Take sustainability serious in healthcare to avoid harming future patients!

 

In a brand new blog post at the BMJ Journal of Medical Ethics blog, me, Davide Fumagalli and Erik Malmqvist write about a severe ethical challenge for healthcare systems that arises due to structural deficiencies in established systems for healthcare resource allocation: 

 Most countries with publicly funded healthcare systems have ethically informed priority setting schemes to decide how to allocate scarce resources. Established principles in such schemes recognise patients’ need of care, the effects of interventions, and background requirements of equal consideration and cost-effectiveness. However, the typical use of such schemes is alarmingly short-sighted, systematically allowing the future resource base of healthcare to be undermined. In short: our way of helping current patients is systematically exposing future patients to serious harm and risk.

As a remedy, we propose that a sustainability principle is added to estableshed ethical framworks that govern this central aspect of health policy. Read more about the challenge, as well as our proposal over at the JME blog!

 

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?

The Ethics of Pharmaceutical Pricing

I don't think I'm alone in having noticed in my own country – as well as throughout that part of the developed world where states run reasonably expansive publicly financed health service schemes – an increased political and general societal problematisation of the costs of new pharmaceuticals.* The background to this increased focus is doubtlessly complex, but four aspects stand out as especially relevant explanatory factors. First, there is the generally splendid public health situation in these countries, with ever increasing average life expectancy and declining morbidity rates at the population level,** but with the side-effect of more and more of this increase being effected by reparative treatment of chronic, aging-related health problems, rather than primary prevention of basic health problems. Second, there is the next step in pharmacological development strategy, whith drugs targeting more and more specific and limited groups of patients and conditions, as a side-effect also providing treatment for extremely rare and serious diseases which have before been a dire fate to bear, with very limited treatment opportunities (many of these monogenic diseases which have been virtually untreatable). Third, there is the increased focus on rationality and ethics of public spending and the organisation of health services, effecting a greater transparency, control and regulation of the assessment, introduction and prioritarisation of new treatments. Fourth, there is the pricing policies of pharmaceutical companies, in extension reflecting the chosen expectations of return on investments of their owners. This post is about the fourth of these factors.

In most discussions of public policy in this area, this fourth factor is and has for a long time been treated as an immovable state of nature. There are three basic reasons usually presented in favour of that stance: First, commercial businesses have to be assumed to act as commercial businesses and strive to maximise profit for their owners, and are – in fact – in most jurisdictions required by law to do so. Second, if pharmaceutical companies would not be allowed to act in this way, they would soon be deprived of investor capital (as this would move to more profitable areas), and this would cripple the development of new drugs. Third, states are not capable of taking on the task performed by pharmaceutical businesses today; if they would, the result would soon be either an even worse cost crisis, or declining development and production. I think that the third argument is worth some critical discussion, especially in some areas of particular societal importance – such as vaccines – but in the present context, I will let it stand unquestioned for the sake of discussion. That is, I assume in the following that states are indeed dependent on private business solutions to have an effective development and production of pharmaceuticals.

But what about the other two arguments? Lately, these have been questioned in the context of debates in several countries about the pricing of a drug called Soliris by its manufacturer Alexion, targetting the rare and very serious hereditary disease Atypical hemolytic-uremic syndrome, or aHUS. In several countries, agencies responsible for assessing the evidence base, cost-efficiency and priority of new drugs have expressed serious complaints about the high price (here, here, here, here). In several of these cases, the national health services have eventually chosen to introduce this drug any way, in order not to have heavily burdened patients caught in the fight between health institutions and drug companies. But the change of tune with regard to pharmacological companies is notable, and raises the more general question of the plausibility and validity of the two arguments above.

I will claim that, given that the thesis supposed to be backed up by the arguments is that national health services, governments and related agencies have no reason to apply normative (ethical or political) judgement regarding the pricing of pharmaceuticals, my assessment is that while both arguments are plausible (as in likely to be true), they are invalid (as in not supporting the conclusion). I will support that claim with two arguments, one ethical and one political, and then sign off by pointing to some complicating factors that I think are mostly overlooked in health policy debates.

1. Even if commercial companies lack moral obligations, their owners don't
It may be debated to what extent commercial companies have moral obligations and, if so, which these are. Most countries have set up a system where, in Milton Friedman's famed words, 'the business of business is business' – that is, beyond keeping to the limits of criminal and necessary civil, and administrative law, commercial companies are not to mind about anything else than meeting the profit expectations of its owners. Based on this, a company may, of course, chose to abide by one or the other moral judgement, but only to the extent that it is thought to be a sound commercial strategy as defined above. Also, while thus using business only for its expected good outcomes of business (usually increased productivity of goods and services), a state may take political action to compensate for its bad side-effects, e.g., with regard to public health. In recent decades, this 'separation thesis' regarding the obligation of commercial companies (to maximise profits for its owners inside the realm of the law) has been questioned as both increasingly irrelevant (due to globalisation, which enables companies to move freely between jurisdictions in an amoral manner, thus emptying the content of the requirement to abide by the law) and for its inability to reply to increased arguments coming from the area of business ethics, corporate social responsibility and political philosophical observations that the separation thesis assumes a demarcation between the realms of business and that of basic public concerns which is simply not to be had.

However, even if we would grant the idea that companies have no other moral obligations than meeting the profit expectations of their owners inside the realm of the law, it doesn't follow that national health services, governments and related agencies have no reason to apply normative (ethical or political) judgement regarding the pricing of pharmaceuticals. This since the separation thesis does not in any way undermine the claim that owners of businesses have moral obligations and ethical reasons to behave considerate towards other people beyond what the law may require. Or, it may do so in the first instance, as many owner's are institutional business parties (banks, funds, and so on), but at the end of the day, there will be actual and quite ordinary people, and these have the same moral obligations as anyone else. In fact, it would seem that the whole idea of the separation thesis rests on the assumption of a well-functioning society within which businesses may operate, and a core part of such a society is that people act decently towards one another. This implies, e.g., the recognition  of basic and reciprocal civic obligations of due diligence, duty of care and general consideration to other people – all stretching beyond what is strictly required by law. Just start to imagine what walking along a street in a city would be like absent such basic cultural arrangements in place. Likewise, imagine a society were no individual assisted another in need according to such principles. I take it that no one would disagree that we hold these sort of moral obligations to one another. However, if we do, these don't just magically disappear if we happen to open a shop or purchase some company stock. Even if not required by law, as owners of businesses, we are still bounded by ethical considerations to other people, e.g., to care for those in dire and undeserved circumstances.***

So how does one discharge these moral obligations in the role as owner of commercial enterprise? Well, since the enterprise itself – a company – works according to the main principle of realising the profit expectations of the owners, the lever available to an owner seems to be exactly these expectations. That is, the material outcome of the duty of the company towards its owners being discharged can be manipulated by the owners' communication into the company structure of what level and rate of return on invested capital is being expected. This creates ample room for an owner to have ethical reasons to adjust such expectations in view of reasons beyond those of "pure business". Transferred to the case of pharmaceuticals, this line of reasoning results in the conclusion that, to the extent that this is required by our normal set of ethical reasons to be considerate towards each other, an owner of such a company has a reason to decrease his or her expectation of return on invested capital, whether in terms of level or rate. In both cases, such an adjustment will enable the company to adjust its pricing downwards without defaulting what it owes its owners. To be true, such a reason need not always be available, but in the case of drugs for very serious diseases, it seems quite reasonable to claim that it does. Note also, that the reasoning can be applied also to argue against withdrawing investment, thus diffusing the argument that reducing profit margins to enable lower pricing would effect investment flight. Maybe it would, but it still holds that investors should not thus flee a slightly less profitable investment that would mean meeting one's general moral obligations to other people. I made this argument myself, in the Swedish debate around Soliris.

In conclusion, the idea that there are sound and valid normative (ethical) claims to make with regard to the pricing of effective drugs for very serious diseases holds up to scrutiny. The (assumed) facts that "the business of business is business" and that (potential and actual) owners of pharmaceutical companies do as a matter of fact not currently seem to act in accordance with their moral obligations (maybe partly because these have not been recognised) do nothing to undermine this claim. Owners of pharmaceutical companies owe it to very sick people to adjust their profit expectations to enable more modest pricing, and potential owners owe the same people not to withdraw from investment due to this obligation.  

2. States owe their citizens not to be money pumps
The second argument does not target individual people in their role as (potential) owners and investors, but rather state institutions in their roles as counterparties in business negotiations. This argument is entirely independent of the first one, and will hold up even if the former would be shown to be somehow faulty. The argument does, however, assume that pharmaceutical companies are behaving more or less according to "the business of business is business" pattern, with owners who as a matter of fact do not moderate their expectations on return on invested capital as they should. Should owners start to behave more in line with their moral obligations, the validity of the present argument will be undermined (although it is still sound).

The behaviour of pharmaceutical companies with regard to pricing of drugs as just sketched means that they try in every instance to find an optimal equilibrium between the price per sold item and the number of items sold. This is the reasons why the so-called "list price" of new drugs is in most cases much higher than the price eventually paid by public health services; the company sets an exaggerated price as it expects a negotiation where the price will be decreased in light of consumer demand, as expressed by the public agencies doing the state's bidding. In my own country, where up till recently, this bargaining has been undertaken by each single county government (responsibly for its health care service region), companies have thus been very savvy at, insisting on commercial secrecy around the agreed price, play all these counties against the middle to maximise bargaining outcome. From a political ethical standpoint, to have state or county agencies – and ultimately tax payers – thus being allowed to be played for suckers is simply unacceptable. For what it means is that the state – in view of the never ever ending demand for health care – allows commercial parties to milk its treasure chest dry. In more technical sense, the state thus allows itself to be what experts on economic bargaining rationality and game theory call a money pump – someone who applies a bargaining or game theoretical choice strategy that systematically leads to a losing position, albeit each single move may appear winning, given the circumstances.**** The argument that one should avoid such strategies (technically, to avoid dutch book strategies) has given raise to the discipline of dynamic choice theory, and is a standard motivation, e.g., for why it is irrational to apply decision strategies that make one succumb to blackmail – as each concession of a black mailer's demands (no matter of well motivated in the single instance) makes it rational for the blackmailer to continue the blackmail and increase the demands. In the case of negotiations about the price of pharmaceuticals, the state or responsible public agency becomes a money pump by being overwhelmed by the reason to accept the offered price presented by needs of single patients, and thus not considering the option of declining the offered product as a live option. Just as the blackmailer in the analogous situation receives increased reasons to continue the blackmail and up the stakes, the pharmaceutical companies are thereby reinforced in their reasons in terms of business logic to increase prices even more, and thus increasingly bleed the public health services budget.

I take it that everyone agrees that a state and its agencies owe it to their people to avoid such positions. As a matter of fact, since the rationality of avoiding being a money pump is so basic, this would seem to hold even on the super-thin libertarian idea of the state as a security business enterprise of its citizens (which I take most people would want to go beyond). But to do that, the state has to create a bargaining situation where the counterparty counts a declining of its offer as a live option to be calculated with. And to create that situation, the state needs to actually decline offered services also when they are necessary to meet important needs.If they don't, the companies will not view such a declining as a live option, and will thus be motivated to increase the stakes. Now, this does not necessarily mean that it is in case of effective orphan disease products such as Soliris, where the most urgent need for such demonstration of actual bargaining power is called for. Rather, one would find it more acceptable to decline state subsidising of treatments for far less serious, albeit more widespread conditons, although that may not harvest much of political popularity. But if the state never says "no" to anything, the money pumping result will eventually affect the entire public health service supply, and it is not unlikely that before long the willingness of citizens to fund very expensive treatments for conditions that strike only very few will falter as a result. Moreover, as more and more drugs for all sorts of condition (many of which will not be as extreme as aHUS) can be expected to become "orphan" in the sense of targeting only very specific patient groups, or add only very minor therapeutic effects (and often considerable side-effects) to serious conditions which are inevitably killing patients very shortly (as is the case with many new cancer medications), the fact that the targeted condition is either rare or very serious cannot by itself be a disclaimer from applying a rational bargaining strategy that also takes into consideration therapeutic effect, cost and opportunity costs in terms of what other treatments to other conditions may may be funded by the same money.

In any case, however, the many difficult priority setting issues which follow from the state and responsible agencies thus taking its responsibility to citizens are handled, the fact remains that the state does have such responsibilities. As much as society has reasons to allocate resources to be able to offer its members publicly available health care services, it has strong obligations to the very same members not to unnecessarily waste these resources. Avoiding the money pump position in relation to pharmaceutical companies seems like an elementary part of performing that duty.

3. Where we are in all of this
In conclusion, there are two separate arguments for the existence of valid and sound normative reasons to apply to the pricing of pharmaceuticals by commercial companies. Both assume only a very minimal idea of ethical and political reasons, which should be acceptable across most otherwise competing ethical and political positions and ideologies. However, there is an interesting dialectic between the arguments, hinted at when I wrote above that the second argument gains in validity to the extent that the first argument is ignored by the acting parties – owners of and investors in pharmaceutical companies. But who are these owners? As pointed out, in the first instance they are probably mostly banks, investment and holding companies, funds and so on, but at the end of the line there will of course be actual people (who hold the ethical obligations claimed in section 1 above). Some of these will, of course, belong to the fabled 1% of repugnantly rich, but most of them won't. In fact, most of them will be like you and me, people who has a bit of insurance, a bank account, a small slice of a pension fund (no matter how modest), loans, maybe even some stock. And even if our possessions of this sort are very modest, we are benefiting from a public health services system, which include funds where the capital to pay for and subsidise pharmaceuticals and public health care investments is stored and managed, and we may even be due for a bit of minimal public pension from funds equally so taken care of to be able to deliver what was originally promised. In other words, we who gasp at the indecent pricing of pharmaceutical companies are the very same people who in section 1 above were claimed to have moral obligations to lower their expectations of return on invested capital. In view of the apparent fact that this seems to imply that most people have to lower their pension-, insurance, savings- and welfare demands, one may quite plausibly doubt our collective capacity to effect such an adjustment, no matter how persuaded we are of its rationale on a theoretical level.

Therefore, as in so many other cases, the most rational solution would seem to be the second one: to press the reasons for the state and involved public agencies to apply effective and rational bargaining strategies against the pharmaceutical companies. Of course, to have effective such systems, it is rational to abandon the subsidiarity system, where each county government make their own bargain, and centralise the process nationally. But that's only the first step, of course, as the same logic tells us to accept multinational bargaining cartels, possibly across the entire EU. That will probably have quite a bit of bite, although it will also necessitate difficult issues of health care policy priorities, due to the need of sometimes actually saying no to the offered goods. Moreover, it will, as in so many other cases where we are unable to do collectively what we should be doing together, force us to accept the concessions (in terms a lowered returns on investments, savings, pension fund, insurance benefits, what have you) we were obliged to accept by ourselves, but failed to do.
  

*) There is, of course, a comparably much more pressing issue about the cost of and access to pharmaceuticals in developing and/or economically deprived settings. This issue has attracted the attention of ethical reflection for a long time, and there is a rich debate addressing its many levels to dip into for whoever feels like it – just make some searches using "orphan drugs", "orphan disease", "ethics" and "access to healthcare in developing countries", and you're set.

**) Granted, there is also in many of these countries stark health inequalities. However, if we plot the curves from the start of these modern health policies at the beginning of the 20th century, even the worst of worst-off groups of today come out considerably better. This is not to say that inequalities of the present are unimportant or that it shouldn't be a priority to decrease them, and to lift the worst off even higher (it should!). But the point remains that also the worst off of today cannot be made much better by primary prevention, but will also need the same shift to expensive reparative treatment of basically incurable conditions and mere aging. 

***) The qualification of "undeserved" is inserted merely to silence objections based on considerations of desert.

****) The classic "money pump argument" regards only the case when such a strategy is the result of a choosing party entertaining intransitive or "cyclical" preferences, and used to motivate why a rational actor must avoid such preference structures. However, the argument apparently rests on the assumption that being "pumped of one's money", as may result in this instance, is a general fault to be avoided by a rational actor, no matter the explanation.

This is Huge: Serious Research Misconduct in Almost 3/4 of FDA Inspected Clinical Trials – Hidden by Both Inspecting Agency and Researchers

First I had problems taking it in: Almost 75% of US clinical trials inspected over a period of 15 years by the Food and Drug Agency, responsible for upholding regulation in this area, display serious misconduct of various kinds. It can't be that bad, I asked myself; if it was, I would have heard something about it before – research ethics in medicine being one of my areas of expertise! Except that I wouldn't, since neither the FDA nor the researchers in question have reported these stunning findings to the outside world. That is, until Charles Seife, an MD but also a journalist, decided to have a look at FDA documents of some of the made inspections between 1998 and 2013. What he found is reported in a recent article in the journal JAMA Internal Medicine, where out of originally 600 trials, 101 where identified where the FDA had found strong reason of issuing complaint, and among these:

Fifty-seven published clinical trials were identified for which an FDA inspection of a trial site had found significant evidence of 1 or more of the following problems: falsification or submission of false information, 22 trials (39%); problems with adverse events reporting, 14 trials (25%); protocol violations, 42 trials (74%); inadequate or inaccurate recordkeeping, 35 trials (61%); failure to protect the safety of patients and/or issues with oversight or informed consent, 30 trials (53%); and violations not otherwise categorized, 20 trials (35%). Only 3 of the 78 publications (4%) that resulted from trials in which the FDA found significant violations mentioned the objectionable conditions or practices found during the inspection. No corrections, retractions, expressions of concern, or other comments acknowledging the key issues identified by the inspection were subsequently published.

 Seife concludes:

The FDA has legal as well as ethical responsibilities regarding the scientific misconduct it finds during its inspections. When the agency withholds the identity of a clinical trial affected by scientific misconduct, it does so because it considers the identity to be confidential commercial information, which it feels bound to protect. However, failing to notify the medical or scientific communities about allegations of serious research misconduct in clinical trials is incompatible with the FDA’s mission to protect the public health /... /

To better serve the public health, the FDA should make unredacted information about its findings of research misconduct more readily available. The agency should make sure that any substantial evidence of misconduct is available to editors and readers of the scientific literature /.../

... most of the burden for ensuring the integrity of the research in the peer-reviewed literature falls to the authors of the articles submitted to peer-reviewed journals. Currently, there is no formal requirement for authors seeking to publish clinical trial data to disclose any adverse findings noted during FDA inspections. Journals should require that any such findings be disclosed.

The nail on the head if there ever was one, and Seife is backed by an editorial, signed by three strong voices from the Yale and UCSF medical schools. FDA is liable to serious criticism for not proactively informing the scientific and medical communities, as well as the general public, of these matters. Journals which not immediately effect the standard indicated by Seife would deserve equally serious criticism. But the worst of all is the fact that such journal policies would be needed in the first place. 

The by far heaviest burden of criticism befalls those researchers, many of which have not only committed scientific fraud and serious ethical breaches, but have all in addition consciously choosen to actively surpress highly relevant information about the quality of the studies they have conducted. Not only is this relevant for the publication screening at journals to safeguard the quality of scientific publications. It is even more relevant for the assessment of the results reported in publications for the purpose of, e.g., licencing or decisions on clinical use, or public funding. These researchers have sold their scientific credibility and honour to whatever bidder (in the vast majority of cases, one suspects the pharmaceutical company funding the study) have incited them to keep mum. People doing such things have no place in either the academic or the medical community.

Seife has a popular report of the significance of his study in Slate, here.

This is, as far as I can see, a major research ethics and regulatory scandal, and it might just be hiding an even larger one. For, given the frequency of serious misconduct now revealed, one may very well ask what would be found if FDA was to cast its inspection net wider and inspect even more trials. And what would be the outcome of similar procedures in, e.g., Europe or Asia?

UK Medical Records Sellout Delayed: NHS Realises It Needs to Inform People of their Rights

So, some of you may recall my rather negative comments on a UK national plan to make NHS medical records which are not even fully anonymised available to not only research universities, but also – totally unnecessary from a medical research standpoint – private industry in the pharma and insurance fields. This in spite of the fact that it takes just a few snippets of information combined with a medical sample to correctly trace the individual from whom the sample has been taken these days. Former posts are here, here and here. A very recent report in the Guardian is here.

Yesterday, the BBC reported that the plan – which unnecessarily jeopardizes the interests, integrity and liberty of masses of people, besides putting them at risk of being discriminated against for health reasons – has been delayed, since the NHS "has accepted the communications campaign, which gives people the chance to opt out, needs to be improved". That is, the "campaign" consisting of no information at all whatsoever, and which was made public only thanks to some vigilant bloggers – especially MedConfidential. The "campaign" consisting of the NHS apparently deliberately making its very best to hide from the public that they have the unconditional right to opt out of the whole scheme and how they may go about claiming that right. No wonder that the lead-heavy players in the field such as "The Royal College of GPs, the British Medical Association and patient watchdog Healthwatch England have all voiced concerns".

The plan is to devise an information campaign, which – lets hope – actually informs people about their right and gives them as easy access to the form to fill out to opt out as they facilitate the sellout of patient medical details and records. By August it will all be ready to roll-out the system, the responsible ones promise. I believe it when I see it.

Just in case they don't: here's once again the link to all you need to opt out. If I lived in the UK, I certainly would fill out and hand it in immediately! The inconsiderate hurry, carelessness and obvious money-hunger of the forces having pushed this setup into place inspire everything but confidence and trust. I'm sure there will be more to come eventually.

UK Set to Sell Out it's Population's Medical Data and Records to Private Industry and Health Insurers

I posted almost a year back about a then apparently more restrictive, but to my eyes still outrageous, move of the UK government to frivolously open up a genomic database created out of the medical records and samples collected within the NHS in the course of normal health care (for diagnostics, safety and quality assurance purposes) for research not only by public research institutions, but also private companies in the pharmacological and medical technological area. Now, if this lengthy account is to be belived, it transpires that, apparently, the data base, which is due to be launched later this year, is not only genomic, but simply a general health research database created out of the entire medical history of the entire NHS "cohort", complete with rather specific personal information. It will not contain straightforward identification of individuals, but even government spokespeople admit that the "pseudo-anonymization" planned to be applied allows any research institution with access to a lot of informationto re-identify individual people, not even mentioning at all the recent discovery that just a little bit of genetic information together with publicly available online information can be used to trace people who have anonymously donated tissue to research.

But that's not the end of it: among the players which will be eligible to apply for access to this goldmine for – true – advanced medical knowledge and – equally true – the health business opportunity of the century are – hold your breath – health insurance companies. Yes indeed, the very same one's who are widely known to do their very best to exclude those people who are in most need of their product from buying it and to refuse paying out compensation if they are ever accidentally let in. These are the ones who the UK government and the NHS experts behind the new Health and Social Care Information Centre (which will be responsible for handling the database and provide the access) think are suitable parties to be helped to identify the heath frailties of individual persons, their children, family and so on. Mark Davies, who is something as peculiar as the "public assurance director" (let that one roll around your palate for a second, doesn't it taste a bit like "top blinker"?) of the HSCIC, pressed by reporters, admits a "theoretical risk" – apparently having never entertained the obvious thought that for an insurance company, identifying people's health risks as part of the general process mentioned above is a rational business procedure. If it's possible (and it is - even more easy than admitted by Mr. Davies), it will be standard procedure for a number possible purposes – everything from even more effectively than now screening people in need out from health insurance or compensation payment, to restructuring existing insurance schemes to more effectively weed out the potentially unprofitable customers by having no product that suits them. The "assurances" about transparency ring hollower than ever before as Julia Hippisley-Cox speaks of the right of people to be able to know who sits on their data and a "clear audit trail". Won't matter much when coverage of your recent surgery bill is being refused, will it?

Not very surprisingly, there's been criticism and debate, but the UK government seems to entertain no plan of setting a few sensible safeguards for those ordinary people who are supposed to profit from the scheme in place. Such as forcing private industry to commission any research using the database from public research institutions – thereby making redundant the reckless move of transferring data into the commercial secrecy protected hands of these far from public interest oriented parties, where as critics point put, no one will know where they will then go or how they will be used.

Read more here.

Senate Probe into Pharma Sponsoring of US Bioethics Center

The last few days, a buzz in the world of bioethics has been about the inclusion into a US Senate probe into the ties between the pain-killer pharma industry and various "medical" and patient interest groups, of the Center for Practical Bioethics, to quote their webpage, "a nonprofit, free-standing and independent organization". The CPB is particularly known in the US for its direct outreach and activism visavis politicians, health care institutions and the medical establishment - not least in the area of end of life and palliative care.

The probe specifically targets the possible ways in which painkiller producing pharma companies, among which are giant Johnson & Johnson, via financial donations and in other ways, have had the mentioned groups - among them CPB - inspire and/or promote "misleading information about narcotic pain-killers". In short: the suspicion is that the companies have paid the organisations money to play up the reasons for using opiate based painkillers (e.g., morphine) or palliative meds that function like opiates, while playing down the salient negative side-effects and risks of such drugs. The background of the probe is said to be "an epidemic of accidental deaths and addiction resulting from the increased sale and use of powerful narcotic painkillers.".

The tie to CPB is thereby established by its well-known and long-term advocacy of effective palliative care and pain-relief. The center's founder Myra Christopher holds the Kathleen M. Foley Chair in Pain and Palliative Care at CPB, sponsored by the company Purdue Pharma, manufacturer of OxyContin and other palliative drugs. According to the Kansas City Star, CPB is well known for its ties to Purdue Pharma as well as several other pharma companies:

...as recently as last month, Purdue was a leading sponsor of the center’s annual dinner and symposium, contributing $25,000 of the $280,000 that the event raised

Myra Christopher is one of the experts mentioned by name in the letter announcing the Senate probe.

Also The Washington Post has reported about the probe, and a longer version of that article can be read here. A particularly fishy part of the story expanded on there is that, as the probe was announced, The American Pain Foundation, self-described as "the nation’s largest organization for pain patients", and one of the organisations targeted by the probe, announced its own shut-down due to "irreparable economic circumstances". From the bioethics and CPB angle, this becomes extra uncomfortable, since Myra Christopher has held honorary positions in APF.

Further details about some publications/reports of Christopher that have had a role in advocating expanded use of strong painkillers, or to play down the ethical importance of, e.g. addiction risks or calling into question routines for monitoring patients who are on painkillers for such risks, can be found in the second half of the Kansas City Star article, which also contains comment by bioethics researchers Carl Elliott and Summer Johnson McGee.

Both of these hold out that the notion of pain and suffering as a health problem in its own right is fully defensible one. In consequence, pain can motivate medication that brings various health risks – just as risk of dysfunction or death can. However, the Senate probe does not seem to question this general point. Both Johnson McGee and Elliott also point to the practical problems created by  a supposed academic and independent institution advocating policies of great financial benefit to certain parties while, at the same time, being funded by these very parties. My own take is that, even if the money does not lead to outright and calculated intellectual dishonesty or fraudulent behaviour, human psychology has to be taken into account. The money arrives because the funding party likes what one is saying and as one becomes increasingly dependent on the financial support, one will (like it or not, conscious or not) become less and less likely to say something else.

Christopher is reported as insisting that the money from Purdue Pharma always has arrived with "no strings attached". It remains to be seen if the Senate probe will unveil information consistent with that claim or not. But even if it did, that does not take away the problem described above, and to me, the problem with CPB financial dependence on the pharma industry grows as the quote hints that Christopher does not realise this elementary point.

Read more here: http://www.kansascity.com/2012/05/11/3607147/senate-panel-studies-bioethics.html#storylink=cpy

Pharma Corps put Money Before Swedish Women's Health, But Why Be Surprised?

Today, the Swedish branch of the international pharma corporation GlaxoSmithKlein (GSK) announced that it will appeal the decision of the united health care regions of Sweden to use the vaccine product of their competitor Sanofi Pasteur MFD (SP), Gardasil, over GSK's Cervarix. The decision is another stalling maneuver in a longwinded process following the decision of Swedish public health authorities to provide young girls and women with a publicly run vaccination programme against Human Papillomvirus (HPV) – causing both cervix cancer and STD's, such as condyloma. It is unknown how long the processing of the appeal will take, but the financial director of GSK in an interview alludes to an earlier court process (see below) that took about 18 months. Thus, due to GSK's decision today, during this time-period potentially all Swedish young females will be provided with no protection against HPV. Possibly, some of these will buy a vaccination with their own money, but that can hardly be credited  as an upside to GSK's decision, given that they could instead have received it for free.

However, this is not the first appeal in this story. In fact, the decision that GSK is now appealing is the result of a former appeal that SP made against an earlier decision to purchase Cervarix. Also in that case, the material effect of the appeal was endangerment of many, many young women's health. Both companies of course argue that their product is the best, but that's just smoke. What they do is to repeat their sales pitch, but now publicly rather than in the original business bid. In the case of GSK, they even have the poor judgement and tasteless arrogance of trying to present their bid as objective argumentation in a debate article. Come on! The assessment of these bids is the business of the buyer, and if the buyer makes a bad decision, that's where the responsibility is to be placed. However, the buyer of a large public health policy order has many things to balance. Of these the effectiveness of the product is, of course one. But effectiveness is a complex matter and in the case of HPV very much so, since different strands of HPV link to several different health problems. In addition to that, the expected effect has to balanced against the cost. This since, at the end of the day, every Swedish Crown spent unnecessarily is a crown that could instead have been spent on other important public health undertakings. Given this situation and given that all information from the bid-makers have their basis in the self-interest of a business organisation (which in the case of becoming a part of a large public health undertaking is huge), the argumentation like the one presented by GSK today is simply not credible. Of course, they have to say that they believe in their product, just as SP has to. But so what? Regardless of this, the buyer has to make an assessment and a decision. What the appeals create is only that this procedure has to be done all over again, the first time by the buyer (according to procedures prescribed in Swedish administrative law), and this last time by a court of law. In neither of these cases will the repetition of GSK and SP of the claim that their product is the best one mean anything. The whole process is so absurd, that the responsible politician for the process of buying the vaccine, Stig Nyman, today urges the government to change the regulation around purchase of health products by the public sector, so that the armies of lawyers of the pharma corps are barred from obstructing orderly processes of great benefit of the public to proceed. Similarly, in Sweden's foremost politically conservative news paper, Svenska Dagbladet, otherwise notorious for its overly charitable interpretations of the intentions and doings of private enterprises, the deadly outcome of GSK's decision is underscored and the analysis is made that the pharma area of business is in fact nothing but callous, inconsiderate and deceitful.

Now, GSK has realised that the decision to appeal yet another time does not put the company's image in a very good light and therefore tries to give an impression of having taken the decision greatly troubled and burdened by ethical considerations. All pharma corps nowadays do their utmost to project such an image of caring about the health of people and minding about ethics, and GSK is no exception. However, is this more than mere branding (a question that applies to SP  just as much, of course)? One of my department's most successful young researchers, Joakim Sandberg, wrote his PhD dissertation Ethical Investing: Making Money or making a Difference? (and numerous papers) on the issue of how much the projected interest of being "ethical" used as a marketing tool by companies in different branches (using the case of investment funds) is grounded in any substantial ethical commitment. The sign of such a commitment is double: (1) that the company has a clear, publicly accessible and plausible idea of the criteria for acting ethically defensible (most of the book is about what that implies) and (2) that this idea at least sometimes is actually motivating the company to make decisions that are less than optimal in business terms. Simply put, if you are not prepared to sacrifice anything for your ideals, you effectively have no ideals. Not surprisingly, perhaps, it appears that the examples of business operations projecting the image of being especially ethical and at the same time meeting condition (2) is a rare species indeed.

In the pharma area, there are numerous examples of this phenomenon. In fact, the list of cases is becoming so long and depressing that the mechanical repetition of the public relations departments of all of the pharma corps around the world that good ethics is a key endpoint of their enterprise is starting to sound like the gibberish of a mad clown who no one think is funny anymore. Just a few years back (before I started this blog, or you would have read about it here), Astra-Zeneca was exposed in a major research ethics scandal,  where they had deliberatly chosen to conduct a clinical trial of psychiatric drug in a country (Russia) that insisted on a placebo arm of the trial, although an existing efficacious treatment was in place. In effect, half of the participants were left with no rather than some treatment and a number of suicides had to occur before A-Z had the sense to abort. What is more, they did this not in order to have a license for the drug in Russia, but to have it in the EU. I and several bioethics colleagues in my country had no problem in harshly criticising A-Z (here, here) and the lame response from A-Z was that they indeed were an ethical company, since they had abided by Russian research ethical regulation - thus pretending that they carried no responsibility for having chosen (obviously for economical reasons) to house the trial in Russia in the first place. This is just one among many, many cases of what in bioethics circles has become known as clinical trial imperialism. Simply put, Western pharma corps systematically try to place their trials of new drugs in countries where the trial will be most cheaply run while still providing results that may get them a license somewhere in the West. As to upholding minimal standards of human subjects protection, reliable oversight and accountability – sod that!

So, to get back to GSK, SP and the HPV vaccination business. What we see happening in this case is just more of the same. Sweden just like all other Western countries are using tax payers money to provide pharma corps with very privileged positions: patent systems, drug subsidises, seed money to ease the establishment of offices and labs, access to the resources of medical schools, university hospitals and public health care systems, close cooperation to smooth the product development process, and support for a market for non-prescription drugs that in most cases actually is detrimental to the health of the population. They do all that because they see no alternative. The development of new pharmaceuticals for serious and widespread disease is a high risk endeavor and very expensive process, and most countries prefer to have it done with the funding accessible through business transactions. But this is no reason to be seduced by their marketing offices. Pharma corps don't care about anyone's health and even less about public health. In fact, the best business sitiuation for a pharma corp is a permanent health problem that never goes away, but where the company can supply a product that slightly mitigate the symptoms. That's far, far better business than anything that cures people or – to name the nightmare of a pharma – that permanently prevents the onset of the problem. Even less do they care about ethics or upholding minimally decent ethical standards. They demonstrate this convincingly by never ever being prepared to sacrifice a buck for adjusting to ethical considerations of any weight. They do, of course, abide by laws, but prefer to place production in countries where efficient industrial operation is combined with the most allowing rules – unless sale efficiency demands otherwise. They do, on homepages and in company prospects, repeat the words "ethics" and "ethical" (as well as "responsible") so often that the cursory reader might mistake them for something out of the Vatican, but, as the Swedish case of GSK and SP regarding HPV vaccination shows, all of this is smoke and bogus. All. That is not a very comforting thought, and in light of our view of pharma corps as necessary, that discomfort may trick us to believe otherwise. But this is, I claim, the sole truth.