma from the burden of marketing and advertising costs, which would no longer be included in development overheads. Perhaps pharma may even need to evolve from the current suppliers of products at the end of the development chain to providing diagnostic/health monitoring services akin to some existing biotech companies who charge very little for hardware and rely more on revenue from accessory consumables. 

Clearly something has to give. What will happen in the future if globalisation follows its logical course? There will be no more emerging markets, labour costs will be standardised throughout the globe and the world population will be stabilised according to sustainable food production and other social factors. Unlike the trends for the latest must-have gadget, our capacity to develop illness is indicative of our evolution. We each have an inherent blueprint of what paths our body will follow to its ultimate destination, barring environmental influence or mechanical damage. With such a finite population and a clearer understanding of disease susceptibility rates, how will today’s demand for year-on-year increasing profits over the competition be achieved?

A final thought to consider; if we are to screen physiological processes throughout our life to capture aberrant processes in their infancy, how do we distinguish between such episodes and those inherent as part of the normal ageing process? Where do we draw the line between early treatment management and attempting to maintain the youthfulness of our bodies? However, discussing the merits and designing a health strategy for creating everlasting life will just have to wait for another day! 

In the meantime, it looks like Tom, Dick and Harry will have a bit of a wait.

Gary Paterson PhD, Evidence & Information Manager, Hayward Medical Communications.

6th June 2017