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Joining Forces to Tackle Obesity, 21-22 January 2002

 

Transcript : Prevention and Management: The Evidence Base

 

Speaker

Mike Kelly
Director of Research and Information

Dr Caroline Mulvihill
Research Specialist in the Health Development Agency

 

DR WILLIAM DIETZ: The title of the next section is "Prevention and Management. The Evidence Base. Findings from the Health Development Agency Systematic Review of Interventions to Prevent and Manage Obesity". This will be introduced by Mike Kelly, Director of Research and Information, followed by Dr Caroline Mulvihill, the Research Specialist in the Health Development Agency. Mike?

 

MIKE KELLY: Can I have the first slide up please? Can someone from the technical side just give me a clue as to how you move these slides on?

 

Okay, well good morning everyone. My name is Mike Kelly and I’m the Director of Research and Information at the Health Development Agency. You already heard a little about that from Imogen, my colleague at the Department of Health, and I’m going to begin by saying just a few things about what we’re doing with respect to evidence generally, and then we’ll go on to talk about evidence specifically, as it relates to obesity.

 

The Health Development Agency was actually set up to have English only jurisdiction by statutory instrument following publication of the Our Healthier Nation white paper. We’re a successive body to the old Health Education Authority but, unlike that body, we have no responsibility for running campaigns, for doing that sort of thing. In particular, we’ve got a role with respect to the development of the evidence base to tackle health inequalities in England. And, in particular, to reduce health inequalities across the broad sweep of public health, including obesity, but also with reference to cancer, coronary heart disease, accident prevention and a whole range of other topics.

 

We’re driven, to some extent, by the research and development strategy of the Department of Health and the overall project in which we’re involved has a number of different elements to it. But what we’re trying to do, is to provide a systematic basis for using scientific evidence in public health. Now, of course, there’s been evidence around in public health for years and years and years. But, the fact is, until relatively recently, there wasn’t a systematic approach, either to pulling it together, to synthesising it or applying it to policy. So our task is to do that.

 

Secondly, to provide high quality evidence about reductions in inequalities and how they might be tackled. I should say that that’s actually a rather tricky problem because if you look at the evidence base in public health in the United Kingdom as a whole, and ask the question, how much of that evidence collected by Universities, funded by the Medical Research Council and others, how much of it actually relates to reducing inequalities and how much is about describing inequalities? Around about 96% of it is about describing the problem and a mere 4% is about solving the problem. So we’ve got to increase that evidence base in that sense.

 

Our task is also to bring the knowledge base together, importantly to identify the gaps - what we don’t know. We had an interesting presentation this morning on one of the sort of real problems we have, is that there are huge sways of material about which we know relatively little and, of course, our task is to underpin the Our Healthier Nation strategy and the NHS plan.

 

We want to move towards evidence informed interventions and improvements in obesity and other fields. We are interested in trying to improve health status, however you manage that, however you measure that. Whether by life expectancy, disability adjusted life years, quality of life, or whatever. We’re interested in improving the health status of the whole population, but we’re also interested in improving the health status for the most disadvantaged. And very importantly, a real trick or a real problem and the trick you’ve got to do to solve it, is that improving the health status of the whole population doesn’t mean that you improve the health status of the most disadvantaged. In fact, over the last 40 or 50 years, we have improved the health status of the population of the whole of this country but at the same time the inequalities gradient has got steeper. In other words, many of the interventions that we have up our sleeve, the things that we can do, improve the health status of part of the population but not the whole of the population. And what we have to do is to be able to break that apart and understand the kind of interventions, which work in different sectors of the population.

 

The materials you’ll find on our website dealing with a range of different topics can be, broadly speaking, characterised as follows. You will find systematic reviews of other research, you’ll find synthesis of research based materials - and I’ll talk a little bit about the synthesis in a second or two - gateways to other evidence based sites, bibliographical information, routine data about the topic in question, links to the public health observatories across the country, sections on what policies are going into practice at the moment and links to other HDA websites as well as a pot-pourri of other relevant material.

 

So, if you come on to the HDA evidence base website, you log on to obesity and nutrition by the end of this financial year - a month or so time - this is the kind of thing that you’ll find.

Our synthesis documents - and in a moment or two my colleague, Caroline, will be talking about one of these relating to obesity - follows the following format. We provide an executive summary on each topic. This is an example drawn from the first one to be published in a week or so time on the prevention of accidental injury. The main document following that executive summary has a protocol, an audit trail, about how we did what we did, how we gathered the evidence together. You’ll find examples of evidence that we know about what works, what’s effective - a series of recommendations relating to research and relating to policy. The headline statements in the content will identify where we know evidence to be strong, how weak it might be, if it’s inconsistent - and a lot of evidence is inconsistent - and how current it is. And that’s not just how up to date with the kind of cultural changes that Will Hutton was talking about in the first section. To what extent, did what we know 10 years ago might it still be applied now, where other changes have occurred?

 

Where are the gaps? What we don’t know - very, very important. What are the implications for inequalities? Very, very important as far as we’re concerned - as far as the ministerial team are concerned, too. What do we know about cost effectiveness, if anything? There are large areas in public health where we’ve got good cost effectiveness data. There are others where we know almost nothing.

 

Recommendations for future work and recommendations for policy. This is the framework of our synthesis documents and by the end of this financial year - in about 6 to 12 weeks time - we’ll have about 10 of these on stock and on our evidence based website for you to look at.

 

Now, we’re going to focus for the rest of the session on the content on this evidence based approach as it applies to nutrition and obesity and the leader of the team at the HDA on nutrition and obesity is Caroline Mulvihill, who is going to come up now and talk you through the headline findings about what we know to be effective with respect to these issues of obesity and nutrition. Caroline?

 

DR CAROLINE MULVIHILL: Good morning everyone. First of all, I’d like to thank the National Audit Office for inviting us to present today. As Mike has introduced our talk, my colleague and I, Rob, who’s sitting over there, have been working on a synthesis of what works to prevent and manage obesity. Now this will be available by the end of March 2002 on our evidence base website. This work will be continuously updated. This is a moving feat because we are conscious that new evidence is coming out all the time. There’s going to be two new Cochran views coming out shortly plus the Centre of Views and Determination review on obesity is currently being updated. When that is available we will put this on our evidence base as well.

 

And as you can see, here’s an example of our evidence base website and if you look at the bottom you can actually search by topic, population, setting and by types of evidence.

Now the vignette of our work is mainly on lifestyle interventions, so its diet, physical activity, behavioural therapy, that kind of thing. Our synthesis will not be covering the surgical or pharmacological treatment of obesity as this work is currently being undertaken by Nice, so it seems pointless to duplicate the work, but we have established links with Nice and at some point we’ll be sharing our learning.

 

The methodology now for developing our synthesis: We did an extensive search of the published literature dating back from 1996 through to December 2001. We followed up any queries with the literature with authors, we checked the reference lists of all the papers that we had coming in and we also consulted outside experts and, at this point, I’d like to acknowledge the help of Doctors’ Caroline Summerbell, who’s been acting as an external adviser to this work, and also to Dr Alison Abinall from the University of Aberdeen who helped us with research. She is currently doing the update of the CRD review of obesity.

 

The literature was collated and the quality was assessed in terms of transparency, for simplicity and relevance, and in total, nearly 140 review papers have been collated at this stage and Rob and I have read all these papers, filled in critical appraisal sheets and we have agreed which ones have gone on to the evidence base.

At this point I’d just like to highlight something about the papers that we have been gathering. We have been looking at reviews of studies where weight loss has been one of the aims of the studies. So where there’s been change in BMI, change in weight, change in percentage overweight, we have included those studies under our evidence base. So there are some interventions, say like healthy eating interventions or physical activity interventions where, although, as a by-product of intervention you would expect some weight loss. If it’s not specifically in the aim of the project we have not included this onto this current piece of work and we decided this at the end stages just to make the work a bit more manageable because, as you appreciate, this work can just grow and grow and grow.

 

As I said, this is very much a review of reviews and not a systematic review of individual trials. There are many centres across the country who are doing systematic reviews and we decided we would just do the review of reviews. Therefore, the work is based on systematic reviews, analysis and synthesis. And where there were no systematic reviews in a particular area we have decided to go down a level of evidence to high quality literature reviews in order to fill that gap.

 

So, as we are mainly speaking to systematic reviews, our finding a main base on RCT trials. However, if we have gone down by a layer of evidence to a high quality literature review these tend to be based on non-RCT, experimental or observation studies and where we have used lower levels of evidence in our synthesis, this will be indicated.

 

I’d now like to go on to present some of our top line findings from this work and it will mainly be on prevention, treatment and maintenance. And, again, I’d like to say this is very much top line findings and I’ve made the point of not going into too much detail about intervention. I’ve been very conscious that some of our later speakers on physical activity and diet are going into this in more detail.

 

So, what is the evidence base for the prevention of obesity in children? As you can see a recent Cochran review has showed there is limited quality data on the effectiveness of obesity prevention programmes and, as such, no generalisation or conclusions can be drawn. And there seems to be a mismatch between the prevalence and significance of the condition and the knowledge base in which to inform preventative activity.

 

Furthermore, another review carried out by Storey on the prevention of obesity in schools has done only a few primary prevention research studies, targeted specifically to obesity prevention, have been carried out and therefore the effectiveness has not been established. However, there has been some school based crime prevention programmes that target cardio vascular risk factors, but these have not proved effective in reducing the percentage of overweight.

 

However, there is some promising findings from the evidence, mainly in relation to sedentary behaviours and there is encouraging reductions in sedentary behaviours, may be useful. And this is based on two studies of American schoolchildren and as you can see the recent Cochran review also reinforces this finding.

Another promising finding, which was found in the, again, the CRD review was that family therapy sessions have been found to prevent the progression of severe obesity in children. And this was based on one study carried out in Sweden.

 

As you can see, talking now about the prevention of obesity in adults. There is very limited evidence to date. Only three community-based studies have been carried out and these have concluded that community based obesity prevention methods have not been proven effective. There is insufficient evidence to recommend in favour for or against community based obesity prevention programmes. And this has been found by a Canadian review carried out by Duccates. However, as we have been discussing for the last two days, many authors consider that with the huge health risks and the financial costs associated with obesity, priority should be given to the prevention of obesity over weight loss interventions. There is, therefore, an urgent need for further research in this area.

But again, like children, there have been some promising findings and some community based education programmes linked with financial incentives may be effective. And this is based on one theory to be carried out in the States, which is the Panda prevention study.

 

Let’s move on to the treatment of obesity in children. There have been from two good quality trials from the USA to suggest that intervention is designed to reduce sedentary behaviour are the most effective, which is very similar to the preventing of obesity findings. There’s lots of conflicting evidence regarding effectiveness of treating children and adults together. There’s been three studies, I think, carried out but they’ve all used small sample sizes and all conducted by the same North American research group.

 

And finally, the benefit of parental involvement may vary according to the age of the child. And may be a greater value of those aged five to eight years. Again this is carried out in studies looking into age groups 5 to 8 years, 8 to 13 years and 12 to 16 years, and the research has found that it was the 5 to 8 years that was most effective. I’m sure anyone out there who are parents appreciate that as children get older they’re less likely to comply with their parents’ wishes.

 

Therefore, there is a lack of high quality research or systematic reviews regarding the role of physical activity in the treatment of obesity in children. However, there is going to be a forthcoming Cochran review on this area, which hopefully should update some of this evidence.

 

I’d like to now move on to the treatment of obesity in adults. I’d just like to cover the main dietary strategies here. The first one being low calorie diets which is classified as a diet of 1,000 to 1,200 calories per day. This is from the National Institute of Health report. It’s an American review carried out in1998 and they found 34 RCT studies - there’s quite a lot of evidence there on the role of low calorie diets - and they found that regardless of the length of the intervention, low calorie diets did result in weight reduction and they can reduce total body weight by an average of about 8% over 3 to 12 months.

 

In addition, four studies that included a long-term weight loss and maintenance intervention lasting 3 to 4½ years reported an average weight loss of 4% over the long term. These effects can be long lasting. And finally, four RCTs show consistently the weight circumference issue, abdominal fat, also decreases with low calorie diets.

 

And next I’d like to move on to very low calorie diets, which is classified as 400 to 500 calories per day. Now, this is basic common sense but very low calorie diets produce greater initial weight loss than low calorie diets obviously because they are lower in calories. However, the long-term effect is no different from low calorie diets. Very low calorie diets is, when in conjunction with behavioural therapy, produce a greater weight loss, post intervention after 6 to 12 months compared to very low calorie diets or behavioural therapy alone. It seems a combination of the two works well together. However, weight regain is an issue for all these treatment options and the effect of providing a maintenance programme following initial weight loss requires further research.

I’d like to move onto lower fat diets. This is, again, from the same American review, which found nine RCTs on effective lower fat diets. These lower fat diets varied from 20% to 30% energy intake from fat and total calories in these diets range from 1,200 to 2,300 calories per day. And, as you can see, they found little evidence to support the use of lower fat diets per se, independent of calorie reduction. And what the second point is trying to say is, lower fat diets work because they reduce calorie intake. If you had a diet which was 2,000 calories but had a low fat diet of say less than 30% intake from fat you will not lose weight. Lower fat diets work because they help you reduce your total calorie intake. Now as you all know, fat is a more energy dense nutrient therefore if you reduce your fat you will reduce your calorie intake.

 

Before any diet here, I would also like to point out that there will be other dietary interventions in our synthesis such as the role of fibre and the provision of meal plans - we just haven’t got time to cover it today.

 

Now, the treatment of obesity to physical activity alone: again, as the slides show, physical activity can be effective in producing modest weight loss - two to three kilograms independent of the effect of calorie reduction through diet. However, if your goal is to use exercise alone as a strategy for obesity reduction you would have to do an exercise programme which would prescribe an energy expenditure of 3,000 to 3,500 calories per week. This has been taken from a review by Ross Inyanson, which although it’s not a high quality systematic review, this is a case where we’ve used a lower level of evidence because he’s found this paper quite interesting. And in order to expend the 3,000 to 3,500 calories, you would have to do apparently 45 to 60 minutes of purposeful walking and it would have to be fairly purposeful for 70% in maximum heart rate on most days of the week. And that’s a fairly high-energy expenditure. That’s about two to three times higher than your average physical activity intervention and, to that, 1 to 1½ days your total energy requirement. So if you wanted to use physical activity alone as a method of treating obesity you would have to burn some fairly serious calories in order to achieve that.

And I’d also like now to talk about the combination of physical activity and diet in the treatment of obesity. It’s found that the combination of reduced calorie diet and increased physical activity produces a greater weight loss than diet and physical activity alone. Now, the combination of the two, you would need two kilograms more than diet alone and five kilograms more than physical activity alone. And again, this is taken from the American review. So it just goes to show that by decreasing your energy intake, increasing your energy expenditure, that does produce that double whammy effect in order to treat obesity and it’s not the "fad" idea as outlined in this cartoon here.

 

We’d like to just talk a bit more about the role of diet in the treatment of obesity. The evidence shows that in order to treat obesity, diet is the more effective method. However, physical activity does have an important role in decreasing mortality and obviously reducing cardio vascular risk factors. Although, obesity does have its own factors that improve with weight loss independent of physical activity, therefore we’d just like to emphasise at this point, that in terms of research and policy there should be greater emphasis on diet rather than physical activity in weight management.

I’d just like to talk briefly about the role of behavioural therapy as well. Now behavioural therapy is the modification of behaviour patterns, new adaptive learning, problem solving, which is often used in conjunction with dietary therapy. As you can see here, the American review found that behavioural therapy used in combination with other weight loss methods provides additional benefits in assisting patients to lose weight in the short term, however, these benefits are not found in the long term. This, therefore, emphasises the great importance of continuing a maintenance programme on a long-term basis.

 

And finally, another quote from this report, they found that no one behavioural therapy appeared superior to any other, rather multi-model strategies work best - so a combination of various methods - appear to work best and those interventions with the greatest intensity appeared to be associated with the greatest weight loss. However, there have also been some promising findings in terms of behavioural therapy, which was found in the CRD review. One of those being queue avoidance, daily weight charting’s been found to be effective, behavioural therapy by correspondence - this is mainly in relation to, like long term outcomes - extending the length of the intervention period and they also said that these interventions would be of benefit when used with in conjunction with other weight loss strategies.

 

At this point, I’d also like to talk briefly about alternative therapies. Now the CRD review was carried out in the UK and the American review did say that they would be looking at alternative therapies. However, they were unable to find any RCTs that would meet their inclusion criteria. They would only include trials where the observation period was over one year so were unable to include any alternative therapies in their reviews, however, as we are not in the business of doing systematic reviews and we’re doing reviews of reviews we have actually found a number of very good systematic reviews on alternative therapies, which we have actually included in our work.

 

The first one being Chitosan. For those of you who are not familiar with Chitosan, Chitosan is a food supplement and it is derived from the cuticle of crustaceans. There has been a very good systematic review on the use of Chitosan and it was found to be effective in five studies. However, concerns were raised about the study design and the buyers. These five studies were carried out by the same research group in Italy and the research was funded by the supplement manufacturers. Therefore the author here, Ernst and Pittlar has suggested, "That effectiveness needs to be confirmed by more rigorous and independent tests".

 

There has also been a very good review on the use of gua gum. And this has not found to be effective for reducing body weight. There is also a number of adverse effects associated with its’ use, therefore gua gum cannot be recommended. It basically causes some fairly nasty side effects to the digestive system.

 

We also found some evidence on the use of acupuncture acupressure. A systematic review found contradictory results on effectiveness. Four trials have been carried out - two positive, two negative - in favour of acupuncture and the most rigorous of these four trials found no effect on body weight.

 

And finally, hypnosis. And there has been a whole series of metro analyses, which have been published on the role of hypnosis. The first paper was published by Kirsch, who’s listed at the bottom, and then there was another paper published in response to that paper by Ellison and then Kirsch responded back so there’s been a whole series of academic debate, more on method analysis, methodology, rather than the actual effectiveness itself. But looking through all these various papers that have been produced, it’s mainly based on one study that’s been carried out in 1980s, which did show some very promising findings, which lasted in the long term. However, there was a problem with drop out rates in the study. So, therefore, at this point we feel that the evidence appears promising but needs to have additional and more rigorous studies carried out to confirm or deny the usefulness of hypnosis, which is normally carried out in combination with behavioural therapy. So we haven’t dismissed this method all together because we think it could have a great potential, but it just needs further confirmation.

 

At this point, I’d also like to talk about the maintenance of weight loss and I’m sure you’re all familiar that it’s generally accepted that lots of people who lose weight tend to regain it. So we’d just like to talk about some evidence that we found on maintenance.

It’s imperative that effective maintenance strategies are built into any weight loss programme. However, there’s been very limited evidence to date that we’ve been able to find and most of it’s in relation to physical activity, therefore we conclude that physical activity may or may not play a role in long term weight control or in the maintenance of weight loss. And this finding was from a very good systematic review carried out by Fockleholm and Kookanan-Hardular which was just done recently and they found that high physical activity levels of about 1,500 to 2,000 calories per week are associated with improved maintenance of body weight and that the impact of the usual prescribed routines remain very limited.

There have been some very mixed results from RCTs and prospective studies on the association between physical activity and weight change and therefore conclusions cannot be drawn.

And finally, I’d just like to summarise with this table, which we’ve done sort of, as an overview of the evidence to date [Reference to visual aid]. As you can see we’ve divided it up into prevention, treatment and maintenance. And what works, and what is promising and what is conflicting. And as you can see, under the treatment in the adult section, that’s where we found the most evidence and it does go down in order of effectiveness. The most effective is diet with physical activity plus behavioural therapy. The next one is diet and physical activity, low calorie diets, very low calorie diets and, lastly, low fat diets and calorie restriction. And as you can see there are some empty boxes there. Now that doesn’t necessarily mean there is a lack of effectiveness, there is just a lack of evidence, and basically more research is definitely needed in order to move some of the interventions that’s in the ‘promising’ ‘conflicting’ boxes over to the ‘what works’.

 

And finally, we have also highlighted some gaps in the evidence, which we’d like to list today. The first one being population groups. Now as we discussed earlier, low-income groups and minority ethnic groups are a very much at risk group of obesity. However, from our research of the literature, there was no mention of these at all. Some mentioned it in the American literature but we haven’t tackled this issue at all in the UK.

 

Also, in terms of research, we feel that a general lack of a process evaluation of the intervention is being carried out. Many of them just describe x calorie diet was given to these people and this amount of exercise, and what we’d like to know is how did they recruit patients? How did they appear to their diet? Any problems they encountered, because this kind of information would be very interesting if we want to do any sort of roll out, at a national level. Also there’s very much a gap in terms of characteristics of effective interventions and also a complete lack of evidence on cost effectiveness and interventions.

 

And finally also, some gaps that we’d like to have filled in. It would be quite nice to have some sort of characteristics of those who have successfully lost weight in the long term. I know that in the States they have a register of people who have successfully lost weight and they use that to get the characteristics. Something like that would be very useful to have in the UK. Also the effectiveness of commercial weight loss programmes has not been proven yet and the benefit of targeting specific groups or applying a blanket approach to obesity to weight management.

 

And finally, is there a need for environmental population based interventions?

 

And that’s the end of my talk. Again, I’d just like to mention this is very much top line findings and the proper brief will be available on our evidence base website by the end of March. Thank you.

 

DR WILLIAM DIETZ: We have time for a few questions. Yes, in the back.

 

QUESTION FROM FLOOR: Thank you. I have a few concerns about some of the methodology that you have used in collating this data. And, in particular, I’m a little bit worried that we’re using different standards of evidence to evaluate different kinds of trials. So, for example, you’ve concluded that in relation to prevention, despite the fact that there are huge community based random out of control trials, which may not be the best model for assessing prevention programmes, but there’s no evidence that any of these work or have anything valuable about them. Yet, with some of the alternative therapies, despite the fact we’ve got very small scale short term studies in which there have been serious concerns raised over the methodology, they’re concluded to be promising. I’m particularly concerned about the Chitosan one, because Professor Ernst who did the review that you referred to subsequently did a follow up study himself which was the most rigorous study of a random out of control trial of Chitosan and showed quite clearly that there was absolutely no benefit over and above the dietary advice. And so, I really do think that if we’re going to take this systematic approach, that it is important to ensure we’re evaluating all studies against the same criteria.

 

ROBERT QUIGLEY: We went into this with a reasonably open mind about whether or not we look at alternative therapies and when we first got our hypnosis paper across the table we thought, "Crank, we’ll throw it out". And then we thought, "Well actually, why don’t we actually sit down and read it and assess what the authors have said about the effectiveness of those processes". For example, the Ernst one that you talk about - the RCT - he has criticised Chitosan quite strongly, especially those five papers and he criticised them based on their time period and the size of their study. The Ernst paper that you talk about had 17 people and went for 28 days so it itself was actually very, very small and over a very short time period. And, I suppose all we’re doing is, we’re going in with an open mind and we have got them in the ‘promising’ / ‘conflicting’ area. We haven’t put the exercise for the community interventions in the ‘conflicting’, we’ve put them in the ‘promising’ area, whereas we’ve put the Chitosan and the hypnosis in the ‘conflicting’ area. It’s just for ease of presentation that we’ve slipped them into the same category.

 

DR WILLIAM DIETZ: One more question - way in the back.

 

QUESTION FROM FLOOR: Thanks. It’s Ken Fox, Bristol University. I’m a little concerned that they’re all using terminology because, one, I don’t want to get into a debate of whether it’s exercise or diet - I think both are critical. But one conclusion that you made was that diet is much more efficacious than physical activity for the treatment of obesity. Surely, you’re talking about weight loss - short-term weight loss - when you make that statement. Because many people in this room would say that the treatment of obesity is about disease management, risk reduction, long term effects, and so I think that we be careful how we use the terminology here because that really does send out messages, which are not really represented in the literature, if you look at obesity treatment as being a long term management issue.

 

ROBERT QUIGLEY: I take the point. We did finish on the final slide saying that the most efficacious treatment is diet plus physical activity plus cognitive behaviour therapy with a maintenance programme that goes on long term. But for treatment, we did break it down by physical activity alone, diet alone and diet plus physical activity combined. And the point we wanted to make was that diet alone is far more efficacious than physical activity alone and that diet plus physical activity is more efficacious than any of those other two alone. So if you are looking at a group of interventions that you wanted to run in a country or in a practice or somewhere, you’d want to look down there and you’d want to make sure that a large number of them focus on changing people’s diets and you’d also want, obviously, some that changed physical activity, but you’d want to make sure that a large number of them focus on diet.

 

MIKE KELLY: What I think would help all of these, in a presentation like this, where we’ve condensed down evidence which, when this is a printed document, runs to about 80 pages, something like that. You’ll be able to decide, first of all a transparent account of the different levels in standards that are being applied which, I think, will answer the first question. We are not attempting to say, this is all the same thing. We are saying these are the different kinds of standards or these are the sorts of criteria with which we’re using and you can judge for yourself in terms of whether we we’ve kept our own standard and criteria.

 

And secondly, trying to weave across a whole range of 140 reviews, and maintain a coherent set of terminology, is simply not possible because for 140 plus all the primary research has been done in the first place, uses a variety of terminology and definitions somewhat differently. We have to, sort of, take a birds’ eye view on this, but you’ll be able to follow the audit trail back through to, I think, unravel some of those problems and difficulties that might emerge from seeing that the headlines of the statements that are in the presentation this morning.

 

DR WILLIAM DIETZ: Thank you. In order to keep the programme on time we’ll take additional questions up here during the break but let’s take a 15 to 20 minute break.