Clinical effectiveness, safety, recurrence, relapse, infections rates

The clinical effectiveness of MM for IH repair has been widely documented in the literature. Hernia International, a non-profit organisation delivering hernia repair operations throughout sub-Saharan Africa, has conducted over 20 000 procedures with non-insecticide treated MM since 2008, without demonstrable impact on adverse events (low-desnity polyethylene MM sourced from AMSA Plastics, India, personal communication with Prof Andrew Kingsnorth). A retrospective analysis by the clinician that first tested the procedure with MM, Ravindranath Tongaonkor, conducted between 1996 and 2002, examined the results of 359 patients across four hospitals in India who underwent IH repair using sterilised MM made of polypropylene and polyethylene copolymer.22 Over follow-up ranging from 1 month to 5 years, there was only 1 recurrence (0.27%) and infection (caused by stitch abscesses) was observed in 4.7% of patients.22 A 2009 analysis of patients undergoing IH repair using sterilised polyester MM in Ghana by surgeons with the charity Hernia International found similar results.23 Of the 95 patients who underwent surgery, at the 6-week and 6-month follow-up, a total of 7 (7%) had suffered wound complications.23 A 10-year retrospective analysis of 615 patients undergoing IH repair using low-density polyethylene MM with 12–18 months follow-up reported no recurrences or mesh rejections. Eleven patients experienced postoperative complications all of which were resolved with conservative management.24

However, single-arm studies provide only limited comparison between MM and CM as they often measure different outcomes and do not control for severity of cases. Several randomised controlled trials (RCTs) have been conducted to allow for direct comparison between the two materials. In 2006, Freudenberg et al compared 100% nylon MM with a CM in a randomised, double-blind study performed at the University of Ouagadougou in Burkina Faso.25 Thirty-five patients with IH were recruited.25 Twenty hernias each were repaired using either MM or CM.25 Study authors measured the difference in preoperative and postoperative quality of life (QOL), as well as the surgeons’ judgement of the ease of handling each of the meshes.25 In both groups, there was a statistically significant difference in preoperative and postoperative QOL, with no difference in mean outcome between the MM and CM groups.25

A 2016 RCT of 302 patients conducted in Uganda found similar results.26 Primary outcomes investigated were postoperative complications at 2-week follow-up and hernia recurrence at 1-year follow-up.26 There was one (0.7%) recurrence of IH in the MM group at the 1-year follow-up, with none reoccurring in the CM group.26 Postoperative complications occurred in 30.8% of patients in MM group, and 29.7% of patients in CM group.26 None of the differences were statistically significant.26

A 2002 meta-analysis of RCTs of IH repair with CM comprising a total of 11 174 patients found that recurrence of hernia was reported in 88 (2.0%) of 4426 mesh repairs, comparable performance with that of MM.27 Two systematic reviews on this topic further strengthen the findings outlined above. In 2012, Sørensen and Rosenberg concluded that in a total of 577 patients who underwent IH repairs with non-CM (comprising 589 meshes inserted in total; 93% of those used were MM), 6.1% had short-term complications (such as infections, or haematomas), and 0.17% had recurrence.28 Patterson et al published the most up-to-date systematic review comparing postoperative adverse effects of MM to CM for IH repair in 2017.29 Five studies were included, ranging from 2006 to 2016.29 A total of 313 MM and 307 CM were inserted across the 5 studies.29 Average study length was 32.1 months (outliers at 6 weeks and 5 years), with follow-up ranging from active follow-up at 2 weeks to passive follow-up at up to 5 years.29 There was a total of 74 (23.6%) and 76 (24.8%) adverse events in the MM and CM groups, respectively.29 The overall OR of pooled adverse effects following IH repair using MM was 0.93 (95% CI 0.63 to 1.35).29 The amount and quality of evidence supporting the equivalent efficacy and safety of MM for IH repair as a ‘cost-effective alternative to [CM] for hernia repair’ is clear.29 Several studies also investigated the ease of handling of MM by surgeons finding it to be comparable to CM23 and very practical.25

Despite the wealth of clinical evidence to suggest comparable outcomes between CM and MM, all of the studies, including the 2018 International Hernia Guidelines,17 fall short of explicitly recommending that MM be used in HIC settings, only in LIC settings.

Physical and material properties

CMs are made from a variety of materials which commonly include polypropylene, polyethylene or combinations of these. Meshes currently used for hernia repair can be characterised according to their weight (heavyweight and lightweight). These vary in pore size, thickness, tensile strength and stiffness. These properties are important because they will dictate how well the mesh can perform its function to reinforce the tissue and also how it will integrate within the host. The type of material used in MM is often not documented but can be made of nylon or similar materials to CM. As with CM, there are several varieties of MM. Deeken and Lake reviewed the CMs available on the market and summarise their main structural and mechanical properties.30 In table 1 and figure 1, we have summarised these values and compared them with different varieties of MM.31–34 This comparison shows that MM tends to exhibit similar pore size and weight to the preferred lightweight CM currently on the market (figure 1), also demonstrated by Sanders et al.34

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Figure 1

Graph showing correlation between pore size (mm) and weight (g/m²) of heavyweight, lightweight commercial meshes and mosquito meshes. Values of pore size and weight of each mesh are provided in table 1.

Weight, thickness and stiffness are important, because together they will determine how flexible or stiff the mesh is. Stiff mesh may be more likely to erode tissue and cause irritation during movement. Tensile strength is important because the mesh needs to resist the intra-abdominal pressures exhibited from bending, straining and lifting. In practice, the ideal-type mesh is one that most closely resembles native human tissue.35 For IH, this is the transversalis fascia and for ventral hernias this is the posterior rectus sheath; both are connective tissue layers beneath the rectus abdominis muscle.

Table 1 and figure 1 show that although MM is comparable to both lightweight and heavyweight CM in terms of thickness it has a much lower stiffness than either of these, without sacrificing tensile strength and indeed is most comparable to native tissue, compared with commercial alternatives. The increased similarity of MM to native tissue suggests that MM may provide an advantage over CM by producing a more favourable biological response. Figure 2 illustrates the comparison of mechanical properties between CM, MM and native tissue. CMs are usually overengineered and are far stronger and stiffer than native tissue. This mismatch in properties may lead to the current complications associated with hernia repair.35

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Figure 2

Column graphs representing values of ultimate tensile strength (A) and stiffness (B) of heavyweight and lightweight commercial meshes,50 mosquito meshes (MM)32–34 and native tissue.51 52 Values of stiffness and tensile strength of native tissue (transveralis fascia and posterior rectus sheath) are measured in the transverse direction. All values of the native tissue of ultimate tensile strength and stiffness are measured in the transverse direction.

Sterilisation standards for mesh

Depending on the composition of the MM (discussed above), the temperature at which MM can be sterilised without compromising the quality of its properties may vary.22 29 36 The UK Medical Device Agency has established strict guidelines surrounding the sterilisation of medical equipment36 and well-recognised European standards require that sterilisation of CM must take place at 134°C, or if there is a risk of warping, then to sterilise using ethylene oxide (EO), to ‘avoid the risk of not destroying agents associated with spongiform encephalopathies’.36 Stephenson et al compared the robustness of copolymer MM meshes and meshes made of 100% polyester autoclaved at 121°C and 134°C, followed by EO sterilisation.36 They found that copolymer mesh became hard, shrunken, non-pliable mass following autoclaving at 134°, although at the lower temperature (121 °C), it retained its texture and pliability. It was subsequently used to repair 54 hernias, with no complications reported at 6-month follow-up.36 Polyester mesh did not shrink significantly at 134 °C and no shrinkage occurred in either mesh following EO sterilisation.36 Despite polyester mesh’s lower proclivity to warping following sterilisation, it does not possess the same handling properties, and was considered less surgeon friendly when compared with the copolymer mesh.36 They therefore concluded that MM, whether polyester or copolymer, should be sterilised at 121 °C.36 In their systematic review, Patterson et al conclude that ‘although the studies indicated in this review demonstrate the safety profile of [MM] sterilized at 121 °C, it seems unlikely that HICs will change their sterilization policies’, as this is a lower sterilisation temperature than that considered acceptable practice in HICs due to the theoretical risk of prion-disease transmission at this lower temperature.29 There are two issues that indicate the presence of a possible double standard between practice that is acceptable for HICs and practice that is acceptable for LICs. First, if there is a risk (although unsubstantiated) of prion disease transmission at 121 °C, then is it acceptable to continue to recommend sterilisation at this temperature for MM hernia repair in LICs? It would seem highly unethical to permit the exposure of patients in LICs to even a theoretical risk of prion disease. Second, if MM mesh of all types are stable to sterilisation by EO, a technique which is used and practised in HICs to avoid risk of CM mesh warping, then would it not be entirely possible to substitute CM for MM in HICs, using EO sterilisation practice as standard? Neither the potential for using EO sterilisation on MM in HICs nor the inappropriateness of autoclave sterilisation at 121°C in LICs for MM have been addressed in any of the literature on MM use for hernia repair to date.

Costs associated with the procedure compared with the current best alternative, modelling on possible savings at national and trust level

The financial imperative for using MM as opposed to CM is clear, although the commercial case is complex. Elective repair of IH for adults can cost, in the NHS for instance, between £1458 and £2607, depending on the complication and comorbidity score of the patient.37 The cost can vary further, depending on the type of procedure (open vs laparoscopic, local vs general anaesthesia) and the type of materials used (single use vs resusable).17 18 NICE estimate the average cost of laparoscopic IH repair to be £1078.18 The most commonly used variety of CM in the NHS is Prolene Mesh, at a cost of approximately £300 per unit.38 Other commonly used CMs can cost up to approximately £500 per unit.39 40 Depending on the quantity purchased, prices can vary. For instance, CM commonly costs more than US$125 (or £100) each when bought in Uganda.26 Conversely, the cost of MM can vary greatly depending on the country of origin and the size of the mosquito net from which the mesh is fashioned.29 Freudenberg et al calculated the cost of a 10×15 cm size MM patch to be US$0.0043,25 constituting a 7000% reduction in price compared with CM in the UK. Löfgren et al suggests the MM costs US$1 (£0.8) in Uganda and Darzi suggest it costs £1.5 if prepared in the UK.15 26 The cost of EO sterilisation of MM in the UK is £120 for an 8 L bag of MM, corresponding to £0.29 for the purchase and sterilisation of an 10 cm × 15 cm unit of MM, not including costs for packaging or distribution. Although the initial cost savings may be small for individual hospitals and trusts, the cost savings accumulated at the national and global levels can be significant. For instance, in the UK, meshes for IH repair alone incur a cost of £2.3 million, which could be cut to £100 000, a saving of 96 per cent.15 Such a price differential could be a challenge to CM producers, potentially disrupting the market. The extent to which commercial providers are willing to pivot their product to the cheaper MM variety is unknown. It will be important for the reduction in costs to be reflected in the wholesale and retail price point so that savings can be accrued by the system as a whole.

Regulatory environment: CE marking, MHRA, NICE

In order to be marketed in the UK, a medical device must first obtain CE marking, indicating conformity with the European Union’s medical device regulations.41 A standard CM is a ‘surgically invasive long-term use and implantable device,’ and would therefore be classified as a Type IIb device.42 Following CE marking and registration with the Medicine and Healthcare products Regulatory Agency (MHRA), the device can be used in the UK. At this stage, the device may be considered for cost-effectiveness analysis through NICE for procurement.43 An additional challenge is the business or commercial consideration for mesh production. There is currently no commercial entity to bear the risk, CE costs and production costs of the MM. Hernia International procures the mosquito nets, prepares and sterilises them through a third-party sterilisation partnership in Eastern Europe and then packages, ships and uses them through charitable donations to the non-governmental organisation (NGO) itself. The viability of MM as a sustainable offering will depend to some extent on whether or not a commercial, for-profit, social or not-for-profit enterprise, or consortium, will emerge to bear the risk and costs associated with MM use. Notwithstanding this, the clinical cost-effectiveness and biomechanical characterisation of MM compared CM provide for a compelling case at least for this to be explored and developed also in HIC settings. The commercial challenges to using MM in the UK do not on their own preclude the recognition, at least, of the value of using MM in the UK context and the need to debate the sterilisation standards that are reasonable to use for MM in the UK and in LICs.

Reverse innovation: policy landscape and advances

There are few documented innovations developed in LMICs and then adopted for use in HICs—particularly implantable medical devices in the type IIb category—that have been introduced into the NHS from LICs thus far. There is little established precedent, therefore, for these so-called ‘reverse innovations’ regarding the procedures that would need to be followed for them to be used in the UK or USA. For instance, there are several exemptions to CE marking that may be applicable, such as exemptions for ‘custom-made devices’ (MM may qualify as ‘custom-made’, as each individual mesh would need to be fashioned out of the larger, complete net, and subsequently sterilised44), and exemptions for ‘non-compliant devices used in exceptional circumstances (humanitarian grounds)’ (MM was established and is heavily used in humanitarian settings36). It is therefore unclear if additional CE marking would be required for use in the NHS.44 Further, considering the difficult legal terrain, as well as the potential costs associated with protecting the MM through the patenting process, it is possible that this would on the one hand delay the introduction of the devices, and on the other hand increase the price of the final product, reducing its cost effectiveness. Further research is required to fully test and investigate the legal frameworks regarding reverse innovations. This would involve, for example, many other professional and regulatory organisations to ensure successful adoption and diffusion of this MM innovation. In addition to registering medical devices with the MHRA, as well as proving cost effectiveness, ideally through a body such as NICE, bodies such as the General Medical Council, the British Medical Association, the RCS and the BHS would need to be consulted for MM to be used clinically. Adoption and diffusion of MM for IH repair will be predicated on the engagement and endorsements of some, if not all these bodies.

There are several barriers to adopting reverse innovations in developed economies, such as the lengthy and expensive process of obtaining CE marking,12 the difficulty of identifying innovations for adoption,45 as well as bias against innovations and ideas originating from contexts other than our own.46 47 Despite clearly established safety and effectiveness of MM for IH repair—evidence supported at the systematic review and meta-analysis level29—the use of MM continues to be promoted in the literature as a solution for IH repair predominantly in ‘resource-scarce’26 or ‘humanitarian’36 settings, or where ‘commercial mesh is not available or affordable’.25 Such recommendations run counter to the aim of evidence-based medicine of ‘systematically locating, appraising and using contemporaneous research findings as the basis for clinical decisions’.48 In the UK, an important first step to using MM in hernia repair has been taken by THET and the Northumbria NHS Trust with their intention to bring MM to the NHS to ‘generate significant cost savings without compromising outcomes’.49 These advances are encouraging and point to a growing effort to address some of the barriers surrounding global diffusion of innovation.