?P?r?e?c?i?s?i?o?n? Medicine: Hindsight or Foresight - Our choice

All of us are students of hindsight. Def: A science of understanding of a situation or event only after it has happened or developed. In many regards the history to-date of precision medicine is peppered with hindsight. A few examples make the case.

Prior to September 1998, HER2-positive breast cancer was associated with poor outcomes and higher mortality rates than other breast cancer subtypes. Might we have foreseen then, that the launch of Trastuzumab (Herceptin) with all of it's targeted impact on disease, would go on to change the paradigm of patients afflicted with HER2-positive breast cancer and by 2021 have accumulated revenues of more than $70bn further paving the way for science to reclassify cancer not by tumor but by molecular subtype? Hindsight!

How might we behave differently about investment in precision testing if we knew back then, that this was not a forever niche (as many leading consultants labelled it at the time), but the catalyst for therapy pipelines everywhere to become interdependent upon an overly complex, often dysfunctional testing ecosystem? Hindsight!

Only two years after the launch of Herceptin, might we have foreseen the importance of next generation sequencing as a technology sent to revolutionize our clinical future, meeting the forthcoming tsunami of clinical trials and ultimately drug approvals? Perhaps we might have regarded NGS as requiring the accelerated investment we pin on AI today... or perhaps we could have avoided the loss of so many patients to treatment in the intervening 20+ years.[i] Today the diffusion of NGS remains sadly very unequal. Hindsight!

Our excitement around the application of precision medicine to clinically ultra rare disease could perhaps have been? better met with a consideration that the reflex commercial business model for therapy launches, where 95% of investment is dedicated to treatment education and 5% on eliminating test access barriers, would not work for 20% of the subsequent therapy launches between 1990 and 2020. [ii] Instead we have painfully discovered ?that this same reflex business model failed to deliver a ?ROI for these treatments. That Pharma unprecedentedly has started handing back therapy assets to the Biotech companies they? in licensed them from is no coincidence[iii]. Hindsight!

A relative of mine is a leading historian, and we occasionally debate if history is merely an observational activity or a learning opportunity. I choose to believe the latter, which is why I believe we should now apply greater industrial foresight to current events on the front line of precision. This determined reading of the current tea leaves might help us better leverage? the opportunities next time round.?I proffer the following.

1. Better testing and better treatment will be measured in a way which illustrates that jointly assessed? patient outcomes are significantly superior to better treatment alone. Payers will be willing to pay more when proof is provided this impact can be delivered to more than merely a third of patients as is the case today.[iv]
2. The determination of value will move from the quantification of the costs of testing, to an assessment of the burden of NOT testing. This will?sensibly integrate all the healthcare costs of patients denied the precision treatment right for their disease, most of whom will have gone on to shortened lives and or created excessive cost burden.
3. The use of testing data to find US patients eligible for precision treatment within days of testing, will enable a re-valuation of the legacy commercial model for therapy launch. Augmenting this “just in time patient finding” with digital communications will support a 50% reduction in the cost of commercializing precision therapy.
4. Spurred on by more informed patient advocates, Patients in Europe will elect to share their healthcare records as a GDPR exception, and in the interests of modernizing their treatment options. This will enable a roll out of smart diagnostic pathways to cut treatment delays and a much needed leapfrog for precision medicine outside the US
5. Payers will incent pathologists , hematologists and Laboratorians? to reflexively choose the right diagnostic tests for patients. This will address the information burden currently placed on Physicians from having to keep up to date with the paradigm of new biomarkers and new test modalities.
6. A backlash against the unfettered use of GLP1 treatments will be avoided by one or more Pharma competitors co promoting a biomarker enabled diagnostic triage for patients. This will remind us that precision medicine is not an oncology niche but the new norm for all disease to target patient outcomes.
7. Shortsighted predictions that precision medicine might have peaked [v] [vi]will be met with the evidence that R&D scientists have already transitioned their pursuit of ALL treatment breakthroughs to be biomarker enabled.

I have numbered the predictions above so you can choose which to agree/disagree with or even add your own.. Either way, please join the debate… and let us put precision medicine hindsight in a box marked… History.

No bell will be rung to tell our Pharma and Payer? “C” suites? when we need to proact differently, but the foresighted amongst us will surely take action today and leverage the win:win opportunities clearly presented by diagnostically enabled better treatment.

References:

[i] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10036891/

[ii] https://joppp.biomedcentral.com/articles/10.1186/s40545-023-00590-9

[iii] https://www.gene.com/media/statements/ps_062923

[iv] https://ascopubs.org/doi/full/10.1200/PO.22.00246

[v] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10036891/

[vi] https://aacrjournals.org/cancerdiscovery/article/doi/10.1158/2159-8290.CD-23-0467/729589/Quantifying-the-Expanding-Landscape-of-Clinical?sf183128105=1

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