I'd like to start this evening's presentation off by welcoming Dr. Helen Ashton,
who is a university clinical lecturer, a practising GP and an actual doctoral fellow.
She has also been a student on this course. So here is one of our success stories and tells that to talk to us today about a project that she devised
and put through to completion and is going to tell us about everything that happened along the road.
Thank you. Thank you very much. And thank you, Emily and Claire, for inviting me to speak today.
It's a great honour. And yet, as class as I was in your seats two years ago, pretty much two years ago today, I think.
And really I wanted to because I realise this is the study design and research methods module focus more than on the research itself,
on the process of kind of what took me from originally having the original idea and taking that all the way through to
publication and the kind of processes that that involves with all the many bumps along the road that go along with that.
So how many people here are doing the empty module at the moment?
The Study Design and Research Methods module. Okay. So most people and how many people are practising clinicians and how many people are surgeons?
Okay. Well, that's just useful for me tonight in terms of how I how I structure.
So most of the talk is made up of pictures. I realise you've been in lectures all day and so I want to try and make this a little bit
more fun and also that some people probably got up really early this morning to be here.
So I don't want you to to fall asleep and do interrupt me if you got anything that isn't obvious as we go along,
although there will be Question Time to ask me questions at the end and also drinks afterwards if you've got anything that you want to to know about.
So first of all, just to give you a little bit bit of background about me.
So as Claire said, I'm a I'm a GP.
I got to this week by doing my medical training at both Cambridge and Oxford,
and these are my lovely colleges that I was at and then did most of my clinical training at the John Ratcliffe Hospital here in Oxford.
After that and since then, I've sort of gradually become more involved in academia and academic work along the way,
and I've really been involved in some very diverse projects,
so ranging for many things, started off with a project on conjunctivitis, sarcoidosis,
a project on breathalysers, childhood immunisation, flu like illness in children.
And then more recently, I've just started a dphil looking at how we can use blood eosinophilia to predict responsiveness to inhaled steroids in COPD.
But what I'm here to talk about today is the Speed Bump Project to say this is a speed bump and talk about, as I say, the process involved in that.
So this is the finished thing.
This is the article which was published in the BMJ coming up for two years ago now, and this is the front cover of the BMJ where it was published.
It was the Christmas edition, which for those of you who don't know,
the UK in the British Medical Journal is very much a kind of fund issue that's published.
That is the final issue that's published before Christmas and often has articles in it which have a slightly a fun element that,
you know, that they have serious research articles but with something more quirky about them than the things that are published weekly.
Obviously, everything published day to day in the BMJ is very interesting, but these are particularly particularly fun articles.
So it really from from that sort of the week before Christmas in 2012 went a bit mad really.
And this is just a flavour of the media attention that this paper got in the week before Christmas.
I mean, I know it's I know this paper's used a lot as a teaching exercise on the courses.
And if you haven't come across it already, you probably will at some point,
particularly if you do the diagnosis and screening module, which I think is great.
So you should definitely do that. And there were a few different things.
So, you know, it ended up in various different newspapers all over the all over the Internet.
And I got to go on a few radio shows as well, which was which was really good fun.
So that's how I ended up. And I'm going to go right back to the beginning now with how it began.
So this is Stoke Mandeville Hospital. The statement of the hospital is now it's in is in Aylesbury, which is about 20 miles from here,
something that I say a bit closer and is known as a spinal rehabilitation hospital.
It was the first one and it's where the first Paralympics were held.
But my attachment, there was nothing.
What's so exciting is that it was just a general surgery attachment in my first, first job as a doctor back in 2009.
And I was what's called a House officer, which is the most junior or one which is the most junior grade of doctor.
And everybody has to do a little bit of medicine and surgery.
And so this was my surgery attachment based pretty much in the emergency Department of State Medical Hospital, which is this delightful building here.
And things really started at about 3 a.m. on a wintry evening back in 2009, when, as is often the case, I would go along with my registrar,
who was a more senior, a more senior surgeon, and make notes while the registrar was was taking the taking the clerk and seeing the patient.
And we saw a young girl who had been admitted with tummy pain, pain on the right side of her tummy.
And she and the registrar was taking the details of the history from the patient.
And then he asked her, how did you get to hospital?
And she immediately said in the car. And we went over the bumps and it was absolutely awful.
And he turned round to me and said, I don't need to ask any more questions.
We're taking her straight to the operating theatre and when asked about this afterwards,
he said he thought that it was a classical sign for knowing whether a patient had appendicitis or not.
Was the fact that the patient complained of having pain when they went over the bumps on the way to hospital.
And it turned out that a few of the other surgeons when when I and also another colleague asked them about this, they said, oh, yeah, you know it.
Everybody knows that. And it wasn't everybody,
but it was certainly something that was known about in that it was something that you could ask about that if patients had paid on the journey,
they may well have appendicitis.
And a colleague of mine, a chap called Khadar, who I worked very closely with at the time, he he actually had the brainchild for this.
I can't take credit for having the idea of actually abscesses up and the idea of of where we could publish it.
And he said, I bet there's no evidence on that. I bet that would make a really good article for the Christmas BMJ.
And so at that point we decided, great, let's, let's, let's go for that, let's aim for the Christmas BMJ.
And so from from that the study the study was born really.
So that was that was the kind of initial, initial starting point.
I realised that my audience isn't entirely from the UK is it.
Where's the furthest place that anybody's for us.
Anybody beat us. I think you do have speed bumps in the US, but I think they might be called speed humps.
Those they are called speed bumps as well. Okay.
That was one of the criticisms we got from the BMJ was that not everybody would know what speed humps were.
So we had to put a very detailed definition and which is a little bit bizarre, but there we go.
So speed bumps are devices, I suppose, that are put in the road to slow traffic.
And there is evidence that they are associated with a reduction in child deaths and that they slow traffic down,
but they are much hated by drivers as the drivers amongst you will realise.
And also because I realise not everybody is a clinician. I just wanted to say a little bit about appendicitis.
I think appendicitis is one of those conditions that it's very common.
People do have a bit of a general knowledge about them.
I don't think you really need to know much more than the general knowledge that you would have anyway.
But you appendix is part of the guts. It's located here and it can occasionally get inflamed.
And when it gets inflamed that's called appendicitis.
And it had the characteristic symptoms that it gives you is pain on the right side of your tummy,
characteristically pain which actually starts in the middle part of your tummy
and then goes to the right hand side a little bit later on in the course.
And that you can get pain. When doctors assess somebody who might have appendicitis, you get pain in that area.
And then you can also have something called rebound tenderness,
which is when you press in and then take your hand off, it's more painful when you remove your hand.
So that's another test that doctors and surgeons sometimes use.
It also gives you nausea and loss of appetite.
And the definitive treatment traditionally has been an appendix to me, an operation to remove the appendix,
which can be done either by an open root or more commonly now by keyhole surgery.
But actually,
there is also some evidence now for treating particularly mild cases of appendicitis with antibiotics rather than the rather than with with surgery.
And so I think that's probably what I'm going to say about the details of appendicitis.
Oh, no, I can say little bit more about it, which is that, as you know, it's common.
It's important not to miss it, because if you if you miss it,
it can lead to perforation that can cause infection in the tummy and, you know, and sepsis.
And potentially be very serious indeed. But there is also a degree of overdiagnosis and there's associated morbidity with overdiagnosis as well.
And in fact, there's a negative appendage accuracy rate of 5 to 42% in the literature.
So that means that of those that are removed, some of them won't actually, when you look at them under the microscope, show signs of inflammation.
And that's looking at the appendix. Under the microscope is often seen as the gold standard test for whether there is an appendicitis.
And as I say, sometimes it's classical and sometimes everybody has every sign in the textbook, but sometimes it's not quite so easy to diagnose.
And so there are scoring systems which exist, which use a combination of history,
examination and lab findings and also more now things like C.T. and ultrasound as well, too.
And to give more detail about them. Is that all right from the surgeon's perspective?
If I said anything that I disagree with that I realise I'm a GP talking about surgery, which puts me on slightly rocky territory.
But there we go. Okay, so the question that we that we came up with of how good a speed bumps at diagnosing appendicitis.
So I think this week and in the first module,
you will have been talking about Picos and I'm not sure quite how far you've got in terms of diagnostic accuracy studies, but they can be.
And instead of looking at a pico, you can look at a peer to peer support instead.
So instead of having the instead of having the comparison and the outcome,
instead you have the patients or participants exactly the same, the index test, the reference test, and then the target condition.
And then you use that, you compare the results of the index test and the reference standard to to get outcomes such as sensitivity and specificity.
Is that something that people have come across before as a concept? Lots of not good.
Okay. So in terms of our research question we looked at up was patients with possible appendicitis,
the index test pain over speed bumps and that was a worsening of pain from baseline.
So lots of these patients would be in pain already, but it was the idea that their pain would get worse when they went over the bump.
The reference standard, as I said, the gold standard test,
looking at the appendix under the microscope and seeing what it looks like is appendicitis on histology and the target condition,
obviously acute appendicitis. So we set up a surgical audit to answer this question.
So we looked at all the patients who'd been referred to the surgical take, either referred by their general practitioner, their GP,
or that had presented directly to the emergency department over a six week period between April and June 2009, and only was one of the junior doctors.
So it was quite easy to get other doctors to fill in a clerking performer or just to write in the notes as part of their clocking.
As I said, many people were asking about speed bumps anyway,
so I just encourage them to specifically write it down so that they could audit it and to fill in an audit proforma.
And then me and a colleague followed these patients through their admission to see what the outcome was,
either whether they were discharged straight home,
whether they were taken to theatre, and if they were taken to theatre, did they have their appendix removed?
And if they did, when they looked, then looked at that under the microscope, did that then confirm appendicitis or not?
And it was only if that confirmed appendicitis that they counted as a positive result.
And these histology details were initially looked at by me,
and then the findings were corroborated by a surgeon who was blinded to all the clinical
details because obviously that that would be quite important to avoid any observer bias,
because I obviously didn't know the clinical details myself. And so it would be possible that I'd be swayed in my result by them.
And the doctors were very obliging.
Lots of people filled them in during this period and 30 we included 32 patients and all of them had travelled over speed bumps,
which was because there was a speed bump on the entry to the hospital site, which was very convenient.
So this is the audit form that we used.
I'm not going to go through it in detail,
but it was just to ask the patients or to ask the doctor that was seeing the patients to particularly make sure they recorded these details.
They often would be recording them anyway. As I said, that these elements of history and examination form up various scores,
and this one particularly called the Alvarado School that we were using at Stoke Mandeville Hospital at that time.
So they were often recording all these details and then they were particularly recording how the patient had given the information, say,
whether they had volunteered that the journey was painful or whether they had to be asked
directly what was the journey like and whether they had to be asked directly about speed bumps.
And the idea was that we could stratify how good the diagnostic test was in relation to.
How strong they how strongly they volunteered the pain in the end with a sample of only 30 to the different number of boxes,
meant that it was it was impossible to do that, but that that was the aim anyway with this.
So I said I talk about a number of bumps along the way.
Does anybody in particular, anybody local to here know where this is?
No, it's Watlington Hill, which is part of the Chilterns is a very pretty area if you ever get to do any exploring while you're down here.
And I used to run I used to be a Brownie leader and Ron Brown, this is related, I promise.
I used to have brownies down in Watlington. And one evening, about two weeks before my wedding, we were doing a campfire on this on this white mark.
It was a good place to have campfires with the brownies. And we all parked our cars just outside along them along the roadside.
And this was my car back then. It was called Leek. And sadly, he's not with me anymore.
But he was a very old car but didn't have a great security mechanism.
You can probably tell where the story is going.
At the time I was collecting all the appendicitis data on these paper audit performers and they didn't have any patient details on them,
but they did have the entirety of the data that was being collected.
And at the end of this, at the end of having finished recruiting with all 32 performers in my car boot,
sadly, Luke was broken into while we were at the well.
We were having the Brownie campfire and I went back to the car and obviously my handbag had gone my wallet,
my phone, my driving licence, and I didn't care about the fact that I'd have to replace all this.
Two weeks before my wedding and honeymoon, all I cared about was the fact that they had taken the appendicitis data,
which, you know, I think the Brownies and the Brownie mums were like, Why are you not worried about the money?
She's worried about a load of sheets of paper, but for some reason, which I don't completely understand now,
instead of doing the sensible thing and calling the police, I decided to give chase to them.
So the guy breaking into the car, the other the other brownie,
the mums of the brownies said that there was a place about five miles away where dodgy things happened in the what like.
So Watlington is a very nice well-to-do area in the chilterns and this was in an area where dodgy things happened.
And so they suggested that this might be a good place to head. So at dusk on this particular evening, I headed to this.
It's a little minor road just behind Junction six of the M40.
So I'd suggest that you don't go down there because it's not a particularly nice place to go particularly late at night.
But as I drove down this little lane, I happened to notice in the hedgerow the Buckinghamshire Hospital Trust Antibiotic Guidelines,
which were on this colourful, you know, these colourful things that they were particularly easy to see.
And so I stopped. And then as I drove along,
I gradually saw more and more things that had been the contents of my wallet until I got to the dead end at the bottom of the road.
And there wasn't anybody, you know, I think by that stage they had gone by the time it takes me to get all my stuff together and follow them.
But in an area of bushes, a little walk away from the road,
I found my bag with all the appendicitis data still in it, which I think is pretty incredible, really.
So that is this is that if I hadn't managed to find this stuff, this probably would have never continued.
I think I probably would've just said, oh, well, it wasn't meant to be.
But anyway, the learning point from that bump is don't leave valuables in your car boot and always keep copies of data.
So there we go. Diagnostic Accuracy studies.
I suspect that you've come across this before a table, a two by two table looking,
comparing index tests to reference tests and using that information to calculate first all
sensitivity and specificity and then positive predictive value and negative predictive value.
If not, I think you'll do it with SU later in the week. Is it so that's doing it.
Yeah. And you may well use this paper as an example and say we did that and this is the results.
So you can see that this shows this positive column here shows all of those who were had a confirmed diagnosis of appendicitis.
So nine out of 11 people and that gave a sensitivity of 8 to 2%.
And then this specificity, which is the number, the number of two true negatives over the total in this column, gives the specificity.
And so you can see that this showed that the test had a relatively good sensitivity and a slightly less good specificity.
One of the major problems, though,
is these confidence intervals that our sample size of 32 meant that we had incredibly wide confidence intervals, so ranging from 48.
So a pretty poor test in terms of sensitivity all the way up to 98%, which would be a fantastic test in terms of in terms of sensitivity.
But we did show even with these results, with the the estimate, as we as we have them,
that this was comparable to or better than other diagnostic tests used in appendicitis diagnosis.
So comparing it to things like the migration of pain or rebound tenderness or nausea and vomiting, this looked better.
So this made us think this is this is obviously know this backs up what we thought in that it is a fairly decent, decent test.
So we presented it to the surgical audit meeting at statement of the hospital and planned to submitted for publication.
And then nothing happened for two years. So this is the second bump, which is just basically with these things.
It's just so easy for other things in life to take over, particularly if you don't have anybody to prompt you and say, get on with this.
You know, it's been six months and I've not heard anything from you.
And the problem with this project is that there wasn't really anybody like that.
It was kind of us that had started it. And so nothing more happened.
So I did lots more lots more medical jobs.
Both the John Ratcliffe and the Churchill bought a house, got married, had very busy uncle incubators, did various medical exams.
And it was only when I then came for my interviews, for my GP,
for the GP academic clinical fellowships that I think they asked at the interview something like Describe a project that you've done.
And I just thought, well, I'll mention the speed bumps for them and the interview panel were really excited by it.
They thought they said, That's fantastic. You know, have you not written this up for publication?
This is wonderful.
And I think I was really surprised that somebody outside of me who'd done the study and, you know, surgeons would be interested in it.
So when I started my my ECF and I had a little bit of academic time to do something,
I said to my supervisor, Anthony Harnden, you know, what do you think about this?
And he was equally very, very excited and said we should you know, yes,
you should definitely, definitely write this up and submitting it to Christmas.
BMJ sounds like a fantastic idea, so we went for it.
The learning point is don't let good potential projects fall to the wayside.
So we set about assembling a team of co-authors to write to submit to the BMJ.
So the surgical colleague that I had been involved in in the beginning was now a radiology trainee,
but wanted to but wanted to stay stay involved here.
And we involved a consultant surgeon so as to have a sort of content expert on the team,
found a medical statistician by wandering around the department.
And I've done a lot of work with Richard Stephens, who will be talking to you later in the later in the course.
I've done a lot of work with him since.
And actually the reason I started working at working with him was that he was the only statistician around on the day the Anthony Hunt.
And then I happened to be wandering around around the department looking for some help with with calculating confidence intervals.
So that's the way that's the way to get get involved in things, I guess.
And he had the unenviable task of trying to retrospectively calculate something resembling a sample size calculation for 32 patients,
which I think is pretty impossible, to be honest with hindsight. But he did a really good job of having a go.
And then also Anthony Harnden stayed involved as a as a sort of GP primary care research expertise person.
The third bump when we came to submit, there's a question on when you try and submit any research, was ethical approval obtained and if not, why not?
So some of you might have noticed that when we had done this originally, we called this an audit and we very much thought of it as an audit.
This was something that lots of the doctors in the hospital were doing already and.
We were just trying to find out whether it linked to whether, you know, what the diagnostic accuracy was.
And we weren't doing anything that kind of involved the patients directly.
However, the research ethics committees didn't necessarily agree with our logic on that,
and that guidance is very clear that any research proposal involving patients and
users of the NHS should go through ethics or should go through ethical approval.
Then there are kind of get out things in terms of surveys and service improvement and ways that you could not get ethics.
And we actually I have a friend who's a medical lawyer and we consulted her because she sits on lots of ethics committees.
And she did think it very much sat on the borderline and that it wasn't a problem to submit it.
You know, clearly we hadn't done anything morally wrong. We hadn't been doing stuff to patients without their consent.
But that probably it would be something which with with hindsight it would have been better to get ethical approval,
say, on the wording for submission. We, we wrote the study protocol was reviewed by a senior member of the Buckinghamshire
Healthcare NHS Trust who ruled that the study was a survey and under NHS research,
governance arrangements did not require formal ethical approval.
Now we never got picked up on that,
but I do wonder if it had got further at that stage we whether it might have sort of caused a problem when it came to publication.
So my learning point from that was always check ethical approval situation before embarking on any project.
And it's kind of made me a little bit obsessional about it with subsequent projects of just making absolutely sure that I've been through all
the hoops and I've got stuff in writing from the from the people that be to absolutely make sure that I don't need to get ethical approval.
However, it was not to be. I had on the 6th of October 2011, thank you for sending us this paper we sent.
It was for peer review, but we're sorry to say that we cannot publish it in the BMJ at this time.
Now, it would be would have been easy to think of this as the mother of all speed bumps.
I think this must be in the States. But we didn't the the reasons for rejection were kind of predictable.
And I don't remember being bitterly disappointed because I think I was sort of half expecting it.
They said we didn't have any specific criticism of the design or methods.
The main problem is the small sample size, which I think, you know, anybody looking at this could say, well, what did you expect?
It wasn't getting it into the BMJ with a sample size of 32 patients, but they said, we suggest that you might gather more data prospectively,
perhaps collaborating with clinicians from another centre to build up a bigger
sample so that a future analysis might not suffer from being underpowered.
If you can do this, we may be interested in seeing a resubmission for next year's Christmas BMJ,
so I'm sure that some people would have seen that and said, oh well that's, you know, it's that's only in a year's time.
This was on the sixth of 6th of October 2011 and getting a whole study together in time for December 2012.
Time for the submission deadline, September 2012, that that might be a bit impossible,
but I think I saw it as a challenge and the other people saw it as a challenge because these were
the comments that I immediately had backed by return from Anthony and Richard Anthony said,
Comments are excellent. Let's discuss extending the study with poor ethics approval.
That was because of the whole problem that we've had with the ethics. And in fact, since BMJ 2012, we may even be able to secure a small grant.
And Richard said this looks like a good opportunity to seek funding and do the study on a larger scale.
You could be really onto something here. So I felt like from the rest of my team that there was lots of positive feeling about it.
And so I thought, let's go for it.
So I think I've put a question mark by the fourth bump because I think actually it wasn't so much as a bump as an opportunity.
So I think seeing opportunity and failure and I think nobody gets anywhere without having failures along the way.
And you know, when this did come out and Christmas and Christmas, everyone was, you know, kind of like, wow, this is amazing.
But actually, it really wasn't a completely smooth pathway.
And, you know, the fact that it didn't get in the year before was very much a major thing along the way.
So as I say, a new challenge. First of all, we had to redesign the study to take account of the criticisms that we'd had,
that we'd had and things that we would have wanted to change anyway.
Doing it on a larger scale, going through ethical approval, and I'd never done a clinical study before.
So suddenly coming across all these ridiculous number of acronyms that you have to get your head around when designing a study.
And I only had about a month in which to get my head around all of it.
So I did my GCP training, which is good clinical practice filled in the IRS form.
I don't even know what that stands for. Some sort of form you fill in. It takes ages.
So yeah, leave more than a month to do it. The there's the research ethics committee, the local trust research and development.
There's this site specific form that needs to be filled in. You also need to get sponsorship.
The university that provides kind of legal cover and general support from a university point of view that clinical trials and research,
governance and then PR is the IS stands for proportionate proportionate review,
I think, which was something that had just come in a few weeks before,
which was really handy and was a two week fast track process for getting things to ethical approval.
Because I think for many things it does take several months and this was part of
a scheme to recognise that for studies that really weren't too controversial,
we could, you know, it could go through a lot more quickly.
We had to design a new protocol, come up with study packs, consent forms, think about funding.
In the end, we didn't actually get any funding. Everybody did it through goodwill and wanting to be involved in the study.
And I got a little bit of funding to pay for the cost of printing all the consent forms from an organisation called UK,
which is the programme that funds the Oxford ECF had to recruit staff because obviously I was
no longer working at Stoke Mandeville Hospital and I didn't have any contacts there anymore,
have the other people that we needed on the team.
So we asked Richard to still be involved as the statistician, and we were aware that we needed somebody to actually do the work,
so to get a research assistant as well, but without having anything to pay that research assistant with,
which was a little bit interesting, we had to get review of the protocol and Donald Sadiq Dick We did a review of the protocol for us,
which was really helpful and we really improved it as a result of getting their input.
And then we had to recruit a lot more patients compared to previously to try and get three to try
and get through the process in order to then submit in time for the Christmas BMJ the year after.
So the study redesign. This time we had some pilot data to go on for the from the first the first study that we've done,
although because of the wide confidence intervals, it again wasn't completely perfect.
But Richard came up with a great sample size calculation so such that we could
say that we needed to recruit between 100 and 150 patients to the study.
And that that was to show a significant difference in likelihood ratio compared
to rebound tenderness so that we were going to outperform rebound tenderness.
That was the goal. This time we were going to get written consent from patients and we couldn't get we couldn't ask the doctors on the
wards to actually take consent because otherwise they would all have had to have gone through good clinical practice,
training and things like that.
So we wanted it to be an entirely written process so that the patients could read all the information and sort of effectively consent themselves,
which is fine for a low intervention study.
We wanted to standardise the index test, so we designed a questionnaire that they had to complete within 12 hours of their arrival in the hospital.
And that was just because we were worried that a longer time than that and there'd be a degree of recall bias.
And then we also arranged a telephone follow up after discharge for those without appendicitis.
And the reason for that was because there was the possibility that patients might have
been readmitted elsewhere with appendicitis that we didn't know about in in that hospital,
because obviously we only had had access to the medical records within the hospital.
So I actually brought along some of the study paperwork because I'm aware that not everybody perhaps, you know, been through study recruitment.
So if you do want to either pass this around or come and have a look afterwards, then I'm very happy for, you know, have a leaf, have a leaflet.
So it's made up of participant information sheets, which patients had a read of beforehand, a consent form,
the patient questionnaire where we asked various details about their demographics, about their symptoms,
and then quite a lot of detail about their pain, whether they were in pain already,
whether the pain got worse when they went over a bump, and also how they got to the how they'd got to the hospital.
Plus, getting their contact details just for the purposes of cooling them, cooling them.
Afterwards, we asked the doctors to complete the data collection form.
As it happens, none of the doctors actually filled in the data collection form,
but the research assistant filled us in afterwards and then recruitment guidance for the clinical staff on the ward.
So Christmas 2011, I've tried to give a slightly Christmas flavour to this, given that it's the 1st of December.
I was saying to Claire beforehand that looking back in preparation for this talk, I went back through my emails in relation to speed bumps,
which I hadn't looked at in over a year, and the amount of email correspondence that went went round.
And at this time I was doing a really busy paediatrics job. And so I must have been, you know,
lots of them were sort of sent three or 4 a.m. and looking back I think what on
earth did I get the energy from to do would have to do all of that at the time.
But this was a I actually sent all the documents off to the university CTG, which was the first stage of getting ethics approval on Christmas Day,
a 7:48 p.m., which I was just amazed at looking back at, I think what on earth was I doing on Christmas Day?
Sending the sending ethics documents? But I think what happened was that we decided to delay Christmas because I was in the middle
of a horrible set of nights and celebrate Christmas several days later when I came off night.
So I'm trying to think that I wasn't being too overly keen and that actually it did it did make sense.
But part of getting this together so quickly was the fact that was the fact
that I had a really great team that was able to reply to emails within a few
minutes of me sending them and were willing to go to great lengths to get all
this ethical stuff in so that we could start recruitment as soon as possible.
So within about six weeks of having had the rejection, we'd already got all the documents ready for sending out to ethics, which, you know,
looking back on it was pretty phenomenal that we managed to do that because now, you know, the pace of research often does go a lot slower than that.
And people don't reply to your emails for ten days and things like that, and nobody did that.
Everybody was just really quick and realised that to get this going and to make a go of this,
we needed to be really quick, really prompt and a particular example of that.
The reason I've got a map of Africa which might seem rather odd is that at the time when I submitted to ethics,
they needed to have hard copy signatures or a real life signature within 24 hours of me submitting the forms.
And it happened that that coincided with Antony Holland and being in Uganda, Nigel,
who was the lead that I had and the surgeon who I'd recruited in Stoke Mandeville to lead the study kind of on the ground.
He was a senior house officer then he was in Egypt and then the other surgeon was somewhere in Europe.
And they were all. They went to the business centres at their hotels,
they scanned in their signatures and they just went to great lengths to kind of sort that out for me.
And I just, you know, I think that was actually amazing. And so, you know, the hard work and dedication from all the team really made this happen.
You know, I did work hard on it, but it really was, you know, it was it was really a team effort.
So in February 2012, recruitment started, we got ethical approval through on the 25th of January,
got all the documents printed within a few days, and I had the printing company primed to get it all done as quickly as possible.
And the idea was to get this so that it was already so that we could start recruitment at doctor changeover at the beginning of February.
Because for those of you that don't know, doctors change over on Wednesdays, which is a little odd.
And the people who were starting the six month jobs, it meant that we could catch them right at the beginning.
And that unfortunately coincided with snow.
And I had to I met with Nigel, who, as I say, is the guy who was running the study on the ground halfway between Aylesbury and Oxford.
And both of us braved the snow. And I met him at about 11:00 at night with all the roads closed, closed due to snow,
just to get all these study packs out state manageable in time for for the new doctors starting
but we did it I always like to put pictures of cats in my presentations so these are my cats,
Agnes and Pippa. And this was the first time that ever experienced the snow.
I think this is an eye garden and I'm not sure quite what they thought of it, but okay.
So the fist bump, I think this is the final bump. So the first four weeks of the study, we sadly only recruited ten patients, which was rather a blow,
given that in the pilot or the audit or whatever you want to call it, we recruited 32 patients in six weeks.
So this is quite a lot slower.
And the reasons for this were that, you know, I was I was probably the most enthusiastic and the keenest and I was based in Oxford.
Nigel who was the CHB running the study was based in High Wickham and all the other study staff were based in High Wickham or Oxford or elsewhere.
And we had recruited we had recruited a research assistant who was somebody who said that they were keen to be involved.
And we said, you know, you can be a co-author if you're the research, but, you know, it's just a bit unreliable, really.
You know, obviously it's very busy when you have, you know, hospital raters,
but just didn't have the kind of impetus to really get involved and go after work and fill in forms and encourage other people to recruit,
which was what we really, really needed. And the ones the the House offices that we wanted to go up to patients and say, there's this study going on.
I won't tell you much about it, but here's a study pack for you to read about and see if you want to fill.
And they just weren't really doing that. We tried to give them you know, we said that they could keep the pen if they wanted afterwards.
Whereas, you know, we we I thought that was great.
You know, you're always looking for a pen.
And in fact, we I kept topping up the pens that we had in the sort of study box that we kept in the emergency department.
And, I mean, we recruited in the end 101 patients.
But the number of pens I'd got through was about three times that.
So I think people were just using it for the whole emergency department must have
been using this box as a source of pens without actually recruiting patients,
which wasn't the idea. But never mind if I could have given pens to St Mary's Hospital then that's great though.
It was also. One of the other major problems was that in the meantime, in the sort of intervening two years,
there'd been a redevelopment of the hospital site so that the speedbump,
which guaranteed that everybody went over a speed bump, was no longer there, which was really, really sad.
So it meant that we'd gone from 100% of patients having gone over a speed bump to only about
two thirds of patients because statement was in quite a residential area in Aylesbury.
So still most patients had gone over a speed bump, but not all of them, which as I say, is just absolutely tragic.
How did we get around that? We recruited a new fantastic research assistant called Diyala, who was just wonderful.
She just had so much enthusiasm and she went off to work each day and recruited patients.
She'd be, you know, she yeah. She's the reason that the study was successful.
The plan Nigel called from Wickham every day to the on call staff because state manual and
Wickham on separate sites which is a little bit inconvenient and so it meant that he was actually
based on the other side most of the time we got the consultant who was meant to be kind of
overseeing the study to send repeated emails to junior staff saying this is absolutely compulsory.
We applied for a major amendment from the Ethics Committee to increase the time window of recruitment to 24 hours.
I thought this would be a minor amendment, but it had to go back through the ethics.
But luckily we didn't have to stop recruitment while we were getting that amendment.
So that increased to 24 hours and we looked at other ways to increase recruitment as well.
So things like chocolate certificates for participation, even more pens.
And so I think my learning point here that the local staff really have to be on board and interested and you have to
think about paying people to take part in your study or they have to have some sort of personal gain to want to do it.
And we reached our recruitment target in July 2012.
This is my data entry spreadsheet, which was very colourful and I was very proud of it.
I think I've done such a colourful data entry spreadsheet since.
So the final decisions after we've gathered all the data, we're chasing up the histology, which there's a kind of month lag on getting that,
which was a bit of an issue given that we were so tight to the publication deadline deciding on
how we were going to deal with the things like patients that had said they were unsure about,
about whether they'd gone over speed bumps, patients who'd been treated with antibiotics instead.
One of the other issues was that everybody was on holiday at the time that we were trying to write it up.
So I think if the deadline for submitting for Christmas BMJ was the 14th of September,
which meant that trying to write it up during August and August and beginning part of September was a bit of a nightmare.
So this is a picture of Castle Drogo,
which is in Devon and is where I was mildly trying to get a Wi-Fi connection to do some statistical analysis and correspond with Richard about things,
which was a bit of a challenge. So I was also I'm really not into it very much about the results because you can read
it in the paper and I wanted to focus on the process rather than the actual results.
But as I say, we recruited 101 patients.
43 of them had confirmed appendicitis, which gave a negative open secondary rate of 20%, which is about average and 68.
So about two thirds had travelled over speed bumps and we excluded four of them.
These are all the results. So you can see the two by two table.
Again, 33 out of 34 patients who were positive for appendicitis had been were positive, also positive for speed bumps.
So that gave us a sensitivity of 97%.
And what that means is that when a test has a really high sensitivity, it means that it's a really good rule out test.
So that means that if you if you don't have pain when you go over speed bumps, it's means it's very unlikely that you will have appendicitis.
The specificity, however, was really low. That's what you'd expect and is because the majority of patients did have pain when they went over bumps.
Most patients who were pain in pain anyway said yes, the bumps are more painful.
So it wasn't very specific. And actually lots of the patients who had pain went onto went on to be diagnosed with something else,
either another serious abdominal problem or didn't you didn't have anything wrong with them at all.
And when we compared the speed bumps to other diagnostic variables, we found that we had set out to prove what we wanted to,
which is that the sensitivity for the pain over speed bumps was better than these three other sensitivity.
So migratory pain, nausea, vomiting and rebound tenderness.
And also in terms of negative likelihood ratio, it was a better negative likelihood ratio than for all these things.
So in terms of proving that, it's making it less likely that you have appendicitis if you don't have that sign and we it was accepted.
So we submitted and we then had a very nice email back saying we were please say we would like to publish the paper in the Christmas BMJ.
We had quite a lot of they have quite a lot of comments and things they wanted to add detail on.
So making it more suitable for the US audience, as I said, some extra sensitivity analyses, more details in the methods.
We'd also got a comment at the end which we thought was quite amusing for Christmas.
BMJ saying that further studies would involve seeing if there was a difference between male and female drivers.
And we, you know, we thought this Christmas BMJ they'll go for it.
But we had several test comments back saying please remove the comment about male and female drivers.
It is unnecessary and not related to the research. And we were like, Yes, but that's the point.
But anyway, they, I think our humour didn't quite match their humour.
And the reason for the picture of Oxford Crown Crown Court is that I was on jury duty at the time and so was trying
to do all these re-editing at the same time as trying to decide whether somebody was guilty of blackmail or not.
And after we submit, after we sent in the revised comments,
we then had a lovely email back saying We are very pleased to be able to publish it this year, which was really exciting.
So this is Christmas 2012 when, as I say, all went it all went very, very chaotic.
So I was doing the MBTI two course two years ago. And during during the course, that was when I heard that they wanted to make a podcast.
And so I had loads of feedback from everyone else in the course about how we could write this podcast.
And, you know, particularly the surgeons in the course, you know, how we could make it relevant to lots of different people and recruited some,
some willing volunteers, particularly from the department, to be in the, in the podcast.
And so we made that a week or so later they they press released it.
And unfortunately the timing of the press releases when I had a full day in GP surgery.
So the reception. S were put on guard to put any reporters through, you need to put them on hold while I finish with my patient x my patient,
and then I try and slot them in between patients and things. So again, that's something that if that if you ever do anything, which is press release,
make sure you clear the day after it's going to be press release because it's not going to be have a full surgery full of patients.
But the university media team and the department media team were absolutely great.
And then I was on several radio shows, as I mentioned, one of them,
I had to come up with a Christmas joke and I managed to put it on Facebook saying, Does anyone have a joke?
And you've managed to find an appendicitis related joke, which was really good.
And there are two sort of good podcasts.
I'm not going to play you that. The BMJ, as I say, made a podcast which featured several people in the department and is very I think is good.
It doesn't just fit to me. It features lots of other people as well and is very, very funny.
I'm just going to pay you the naked scientists one,
just to give you a flavour of the sort of things that I had to talk alongside in the run up to Christmas.
And so Happy Christmas and welcome to the final episode of The Naked Scientists of 2012.
It's Christmas Eve. And so and only here with you.
And to celebrate this festive period, we're going to be taking a look at the lighter side of science this week,
including finding out why speed bumps are the best way to diagnose appendicitis, potentially.
Also, why reindeer have red nose.
This will speak to some of these animals on treadmills to find out is a real physiology experiment and we'll be meeting Cliff,
the dog that can sniff for sea do catch the one.
We also need you to send in your science questions first to us.
That's all I'll play. But it was kind of it was this bizarre thing because there was a kind of serious
aspect to our research and that this is a sign that you can use in practice.
But because it came out in the week before Christmas, it was you know, there were lots of things like the Christmas joke.
And everywhere that it was, it was presented it was presented as alongside this other article,
which was how Rudolph has his red nose, which was just quite, quite funny.
So I think that's all I'm specifically going to say. I've got a huge list of acknowledgements that I'm not going to go through specifically.
But, you know, as I said before, it was really, really very much a team effort.
And although I did work hard, you know,
everybody else played a really key role and I couldn't have done it without everybody else helping me, helping me along.
And lastly, I just wanted to thank my poor longsuffering husband, Michael.
This is a picture of him on the 23rd of December 2012, which was when I had promised to make a batch of sausage rolls for 20 people.
And unfortunately, I wasn't able to do it because of all the press release stuff.
And I ended up having to go on the Naked Scientist Show while at the time of making the sausage rolls.
And so this is him downstairs in the kitchen making it very meticulously making sausage rolls,
because I think the I think there was a I think you had to make them two and a half centimetres or an inch thick or something.
And well, normal people would just have guessed it. He did it with a tape measure.
But anyway, that's him while I was on them, while I was on the radio.
And so, yeah, I think that's all I have to say. And Merry Christmas and.