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<?xml version="1.0"?>

<!DOCTYPE TEI.2 SYSTEM "base.dtd">




<title>Abdominal Aortic Aneurysms: Trial and Error</title></titleStmt>

<publicationStmt><distributor>BASE and Oxford Text Archive</distributor>


<availability><p>The British Academic Spoken English (BASE) corpus was developed at the

Universities of Warwick and Reading, under the directorship of Hilary Nesi

(Centre for English Language Teacher Education, Warwick) and Paul Thompson

(Department of Applied Linguistics, Reading), with funding from BALEAP,

EURALEX, the British Academy and the Arts and Humanities Research Board. The

original recordings are held at the Universities of Warwick and Reading, and

at the Oxford Text Archive and may be consulted by bona fide researchers

upon written application to any of the holding bodies.

The BASE corpus is freely available to researchers who agree to the

following conditions:</p>

<p>1. The recordings and transcriptions should not be modified in any


<p>2. The recordings and transcriptions should be used for research purposes

only; they should not be reproduced in teaching materials</p>

<p>3. The recordings and transcriptions should not be reproduced in full for

a wider audience/readership, although researchers are free to quote short

passages of text (up to 200 running words from any given speech event)</p>

<p>4. The corpus developers should be informed of all presentations or

publications arising from analysis of the corpus</p><p>

Researchers should acknowledge their use of the corpus using the following

form of words:

The recordings and transcriptions used in this study come from the British

Academic Spoken English (BASE) corpus, which was developed at the

Universities of Warwick and Reading under the directorship of Hilary Nesi

(Warwick) and Paul Thompson (Reading). Corpus development was assisted by

funding from the Universities of Warwick and Reading, BALEAP, EURALEX, the

British Academy and the Arts and Humanities Research Board. </p></availability>




<recording dur="00:42:43" n="5752">


<respStmt><name>BASE team</name>



<langUsage><language id="en">English</language>



<person id="nf0279" role="main speaker" n="n" sex="f"><p>nf0279, main speaker, non-student, female</p></person>

<person id="nf0280" role="participant" n="n" sex="f"><p>nf0280, participant, non-student, female</p></person>

<person id="sm0281" role="participant" n="s" sex="m"><p>sm0281, participant, student, male</p></person>

<person id="sm0282" role="participant" n="s" sex="m"><p>sm0282, participant, student, male</p></person>

<personGrp id="ss" role="audience" size="l"><p>ss, audience, large group </p></personGrp>

<personGrp id="sl" role="all" size="l"><p>sl, all, large group</p></personGrp>

<personGrp role="speakers" size="6"><p>number of speakers: 6</p></personGrp>





<item n="speechevent">Lecture</item>

<item n="acaddept">Medicine</item>

<item n="acaddiv">ls</item>

<item n="partlevel">UG/PG</item>

<item n="module">Health and Disease in Populations</item>




<u who="nf0279"><kinesic desc="projector is on showing slide" iterated="n"/> i'm <pause dur="0.2"/> <gap reason="name" extent="2 words"/> <pause dur="0.8"/> and <pause dur="0.6"/> i'm very pleased to be lecturing in this course and i <pause dur="0.3"/> saw some of the things on the board <pause dur="1.1"/><kinesic desc="indicates board" iterated="n"/> and i thought probably what i'd do is start with a single equation <pause dur="0.3"/> and this is the only equation you're going to see in this lecture <pause dur="0.2"/> and it's on the board there now <pause dur="0.7"/> now what does that tell you <pause dur="2.8"/> does it look even vaguely familiar <pause dur="0.6"/> to anyone <pause dur="6.2"/> <vocal desc="laughter" iterated="y" n="ss" dur="1"/> no i've probably got it wrong <pause dur="0.2"/> i thought it was something like the equation of relativity <pause dur="0.4"/> and the real reason i put it up there is that <pause dur="0.2"/> Albert Einstein <pause dur="0.5"/> was one of the very famous people <pause dur="0.3"/> to have an abdominal aortic aneurysm <pause dur="1.2"/> and i'm going to talk to you <pause dur="0.6"/> about <pause dur="0.2"/> abdominal aortic aneurysms <pause dur="0.3"/> so a more clinical flavour <pause dur="1.0"/> and how we use trial <pause dur="0.2"/> error <pause dur="0.4"/> and statistics <pause dur="0.6"/> in a real health <pause dur="0.2"/> problem <pause dur="3.5"/> i've sorted myself out with how to use this but i don't know whether i've got <pause dur="0.4"/> any sort of pointer </u><pause dur="0.3"/> <u who="nf0280" trans="pause">

yes there's a mouse <gap reason="inaudible" extent="1 sec"/> </u><pause dur="0.9"/> <u who="nf0279" trans="pause"> i use the mouse </u><pause dur="0.2"/> <u who="nf0280" trans="pause"> yeah </u><pause dur="0.7"/> <u who="nf0279" trans="pause"><event desc="finds pointer" iterated="y" dur="3"/> # well that's great 'cause the screen's gone off so i # <pause dur="0.2"/> oh okay <pause dur="0.2"/> right fine i've got you <pause dur="2.0"/> this is a cartoons of the aorta <pause dur="0.4"/> this is your aorta's nice and young and healthy <pause dur="1.8"/> these are the main branches of <trunc>th</trunc> the renal arteries <pause dur="0.3"/> this is the diaphragm <pause dur="1.9"/> as you get older the i mean i suppose one of the most obvious facial characteristics when people get older <pause dur="0.2"/> apart from greying hair like mine is wrinkles <pause dur="1.1"/> well just like your face wrinkles <pause dur="0.2"/> your blood vessels wrinkle too in a sense <pause dur="0.4"/> and they start sagging <pause dur="0.2"/> and this is what we call ectasia <pause dur="1.9"/> but in some people <pause dur="0.2"/> when they get older <pause dur="0.6"/> they actually balloon out <pause dur="0.5"/> their abdominal aorta <pause dur="0.6"/> and you probably remember from your anatomy if you've got that far <pause dur="0.4"/> that this bit <pause dur="0.3"/> the <trunc>but</trunc> the iliac bifurcation is about at the level of your umbilicus <pause dur="3.8"/> this nice little swelling of the aorta <pause dur="1.5"/> doesn't do anything you don't feel it usually <pause dur="0.4"/> no problems <pause dur="0.5"/>

in fact many <pause dur="0.3"/> people have no problems <pause dur="0.4"/> until it grows so big <pause dur="0.4"/> that it bursts <pause dur="3.1"/> and the diameters here <pause dur="0.9"/> whoops <pause dur="2.1"/> normal aorta <pause dur="0.4"/> somewhere between one-point-six and two-point-two centimetres <pause dur="0.7"/> and we start to call it an aneurysm <pause dur="0.3"/> when the diameter here exceeds three centimetres <pause dur="1.0"/> and they can grow really very big <pause dur="0.2"/> up to fifteen centimetres or more <pause dur="2.3"/><kinesic desc="changes slide" iterated="n"/> so this may not provide any symptoms <pause dur="0.4"/> but when this happens <pause dur="0.7"/> and the blood pours out into your belly <pause dur="0.3"/> onto the retroperitoneum <pause dur="1.5"/> extreme pain <pause dur="0.5"/> and collapse <pause dur="0.7"/> and the survival rate <pause dur="0.2"/> is very poor <pause dur="2.4"/><kinesic desc="changes slide" iterated="n"/> we can detect <pause dur="0.9"/> aneurysms <pause dur="0.9"/> using ultrasonography <pause dur="0.7"/> even though a person may not know they've got them <pause dur="0.5"/> if we do an ultrasonogram <pause dur="0.2"/> of the aorta <pause dur="1.2"/><kinesic desc="changes slide" iterated="n"/> we can see here <pause dur="0.3"/> this is an example of a very large aorta <pause dur="0.6"/> and in the middle here you've got colours 'cause this is colour flow showing the blood flow <pause dur="0.9"/> so here you've got an aorta <pause dur="0.2"/> slightly irregular <pause dur="0.4"/> but probably about seven centimetres in diameter <pause dur="2.7"/><kinesic desc="changes slide" iterated="n"/> if you go and do this to the general population <pause dur="1.2"/> and you choose men over

sixty years <pause dur="1.0"/> you'll find that five per cent of them <pause dur="1.6"/> have a small swelling of the aorta <pause dur="0.2"/> or an <pause dur="0.2"/> occult <pause dur="0.3"/> abdominal aortic aneurysm <pause dur="1.5"/> so it's not rare <pause dur="0.3"/> it's quite common <pause dur="0.7"/> and rupture of an aortic aneurysm <pause dur="0.9"/> is a common cause of sudden death <pause dur="1.1"/> and often <pause dur="1.0"/> you will see on a death certificate <pause dur="1.2"/> died from a heart attack or myocardial infarction <pause dur="0.5"/> actually it would be very difficult to discriminate if you didn't know anything about the history <pause dur="0.8"/> whether it was from a sudden major heart attack <pause dur="0.4"/> or a ruptured aortic aneurysm <pause dur="3.2"/><kinesic desc="changes slide" iterated="n"/> now the natural history <pause dur="0.7"/> of this condition <pause dur="0.5"/> is that once you've got a swelling <pause dur="0.7"/> it gradually increases in size <pause dur="1.3"/> and just like a balloon <pause dur="0.2"/> you might suspect that as it increases in size <pause dur="1.7"/> there's a bigger chance of it bursting <pause dur="0.3"/> or rupturing <pause dur="1.5"/> we've actually quantified this <pause dur="1.0"/> in <pause dur="0.2"/> over seventeen-hundred patients <pause dur="1.3"/><kinesic desc="changes slide" iterated="n"/> and the way we've done this <pause dur="0.4"/> is to break these <pause dur="0.4"/> aneurysms down by size <pause dur="0.4"/> we've put them into three groups <pause dur="0.5"/> very small <pause dur="0.4"/> small <pause dur="0.5"/> and larger <pause dur="1.9"/> and we've looked at a crude rupture rate <pause dur="0.4"/>

per a hundred person years <pause dur="1.9"/> very very small for these aneurysms <pause dur="1.5"/> becoming significant for these aneurysms <pause dur="2.2"/> and <pause dur="1.1"/> more than one in four likely to rupture <pause dur="0.6"/> for these larger aneurysms <pause dur="1.5"/> i understand you haven't learned about hazard ratios <pause dur="0.5"/> but this is another way of quantifying the risk <pause dur="1.3"/> as to how much the risk increases for each centimetre in diameter of the aorta <pause dur="1.9"/> and because various other things might influence rupture <pause dur="0.4"/> such as smoking status and blood pressure <pause dur="0.7"/> we've needed to adjust for those <pause dur="5.3"/><kinesic desc="changes slide" iterated="n"/> and from these series we looked at a hundred-and-three patients with ruptured aortic aneurysm <pause dur="0.2"/> and this was their fate <pause dur="1.8"/> twenty-six <pause dur="0.2"/> or <pause dur="0.5"/> about a quarter died without even reaching hospital <pause dur="2.0"/> fifty-three arrived in hospital <pause dur="0.5"/> but were too sick or ill to contemplate corrective surgery <pause dur="2.5"/> corrective surgery was planned in less than a quarter <pause dur="2.0"/> and # only a very small proportion <pause dur="0.5"/> about ten per cent <pause dur="0.6"/> were alive thirty days after the surgery <pause dur="1.6"/> so <pause dur="0.6"/> pretty dire consequences <pause dur="0.3"/> if your

aneurysm ruptures <pause dur="1.3"/><kinesic desc="changes slide" iterated="n"/> what does the surgeon do <pause dur="0.9"/> well the surgeon opens you up and has a look at your aneurysm and this is one here <pause dur="2.5"/><kinesic desc="changes slide" iterated="n"/> and he opens it up <pause dur="1.1"/> and he corrects it by inserting a Dacron tube <pause dur="0.2"/> or she preferably <pause dur="1.5"/> she's have got much better hands and more nimble hands than men <pause dur="0.2"/> whatever <gap reason="name" extent="2 words"/> might say in <gap reason="name" extent="1 word"/> <pause dur="3.3"/><vocal desc="laughter" iterated="y" n="ss" dur="2"/> so this is a cartoon of the operation <pause dur="2.0"/> now then <pause dur="0.2"/> you can't do this operation <pause dur="0.9"/> without some risks <pause dur="1.6"/> and it's quite difficult to ascribe <pause dur="0.3"/> a risk to this operation <pause dur="1.1"/> 'cause you can do this operation <pause dur="0.5"/> electively <pause dur="0.7"/> that is if you find <pause dur="0.3"/> by chance <pause dur="0.3"/> a large aneurysm in a patient <pause dur="0.8"/> say an eight centimetre one <pause dur="0.3"/> you might think the risks of this bursting are so high <pause dur="0.7"/> i need to do an operation to correct it <pause dur="2.9"/> if you go and read all those learned journals <pause dur="0.7"/><kinesic desc="changes slide" iterated="n"/> you will see <pause dur="0.4"/> that the risk of this operation <pause dur="0.9"/> depends very much on the type of study <pause dur="0.4"/> whether it is <pause dur="0.2"/> prospective <pause dur="0.4"/> or retrospective <pause dur="1.6"/> whether it's population <pause dur="0.3"/> based <pause dur="0.6"/> hospital based <pause dur="0.8"/> or

comes from a very selected hospital <pause dur="0.4"/> such as <pause dur="0.2"/> the National Heart and Lung Hospital <pause dur="3.0"/> and <pause dur="0.2"/> perhaps what you'll notice here <pause dur="0.7"/> is that the As <pause dur="0.3"/> the population based studies <pause dur="0.7"/> indicate that the mortality rate for this operation <pause dur="0.7"/> is quite high <pause dur="0.4"/> it's # probably somewhere in the region of eight per cent <pause dur="1.8"/> if you go and look at hospital based studies particularly retrospective ones <pause dur="1.3"/> the mortality rate drops <pause dur="1.6"/> and selected series <pause dur="0.7"/> published in the nineteen early nineteen-nineties <pause dur="0.8"/> from a very smart important hospital suggested that the mortality rate <pause dur="0.6"/> in really good surgeons' hands was only about two per cent <pause dur="2.2"/> now of course how do you report your <trunc>r</trunc> <pause dur="0.2"/> mortality rates <pause dur="2.4"/> you usually keep <pause dur="0.5"/> a record of consecutive patients that come to see you with this condition <pause dur="2.4"/> you can start that record <pause dur="0.3"/> when you like <pause dur="0.9"/> and you can stop it when you like <pause dur="2.6"/> so supposing <pause dur="0.9"/> that i have <pause dur="0.2"/> approximately two-hundred patients like this come to see me each year <pause dur="1.5"/> at the beginning of two-thousand-and-two <pause dur="1.3"/> the first two patients

operated on <pause dur="1.5"/> died within thirty days after surgery <pause dur="0.8"/> so i thought it would be better to start my series on the first of February <pause dur="0.4"/> two-thousand-and-two <pause dur="2.0"/> we then did a hundred operations <pause dur="0.8"/> and <pause dur="0.2"/> all the patients survived and did wonderfully <pause dur="3.1"/> by the time we came to patient a hundred-and-three in October two-thousand-and-two <pause dur="0.6"/> we had a little bit of run of bad luck <pause dur="0.9"/> and a few more patients died <pause dur="1.7"/> so when we wrote up this series for a learned journal <pause dur="0.7"/> we decided only to include those consecutive patients <pause dur="0.4"/> between the first of February two-thousand-and-two <pause dur="0.8"/> and the thirtieth of September two-thousand-and-two <pause dur="0.4"/> 'cause this gave us a perfect record <pause dur="1.6"/> it's very difficult to work out what the true mortality rate is <pause dur="0.5"/> for this operation <pause dur="3.6"/><kinesic desc="changes slide" iterated="n"/> but quite clearly <pause dur="0.2"/> given that there is a significant mortality rate <pause dur="1.2"/> if you find one of these aneurysms in somebody <pause dur="0.8"/> what do you do <pause dur="0.9"/> do you let it grow and rupture <pause dur="1.7"/> or do you offer them an operation <pause dur="1.1"/> and where's the balancing point <pause dur="0.5"/> in terms of the size

of this aneurysm <pause dur="1.3"/> and what else does it depend on <pause dur="1.2"/><kinesic desc="changes slide" iterated="n"/> and if you ask a vascular surgeon <pause dur="0.4"/> this person who operates on these <pause dur="0.7"/> they'll think it's going to be depend on the age perhaps the sex <pause dur="0.4"/> how fit are these patients can they still walk about <pause dur="0.8"/> have they got very good lung function <pause dur="0.3"/> and other physiological parameters <pause dur="1.6"/><kinesic desc="changes slide" iterated="n"/> so to find out about this and this was now about twelve thirteen years ago <pause dur="0.4"/> we did a survey of vascular surgeons in Britain <pause dur="1.2"/> and it's very useful <pause dur="0.3"/> to get information <pause dur="0.3"/> via professional bodies <pause dur="2.8"/><kinesic desc="changes slide" iterated="n"/> and it turned out <pause dur="0.2"/> that surgeons really <pause dur="0.2"/> had no idea what to do <pause dur="0.7"/> what was the best policy <pause dur="0.5"/> if they found a patient who had one of these swellings which was between <pause dur="0.4"/> four and five-and-a-half centimetres in diameter <pause dur="1.3"/> they didn't know <pause dur="0.4"/> this is a grey area <pause dur="0.5"/> and therefore <pause dur="0.3"/> it's an excellent area <pause dur="0.6"/> for a clinical trial <pause dur="1.6"/><kinesic desc="changes slide" iterated="n"/> and you might ask whether it was better <pause dur="0.4"/> to have a policy of early elective surgery <pause dur="1.0"/> or just monitor the size of the aneurysm there <pause dur="1.7"/> and see <pause dur="0.6"/> which was the best <pause dur="0.5"/>

treatment method <pause dur="0.6"/> with respect to <pause dur="0.2"/> how many deaths occurred <pause dur="3.0"/> vascular surgeons can't do this by themselves <pause dur="0.9"/> they need a lot of skills to put together a clinical trial <pause dur="0.3"/> including a statistician <pause dur="0.7"/> very good to have an important statistician <pause dur="0.4"/> however much you may think that <trunc>st</trunc> statistics is very difficult <pause dur="3.0"/><kinesic desc="changes slide" iterated="n"/> once you're doing a big complex trial it's useful to look at more than mortality <pause dur="1.7"/> and we wanted to look at quality of life of two treatments <pause dur="0.5"/> the costs of two treatments <pause dur="0.9"/> and the cost-effectiveness of two treatments <pause dur="2.8"/> also allowed us to look at other things <pause dur="1.1"/> such as the risk of aneurysm rupture <pause dur="0.4"/> perhaps some biological things as genes <pause dur="0.6"/> predicting <pause dur="0.3"/> prognosis or the rate of aneurysm growth <pause dur="0.6"/> and it allowed us to do some real statistical work <pause dur="0.6"/> which the statisticians did <pause dur="0.4"/> on how you model aneurysm growth <pause dur="0.6"/> and depending how the time goes as to whether i'll talk about that later <pause dur="2.3"/><kinesic desc="changes slide" iterated="n"/> design <pause dur="0.4"/> is always best when it's simple for something like this <pause dur="1.3"/> and <pause dur="0.2"/> from our poll of vascular

surgeons this was the grey area <pause dur="0.5"/> this was the area where they didn't know what to do so they could put their hands on their heart and say to the patient <pause dur="0.5"/> i don't know what to do <pause dur="0.9"/> i think you <pause dur="0.2"/> might have just as good a chance with early surgery <pause dur="0.5"/> or observation surveillance for growth <pause dur="0.9"/> and i'd like you to join us in a trial <pause dur="0.4"/> to see what's best for patients <pause dur="4.4"/><kinesic desc="changes slide" iterated="n"/> we had to try and work out before we started <pause dur="0.6"/> how many patients we would need <pause dur="1.4"/> and because you'd seen that on the group of people doing this <pause dur="0.9"/> the most populous group was vascular surgeons <pause dur="0.4"/> there was the automatic assumption <pause dur="0.6"/> that surgery <pause dur="0.4"/> would be best for these patients <pause dur="2.0"/> and i said it's quite difficult to know what the operative mortality is <pause dur="0.9"/> but they thought they'd go with the <pause dur="0.2"/> figures that suggested <pause dur="1.3"/> if you did an # <pause dur="0.2"/> operation electively <pause dur="0.4"/> two per cent of these patients would die <pause dur="0.5"/> within thirty days thereafter <pause dur="1.2"/> and because this is an <pause dur="0.4"/> older group of people <pause dur="0.9"/> there's a general mortality which they thought was six per cent per annum <pause dur="2.6"/>

they thought if you just had your aneurysm watched <pause dur="0.8"/> you probably had a two-and-a-half per cent per annum <pause dur="0.3"/> chance of your aneurysm rupturing <pause dur="0.4"/> and most of you would die if your aneurysm ruptured <pause dur="0.5"/> plus <pause dur="0.4"/> the normal six per cent per annum <pause dur="1.4"/> and on that basis <pause dur="0.9"/> we thought <pause dur="1.2"/> that after five years <pause dur="0.4"/> the survival <pause dur="1.5"/> and the survival is here on the vertical axis <pause dur="0.4"/> would be seventy-one per cent in those that had an early operation <pause dur="1.2"/> and <pause dur="0.2"/> sixty-two per cent <pause dur="0.7"/> in those that were just monitored to see whether they grew bigger <pause dur="0.3"/> to arrange where surgeons were convinced you needed an operation <pause dur="2.1"/> i understand that this is something you haven't dealt yet <pause dur="0.3"/> with yet is power <pause dur="1.0"/> but <pause dur="0.4"/> this is something we needed to have any chance of showing this definitively <pause dur="0.4"/> we had to recruit about a thousand patients <pause dur="2.7"/><kinesic desc="changes slide" iterated="n"/> we had to be careful about how we randomized these patients <pause dur="0.7"/> we couldn't allow any fiddling we couldn't have a series of closed envelopes in each centre <pause dur="0.3"/> where we were going to recruit patients <pause dur="0.3"/> 'cause we had

to do this through lots of hospitals <pause dur="0.3"/> and in fact we did it through ninety-three hospitals in Britain <pause dur="1.3"/> and so we used a central <pause dur="0.5"/> computer <pause dur="0.3"/> for randomization <pause dur="0.4"/> to avoid bias <pause dur="5.0"/><kinesic desc="changes slide" iterated="n"/> measurement <pause dur="0.8"/> trial and error <pause dur="0.3"/> and this is where we start talking about error <pause dur="0.9"/> and again this is a cartoon <pause dur="1.0"/> of using an ultrasound probe <pause dur="1.3"/> to measure both the maximum diameter <pause dur="1.0"/> and to see whether we could work out the ratio <pause dur="0.3"/> of the normal diameter here <pause dur="0.5"/><kinesic desc="indicates point on slide" iterated="n"/> to the maximum diameter here <pause dur="1.7"/><kinesic desc="indicates point on slide" iterated="n"/> and although it would be very nice to do this <pause dur="0.4"/> it turns out that <kinesic desc="indicates point on slide" iterated="n"/> here the # images are so fuzzy <pause dur="0.7"/> it's very difficult even for experienced people to measure <pause dur="1.9"/> and if you do it here <pause dur="0.5"/><kinesic desc="indicates point on slide" iterated="n"/> you can measure the diameter either from front to back <pause dur="0.4"/> A-P <pause dur="0.2"/> anterior posterior <pause dur="0.8"/> or from side to side <pause dur="1.0"/> and because of the actual physics of ultrasound <pause dur="0.6"/> you can measure it more accurately <pause dur="0.2"/> from anterior <pause dur="0.2"/> to posterior <pause dur="2.8"/><kinesic desc="changes slide" iterated="n"/> but we wanted to design this trial to work through five regions in Britain <pause dur="1.1"/> and each one have a dedicated trial coordinator who are going to

look after the patients and measure the size of their aneurysm <pause dur="1.1"/> so a question that <pause dur="0.3"/> came to our mind was <pause dur="1.2"/> could we be sure that different people <pause dur="0.4"/> would measure an aneurysm <pause dur="0.2"/> in the same way <pause dur="1.7"/> so we actually did <pause dur="0.2"/> a little experiment <pause dur="0.7"/> taking <pause dur="0.2"/> different people <pause dur="0.2"/> who knew how to use an ultrasound machine observers <pause dur="0.4"/> giving them <pause dur="0.3"/> an array of patients <pause dur="0.4"/> with different diameter aortas <pause dur="0.3"/> to see how well they did <pause dur="2.2"/><kinesic desc="changes slide" iterated="n"/> and we <trunc>h</trunc> <pause dur="0.6"/> the first study we did we had ten patients <pause dur="0.3"/> and then we increased the number of patients <pause dur="1.6"/> and we also looked <pause dur="0.3"/> and i'll tell you about that later on <pause dur="0.3"/> # looking measuring aneurysm diameter using a different modality <pause dur="0.2"/> computed tomography <pause dur="0.3"/> or C-T <pause dur="2.5"/><kinesic desc="changes slide" iterated="n"/> right <pause dur="0.6"/> here's the ultrasound <pause dur="1.2"/> the one you saw before <pause dur="0.3"/> you can measure this either in this dimension transverse <pause dur="0.5"/> or this dimension <pause dur="1.1"/> A-P <pause dur="4.0"/> using A-P <pause dur="1.1"/> and a large number of different patients <pause dur="0.4"/> we took just two <pause dur="0.3"/> single <pause dur="0.2"/> experienced ultrasonographers <pause dur="1.6"/> and we said <pause dur="0.4"/> measure these aneurysms for us and record them <pause dur="1.9"/> and this shows that data <pause dur="1.4"/> this is the

difference in aneurysm diameter <pause dur="0.3"/> recorded between <pause dur="0.2"/> ultrasonographer A and ultrasonographer B <pause dur="0.8"/> against the mean aneurysm diameter <pause dur="0.8"/> the mean of those two observers <pause dur="4.5"/> you can see <pause dur="0.3"/> that the distribution <pause dur="0.4"/> of results <pause dur="0.2"/> is around the zero line <pause dur="1.2"/> but for instance <pause dur="1.0"/> in this particular case <pause dur="1.2"/> observer A <pause dur="0.2"/> measured the aneurysm diameter <pause dur="0.9"/> at <pause dur="0.3"/> point-four of a centimetre bigger than observer B <pause dur="1.8"/> whilst here <pause dur="0.8"/><kinesic desc="indicates point on slide" iterated="n"/> they had measured it point-four of a centimetre <pause dur="0.4"/> smaller <pause dur="2.6"/> this type <pause dur="0.2"/> of display of data <pause dur="0.3"/> is known to me at least as a Bland Altman plot <pause dur="0.3"/> after two <pause dur="0.3"/> quite famous <pause dur="0.2"/> British statisticians <pause dur="0.4"/> Martin Bland <pause dur="0.4"/> and his partner Altman <pause dur="1.2"/> not partner <pause dur="0.8"/> domestic partner statistical partner <pause dur="2.9"/> <vocal desc="laughter" iterated="y" n="ss" dur="1"/> and it's a very useful way <pause dur="0.2"/> of displaying measurement data <pause dur="0.3"/> for error <pause dur="1.4"/> so <pause dur="0.3"/> we looked at this and we were appalled <pause dur="0.4"/> how could we hope to recruit patients from all over Britain <pause dur="1.3"/> measure aneurysms to make sure that they didn't grow bigger than five-point-five <pause dur="0.4"/> and have

this done reliably <pause dur="1.8"/> how do you think we could improve on this </u><pause dur="4.0"/> <u who="sm0281" trans="pause"> <gap reason="inaudible" extent="1 sec"/> </u><pause dur="2.6"/> <u who="nf0279" trans="pause"> one suggestion </u><pause dur="2.4"/> <u who="sm0282" trans="pause"> use the same person to measure all your aortas </u><pause dur="0.8"/> <u who="nf0279" trans="pause"> yes <pause dur="1.5"/> now if we're going to recruit people in Edinburgh and Plymouth </u><pause dur="0.2"/> <u who="sm0282" trans="pause"> <gap reason="inaudible" extent="1 sec"/></u><u who="nf0279" trans="overlap"> they're going to be <pause dur="0.2"/> pretty busy aren't they <pause dur="1.2"/> and interestingly <pause dur="0.7"/> a good way to reduce error <pause dur="0.2"/> and it must be very obvious to you when i say it <pause dur="0.3"/> is training <pause dur="1.1"/> in fact we wanted to make this trial work using just five people <pause dur="1.2"/> and we found if we trained them and trained them and trained them <pause dur="0.6"/> you use this part of the line <pause dur="0.3"/> to place your cursor <pause dur="0.6"/> for your measurement <pause dur="0.6"/> you angle the probe this way so you make really sure <pause dur="0.3"/> you've got the maximum diameter <pause dur="0.7"/> we found that we could do much better <pause dur="1.0"/><kinesic desc="changes slide" iterated="n"/> and here are just ten patients and five coordinators the ones we used for the trial <pause dur="1.3"/> and you can see that you still get a spread of aneurysm diameter this is now the patient number <pause dur="0.8"/> and this is the aneurysm diameter <pause dur="0.8"/>

measured by <pause dur="0.3"/> five different coordinators in different colours <pause dur="0.6"/> and you're still getting a spread of about <pause dur="0.4"/> point-three point-four millimetres <pause dur="0.7"/> but it's a lot better <pause dur="0.2"/> than the previous one <pause dur="0.7"/> with no training and no training together <pause dur="3.1"/><kinesic desc="changes slide" iterated="n"/> so <pause dur="0.8"/> i haven't shown you all of this but you need to measure the anterior posterior diameter <pause dur="1.4"/> you can't measure diameter that <trunc>re</trunc> reproducibly <pause dur="0.7"/> and this measurement error <pause dur="0.3"/> is really important in the way you design <pause dur="0.5"/> any work you do <pause dur="2.7"/><kinesic desc="changes slide" iterated="n"/> and what about computer tomography <pause dur="0.7"/> this is a C-T scan of an abdomen <pause dur="0.7"/> and this is the abdominal aorta here <kinesic desc="indicates point on slide" iterated="n"/><pause dur="1.5"/> <kinesic desc="indicates point on slide" iterated="n"/> this red line is the transverse diameter <pause dur="1.7"/><kinesic desc="indicates point on slide" iterated="n"/> this grey stuff round the side here <pause dur="0.3"/> is mainly laminated thrombus filling up <pause dur="0.2"/> the centre of the aorta <pause dur="1.7"/> and <kinesic desc="indicates point on slide" iterated="n"/> this is the outline it looks a little bit dark partly <pause dur="0.4"/> and white because partly because this is calcification in the aortic wall <pause dur="4.2"/><kinesic desc="changes slide" iterated="n"/> here we have <pause dur="2.9"/> a limited number of patients <pause dur="0.8"/> with known C-T aneurysm diameter <pause dur="1.2"/> we've taken our five observers

we used in the trial <pause dur="0.7"/> and we've asked them to measure it by ultrasound using the anterior posterior diameter <pause dur="1.0"/> and this is what we come up with <pause dur="2.6"/> first of all you will see that <kinesic desc="indicates point on slide" iterated="n"/> this line <pause dur="0.8"/> lies above the zero <pause dur="1.0"/> so the difference between ultrasound and A-P <pause dur="0.5"/> A-P <unclear>in</unclear> the C-T diameter <pause dur="0.4"/> is usually positive <pause dur="0.9"/> I-E <pause dur="0.3"/> we appear to be measuring the aneurysm larger when we use ultrasound <pause dur="0.3"/> than we <trunc>u</trunc> when we use C-T scan <pause dur="2.1"/> in addition there is something we haven't seen before <pause dur="0.8"/> in that there appears to be a positive skew up <kinesic desc="indicates point on slide" iterated="n"/> here <pause dur="1.5"/> that the difference <pause dur="0.8"/> between ultrasound <pause dur="1.5"/> and C-T appears to increase <pause dur="0.3"/> with increasing aneurysm diameter <pause dur="1.8"/> so here we have some evidence that there's some magnification <pause dur="0.3"/> or relative magnification <pause dur="0.5"/> associated with ultrasound <pause dur="0.8"/> but we don't actually know which the gold standard is <pause dur="0.3"/> and which is better <pause dur="1.6"/> this is again is a kind of Bland Altman plot <pause dur="0.9"/> and i suggest to you is much more informative <pause dur="0.4"/> than a straightforward correlation

line <pause dur="1.1"/><kinesic desc="changes slide" iterated="n"/> if we'd done a correlation line <pause dur="0.3"/> we'd have seen something lice nice like this <pause dur="0.5"/> oh <pause dur="0.3"/> fantastic agreement between the two different sorts of measurements <pause dur="0.8"/> and when you think about it <pause dur="0.3"/> you're measuring exactly the same thing <pause dur="0.3"/> you're measuring how wide the aorta is <pause dur="0.4"/> and just one you're using a C-T scanner and one you're using ultrasound <pause dur="0.7"/> so <pause dur="0.2"/> if it didn't agree very well <pause dur="1.0"/> well it wouldn't look very good would it <pause dur="0.9"/> and you <trunc>ca</trunc> <pause dur="0.4"/> not very informative at all <pause dur="1.5"/><kinesic desc="changes slide" iterated="n"/> so <pause dur="0.6"/> measurement <pause dur="0.6"/> <trunc>repea</trunc> <pause dur="0.6"/> random error <pause dur="0.3"/> reproduceability <pause dur="0.5"/> very very important <pause dur="1.5"/> but <pause dur="0.3"/> because ultrasound is safe <pause dur="0.4"/> it's cheap <pause dur="0.2"/> it's non-invasive <pause dur="1.0"/> and there are very few false positives or false negatives <pause dur="0.9"/> and it can detect ninety-nine per cent of aortas <pause dur="1.1"/> it's the chosen method <pause dur="0.8"/> for screening and surveillance <pause dur="0.7"/> of aortic aneurysms <pause dur="2.8"/><kinesic desc="changes slide" iterated="n"/> right <pause dur="0.6"/> so we did this trial <pause dur="1.2"/> we recruited patients <trunc>w</trunc> slightly more than the thousand we thought we needed <pause dur="0.4"/> over a four year period we followed them up to see how they did <pause dur="1.9"/> we flagged these patients with the

Office of National Statistics and this is a very valuable resource that we have <pause dur="0.4"/> in Britain <pause dur="1.4"/> whereas you can get <pause dur="0.3"/> at the end of a research project <pause dur="0.9"/> the date of death <pause dur="0.3"/> and the cause of death <pause dur="0.3"/> of patients entered into this 'cause they're all recorded centrally in Southport <pause dur="3.6"/><kinesic desc="changes slide" iterated="n"/> and this was the principal results of the trial <pause dur="0.3"/> as reported in the Lancet in nineteen-ninety-eight <pause dur="0.7"/> on the vertical axis here <pause dur="0.4"/> we had the proportion of patients surviving <pause dur="0.9"/> this is the time in years <pause dur="0.7"/> and this is the number of patients at risk at each time interval <pause dur="2.0"/> this kind of display is known as a life table <pause dur="1.4"/> we can see here in yellow the patients <pause dur="0.3"/> undergoing <pause dur="0.3"/> surveillance of their small aneurysm <pause dur="0.3"/> as opposed to those with early surgery <pause dur="1.2"/> and what we'd predicted was <pause dur="0.6"/> that the <pause dur="0.2"/> blue line would <trunc>h</trunc> be up here at five years <pause dur="0.3"/> and the yellow line <pause dur="0.5"/> would be <pause dur="1.0"/> down here <pause dur="0.2"/> <trunc>dow</trunc> way down here at five years <pause dur="2.4"/> we didn't find that <pause dur="2.6"/> fairly <trunc>f</trunc> steady attrition in the surveillance arm <pause dur="2.7"/> surgery arm <pause dur="0.9"/> marked attrition early <pause dur="0.9"/> levelling

off <pause dur="1.8"/> bearing in mind that <pause dur="0.3"/> out here having started with more than five-hundred patients in each arm of the trial <pause dur="0.4"/> not very many patients <pause dur="0.9"/> with so few patients the error around here <pause dur="0.3"/> is probably quite large <pause dur="2.6"/> but <pause dur="0.2"/> the statisticians the trial steering committee <pause dur="0.6"/> the journals and the public <pause dur="0.8"/> were convinced enough to <trunc>s</trunc> <pause dur="0.4"/> that this result suggested <pause dur="0.8"/> that there was no difference <pause dur="0.4"/> in survival <pause dur="0.7"/> if you operated early <pause dur="0.8"/> on this <trunc>condi</trunc> for this condition <pause dur="0.2"/> or whether you left it till later <pause dur="2.4"/><kinesic desc="changes slide" iterated="n"/> now very often one trial isn't <trunc>en</trunc> <pause dur="0.6"/> sorry <pause dur="1.5"/> we also looked at the health service cost 'cause i said we wanted to look at more things <pause dur="0.6"/> and this were the costs of the two treatments <pause dur="1.5"/> here <pause dur="0.2"/> early surgery and surveillance and you can break this down into how much the surveillance costs how much the hospital treatment for repair costs <pause dur="0.5"/> how much other health service costs are <pause dur="0.8"/> and the bottom line for this is <pause dur="1.1"/> that surgery is a much more expensive treatment option <pause dur="0.4"/> than surveillance <pause dur="1.3"/> and of course we live in

a <pause dur="0.2"/> cash-strapped <pause dur="0.3"/> National Health Service <pause dur="0.4"/> so this is important <pause dur="1.5"/> it perhaps wouldn't have been so important <pause dur="0.3"/> if quality of life <pause dur="0.8"/> had been <pause dur="0.5"/> different <pause dur="0.3"/> in the two treatment arms <pause dur="0.9"/> but there was almost no different in quality of life between the two treatment arms <pause dur="1.8"/> so therefore with a similar survival <pause dur="1.0"/> similar quality of life <pause dur="0.7"/> but one treatment <pause dur="0.5"/> costing <pause dur="0.2"/> much more <pause dur="0.2"/> than the other <pause dur="1.5"/> what do you think the National Health Service wants <pause dur="1.6"/> surveillance <pause dur="1.8"/> and in fact vascular surgeons across Europe <pause dur="0.6"/> were quite happy <pause dur="0.3"/> with this result <pause dur="1.1"/> and for these reasons <pause dur="0.8"/> probably wouldn't <pause dur="0.4"/> would no longer recommend <pause dur="1.3"/> elective surgery <pause dur="0.7"/> for patients with aneurysms less than five-and-a-half centimetres <pause dur="2.1"/><kinesic desc="changes slide" iterated="n"/> but you see here <pause dur="1.7"/> that the operative mortality rate <pause dur="0.4"/> in this population based study <pause dur="0.8"/> was far more <pause dur="0.2"/> than we'd used in the power calculations <pause dur="0.4"/> we'd expected two per cent <pause dur="0.4"/> taking from best vascular surgeon series <pause dur="0.6"/> and in fact it was five-point-six per cent <pause dur="5.5"/><kinesic desc="changes slide" iterated="n"/> and when since we started the trial <pause dur="0.2"/> there were several other <pause dur="0.4"/>

population based studies <pause dur="0.3"/> reporting the mortality <pause dur="0.4"/> for this operation <pause dur="2.2"/> turns out it for some reason it's lowest in Western Australia <pause dur="0.7"/> and i don't think it's just 'cause they have the most fantastic surgeons in the world in Perth <pause dur="0.4"/> or that it's the most fantastic place in the world to live <pause dur="2.1"/> i think very much probably most of these are very similar <pause dur="2.9"/> and the mortality associated with the elective repair of this condition <pause dur="0.5"/> is probably somewhere between five and six per cent <pause dur="1.3"/> it's not such a safe operation <pause dur="1.9"/> if you <trunc>thi</trunc> think of it another way <pause dur="1.1"/> probably somewhere between one in seventeen and one in eighteen patients <pause dur="0.9"/> that you operate on <pause dur="0.5"/> electively is going to die <pause dur="3.9"/> so we'd # managed to convince Britain and Europe that perhaps you shouldn't operate on these small aneurysms <pause dur="0.9"/> the Americans of course weren't convinced they don't have <pause dur="0.3"/> a <pause dur="0.2"/> National Health Service <pause dur="0.4"/> they have insurance based private <pause dur="0.2"/> care for most of their patients <pause dur="1.1"/> and they mounted a very similar trial <pause dur="0.3"/>

started the same time as the British trial <pause dur="0.8"/> and it's always nice to beat the Americans <pause dur="0.5"/> 'cause they didn't report their results until two-thousand-and-two <pause dur="0.2"/> four years later <pause dur="2.4"/> but they found exactly the same thing <pause dur="2.1"/><kinesic desc="changes slide" iterated="n"/> # <pause dur="0.3"/> almost exactly the <trunc>sa</trunc> # <trunc>s</trunc> <trunc>s</trunc> <pause dur="0.2"/> same numbers of patients <pause dur="1.4"/> that in terms of mortality <pause dur="1.1"/> although this is plotted as survival <pause dur="0.4"/> no difference <pause dur="1.4"/> depending whether you operate early <pause dur="0.6"/> or you don't you just watch it <pause dur="2.3"/> but however this was four years later <pause dur="0.8"/> and by that time <pause dur="0.2"/> because of the Office of National Statistics <pause dur="0.4"/> we had four years more information <pause dur="0.4"/> on the patients that we'd had in the British trial <pause dur="2.0"/> and what i'd said to you before was that we didn't have very many numbers out here <pause dur="1.6"/><kinesic desc="changes slide" iterated="n"/> we didn't we only had about fifty-two and sixty-three <pause dur="3.0"/><kinesic desc="changes slide" iterated="n"/> by the time we get to two-thousand-and-two <pause dur="0.4"/> we've got large numbers of patients out here <pause dur="0.5"/> we've removed some of the noise in these curves <pause dur="1.0"/> and we can see that these curves appear to be <pause dur="0.3"/> starting to separate <pause dur="1.1"/><kinesic desc="changes slide" iterated="n"/> ah and the vascular surgeons shout with

glee <pause dur="0.3"/> now we've got evidence that we can operate on these people <pause dur="0.3"/> 'cause they like operating <pause dur="1.6"/> but actually caution caution caution <pause dur="0.3"/> it doesn't really show that at all <pause dur="1.6"/><kinesic desc="changes slide" iterated="n"/> and you can look at this data another way <pause dur="0.4"/> you can integrate the areas under those curves <pause dur="0.5"/> and you can look at the average life expectancy of patients since their <trunc>ori</trunc> original enrolment in the trial <pause dur="1.6"/> and you can see that if you have early surgery <pause dur="0.3"/> that's your life expectancy <pause dur="0.6"/> if you have surveillance <pause dur="0.4"/> that's your life expectancy <pause dur="0.5"/> and there's absolutely no difference between the two of them <pause dur="1.5"/> again <pause dur="0.2"/> right out at the long time periods we don't have that many patients <pause dur="0.4"/> there's a large degree of error <pause dur="1.8"/> but there are some interesting reasons <pause dur="0.3"/> as to why those curves <pause dur="0.3"/> might diverge at a <unclear>late</unclear> <pause dur="0.2"/> time points <pause dur="0.6"/> and those reasons are principally attributable to the fact <pause dur="1.1"/> that the operation <pause dur="1.6"/> is quite a major trauma <pause dur="0.7"/> patients are in hospital for more than a week <pause dur="1.1"/> and the one thing it really <trunc>f</trunc>

does force them to do is to stop smoking <pause dur="1.6"/> and most of these patients <pause dur="0.4"/> smoke <pause dur="1.8"/> or have smoked <pause dur="1.0"/> or will tell you they've stopped smoking and are still smoking <pause dur="1.2"/> a prolonged hospitalization of seven to ten days <pause dur="0.3"/> really enforces that <pause dur="0.6"/> and a lot of the late benefit we might see <pause dur="0.4"/> might be simply attributable to the fact <pause dur="0.3"/> that those who have their operation early <pause dur="0.3"/> stop smoking early <pause dur="4.6"/><kinesic desc="changes slide" iterated="n"/> so <pause dur="1.5"/> if you come to a consultation at the end of last year or even at the beginning of this year <pause dur="0.9"/> and what's the evidence <pause dur="0.7"/> we've now got two trials <pause dur="0.6"/> and i think the evidence from both trials is <pause dur="1.1"/> don't operate on these aneurysms when they're small <pause dur="0.4"/> the risks <pause dur="0.4"/> of your patient dying <pause dur="0.6"/> afterwards are too high <pause dur="3.9"/><kinesic desc="changes slide" iterated="n"/> recently we've seen reported <pause dur="1.3"/> a trial of screening 'cause obviously one of the important questions would be <pause dur="0.3"/> well <pause dur="0.3"/> 'cause we can detect these and five per cent of people over sixty have got them men <pause dur="0.5"/> do we need to do a screening programme for them <pause dur="1.4"/> a screening trial was reported recently and suggested <pause dur="0.4"/> might

be cost-effective <pause dur="2.0"/> # <pause dur="0.7"/> but of course if a screening trial's really going to be cost-effective you need to find these things when they're small <pause dur="0.3"/> and you need to stop them growing <pause dur="0.9"/> how can we stop them growing if we don't know how to measure growth <pause dur="2.7"/><kinesic desc="changes slide" iterated="n"/> now there's a suggestion <pause dur="1.8"/> from retrospective studies <pause dur="1.0"/> that small aneurysms <pause dur="1.4"/> grow <pause dur="0.2"/> <trunc>s</trunc> <pause dur="1.0"/> more slowly <pause dur="0.4"/> than medium <trunc>s</trunc> <pause dur="0.4"/> size aneurysms <pause dur="0.5"/> and the largest aneurysms <pause dur="0.3"/> grow fastest of all <pause dur="3.0"/> we looked at growth rates <pause dur="0.6"/> of again <pause dur="0.3"/> seventeen-hundred patients <pause dur="0.6"/> this was their starting aneurysm diameter so that you can see that the main aneurysm diameter at the start <pause dur="0.4"/> is somewhere about four-and-a-half centimetres <pause dur="1.2"/><kinesic desc="changes slide" iterated="n"/> this was the nine longest series for aneurysm growth <pause dur="1.6"/> and the first thing you can see is just by looking at the shapes is <pause dur="0.5"/> that actually they're all different <pause dur="0.3"/> and actually <pause dur="0.4"/> one of them even gets smaller <pause dur="2.2"/> tells you we don't know very much about this condition <pause dur="1.7"/> some of them seem to fit nicely to exponential curves some to straight lines <pause dur="2.1"/> if you

look in the literature the only thing that had ever been used before <pause dur="0.4"/> for modelling aneurysm growths and taking <pause dur="0.2"/> data points and working out how fast do they grow <pause dur="0.3"/> was linear regression modelling <pause dur="0.8"/><kinesic desc="changes slide" iterated="n"/> and i'm sure you'll have heard of that <pause dur="0.5"/> trying to draw a <trunc>s</trunc> <pause dur="0.6"/> the best straight line <pause dur="0.5"/> between your points <pause dur="1.0"/> and i've drawn three lines on here <pause dur="0.4"/> four lines <pause dur="0.2"/> and you can see how bad they are <pause dur="0.5"/> for most of the cases <pause dur="0.5"/> if you draw just straight lines <pause dur="3.1"/><kinesic desc="changes slide" iterated="n"/> there's another problem <pause dur="1.0"/> when you've got real people <pause dur="0.5"/> and you've got continuous measures of data <pause dur="0.5"/> and i'm going to talk about aneurysm diameter but it could relate to anything <pause dur="0.8"/> and that's to do <pause dur="0.2"/> with truncation of series <pause dur="0.4"/> what makes <pause dur="0.2"/> you stop looking at someone <pause dur="2.5"/> going to consider a <pause dur="0.9"/> conceptual patient here or a virtual patient who starts with an aneurysm diameter of four centimetres <pause dur="0.8"/> has that diameter measured every six months <pause dur="0.7"/> no change no change <pause dur="0.9"/> no worries <pause dur="0.4"/> suddenly <pause dur="0.5"/> eighteen months <pause dur="1.1"/> there's a high reading and they've gone to

the five-point-five centimetre threshold where you might think about surgery <pause dur="1.1"/> the person's nice and fit <pause dur="0.3"/> still plays two rounds of golf a week or whatever <pause dur="1.2"/> and the surgeon says <pause dur="0.4"/> come in for an operation <pause dur="2.4"/> now perhaps if that <pause dur="0.2"/> patient had been coughing and spluttering <pause dur="1.4"/> the surgeon would have said <pause dur="0.6"/> i think we need to have a some sort of fitness programme before i think about operating on this <pause dur="0.4"/> come back and see me do this this and this we'll have some physiotherapy <pause dur="0.6"/> come back in so many months <pause dur="0.7"/> next time they come back <pause dur="2.3"/><kinesic desc="changes slide" iterated="n"/> the reading is <pause dur="0.3"/> ah <pause dur="0.4"/> just under four centimetres <pause dur="1.5"/> trial and error <pause dur="0.2"/> measurement error <pause dur="0.5"/> we can't measure it exactly <pause dur="1.7"/> ah <pause dur="0.4"/> not to worry now <pause dur="0.7"/> we'll keep on following you up <pause dur="0.3"/> and this is what happens <pause dur="1.8"/> and you can see that if you draw straight lines between these points <pause dur="0.3"/> you get quite slow aneurysm growth <pause dur="1.0"/> if you draw it between these <kinesic desc="indicates point on slide" iterated="n"/><pause dur="0.5"/> you get quite high aneurysm growth <pause dur="0.8"/> you truncated your series here <pause dur="0.5"/> and you've got an artifically high growth rate <pause dur="0.4"/> using this approach <pause dur="1.7"/> of course

that's not the only thing that happens to patients <pause dur="0.6"/> patients die <pause dur="1.7"/> let's take another patient <pause dur="2.0"/><kinesic desc="changes slide" iterated="n"/> four measures <pause dur="0.8"/> and suddenly they die <pause dur="0.3"/> from a myocardial infarction <pause dur="1.5"/> so <pause dur="0.7"/> you simulate their growth <pause dur="1.2"/> you get a nice line across here <pause dur="0.9"/> but if they hadn't died <pause dur="0.5"/> perhaps this would have happened <pause dur="1.2"/> and the growth rate would have been quite different <pause dur="1.3"/> so by not having this <pause dur="0.2"/> continuity that you can have in laboratory experiments <pause dur="0.3"/> where you can go and watch cells dividing <pause dur="0.7"/> for <pause dur="0.2"/> days on end <pause dur="0.9"/> people are different and there are other problems <pause dur="0.3"/> when it comes to trying to measure things and work things out <pause dur="1.5"/><kinesic desc="changes slide" iterated="n"/> statistician very clever no equations here <pause dur="0.4"/> use some flexible modelling <pause dur="0.5"/> i don't understand what any of this means and if <pause dur="0.2"/> you do you're all <trunc>h</trunc> absolute heroes and heroines <pause dur="1.6"/><kinesic desc="changes slide" iterated="n"/> but <pause dur="0.2"/> we can try and make some pragmatic rules <pause dur="0.6"/> using this modelling <pause dur="0.4"/> we want to know how to use data in clinical practice <pause dur="1.6"/> and we can therefore say that if you've got an aneurysm of four centimetres <pause dur="0.9"/> on average <pause dur="2.4"/> after five

years <pause dur="0.5"/> seventy per cent of them <pause dur="0.4"/> will have reached the five-point-five centimetres threshold where you can consider surgery <pause dur="2.6"/> if you start <pause dur="0.2"/> at four-point <pause dur="0.4"/> sorry i showed you four-point-five centimetres <pause dur="0.6"/> if you start higher # bigger find aneurysms bigger <pause dur="0.4"/> you'll probably know that <pause dur="0.3"/> your chance of reaching <pause dur="0.3"/> the <trunc>fi</trunc> <pause dur="0.2"/> the threshold <pause dur="1.8"/> the surgery <pause dur="1.0"/> within five years is almost a hundred per cent for big aneurysms <pause dur="1.1"/> so it can tell you <pause dur="0.6"/> start to be able to give you information so that you can sit down with a patient with a five centimetre aneurysm and say <pause dur="0.6"/> well i suspect your aneurysm's going to keep on growing <pause dur="0.3"/> and the likelihood is <pause dur="1.0"/> that probably in about five years' time <pause dur="0.3"/> we might have to think of an operation <pause dur="0.7"/> but don't worry about it at the moment <pause dur="0.5"/> and there's another reason not to worry about it at the moment <pause dur="1.1"/> now i'm going to go quite quickly <pause dur="0.3"/> 'cause having said that i want to get to the end <pause dur="0.4"/> and i know that it's nearly lunchtime <pause dur="2.1"/><kinesic desc="changes slide" iterated="n"/> but just to reinforce <pause dur="0.2"/> let's show you what <pause dur="0.2"/>

smoking does to aneurysm growth <pause dur="0.5"/> flexible modelling <pause dur="0.5"/> most of these patients with aneurysms have smoked <pause dur="0.7"/> this is the growth rate millimetres per year <pause dur="0.6"/> people who never smoked <pause dur="0.7"/> only twelve of those might as well forget about them <pause dur="0.7"/> ex-smokers <pause dur="0.4"/> some of these probably still smoking smokers don't like to tell you they can't stop smoking <pause dur="1.5"/> growth rate <pause dur="0.2"/> about two-point-four <trunc>millini</trunc> metres a year <pause dur="1.0"/> those who are actively smoking <pause dur="1.3"/> two-point-nine millimetres a year <pause dur="0.4"/> big difference <pause dur="0.3"/> so if you keep smoking <pause dur="0.3"/> you're going to grow faster <pause dur="0.3"/> you're going to come to surgery faster <pause dur="1.1"/> your lungs are going to be in worse shape <pause dur="0.2"/> and you're probably more likely to die <pause dur="2.0"/><kinesic desc="changes slide" iterated="n"/> if you'd used linear regression modelling <pause dur="0.4"/> this is what we'd have seen <pause dur="1.4"/> linear regression modelling <pause dur="1.2"/> exaggerates <pause dur="0.5"/> the effects of smoking <pause dur="1.4"/> and the possibility of giving up smoking <pause dur="0.7"/> in terms of helping your aneurysm growth <pause dur="1.6"/> and if we're going to be fair to patients we have to tell them this is what happens <pause dur="0.9"/> and not this <pause dur="0.6"/> and the reason this has

arisen <pause dur="0.6"/> is probably because of truncation of patients <pause dur="4.5"/><kinesic desc="changes slide" iterated="n"/> right <pause dur="0.3"/> good reasons for your patients to wait <pause dur="1.0"/> technology <pause dur="0.5"/> is moving very very fast <pause dur="1.9"/> you no longer have to repair aneurysms using conventional open surgery <pause dur="0.6"/> and you can use endovascular repair <pause dur="1.9"/> you can insert a device <pause dur="1.1"/> through the femoral artery <pause dur="1.3"/> sometimes under local anaesthesia <pause dur="1.6"/> anchor it here with expandable stents <pause dur="2.1"/> probably don't anchor it here <trunc>y</trunc> most of the new devices come down into the iliac arteries <pause dur="0.4"/> and look a bit like this <kinesic desc="indicates point on slide" iterated="n"/><pause dur="0.2"/> pair of trousers <pause dur="0.5"/> or like this <kinesic desc="indicates point on slide" iterated="n"/><pause dur="0.8"/> and you can <trunc>s</trunc> insert these <pause dur="0.5"/> through quite small catheters through the femoral artery <pause dur="1.1"/> new technology <pause dur="1.6"/> how do we find out whether it works <pause dur="8.3"/> blind faith from the manufacturers <pause dur="1.3"/> Johnson and Johnson to the success again making more money <pause dur="0.5"/> i'm now going to charge you <pause dur="0.6"/> oops <pause dur="0.9"/> i'm now going to charge you five-thousand pounds for one of these <pause dur="0.3"/> whereas a little bit of Dacron tube i sold you previously was only fifty quid <pause dur="1.1"/> fantastic <pause dur="2.1"/><kinesic desc="changes slide" iterated="n"/> this is one of those # <pause dur="1.5"/>

endovascular grafts being placed with a measuring device you can see all the little buttons going up there in the aorta to try the thoracoscopy when you place one <pause dur="1.1"/> and actually <pause dur="1.5"/> in population terms the health of the population <pause dur="0.3"/> we've got to find out <pause dur="0.6"/> whether the new technology is any good <pause dur="1.2"/><kinesic desc="changes slide" iterated="n"/> so we're starting all over at the beginning again <pause dur="0.2"/> although it's now been ongoing for two or three years <pause dur="0.5"/> with a new <pause dur="0.3"/> trial <pause dur="1.3"/> this time <pause dur="0.2"/> surgeons don't know whether it's better <pause dur="0.4"/> to treat these larger aneurysms <pause dur="0.5"/> with either the conventional open <pause dur="0.3"/> operation which everybody's been trained to do <pause dur="0.4"/> or with the new technology <pause dur="0.9"/> and this is being evaluated <pause dur="1.2"/> again <pause dur="0.2"/> we have to be aware of trial and error <pause dur="0.4"/> and measurement <pause dur="0.9"/> and we're very reliant on our statisticians <pause dur="0.9"/> to keep us in order give us the correct trial design <pause dur="0.3"/> and analyse the results correctly <pause dur="1.5"/> and even though i haven't <unclear>referred</unclear> to you <pause dur="0.3"/> any equations <pause dur="0.5"/> statisticians are absolutely vital <pause dur="0.5"/> for getting it right <pause dur="0.5"/> and getting the right information for the patients <pause dur="1.2"/> thank you for your attention <kinesic desc="applause" iterated="y" n="ss" dur="5"/>