It is easy to see “precision medicine” and “precision health” complementing one another. We want precisionmedicine available to us when we are unfortunate enough to be faced with a life-threatening cancer that could be cured or managed with a targeted cancer therapy. At the same time, we would rationally prefer to take advantage of whatever medicine might offer us that would prevent the emergence of that cancer in the first place or treat it in its earliest stages, which is the goal of precision health. However, precision medicine and precision health can just as easily and realistically be seen as competing for resources with one another, as we will explain below.

Just Caring: Cancer, Targeted Therapies, and Cost Control

The fundamental ethical and economic problem with health care today is that we have limited resources (money) to meet virtually unlimited health care needs. From an ethical perspective, this is what I refer to as the “Just Caring” problem (Fleck 2009). What we would identify as health care needs have multiplied exponentially as a result of very costly, life-prolonging medical technologies that have been developed over the past fifty years, targeted cancer therapies being one pre-eminent example.Footnote 1 This has strained social budgets in both the United States and the European Union, as much recent research has demonstrated (Vokinger et al. 2020; Wilking et al. 2017; Hofmarcher et al. 2020; Peppercorn 2017; Yabroff et al. 2019; Bender 2018; Leopold et al. 2018).Footnote 2 Relieving that strain means controlling health care costs by controlling access to these very expensive life-prolonging technologies, especially in clinical circumstances where the clinical benefit is very marginal relative to costs. This is health care rationing that has ethically substantial consequences. Hence, the ethical challenge is to determine how such limitations can be justly decided. Having said that, we might not see very easily how this challenge has anything to do with pursuing precision health at the expense of precision medicine and unlimited access to these targeted cancer therapies.

Prevention is supposed to be quite inexpensive: do not smoke, consume alcohol in moderation, use sunscreen, get a reasonable amount of exercise, eat a healthy diet. However, in spite of adhering with saintly devotion to these health directives, some individuals will still find themselves faced with a cancer diagnosis. This could be for genetic reasons, or environmental reasons, or just the random breakdown of cellular machinery. Roughly 40% of Americans will develop a cancer over the course of their life. The projections in the United States for 2020 are that 1.8 million individuals will be diagnosed with cancer; cancerdeaths will be a little over 600,000 (National Cancer Institute 2020). Comparable figures for Europe are 3.9 million cancerdiagnoses in 2018 and 1.9 million deaths (Ferlay et al. 2018). These cancerdeaths are the product of metastatic disease. Metastatic cancer is a terminal condition. The targeted cancer therapies and immunotherapies that are at the leading edge of cancer research are all used to treat metastatic disease. However, none of them can justifiably claim to yield a cure. In the vast majority of circumstances these interventions yield marginal gains in life expectancy measurable in months, though for a small fraction of patients there will be extra years of life. From a social point of view, it is unclear that this represents either a wise or just use of social resources.

Cancer: Finding the First Cell/Preventing Future Cells

If cancer cannot be completely prevented by good health behavior, and if metastatic disease is essentially incurable, then the next best preventive strategy would be to identify and attack cancer at its earliest possible stages. This is the perspective embraced by Dr. Azra Raza in her recent book, The First Cell (Raza 2019). Dr. Raza is an oncologist who has been in practice for more than thirty years. Her cancer research has been focused on myelodysplastic syndromes [MDS], a pre-leukemic condition. Her husband’s research was in the same area, though, ironically, he died of acute myelogenous leukemia [AML], which happens in about 33% of patients with MDS. The basic thesis of her book is that we are wasting tens of billions of dollars every year on cancer therapies that are extraordinarily costly and that yield only marginal gains in life expectancy and maximal increases in suffering (physiological, psychological, financial and social). She believes that these same resources should be redirected to destroying cancer in its earliest stages, those “first cells,” through multiple preventive strategies. On one level, this is an eminently reasonable position for which she advocates. On another level, this is an ethically radical proposal, given that she wishes to redirect tens of billions of dollars from aggressive life-prolonging care to a preventive strategy that would reduce the need for such aggressive life-prolonging care. This generates the key questions we will address in this chapter: Is this strategy ultimately ethically defensible? Is this a strategy that ought to be embraced by a “just” and “caring” society, given that the consequence of embracing such a strategy would be the “premature” death of hundreds of thousands of metastatic cancer patients each year, most of whom would be denied extra months of life?Footnote 3

A first response to this ethics problem might be that it represents a false choice. We should be doing whatever is possible to prevent cancer, or to attack it in its earliest stages, but if those efforts fail, then we certainly ought to pursue therapeutic life-prolonging options for those unfortunate patients who are faced with metastatic disease, even if those efforts might never be curative. Why would Raza not endorse that view? Here is one scenario Raza has in mind that would suggest a response to this question. She suggests that “everyone from birth to death is regularly screened for the first appearance of cancer cells in the body.” Once those cancer cells had been identified “protein markers would be identified, providing a zip code for the cancer cells. A tube of blood from the individuals would be obtained, and T cells would be isolated, activated, and armed with the address for the cancer based upon the unique protein bar code and the RNA signature it expressed” (Raza 2019, 238). This scenario has something of a futuristic quality to it.Footnote 4 However, what we do have in reality is a new “liquid biopsy” test introduced by a company named GRAIL (Oxnard 2019). This test can detect twenty different cancers in their earliest stages by examining cell-free DNA in the blood. More recent news reports suggest that the test might be capable of detecting fifty different cancers as well as the source of that cancer in 89% of cases. To be clear, this is not a perfect test. Dana-Farber reports that the test has a sensitivity of 32% for a Stage I cancer, 76% for Stage II, 85% for Stage III, and 93% for Stage IV (Oxnard 2019). The test is far from ready for clinical deployment. Consequently, no price has been announced for the test. However, another company offers a liquid biopsy test for eight cancers, which is priced at $500. This figure is likely too low for the GRAIL test. Recall in the quotation above Dr. Raza imagining that individuals would be “regularly screened” with such a test. What might that mean?

Though cancer is much more of a threat to older individuals, a significant number of young adults are diagnosed with a cancer, and some of them will die from that cancer. Given that everyone has a 40% lifetime risk of a cancer diagnosis, it would not be unreasonable to have this screening test on an annual basis. If the test is only offered to adults over twenty-one, that would be 198 million individuals in the United States. At a cost of $500 per test, the potential cost to “society” would be $99 billion per year.Footnote 5 That figure brings into sharp focus Dr. Raza’s imperative that funding this preventive effort ought to come from what she regards as wasteful and marginally effective spending on these targeted cancer therapies for metastatic disease. This, in turn, raises a number of ethics issues which must be addressed.Footnote 6

We may start by noting that Dr. Raza deserves to be ethically commended for requiring for this preventive effort come from within current cancer spending, as opposed to taking that money from heart disease, or resources dedicated to treating addictions or mental illness, or some other disease category. Her basic argument is that most of the targeted cancer therapies represent low-value care, too little good for too much money. We can readily imagine a reasonable argument for saying that it would be unjust to take resources from some other area of health care need where the care provided there was of high-value in order to purchase in its place low-value cancer care. For now, we will simply pass over this issue and focus on ethics issues that arise within the context established by Dr. Raza’s proposal.

Trading off Identified Lives and Statistical Lives: Ethical Issues

Perhaps the most salient ethical concern would pertain to the implied tradeoff between the identified lives of patients with metastatic cancer and the statistical lives that we would hope to save through annual preventive liquid biopsies (Daniels, 2012). The defining feature of statistical lives is that they are nameless and faceless. This is typically true both before the fact and after the fact when considering preventive measures. If we install guardrails at dangerous curves on state highways, we might save fifty lives per year. One year later we might see a decline in fatal slides off the highway of forty-five lives. We would have no idea who those forty-five individuals might have been whose lives were saved, or if the guardrails were necessarily what made that difference. By way of contrast, we know with perfect clarity the identities of individuals with metastatic cancer whose lives were extended (if only for months) as a consequence of their having received one of these targeted cancer therapies. Grail’s liquid biopsy may correctly identify individuals with a very early stage cancer (no clinically evident symptoms). That cancer may eventually manifest itself symptomatically, at which point it will most likely be effectively treated (minimal likelihood of recurrence). This is why we currently have 17 million cancer survivors in the United States today (Simon 2019). Projections put that survival figure at 21.7 million by 2029. This projection would not include any assumption about the successful clinical deployment of Grail’s liquid biopsy.

We need to emphasize that the vast majority of these cancer survivors will ultimately die of something other than their cancer. Why does this matter? It matters because Grail cannot claim that its liquid biopsy would have saved all these lives. Most of these lives would have been saved by current cancer therapies provided at the appearance of clinical symptoms. This point is important for judging whether Grail’s liquid biopsy represents high-value care. If Grail’s liquid biopsy reduced the number of metastatic cancerdeaths by 70%, that would constitute significant evidence for thinking of the test as representing high-value care. However, that will still leave us with both ethical and economic concerns.

Keep in mind that we are assessing Dr. Raza’s proposal (as I have constructed it). The hypothetical under discussion says that we would reduce the number of metastatic cancerdeaths in the United States by 400,000 annually. That would still leave 200,000 individuals with a terminal metastatic condition. Dr. Raza would provide those individuals with comfort care, but they would be denied these extraordinarily expensive targeted cancer therapies that for most of them would only yield extra months of life. These are clearly identified individuals, most of whom might desperately wish to gain whatever additional life might be possible with access to these targeted therapies. We are trading off for their sacrifice of that additional life indefinite gains in life expectancy (something close to or better than a normal life expectancy) for these 400,000 other individuals who also would otherwise have died prematurely from their metastatic disease. From a purely rational, utilitarian maximization perspective, this looks like an eminently reasonable tradeoff. However, those 400,000 individuals are statistical lives.

It may sound odd to say that these are statistical lives, but the fact is that we have no ability to identify who those 400,000 individuals might be. Consequently, they have something of an abstract, ghostly status. This is certainly true from a psychological perspective, compared to those patients with metastatic cancer who want to live longer. To clarify, 1.8 million individuals in the United States are diagnosed with cancer each year. Some of them are diagnosed with metastatic disease. However, the vast majority of those cancerdiagnoses will be treated with current therapies. Some portion of those individuals, despite treatment with curative intent, will go on to have metastatic disease. Most of those metastatic cases will not be predictable at the time of initial treatment, even though that treatment might have been early in the disease process. Others might have gone on to have metastatic disease, except that they were treated early and effectively. At this point in time these are all statistical lives.

Eventually, however, in this hypothetical example we end up with 200,000 identifiable individuals with metastatic disease. Is it just and justified that we would deny these individuals our very expensive targeted therapies, as proposed by Dr. Raza, because that $99 billion was allocated to the preventive effort which (by hypothesis) saved 400,000 lives that otherwise would have died prematurely? That brings us back to the question regarding the ethical weight that ought to be attached to statistical lives versus identifiable lives when we are allocating resources for purposes of saving/prolonging lives.

Should identifiable lives (patients with metastatic cancer) have more moral weight (greater just claims to health care resources) than statistical lives (patients at risk of a premature death from cancer)? Brock (2015) would answer this question negatively.Footnote 7 He considers and rejects a number of arguments in support of the opposite conclusion. I will consider his arguments in the specific context of this chapter. He first calls attention to the Rule of Rescue. The Rule of Rescue might seem to require prolonging the lives of the identifiable metastatic cancer patients, in part because we have at hand the capacity to do so readily with these targeted cancer therapies. By way of contrast, 99% of the liquid biopsies performed annually would have saved no one since the results would be negative for any cancer cells. However, the typical application of the Rule of Rescue involves huge societal expense to rescue trapped miners deep underground (or others in various dire circumstances, such as the cave rescue in Thailand).Footnote 8 It would be tragic if we (society) were aware of these situations but had no ability at all to prevent that loss of life. However, it would be unconscionable if we had the ability to intervene but simply ignored the plight of those desperate individuals and allowed them to die. This is the moral logic that says we must do what we can to prolong the lives of those metastatic cancer patients.

Notice that I did correctly describe this latter situation by saying that our goal would be to prolong, not save, the lives of these patients. In the typical successful rescue situation individuals have their lives saved; they have an indefinite life expectancy, as in the Thai cave rescue story. That is precisely what is not true with regard to our metastatic cancer patients. Consequently, the moral logic embedded in the Rule of Rescue does not apply in this situation. Perhaps a minor correction is in order when I assert that it is “not true” that these metastatic cancer patients can be saved. In fact, a very small percentage of these patients, sometimes referred to as “super responders”, will gain extra years of life from one of these targeted cancer therapies. They may well die of something other than their cancer ten or more years from now.Footnote 9 What should we conclude from this? Does this mean that the Rule of Rescue does apply, even though the rescue effort in the vast majority of cases will be unsuccessful? Does this mean that these rescued identifiable lives outweigh the merely statistical lives we would hope to save with our liquid biopsy intervention?

This last question brings us to a second consideration by Brock that would favor allocating life-prolonging resources toward identified lives over statistical lives, namely, the uncertainty associated with preventive efforts.Footnote 10 We might invest $100 million in an anti-smoking campaign, hoping to save 100,000 lives from lung cancer. The campaign might fail abysmally because smoking is addictive and woven in complex ways into the lives of individuals. Lots of uncertainty seems integral to many preventive efforts. By way of contrast, we are certain to get some benefit in the form of additional life when we provide various targeted therapies to individuals with metastatic lung cancer.Footnote 11 However, making an analogy with an anti-smoking campaign would be misleading in this case. By hypothesis, we are certain that 400,000 lives will be saved from a cancer death through reliance on annual screening with this liquid biopsy. We are uncertain which particular lives will have been saved, but those statistical lives are not merely statistical lives. Those are real lives (Menzel 2012) that should have substantial moral weight in allocating life-saving resources, as Dr. Raza would insist. In addition, I must emphasize again that in almost all cases no lives are saved among the metastatic cancer patients. Only a marginal gain in life expectancy is achieved compared to the 400,000 lives correctly described as being saved.

A third ethically relevant consideration that comes into play is urgency of need. Metastatic cancer patients who have failed several therapeutic regimens surely have an urgent need for one of these targeted cancer therapies since they have exhausted all other therapeutic possibilities. In contrast, those individuals who would be discovered to have a relatively early stage cancer through the liquid biopsy would have a substantially less urgent need because they would have many other options for treating their cancer. The conclusion we are supposed to accept, contrary to Dr. Raza, is that these metastatic cancer patients have a stronger just claim to costly targeted therapies than the statistically possible cancer patients have a claim to an annual liquid biopsy.

Daniels (2015) offers a supporting argument to this last conclusion. He refers to this as the “concentration of risk” argument. He asks us to imagine Alice, who has a life-threatening infectious disease certain to kill her unless she receives five life-saving tablets of some drug. Five other women have been exposed to Alice. There are only these five tablets. If each of these women receive one preventive tablet, their lives are certain to be saved. If all the tablets are given to Alice, then one of these five women will end up dying as a result of the exposure. It appears we have one death either way. Should we just flip a coin? Daniels opposes that idea and asserts that 100% of the risk of death is concentrated in Alice, whereas only a 20% risk of death is associated with each of the five women. Therefore, Alice has the strongest just claim to the five tablets. Again, there is a dis-analogy between the Alice example and our 200,000 metastatic cancer patients.

Alice has her life saved, but our 200,000 metastatic cancer patients are still doomed to die (with few exceptions) in a relatively brief period of time. We might be tempted to call attention to that small cadre of super-responders among those 200,000 metastatic patients. Those individuals can be correctly regarded as being Alice-like; their lives will be saved. However, returning to Dr. Raza’s main point, if saving the Alice-like super responders required re-allocating that $99 billion to these targeted cancer therapies for metastatic cancer patients, then we would be sacrificing the 400,000 Alice-like lives that (by hypothesis) would be saved by investing in population-wide screening with our liquid biopsy for the sake of that small cadre of super responders. Those may well be statistical lives, but they are not merely statistical lives. They have as much moral worth as the lives of any of those metastatic cancer patients.

Brock next calls our attention to the “aggregation” problem as the basis for (in our case) preferring to allocate resources to the metastatic cancer patients as opposed to screening with the liquid biopsy for preventive purposes. In brief, the aggregation problem involves giving very high priority to a small number of patients who will derive very substantial benefits over a very large number of other patients who will only receive a small benefit with some limited budget. For example, we can spend $5 million to save ten patients by implanting in each of them an artificial heart (without which they would all have died in six months), or we can use that same money to stabilize 10,000 sprained ankles. We will stipulate that treating the sprained ankles will yield many times the health benefits (by whatever measure) than saving the lives of those ten patients needing the artificial heart. Still, our fundamental moral intuition would be that such a trade-off would be unconscionable. Once again, however, it can be argued that there is a dis-analogy here. It is a relatively small benefit that accrues to our metastatic cancer patients and an enormously greater benefit that would be denied to those 400,000 individuals whose cancer will go undetected without the liquid biopsy and result in their premature deaths. We may not know the identity of those individuals, either before the fact or after the fact. Nevertheless, that fact does not alter the moral equation.

Finally, there is the argument that the “medically least well off” ought to have priority for limited life-prolonging resources over those who are relatively healthy but at risk for serious illness. When stated in this very abstract form, this argument would strike many as being eminently reasonable. However, specification regarding patients who are among the medically least well off will yield results that are far from being either fair or reasonable. The assumption has to be that the medically least well off have some capacity for significant benefit if society makes available the necessary resources. Patients in a persistent vegetative state or in the late stages of dementias are clearly among the medically least well off. Just as clearly, they are incapable of significant benefit beyond bare life maintenance at costs in excess of $100,000 per year. Daniels (1985) has argued that what health care justice requires is protecting fair access for all to the normal opportunity range of a society. These are patients who are entirely outside that opportunity range. They have no capacity to participate in life.

Our metastatic cancer patients are also rightly thought to be among the medically least well off. Most of them would still have some access to the opportunity range of a society, though that access will be limited. They are not like patients with very advanced dementia. In most cases they will have had access to multiple cancer therapies that had already provided them with extra years of life that otherwise would have been denied them. In that respect they have not been unjustly ignored. Their just claims to needed health care have been met. If these targeted cancer therapies yielded, say, five extra years of life on average at a cost of $150,000 per life-year gained, we would have a much more difficult problem in determining whether that $99 billion should not be spent on them or should be spent instead on cancerscreening with the liquid biopsy. However, given the factual scenario that is current cancer care, as Dr. Raza would attest, the benefits for the vast majority of these patients are marginal. If we were to forbid allocating that $99 billion to liquid biopsyscreening, we would be sustaining an annual population of 600,000 or more individuals with metastatic cancer who would be for that last year of life among the medically least well off, instead of reducing that population to 200,000 per year by using the liquid biopsy screening technology. On the face of it, that outcome would not seem to be either reasonable or just, whether we were egalitarians or utilitarians or prioritarians in our understanding of health care justice.

Can We Just Abandon Metastatic Cancer Patients to Save Money?

Up to this point I have presented what I would regard as the most compelling arguments in support of Dr. Raza’s position. However, there are ethically problematic features of her position that we now need to consider. In spite of all the arguments above, it will still feel ethically awkward to deny social funding for targeted cancer therapies or immunotherapies for those 200,000 (hypothetical) metastatic cancer patients who would not have benefitted from having annual access to our liquid biopsyscreening protocol (Verweij 2015).Footnote 12 Though I have emphasized marginal gains in life expectancy along with a small cadre of super responders who would gain multiple extra years of life, that is ultimately an inaccurate characterization. There will be a continuum of gains in life expectancy. The most unfortunate patients may suffer harm; others will gain nothing; others will gain a few months; still others will almost gain a year; and more fortunate patients will gain an extra year or two. This makes it a lot harder to endorse with ethical equanimity redistributing all our life-prolonging cancer resources to the preventive liquid biopsy strategy. A simple solution would be to just pour more money into cancer treatment. However, that means we would fail to take seriously the “Just Caring” problem. There are limits to what any society can afford to spend on meeting health care needs, given multiple other legitimate and compelling non-health care social needs. In addition, I am unaware of any arguments that would justify spending unlimited sums of money to meet the needs of cancer patients, as opposed to patients with any of a number of other life-threatening medical conditions.

Cancer is not ethically special. Dr. Raza is clearly correct in calling attention to the vast sums of money we currently spend on low-value care for metastatic cancer patients. The problem, of course, as things are now, is that we only know after the fact that what we provided was low-value care because we spent $50,000 for a patient who gained only three extra months of life. I will put aside for the moment issues related to efforts at identifying who such patients might be before the fact through the use of predictive biomarkers. Instead, I want to consider the challenge that the liquid biopsy strategy I have described also represents low-value care. This might sound odd since the scenario I sketched suggested that 400,000 lives annually would be spared by such a strategy from progressing to a terminal metastatic disease state. I will remind the reader that this was an arbitrary number, not based upon any empirical evidence at all. The objective was simply to establish an initial framework for ethical analysis.

My critic will point out that if we are doing 198 million liquid biopsies each year, more than 99% of them will be negative at a cost of $99 billion. That will strike many as an obvious instance of low-value care. In addition, it is far from clear that simply calling attention to the 400,000 lives annually spared from a premature cancer death because of this preventive effort would sufficiently justify this massive expenditure of resources.Footnote 13 The obvious solution would be to be far more selective in the population screened with our liquid biopsy strategy. Here are some possible options: (1) Screen only those individuals and first-degree family members where there has been a family history of cancer. (2) Add to (1) individuals with established behaviors likely to result in increased risk for various cancers, such as smokers or individuals with significant sun exposure. Roughly 40% of all cancers are attributed to behavioral choices by individuals. (3) Add to (1) and (2) individuals who have been diagnosed with a cancer and successfully treated (the assumption being that they are likely at increased risk of cancer recurrence). (4) Add to (1), (2), and (3) individuals who have compromised immune systems that might increase their risk of cancer. (5) Add to all the previous categories individuals above the age of 50, the assumption being that cancer is most often a disease for which older individuals are at risk. Note: In all these cases we are assuming that the cost of this testing would be a social expense. Individuals outside these categories would be free to obtain this testing at their own personal expense.

Trying to identify categories of individuals who would have the most reasonable and strongest just claims to this annual liquid biopsyscreening would likely have a strong arbitrary component, as we discuss below. We might imagine avoiding the need to draw these lines if we could show that our initial proposal made economic sense when viewed in total. If we are saving 400,000 lives from a premature death from metastatic cancer each year, then we are also saving the cost of treating those metastatic cancers. We can assume that cost might be $100,000 per metastatic cancer patient saved. If so, that savings would amount to $40 billion. That would still leave $60 billion in screeningcosts each year for which there were no offsetting economic gains.

Though ethicists would likely not endorse this next point, economists would note that those 400,000 individuals are still going to die, and it would be extremely unlikely that they would die cheaply. Those deaths would most likely be of other chronic degenerative conditions with multiple years of high healthcosts. A substantial number will develop dementia and require at least a couple years of long-term care at $100,000 per year. Consequently, if our concern with controlling health care costs is about allhealth care costs, then the bottom-line savings would be substantially less than $40 billion. For the sake of argument, let us say that the net savings would be $20 billion.

Someone might then argue that $20 billion in savings ought to be used to provide $100,000 worth of targeted cancer treatments for each of the 200,000 individuals each year who would still end up with metastatic cancer in spite of the screening program. However, our erstwhile economist will again call our attention to an awkward economic fact, namely, that the savings we would expect to achieve by not having to pay for targeted cancer therapy for 400,000 individuals will only be realized more than two decades into the future. The costs of doing the screening will all be incurred in the present and represent additions to current health care costs. The assumption behind this conclusion is that it would be unethical for reasons of both justice and compassion to deny the current 600,000 patients who will die this year from their metastatic cancer the targeted cancer therapies and immunotherapies that can give them additional months (sometimes years) of life in order to offset the current costs of the proposed liquid biopsyscreening program. In other words, transitioning from our current metastatic cancer therapeutic protocols to the biopsy screening protocol proposed by Dr. Raza would be ethically, economically, and politically problematic. Is there a just and reasonable way of addressing the “transition” challenge?

The Transition Challenge: Efficiency versus Compassion

Menzel (2012) has addressed the transition challenge. He addressed it very broadly, maybe too broadly. This is the question that Menzel started with: “Should we provide relatively inefficient treatment to identifiable individuals at relatively high risk for relatively immediate harms rather than more efficient preventive care to equally identifiable individuals at lower risk for more distant harms” (214; his italics). He defends what he calls the equivalence thesis, namely, that the lives on either side of the equation are equally worthy of being saved through the allocation of social resources. However, the identifiable individuals at high risk can only have their needs met inefficiently. In other words, this is an unwise use of social resources, which is what Dr. Raza would argue. Society, he contends, in the form of future generations, would be much better off if the resources now being used inefficiently to purchase marginal gains in life expectancy were to be used instead in the preventive mode to prevent the need for the future inefficient uses of those resources. However, he argues, we cannot afford to do both things during some sort of transition period. This has the ethically problematic consequence of sacrificing the lives of a whole generation (in our case) of metastatic cancer patients who would all be denied access to these expensive targeted therapies in order to eliminate the need for such therapies for future generations. This does not appear to be either fair or compassionate.

Menzel asks us to consider the alternative. If we agree that it would be wrong to sacrifice this generation for the sake of future generations, then how would we ever make the transition that he would argue is rationally, ethically, and economically required? We would be stuck in the present circumstances. We would be compassionate to the current generation of metastatic cancer patients but we would be sustaining the pain and suffering and costs associated with metastatic cancer for numerous future generations who would not otherwise need that compassion because they would not have to endure this suffering if we now made a different decision aimed at preventing the need for such care in the future. Menzel writes: “By spending at a lower health productivity rate for that prevention than we do for treatment, we would fail to decrease the incidence of these very diseases for future generations, condemning more people than necessary to never being situated where they can find in their rational self-interest to vote for a more limited priority for treatment, with all the benefits of such a policy” (2012, 214). Menzel sees the “long run” perspective associated with prevention as justifying the “unfairness” objection raised in connection with denying life-prolonging care to a current generation of seriously ill patients. This is essentially a utilitarian perspective.Footnote 14

One way of reading Menzel is to imagine a very costly preventive intervention that is completely successful in eliminating that disease from future generations. This reading makes sense since Menzel thinks of this situation as requiring tragic sacrifice from just one generation of patients. However, that is not the scenario that we have sketched with regard to our annual liquid biopsy protocol. In our scenario we do save 400,00 individuals every year from dying as a result of metastatic cancer. That would still leave those 200,000 individuals each year who will die as a result of their metastatic cancer. Consequently, what we would have to be willing to sacrifice are those 200,000 individuals every year far into the indefinite future, as opposed to “just” one generation of metastatic cancer patients. That seems to require much more in the way of ethical justification than the scenario Menzel has in mind. We can readily imagine the situation Menzel envisions as being tragic, ethically necessary to effect a greater life-saving result, but still regrettable. It is much more difficult to justify as a “regrettable tragedy” a situation that occurs repeatedly and persists far into the indefinite future without any obvious effort to end it.

If we consider the situation from a very “raw” utilitarian perspective, then the argument can be made that we save 400,000 lives with our liquid biopsy protocol while “only” giving up 200,000. In addition, the 400,000 lives are restored to having an indefinite life expectancy while the vast majority of the 200,000 will have lost less than a year of potential life if provided with some targeted cancer therapy. Still, perhaps 20% of those 200,000 individuals, would end up losing prematurely anywhere from one to ten extra years of life (the higher numbers pertaining to the super responders). Of course, as things are now, we would not know who those individuals were who had so much more to lose without treatment. However, to tolerate this outcome as a society, we would have to harden our hearts, close our eyes, and numb the compassion-generating portion of our brains. That, by itself, suggests the need for more critical and creative thinking. How, then, can we effect the transition Dr. Raza recommends in a way that is congruent with what a just and caring society ought to be?

Whole Genome Sequencing: Another Precision Health Ethical Challenge

That brings us back to the need to slim down dramatically the liquid biopsyscreening protocol. Can that be done in a way that is at least “roughly just”? We noted above that one group of patients who would seem to have top priority for access to these liquid biopsies would be those identified as being at risk for hereditary cancers. That represents only about 10% of all cancers (National Cancer Institute 2017). How would we imagine identifying them? The short answer would be that we do Whole Genome Sequencing [WGS] of almost all Americans alive today and every child born each year. Such sequencing with professional analysis and interpretation and counseling would cost about $5000 per person, or $1.5 trillion for 300 million Americans today. In addition, it would cost $20 billion per year to do WGS of each birth cohort. In the real world we do not have the technological capacity or personnel that would be needed to accomplish this task, never mind managing such huge economic costs. As with our liquid biopsyscreening protocol, we would have to slim down and prioritize who would have access to such WGS at social expense. How can that be done fairly?Footnote 15

I would certainly not endorse as “just enough” the libertarian view that it should be up to individuals with their own resources to determine whether such WGS was “worth it” to them. This would clearly disadvantage the financially less well off who would be at risk of a premature death from metastatic cancer that could have been avoided with access to WGS and/or our proposed liquid biopsy. What about an egalitarian perspective? There are several varieties of egalitarianism. Broadly speaking, egalitarians are committed to equal concern and respect for all. Would that mean everyone has an equal claim to WGS to establish their vulnerability to cancer? That would be a practical impossibility and ethically indefensible, given limited resources for meeting unlimited health care needs, not just cancer-related needs. Egalitarians will generally accept the view that greater health needs justly command more social resources (appendicitis commands more resources than a sprained ankle). How serious or urgent is the need for WGS to establish lifetime cancer risk relative to managing heart disease or Parkinson’s or multiple sclerosis or dozens of other chronic degenerative conditions? This would not be an easy or obvious answer for an egalitarian.

Keep in mind that if the whole US population underwent WGS, 60% of those individuals would never develop cancer over their entire lifetime.Footnote 16 Given that statistic, utilitarians would not endorse WGS for the population as a matter of social justice. Prioritarians want to ensure that a society meets the just claims for needed health care for those who are “medically least well off.” We might imagine that the 10% of the population at risk for some hereditary cancer would fit that criterion. That would certainly be true if we restrict ourselves to considering only patients at risk for cancer. However, this is where prioritarians might find themselves internally conflicted. There are the metastatic cancer patients who desperately need the targeted cancer therapies for some additional gain in life expectancy (sometimes a significant gain in life expectancy, as discussed above), not to mention all the other patients at substantial risk for premature death because they are in the advanced stages of some chronic degenerative condition. These are all patients with urgent, imminent, actualhealth care needs, as opposed to the potentialhealth care needs of individuals with a hereditary risk of cancer. In the debate over the moral weight that should be attached to identified lives as opposed to statistical lives for purposes of allocating life-prolonging resources, prioritarians would generally strongly endorse giving more weight to those identified lives. What we need to keep in mind is that having a hereditary risk for cancer does not necessarily mean that one will actually have cancer during one’s lifetime. Women with a BRCA1 mutation will have a lifetime risk of breast cancer in the 40% to 85% range, depending upon which of several hundred mutations in the gene they might have.

For the moment, let us put aside the practical and ethical challenges of determining who would have a just claim to WGS at social expense. We would (presumably) want to identify the 10% of the population at risk for a hereditary cancer, even though it is a high lifetime risk, but not a certainty. However, we would also have the capacity to determine a polygenic cancer risk score for virtually everyone. Such a score would be the product of literally hundreds of genetic variants in an individual each of which might increase very slightly their lifetime risk of cancer. Their lifetime risk would likely not be as great as someone at risk for a hereditary cancer. They might be told that their lifetime risk was “just average,” that is, at 40%. Would they feel that they had a just claim with regard to our annual liquid biopsy? An enormous number of people would get a result like that, which would defeat the need to reduce the use of annual liquid biopsies at social expense. A significant number of individuals would also be told that their lifetime risk of cancer was below average, say at 20% or 30%. That is not zero. Some of these individuals will develop a cancer. Most of them will have that cancer caught at an early and treatable stage. Others will be less fortunate. They will progress to metastatic cancer and a premature death. So, one of the things we need to keep in mind, whether for the average or below average cancer risk patients, is that the fewer annual liquid biopsies we do, the greater (statistically) will be the increase in patients with metastatic disease. Should we see this as being unjust, ethically problematic? This is what is referred to in the literature as the “ragged edge” problem (Callahan 1990, chap. 2) or the “cutoff” problem (Rosoff 2017). No perfectly rational or perfectly just rationale can be offered for drawing a line at one point rather than another point. A line has to be drawn (as we have argued above) because we have only limited resources for meeting unlimited health care needs. There will always be patients with health needs or health risks just below that line who could make a reasonable just claim for the resources being provided to those above the line. The most we can reasonably hope for in this regard is rough justice.Footnote 17

Lots of things muck up our intuitions regarding what is ethically required of a just and caring society for purposes of allocating resources toward precision health. We noted earlier that roughly 40% of cancers are linked to individual behavioral decisions (Mendes, 2017). This is something that would get the attention of luck egalitarians, who are committed to a responsibility-sensitive conception of justice. We might imagine luck egalitarians would endorse WGS that provided a polygenic cancer risk score, primarily as a way of educating everyone regarding their cancer risk. Unfortunately, most humans do not seem to be open to educational efforts to alter pleasurable behavior that represents a threat to health. What we might imagine instead as being more likely is that individuals with average or above average or somewhat below average cancer risk scores would be the first to demand annual liquid biopsyscreening with the hope that this would catch an early treatable cancer without having to change the behavior that might have generated that cancer. Given this scenario, luck egalitarians would likely oppose WGS for a population at social expense as both wasteful (unjust) and irresponsible.

Economists again contribute to mucking up our intuitions regarding preventive efforts to reduce the incidence of fatal cancers in our society. We want efficiency, justice and compassion reflected in our efforts to prevent (reduce) the incidence of fatal cancers. We noted above that the total annual cost of providing access to a liquid biopsy as a screening tool in the US would be $99 billion. We hypothesized (for the sake of argument) that this effort would save 400,000 individuals annually from a premature death from cancer. That yields a cost-per-life-saved of about $250,000. This is not an unreasonable figure.Footnote 18 What makes that even more reasonable is if the average gain in life expectancy for those 400,000 individuals is twenty years. That means the cost-per-life-year-saved is $12,500. Compare that to the 200,000 individuals per year who would die from metastatic disease but whose lives could be extended (mostly briefly) if they were provided with some of these targeted cancer therapies. If each of those individuals were given a $100,000 targeted cancer therapy, then for those individuals who gained only three extra months of life, the cost-per-life-year-saved would be $400,000. This is the sort of number that would support Dr. Raza’s proposal for shifting resources away from treating these patients toward the preventive efforts represented by the liquid biopsyscreening protocol. However, a significant number (at least 20%) of those 200,000 metastatic cancer patients would gain at least an extra year of life for that $100,000. This is very close to what we spend per year for end-stage renal patients needing dialysis. From the perspective of health care justice and compassion, that makes it much more difficult to justify sacrificing these lives for the sake of putting in place the proposed preventive effort. What makes it even more difficult to justify such sacrifice would be the 5% to 10% of patients in this category who would gain multiple extra years of life from access to one or more targeted therapies (albeit at a cost of at least $100,000 for each of those extra life-years gained). What is the right thing to do, all things considered?

Answering this question is made more difficult because, for the most part, we do not know before the fact which individuals with metastatic cancer are likely to live an extra year or more with the help of a targeted therapy. This is mostly a true statement. However, much research regarding cancerbiomarkers is resulting in our identifying before the fact patients who are more likely to benefit substantially from access to a targeted cancer therapy. One type of targeted cancer therapy are the drugs known as checkpoint inhibitors, such as nivolumab and pembrolizumab. These drugs target PD-1 and PD L-1 (programmed cell death protein 1), whose job it is to regulate the immune system from over-reacting and generating one of a number of immune disorders. However, cancer cells can use these proteins to hide themselves from the immune system. The checkpoint inhibitors are intended to suppress PD-1 and make the cancer cells more visible to the immune system. For some types of cancer, higher levels of PD-1 expression are a good biomarker of a more effective response to these checkpoint inhibitors. The actual literature in this regard is mixed (Dudley et al. 2016; Ugurel et al. 2020; Yi et al. 2018). What if, however, a slight majority of cancer patients with these higher levels of expression gain one or two extra years of life, not just seven months? Do all these patients then have a just claim to have access to these checkpoint inhibitors at social expense? High levels of tumor mutational burden are also a good (not perfect) biomarker for a more effective response to these drugs (Chan et al. 2018).

These are just illustrative examples I have offered. I could have picked a dozen others. The core ethics question is this: If we develop the capacity to identify with a high degree of likelihood, using various biomarkers, patients who are most likely to gain an additional year of life from access to various targeted cancer therapies or immunotherapies, should we use that capacity to separate moderate and strong responders from marginal responders for purposes of allocating these therapies at social expense? In other words, would considerations of justice and compassion justify this rationing practice as part of an effort to balance providing limited resources to both prevention (our liquid biopsy protocol) and treatment?

We need to consider one more possible scenario. The basic premise behind Dr. Raza’s proposal is that the vast majority of metastatic cancer patients today achieve only marginal gains in life expectancy with access to these targeted cancer therapies, which is why she believes we ought to pursue aggressive cancer prevention rather than aggressive treatment. However, that might be changing, perhaps significantly. Many researchers (Cajal et al. 2020; Prasetyanti and Medema 2017; Dagogo-Jack and Shaw 2018) now believe that because of the genetic heterogeneity of cancer, and its evolving nature within an individual, multiple targeted therapies need to be used, either in combination with one another or sequentially, a strategy which has yielded considerable success in the treatment of HIV. This can increase substantially the cost per patient per year to achieve several extra years of life with “managed” metastatic disease (nothing curative). For example, Workman et al. (2017) note that the cost of combining nivolumab and ipilimumab would be priced at about $252, 000 per year for the treatment of advanced melanoma. More recently, Larkin et al. (2019) show a five-year overall survival rate of 52% for these same patients with this same combination of targeted therapies. Again, these examples are only intended to be illustrative of the direction of advances in cancer care at present.

What I ask you to imagine is that future research is successful in finding combinations of these targeted therapies that yield three to five additional years of life for 75% of that batch of 200,000 metastatic cancer patients. How should that alter the balance in the distribution of social resources between our liquid biopsyprevention strategy and the effective treatment needs of these 150,000 metastatic cancer patients? My hypothetical scenario is that we are using combination cancer therapy to achieve this result at a cost of $200,000 per patient per year for an average of a three-year gain. That would amount to $30 billion for that first cohort of patients, $60 billion for that second cohort, and $90 billion for that third cohort and every year thereafter. To be clear, that $90 billion is only for the care of these metastatic cancer patients, not any other cancer patients who are treated and cured in any given year. This is roughly the amount we would have to pay every year for our annual liquid biopsy screening proposal of every adult American. This also assumes that we would provide comfort care only for that other 50,000 metastatic cancer patients each year who were not candidates for any of these more successful therapies. That is, we would not provide them with low-value targeted cancer therapies (which would raise the same ethics issues as earlier discussed, albeit on a smaller scale).

As a matter of health care justice, would we be ethically obligated to increase by $90 billion per year what we spend on cancer, keeping in mind that whatever the moral logic was that justified an affirmative answer to this question would have to provide a similar answer in every other area of medicine where lives could be prolonged at a similarly high cost? That would represent a rejection of the basic premise behind the “Just Caring” problem. We have only limited resources to meet virtually unlimited health care needs. Alternatively, we could trim the costs of our liquid biopsy protocol. Let us say that we would screen annually only half the American population, thereby saving $50 billion per year.Footnote 19 Unless we somehow managed to choose the exactly correct 50% who were at the highest risk for cancer that became metastatic, we would in fact increase the number of patients who would eventually be faced with metastatic disease.

Simple math (under this scenario) would suggest that we would increase the number of annual metastatic cancer cases by 200,000. We will assume instead that we are cleverer than that, and consequently, the increase would be 125,000 (for the sake of argument). 25,000 of that annual cohort would be added to the 50,000 who would receive comfort care only; no targeted therapies or immunotherapies at social expense. The other 100,000 would receive the advanced targeted therapies described above at an annual cost of $20 billion for the first cohort, $40 billion for the second cohort and $60 billion for the third cohort and every year beyond that, which would really amount to $150 billion for each of the out years under this scenario for treatment and $50 billion for the ongoing preventive screening effort. Again, this would be in addition to whatever the current annual costs for cancer treatment are. What choices should a “just” and “caring” society make that has only limited resources for meeting virtually unlimited health care needs? This question is asked with regard to the use of social resources, not private resources. A companion question might be: What choices with regard to all of our scenarios above may a “just” and “caring” society make that would relegate the cost of those choices to individual willingness and ability to pay? I take it that a society that left access to treatment for a heart attack or appendicitis to individual ability to pay would be correctly judged to be both unjust and uncaring. Likewise, a society that refused to pay for purely cosmetic procedures (not needed as a result of disease or accident) would not be open to justified moral criticism. Where do our questions fit between these two poles?

Rational Democratic Deliberation: Not Precision Ethics But “Roughly Just”

We have raised a large number of ethically challenging questions above; we have not offered to defend any particular response to those questions. This is because, as I have suggested, there is no “most just” or “most reasonable” response to most of these questions. Many trade-offs are possible that would be “just enough” and “reasonable enough.” To be clear, unjust and unreasonable trade-offs are possible as well. The trade-offs are among the core values that define competing conceptions of distributive justice, as well as with other fundamental social values. The trade-offs we have in mind pertain to policy choices, not choices made by individuals. Consequently, a sufficient level of social agreement is necessary for these policies to be both fair and legitimate. I have argued elsewhere (Fleck 2009, chap. 5) that this agreement should be achieved through fair and inclusive processes of rational democratic deliberation governed by what I refer to as “constitutional principles of health care justice.” Before elaborating a bit on that, let us review our key questions for democratic deliberation.

  • Should resources currently used to treat metastatic cancer patients be redirected to efforts at either preventing the emergence of cancer or identifying and treating it in its earliest stages?

  • Should identified lives of patients with metastatic cancer be given equal moral weight for the distribution of life-prolonging resources with the statistical lives (future possible patients) whose early cancer can be prevented from progressing to metastatic disease?

  • Should resources be allocated in a more balanced way between treating metastatic cancer patients and minimizing through prevention the number of cancer patients who progress to metastatic disease? If so, what justice-relevant criteria should be used to limit our screening efforts and to limit our treatment efforts?

  • What is the fairest and reasonably cost-effective way of meeting the “transition challenge” as we sought to shift resources from aggressive treatment of metastatic disease to prevention aimed at reducing the number of future patients with metastatic disease?

  • Should we do Whole Genome Sequencing of every American early in life to establish a lifetime cancer risk score that would then be used to identify individuals most likely to benefit from more targeted preventive efforts?

  • Should we as a society invest in more research aimed at identifying biomarkers that would allow us to identify and predict more reliably which individuals with metastatic cancer would gain the most in life expectancy if provided with the relevant targeted therapies at social expense?

  • If we were successful in improving the survival of 75% of metastatic cancer patients for an average gain in life expectancy of three years at a cost per patient of $600,000 for those three years, should the resources needed to cover that expense come from the preventive screening efforts we have described?

Why do we need rational democratic deliberation to address these issues? The short answer is that all these questions are about public goods whose fair distribution or resolution cannot be fairly or adequately addressed through any private decisional mechanism. Does the Grail protocol that I described represent high-value care that would justify a very high level of social investment? This is not a question that can be answered fully by asking the relevant experts to work out the cost-effectiveness equations. Multiple other social values would need to be considered and trade-offs assessed that are not in the realm of any particular area of expertise. To be sure, lots of relevant expertise needs to be introduced into the social conversation, but the conversation itself should be a matter of inclusiverational democratic deliberation.

In the European context we would be asking the question whether a commitment to solidarity required public funding for the Grail protocol and permitted reducing or eliminating funding for targeted cancertherapies for patients with metastatic cancer. In the American context we would be asking whether a commitment to individual liberty meant that individuals should make the decisions for themselves whether it was worth it to them to pay for annual cancerscreening with Grail’s liquid biopsy. Alternatively, should annual liquid biopsy screening be seen as a public health measure, a dramatic measure to reduce premature deaths from cancer, for much the same reasons that we carefully assess the processing of our food supply or the introduction of pharmaceuticals to protect the health of all. This is a matter of equal concern and respect for all. However, this would be an additional $99 billion-dollar cost in the United States.

Where should that money come from? Should that money come from additional taxes or increased insurance costs? This is one option. However, it would raise the political and ethical question of whether giving cancer this “special” or “supreme” health status would be justified relative to many other possible healthinvestments in other disease areas where we might be able to save more lives at a lower cost. The alternative proposed by Dr. Raza would have us simply take those funds from what we now spend to provide these targeted cancer therapies and immunotherapies to metastatic cancer patients. It is easy to imagine the reluctance (maybe horror) many would experience in contemplating that option. Of course, nothing requires us to do annual screening with our liquid biopsy for everyone. We could limit that screening to some range of high-risk cancer groups in order to protect funds for treating metastatic cancer patients. However, we could then imagine the anxiety that would provoke in many Americans, knowing that their lifetime risk of cancer was 40% (maybe higher) and that the cancer that might afflict them did not present symptoms until a very advanced stage, such as pancreatic cancer. Finally, we might ask, given the emotional overtones expressed in these last few sentences, how we could possibly have a rational, civil, mutually respectful conversation about such controversial and emotionally charged issues. How could self-interest not corrupt and disrupt the possibility of such a conversation?

John Rawls (1971) introduced into discussions of political philosophy the notion of a “veil of ignorance.” Individuals behind the veil of ignorance would know nothing about their own social or economic or health status. We could imagine this as 330 million life slots in America today. Individuals would, however, know all the possible political, economic, and social structures and policy options that could constitute the basic structure of their society as well as the life prospects for various individuals living within that basic structure. Individuals behind the veil of ignorance would be charged with determining what the principles of justice should be that would determine the basic structure of society. They would know that, after they had achieved agreement, they would be randomly assigned to one or another personal identity in that society. Their life prospects in that identity might be reasonably good or somewhat less good. Their motivation behind the veil of ignorance would be to choose principles of justice that would maximize as much as possible in that framework life prospects for those who were socially and economically among the least well off.

Rawls has been criticized on the grounds that the veil of ignorance thought experiment is totally unrealistic because everyone knows what their interests are. Consequently, no such social conversation regarding justice is possible under that scenario since most people would argue for policies that would protect their personal interests. However, without going into any defense of Rawls’ overall views, it is factually true that the vast majority of us at any point in our life are largely behind a health status veil of ignorance. Even at my advanced age, I have no idea what my most likely health risks are or the most likely cause of my future death. Alternatively, we can pretend that in my early twenties I underwent a genetic test that indicated I had a 70% chance that I would die of some specific cancer before age 60. Would I then want all sorts of social resources allocated for research and treatment of my specific cancer?

In purely private moments I might answer that last question affirmatively. But if I am part of a social policy conversation regarding the allocation of health dollars for social health insurance, as well as prevention and research, I would be reminded by my fellow citizens that, if I seemed too single-minded an advocate for my cancer, many members of my family, as well as friends and co-workers, were vulnerable to many other health problems that could result in their succumbing to a premature death. I would also be reminded that I likely had forty years ahead of me and that I was vulnerable to lots of other diseases or serious injury related to accidents for which social resources would need to be allocated. It would be irrational for me to focus exclusively on my risk of that cancer. In addition, it would be unkind for me to ignore the health risks to which all whom I cared about were vulnerable.

I would also be reminded that I was engaged in this very broad social conversation regarding the allocation of health care resources. We could allocate as much money as we wished to meeting health care needs, not just my health care needs, but everyone else’s health care needs as well. However, if we wanted to increase the size of the health care budget to cover anything and everything in the way of treatment that might be offered by contemporary medicine, then I would have to be willing to pay unlimited sums as taxes or insurance premiums to make that possible. On the other hand, if I want limits on that budget and my wallet, then I would have to work with everyone else who is part of this social conversation to establish what sort of health needs will justify accessing that social budget to meet those needs.

I do understand what health needs are, and how unmet health needs can greatly disrupt or shorten a life. Consequently, I want allocation policies that are fair, compassionate, and that represent a wise use of limited resources. I want those policies to reflect the best medical and scientific knowledge that is available so that we are funding therapies that are most likely to be effective. I am certainly inclined to be mindful of the health care needs of my friends and family and acquaintances. It is more difficult to be very mindful of the health needs of the numerous faceless strangers who make up our society. However, I will be reminded that I am a complete stranger to all of them as well. I do endorse the view that every member of our society is entitled to equal concern and respect. I can imagine a situation in which at age sixty I am afflicted with the cancer that I have feared. I am not ready to die. I can imagine a targeted cancer therapy that would cost $200,000 and offer me only a 25% chance of six extra months of life. I would want to have that paid for from this insurance pool. Given a commitment to equal concern and respect, that would mean that I would have to be willing to absorb those same costs for all the other metastatic cancer patients who would want that costly treatment for a very uncertain marginal gain in life expectancy. If I thought that was a poor expenditure of my money for those others who are strangers to me, then they would have the right to make the same judgment regarding the cancer treatment I want for myself since I am just as much a stranger to them.

What this last paragraph illustrates is how, in reality, we can begin to achieve social agreement regarding health care priorities and corresponding limits. Individuals must be willing to be reasonable. If I want to be treated justly, then I must be willing to treat others justly as well. What counts as being “just enough” will have to be articulated through this process of rational democratic deliberation.

What keeps this deliberative process from becoming biased, dominated by special interests that skew the results unfairly? First, the relevant medical and scientific facts (such as they are at a point in time) must be rationally respected. Some facts are mushy, such as survival curves with most of these targeted cancer therapies, which adds to the complexity of social decision making through democratic deliberation. Second, there are what I (Fleck 2009, chap. 5) refer to metaphorically as “constitutional principles of health care justice.” These principles are intended to prevent majoritarian abuse and tyranny of those who are not capable of defending their basic interests. For example, in the United States today with employer-based insurance, many of these policies include very high deductibles and co-pays, especially with regard to these targeted cancer therapies. What that means in practice is that well-paid managers and executives can afford those co-pays and deductibles. Hence, they have effective access to these therapies. Ordinary workers would find it impossible to meet those requirements. Hence, they have no practical access to these therapies, though a portion of the cost of that insurance will be paid by them. In other words, they will be subsidizing access for the very well off. That would violate “equal concern and respect” as a constitutional principle of health care justice, which is to say that such a policy would not be an option for democratic deliberation, much less legitimation. It represents a form of exploitation.

Third, Rawls’ notion of “wide reflective equilibrium” constrains democratic deliberation as well (1971, 1996).Footnote 20 Complex policy choices typically have wide-ranging dispersed consequences. What needs to be avoided are policy choices that generate a more unjust situation than the situation a policy change was intended to correct. If enormous social resources flow into cancer treatment, research, and prevention and yield mostly marginally beneficial results, other areas of medicine can justly inquire why comparable resources are not available for treatment, research, and prevention where there is a greater likelihood of more substantial health outcomes. This is the sort of “imbalance” that needs to be avoided or corrected in order to maintain overall a wide reflective equilibrium with respect to the just allocation of health care resources. In the earlier portions of this chapter I have tried to illustrate the sort of imbalances between our liquid biopsy protocol (precision prevention) and targeted cancer therapies (precision medicine) that must be addressed.

Let me conclude with an illustration of how a deliberative question might be talked through. I assume we cannot afford to do that annual liquid biopsy for all adult Americans at social expense. I also assume we would not endorse providing only comfort care for metastatic cancer patients in order to afford the liquid biopsy protocol (given that some patients might gain several extra years of life from one or another targeted therapy). I also assume we would not endorse providing unlimited access to all cancer therapies, no matter how high the cost, no matter how marginal the benefit. All these assumptions are ethical and economic; all (I believe) are reasonable (even if not self-evident). That means we need limits and compromise in all three regards.

Can we come to agreement regarding when it is ethically permissible to allow access to either advanced cancer therapies or our preventive liquid biopsy on the basis of an individual’s willingness and ability to pay from their own resources? I think we could agree that if we can identify individuals at reasonable cost who are at significantly elevated risk for cancer, then those individuals ought to have access at social expense to our liquid biopsy annually. We will recall that any random American has a 40% lifetime risk of cancer. That is a significant number. However, if that is a number that triggers anxiety in a large portion of the population who demand annual liquid biopsy testing for a potential cancer at social expense, then we would be compelled to spend (wastefully) that $99 billion per year. What can be pointed out in the deliberative process is that 70% of individuals diagnosed with cancer will have it treated successfully and will not die of their cancer. We noted earlier that 40% of cancers are linked to behavioral choices by individuals. Increased efforts at public health education in this regard would be much less expensive than funding annual liquid biopsies.

Given this background, it would be neither unreasonable nor unjust to expect that individuals with very high anxiety levels regarding cancer could pay from their own resources the cost of annual liquid biopsy screening. Somewhat wealthier individuals would make this choice. Somewhat poorer individuals could not make that choice. Does that represent an injustice? I would argue that it does not represent an injustice because this is a very low-value intervention relative to all the other health care needs poorer members of our population might have to which they would have just claims, such as effective treatments for early stage cancers. In addition, the poor are not made worse off by the purchases of these liquid biopsy tests by the financially well off. Of course, we have to consider the fact that not providing this test at social expense will increase the number of individuals with metastatic disease relative to the 400,000 hypothetical individuals saved from metastatic disease in my scenario. What does a just and caring society owe those unfortunate individuals?

We owe these unfortunate individuals effective and cost-effective cancer treatments that yield significant benefit. As things are now, there are somewhat costly and somewhat effective treatments for many forms of metastatic disease. The very costly targeted therapies and immunotherapies are typically offered after these prior lines of treatment have been used, though many researchers and oncologists would like to see these targeted therapies become first-line treatment for metastatic disease. This might make medical, ethical and financial sense in some range of cases. This can then be seen as the trade-off for individuals who would have given up on endorsing social payment for the liquid biopsy option. Still, the implication of this view is that not everyone diagnosed with metastatic cancer will have access to these very expensive targeted cancer therapies at social expense. To preserve fairness and objectivity in this regard, we ought to fund research aimed at identifying reliable predictive biomarkers that would identify before the fact patients most likely to achieve substantial benefit from one or more targeted therapies, the precise definition of “substantial benefit” being left to the deliberative process. Again, the wealthy could buy access to targeted cancer therapies likely to be only very marginally beneficial. This does not represent an injustice to the non-wealthy who are no worse off as a result of permitting such purchases.Footnote 21

The limits we would collectively place on accessing targeted cancer therapies at social expense should be congruent with comparable limits we place on accessing comparable life-prolonging therapies in many other areas of medicine. As noted above, this is what would be required for maintaining a just reflective equilibrium in the deliberative process. Finally, creative options are possible. We could endorse a policy of permitting individuals who were hyper-anxious about their cancer risks (without any objective basis for that anxiety) to have annual liquid biopsies at social expense with the understanding that they would give up their right to expensive targeted therapies should they still be unfortunate enough to end up with metastatic disease. Speaking personally, I would not see this as a wise trade-off. However, in a liberal, pluralistic society that places a high value on maximizing individual liberty, so long as that liberty is not used to violate the equal rights of others or public interests, this might be an option that should be permitted.Footnote 22

In conclusion, it is reasonable for us, future possible cancer patients, to want both precision medicine and precision health. However, if we want both to the maximal degree that is technologically possible, we will create ethical, economic, and political challenges that would be ethically disruptive, economically unsustainable, and politically divisive. If we want a society that is just and caring, given limited resources and unlimited health care needs, we will need to define limits and legitimate trade-offs that are reasonable and “just enough.” Competing theories of justice, as articulated by philosophers, will be too abstract for the inherent complexities associated with health care rationing and priority-setting in the real world. What we require instead are fair, well-structured and inclusive processes of rational democratic deliberation to address these issues. Such processes are most congruent with what a liberal, pluralistic, tolerant democratic society aspires to be. The role of philosophers in this process is to guide the construction of public reason, that is, the rational capacities and value commitments necessary for sustaining effective civil discourse regarding the most controversial social problems a democratic society must address. Precision medicine, unguided by just public reason, will yield unhealthy public policy and noxious injustices in our health care system.