Introducing new anaesthetic equipment into clinical practice

Anaesthesia, 2008, 63, pages 571–575 .....................................................................................................................................................................................................................

Editorial Introducing new anaesthetic equipment into clinical practice A recent editorial in the British Medical Journal posed the question ‘How can we regulate medicines better?’ [1]. The authors concluded that European licensing regulations gave precedence to the interests of the drug companies rather than to the needs of the patients and doctors. There is a similar debate occurring in anaesthesia on the introduction of new medical devices into clinical practice: manufacturers are allowed to market many devices without being required to provide evidence of their efficacy [2, 3]. We recently published a paper on the Frova introducer in Anaesthesia [4]. During the review process, we were asked to provide ‘a statement outlining where you feel we should go comparing existing devices’. Here we outline our proposals to address this issue.

Related developments Recently, the Difficult Airway Society (DAS) has set up the UK Airway Device Evaluation Group to coordinate clinical studies on new devices [5]. The Association of Anaesthetists of Great Britain and Ireland (AAGBI) is revising its guidelines on the procurement of anaesthetic equipment published in 1994 [6]. The Centre for Evidencebased Purchasing (CEP), part of the NHS Purchasing and Supply Agency (PaSA) has recently funded Buyers’ Guides for laryngeal masks, to be published soon on its website (http:// www.pasa.nhs.uk/cep), and for laryngoscopes, to be published later this year. These guides contain suggestions of how to carry out trials on these devices. Introducers, laryngeal masks and laryngoscopes are examples of high volume, low cost medical devices where small differences in cost per item can lead to substantial annual savings for a Trust.

But, how can purchasers make an informed choice based on evidence of the efficacy of a device from the burgeoning number of devices on the market?

Why is making a choice so difficult? The sheer number of different devices within the same category of equipment makes it difficult for a purchasing group to make a choice. This is a comparatively recent phenomenon. Just a decade ago, the anaesthetist would use a re-usable laryngoscope to obtain a view of the patient’s larynx prior to intubation and then use a re-usable introducer if difficulty was encountered, over which the tracheal tube would be railroaded. The laryngeal mask airway was introduced in 1988 as an alternative to the tracheal tube, and this was yet another re-usable device. This equipment was intended for use on many patients. The methods of decontaminating and sterilising the devices then in use were assumed to be effective. In 1996, a new variant of Creutzfeldt–Jakob disease (vCJD) was described which was thought to be caused by an abnormal prion protein [7]. Patients succumbing to vCJD tended to be young adults and the disease was invariably fatal. Prions were discovered in the lymph system, including tonsillar tissue [8]. Laryngoscopes, introducers and laryngeal masks are placed close to the tonsils and are commonly contaminated when removed [9–13]. Subsequently, it was found that prions were not denatured by commonly used sterilising techniques [14]. The use of multiple-use equipment therefore posed an infection risk to the patient. This led to the AAGBI issuing guidelines recommending the use of single-use equipment where possible [15]. Subsequently, single-use versions of the laryngoscope blade, introducer

2008 The Authors Journal compilation 2008 The Association of Anaesthetists of Great Britain and Ireland

and laryngeal mask all became available. Although marketed and intended to reduce the risk of transmission of vCJD, the move to using single-use devices may have inadvertently increased the risk of causing harm to patients [16]. Therefore, there is a balance to be struck between the risk of acquiring vCJD (which now appears to be minimal) and the risk of causing harm, or worse, to the patient by using inferior single-use equipment. In addition, the marketplace has become much more competitive: for commercial reasons many suppliers now offer devices intended for the same purpose to the anaesthetist. For example, when the patent expired on the cLMA in 2003, other manufacturers placed similar devices on the market. Thirty different laryngeal masks were included in the CEP Buyers’ Guide (single-use and multiple-use, standard and flexible) obtained from 12 suppliers. Even more have become available since the report was drafted. Only a few of these new devices have been tested in clinical trials. Similarly, there is a plethora of new laryngoscopes (blades and handles, both single-use and multiple-use) available for use with adults [17] and children [18], and many introducers are also now available to the anaesthetist [19]. Again, few of these have been tested in clinical trials. It might only become apparent that a new device is not as effective as the device that it is intended to replace when an anaesthetist uses it in a patient in clinical practice. When a difficult intubation is encountered, and the anaesthetist has to work quickly to provide adequate oxygenation, any delay caused by an inadequate device is unacceptable. Patient safety is paramount and must underpin any choice of equipment.

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Editorial Anaesthesia, 2008, 63, pages 571–575 . ....................................................................................................................................................................................................................

Introducing new equipment – current practice The current guidelines published by the AAGBI in 1994 [6] predated the introduction of the Medical Device Directive (MDD) in 1995. All medical devices now placed on the market in the United Kingdom have to bear the CE Mark, meaning that the manufacturer declares that the device complies with the Essential Requirements of the MDD. A novel, innovative device has to go through rigorous trials to demonstrate that it is safe. Another manufacturer might then place a ‘me too’ device on the market. This manufacturer merely has to claim that its device is equivalent to the existing product and, in many cases, the manufacturer then does not need to carry out any substantial testing or clinical assessment on the device before applying the CE Mark. The classic laryngeal mask airway (cLMATM) (Intavent Orthofix, Maidenhead, UK) is an example of a novel device. There is substantial evidence that it provides a high first time insertion success rate, an adequate seal and that it is easy to insert and remove in both adults [20] and children [21]. Randomised controlled trials (RCTs) have been carried out to compare some of the newer laryngeal masks [22–31] with the cLMA, but not the majority of devices included in the report prepared for the CEP: RCTs are undertaken in a rather haphazard and uncoordinated manner. In addition, the cLMA is recommended for use as a rescue device in the DAS guidelines on the management of the difficult airway [32], but it is not clear whether other laryngeal masks are as suitable in this scenario. One route to placing the CE Mark on a device is to demonstrate compliance with the relevant standard for that device. Unfortunately, at present, not all medical devices have a particular standard. For example, there is currently only a draft standard for laryngeal masks and other supralaryngeal airways [33]. However, even when a standard is published, it is not mandatory for a device to comply with the requirements of that standard [34].

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Hence, problems with a new device may only become apparent when it is actually used on patients. In accordance with the MDD, every manufacturer is required to have a surveillance system in place so that any problems reported during use are investigated. Thus, anaesthetists are an essential part of this vigilance system. Any incident with a device that harmed or could have harmed the patient or staff must be reported to the manufacturer and, in the UK, to the Medicines and Healthcare products Regulatory Agency (MHRA), as the competent authority. The report can be made on the MHRA website at http://www.mhra. gov.uk. However, from our experience with introducers [35], devices continue to be sold that demonstrably could cause trauma and have poor placement characteristics. In addition, from our recent survey [19], it is clear that incidents where introducers have caused trauma have not been publicised in the literature or presumably reported to the MHRA. The guidelines published by the AAGBI in 1994 [6] state that the reasons for the choice of equipment should be produced by the anaesthetists who will be using the equipment. But how is a person responsible for ordering equipment able to choose a safe and efficacious device from all the different products available in a particular category? In many Trusts, trials are carried out on new devices and the results of those trials are presented at audit meetings. During the preparation of the report for CEP, audit presentations were sent to us. The results may have made the choice easier for that particular Trust, but that audit might be repeated at many other Trusts, duplicating scarce resources and potentially harming patients if devices with poorer efficacy were being used. In addition, fiscal pressure results, in many cases, in the cheapest equipment being purchased without any evidence of its safety and efficacy. Such equipment could potentially cause harm to a patient. A different system is required to provide the necessary evidence. Our proposal is as follows.

The proposed scheme A structured, coordinated approach for choosing which devices to assess is needed. A Device Evaluation Centre needs to be established to operate the scheme. A Panel of Experts drawn from professional bodies needs to be established to critically appraise the available evidence on devices and make recommendations of which are suitable for use, in a similar way to that on the Bandolier website (http://www.jr2.ox. ac.uk/bandolier). The Panel should also list products considered to be the ‘gold’ standard within that category of device. A website should be established so that relevant information is freely available to healthcare professionals, manufacturers and the general public. Considering the number of devices of a particular type (e.g. laryngeal masks) on the market, to compare each and every new device against a ‘gold standard’ would take some considerable time. Therefore, some of the poorer devices could be initially removed from a list of potential alternatives using the results from simple laboratory-based assessments, perhaps testing to published or draft standards where these are available. Anaesthetists would then assess those devices that complied with the requirements of these tests using manikins. Protocols for testing introducers [35], laryngeal masks [36] and laryngoscopes [17, 18] using manikins have been described. Finally, clinical studies would then be carried out comparing suitable devices that are likely to be an acceptable alternative to the ‘gold standard’ device in that category. One problem with such a comparative clinical study is that the outcome is likely to be ‘negative’: the new device is not required to be superior to the existing ‘gold standard’ device clinically, but just as good as that device. The advantage of the new device could be that it is more competitive in terms of cost or its environmental impact, for example. In this case, the type of study required to compare a new device with the existing ‘gold standard’ is not the usual superiority-type trial, but either an equivalence or non-inferiority study [37]. The new device is an acceptable


Anaesthesia, 2008, 63, pages 571–575 Editorial . ....................................................................................................................................................................................................................

Establishment of a Device Evaluation Centre The Device Evaluation Centre should: coordinate assessments of a defined range of medical devices used in anaesthesia; establish and manage a website containing details of all relevant information on products including clinical trials in progress, timescales, outcomes and recommendations; list devices that are considered to be the ‘gold’ standard for that particular category of equipment; list new devices requiring further study; pro forma study protocols and ethics forms; and provide statistical help and advice.

Establishment of a Panel of Experts The Panel of Experts should: decide on examples of ‘gold standard’ devices; provide limits of acceptability for different outcomes when designing studies; critically appraise the available evidence and make recommendations on devices that are suitable for use.

Establishment of a Purchasing Group in each Trust The Purchasing Group must include a nominated Consultant Anaesthetist. The roles and responsibilities of the Purchasing Group will be described in the new guidelines published by the AAGBI. The Groups should only select products from those recommended by the Panel of Experts as stated on the website and they should not select products which have not been through the assessment scheme. The written responsibilities should include the level of accountability should equipment be purchased that is not recommended by the Panel of Experts which subsequently proves to be unsuitable or even dangerous.

Anaesthetists All anaesthetists should be encouraged to carry out trials on new devices, with support from the Device Evaluation Centre.

Figure 1 A way forward.

alternative to the ‘gold standard’ device if it is either equivalent (within certain limits) or not inferior (no worse by a certain limit). The study is powered to demonstrate equivalence or non-inferiority within or above these limit(s), respectively, on one primary outcome measure, for example first time insertion success rate. The main problem here is deciding what constitutes ‘equivalence’ or ‘not inferior’. This may require input from the Panel of Experts to provide appropriate guidance. Accepting only a small difference in performance between two devices would require recruiting large numbers of patients for the study, which might require a multi-centre approach. Accepting a large difference in performance would require fewer patients but might lead to the risk of a clinically unacceptable device being deemed ‘not inferior’, a problem highlighted with drug trials [1]. As an alternative to an RCT, an anaesthetist could carry out a case series with a particular device, such as the recent study on the ProSeal LMA [38] and our study on the Frova introducer [4]. Such studies are not as robust as RCTs, but if every anaesthetist chose one device, diligently recorded the patient’s details and outcomes every time they used that device, and then

made that data available after a certain number of uses, such information could further rationalise purchasing in the UK and elsewhere.

Operating the scheme The provisions of the Medical Device Directive prohibit placing additional hurdles to the placement of medical devices onto the market in Europe. Hence, any scheme such as that described here would have to be voluntary rather than mandatory. This voluntary scheme could only be carried out through the AAGBI, Royal College of Anaesthetists and DAS (for the categories of products discussed here), as such a scheme would require funding for it to become structured, coordinated and managed by the Device Evaluation Centre in an appropriate academic department, and input would be required from the professional bodies. The dedicated website should include information of all current relevant clinical trials in a similar way that information is available on the National Research Register (http://www.nrr. nhs.uk)1. This database is searchable 1 The data are currently being moved to the UK Clinical Research Network Portfolio Database (http://public.ukcrn.org.uk/search/).


and can be used to help researchers from different centres avoid duplicating investigations. New equipment suitable for clinical studies could be listed. Studies would need to be carried out at the start of a product’s life-cycle and completed within an agreed and reasonable timescale. Information on any updates to the products, particularly in response to the studies, would need to be logged and made available to purchasers and anaesthetists through the website. The conduct of trials could be streamlined by having template protocol and ethics forms available on the website. It would be an interesting and useful development if the National Research Ethics Service (http://www. npsa.nhs.uk) would allow pro forma ethics forms to be available to allow trials to be started quickly on suitable equipment; trials should avoid equipment that did not pass the preliminary laboratory-based tests. A sample size calculator should also be available to establish the number of patients needed to be recruited based on estimated outcomes and limits of acceptability. Help and advice on analysing the data should be provided. Access to examples of published studies considered to represent ‘good practice’ would be beneficial. 573

Editorial Anaesthesia, 2008, 63, pages 571–575 . ....................................................................................................................................................................................................................

The Panel of Experts should choose examples of devices that represent the ‘gold standard’ in that particular category. For re-usable introducers and laryngeal masks, the ‘gold standards’ were, and probably still remain, the Eschmann introducer and the cLMA, respectively. However, for single-use equipment, there is much more choice. In our opinion, based on available evidence, the Frova is a likely contender for the ‘gold standard’ single-use introducer, although there is the potential for trauma associated with its use [4, 35], so there is a need for further improvements in its design. Results should be published in a peer-reviewed journal. This might require a change of emphasis for the journal to accept more ‘negative’ studies. Results should also be available on the website. Researchers would be obliged to publish promptly; any delays might mean that the results are not relevant or applicable to products available for purchasing, and this would cause unnecessary and unacceptable delays to making purchasing decisions. The Panel of Experts could then critically appraise the available evidence on a particular product to make a recommendation on the website whether the product is suitable for its intended purpose or not. Manufacturers would be obliged to remove devices deemed to be unacceptably inferior from the market.

Advantages of the proposed scheme The development of such a transparent, open access, publicly-available system could provide an evidence base for the use of all devices available on the market. As purchasers in Trusts became used to the idea of evaluations being carried out and information on new devices becoming available rapidly, this would reduce the number of audits required. In turn, this would mean that manufacturers would need to supply fewer free samples, but with the expectation of having a more robust outcome than ‘it seems okay’. Furthermore, such a system would enable trainees to have the opportunity to participate in such studies, under

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academic and consultant supervision, where they would be exposed to the full rigour of academic research. This would include: study design, application for ethics committee approval, data analysis, interpretation and presentation of the results and submitting a paper for publication in a peer-reviewed journal. This system should improve the take up of new products within the NHS: the NHS was identified as a slow adopter of new devices in the Healthcare Industries Task Force report [39]. The Medicines and Healthcare products Regulatory Agency has published guidelines on the management of medical devices, including their acquisition [40]. This proposed scheme would support one of the key points for acquiring equipment stated in the MHRA guidelines that ‘safety, quality and performance considerations to be included in all acquisition decisions’.

A way forward It is clear that there needs to be collaboration between academia, the NHS and industry to move this scheme forward. The key points for the development of the scheme are outlined and summarised in Fig. 1. The development of such a scheme is surely necessary and timely. A. R. Wilkes,1 I. Hodzovic2 and I. P. Latto3 1 Senior Research Fellow, 2 Senior Lecturer and 3 Consultant Anaesthetist (Rtd.), Department of Anaesthetics and Intensive Care Medicine, School of Medicine, Cardiff University, Heath Park, Cardiff CF14 4XN, UK E-mail: [email protected]

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