tag:label.svbtle.com,2014:/feedLucy Abel2018-09-05T03:14:26-07:00Lucy Abelhttps://label.svbtle.comlucy.abeluk@gmail.comSvbtle.comtag:label.svbtle.com,2014:Post/car-t2018-09-05T03:14:26-07:002018-09-05T03:14:26-07:00Has the NHS put the CAR-T before the horse? <p>CAR-T is going to be made available on the NHS for children who have an advanced form of a blood cancer, acute lymphoblastic lymphoma, that has not responded to other treatments. The <a href="https://www.bbc.co.uk/news/health-45407514">BBC reports</a> that an estimated 15 children a year will be eligible to receive the treatment, which works by extracting, editing and re-purposing the child’s own immune system. This treatment is exceptionally expensive, both for the drugs themselves and for the extra care patients require as a result. The treatment has been reported as costing upward of $300,000, with care costs topping $1 million in the USA. While care costs are usually substantially lower in the NHS, this will still be a very expensive treatment. </p>
<p>So if it is being made available on the NHS, does that mean it’s cost-effective? In a word, maybe. Realistically, probably not. Under the health economic model of cost-effectiveness, if the NHS funds treatments that are not cost-effective, someone else loses more health than the patient receiving the new treatment receives (to get an idea of what this looks like in practice, read Chris Gibbon’s brilliant <a href="https://donteatthechalk.wordpress.com/2018/02/19/innovation/">blog post</a> on a highly cost-effective intervention named Neil). To counter this, the NHS uses NICE to review new drugs and decide if they are cost-effective. If not, they aren’t funded. In this case, though, we just don’t know yet, because that evaluation hasn’t been done.</p>
<p><strong>Why don’t we know if CAR-T is cost-effective?</strong><br>
In practice, the decision making process involves a lot more nuance than just cost-effectiveness. People feel very strongly that new drugs should be made available, and patient groups have increasingly loud voices in the health policy arena. The people who could benefit from new drugs are aware they exist and can see exactly what they’re losing by not receiving them. Conversely, patients who will lose out through funding being redirected aren’t aware of it. Disinvestment is usually a quiet business - local authorities don’t tend to shout about services they are cutting. The political consequence of this is that there is a constant upward pressure on cost-effectiveness decisions, as decision makers face strong condemnation for rejecting drugs. While decision makers like NICE have a well-defined role that insulates them from the worst of the political pressure, politicians and governments are more exposed. Around the world, the pressure to approve and make new drugs available is mounting. In the US, for example, the FDA is <a href="https://www.reuters.com/article/us-fda-hearing-testimony/fda-aims-to-approve-more-drugs-based-on-early-clinical-data-idUSKBN1DU2DS">introducing</a> approval processes based on earlier and earlier trials. In the UK, this pressure manifested in the introduction of the Cancer Drugs Fund (CDF) in 2010. </p>
<p>The CDF provided an alternative way for cancer drugs to be made available on the NHS. Doctors could request drugs intended to extend the life of cancer patients, regardless of their cost-effectiveness. The consequences of this were rapid and unsurprising: the allocated budget ballooned, and by 2016 £1.3 billion of the NHS budget had been reallocated to the CDF, well beyond the original £50 million annual budget. More alarmingly, most drugs funded through the CDF didn’t do anything to extend patients’ lives at all. <a href="https://academic.oup.com/annonc/article/28/8/1738/3768075">One review</a> of CDF drugs found that only 18% had been shown to increase overall survival at all, and then by only 3 months on average. </p>
<p>In response to this, in 2016 the CDF was <a href="https://www.bmj.com/content/352/bmj.i1208">relaunched</a> in a more constrained capacity. Now drugs had to demonstrate “plausible potential” to be cost-effective. Evidence on patient outcomes from their use in the NHS had to be collected, and the drugs would be re-evaluated after two years, when a final approval decision would be taken. </p>
<p>It remains to be seen how drugs in this new CDF will perform, but while there are constraints, that phrase “plausible potential” still leaves it pretty much a free-for-all. The bar is low and fuzzy and you only need one good (lucky) study to clear it. This is the standard that CAR-T has met so far. </p>
<p><strong>The Fight</strong><br>
Back in April, the Chief Executive of the NHS, Simon Stevens, <a href="http://www.pharmatimes.com/news/car-t_therapy_could_be_available_to_nhs_patients_this_year_1233435">told</a> the ABPI, the British Pharma industry body, that CAR-T could be available on the NHS by the end of the year. He qualified this by saying that Pharma needed to set “fair” prices for this to happen, but so far there is no evidence that this has happened. CAR-T is in the CDF, albeit for a very small population. If it turns out to be cost-effective, in two years time we will find that out and it will be funded routinely, to the benefit of these child cancer patients and their families. If it isn’t then the NHS will have wasted tens of millions of pounds and cost patients across the NHS their health. If that happens, the process should be to defund CAR-T. But will that happen? Patients will have had two years of access and Pharma will have spent two more years lobbying. Simon Stevens has already told industry he wants these drugs to be available, without knowing they work yet. My bet is that CAR-T won’t be cost-effective (so few of these drugs are) and that decision makers will have a fight on their hands to get that money allocated where it will do most good. </p>
<p>Let’s hope I’m wrong. See you back here in two years. </p>
tag:label.svbtle.com,2014:Post/population-health2018-03-09T08:34:59-08:002018-03-09T08:34:59-08:00Value-based health care: just reinventing the cost-effectiveness wheel?<p>If you follow me on Twitter you will know that I have an ongoing curiosity for value-based healthcare (VBHC). VBHC is a relatively new approach to making decisions about health service provision. It is currently in vogue with local decision makers, largely, it seems to me, because of the advocacy of Sir Muir Gray’s <a href="https://www.phc.ox.ac.uk/research/value-based-healthcare">research group on VBHC</a>. </p>
<p><a href="https://svbtleusercontent.com/escwyvk7nlnga.png"><img src="https://svbtleusercontent.com/escwyvk7nlnga_small.png" alt="triplevalue.png"></a><br>
<em>The VBHC Research Group’s illustration of the “Triple Value” framework</em></p>
<p>Because it is concerned with how to make decisions about healthcare provision, VBHC necessarily overlaps substantially with cost-effectiveness analysis, which is the approach advocated by health economists. VBHC breaks away from cost-effectiveness methods in more explicitly considering equity considerations (who benefits from an intervention, as well as just how much they do). It also discusses “personal value”, which seems to be largely about advocating for patient-centred care and shared decision making. Where it really comes into potential conflict with health economics is in the third approach: allocative value, which explicitly concerns itself with resource allocation (another word for healthcare decision-making).</p>
<p><a href="http://journals.sagepub.com/doi/full/10.1177/0141076817732523">A paper</a> has recently been published on VBHC in the <em>Journal of the Royal Society of Medicine</em> (in the interests of full disclosure, by members of my own Department, which happens to include Gray). It’s a commentary that presents an interesting summary of the history of, and current thinking around, precision medicine, shared decision making and the increasing role of the patient in medical decision making. However, before getting into this, there is a short discussion of the VBHC framework in terms of population-level decision making (ie, allocative value, or resource allocation). </p>
<p>I have a couple of issues with this section, and I think it illustrates some of the ways in which VBHC has a tendency to reinvent the wheel on issues that health economics has been addressing for years. </p>
<p><strong>Defining value</strong></p>
<p>The first couple of paragraphs are largely common sense: population changes are reflective of changes happening at the level of individual patients, so it’s clear the two are related. The unit of analysis in any cost-effectiveness analysis is the patient; health outcomes for each individual are added up to give the population level effects. Where things get rocky is this line:</p>
<blockquote>
<p><em>The second reason is that the value for each individual changes just like the value for the population as the investment in a service increases</em> </p>
</blockquote>
<p>What is the definition of value here? Is it patient health, and if so how do you define and measure health? Is it patient preferences? What about their family’s preferences? Should wider society get any say in what is “valuable”? Health economists have wrestled with these questions for decades. The way cost-effectiveness analysis currently does this is to define value as a combination of mortality and health-related utility (the economic term for preferences), known as the quality-adjusted life year (QALY).</p>
<p>This is probably the single largest issue I have with VBHC. Valuing health is, as I have <a href="https://label.svbtle.com/harms-of-hope">written</a> about <a href="https://label.svbtle.com/valuing-health">before</a>, a messy, uncomfortable process, and so far much of VBHC seems to gloss over this.</p>
<p><strong>Linear harms and benefits</strong></p>
<blockquote>
<p><em>In Explorations in Quality Assessment and Monitoring, Donabedian described not only the concept of structure, process and outcome but also his ‘unifying model of benefit, risk and cost’. The power of this model is that it quantifies for the first time the relationship between resources invested in healthcare and the amount of value obtained from that level of investment.</em></p>
</blockquote>
<p>I haven’t been able to access the book the authors cite here, although I did manage to find a <a href="http://www.jstor.org/stable/3348969?seq=1#page_scan_tab_contents">1966 review of the same name</a>. This review is an exploration of the methods and challenges associated with identifying and measuring outcomes in healthcare, and makes no mention of cost at all. </p>
<p>In fact there have been numerous attempts to quantify the relationship between health investments and health outcomes, both theoretical (beginning with the Arrow paper, in 1963, and developed by the Grossman model) and empirical, using cost-effectiveness analysis and health econometrics. The most famous of the latter is probably the <a href="https://www.rand.org/content/dam/rand/pubs/reports/2006/R3055.pdf">RAND health insurance study</a>, which allocated 5809 American participants to different levels of health insurance coverage and measured their health outcomes over 8 years, from 1974 - 1982. Besides this, cost-effectiveness analyses in one form or another have been <a href="https://journals.lww.com/lww-medicalcare/Citation/1968/01000/Cost_Effectiveness_Analysis_Applied_to_the.5.aspx">published since 1968</a>, and the earliest record of a study that quantifies the relationship between investment and health outcomes that the health economists of Twitter could think of is actually from 1927. </p>
<blockquote class="twitter-tweet">
<p lang="en" dir="ltr">While not the first, Earp’s 1927 study CORRELATION OF INFANT SALVAGE WITH NURSING EFFORT is a classic. No only does it estimate and apply a regression model, but also has a discussion of causality including use of the term “spurious correlation”. <a href="https://t.co/iMJropsrUN">https://t.co/iMJropsrUN</a> <a href="https://t.co/f5rbX1rvXs">pic.twitter.com/f5rbX1rvXs</a></p>— Philip M Clarke (@pmc868) <a href="https://twitter.com/pmc868/status/970444300818333696?ref_src=twsrc%5Etfw">March 4, 2018</a>
</blockquote>
<p>The paper continues:</p>
<blockquote>
<p><em>Donabedian showed that as healthcare resources are increased, benefit increases initially, but the increase then flattens off, illustrating what some people have called the law of diminishing returns. Importantly – and this is often overlooked – the amount of harm done does not diminish as resources invested. For each unit increase in resource, there is a unit increase in the number of people treated and consequently a unit increase in the amount of harm done. In fact, there may be a progressive increase in the amount of harm done if, with each unit increase in the availability of care, patients who are less fit and more at risk of harm are covered by the service.</em></p>
</blockquote>
<p>The idea of diminishing returns on an investment is an economic concept that makes intuitive sense. This does not necessarily mean it is universally true, though. It provides a useful starting assumption in the absence of evidence on how effective a treatment actually is in different populations, but it is easy enough to think of situations where it may not apply. For example, drugs that are more experimental may be given more readily to patients who have few other treatment options, even though it may later turn out that the drug is more effective in patients with a less severe form of disease. </p>
<blockquote>
<p><em>Harm occurs in all health services, even those that are of the highest quality, as an inevitable consequence of the risks associated with the act of interventions such as X-rays, drugs and anaesthetics. As a consequence, there may come a point at which the investment of additional resources will lead to a reduction in the net benefit, calculated by subtracting the harm from the benefit, and there comes a point beyond which additional investment reduces the value derived from the resources. He called this the point of optimality</em></p>
</blockquote>
<p>Harms may be linear, but harms such as adverse events are not necessarily random, and therefore may not increase linearly with the number of people treated. The relationship between patient characteristics and likelihood of experiencing harms may also correlate with how effective the treatment is. For example, patients who experience more adverse events because they are frail might also benefit less from the treatment.</p>
<p>That said, the idea of balancing benefits and harms is integral to cost-effectiveness analysis, and nothing here is particularly counter to that. Many treatments will follow this shape of diminishing benefits and increasing costs and harms. </p>
<p><strong>Opportunity cost</strong></p>
<p>The more controversial point is the “point of optimality”. On the diagram below (Figure 1 in the paper), this is the point, supposedly, when net benefits (benefits minus harms) are at their highest. This is the same calculation used in cost-effectiveness analysis, only with costs in place of (and encompassing) harms. Here costs are listed on the x axis, but don’t come into the net benefit equation at all. It is just taken as a given that increasing costs linearly increase both benefits and harms. </p>
<p><a href="https://svbtleusercontent.com/30bubyzu2vdkta.gif"><img src="https://svbtleusercontent.com/30bubyzu2vdkta_small.gif" alt="optimality.gif"></a></p>
<p>This diagram pays lip service to costs, but in fact you could remove them entirely and nothing would change in this figure: even if all treatments were free, there is a point where the total health gains are reduced because of increasing harms. This is the point where we should stop investing. </p>
<p>Cost-effectiveness analysis considers all of this, but also considers the opportunity cost: the fact that money not spent on this would be spent on something else. The “point of optimality” in a cost-effectiveness analysis is one in which net benefits are highest when <em>taking into account</em> what benefits would have been acquired by spending that money differently. Specifically, the costs are considered in terms of the benefits that would have been gained if that money had been spent on other treatments in the health system. If this opportunity cost is not considered, then the only constraint on spending is harms of testing and treating. </p>
<p>Harms from overdiagnosis and ineffective treatments are certainly a problem in healthcare, but if you allocated resources on the basis of minimising clinical harms, ignoring costs, you would very quickly run out of money. </p>
<p><strong>The irony of allocative efficiency in research</strong></p>
<p>VBHC has clearly captured the imagination of many decision makers. The breadth of its scope, opening up the possibility of considering decision making in healthcare through several lenses, is interesting. </p>
<p>Unfortunately these issues - ignoring opportunity cost, not defining value, and assuming the relationship between costs and outcomes is clear-cut and predictable - would be enough to send any cost-effectiveness study home from peer review with a note. VBHC must engage with the past 50 years of health economics research, or risk adding very little new to the decision-maker’s toolbox.</p>
<p>Ironically, while VBHC advocates continue to reinvent this wheel they absorb resources that could be better spent elsewhere, generating new evidence that might actually benefit patients. I’d hate to see the enthusiasm and influence of this field succumb entirely to allocative inefficiency.</p>
tag:label.svbtle.com,2014:Post/hesg-or-why-our-conference-is-better-than-yours2018-01-15T08:32:15-08:002018-01-15T08:32:15-08:00HESG: an explanation, or,
Why our conference is better than yours<p>Health economists know how to host a good conference. So much so that it inspires adulation on a level better associated with alcohol and comfort food. In fact, it briefly inspired its own meme.</p>
<blockquote class="twitter-tweet">
<p lang="en" dir="ltr">I love <a href="https://twitter.com/MetWalkers?ref_src=twsrc%5Etfw">@MetWalkers</a>, and I love <a href="https://twitter.com/UK_HESG?ref_src=twsrc%5Etfw">@UK_HESG</a> and that’s it :) Happy weekend, everyone :)</p>— Caroline Clarke (@cazline42) <a href="https://twitter.com/cazline42/status/952375754335154176?ref_src=twsrc%5Etfw">January 14, 2018</a>
</blockquote>
<blockquote class="twitter-tweet">
<p lang="en" dir="ltr">I love <a href="https://twitter.com/campari?ref_src=twsrc%5Etfw">@campari</a>, and I love <a href="https://twitter.com/UK_HESG?ref_src=twsrc%5Etfw">@UK_HESG</a> and that’s it :) Happy weekend, everyone :)<a href="https://twitter.com/hashtag/healtheconomistsconfessions?src=hash&ref_src=twsrc%5Etfw">#healtheconomistsconfessions</a> <a href="https://t.co/3gOLX1hEAW">https://t.co/3gOLX1hEAW</a></p>— Matt Sutton (@MattXSutton) <a href="https://twitter.com/MattXSutton/status/952487841942134785?ref_src=twsrc%5Etfw">January 14, 2018</a>
</blockquote>
<blockquote class="twitter-tweet">
<p lang="en" dir="ltr">I love <a href="https://twitter.com/PotNoodle?ref_src=twsrc%5Etfw">@PotNoodle</a>, and I love <a href="https://twitter.com/UK_HESG?ref_src=twsrc%5Etfw">@UK_HESG</a> and that’s it :) Happy weekend, everyone :)<a href="https://twitter.com/hashtag/healtheconomistsconfessions?src=hash&ref_src=twsrc%5Etfw">#healtheconomistsconfessions</a> <a href="https://t.co/21sRUriJZu">https://t.co/21sRUriJZu</a></p>— Chris Sampson (@ChrisSampson87) <a href="https://twitter.com/ChrisSampson87/status/952628947203837954?ref_src=twsrc%5Etfw">January 14, 2018</a>
</blockquote>
<p>So far I’ve not encountered any other academic fields who do something similar. This seems like a shame, so in the spirit of this evangelism I thought I’d provide a quick overview of what makes the Health Economic Study Group meetings (HESG) great. If you’re a health economist planning to attend your first one, hopefully this will help give you some sense of what to expect. </p>
<p><strong>THE FORMAT</strong></p>
<p>The HESG format works like this: </p>
<ol>
<li><p>Submit an abstract, like any other conference. The work you submit is probably at the same stage of completion as any abstract you might submit to another conference, but unlike other conferences, you don’t have to lie to yourself that you’ll have it finished in time, because…</p></li>
<li><p>Write up an unfinished bit of work. Your paper should be something that still needs work, since this is a study group, not a traditional conference. The aim is to use HESG to improve your work, rather than just show it off.</p></li>
<li><p>Have your paper discussed. This is where the interesting bit comes in. Rather than presenting your own work, another HESG attendee will do it for you. They’ll provide an overview of your work, suggest a few points they think could improve it, and generally kick off…</p></li>
<li><p>The discussion! What HESG is all about: 40 minutes of free-form academic jazz. The author is given a couple of minutes to make a few clarifications, and then the floor is open for anyone to add comments, usually of a more general flavour than your standard conference questions. The best discussions are wide ranging and consider the direction of the field as a whole in addition to the contribution of the paper in question. Authors usually come out with ideas for at least four more papers they could write. </p></li>
</ol>
<p><strong>THE BENEFITS</strong></p>
<p>This format makes for intense and engaging discussion, but also a very social conference. Attendance is in the range of 100-200, which is small enough to network meaningfully. Talks usually have around 20-40 attendees, which is small enough for everyone to participate. </p>
<p>This means you can get a good sense of who everyone is and what they’re working on, making it easier to strike up conversation over coffee. And later dinner, wine, more wine… The conversation might not be as coherent after the conference dinner, but, well…</p>
<blockquote class="twitter-tweet">
<p lang="en" dir="ltr">Pretty sure I proposed about 4 special interest groups in the pub last night. The academic version of fixing the NHS after a few pints.</p>— Lucy Abel (@LittlerLabel) <a href="https://twitter.com/LittlerLabel/status/951738155744538624?ref_src=twsrc%5Etfw">January 12, 2018</a>
</blockquote>
<p>The format also encourages genuinely useful feedback. Discussing someone else’s paper is good fun, but it’s also a responsibility. The author will be sitting in front of you, and as with all open peer review, it’s hard to be rude when your name and reputation are on the line, in front of an audience. As a result, feedback is overwhelmingly constructive. Even if no one else has anything useful to say (and very technical papers can suffer a bit for this) someone qualified and willing has just spent 20 minutes providing an in-depth review of your work. How often do you get that during peer review? </p>
<p>Finally, as a participant I find that the format encourages people to speak up - there’s 40 minutes to fill, after all. As a result, even the most junior participants may feel able to contribute. I wonder if this is one of the reasons health economics has such a vocal cohort of early career researchers. I certainly think it bears some responsibility for the field’s active Twitter presence, which I credit with almost single handedly getting me through my first year in academia, lacking as I was in the supportive network you get at larger units. </p>
<p><strong>WHY IT WORKS</strong></p>
<p>Obviously not every format works in every setting. There are a few reasons I can think of for why HESG works so well, and how you might be able to replicate it in other fields:</p>
<ol>
<li><p><em>Keep it small</em> <br>
As mentioned above, the discussions need to be small enough to allow for a free flowing discussion where everyone can participate. </p></li>
<li><p><em>Emphasise chairing</em><br>
The best sessions have a chair whose priority is getting the discussion going and making everyone heard. Tactics for doing this vary, from withholding lunch until everyone has asked a question, to ruthlessly cutting off garrulous professors. </p></li>
<li><p><em>An evolving field</em><br>
This is a key one. Before I switched careers, I attended biomedical conferences as a publisher. These conferences were characterised by a strong sense of right and wrong, and the people who were “right” were generally old male professors. Yes, there were disagreements, but they came from a place of “I’m right, and I just need to prove it”. At HESG the discussion is (largely) much less confrontational. This is partly related to the field of health economics, which is young and fast evolving, with many of the rules less set in stone. It’s also unsurprising given so much of work relates to values and preferences. It’s hard to exist in a black and white world when your subject matter is grey. Finally the quality of the papers presented is generally very high. I’ve seen presentations of much weaker work at other conferences, and it makes it much harder to move the conversation on if the authors have made fundamental mistakes. That’s one the organising committee have to consider when reviewing abstracts. </p></li>
</ol>
<p>So, if you’re thinking of changing up your conference format, or just wondering what all the fuss is about, hopefully this helped. And if you’re planning to come to HESG in the future (it’s in Bristol in June, just FYI) then welcome! We’re delighted you’re here.</p>
<blockquote class="twitter-tweet">
<p lang="en" dir="ltr">Rather shamefully, I definitely broke most of these rules <a href="https://twitter.com/hashtag/HESGCity?src=hash&ref_src=twsrc%5Etfw">#HESGCity</a> <a href="https://t.co/HetA8icZdy">https://t.co/HetA8icZdy</a></p>— Lucy Abel (@LittlerLabel) <a href="https://twitter.com/LittlerLabel/status/952629343016095745?ref_src=twsrc%5Etfw">January 14, 2018</a>
</blockquote>
tag:label.svbtle.com,2014:Post/harms-of-hope2017-07-25T02:12:09-07:002017-07-25T02:12:09-07:00Charlie Gard and the harms of hope<p>The tragic story of Charlie Gard is now coming to an end, and with it some key information has been released by Great Ormond Street Children’s Hospital (GOSH), where Charlie is being treated. </p>
<blockquote class="twitter-tweet">
<p lang="en" dir="ltr">Latest GOSH statement on Charlie Gard case. As others have noted para 10 both eyebrow-raising and jaw-dropping <a href="https://t.co/FQuOXpngIl">https://t.co/FQuOXpngIl</a></p>— John Appleby (@jappleby123) <a href="https://twitter.com/jappleby123/status/889527367969976321">July 24, 2017</a>
</blockquote>
<p>The above tweet describes the most recent statement released by GOSH and its legal team, and the paragraph of interest runs as follows:</p>
<blockquote>
<p><em>When the hospital was informed that the Professor had new laboratory findings causing him to believe NBT would be more beneficial to Charlie than he had previously opined, GOSH’s hope for Charlie and his parents was that that optimism would be confirmed. It was, therefore, with increasing surprise and disappointment that the hospital listened to the Professor’s fresh evidence to the Court. On 13 July he stated that not only had he not visited the hospital to examine Charlie but in addition, he had not read Charlie’s contemporaneous medical records or viewed Charlie’s brain imaging or read all of the second opinions about Charlie’s condition (obtained from experts all of whom had taken the opportunity to examine him and consider his records) or even read the Judge’s decision made on 11 April. Further, GOSH was concerned to hear the Professor state, for the first time, whilst in the witness box, that he retains a financial interest in some of the NBT compounds he proposed prescribing for Charlie. Devastatingly, the information obtained since 13 July gives no cause for optimism. Rather, it confirms that whilst NBT may well assist others in the future, it cannot and could not have assisted Charlie.</em> </p>
</blockquote>
<p>For context, the Professor in question is the American doctor who had offered Charlie’s family the chance for nucleoside therapy. It’s not surprising that the medical community of Twitter has been disheartened by this report. Without knowing any more, it looks an awful lot like this doctor misled the parents of a very sick child, without even examining the child, with the promise of a treatment that a litany of other experts had already concluded was not going to work (the other paragraphs of the statement explain this). It is not unreasonable to say that without this doctor’s input, this saga would have ended in January, potentially sparing Charlie and his family 6 months of suffering. </p>
<p>Throughout this case, the general argument in favour of letting Charlie go to the US has been “why not give him a chance?”. The GOSH statement suggests strongly that this chance never existed in the first place. The whole case rested on the idea of hope, which now looks like false hope. </p>
<p>The value of hope is an issue that has popped up in health economics recently. Cost-effectiveness analysis is increasingly being used in the US, and as happens in every country, health economists there are grappling with their own questions around societal values, and what costs and effects should be included in their analysis. At the recent International Health Economics Association Congress, which I attended, the cheerleaders of this work, the Institute for Clinical and Economic Review (<a href="https://icer-review.org/">ICER</a>), presented their approach to this, along with a value framework that outlines what they think cost-effectiveness in the US should consider. </p>
<p>They included the value of hope as a benefit. </p>
<p>In my <a href="https://label.svbtle.com/valuing-health">last blog post</a> I outlined the difficulties of deciding where to draw that line at what should be counted as an effect. Should we only consider health itself, or should we also consider wider benefits, for example the ability to go back to work? In the UK we generally don’t consider non-health benefits, but other countries do it differently. Sweden includes wider benefits such as productivity outcomes. </p>
<p>The issue with this, as I described before, is that in a health system with a budget (which all health systems have, whether they admit it or not) you are then trading these other benefits against health, because the money to pay for them would otherwise pay for other treatments. How many years of life would you give up to go back to work? How many years of life would you give up so <em>someone else</em> can go back to work? </p>
<p>Some of these non-health benefits may genuinely be worth giving up actual health for. I’ve not seen much evidence that they are, but that doesn’t mean it’s not out there. Hope, though? Merely increasing the uncertainty surrounding whether a miracle cure may exist? That’s a messy one.</p>
<p>First up, from an analysis point of view if you include hope as a benefit then you have to subtract it as more evidence becomes available. If that 1 in 1000 chance becomes zero, because a new test is developed that means doctors can identify the 1, then you have to count that against the new test, because it is taking away hope from 999 other patients. </p>
<p>But beyond that, I think what the Charlie Gard case shows is that hope can have real, harmful consequences. Hope is only a positive before treatment has started, and failed. Once it begins to fail, hope is eviscerated, and all that remains are the costs; economic, emotional, and possibly physical, if suffering is prolonged needlessly or there are side effects from treatment.</p>
<p>Of course choice is important in all of this. Most of us would cling to hope if given the chance, and understandably so. But this is about the broader point of whether <em>society</em> should value hope. In other words, would it have been better for Charlie Gard and his parents if they had never had that hope at all? Or should it be something we actively count as a benefit in decision making, even when the final health outcome will be the same. </p>
<p>From where we are sitting now, with the benefit of hindsight, I wonder if many parents would choose to have kept fighting for a futile treatment on the basis of hope. I wonder if the costs of the past 6 months would have been worth it. </p>
tag:label.svbtle.com,2014:Post/nivolumab-for-head-and-neck-cancer-why-did-nice-say-no2017-04-12T08:11:52-07:002017-04-12T08:11:52-07:00Nivolumab for head and neck cancer: why did NICE say no?<p><a href="https://www.nice.org.uk/">NICE</a> has published draft guidance that an immunotherapy treatment, nivolumab, is not cost-effective for metastatic head and neck cancer. The guidance is still in consultation and therefore may change. But in the meantime the initial evidence has been <a href="https://www.nice.org.uk/guidance/indevelopment/GID-TA10080/consultation/html-content">published</a>, so we can see what NICE’s reasoning was. </p>
<p><a href="https://svbtleusercontent.com/5ajwuiwrpmubqg.png"><img src="https://svbtleusercontent.com/5ajwuiwrpmubqg_small.png" alt="Nivo.PNG"></a></p>
<p>In this blog I’m going to take a look at what NICE has said and compare it with this <a href="http://www.icr.ac.uk/news-archive/nivolumab-not-recommend-for-relapsed-or-metastatic-head-and-neck-cancer-on-the-nhs">news piece</a> from the Institute of Cancer Research (ICR). I want to see what gets lost in translation.</p>
<p>The first thing I did when opening the appraisal consultation was to scroll straight down to the cost-effectiveness result. This section presents a variety of results, with the assumptions of each (poorly) explained. The results are presented as incremental cost-effectiveness ratios (ICERs). An ICER is simply the amount of money it would cost to get one unit of benefit from the new treatment. In this case, if we switch to using nivolumab, we expect that patients will live slightly longer with slightly better quality of life. These two measures can be combined into a quality-adjusted life year (QALY). So the ICER measures the cost of one extra QALY. </p>
<p>NICE’s cost-effectiveness threshold, the amount it is willing to pay for that extra QALY, is £20,000-£30,000. It is immediately clear that the ICERs for nivolumab are much higher. The lowest is £38,000, the highest nearly £70,000. The reason this value varies is that it is the result of calculation that includes assumptions about, for example, how effective nivolumab is, how long patients with this type of cancer live normally, and what the costs of their other treatments are. When the Pharma company submitted their drug for evaluation, they included their own calculation based on their own assumptions. Different parties, including the decision making committee at NICE and an economic review group that act as expert reviewers, have changed some of these assumptions, which in turn changes the ICER value.</p>
<p>So it is pretty clear that this isn’t a cost-effective treatment for the NHS. The NHS would have to spend more money trying to implement this than it would be worth. This is because that money is currently spent somewhere else in the NHS, where it does more good for patients than nivolumab would.</p>
<p>Comparing NICE’s guidance to the ICR’s news coverage, one point that jumps out is the mention of comparators. These are alternative treatments for the patients who would be eligible for nivolumab if it became available. The ICR coverage makes it sound like this is a treatment with no alternatives, and therefore the loss for patients is particularly acute. NICE, on the other hand, includes 3 alternative treatments in their assessment.</p>
<p>We don’t know anything about how good these comparators are at treating head and neck cancer, but the very fact that the ICER for nivolumab is so high (ie, expensive) suggests that the health benefits compared to the current treatment must be small. While NICE acknowledges that this is a disease without many treatment options, if this was a real breakthrough treatment you would expect a smaller ICER, which would mean a big health benefit for the extra money. The fact the ICER is high suggests that the benefits aren’t all that impressive. </p>
<p>Finally, NICE references the idea that some patients might benefit more than others. Specifically, patients whose tumours express high levels of PDL1. There is evidence that the treatment may be more effective in these patients, and NICE makes a point of asking for more evidence so that it can look at the cost-effectiveness of nivolumab just in these patients. It is the manufacturer (Bristol-Myers-Squibb) who consider that this analysis would be “inappropriate”, although they don’t say on what grounds. In fact they do provide evidence from their clinical trials on these patients, which shows that the treatment only seems to have an effect in these high-expressing patients. The survival in low expressing patients is 5.7 months in those given the comparator treatment, and 5.8 in the nivolumab-treated group.</p>
<p>The cynic in me wants to know how many fewer units of the drug BMS would sell if only high-PD-L1 expressing patients were eligible for treatment. </p>
<p>So, in summary, this is a treatment that may, in fact, be effective in a select subgroup of patients. But in all patients, compared with all the treatments the NHS already uses, approving this drug at this price would leave the NHS worse off, both financially and as a provider of good health. If this drug was approved in all patients, the initial evidence suggests that it might actually do no good at all for those who don’t have high PD-L1 expression. </p>
<p>And almost none of that made it into the ICR’s coverage. </p>
tag:label.svbtle.com,2014:Post/valuing-health2017-02-24T06:36:45-08:002017-02-24T06:36:45-08:00The price of life? The good, the bad, and the ugly of valuing health<p>There is a certain kind of person I meet a lot at conferences. They’re often patient representatives - engaged, educated people who have dedicated enormous amounts of time to improving medicine for the people they represent. They often recognise the importance of health economics, but as a general rule they have one big issue with it: The QALY, and more particularly, the EQ-5D. </p>
<p>QALY stands for quality-adjusted life year, and it’s the main health outcome used in health economics, at least in the UK. As you’d expect, it’s a measure that combines length of life and quality, and mathematically it’s very straightforward. You multiply the length of life, say 5 years, by a quality adjustment, also called a health utility, that ranges between 0 (death - although scores can go negative, i.e., worse than death) and 1 (perfect health). So five years of some condition with a quality of life of 0.8 is equal to 4 QALYs (0.8 x 5). </p>
<p>The nice thing about QALYs is that quality of life is valued in a way that trades off length against quality. To do this, rather than simply ranking health conditions, you ask people how much time living with one condition they would be willing to give up to avoid a worse one. This means that 4 QALYs always represents that same amount, irrespective of whether that is 4 years of perfect health or 8 years at a quality value of 0.5. </p>
<p>Where it becomes problematic, though, is in trying to assign that quality value to a named condition, for example cancer. The values themselves are developed using something called “health states”. These are lists of health problems of varying severity, for example: “you can do usual activities, experience moderate pain, take care of yourself with no problems, have extremely impaired mobility and are moderately depressed”. </p>
<p>By getting patients with the health condition of interest to complete a questionnaire that produces a result like the one above, we can convert a health condition with a name into a generic health state and assign it a quality of life value.</p>
<p>It’s a system that works quite well for the purposes of comparison, but has some pretty obvious flaws. The health state I gave as an example above is taken from the EQ-5D, which is the most commonly used questionnaire, and the one that must be used in <a href="https://www.nice.org.uk/">NICE</a> health technology appraisals. Every variant of that example (with no, some or extreme problems in each category) gives a maximum 243 possible health states. That number is sufficient to cover the essential differences between health conditions pretty well for the purposes of decision making. That said, it is not hard to see how a five category questionnaire can look pretty inadequate when you’re a patient. </p>
<p>So that’s why the EQ-5D, and QALYs in general, aren’t a patient representative’s favourite thing. They don’t capture the full experience of living with a condition. At the moment the general case for them is that they aren’t designed to. That despite being called “quality of life” values, they are only designed to capture what is called health-related quality.</p>
<p>In other words, if a health condition includes some element of health that isn’t covered by the EQ-5D, that’s only a problem if the health condition would be valued much better or worse, relative to other conditions, if that element were included. In that case, the decisions around making treatments available might change because a new medicine that improves the missing element might not look cost-effective when it actually is, which risks denying patients effective care and reducing how effective the health system is as a whole. </p>
<p>And it is easy to identify parts of a health condition that are not fully covered in the EQ-5D. Anyone with experience of an illness can find something missing. Beside aspects of what is classically thought of as medical problems, there are also emotional, social and economic benefits. Why not include them? These are all important to patients. </p>
<p>This is where it starts to look really messy. If we don’t limit quality of life to just pure medical benefit then there is a risk that we start using health budgets to subsidise other things. For example, treating conditions that get people back into work looks good for the economy, but should we therefore spend more money treating these younger, less sick patients who can plausibly get better than we do on dementia patients, most of whom are are retired anyway?</p>
<p>It is tempting to continue adding extra benefits to the treatment you want to approve. This happens a lot in pregnancy, where the choice of whether to count the health of an unborn child among your benefits is strongly predicted by whether that makes your treatment look <a href="https://www.ncbi.nlm.nih.gov/pubmed/25926281">more or less cost-effective</a>. Besides raising questions about whose health matters, this approach usually also ignores that every other treatment you are comparing against will have its own non-health benefits. If the threshold we used to measure cost-effectiveness included all those extra benefits it would be higher, and the bar would be raised yet again.</p>
<p>That’s not to say that we shouldn’t include extra benefits, and methods exist to do so in a small number of cases. Doing so tends to bring its own challenges, though, which I’m planning to do another blog post on soon. </p>
tag:label.svbtle.com,2014:Post/reflections-on-hellish-local-decision-making2017-02-15T07:56:32-08:002017-02-15T07:56:32-08:00Reflections on "hellish" local decision making<p>The purpose of health economics is to spend the health budget as wisely as possible. In economic lingo, to maximise health within the constraints of limited resources. Nationally, we have been putting this into practice since before 1999, when <a href="https://www.nice.org.uk/">NICE</a> was set up. Locally, however, the picture is different. </p>
<p>This became apparent to me at the <a href="https://www.phc.ox.ac.uk/events/hellish-decisions-in-healthcare-2017">Hellish Decisions in Healthcare</a> conference I was at in January, which brought together decision makers and decision informers, such as health economists and health services researchers, to consider the challenges facing the NHS, in particular at the local level, where decision making is still fairly ad hoc. </p>
<p>There are two big challenges that I see with local decision making. One is that the way local decision makers are organised isn’t compatible with national decision making, leading to inefficiency. Another is that pressure from patients for certain decisions to be taken is felt much more acutely locally. </p>
<p><strong>On organisation</strong><br>
Local decisions have to be taken about all conditions, all the time. Unlike NICE, a Clinical Commissioning Group (CCG) responsible for providing healthcare to their local area can’t pick and choose what decisions to make, they have to provide care now, regardless of whether that care is optimal. </p>
<p>And that decision making is much messier than our economic models allow for. Our assumptions rely on unlimited budgets that can be freely reallocated, unlimited resources to provide care to all who need it, and perfect implementation. But the very reason these decisions are made is because budgets and resources are limited. This difference doesn’t usually matter for central decision making. We use a cost-effectiveness threshold that represents those limitations in the abstract, and implementation can be considered in the analysis. We can still make useful decisions within those constraints. </p>
<p>Locally, the picture is different. Budgets are siloed in anachronistic pools that don’t reflect how health is achieved, but rather how it is provided. So diagnostics go in one pool, surgery in another, and so on. Trying to improve cancer outcomes might involve spending more money on diagnostics in primary care, but the benefits from doing so appear in oncology, with no way for any savings made there to be reallocated. So primary care then has to make even more savings to fund their new investment, cutting into treatments that might have real, measurable benefits for patients.</p>
<p>Local authorities, at least at this conference, which admittedly probably isn’t representative, seemed to value cost-effectiveness. They understand and appreciate what it is for and why it’s important. But even before the question of whether the evidence is there is the question of how they can possibly implement it in this system.</p>
<p>And even that willingness needs refinement, too. Common misunderstandings about what is included in economic analysis were rife (the most common question I heard was “do you include [relevant health outcome] in cost-effectiveness analysis?” - for the record, the answer was always yes). A lot of this is because of the shortage of health economists. We’re a rare, and as a result expensive, breed. There isn’t one in every CCG, as there ideally should be. CCGs need much better tools for applying economic evidence to their decision making.</p>
<p><strong>On patients</strong><br>
Local decision makers are also much closer to patients than central decision makers are. They must balance their budgets, local demand from both patients and clinicians, pressure from device and drug manufacturers, and further requests for exceptional funding, in the form of individual funding requests (IFRs). Which came up repeatedly as a particularly sticky area.</p>
<p>IFRs are requests for funding for treatments that are not routinely provided, on the grounds that the patient is exceptional. The basis for this is that as cost-effectiveness decisions are based on averages, there will be some patients to whom those averages don’t apply, for whatever reason. Less strictly economically, exceptionality can also be used in cases where the patient not receiving treatment would have significant consequences, for example for a single mother with young children. Cost-effectiveness decisions don’t generally account for these externalities for sensible reasons: it is not the job of the health service to subsidise other parts of government, so non-health effects (the social care costs of the children left behind) should not feature in decision making. You don’t have to think too hard to see why this argument might be problematic in some cases. </p>
<p>In this context, we must of course remember the patients that lose out every time a treatment that isn’t cost-effective is handed out. We can only see the mother in front of us who needs expensive treatment, rather than the 12 who could be saved with currently available drugs using the same money. </p>
<p>And local authorities actually seem to be doing a pretty good job with IFRs. The vast majority of claims are rejected, with local authorities holding to the exceptionality rule, and not caving to let it simply mean “human”. If the job of health economists in the NHS is to make the invisible patients who stand to lose from a funding decision visible then, well, local decision makers probably understand that more clearly than anyone else. </p>
<p>But what to do about the <em>visible</em> patients who lose? Having your IFR rejected is hurtful and frightening for patients, as was demonstrated in a 2015 Channel 4 documentary called “£2 Billion a Week”, about funding in the NHS. The programme followed patients on their care journey, showing the decisions being taken, how much they cost, and giving examples of what that money could have bought elsewhere. It was an inflammatory and divisive bit of media, but it pulled these issues out and aired them publicly, in a way that felt like progress. </p>
<p>One question that arose in the discussion surrounding IFRs was how we can mitigate the pain of rejection for patients who have their IFRs turned down. Could we talk to the patient and their family, explain the decision making process? My feeling is not. I don’t think there is anything anyone could say that would make this easier or better for them, particularly where life or death conditions are concerned. Knowing that there is a treatment, convincing yourself that <em>that</em> is what you need, and having it blocked… Nothing is going to make that seem reasonable. I suspect that in this situation the only response is to let yourself be hated. Someone has to be the bad guy, why not us? </p>
<p>The natural concern is that being the bad guy could eventually lead to government pressure and policy change, which would be disastrous. My response is that the people we need to convince are not the people living through being on the wrong side of a decision, but those who <em>could</em> be there - the general public. The family will be furious, but if their neighbours and acquaintances understand the bigger picture, then the snow storm won’t build to an avalanche. </p>
<p>This requires better communication on all sides. My blog posts are taking on a bit of a theme at the moment. That’s because everywhere I look this feels like the biggest problem we face. Change is happening, and interest in where spending on the NHS actually goes is building - unfortunately not always in a helpful way, what with the constant tabloid focus on the non-problem of health tourism. </p>
<p>What’s needed is probably more discussion of fairness in the health service, and why our budgets are limited, more transparency about how money is spent, and better resources for local decision makers to start implementing evidence-based decision making. A walk in the park, then!</p>
tag:label.svbtle.com,2014:Post/patient-choice-and-cancer-risk2016-12-20T09:41:38-08:002016-12-20T09:41:38-08:00Too much information? Weighing the harms of knowing everyone's cancer risks<p>Screening, monitoring, and prophylactic (just-in-case) treatment of cancer is one of the big areas in medicine at the moment. The cases of <a href="http://scienceblog.cancerresearchuk.org/2013/05/14/angelina-jolie-inherited-breast-cancer-and-the-brca1-gene/">Angelina Jolie</a> and <a href="https://medium.com/cancer-moonshot/the-prostate-cancer-test-that-saved-my-life-613feb3f7c00#.fua6n9rg5">Ben Stiller</a> have achieved their aims of raising awareness, but, as always, the health economist’s thoughts turn to “at what cost?”. </p>
<p>One problem with testing, particularly routine testing, which both of these celebrities have advocated, is not so much the possibility of finding something wrong, but instead of finding the <em>potential</em> for something. A genetic mutation, for example, that increases your risk of developing a certain cancer. </p>
<p>One of the risks of genomic testing is that you might find out you have a predisposition to a condition, such as Alzheimer’s, for which there is no cure. The consequences are obvious - there are no health benefits to knowing this, and the potential psychological harms are significant. Some patients, having already suspected a predisposition because of family history, might find relief in knowing what they are facing, and maybe in trying to <a href="http://www.nhs.uk/Conditions/Alzheimers-disease/Pages/Prevention.aspx">reduce their risk</a>, although whether that genetic risk can actually be mitigated remains unknown. </p>
<p>Unlike Alzheimer’s, Angelina Jolie’s mutation offered her the opportunity to act. And not just a little. Her case made headlines when she went public about the decision to have first a double mastectomy, and then, two years later, to have her ovaries removed. </p>
<p>Last week the BMJ <a href="http://www.bmj.com/content/355/bmj.i6357">published research</a> that examined whether Jolie’s <a href="http://www.nytimes.com/2013/05/14/opinion/my-medical-choice.html">New York Times article</a> had the number of American women being tested for the BRCA mutation. The authors compared the rate of testing in the 15 days before and after the piece was published to the same period of time the year before. The aim here isn’t to look at the total change in the rate of testing over that period, which could be the result of all sorts of factors, but instead to look at the change that is only attributable to the article itself, by controlling for standard changes over time with the other time periods. For this reason the analysis is called difference-in-difference analysis. It’s not perfect - you have to assume the rate of change would otherwise have been identical between your time periods, which I think is a bit strong here. However, the authors found quite a large effect - more than twice as many tests per 100,000 women took place in the 15 days after the article, and even accounting for the expected change seen in the control time period, this still represented a 64% increase in testing. </p>
<p>So more women were getting tested. Unfortunately the authors couldn’t find any evidence that they were the right women - women who were likely to actually be carrying the mutation. In fact, the number of extra mastectomies following this bump in testing didn’t change at all, and the percentage of women who had further treatment went down, from 10% to 7% of women tested. To be clear, this isn’t the same as saying that all the extra women tested negative, as it could be that more women in this cohort with positive test results opted for less invasive treatment, such as surveillance. The assumption that they would choose the same treatment at the same rate as other women seems sensible to me though. </p>
<p>What this suggests, then, is that more women were tested but that they were women who didn’t benefit from it. It is reasonable to suggest that most of those tests weren’t necessary, that those appointments could have gone to patients in more urgent need, and that (given this is America), those women probably wasted their money. </p>
<p>But what of those who did test positive? </p>
<p>There is some evidence that, at least hypothetically, patients are willing to <a href="http://www.bmj.com/content/350/bmj.h980">tolerate a lot of harm</a> for the sake of not missing a diagnosis. But what of the potential for a diagnosis at some point in the future? How much harm, both medically and economically, are willing to put up with to reduce the risk of something that is not certain to happen in the first place? Jolie’s risks were high (supposedly - we don’t actually know how those risks were calculated), but other womens’ might not be. Is the psychological burden of even having to make that choice worth the potential health gains? Are the costs and surgical risks reasonable? And are doctors qualified to assess this?</p>
<p>Doctors are better than the general population at assessing risk and uncertainty, but they <a href="https://bmcmedinformdecismak.biomedcentral.com/articles/10.1186/s12911-016-0391-3">still aren’t great at it</a>. From my involvement in the <a href="http://www.cebm.net/">Centre for Evidence Based Medicine</a> I’ve learned how poor medical education often is at teaching doctors how to assess evidence and balance risks. Acting on the results of tests like these requires understanding of both the potential gains and the risks. Decisions like these will and should always involve some element of patient choice. They cannot be resolved with guidelines alone, although guidelines can help. It is therefore vital that doctors are properly educated on how to manage risk. Primary care doctors do this all the time - most of the patients they see who think they have cancer probably don’t, and GPs are adept at managing these risks. Now secondary care doctors, particularly oncologists, need to learn to do the same. </p>
<p>The importance of quantifying the potential harms of risk information such as this is really highlighted in this <a href="https://www.the-pool.com/health/health/2016/51/jean-hannah-edelstein-on-the-angelina-effect">first person piece</a> about a woman trying to navigate the murky waters of cancer risk statistics. Being able to make an informed choice on the basis of likely outcomes is one of the gifts of modern medicine. One of the central tenets of both evidence-based medicine and health economics is patient preferences and patient values, and this kind of information can empower patients who would otherwise be sitting ducks for a probable cancer diagnosis. However. If these success stories lead to overtesting, with overeager doctors intervening where even the slightest risk presents itself, we will readily find ourselves doing more harm than good, both to these patients, and to everyone else who finds their waiting lists longer and resources thinner on the ground. </p>
tag:label.svbtle.com,2014:Post/how-do-you-value-a-ticking-time-bomb2016-12-02T04:13:49-08:002016-12-02T04:13:49-08:00How do you value a ticking time bomb? <p><a href="https://svbtleusercontent.com/w6khofkhsgtg.jpg"><img src="https://svbtleusercontent.com/w6khofkhsgtg_small.jpg" alt="3831365675_4d741b80b8_o.jpg"></a><br>
<em>Photo credit: <a href="https://www.flickr.com/photos/oliverdodd/3831365675/in/photolist-6QyKwT-fqtcKe-ftEPGV-nLFuq8-9K1YGB-4hkdao-nqpbiW-HadHr-f5nMLV-t1cg-8tPiUM-Evq3KM-j4uLGn-kNmLHd-a2Ltvs-axXAYt-6Sqgy7-ejmn6K-7idGEu-BvuhSP-fqthsg-B5gxH4-dTdqaR-rcsZV8-bW7BKj-fb5Sra-fji5g5-faAzom-95ivKS-49ShAT-bMknsD-iRuEx1-pVCjgF-dXDoqh-4URuVh-efYR79-fWqQsm-bAoP5E-fbk8xu-b2eMWn-77VpEW-ddZP63-pgoERs-fbbeCE-fQ7CWB-mhxdxa-a4RLq5-DttWY9-9y4sDM-ctvCkC">Oliver Dodd</a></em></p>
<p>Antibiotic resistance is a crisis waiting to happen. Widespread resistance would mean the end of most surgery and cancer treatments and the return of 1950s-style infectious diseases, complete with long-since forgotten child mortality rates. Much of the medical progress of the last 75 years would vanish, and yet for some reason almost nothing is being done. </p>
<p>We do know what needs to be done. Prescriptions need to be restricted to only cases where we have good evidence that they will work, and patients need to finish their courses of antibiotics in full, reducing the chances that the bacteria will survive the drug and go on to develop resistance.</p>
<p>We also need to change agriculture. Antibiotics are currently <a href="http://www.nhs.uk/news/2015/12December/Pages/Antibiotic-use-in-farm-animals-threatens-human-health.aspx">widely used</a> in agriculture to improve livestock growth. Feeding animals a low dose of antibiotic prevents periods of sickness, increasing the short-term health of the herd and getting them to market weight faster. But this permanent dosing also provides training for bacteria, with the animals acting as the beginner levels on the resistance game - enough animals and enough different antibiotics (almost every antibiotic used in medicine has also been used in this way, include <a href="http://phenomena.nationalgeographic.com/2015/11/21/mcr-gene-colistin/">vital last-line drugs</a>) inevitably leads to resistance. And once a gene for resistance has developed bacteria can share it, propelling it through the population like flu moves through an office. </p>
<p>And a similar phenomenon is happening in primary care. Patients come in for sore throats, aches and pains that are readily self-diagnosed as bacterial infections. In the absence of testing and education, antibiotics are an easy solution; patients feel treated, doctors can get on with their overburdened day and harms tend to be minimal, although side effects do exist and can be dangerous. This happens despite the majority of these conditions not being caused by bacteria at all: 70% of throat infections are <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3135445/">caused by viruses</a>. Antibiotics, like all antibacterial products, have no effect on viral infections. Fortunately the vast majority of these illnesses are self-limiting: patients would have got better within a few days either way. As it is, patients attribute their recovery to the antibiotics, setting the stage for the next request when they subsequently fall ill. </p>
<p>These issues are well-known, and they have simple solutions: better education, stronger disincentives against inappropriate use of antibiotics, and broader use of diagnostic tests and protocols like clinical decision rules to make sure use is appropriate. But for some reason change comes slowly. </p>
<p>There are several reasons for this. One is the patient expectation described above. Another is cost. Antibiotics cost pennies - almost no new antibiotics are being developed, so those that are widely used are off-patent and cost little. This means there is little incentive not to prescribe them, from an economic point of view. The way health economics compares costs and benefits means that antibiotics don’t have to be that effective to be cost-effective, so they usually are. </p>
<p>This is a weakness of the methods. The biggest cost associated with antibiotics (using the economic definition of cost) is resistance. But it is a future cost, and one that is hard to measure at that. Future patients will get slightly more ill as a result of each antibiotic prescription we use now. That additional sickness is a cost all on its own, but on top of that those patients will be treated, and that treatment will cost. These combined future costs are likely to be significant; in fact they could be catastrophic. The solution, then, is to find ways of adding these costs into our calculations, presenting a more realistic picture of how much an antibiotic prescription truly costs. </p>
<p>There have been several attempts to quantify the cost of resistance, mostly from government agencies. These <a href="http://www.rand.org/randeurope/research/projects/antimicrobial-resistance-costs.html">tend to concentrate</a> on the productivity hit that would result from a sicker population. Ill people work less and spend less, either because they die earlier, or because of time taken off work to recover. These measures don’t account for the cost of illness itself to a group of people - the intrinsic value a society places on health. This is important because accounting only for the value humans have to productivity measures results in some distasteful findings. Namely that high-earning, working age males are the most valuable people in society. </p>
<p>Health economics has the tools to quantify the costs of future harm from antibiotic resistance, but currently the field hasn’t developed ways of measuring this, beyond the standard, unsatisfying productivity measures. In this area, at least, though, change is coming. Academic units are beginning to conduct research in this area, and a <a href="https://www.ncbi.nlm.nih.gov/pubmed/27402969">recent paper</a> even applied some of the future cost calculations to a cost-effectiveness analysis of antibiotics for chest infections, albeit using the old productivity measures of cost.</p>
<p>Health economics exists to try and address the question of what health is worth to society, and therefore what we should pay for it. Applying the tools economists have developed to answer this to the challenge of antibiotic resistance is likely to be key to illustrating the true human cost of this crisis, and pushing forward real change.</p>
tag:label.svbtle.com,2014:Post/do-we-want-to-be-precise-or-do-we-want-to-be-useful2016-08-12T11:29:40-07:002016-08-12T11:29:40-07:00Do we want to be precise... Or do we want to be useful?<p>The advantage of being in a department surrounded by non-health economists is that you get to hear all the opinions of health economics held by people who understand some, but not all of it. Clinicians, statisticians, etc. People who understand its applications but not its principles. </p>
<p>What I’ve learned from this is a greater understanding of where our communication falls down - that people don’t understand the cost-effectiveness threshold, or what a cost is, or why we count some values but not others when measuring health. Even if they can define a QALY and explain what NICE does, they don’t understand why. This won’t be surprising, but it <strong>should</strong> be. Our debates about health and costs should not be starved of the oxygen that is diversity of knowledge and experience. Understanding a health production function should not be a precondition to contributing to a debate on the value of health. We see this in other fields all the time - for goodness sake, recognising the contribution of non-experts is the entire basis for PPI, and, love or loathe it, its benefits are widely recognised. </p>
<p>But there’s more than this. The very nature of how we communicate our research requires economic knowledge. The mechanism for communicating research <em>du jour</em> is net monetary benefit. We take a universally understood value: health, and turn it into a price. Despite no-one understanding what a threshold means; despite no-one who does understand agreeing what that threshold should be in the first place; and despite the fact that we know people respond poorly to monetising health. It is a completely unintuitive way of representing health for anyone who is not already an economist. </p>
<p>And this has costs. If even clinicians don’t really get what the point of your numbers are, and you are dealing with a health system where clinicians are the predominant day-to-day decision makers, then surely you have a problem. The very way we calculate cost-effectiveness is inherently difficult for its primary users to understand. As a result, its primary users are not its users at all, instead we rely on an intermediary to proscribe from on high, and then are surprised when there is backlash from the people affected by these opaque decisions. And further, this then forces us back into our shells. Our work occasionally teeters on the edge of being truly useful for the health system we have, rather than the one we would like - value of information for the evidence we have; value of implementation for the, well, implementation we have. There are movements towards estimating the world as it is, rather than as we assume it is. But we have so far to go. We wonder at how decision makers disinvest from cost-effective treatments and provide no framework for them to make better decisions. We despair at the cost of “efficiencies” that are no such thing, but continue to value at the predetermined, evidence-free threshold. </p>
<p>The health economic literature, the blogs, the twitter streams are full of the precise language of economic theory. Hours upon hours go into trying to find the perfect definition for a specific health condition, and the purest consequence of a change in perspective. This is wonderful, interesting stuff; long may it continue. We are a field of applied researchers: the reason we try to nail down that perfect value is because it matters to patients. A bias in our analysis has a life or death consequence, somewhere down the line, for a person, or their mother, or child. We have a duty to get it right. </p>
<p>But we also have a duty to be understood. For the decisions we recommend to be taken up, the decision makers - the real decision makers; commissioners, GPs, nurses, patients, must understand why we have made them. In the era of value- and evidence-based medicine, when old truths are being questioned, and the curtain of the way things are done is pulled back to reveal that wizened old man, Habit, and nothing more, then we risk losing the fight we are all, in the end, fighting for: better health care, for more people, in the world as it is, in the hope that it might one day resemble the world we would like. </p>