Personalised, Individualised or Precision Medicine: Three Unaddressed Socio-economic Hurdles

After the BRAIN initiative of 2013, in 2015 US president Obama announced another large scale government funding scheme for biomedical science, on so-called Precision Medicine. Just recently this initiative announced its first pilot study. Leaving the unfortunate terminological analogue of "precision bombing" (eventually known precisely for its lack of precision) to a side, precision medicine is basically nothing new compared to what's already been known among medical scientists as individualised or personalised medicine, except that the Obama initiative has added large scale so-called Big Data methodology to the mix. The vision (described in these reports by the European Science Foundation in 2012) is that of a new strategy in pharmacological treatment consisting of two broad dimensions:

• Individually designed choice and style of medication (types of drug, dosage scheme, etc), based on complex analyses of pretests of genetic and other factors of relevance.
• Vastly increased use of presymptomatic screening of people to pick up possible early fragilities disposing for or signs of illness, to then attack with the mentioned new treatment strategies in early stages.

I'll call these dimensions treatment and screening respectively below. Both offer tremendous scientific challenges, still mostly to be overcome. But in this post I'll be assuming that the science has been worked out and instead point to three seemingly rather difficult socio-economic hurdles for the personalised, individualised or precision medicine ultimate agenda to ever be realised. For, naturally, the endpoint is not about the science as such, but to take significant additional steps in bettering human health and the fighting of disease. For that to occur, the existence of scientifically demonstrated natural mechanisms and technological solutions is far from enough. There also has to be a realistic socio-economic production and delivery system with a potential to make the mechanisms and technologies further the ultimate aim.

Hurdle 1: Practical inconsistency and the societal costs of screening

The first hurdle becomes visible when appreciating that the two dimensions are bound to partly work against each other. This as the screening dimension, due to elementary features of statistics and scientific measurement, will most probably mean increased imprecision; the more potential signs of conditions that are picked up in more people, the more likely it will be that signals for possible disease are what is known as false positives, and the more likely it will be that any signal is untrue due to weak predictive value. This, in turn, is especially likely the more the screening dimension addresses conditions as these will be defined in the treatment dimension: these condition will then be increasingly rare (due to the increased precision and individualisation in characterising them), a factor well-known to decrease the precision of screening programmes. This, in turn, will mean that the screening dimension is very likely to boost two well-known problems in medical screening, overdiagnosis and overtreatment, both of which cost both money and suffering. That is, whatever possible increased effectiveness in the fight for health and against disease brought by the treatment dimension is likely to be undermined – overrun even – by these expected outcomes of the screening dimension of precision medicine. Anyone wanting to dig deeper into these kinds of problems are welcome to treat themselves to the wider and deeper explorations of Niklas Juth and myself in our book on the ethics of screening.

Hurdle 2: The medicalisation of life and the exponential increase of health care costs

The next hurdle is linked to the one just described and connects to the concept of medicalisation, which is the process through which we start to view aspects of our life as suitable for biomedical interventions. Medicalisation is partly driven by a well-known socio-psychological tendency of pathologisation of the previously normal, i.e. our tendency of starting to view negative aspects of life or society as seriously problematic to warrant practical attention (rather than merely generally pesty aspects of life as it happens to be, to be reckoned with as part of the normal variation) as they become increasingly rare. One example of this is how we now view the death of a person in Europe at the age of 60 a tragedy warranting serious concern about something having gone wrong, while only 3-4 decades back it wouldn't have raised many eyebrows, even less prompting any probing of fault. But medicalisation is also driven by other mechanisms, two of which are the increasing tendency of viewing risk and indirect indicators of possible future disease as equal to disease, and the increasing tendency of viewing the consumption of a biomedical product or service as the apt response to an increasingly wider sector of perceived problems in life. Especially the latter two mechanisms are bound to be driven by the screening dimension, meaning that increasingly many people can be expected to view an increasing amount of states of their lives as either equivalent to disease or fit for a biomedical response, or both. This forceful increase of consumer demand can then, by ordinary economic mechanisms, be expected to effect a surge in health care costs. However, this surge will at the same time undermine the ultimate aim of precision or personalised medicine, since the surging costs makes it less likely that people, insurers or public health systems can afford meeting the demand and at the same time take up the new treatments from the treatment dimension.

Hurdle 3: Exponential increase in treatment costs for uncertain value

This brings us to these very treatments and what I take to be the core of the vision of personalised, individualised or precision medicine, namely that a radically shrinking number of patients are to be subjected to selected treatments out of a radically increasing number of potential candidates, based on a new addition of test-batteries. As I pointed out not long ago in a post on the surge in drug prices in recent years,  the mere logic of ordinary business means that such a pattern of development will lead to drastic price increases of each personalised/precision product produced by the treatment dimension. Moreover, this effect will be stronger, the more that the treatment dimension turns out to be successful. Assuming full scientific success, it can safely be assumed to become exponential. The reason for this expectation is very simple: for any product it holds, that the fewer expected consumers, the more each product sale has to carry a larger part of covering the development and production costs and profit expectations making up the price necessary for commercial production to be at all viable. But, of course, this implies further scepticism as to whether the ultimate vision of precision medicine will ever be likely to be in sight. The treatment dimension will have to deliver huge increases of the effectiveness of treatments if this is ever to become even close to likely and even if we assume the scientific challenge to have been met it very much remains to be seen what this will mean in terms of actual effects, especially on common diseases such as auto-immune conditions (e.g., diabetes or arthritis), cancers, dementias and cardiovascular diseases. And, of course, the higher the target is set, the less likely becomes the scientific prospect.

In sum, both from the perspective of a private consumer, a health insurer or a state running a public health care system, the precision, personalisation or individualisation medicine visions, even if scientifically viable, look like potential dead ends from a socio-economic standpoint. At least as long as realistic strategies to remove or bypass the hurdles described above have not been presented. And then I haven't even started on such elementary health policy facts that most serious ill-health still depends on social determinants, quite possible to attack by political means, or that the brief historical paranthesis where we could stop worrying about ordinary infectious disease thanks to antibiotics is very close to come to and end rather soon. Political leaders would thus seem well advised to turn their gazes elsewhere than the currently unrealistic lure of a pharmacological industry that as always hunts a way to get us hooked, lined, sunk and landed for good in a trap of ever increasing consumption of ever increasingly unnecessary gadgets, while increasingly convinced of their utmost necessity. Instead tell them, sorry we can't afford it, but here's something we would really want, and maybe they will become more disposed to deliver something of actual social value and potential for promoting health. After all, the customer's always right. Right?

Further Complications with the US Argument for 'Punishing' Syria for Chemical Attacks: Hypocricy and Lack of Foundation

So, yesterday I had a post pointing to a piece by Udo Schuklenk, rather convincingly picking apart the US case for military attacking Syria as a 'punishment' for the current regime's alleged chemical warfare attacks against civilians. Today, I found two further reasons against any such idea, besides the numerous ones presented by Udo:

1. Articles in The Daily Mail, making public solid evidence to the effect that the UK, whose prime minister David Cameron has apparently swallowed president Obama's argument for an attack whole and unchewed and made motions in parliament to gain support for this line (to no effect, so far), has for many years when Syria was suspected of stockpiling chemical weapons agents, like sarin, exported ingredients for manufacturing exactly such agents to Syria with the government's and relevant agencies' open approval and license. The ingredient in question is one that in other contexts is perfectly innocent or benign, namely sodium fluoride (an ingredient in almost all tooth paste and sometimes added to drinking water to boost population dental health), but as here described, also a necessary bit in the manufacturing of sarin, which is exactly the gas claimed by the US to have been used by the Assad regime (and famous since the terrorist attacks in the Tokyo underground in 1995). It wouldn't surprise me one bit if also other of those countries now contemplating jumping onto the US attack wagon, at least if UN support can be produced, similarly have exported this or some other part of the alleged Syrian chemical weapons arsenal – in fact, I wouldn't be surprised if also the US government can be found to have done the same.

The relevance of this for Obama's argument is the following: If the Syrian regime is to be punished by a military attack (that will most certainly kill lots of people having nothing to do with the matter, besides being unlucky enough to reside inside Syrian territory – nobody believes in the fairy tales about precision warfare anymore), then surely a proportional punishment has to be directed at those that have aided and abetted such a serious act. That is, if the alleged action of the Assad regime is to be seen as a crime worthy of such a degree of punishment (including foreseeable collateral damages of substantial proportion), surely aiding and abetting such a crime must be viewed as deserving a punishment in the same ballpark, although at a more moderate proportion in the same way that assisting a murder deserves less punishment than the murder itself. Note that the argument that the aiding was unwitting does not hold up to scrutiny, since the UK and the rest of the countries here viewed Syria as a danger from the chemical weapons perspective already in those times and were fully well informed about the military application of sodium fluoride.

So, it would seem, that the same legal logic invoked by president Obama to motivate attacking Syria would force him to the conclusion that if, say, Damascus is to be bombed in punishment for the alleged attack, then some more minor part of the UK – say Middlesbrough or Bristol – should be in for a similar treatment.And it doesn't end there, for it would also seem that David Cameron himself, as a matter of legal logic, would have to accept and support such a conclusion. Lovely, isn't it?

2. Now, and this is something that dawned on my today, there's a basic fault of the whole attempt to try to make a legal argument in support of a military attack aimed at punishing a country's leaders or its officer's at lower levels for an alleged crime. This argument requires that due process is applied, and what Obama has suggested is far from that. Due process would seem to require that those that are suspects in the crime are apprehended for subsequent inquiry and investigation by the International Criminal Court – not that Damascus or whatever other place is contemplated by the Washington hawks as a fitting target is reduced to a pile of rubble, possibly killing the Syrian leadership possibly responsible for chemical attacks together with a huge bunch of other people, without anything even resembling trial. There is only one problem: the USA, for entirely selfish reasons, is on record as actively working against the ICC and its underlying idea of installing a legally secure institution for punishing war crimes and crimes against humanity. In conclusion: Obama's argument relies on the idea of applying due legal process and rule of law, while what he suggests is the opposite. Not only that, he represents a country that is an active enemy of the very notion of such rule of law.

So, in the end, it would seem that, even discounting for the blind eye towards those who have made the alleged chemical attack possible and the hypocricy implied by that – the entire attempt of the US regime and president Obama to dress up in legal garment what is, I suppose, in the end the same old 'preventive self-defense' rubbish as usual, fails even more splendidly than argued by Udo yesterday.

Now, should Obama change his mind and accept, as EU leaders now seem keen on, that an ICC-based due process handling of the alleged chemical attack of the Syrian regime is applied, as would seem logical in view of the legal argument made, such a due process would also have to include, of course, the crime of aiding and abetting such alleged criminal behaviour, which in turn would seem to imply that David Cameron and relevant ministers (of security, defense and foreign trade) should, at the very least, be held for questioning and possible a number of other governments should be in for the same treatment. A little something for the EU council of ministers to contemplate in their further musings on this matter.

What to Read to take a Stand on the Syria Military Attack Issue

I'm so happy that my bioethics colleague Udo Schuklenk of Queens University, Canada, and editor in chief of the journal Bioethics got around to writing this post. It's frankly the only thing you need to read to base a decided opinion on the issue of whether or not there should be a military strike against Syria, as has been so eloquently proposed by US president Obama in a recent speech.

Udo hits the head on the nail: if you're all for retribution whatever the consequences on the basis of arbitrary rules, then you should be for an attack - otherwise not. If you're that sort of soft bloke that, together with Udo and myself, actually thinks that what happens to people in Syria and other places should be the main factor to consider when making decisions like these, you might also want to weigh in the factor that Russia today declared that it will use the military capability of its warships , present off the Syrian coast, to rebut any attempt to attack from out side Syria, and muse a bit on the implications of that before picking your side.

Happy thinking!

US Stem Cell Legal Debacle the First Step In a Long Fight Based on Absurdity and Stupidity

Today The New York Times reported that US president Barack Obama's about one and a half year old turnaround of US policy on embryonic stem cell research has been halted by Chief Judge Royce C. Lamberth of the Federal District Court for the District of Columbia. Judge Lambert issued a temporary injunction against Obama's policy change that made federally funded research on embryonic stem cell lines legal regardless of when these lines were created. Before the change, federal funding (i.e. NIH grants) could only be granted to projects utilising cell-lines created prior to 9:00 P.M. EDT on August 9, 2001. The judge's argument for the ruling is that President Obama's policy change violates a 14 year old ban on the use of federal money for stem cell research involving the destruction of embryos. The complete ruling can be found here. US stem cell scientists have reacted with shock and the news have quickly waltzed around the world, giving quick and strong echo also in my own country (here, here, here, here, here, here, here, just to name a few), thus illustrating the importance of US policy in this area for scientists and clinicians all over the world, also in countries like my own, that allows stem cell research on the same conditions of ethical review as other types of human subject research.

Judge Lamberth's ruling is the direct result of a suit against Obama's policy change made by the so-called Alliance Defense Fund, a Christian lobbyist and legal activist organisation that describes itself as "defending the right to hear and speak the Truth". One may justifiably rant about the obvious absurdity of this claim in light of the fact that the suit against embryonic stem cell research is an obvious move to stop stem cell scientists to be able to find and speak the truth about stem cells and their role in the human body and impact on human health. However, at the same time, I was not surprised by this attempt from the world (in)famous US "religious right". After all, the basic ethical stance underlying this particular opposition to embryonic stem cell research is that the destruction of human embryos involved in creating the cell lines in question equals first degree murder. In consequence, using the products of such destruction for research equals a deeply immoral exploitation on the occurrence of what people holding this view logically has to regard as mass murder of the same epic proportions as the Holocaust, Stalin's terror and the "year zero" slaughter of Khmer Rouge Cambodia.

On the other side of the hedge, however, are all those people who do not subscribe to this extreme ethical view. Pointing to the enormous potential benefits to life and health of embryonic stem cell research they claim that even if human embryos are not "things" and worth protection (none of these people claim, e.g., that embryonic stem cell research should be unregulated or exempted from the requirement of research ethical review), the research is defensible.

In effect, we may probably look forward to a long legal battle in the US, Judge Lamberth's ruling being but the first step. But in the meantime we may ask about the ethical basis both for the ban on federal funding of embryo research and for Judge lamberth's application of this ban to stem cell research.

I must be honest and declare from the outset that US policy on embryo research has always struck me as part absurd, part plain stupid (no disrespect to US federal politicians intended, the stupidity is structural). This is not because I disagree with the basic ethical view on the moral importance of human embryos described earlier. That is, I do disagree with it, but even if this view is granted as an axiom, one would, I suggest, have to agree that US policy in this area suffers from a complete lack of supporting arguments. Having been involved in the academic ethics debate about embryo research as well as the process of political debate leading to the clear legalisation of embryonic stem cell research in Sweden in the early years of this century, I have had the opportunity to think about this topic once again recently, due to new research on the ethics not of stem cell research but that of regulating stem cell research, undertaken in cooperation with Daniela Cutas, and very recently published in the book Contested Cells - Global Perspectives on the Stem Cell Debate.

So let's start with the absurdity. The idea of the destruction of human embryos being murder, and the systematic such destruction thus being a case of genocide, does not directly imply that it is immoral to use cell lines resulting from such destruction for research or other purposes. For instance, even today, hospitals and doctors all over the world are making use of the results of the Nazi freezing experiments without any representative of the US religious right raising his voice in protest. However, we may also compare to how anyone of us would react if we learned that the hospitals of our country were making use of tissue and organs for transplantation that had been produced by the elaborate murder of people in other countries in order to obtain these organs and tissue. It is, I believe, in this vein that the opposition to embryonic stem cell research has to be understood - again, assuming for the sake of discussion the basic premise regarding the moral importance of embryos. Now, what is the logical conclusion of such a piece of reasoning? Well, I conjecture, it is certainly not that the sort of policy we find in the US is justified.

Consider the Bush policy of banning the funding of research on cell lines produced after August 9, 2001. As I understand it, the result of the ADF suit and Judge Lamberth's subsequent ruling is that this is the policy that is now in effect until further legal notice. However, this policy is not supported by the ethical argument just set out. This argument makes no difference between the destruction of embryos or the use of the cell lines thus produced on the basis of when this destruction and production took place. Murder remains murder even if it occurred before August 9, 2001, and what is, in virtue of the reasoning explained above, an immoral exploitation on the occurrence of murder remains so whenever the murder is supposed to have taken place. In fact, Dr. Cutas and myself conclude, in the chapter mentioned above, the only way to square the Bush policy with the view on the moral importance of embryos entertained by its supporters would be to revise the latter so that strong moral importance is attached only to embryos that exist after August 9, 2001. The absurdity of this sort of standpoint should be obvious even to the most nutty "pro-lifer". That is, had Judge Lamberth been consistent in his ruling, he would have invalidated not only Obama's but also Bush's policy on embryonic stem cell research. His current ruling is, in effect, genuinely paradoxical.

So, over to stupidity. This point regards not only US policy on stem cell research, but its entire legal take on all sorts of embryo research. Again, I'm assuming for the sake of discussion, the validity of the view on the moral importance of embryos already mentioned. Morally speaking, embryo research is in effect genocide. If true, this is excellent reasons indeed to ban embryo research, isn't it?! Indeed it is, however, US policy is not about banning embryo research. You may destroy human embryos by doing research or any other thing, as long as you are not funding your activities through federal taxes. Genocide is OK if you pay for it yourself!! In fact, it is well known among scholars studying the ethical, legal and social implications of genetics and reproductive technology that the chief effect of the US ban on federal funding of embryo research is that all activities where embryos are destroyed are now safely out of reach of any sort of regulation within the confines of the commercial secrecy of corporations and private enterprises. In consequence, embryos are being destroyed at least as much as ever, but due to the ban even farther off from the reach of the long arm of the law than before. This is simply stupid. Especially people who view embryo research as genocide should think so - on this basis, the conclusion has to be that the ban makes a bad thing even worse. And to get away from this stupidity, the only way would seem to lead back to absurdity; claiming that embryo destruction is not murder as long as US federal tax payers don't pay for it. Again, even the nuttiest of pro-lifer should recognise the absurdity of such a claim, and thus oppose and fight the ban regarding embryo research.