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The pandemic preparedness paradox

Why our efficient ‘just in time’ mentality must be replaced with a resilient ‘just in case’ activity

- PMLiVE

As 2020 came to a close, there was no shortage of news: of errors, of horrors and of pioneering human achievements.

History will long remark on this year, and while our collective facts and milestones are worthy of examination, several important paradoxes have also been exposed. These we would do well to examine, lest we lose their lessons.

A barber is one who shaves those who do not shave themselves. Does the barber shave himself? If he does, he does not. If he does not, he does. This is a pleasing and subtle puzzle made popular by Bertrand Russell. While real-life paradoxes are rarely so tidy, pandemic preparedness is often viewed in this light, by both the lay public and by our elected representatives.

If we prepare perfectly for pandemics, we’ll have nothing to show for it: no mass morbidity and mortality, no economic catastrophe and no fear, that is to say, no rationale for the work of preparation. We will have pre-empted each potential pandemic altogether.

A small cluster is identified, mitigated and stopped before it turns into an outbreak, or epidemic or pandemic. Alternatively, and as we saw in 2020, if we don’t prepare, or prepare ineffectively, the rationale for preparedness is writ large.

If we do invest, we will have no evidence (no pandemic, no global economic disruption) that we had to make such investments. If we don’t invest, we will once again have more evidence than we can handle. This paradox is anything but subtle.

As healthcare executives, our remit is to improve human health and provide a return to shareholders. In most segments of our industry, these goals are highly correlated: if a firm can improve healthcare outcomes, financial returns follow, and rightly so. Here again, pandemics prove thorny.

If we had a perfect cure for SARS- CoV-2 in 2018, the CEO who developed it would have been fired, and the cause (and perhaps the company) written off. Development costs are large and (roughly) fixed, yet there is no market for diseases without incidence. There is no market for sporadic infectious diseases.

Even the use of the word ‘market’ is incorrect. A market must comprise a buyer and a seller. Without incidence, there is no buyer. Then during a pandemic, there are buyers but no sellers, at least until the sellers can catch up, react and develop products, after which time the devastation has already occurred.

Taking this example even further, if a seller is prescient and successful and brings an effective product to market, that product will – ideally – save the world and be a financial failure of unique proportions, ie, if sufficiently successful, a few patients in a small cluster are treated, there is no outbreak, the world saves trillions in economic damage and millions of lives, and the seller has captured a large and negative return (recall, the cost of development is fixed). This is nothing more than a paradox born of a business model.

In the United States, where many lessons are currently on offer, pandemic preparedness investments have been cut and then reinstated on a four year cycle, independent of the political party in charge. Preparedness is an easy target for an incoming leader, removing a predecessor’s legacy project while also reducing spending.

Only repeated serendipity – from a penchant for popular fiction to an actual outbreak – encourages modest investment once again. Maybe 2021 will be different. Maybe we can break the panic-neglect cycle. But hoping that famously ephemeral public support will remain steadfast over the coming decade is not a reasonable strategy. So, what should be done about this existential paradox?

Cutting the Gordian Knot

In the second half of 2020, the power of focused investment and scientific innovation – the power of our industry – was proudly on display. In less than a year, hundreds of thousands of participants were enrolled in trials worldwide, and the first vaccines across the finish line each boast outstanding short-and mid-term safety and eye-watering efficacy.

This industry can react like few others. However, this near-perfect reaction is anything but sufficient. Vested interests rationally lobby for ‘more investment in the same ideas’ and, indeed, those investments should be made, but if a near-perfect reaction is insufficient, perhaps we should not bet our species’s existence solely on the ideas that led us into 2020.

The hope for a (heavily incentivised) ‘free market’ solution, also known as Adam Smith’s ‘invisible hand’ and more recently envisioned as a ‘conductorless orchestra’, has brought us to this place. In our experience, orchestras do markedly better with a conductor.

We are therefore proposing the creation of a purpose-built, operating, drug-developing, public- private partnership (PPP) to proactively develop tests and medicines against the highest threat pathogens. Why should we do this?

We must build resilience

Pandemic threats are existential. For existential threats we must have contingencies, we must have layers of protection. Resilience means redundancy, which is neither efficient nor free. Our efficient ‘just in time’ mentality must be replaced with a resilient ‘just in case’ activity. Which leads to the second tenet.

We must be proactive

We need to improve our ability to react, but reacting – no matter how fast, no matter how effectively, is too slow. We are not dealing with linear phenomena; time is everything. How can we gain time? Anticipate. Prepare! Develop drugs and tests in anticipation, some of which we will never use. Our healthcare professionals need tools to help patients and to protect themselves.

The better the tools, the better the outcomes. The last 40 years have been the era of biotech, and we have witnessed unparalleled leaps forward in our ability to design and develop new medicines. Dexamethasone was first made in 1957. Surely we can do better. And there is reason for hope.

We know what to do

In the United States, the National Institute of Allergy and Infectious Diseases alone spends $6bn annually in the labs of some of the best and brightest scientists in the world. The result is impressive: two granted patents… every day.

There is plenty of invention. And we know how to translate academic inventions into medicines that can help patients, but today that’s not happening, because there is no market for sporadic infectious diseases. If we can’t rely on market forces, and our efforts to create artificial market forces (push and pull incentives) have been insufficient, in addition to attempting to improve the current ideas, why not also hire a conductor?

An operating, drug-developing PPP focused solely on translating the most promising inventions into the most impactful medicines against the most dangerous pathogens has the benefits of agency, ownership, coordination, scale… it is both fundamentally different and highly likely to succeed. This can be done and we know how to do it.

But this requires investment from the public, and in every previous outbreak, the gap between what should have been changed and what was actually changed has been cavernous, and so…

We must act now

It would be easier to start this work after COVID-19, after we all have our feet under us once again. This is the mistake our community has made repeatedly – the scientists and medical professionals understand what must be done, but once society and our elected representatives feel that we’re in control of COVID-19, the next emergency will draw all attention and sap the collective will.

Support for pandemic preparedness spending can be expected to decline faster than the case counts, especially when the world starts thinking about how to pay the tab for COVID-19. This is the political reality. We simply cannot wait.

So, to go back to the earlier puzzle: ‘Who shaves the barber?’ Russell’s barber is tidy and trim because he is a figment, and under some examination his very premise evaporates in a puff of impossibility. Vastly improved pandemic preparedness is anything but tidy and trim, and that is an opportunity.

It is neither impossible to achieve, nor even controversial. The greatest gift this difficult year has given us is the will and the imperative to better prepare for the next pandemic, and to do so with urgency. With sufficient investment, planning and competence, perhaps the next potential pandemic won’t even make the news.

Jake and his team at Celdara formed the Pandemic Security Initiative, which is designed to protect the nation from future pandemics by developing drugs that integrate the best of groundbreaking science, entrepreneurial innovation, public-sector investment and private-sector efficiency. Celdara initiated this work in 2014 and formalised it under the Pandemic Security Initiative umbrella in early 2020 to capture learnings and aid in the response to COVID-19.

Jake Reder is president and CEO and Colleen Doyle Cooper is a Principal Scientist, both at Celdara Medical

21st January 2021
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