The EVAR trials were designed in 1996 and begun in 1999 for the purpose of scrutinising the safety and efficacy of the procedure. As is now well known, two populations of patients were available for the consideration of EVAR, those fit for open repair and those unfit. The DREAM trial had a similar protocol to EVAR 1 as does the OVER trial, based in the US. The latter is well under way and approximately three years behind EVAR 1. The OVER trial results are eagerly awaited, as it is vital to have confirmation of such important issues. And thus far, EVAR 1 and DREAM are remarkably in agreement.
Sadly, EVAR 2 remains unique and there seem no plans anywhere in the world to test EVAR 2 despite considerable surprise in the findings. This is regrettable as the trial points to the unexpected failure of EVAR to improve the lot of a patient unfit for open repair. Some doctors, frankly do not believe the result and are trying to carry on as if EVAR 2 never happened. However, there is ever more evidence that the fitness of the patient is of paramount importance in the decision-making. It would seem that there is a trend towards EVAR doing increasingly better than open repair, the fitter the patient. Thus there could be a range of patients for whom EVAR has been considered and in fact it may be predictable which is more likely to benefit from EVAR. In the future the range would point to poor or even no benefit in the very sick patients (EVAR 2) and a widening benefit gap over open repair for the fittest. This was not always visualised and, at first, there was a squabble over unfitness for open repair, and some clinicians suggested that these were “high risk” patients. It was later appreciated that “high risk” patients appear in EVAR 1 and unfitness for open repair means just that. In those circumstances, EVAR has a tough task to score any benefit. All over the world, on second thoughts, there are many instances now reported in which experts are saying that they find a small but recognisable group of patients with aneurysm, so ill that intervention simply is unlikely to alter the date of expected death.
We did not always know this and it was hoped that lives would be saved by speedy EVAR. There is another aspect which we have learned. At first we all learned EVAR with one device or another and some were more liberal with anatomical considerations than others. In the UK, Holland, Belgium, and now the US, colleagues have done very well to collaborate in these trials and the enthusiasm and concern to check the new technology has been very commendable on behalf of the patient interest. Results of many centres have been assessed by the radiologist locally and sent to the trial centre. It is clear now that some centres have demanded more of a device than others and, again, there is a gradation of anatomical suitability such that the most conservative clinicians can expect perhaps less reinterventions. Is this really so? We do not know for sure but if the same centre is performing and reporting, there are no quality checks. Thus, a core laboratory of three-dimensional measurements is desirable so as to be able to examine range of anatomical characteristics and how outcomes relate to them, if they do.
Is this important? It is at about this time that the regulatory bodies of various countries will start to examine evidence for safety and efficacy on behalf of the patient. The best data that are available and the longest running in terms of follow-up are these trials. The problem is that the trials covered an important early stage and we need to model the future with newer devices and more knowledge on patient fitness and anatomical suitability.
Modelling is the way to assess cost effectiveness. This is because cost effectiveness is a function of cost and of clinical benefit. Time must elapse to measure the benefit and regulatory bodies rely on a “model” to point them in the right direction. This places a great responsibility upon the team of clinicians and health economists who are charged with doing this task. Various “assumptions” are made as “best estimates” for the model and it is important to get this right.
From the above, it is clear that cost effectiveness will be influenced by a number of factors and EVAR will not be as cost effective to the same extent for every situation. Thus, for the very unfit patient with a large aneurysm where no open repair is possible, but EVAR is an option (EVAR 2) the mortality benefit in the one and only trial is zero and the cost is much greater by virtue of the procedure. It is not difficult to work out that the possibilities of funding available for this will be hard to come by! But the fit patient with a simple aneurysm anatomically would carry a 3% better operative mortality and probably even more than 3% better in the very favourable. Are the regulatory bodies going to find against that? I doubt it.
However, endovascular specialists cannot relax at this critical time and must be aware that EVAR is under minute scrutiny. Just look what happened when the National Institute of Clinical Excellence (NICE) released its findings on drug-eluting stents in the coronary circulation. Drug elution was conferring benefit but NICE did not like the price the taxpayer was expected to pay for this accepted benefit. So there you have it. If the clinical benefit is small and the cost is high, one body chooses not to buy. Does this affect just that country? No way. These bodies speak to each other. These decisions affect markets throughout the world and as a result of the NICE report on the drug-eluting stent, one really major company, is putting its non-cardiovascular business up for sale!
There are three main companies manufacturing EVAR stent graft systems: Cook, Medtronic and Gore with other important groups contributing a small share. The “big three” are putting much research funding into EVAR. Clinicians are using EVAR for their patients because they see the possibility of a relatively minor procedure, possible under local anaesthetic with little post operative pain. It is clearly important to assess formally what is the patient benefit. In the opinion of the patient not the doctor! It is not a case of which is the procedure the surgeon likes to do most or which earns him more money. The patient is the important witness!
What can we clinicians do at this stage to influence events? Can the companies play a useful role? The assessment procedure must be “whiter than white”. Of necessity, there is distance between the assessors and those assessed viz, companies and products and clinicians and techniques. However, it is clear that companies would be wise not to chose this time to hike the selling price upwards. They can also adopt a plan to prioritise the need to reduce the need for reintervention as this is disturbing for the patient and costly. Routine CT follow-up needs to go and clinicians need to be sensitive to ranges in terms of patient fitness and anatomy and to attempt to “pick winners” much more in the future than we have at the beginning of our experience. Core lab data could help in this regard and we should seek a scale of overall suitability for EVAR, which could tell us the likelihood of a good result with EVAR. We have to be prepared not to operate on the patient, which will “ruin the argument” ie. the justification of EVAR by the regulatory bodies. It would be a mistake to apply EVAR across the board without regard to outcome expectation and I predict that the regulatory bodies will find EVAR very good, safe and effective and the procedure of choice, provided selection is careful. However, cost effectiveness of EVAR remains in the balance.