The clinical and cost-effectiveness of open mesh repairs in adults presenting with a clinically diagnosed unilateral, primary inguinal hernia who are operated in an elective setting: systematic review and economic evaluation

Introduction

Surgical repair (herniorrhaphy) is undertaken in most people presenting with inguinal hernia in order to close the defect, alleviate symptoms of discomfort and prevent serious complications. Inguinal hernia repair is the most frequent and resource-consuming surgical intervention in the UK. 1,2 It is also the most common general surgical intervention performed in Europe1,3,4 and the USA. 5 Various surgical techniques and approaches are available for inguinal hernia. These can be classified in three main categories: open repair with suture (e.g. Bassini and Shouldice repair), open repair with mesh (e.g. Liechtenstein repair or preperitoneal repair) and laparoscopic repair with mesh [e.g. totally extraperitoneal (TEP) repair or transabdominal preperitoneal (TAPP) repair].

Open and laparoscopic ‘tension-free’ repairs, which are based on the use of ‘mesh’ (prosthetic and biological), are widely performed and considered superior to the traditional ‘tissue-suture’ repairs, such as the Bassini or Shouldice techniques. 6,7 Compared with the traditional sutured techniques, a reduction in the risk of recurrence between 50% and 75% has been demonstrated after mesh repair. 8,9 However, the laparoscopic mesh repair has a longer learning curve and higher resource cost compared with the open mesh repair. 2,7,10–12 Different open repairs with mesh, such as the Lichtenstein repair and the preperitoneal repair, have shown similar results and very low recurrence rates, ranging from 2% to 5%. 13,14 The preperitoneal mesh repair has demonstrated similar or better outcomes compared with the laparoscopic mesh repair. 15

Considering the low recurrence rate reported in the literature after surgical repair of inguinal hernia, the current key outcomes on which to measure the clinical success of hernia recovery include chronic pain, complications, time to return to normal activities and quality of life (QoL). 16,17 Published evidence assessing the effects of common mesh techniques (including open preperitoneal repair, Lichtenstein repair and laparoscopic repair) in lowering chronic pain and improving major clinical outcomes have produced inconsistent results. 3,15,18–20 The aim of this assessment was to evaluate the clinical effectiveness and cost-effectiveness of open preperitoneal repair compared with Lichtenstein repair in adults presenting with a clinically diagnosed primary unilateral inguinal hernia.

Aetiology, pathophysiology and clinical presentation

An inguinal hernia is a protrusion of the contents of the abdominal cavity through a defect in the inguinal canal. It manifests as a lump or swelling in the groin that may cause discomfort and pain, and impact on daily activities and ability to work. Unilateral hernias occur on one side of the lower abdominal wall, whereas bilateral hernias occur on both sides of the lower abdomen wall. Symptoms of inguinal hernia include swelling, pain or aching sensation in the groin, which develops gradually over time. Pain worsens with prolonged activities. 21 The bulge of the hernia increases in size with activities that cause intra-abdominal pressure, such as coughing, lifting or straining. Occasionally the hernia sac contents may get incarcerated causing obstruction or strangulation of the intestine, leading to ischaemia, necrosis and even perforation of the intestine. Rarely, inguinal hernias are asymptomatic.

Inguinal hernia is commonly diagnosed by clinical physical examination. Physical examination involves careful inspection of inguinal areas for bulges or impulses while the patient is standing and during a Valsalva manoeuvre (i.e. forceful attempted exhalation while keeping the mouth and nose closed). The sensitivity and specificity of physical examination for the diagnosis of inguinal hernia have been reported to be 75% and 96%, respectively. 22 In specific clinical situations such as recurrent hernia, hernia in female patients, surgical complications with chronic pain or uncertain aetiology, diagnosis of inguinal hernia can be improved by various imaging techniques (e.g. ultrasonography, magnetic resonance imaging or computerised tomography). 21 In particular, magnetic resonance imaging and ultrasonography have shown high sensitivity and specificity estimates (> 80% and > 90%, respectively) for the diagnosis of groin hernia. 22

The classification of hernia is a prerequisite to describe the anatomy or size of inguinal hernia and to choose the best management. 3,23 Many classifications of inguinal hernia have been proposed and they are all based on the presence of indirect hernia (occurs because of the natural weakness in the internal inguinal ring), direct hernia (caused by the weakness in the floor of inguinal canal) and femoral hernia (less common groin hernia occurring mostly in women). 23 Table 1 illustrates a number of different classifications currently available.

Epidemiology and prevalence

A large population-based prospective study conducted in the USA (National Health and Nutrition Examination Survey, 1971–5) reported a 20-year cumulative incidence of hospitalisation with inguinal hernia of 6.3%. 24 The condition is observed more frequently in males and incidence increases with age. 24 The lifetime chance of getting inguinal hernia is estimated to be 27% in men and 3% in women. 25 Most inguinal hernias are found in men because of the vulnerability of the male anatomy to the formation of hernias in this region. 26 The average age group for the manifestation of inguinal hernia has been reported to be 10 years older in women (60–79 years) than in men (50–69 years). 27

A register-based 5-year study conducted in Denmark found that 97% of all groin hernia repairs (n = 46,717) were inguinal hernias. 4 In the Netherlands, approximately 30,000 inguinal hernia repairs are carried out annually. In the USA, data from the National Centre for Health Statistics suggest that approximately 800,000 groin hernia repairs were performed in 2003, with over 90% of these surgeries performed on an outpatient basis. 5

Impact of health problem: significance for the NHS and burden of disease

Symptomatic patients often present with pain and discomfort. Patients may experience a localised pain or aching (burning or gurgling) sensation at the site of hernia defect or a heavy or dragging sensation in the groin. There are various factors that may contribute to pain, including stretching or tearing of the tissue around the hernia defect, prolonged activity or Valsalva manoeuvres. 21 A prospective study by Hair and colleagues,28 evaluated the association between hernia symptoms and time from hernia presentation in 699 patients. About 65% (457) of patients complained of pain and discomfort at the hernia site on presentation, with the cumulative probability of pain increasing to almost 90% at 10 years, whereas more than one-third of patients (267/699) were asymptomatic. Patients with inguinal hernia are at risk of bowel strangulation, which requires emergency resection. A retrospective study,29 reported a cumulative probability of strangulation for inguinal hernias of 2.8% at 3 months and 4.5% after 2 years.

Severe chronic pain, wound infection and recurrence are among the postoperative complications that are reported after inguinal hernia repair. 16,17 With incidence rates ranging from 10% to 54%, chronic pain is undoubtedly the dominant complication after inguinal hernia repair. 16,30,31 The reason for long-term postoperative pain is complex and often related to intraoperative nerve damage, which is often associated with technical aspects of the surgical procedures as well as with surgeon’s dexterity and expertise. 32 The position of the mesh is likely to be another crucial factor.

Management of condition and current service provision

Anterior Lichtenstein repair (open mesh)

Irving Lichtenstein developed the anterior open tension-free approach in 1984. 37 It is a very common and reproducible approach, and is relatively easy to perform. 7 The technique involves the placement of flat mesh (polypropylene) on top of the hernia defect through anterior dissection of the inguinal wall under local or general anaesthesia. Mesh is positioned between the internal and external oblique muscle and is sutured to the inguinal ligament such that there is adequate overlap of the posterior wall. At present, the Lichtenstein repair is considered the gold standard among open inguinal hernia procedures. Since its advent, the incidence of hernia recurrence has reduced up to 2%. 14

Different meshes and/or devices used for anterior open approach have been developed, including the mesh plug, the Prolene Hernia System (Ethicon, Somerville, NJ, USA) and the Hertra sutureless mesh (Herniamesh, Chivasso, Italy). Systematic reviews6,15,38,39 and clinical guidelines have assessed the effect of mesh plug repair and the Prolene Hernia System compared with Lichtenstein mesh repair. The Groin Hernia Guidelines published in 2013 included a meta-analysis of eight randomised controlled trials (RCTs), with a total of 2912 patients assessing the effects of mesh plug repair versus Lichtenstein repair. Meta-analyses results were similar with regard to postoperative complications and return to daily activities. 6 Similarly, a meta-analysis of 10 RCTs with a total of 2708 patients did not find significant differences in the number of recurrences between the Lichtenstein mesh repair, mesh plug repair and the Prolene Hernia System. 38 Another meta-analysis of six RCTs and a total of 1313 patients, which assessed the effects of the Prolene Hernia System versus the Lichtenstein repair, showed that the Prolene Hernia System was associated with a higher rate of perioperative complications. However, no significant differences were observed between the two techniques with regard to duration of operation, time to return to work, chronic groin pain or incidence of recurrences. 39 A more recent report commissioned by the US Agency for Healthcare Research and Quality (AHRQ), assessed the effectiveness of Lichtenstein open mesh with various mesh plug techniques. 15 Based on the findings of 21 studies (20 RCTs and one non-RCT), the report concluded that return to work was shorter after Lichtenstein mesh repair. No other significant differences were observed between the surgical procedures. In conclusion, current evidence seems to indicate that the standard Lichtenstein mesh repair performs better than mesh plug repairs and the Prolene Hernia System.

Posterior open repair (open preperitoneal mesh)

The open preperitoneal mesh approach involves incision of the abdominal wall and implantation of the mesh in the space between the peritoneum and the muscle layers. The mesh is held in place with intra-abdominal pressure and requires less or no fixation. Implantation of the mesh can be achieved through (1) a transinguinal method (e.g. Rives), (2) a small incision (2–3 cm) made in broad abdominal muscles [e.g. Kugel repair (Davol, Warwick, RI, USA)] or (3) a lower midline abdominal incision (e.g. Stoppa repair). 40 Open preperitoneal mesh repairs are mostly performed under general anaesthesia. The first open preperitoneal technique was reported by Stoppa in 1980 (i.e. Stoppa repair). 7 Since then a number of different techniques have been developed including the Kugel patch, the Nyhus repair, the Read–Rives repair and the transinguinal preperitoneal (TIPP) technique. There is a lack of robust evaluations comparing the clinical efficacy of each of these techniques. Kugel, using a specially designed hernia patch, observed only five recurrences out of 808 hernia repairs. 41 A retrospective study found similar results between the participants who underwent TIPP repair and those who underwent Lichtenstein mesh repair, with low incidence of chronic pain in both intervention groups. 11

The open preperitoneal technique with soft mesh has been reported to be a safe and potentially cost-effective approach with a short learning curve. 41–44 Irrespective of either open or laparoscopic techniques, the position of the mesh is considered an important factor in the interpretation of chronic pain because of the location of the nerves in the inguinal canal. Recent systematic reviews and meta-analyses, which assessed the effects of common open mesh techniques in lowering chronic pain and improving major clinical outcomes, have failed to provide definite conclusions. 15,18–20 A Cochrane review20 based on the findings of three RCTs showed some potential benefits of the open preperitoneal mesh repair compared with the Lichtenstein mesh repair in terms of incidence of acute and chronic pain and recurrence rate. However, the evidence base of this review was limited. A recent meta-analysis of 12 RCTs19 found that open preperitoneal mesh repair was associated with a lower risk of developing chronic groin pain than the Lichtenstein mesh repair, and the two techniques were comparable with regard to rate of recurrences and complications. It is worth noting that this meta-analysis did not focus exclusively on people with primary unilateral inguinal hernia but included people with recurrent and incarcerated hernias. Two further systematic reviews in the literature15,18 confirmed that various open repair procedures yielded similar results with further potential benefits for the open preperitoneal mesh techniques. The results of these systematic reviews were, however, inconclusive as both included trials assessing the Prolene Hernia System versus the Lichtenstein mesh repair.

Ralph Ger first introduced the use of a laparoscopic approach in 1982. 45 Laparoscopic repairs are minimally invasive and are performed under general anaesthesia. Small incisions are made for the insertion of the operating instruments and prosthetic mesh is placed to close the hernia defect. Mesh is placed in the preperitoneal plane by using one of the two approaches:

1. TAPP repair: the abdominal cavity is entered and a flap of the peritoneum is deflected to expose the preperitoneal plane. A mesh is inserted to cover the hernia defect in the inguinal region. The peritoneum is then closed over the mesh.

2. TEP repair: the mesh is inserted via the preperitoneal plane without entering the peritoneal cavity to cover hernia defects while remaining outside the peritoneum.

The effects of open versus laparoscopic techniques have been assessed in a considerable number of RCTs. A UK Health Technology Assessment (HTA) report published in 200513 identified 37 RCTs that compared open mesh repairs with laparoscopic mesh repairs. A more recent report by the AHRQ, published in 2012, assessed the effectiveness and adverse effects of various surgical interventions for inguinal hernia in both adults and children. 15 The report identified 123 RCTs, two clinical registries and 26 non-randomised studies published between January 1990 and November 2011. 15 Thirty-six of the included 123 RCTs compared open mesh repairs versus laparoscopic mesh repairs for primary inguinal hernia (indicating that the size of the evidence base for this comparison has not significantly changed since 2003), while 20 RCTs assessed various open mesh repairs (some of which no longer reflect the repairs commonly performed in clinical practice). Both these reports concluded that people who underwent laparoscopic mesh repair had faster return to normal activities, less chronic pain and numbness, and fewer postoperative complications (infection and haematoma), while those patients who underwent open mesh repair had lower rates of serious complications (especially visceral injuries). The AHRQ showed a lower risk of recurrence after open surgery (2.49%) than after laparoscopic surgery (4.46%) for the treatment of painful primary hernias in adults,15 while the UK HTA report observed similar recurrence rates between laparoscopic (2.47%, 26/1052) and open procedures (2.07%, 22/1062). 13 However, there is conflicting information on whether or not laparoscopic repair is better than open mesh repair in terms of lowering the incidence and severity of pain outcomes. 6,21,34 The uptake of laparoscopic technique by surgeons is very low (16% in the UK, ≈ 10% in the USA), probably owing to the complexity of the procedure, potential serious complications, long learning curve and high cost. 3,35

Population

The population considered for this assessment was adults presenting with a clinically diagnosed primary unilateral inguinal hernia who are operated in an elective setting. No relevant subgroups were identified. Recurrent or bilateral inguinal hernia will not be considered in this assessment.

Clinical diagnosis of inguinal hernia is usually established by physical examination. Imaging techniques such as ultrasonography, magnetic resonance imaging or computerised tomography may be used to confirm uncertain or challenging diagnoses. In particular, magnetic resonance imaging and ultrasonography are considered highly accurate techniques for the diagnosis of groin hernias. 22

Intervention

Surgical repair with ‘mesh’ is the recommended treatment for inguinal hernia. 2,7 Mesh repair methods include those involving mesh to strengthen the inguinal wall (e.g. Liechtenstein open mesh repair, open preperitoneal mesh repair and laparoscopic mesh repair). The Lichtenstein mesh repair is the most commonly performed procedure for hernia repair in the UK. 16 The laparoscopic mesh repair is technically more complex and requires longer operation time, special equipment and high surgeon’s experience and, therefore, is not routinely used in the UK. 46 The open preperitoneal mesh repair has shown similar or better outcomes compared with the laparoscopic approach. 15 Open preperitoneal techniques with soft mesh have been reported to be safer and potentially cost-effective with a short learning curve. 42–44 Published evidence comparing open preperitoneal mesh repair with Lichtenstein mesh repair with regard to relevant clinical outcomes, such as chronic pain and QoL, have produced conflicting and inconclusive results. 15,19,20

The following open mesh repairs of inguinal hernia are considered in this assessment:

• Anterior Lichtenstein mesh repair: Lichtenstein mesh repair is a very common approach that involves the placement of flat mesh on top of the hernia defect through anterior dissection of the inguinal wall under local or general anaesthesia.

• Open preperitoneal mesh repair: the open preperitoneal mesh approach involves incision of the abdominal wall and implantation of the mesh in the space between the peritoneum and the muscle layers. The mesh is held in place with intra-abdominal pressure and requires less or no fixation. Open preperitoneal repair can be performed using various methods including the Kugel patch, the Nyhus repair, the Read–Rives repair, the TIPP repair and the Stoppa repair.

Non-mesh techniques requiring suturing (e.g. Shouldice, Bassini, McVay, Maloney darn and plication darn techniques) will not be considered in this assessment as they have been proved to be inferior to current mesh techniques and hence no longer recommended. 7–9 Similarly, plug mesh repair and the Prolene Hernia System will not be included in this assessment as they have not demonstrated to be superior to the standard Lichtenstein method. 6,15,18,39 The effects of open versus laparoscopic mesh techniques have been assessed in a considerable number of RCTs. 13,15 In general, evidence has shown similar results with very low recurrence rates. 13–15,18 However, there is conflicting information on whether or not laparoscopic mesh repair is better than open mesh repair in terms of lowering the incidence and severity of pain. 2,21,34 Moreover, laparoscopic mesh repair is not commonly performed in the UK. Laparoscopic mesh techniques will not be considered in this assessment.

Identification of studies

Comprehensive electronic searches were conducted to identify reports of published randomised trials. Highly sensitive search strategies were designed, including appropriate subject headings and text word terms, to combine the search facets for inguinal hernia repair, the surgical interventions under consideration and randomised trials. Final searches were carried out on 31 October and 1 November 2014 and were not restricted by year of publication or language. Full details of the search strategies are reported in Appendix 2. The databases searched were MEDLINE (1946 to October week 4 2014), MEDLINE in Process & Other Non-Indexed Citations (31 October 2014), EMBASE (1947 to 2014, week 44), Bioscience Information Service (BIOSIS; 1980 to 1981 November 2014), Science Citation Index (1980 to 1981 November 2014), Scopus Articles In Press (inception to 31 October 2014) and the Cochrane Central Register of Controlled Trials (inception to 2014). Evidence syntheses were sought by searching the Cochrane Database of Systematic Reviews (inception to 2014), Database of Abstracts of Review of Effectiveness (inception to 1 November 2014) and the HTA database (inception to 1 November 2014). Reference lists of all included studies were perused for further evidence. Members of our advisory group were contacted for details of additional reports.

Eligibility criteria

The studies fulfilling the following criteria were included in the assessment.

Data extraction and management

Two reviewers (PS and MC) independently screened the titles and abstracts of all citations identified by the search strategies. Full-text copies of all potentially relevant studies were retrieved and assessed independently by the two reviewers for eligibility using a screening form developed for this purpose (see Appendix 3, Table A). Full-text copies of non-English-language studies deemed to be potentially relevant were translated before they were assessed for eligibility. Any disagreements during study selection were resolved by discussion or in consultation with a third reviewer (MB or IA).

A data extraction form was specifically designed and piloted for the purpose of this assessment (see Appendix 3, Table B). Two well-conducted RCTs were used to pilot the data extraction form. Detailed information on study design, characteristics of participants, settings, characteristics of interventions and outcome measures were recorded. Three reviewers carried out data extraction (PS, MC and NS); one reviewer completed the data extraction form for all selected studies and two other reviewers cross-checked the details extracted by the first reviewer. There were no disagreements between reviewers.

Further information from the included studies (methodological details or outcomes data) was requested by written correspondence to the original investigators (using open-ended questions and outcome tables for missing outcome data). Principal investigators of relevant ongoing trials were contacted to obtain unpublished data. Any relevant information retrieved in such a manner was included in the review. We contacted eight trial investigators and received further information from three of them. Where trials reported more than two study arms, only data from the relevant arms were extracted.

Where possible, means and standard deviations (SDs) were extracted for continuous data. When SD values were not available, we attempted to (1) calculate SD values using other reported values and (2) contact the original trial investigators for further details. Only when these attempts proved unfeasible or unsuccessful, values were imputed using the average of the SDs from other trials reporting the same outcomes.

Quality assessment strategy

The potential risk of bias for included studies was assessed by a single reviewer (PS or MC) and cross-checked by a second reviewer (PS or MC). Disagreements were resolved by consensus or arbitration with a third reviewer (MB). Studies were not included or excluded on the basis of their methodological quality. The Cochrane risk-of-bias tool was used to assess the risk of bias of all included RCTs48 (see Appendix 4). Critical judgements were made for all main domains: selection bias (random sequence generation, allocation concealment), performance bias (blinding of participants), detection bias (blinding of outcome assessor), attrition bias (incomplete outcome data), reporting bias (free of selective reporting) and other sources of bias (e.g. bias related to the validity of the tools used for measuring outcomes and bias related to inappropriate source of funding). The domains ‘blinding of outcome assessment’ and ‘incomplete outcomes data’ were assessed for each outcome of interest. The blinding of personnel delivering the intervention was not considered relevant for this assessment, as in clinical practice it is not feasible to blind the surgeon who performs the operation.

Each included study was judged to be at ‘low risk of bias’, ‘high risk of bias ‘or ‘unclear risk of bias’ according to the criteria described in the Cochrane Handbook for Systematic Reviews of Interventions. 48 Adequate sequence generation, allocation concealment, blinding of participants and blinding of outcome assessor were identified as key domains for the assessment of the risk of bias of the included trials. Studies were classified as follows: (1) high risk of bias, if one or more key domains were at high risk; (2) unclear risk of bias, if one or more key domains were judged to be at unclear risk; and (3) low risk of bias, if all key domains were judged to be at low risk.

Method of analysis/synthesis

For binary outcomes, the Mantel–Haenszel approach was used to pool risk ratios (RRs) derived from each study. However, because some adverse outcomes were expected to be relatively uncommon for outcomes with rare events (i.e. < 5%), the Peto odds ratio (OR) approach was considered the most appropriate meta-analysis approach. For continuous outcomes, mean differences between groups were pooled using the inverse variance method. For time-to-event outcomes (recurrence and time to return to normal activities) we planned to pool hazard ratios if suitable data were available.

The statistical heterogeneity across studies was explored using the Chi-squared and I-squared statistics. The primary analysis used a random-effects model to calculate the pooled estimates of effect. This was not possible when the Peto approach was used for binary outcomes with rare events.

If a sufficient number of trials were available, sensitivity analyses restricted to trials at low risk of bias were planned.

Quantity and source of the evidence

The original primary searches and the subsequent updates retrieved a total of 1204 records. After reviewing all titles and abstracts, 1122 records were subsequently excluded because they were not relevant. Full-text copies of 82 potentially relevant reports were obtained and screened for inclusion. Six non-English full-text articles published in Dutch (n = 1), German (n = 1), Italian (n = 1), Spanish (n = 2) and Persian (n = 1) were identified and assessed. Colleagues from the School of Medicine and Dentistry, University of Aberdeen, who were native Dutch, German, Italian or Spanish speakers, translated five of these articles professionally. A full-text article, published in Persian, was initially translated using the Google (Google Inc., Mountain View, CA, USA) translator tool and subsequently checked by a colleague who could read Persian. After translation, only two non-English-language papers (published in Persian and Spanish) met the prespecified inclusion criteria and were included for further assessment.

Three systematic reviews of RCTs assessing open mesh repair versus Lichtenstein mesh repair were deemed suitable for inclusion (the Cochrane review by Willaert and colleagues,20 the meta-analysis by Sajid and colleagues,19 and the systematic review by Li and colleagues18). In line with the prespecified research protocol, these systematic reviews were used as a source of existing evidence but were not formally updated. Further methodological details and missing data from one included ongoing RCT51 were derived from the systematic review by Willaert and colleagues,20 which cited this RCT and was based on individual participant data, as we were not able to make contact with the principal investigator.

In total, 12 RCTs (11 RCTs published in 13 full-text papers and one ongoing RCT) met the inclusion criteria and were included for the clinical effectiveness assessment. 42,51–63 One of the included trials53 used a quasi-random method to allocate participants to interventions (i.e. order of admittance).

Figure 3 shows the flow diagram of the study selection process. Appendix 5 lists all the studies included in this assessment, together with the systematic reviews that were used as a source of relevant evidence.

FIGURE 3.

Flow diagram of the study selection process.

Appendix 6 lists the studies excluded after full-text scrutiny together with the reasons for their exclusion. Sixty-six studies were excluded because they failed to meet one or more of the specified inclusion criteria with regard to study design, participants, intervention or outcomes. In particular, 45 studies were excluded because they were non-RCTs, one study because patients did not present with primary inguinal hernia, 15 studies because they did not include a relevant comparison and five studies, published in non-English languages, because they could not be obtained.

Risk-of-bias assessment of included studies

Figure 4 illustrates the summary of the risk-of-bias assessment for all 12 included studies. 42,51–63 Risk of bias of individual studies is detailed in Appendix 7, Tables 30 and 31.

FIGURE 4.

Summary of risk-of-bias assessment of included 12 studies.

Generally, trials were at high or unclear risk of bias. Only two trials were judged to be at low risk of bias, with adequate sequence generation, allocation concealment, blinding of participants and blinding of outcome assessor. 52,56 Two trials were judged at high risk of selection bias because of the inadequate randomisation process,53,59 whereas one trial was judged at unclear risk of selection bias because not enough information was provided on allocation concealment. 61 One trial51 did not blind participants or outcome assessors, and was considered at high risk of performance and detection biases. Six of the included trials,54,55,57,58,60,63 failed to provide sufficient information to formulate a reliable judgement about risk of bias and no additional details were obtained from the corresponding authors.

Study characteristics

Details of all included studies, including baseline characteristics of participants, description of surgical interventions (i.e. open preperitoneal mesh repair and Lichtenstein mesh repair) and clinical outcomes are tabulated in Appendix 8, Tables 32–34.

Included trials were conducted in Turkey (four studies),52–54,63 the Netherlands (two studies),56,59 Belgium (one study),51 Egypt (one study),55 Iran (one study),57 India (one study),60 the USA (one study)58 and Mexico (one study). 61 Four trials were sponsored by professional organisations. 51,55,56,61 In the remaining eight trials, the source of funding was not specified. 52–54,57–60,63

Among included studies, the lengths of follow-up ranged from 1 week63 to 110 months. 58 Only two trials had long follow-up assessments; the trial by Gunal and colleagues,54 conducted in Turkey, reported mean length of follow-up of 98 months and the trial by Muldoon and colleagues,58 conducted in the USA (224 participants in total), had a median length of follow-up of 82 months (range 24–110 months). In the remaining trials the mean length of follow-up was 17.3 months (range 0.25–54.5 months; median 12 months).

Assessment of outcomes and follow-up

Table 3 highlights the type of outcome measures that were assessed in the included trials. Pain was measured at different time points after surgery and during follow-up (see Appendix 8, Table 32). In total, seven trials assessed chronic pain (≥ 3 months),51,52,56,58–61 nine acute pain51,54–57,59–61,63 (< 3 months) and four chronic numbness56,58,59,61 (≥ 3 months).

The definition of pain and time points when pain was measured varied among trials (see Appendix 9, Tables 35–40). Four trials used the VAS score to measure chronic pain. 51,56,59,61 The VAS is a validated instrument for measuring pain on a scale ranging from 0 (no pain) to 10 (worst pain imaginable). Three of these four trials51,56,59 defined chronic pain as ‘any VAS score above zero which lasts for more than three months as defined by the International Association for the Study of Pain’ and reported chronic pain at 3 months,59 1 year56 and 2 years. 51 One trial61 defined chronic pain as ‘any VAS score between 3 and 10’ and reported chronic pain at 3 and 6 months. A different trial52 defined chronic pain as ‘a pain lasting for more than 6 months after surgery according to the Sheffield scale’. The Sheffield scale is a tool that measures pain using a score from 0 to 3, where 0 indicates no pain, 1 indicates no pain at rest but some pain during movement, 2 indicates temporary pain at rest and moderate pain during movement and 3 indicates constant pain at rest and severe pain during movement. The remaining two trials58,60 did not specify the instrument used to measure pain, but reported the number of participants suffering from ‘chronic pain’ at 6 months.

Of the nine trials that assessed acute pain51,54–57,59–61,63 (measured within 3 months after surgery), seven measured pain using the VAS score or reported the proportion of participants suffering from pain. 51,54–57,59,61 Follow-up measurements of acute pain varied among these seven trials (see Appendix 9, Tables 37–39). One trial assessed pain 1 month after surgery but did not specify how pain was measured60 and one trial reported postoperative pain levels by assessing the need for analgesia during the first 24 hours after surgery. 63

In five trials,51,52,56,59,61 chronic pain was the primary outcome. Four of these five trials52,56,59,61 were powered to detect differences in chronic postoperative pain.

Eleven of the 12 included trials51–61 assessed recurrences and complications,63 and five trials52,55–57,60 assessed length of hospital stay and time to return to normal activities.

None of the included trials specifically assessed QoL, but two of the trials reported health measures42 and patient satisfaction57 after open preperitoneal mesh repair and Lichtenstein mesh repair.

Results of the individual studies and data synthesis

The 12 trials identified included a total of 1568 participants; 771 randomised to open preperitoneal mesh repair and 797 to Lichtenstein mesh repair. Eleven trials with a total of 1523 participants provided suitable data for statistical analyses relevant to the comparisons and outcomes of interest. The main results are reported under two broad sections entitled Patient-reported outcomes and Clinical outcomes. See Tables 4–7 for the results and Appendix 9, Tables 35–44 for the results from individual studies.

Chronic pain

Figure 5 shows the meta-analysis results for chronic pain. There was considerable variation in the definition of pain used (see Assessment of outcomes and follow-up) by the individual trial investigators and the reported rates of chronic pain (see Appendix 9, Table 35). With the exception Arslan and colleagues,52 who reported a high proportion of participants with chronic pain (90%) in both intervention groups, all the remaining trials reported relatively low rates of chronic pain.

FIGURE 5.

Open preperitoneal mesh repair vs. Lichtenstein mesh repair: chronic pain. df, degrees of freedom; M–H, Mantel–Haenszel.

The random-effects meta-analysis showed a RR of 0.50, indicating a 50% reduction in the risk of chronic pain among participants who underwent open preperitoneal mesh repair compared with those who underwent Lichtenstein mesh repair. The difference between intervention groups was not statistically significant [95% confidence interval (CI) 0.20 to 1.27] and there was evidence of high statistical heterogeneity among trials (I² = 92%). The observed variation in the rates of chronic pain between trials can be partly explained by the way trial investigators described chronic pain. ‘Chronic pain’ was (1) defined according to the definition of the International Association for the Study of Pain (IASP), including a VAS score above 0 which lasts for more than 3 months; (2) defined by a VAS score between 3 and 10; or (3) was not defined at all. Other possible sources of heterogeneity include the position of the mesh and the type of mesh fixation, the type of techniques used for inguinal hernia repair and the surgeon’s clinical expertise.

Chronic numbness

Four trials reported the proportions of participants with chronic numbness. 56,58,59,61 There was evidence of high heterogeneity (I² = 91%). Two trials58,61 reported considerably higher rates of numbness following Lichtenstein mesh repair but the other two trials56,59 reported similar rates in each group. The random-effects meta-analysis did not provide evidence of statistically significant differences between the intervention groups (RR 0.48, 95% CI 0.15 to 1.56) (Figure 6). Potential sources of heterogeneity include the definition and measurements of numbness, the position of the mesh and the type of mesh fixation, the type of techniques used for inguinal hernia repair and the surgeon’s clinical expertise.

FIGURE 6.

Open preperitoneal mesh repair vs. Lichtenstein mesh repair: chronic numbness. df, degrees of freedom; M–H, Mantel–Haenszel.

Acute pain

Five trials54–57,59 reported mean VAS scores (Figure 7) and were included in a random-effects meta-analysis. The trial by Gunal and colleagues54 reported unrealistically high standard error (SE) values. It was assumed that these values indicated SDs rather than SEs, even though no confirmation from the authors was obtained. It is worth noting, however, that the Cochrane review by Willaert and colleagues,20 which included individual participant data, also interpreted these values as SDs. The trial by Moghaddam and colleagues57 did not report any measure of variability and, therefore, SD values were estimated using a simple average of the measures reported in the other trials (excluding the trial by Gunal and colleagues54).

FIGURE 7.

Open preperitoneal mesh repair vs. Lichtenstein mesh repair: acute pain. df, degrees of freedom; IV, instrumental variable.

The meta-analysis results showed no clear evidence of a difference between intervention groups (mean difference –0.49, 95% CI –1.06 to 0.09). Acute pain tended to be lower after open preperitoneal mesh repair, but moderate statistical heterogeneity was evident between trials (I² = 53%).

Four trials51,57,60,61 reported the proportion of participants with acute pain assessed between 1 week and 1 month after surgery. In general, fewer participants suffered from acute pain after preperitoneal mesh repair than after Lichtenstein mesh repair at week 1 (62.2% vs. 84.4%),61 at week 2 (6.7% vs. 38.7%)51 and at 1 month (0–26.7% vs. 8.6–51.1%)57,60,61 (see Appendix 9, Table 38).

Two trials57,63 reported the postoperative need for analgesics. The use of analgesics during the first 24 hours after surgery was lower among participants who underwent Lichtenstein mesh repair than among those who underwent open preperitoneal mesh repair (see Appendix 9, Table 39).

Mortality

Four trials reported mortality data. 53,56,57,59 There were only six deaths in total and this was balanced between the intervention groups. Three deaths occurred after open preperitoneal mesh repair and three after Lichtenstein mesh repair (Peto OR 1.05, 95% CI 0.21 to 5.25) (Figure 8).

FIGURE 8.

Open preperitoneal mesh repair vs. Lichtenstein mesh repair: mortality. df, degrees of freedom.

Complications

Eleven trials51–61 reported postoperative complications (see Appendix 9, Table 41). There was a considerable variation across trials in the way type of complications and time of assessments were reported. In many trials, complications were categorised as ‘early or ‘late’ by the trial investigators. When an adequate definition was not provided, any complication reported after 6 months was classified as ‘late’. Where time points were not specified, we consulted with our clinical experts to classify the complication as late or early. Complications, such as haematoma, seroma or urinary complications, were assumed to occur soon after surgery and were categorised as ‘early’ complications.

Ten trials51–58,60,61 reported data on early complications (see Table 6), including wound infection, haematoma, seroma, cord oedema, scrotal oedema and urinary complications (urinary retention/urinary tract infection). One trial59 reported overall complications data (haematoma, dysejaculation and infection) without separating the results for open preperitoneal group and Lichtenstein group. This trial, however, reported one participant with higher urinary frequency in the open preperitoneal group. While some trials reported each type of complication separately, others reported broad categories of complications. For three trials55,57,58 it was unclear whether complications were presented as number of people with any complication or as a total number of events. Owing to the lack of consistency among trials and taking into account the potential risk of double-counting events, a formal meta-analysis for early complications is not presented. Separate meta-analyses were, however, conducted for the following complication categories: wound infection, haematoma/seroma and urinary complications.

There was no clear evidence of differences between intervention groups for the incidence of wound infection (Peto OR 0.53, 95% CI 0.21 to 1.36), haematoma/seroma (Peto OR 1.29, 95% CI 0.75 to 2.20) or urinary complications (Peto OR 0.87, 95% CI 0.37 to 2.07) (Figures 9–11).

FIGURE 9.

Open preperitoneal mesh repair vs. Lichtenstein mesh repair: incidence of wound infection. df, degrees of freedom.

FIGURE 10.

Open preperitoneal mesh repair vs. Lichtenstein mesh repair: incidence of haematoma/seroma. df, degrees of freedom.

FIGURE 11.

Open preperitoneal mesh repair vs. Lichtenstein mesh repair: urinary complications. df, degrees of freedom.

Three trials reported information on late complications, including testicular atrophy58 and mesh infection/reaction. 51,53 Overall, events were balanced between intervention groups: one case of testicular atrophy and two cases of mesh infection/reaction were reported in the open preperitoneal groups while three cases of testicular atrophy were reported in the Lichtenstein groups. No trials reported any vascular/visceral injury, port site hernia or any other serious complications.

Recurrence/reoperation

Information on recurrence or reoperation was available in 11 trials. 51–61 Rates of hernia recurrence were generally low. Overall, there were 14 recurrences among participants who underwent open preperitoneal mesh repair and 19 among those who underwent Lichtenstein mesh repair. There was no clear evidence of a difference between the two surgical procedures (Peto OR 0.76, 95% CI 0.38 to 1.52) (Figure 12).

FIGURE 12.

Open preperitoneal mesh repair vs. Lichtenstein mesh repair: rate of recurrence/reoperation. df, degrees of freedom.

Time to return to normal activities

Five trials42,52,55–57 reported the time to return to work or to usual activities. There was considerable variation in the definition of the activities assessed but all of them included the word ‘work’ (see Appendix 9, Table 44). The SD values were not reported in one study;57 therefore, an average of the measures used in the other studies was imputed for the purposes of the meta-analysis.

Figure 13 shows the result of the random-effects meta-analysis. Overall, there was evidence that participants who underwent open preperitoneal mesh repair returned to normal activities around 1.5 days earlier than those who underwent Lichtenstein mesh repair (mean difference –1.49 days, 95% CI –2.78 to –0.20 days). There was evidence of statistical heterogeneity (I² = 83%).

FIGURE 13.

Open preperitoneal mesh repair vs. Lichtenstein mesh repair: time to return to normal activities. df, degrees of freedom; IV, instrumental variable.

Search strategy

A review of existing economic evaluations assessing open preperitoneal mesh repairs versus standard Lichtenstein mesh repair was performed following similar objectives, clinical inclusion and exclusion criteria, and data extraction methods to those detailed in the clinical effectiveness review (see Chapter 3, Methods for assessing the outcomes arising from the use of the intervention). Comprehensive search strategies were designed to identify economic evaluations of inguinal hernia repair (see Appendix 2). Final searches were undertaken on 31 October and 1 November 2014. The following databases were searched: NHS Economic Evaluations Database (inception to 1 November 2014), HTA Database (inception to 1 November 2014), MEDLINE (1946 to October week 4 2014), MEDLINE In-Process & Other Non-Indexed Citations (31 October 2014), EMBASE (1947 to 2014, week 44) and Research Papers in Economics (inception to 1 November 2014). Websites of HTA organisations were consulted for additional reports. Reference lists of all included studies were scanned and appropriate experts were contacted for details of additional reports of cost-effectiveness.

Separate searches were undertaken on 31 October or 3 November 2014 to identify QoL studies (see Appendix 2). Databases searched were included MEDLINE (1946 to October, week 4 2014), MEDLINE In Process & Other Non-Index Citations (31 October 2014), EMBASE (1947 to 2014, week 44), Science Citation Index (1995 to 1993 November 2014) and the Cost-effectiveness Analysis Registry (3 November 2014).

A health economist (DB) screened the title and abstract of all citations identified by the search strategies for economic evaluations for inclusion. Full-text papers of potentially relevant studies were retrieved and formally assessed for inclusion. Any uncertainty regarding studies selection was discussed with a second health economist (RH) and the review team clinical expert (IA).

Inclusion and exclusion criteria

Only studies reporting a comparison between open preperitoneal mesh repair and Lichtenstein mesh repair were included. The criteria for studies inclusion were similar to those of the review of clinical effectiveness. In particular, studies had to (1) focus on people undergoing elective surgical repair for primary unilateral inguinal hernia and (2) present results in the form of cost minimisation analysis, cost-effectiveness analysis, cost–utility analysis or cost–benefit analysis. Formally, cost comparison studies were not included in the review but were retained as potentially useful information for populating resource use and costs in the economic model.

Economic evaluations in the form of both decision models and trial-based analyses were considered suitable for inclusion. Papers that reported decision models and/or utility values for hernia patients, but that did not meet the prespecified inclusion criteria were retained for informing the development of the de novo model structure and parameters.

Comparisons of different methods of open preperitoneal mesh repair (e.g. Kugel vs. TIPP), plug and patch repair, and non-mesh techniques were outside the scope of this assessment and were therefore excluded. Furthermore, studies that focused on a very specific technical aspect of surgical repairs, such as studies comparing the use of different types of mesh, methods of sealant and methods of anaesthesia, were not deemed suitable for inclusion.

Data extraction

Data were extracted from included studies using a prespecified data extraction form. A copy of the data extraction form is presented in Appendix 10. Where possible, data extracted included:

1. background information, such as research question, study design, intervention and comparator details

2. costing methodology, in particular the perspective, year, currency and the discount rate applied

3. characteristics of the study population (e.g. age, hernia type, setting, inclusion criteria, exclusion criteria)

4. methodology with a focus on statistical/regression methods for the analysis of costs, effectiveness and uncertainty

5. mean costs and outcomes, incremental costs and outcomes for differences between groups and incremental cost-effectiveness ratios (ICERs)

6. data on uncertainty, such as results of bootstrapped data and 95% CIs

7. study strengths and limitations as reported by the study authors

8. conclusions and suggestions for further research as reported by the study authors.

Quality assessment of included studies

Studies that reported economic evaluations alongside RCTs were quality assessed against the British Medical Journal checklist for referees of economic evaluations. 65 Where possible, results were assessed from the UK NHS perspective. However, as no decision modelling studies matching our inclusion criteria were identified, no studies were appraised against the NICE reference case. 49,63

Data synthesis

A formal data synthesis proved unfeasible, as only one study that matched our inclusion criteria was identified. 66,67

Results of the cost-effectiveness searches

Our literature searches identified only one study assessing the cost-effectiveness of open preperitoneal mesh repair compared with Lichtenstein mesh repair that met our inclusion criteria. 66,67 We did not identify any decision modelling studies in the current literature. Two further Markov economic models13,36 that failed to meet our inclusion criteria were used to inform the development of the economic model structure.

Koning and colleagues,66,67 provide the only available evidence on the cost-effectiveness of open preperitoneal mesh repair versus Lichtenstein mesh repair for primary inguinal hernia. The study conducted a cost minimisation analysis alongside a RCT comparing the TIPP technique (randomised n = 143) with the Lichtenstein mesh repair (randomised n = 159) with 1-year follow-up. Costs were measured separately from a Dutch hospital and societal perspective. From a health services perspective, there was no significant difference in costs between TIPP and Lichtenstein mesh repair (mean difference –€13, 95% CI –€128 to €101). When a wider perspective of costs was adopted, cost savings in the TIPP group were statistically significant at the 5% level. From a societal perspective, TIPP was €1472 less costly than Lichtenstein mesh repair (95% CI –€2620 to –€325), indicating that incremental costs were heavily influenced by productivity gains generated by earlier return to work for non-retirees in the open TIPP repair group. The societal perspective analysis forms the main part of the authors’ conclusions.

Within the Koning and colleagues study,66,67 data were available on quality-adjusted life-weeks at 1-year follow-up and utilities were measured using the SF-36, converted to the Short Form questionnaire-6 Dimensions (SF-6D) measure of QoL, using published algorithms. 68 The authors found no difference in utility, based on the results from the SF-36. Mean quality-adjusted life-weeks difference for TIPP versus Lichtenstein mesh repair was 0.00983 (95% CI –1.01250 to 1.03217). They justified their decision not to conduct a cost–utility analysis on the basis of no difference in QoL between randomised trial arms.

If the data presented for QoL were combined with the reported cost data, TIPP would, on average, be less costly and more effective than Lichtenstein mesh repair and would thus be the most efficient, dominant treatment strategy. However, such results would be subject to a high degree of uncertainty. Furthermore, detailed sensitivity analyses and an extrapolation of results over a longer time horizon would be required before sound recommendations could be made on cost-effectiveness.

Quality assessment of the evidence

Quality assessment of the study by Koning and colleagues66,67 was performed according to the British Medical Journal guidelines for reviewers of economic evaluations. The study question was clear with justification for the approach used.

Quality of life measured over a period of only 1 year may be considered of insufficient duration to fully capture the impact, especially for those patients whose pain persists over time or who may suffer from longer-term recurrences. Responses to the SF-36 questionnaire were converted to the SF-6D preference-based measure of QoL and further adapted to derive utilities. 68 Although the SF-6D is a generic choice-based measure of QoL and is an accepted approach, it is not directly recommended for decision-making in a UK context, where the European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) is the preferred QoL instrument. 13,49 Furthermore, results are presented mainly from a societal perspective and, as such, are not directly transferable to a UK decision-making context where a health services perspective is normally adopted.

In general, the reporting of methods for the economic evaluation lacked details on analysis models used to estimate incremental costs and outcomes. There was little exploration of uncertainty in the study results, with the exception of some simple bootstrap analysis of incremental costs. The generalisability of results to inform UK policy-making regarding cost-effectiveness is likely to be limited because of the short time horizon and the differences between the methods used in the study and those typically used in a UK decision-making process. Nonetheless, the results of this study are promising for the potential cost savings, without any decrement in QoL associated with TIPP repair. In particular, earlier return to work and normal activities would be preferred from a patient and societal perspective if it could be achieved, especially if this also generated NHS cost savings in the longer term. Further research is needed to synthesise all the relevant outcomes of open preperitoneal mesh repair versus Lichtenstein mesh repair techniques for primary inguinal hernia. For this reason, we developed a de novo decision analysis model.

Introduction

Owing to a paucity of evidence from the review of the literature, we developed a de novo economic model to assess the relative efficiency of open preperitoneal mesh repair versus Lichtenstein mesh repair for the treatment of primary inguinal hernia from a UK health services perspective. All methods of Lichtenstein mesh repair were considered equivalent for the purpose of the model. Similarly, all methods of open preperitoneal mesh repair (e.g. Kugel, TIPP) were assumed to be equivalent. The decision to group all open preperitoneal methods together was justified by the lack of available data from the systematic review of clinical evidence to populate a model based on specific repair techniques.

Methods

A probabilistic Markov model was developed by TreeAge Pro^TM 2014 software (TreeAge Software, Inc., Williamstown, MA, USA) to estimate expected values for costs from a NHS perspective and outcomes measured in terms of quality-adjusted life-years (QALYs) over a 25-year time horizon. The model was used to assess the relative efficiency of open preperitoneal mesh repair versus Lichtenstein mesh repair. Results were obtained with a Monte Carlo (probabilistic or second order) simulation of the developed Markov model with 100,000 iterations. The model parameters were drawn from appropriate distributions attached to baseline data, relative effect sizes, costs and utilities. Baseline results were presented as mean costs and QALYs from the iterations, and the simulation was used to present uncertainty in modelled outcomes.

Description of the model/model structure

Two key studies13,36 identified from the literature review of cost-effectiveness were consulted to assist with the development of the model structure. McCormack and colleagues13 assessed laparoscopic versus open repairs and found that recurrences and chronic pain were important drivers of cost-effectiveness. The base-case model file from this study was obtained from the authors. Achelrod and Stargardt36 developed a Markov cohort model with only a 1-year time horizon to compare heavy mesh techniques versus lightweight mesh techniques for the repair of inguinal hernia. The authors identified chronic pain as the most relevant factor contributing to cost-effectiveness and developed their model structure based exclusively on the development of chronic pain, for which an aggressive treatment protocol was used. We developed treatment pathways and appropriate health states after examining the above literature and after consultation with the members of the advisory group for this assessment, which consisted of hernia specialist surgeons, patient representatives and a general practitioner (GP). Revisions to the model structure were made according to the feedback received from the members of the advisory group.

Given the chronic nature of inguinal hernia and the potential for the development of chronic problems after surgery, a Markov state-transition model is regarded as the most appropriate method to estimate longer-term costs and health outcomes of the two index surgical procedures. The structure of a Markov model allows patients to move between defined mutually exclusive health states in a controlled manner over specified time periods. Patients after repair of primary inguinal hernia may enter one of the following mutually exclusive health states: (1) to recover from surgery with no further short-term consequences; (2) to develop short-run complications (within the first 3 months); (3) to develop chronic pain or numbness; (4) to have a recurrence; or (5) to die of natural causes. Transitions are allowed to occur over 5 years, where the best available data exist. Beyond this point, for the duration of the 25-year model time horizon, participants are assumed to be either well or to die of natural causes.

For ease of presentation, the model structure is presented in two diagrams. Figure 14 illustrates the transitions within the first model cycle and Figure 15 presents transitions for all remaining cycles of the model.

FIGURE 14.

Diagram of model structure (first 3-month model cycle).

FIGURE 15.

Diagram of model structure (longer-term health states). Note that the dotted arrows refer to tunnel states where patients may spend more than one cycle; for example, recovering from a recurrence or a late complication.

All patients enter the model at the ‘initial surgery’ health state, having a primary inguinal hernia repair (either open preperitoneal mesh repair or Lichtenstein mesh repair). Within the first 3-month model cycle, patients may recover (entering the ‘well’ health state), develop postoperative pain or numbness, incur other early complications (such as wound haematoma, seroma or urinary problems) or experience an early recurrence.

Transitions between states for the remainder of the model are dependent, in part, on a patient’s health state in the first cycle of the model. Early complications are assumed to be resolved within the cycle in which they occur. All patients having a recurrence in the first cycle (see Figure 14) enter the recurrence health state in Figure 15, where they join a separate model process. Patients with unresolved pain or numbness following the first model cycle progress to the chronic pain or the chronic numbness health states, respectively. All patients may recover, die, develop a recurrence or experience late complications at any point throughout the model. Patients may enter the death state because of operative mortality from initial surgery or because of all-cause mortality from any state in the model.

The next two sections present further details on the structural assumptions underpinning the economic model.

Baseline probabilities

In order to estimate reliable absolute differences in costs and outcomes between treatment strategies, it is important to ensure that relative effect sizes from the meta-analyses are applied to appropriate baseline data. Two sources of baseline data were used. Data on proportions of the modelled patient cohort with pain and numbness at 3 months, 1 year and 5 years were sourced from the Lichtenstein mesh repair arms of studies included in the systematic review of clinical evidence (see Chapter 3). For complications and recurrences, transition probabilities were sourced from the Lichtenstein mesh repair arm of studies included in the systematic review conducted by the AHRQ. 15

Relative effect sizes

Absolute parameter values for open preperitoneal mesh repair were calculated by applying relative effect sizes (for open preperitoneal mesh repair vs. Lichtenstein mesh repair) to baseline probabilities of pain, numbness, complications and recurrences. All relative effect sizes are incorporated into the model as point estimates of RRs with 95% CIs, estimated using the Mantel–Haenszel random-effects method. There was insufficient information available from our review of clinical evidence to develop a RR of the majority of individual outcomes for all the time points of interest. We therefore assumed that the RR remained constant at all time points up to 5 years following surgery. However, data were available to split into early (up to 3 months) and late (beyond 3 months) complications (Table 9). Data for 3-month complications were used to construct log-normal distributions around the estimates. However, for late complications we simply used the point estimate of the RR of 1.1 from the meta-analysis, without sampling from the respective probability distribution. The assumption of a constant RR for late complications was made because of the rarity of the events, the high level of uncertainty (RR 1.1, 95% CI 0.08 to 14.79 for late complications) and the unlikely impact on cost-effectiveness results. In the absence of any data to suggest otherwise, the RR of having a second recurrence was assumed to be the same as having a first recurrence.

Effect sizes for rare events are reported in Chapter 3 using Peto ORs. However, in order to apply risk estimates to baseline probabilities, the economic model uses RR estimates. The decision to use RRs, rather than Peto OR is unlikely to impact on cost-effectiveness outcomes because of the low incidence of recurrences and late complications.

We have assumed no difference in mortality risk between open preperitoneal mesh repair and Lichtenstein mesh repair strategies.

Table 9 details point estimates and 95% CIs of relative effect sizes used in the model. Uncertainty surrounding the point estimates was characterised using log-normal distributions. Data used to define the distributions are presented as mean and SEs of the log estimates.

Utilities and quality-adjusted life-years

Utility values for surgery (0.68), well (0.956), pain (0.836) and numbness (0.919) health states were sourced from data published in the UK Medical Research Council (MRC) hernia study,72 based on responses to the EQ-5D-3L and valued using UK general population tariffs estimated using the time trade-off technique. 73 No published data were available for the remaining health states, namely complications (early or late) or recurrences. Based on discussion with our clinical experts and on previous modelling conducted by McCormack and colleagues,13 for the base-case analysis we have applied the same utility weights to complication and recurrence health states and to chronic pain (0.836). For recurrences, this is likely to reflect the impact of suffering a recurrence event on QoL, where a patient might be expected to be in significant pain or discomfort. Utility weights for second recurrences were assumed equal to those of a first recurrence. For complications, this assumption may represent an overestimation of the utility decrement for minor complications. We therefore explore the use of a utility decrement for a milder health state (numbness) and apply this decrement to all complications as a sensitivity analysis.

Utility data applied to model health states were sourced from the MRC study. 72 Data for all individuals (both those receiving open and laparoscopic repair) in a health state (e.g. experiencing chronic pain) were used to inform the utility calculation. This could be argued to be a questionable approach given our research question focuses on different methods of open hernia repair. However, patients for whom utility data were available by trial arm for individual health states in the MRC study72 were sparse. Pooling the data across arms allowed for a larger sample and generated utility estimates with greater face validity for individual health states. It is unlikely that the utility of individual health states would be dependent on the index surgery; therefore, we have assumed that the utility estimates from the pooled data are applicable to the current model.

There were not enough data to stratify health states owing to severity of condition. All chronic pain patients receive the same utility, regardless of severity. The MRC study provides the best available utility data, based on EQ-5D-3L. The data and assumptions outlined above have been successfully used in previous cost–utility analyses and in decision modelling studies of hernia repair. 13,36 Nonetheless, alternative sources of utility data were available, and despite limitations, their incorporation into the economic model was explored by means of sensitivity analyses.

Table 10 reports the point estimate base-case utility, together with the attached beta distributions (and corresponding parameters). Utility weights reported below were further adjusted by the UK population norms for males and are age adjusted using published weights74 following recommended best practice. 75 Half-cycle corrections were applied to all utilities in the model and QALYs accruing into the future were discounted at 3.5% per annum in line with current NICE guidance. 49

Resource use and costs

Costs were calculated from the perspective of the NHS and reported in 2013/2014 UK pound sterling. Resource-use data were estimated using a combination of published literature and clinical expert opinion. Unit costs were taken from NHS reference costs for secondary care,76 the Personal and Social Services Research Unit77 unit costs for primary care and the British National Formulary for medication costs. 78 The main components of total cost in the economic model were the costs of surgery and the cost of treating chronic pain. All resource-use assumptions and costing assumptions were confirmed as clinically relevant in a UK setting by the clinical experts of our advisory group.

Changes to baseline model parameters

For the base-case analysis, data on chronic pain and numbness were derived from the systematic review of clinical evidence, while data on recurrences and complications were derived from the AHRQ review. 15 Data were uncertain, particularly in relation to the progression of chronic pain over time. A number of sensitivity analyses were carried out (Table 14). The first explored the impact of using AHRQ data, while the second explored the impact of using data from our systematic review of clinical evidence (see Chapter 3) for all baseline data. The advantages and disadvantages of alternative sources have been addressed (see Model parameters, baseline probabilities). In all cases, data are sourced from the Lichtenstein mesh repair arms of the included RCTs.

Differences across studies at different time points contributed to increase the uncertainty related to the progression of pain over time. The studies in our systematic review did not present details of a treatment protocol for patients with chronic pain. It was, therefore, unclear whether the baseline data referred to patients managed conservatively, aggressively or not treated at all. Thus, base-case data may have over- or underestimated the true pain profile over time. Similar concerns exist for numbness, although the impact on cost-effectiveness would be less given the lower utility decrement and lower treatment costs. We therefore explored two extreme analyses for both pain and numbness, assuming that (1) the baseline probability at 3 months does not fall over time (i.e. no one with chronic pain/numbness is cured over the first 5 years) and (2) the proportion with chronic pain/numbness at 1 and 5 years is 0 (i.e. all problems resolved by 1 year after surgery).

Changes to risk ratio parameters

The results of the base-case economic analysis were strongly influenced by the chosen RR data. As outlined in Chapter 3, all the point estimates from the RR data tended to favour the open preperitoneal mesh repair approach. However, results lacked statistical significance based on random-effects meta-analyses, therefore, some uncertainty remained. The two most likely parameters to impact on cost-effectiveness (e.g. those that generate the highest treatment cost and greatest loss of utility) are chronic pain and recurrences. We explored a potentially worst-case scenario analysis against open preperitoneal mesh repair, by combining the upper ends of the CIs for the RR of chronic pain (1.27) and recurrence (1.57). Although highly unlikely, the analysis serves to explore a plausible combination of effect sizes which could be seen as being most unfavourable, illustrating a lower bound on the probability of cost-effectiveness of open preperitoneal mesh repair. A two-way sensitivity analysis combining RRs of pain and recurrence is also presented to demonstrate the relative impact of these key parameters on the optimal treatment strategy. Two-way sensitivity analyses were based on identifying the treatment option with the greatest net benefit at a WTP of £20,000 for a QALY gained. Table 15 outlines the sensitivity analyses considered for RR parameters.

Changes to utility parameters

Utilities for surgery, ‘well’, chronic pain and numbness health states were available from the UK MRC hernia trial72 and were used in the base-case model. However, uncertainty surrounded the most appropriate utility weights to choose for complications and recurrences. For the base-case analysis, it was assumed, as in McCormack and colleagues,13 that the utility of a recurrence was equivalent to the utility of chronic pain (0.836). For the purposes of the current model, we made a similar assumption for complications. However, the impact of complications on QoL may be minimal, especially for minor complications identified in the systematic review of clinical evidence (e.g. urinary infection or minor haematoma). We also conducted a sensitivity analysis to explore the use of the numbness utility applied to all complications (0.919) (as this may represent a plausible estimate, especially for less severe complications).

Patient-reported outcome measures (PROMs), based on EQ-5D (European Quality of Life-5 Dimensions) data, were available for groin hernia repair in England. 82 Data were available in aggregate form for wound complications (grouping numbness and pain), reoperation and readmission. However, it was not possible to disentangle the utility weights for numbness and pain. It was also unclear which readmissions were for a recurrence or which were for other complications. However, by assuming that the majority of readmissions were for hernia recurrence, utility data for readmissions provided a plausible alternative estimate for recurrence utility, which could be explored within the model. Data were based on the full data release from April 2012 to March 2013,82 in which records are reported 4 months following all types of hernia surgery. The mean estimated utility for recurrence using PROMs data was 0.858 (SD 0.2083). These estimates were based on 3393 completed EQ-5D-3L profiles for readmissions out of 22,314 total records.

Alternative sources of utility data were available, although their appropriateness for use in the current decision model is questionable. QALY data from Koning and colleagues42,67 were available for TIPP repair (0.8588) versus Lichtenstein mesh repair (0.8566) at 1-year follow-up, based on SF-36 responses, converted to SF-6D utilities. 68 The data were not health-state specific; they were based on a measurement inconsistent with current recommended practice for UK-based analyses49 and, therefore, were of potentially limited value for the economic model. Nonetheless, the data were based on preference-based QoL measures and presented a plausible alternative. Therefore, we conducted sensitivity analyses to explore their use within the first year of the model analysis (adjusted to a 3-month cycle length). Data included beyond 1 year were the same as those used in the base-case analysis.

Data were available from the MRC study72 for a convalescence period at 3 months following surgery, but were not used in the base-case analysis, owing to the potential for counterintuitive results attaching greater weight to the numbness health state than 3-month surgical convalescence. The base-case analysis assumed that patients who were well 3 months following surgery had the same QoL as all patients in the ‘well’ health state (0.952). However, as a sensitivity analysis, we applied the convalescence utility (0.86) to all patients at the end of the first 3-month cycle. Although the base-case analysis may have overestimated the assumed time to recovery from surgery, the sensitivity analysis may underestimate the impact of chronic pain or recurrence within the first 3-month cycle. Summary details of all sensitivity analyses on utilities are presented in Table 16.

Changes to cost parameters

Open preperitoneal mesh repair and Lichtenstein mesh repair require similar staff and theatre resource use, equipment and time. Both procedures map to the same HRG and so received equal surgical costs for the base-case analysis. However, the base case negates the fact that open preperitoneal mesh repair is not routinely used in the UK. If the open preperitoneal mesh repair approach were to be recommended as standard UK practice, surgeons would face a learning curve while they become skilled in the technique. There may be an initial increase in operative times and/or supervisory requirement for training clinicians in the early post recommendation phase. There may be also differences in the percentage of procedures performed under general or local anaesthesia, which are not captured in HRG codes. We, therefore, conducted a sensitivity analysis where open preperitoneal mesh repair was 20% more costly than Lichtenstein mesh repair. We also explored an analysis where Lichtenstein mesh repair was 20% more costly. A threshold analysis is presented to determine the additional surgical cost that would be required for open preperitoneal mesh repair in order to render Lichtenstein mesh repair the preferable option.

The base-case model assumed a conservative treatment approach for chronic pain. A sensitivity analysis explored a more aggressive approach, as outlined in the study by Achelrod and Stargardt,36 costing £855.98 per cycle and a ‘no treatment’ approach where the cost per cycle was assumed to be nil. Two-way sensitivity analyses investigated the impact various combinations of risk and cost of treating chronic pain on the optimal treatment strategy. Table 17 summarises the sensitivity analyses on cost data.

Structural uncertainty

The base-case model assumed that patients having a recurrence would transition into a separate model process whereby they run the risk of having a second recurrence, being well for the remainder of the model time horizon or dying from natural causes. There were insufficient data to model pain, numbness or other complications following the recurrent surgery. However, a sensitivity analysis tested the impact of allowing all patients having a recurrence to develop pain, other complications, or numbness with the same likelihood as those having an index surgery.

Other methodological uncertainty

Base-case results were analysed using a probabilistic model from which values for RRs were sampled from a log-normal distribution. However, the mean of a log-normal distribution calculated using the standard approach would not return the original point estimate of the RR from the meta-analysis. This reflects that the standard reporting for RRs is the modal value on the RR scale, as opposed to the mean. As a sensitivity analysis and validation check on the results, we incorporated the deterministic value of the RR point directly from the meta-analysis.

Standard methodological practice recommends that discount rates are tested within sensitivity analysis for both cost and QALY outcomes. We specifically tested the impact of varying the base-case discount rate of 3.5% per annum for costs and QALYs between 0% and 6%. Alternative discount rates were applied jointly to costs and QALYs in the sensitivity analysis.

The base-case analysis modelled utilities to account for age- and sex-adjusted UK population norms. 73 This reflects that as a patient grows older, their utility falls over time. A sensitivity analysis was conducted where the population norm adjustment was not carried out and data reported in the UK MRC study were incorporated directly into the model. 13,72

The most accurate data to populate model parameters were available at 1 year following surgery, with data becoming comparatively scarcer for longer follow-up periods, with no accurate data available beyond 5 years. Three alternative model time horizons were explored: short (1 year, from which the best trial data exist); medium (5 years, for which some data exist); and longer term (25 years, as in the base-case analysis). All methodological sensitivity analyses are summarised in Table 18.

Subgroup analyses

There was a lack of available data to populate the economic model for individual subgroups and, therefore, no formal subgroup analyses were possible. However, a separate analysis is presented allowing the model to run, assuming a starting age of 40 years old and a starting age of 70 years old. It is worth noting that the only parameters to vary within these analyses were those relating to age-adjusted population utility and all-cause mortality. As such, the subgroup analyses should be considered exploratory in nature.

Base-case cost-effectiveness results

Results for the base-case probabilistic analysis for the comparison of open preperitoneal mesh repair with Lichtenstein mesh repair are presented in Table 19. We have followed best practice guidelines for economic evaluation and presented results in terms of a probabilistic analysis. 83 The results of the economic model, based on expected values of costs and QALYs show that the open preperitoneal mesh repair improves health outcomes measured as QALYs. The additional QALYs can be achieved while also saving NHS costs. Open preperitoneal mesh repair is thus the dominant treatment strategy, with a very high probability of cost-effectiveness at all usual threshold values of WTP for a QALY gain in the UK,49 including if decision-makers were not willing to pay any additional cost for health gains. The strength of the base-case conclusions in favour of open preperitoneal mesh repair is driven by a reduction in hernia-related problems after surgery. Patients receiving the open preperitoneal mesh repair are, on average, less likely to experience chronic pain, recurrence, chronic numbness or early complications. There is greater uncertainty surrounding late complications, although events are extremely rare. Overall cost savings to the NHS are achievable by the reduction in requirement for costly treatments post surgery, especially those for chronic pain, which can be achieved without any additional surgical cost.

Uncertainty in the modelled results is illustrated in a number of ways, based on the output from the probabilistic analysis, namely: (1) data that reports the likelihood of cost-effectiveness at each threshold value (£0, £10,000, £20,000, £30,000 and £50,000) (see Table 19); (2) as CEACs (Figure 16); and (3) as scatterplots of incremental costs and outcomes, presented on the cost-effectiveness plane (Figure 17).

FIGURE 16.

Base-case CEAC.

FIGURE 17.

Scatterplot of the cost-effectiveness plane.

The results clearly show that, based on our model base-case assumptions, open preperitoneal mesh repair is highly cost-effective, with < 2% chance of Lichtenstein mesh repair being the preferred treatment strategy, regardless of WTP for a QALY. The scatterplot visually represents the likelihood of cost-effectiveness at a typical threshold value of WTP for a QALY of £20,000. 49 The majority of simulations (97%) fall within the south-east quadrant of the cost-effectiveness plane, indicating the strength of the base-case dominance conclusions for open preperitoneal mesh repair.

Results of sensitivity analyses

The probabilistic analysis captures the uncertainty in data inputs and simultaneously varies all parameters to which distributions are attached. It is therefore a good representation of overall sampling uncertainty. The analysis, however, does not account for methodological or structural uncertainty in the model, nor does it identify the individual parameters to which the model outcomes are most sensitive. We therefore undertook a range of one- and two-way sensitivity analyses of parameter values and methodological and structural assumptions used in the base-case model. See Tables 14–18 for details of the analyses carried out and see Tables 20–26 for the results from these analyses for baseline parameters, RRs, utilities, cost, structural assumptions, methodological uncertainty and exploratory subgroup analyses, respectively. All sensitivity analyses are presented as probabilistic estimates of expected values for costs, QALYs and ICERs, together with the probability of cost-effectiveness, as for the base-case analysis.

Changes to relative effect sizes

Base-case model results are informed by random-effects meta-analyses. The use of fixed-effects meta-analyses generates relative effect sizes with greater statistical precision. As effect sizes favour open preperitoneal mesh repair, the use of fixed-effects meta-analysis would further improve the cost-effectiveness case for open preperitoneal mesh repair. Table 21 presents results of further sensitivity analyses conducted around relative effect sizes used in the model. A plausible but worst-case scenario for open preperitoneal mesh repair is created by combining the upper ends of the 95% CIs for two of the main model result drivers, namely chronic pain (1.27) and recurrence (1.57). In this analysis, open preperitoneal mesh repair remains more effective (QALYs gained), but is also more costly, with an ICER of £15,109 per QALY gained. Open preperitoneal mesh repair is thus potentially cost-effective. However, great uncertainty exists with a probability of 49% and 53% of cost-effectiveness at £20,000 and £30,000, respectively.

TABLE 21 - Sensitivity analyses: changes to relative effect sizes

Combining upper bound of CIs: RR of chronic pain (1.27) and recurrence (1.57) – potential worst-case scenario for open preperitoneal mesh repair.

Surgical Strategy	Costs (£)	Difference in costs (£)	QALYs	Difference in QALYs	ICER (£/QALY)	Probability of cost-effectiveness at threshold values of WTP per QALY gained (%)
						£0	£10,000	£20,000	£30,000	£50,000
Lichtenstein	2292	–	10.677	–	–	97	63	51	47	43
Open preperitoneal	2411	+119	10.685	+0.008	15,109	3	37	49	53	57

Overall, the analyses presented in Table 21 show that the model is sensitive to extreme assumptions regarding the RRs of pain and recurrence. Noting this sensitivity, we conducted a two-way analysis of alternative combinations of RR for chronic pain and recurrence (Figure 18).

FIGURE 18.

Two-way sensitivity analysis comparing RRs of chronic pain with RRs of recurrence. LR, Lichtenstein repair; OPP, open preperitoneal.

Figure 18 shows that the model conclusions are much more sensitive to the RR of chronic pain than they are to the RR of recurrence. This is driven by comparatively fewer recurrence events compared with chronic pain. No plausible values of recurrence would change the cost-effectiveness conclusions alone, however, when combined with RRs of chronic pain above 1.25, greater uncertainty exists. However, given that the upper end of the CI for RR of chronic pain is 1.27, it is unlikely that feasible combinations of risk of recurrence and pain would change cost-effectiveness conclusions.

Changes in costs

Changes to cost data used in the model have a proportionally greater impact on results than changes in utility data. A number of assumptions have been made regarding costs, each of which is tested in Table 23.

TABLE 23 - Sensitivity analyses: changes to costs

Costs and cost differences are rounded to the nearest whole number and as such may not be directly calculable from data in the presented tables.

Surgical strategy	Costs (£)	Difference in costs (£)	QALYs	Difference in costs QALYs	ICER (£/QALY)	Probability of cost-effectiveness at threshold values of WTP per QALY gained (%)
						£0	£10,000	£20,000	£30,000	£50,000
More heavily treated chronic pain.36 Cost = £855.98 per cycle
Lichtenstein	3681	–	10.677	–	–	3	2	2	1	1
Open preperitoneal	2783	–897	10.718	+0.041	Dominant	97	98	98	99	99
No treatment for chronic pain (assume cost per cycle = £0). Also assumes chronic pain resolves by itself over a period of time
Lichtenstein	1825	–	10.677	–	–	4	1	2	2	2
Open preperitoneal	1785	–41	10.718	+0.041	Dominant	96	99	98	98	98
Assume that cost of surgery is 20% higher for Lichtenstein mesh repair vs. open preperitoneal mesh repair (cost Lichtenstein mesh repair = £1968)
Lichtenstein	2620	–	10.677	–	–	0	0	0	0	1
Open preperitoneal	2036	–584	10.718	+0.041	Dominant	100	100	100	100	99
Assume that cost of surgery is 20% higher for open preperitoneal mesh repair vs. Lichtenstein mesh repair (cost of open preperitoneal mesh repair = £1968)
Lichtenstein	2292	–	10.677	–	–	71	12	6	4	3
Open preperitoneal	2364	+72	10.718	+0.041	£1,778	29	88	94	96	97

The model is most sensitive to the assumed equal costs for both index surgical procedures. A scenario where open preperitoneal mesh repair is 20% more costly than Lichtenstein mesh repair generates more uncertainty in the modelled estimates of cost-effectiveness, especially at lower threshold values of WTP for a QALY gained. Trade-offs will occur when additional surgical cost of open preperitoneal mesh repair is compared with cost savings attributable to a reduction in future hernia-related problems such as chronic pain. However, in the modelled scenario, open preperitoneal mesh repair remains the most cost-effective treatment strategy, with an ICER of £1778 and a probability of cost-effectiveness of 94% at a threshold value of WTP for a QALY gained of £20,000. Noting the sensitivity of the modelled estimates of cost-effectiveness to the cost of surgery, a threshold analysis was conducted, indicating that the surgical cost for open preperitoneal mesh repair would need to be £2601 (59% greater than Lichtenstein mesh repair) to change cost-effectiveness conclusions from a net monetary benefit point of view with a threshold value of WTP of £20,000 per QALY gained. Such a scenario is unlikely, given similar equipment, resource use, staff time, theatre time and time to discharge for both groups.

Other than the assumption of equal surgery costs, the magnitude of incremental costs is primarily driven by the costs attached to chronic pain treatment. An aggressive treatment scenario, with very high costs, improved the case of cost-effectiveness for open preperitoneal mesh repair, as comparatively fewer patients need to incur such costs under that treatment strategy. A scenario where no chronic pain is treated but utility decrements remain constant is the least favourable for open preperitoneal mesh repair. Although the cost attached to chronic pain has a large impact on incremental costs, in all cases, open preperitoneal mesh repair remains dominant and has a high probability of cost-effectiveness (> 98% at a WTP of £20,000 per QALY gained).

The results presented throughout this section confirm the robustness of the model conclusions for a range of parameter estimates. However, while they do not alter conclusions, analyses that vary RRs within plausible ranges and those that simultaneously vary the cost of treatment, especially chronic pain, appear to have the greatest impact on the strength of cost-effectiveness outcomes. Figure 19, therefore, presents a two-way sensitivity analysis illustrating the preferred strategy following a net benefit approach for alternative combinations of treatment cost per cycle and RR of pain for open preperitoneal mesh repair compared with Lichtenstein mesh repair.

FIGURE 19.

Two-way sensitivity analysis comparing per cycle treatment cost and RR of developing chronic pain in open preperitoneal mesh repair and Lichtenstein mesh repair. LR, Lichtenstein repair; OPP, open preperitoneal.

Higher treatment costs for chronic pain favour open preperitoneal mesh repair; however, RRs of chronic pain would need to be > 1.2 before any treatment cost for chronic pain would alter cost-effectiveness conclusions. Figure 19 illustrates some uncertainty but indicates that only in highly unlikely scenarios could Lichtenstein mesh repair be considered cost-effective.

Clinical effectiveness

There is evidence that participants who underwent open preperitoneal mesh repair returned to work or usual activities around 1.5 days earlier than those in who underwent Lichtenstein mesh repair. In general, participants randomised to open preperitoneal mesh repair tended to have a lower incidence of pain and numbness, fewer recurrences and fewer complications than those randomised to Lichtenstein mesh repair. However, CIs for treatment effects were wide and most of our meta-analyses results were not statistically significant at the conventional 5% level.

The advent of tension-free mesh repairs has reduced considerably the incidence of recurrence, and as such, other postoperative complications, including chronic pain, have gained importance in the assessment of surgical approaches for inguinal hernia. Chronic pain after inguinal repair is common. Evidence suggests that approximately 20% of patients suffer from chronic pain28,31,84 and this has a substantial impact on patients’ daily activities, such as walking, working and sleeping, as well as on personal relationships and social interactions. 28

Our meta-analysis, which included data from six published trials52,56,58–61 and one unpublished trial,51 showed a 50% reduction in the risk of chronic pain after open preperitoneal mesh repair (RR 0.50, 95% CI 0.20 to 1.27), but failed to demonstrate a statistically significant difference between the two surgical approaches. This finding is in line with previously published systematic reviews. 18–20 A meta-analysis of 12 RCTs, with a total of 1437 participants published by Sajid and colleagues19 in 2013, showed that the risk of developing chronic groin pain was reduced after open preperitoneal mesh repair (RR 0.48, 95% CI 0.26 to 0.89; p < 0.02). This meta-analysis, however, assessed specifically the effects of TIPP versus Lichtenstein mesh repair and did not focus exclusively on participants with primary unilateral inguinal hernias but included bilateral, recurrent or incarcerated inguinal hernias. Similarly, a meta-analysis by Li and colleagues18 published in 2012, which included 10 RCTs and two comparative studies, concluded that the ‘open preperitoneal approach is a feasible alternative to the Lichtenstein procedure with similar complication rates’. Li and colleagues18 included, however, the Prolene Hernia System as a relevant comparator. On the other hand, a Cochrane review by Willaert and colleagues20 published in 2012, comparing open preperitoneal techniques versus Lichtenstein mesh repair for elective inguinal hernia, failed to provide firm conclusions owing to the of dearth of suitable RCTs (only three RCTs were included) and the variation in the outcome data across trials. 20

Incidence of numbness was not consistently assessed in the included trials perhaps because among all the possible postoperative complications, numbness is not considered as relevant as chronic pain. Only four trials56,58,59,61 contributed to our meta-analysis and rates varied between trials. Overall, we did not find a statistically significant difference between the two surgical approaches (RR 0.48, 95% CI 0.15 to 1.56). Our results are consistent with those of Li and colleagues18 who did not find any significant difference in postoperative numbness between open preperitoneal mesh repair and standard Lichtenstein mesh repair (RR 0.50, 95% CI 0.18 to 1.43).

Return to work or usual activities tended to be earlier following open preperitoneal mesh repair than following standard Lichtenstein mesh repair and it was found to be statistically significant (mean difference –1.49 days, 95% CI –2.78 to –0.20 days; p = 0.02). Some systematic reviews18–20 did not assess ‘time to return to normal activities’, which is an important measure for establishing patients’ recovery after hernia surgery and for assessing the cost-effectiveness of different surgical strategies from a wider patient and societal perspective.

We did not observe any statistically significant differences between the open preperitoneal approach repair and the Lichtenstein approach in terms of number of deaths, recurrences, complications (i.e. wound infection, haematoma/seroma or urinary problems) and length of hospital stay. In particular, the risk of developing recurrences and complications observed in our analyses is consistent with that of other systematic reviews in the literature. 19,20 It is also worth observing that while in the past recurrence of inguinal hernia was an important postoperative complication, after the advent of the tension-free mesh technique the risk of recurrence has decreased considerably and the current incidence rates are as low as 1–4%. 14,85

Cost-effectiveness

The probabilistic Markov cohort model developed as part of this assessment is the first attempt within the literature to synthesise systematically evidence on costs and outcomes of open preperitoneal mesh repair versus Lichtenstein mesh repair for the treatment of primary inguinal hernia. It is currently the most complete evidence base on cost-effectiveness in a UK context. Results of a cost-minimisation analysis from a Dutch societal perspective, over a 1-year time horizon, conducted alongside a RCT are available in the literature. 67 However, the follow-up period of this cost-minimisation analysis is insufficient to capture all costs and benefits of different surgical approaches and it is uncertain whether or not the findings may apply reliably to a UK setting.

The results of our economic evaluation were informed by data from the systematic review of clinical effectiveness. On average, patients who underwent open preperitoneal mesh repair were less likely to experience chronic pain, chronic numbness, early postoperative complications and recurrences. Fewer postoperative problems resulted in an average of 0.041 QALYs gained over the 25-year horizon. As both procedures require similar resource use (e.g. staff, equipment, mesh, time in theatre and time to discharge), we assumed equal costs in the model. Fewer postoperative problems resulted in fewer treatment requirements and a reduced NHS burden of treating complications such as chronic pain. We found that because of similar surgical costs and reduced costs in the follow-up period, the open preperitoneal mesh repair was £256 less costly per case completed compared with the Lichtenstein mesh repair using base-case model assumptions.

By generating greater QALYs and potentially saving NHS resources, the open preperitoneal mesh repair appears to be the dominant, most efficient treatment option for inguinal hernia with a high probability of cost-effectiveness (> 98%) at the typical threshold values of WTP for a QALY recommended by NICE. 49 Furthermore, from a wider societal perspective, lower incidence of chronic pain and numbness and earlier return to work or to normal activities would probably be preferred from a patient and family perspective with fewer days of lost wages and potentially lower costs of self-medication for the management of chronic pain after surgery. Earlier return to work would also be preferable from an employer point of view, as fewer days of absence would reduce productivity losses.

Despite some differences, our results are broadly consistent with those of Koning and colleagues67 who found that TIPP was significantly less costly from a societal perspective than the Lichtenstein mesh repair. Although the direction of effect was similar to that of our results, from a health-care perspective, their results were less convincing over a 1-year time period. Our results present a stronger case for open preperitoneal mesh repair owing to the longer time horizon in which the full costs of treating long-term complications such as chronic pain, numbness and recurrences become apparent.

The results of the CEA were robust to a range of different model input data, especially where alternative choices of data were available for baseline probabilities and utilities. Results were more sensitive to estimates of cost and especially the cost of treatment for chronic pain. Different estimates of treatment resource use and cost such as the modelled conservative base-case assumptions, aggressive treatment assumptions,36 or no treatment at all generated substantial differences in incremental costs (and hence estimates of potential cost savings to the NHS). However, in all cases the conclusion of dominance remained unbroken.

Similarly to the findings reported by Achelrod and Stargardt,36 we found chronic pain to be an important driver of cost-effectiveness outcomes. Achelrod and Stargardt modelled a decision to perform laparoscopic hernia repair using heavy- versus lightweight mesh and used similar model input data to those in our model (especially around utility weights). 36 They modelled the development of chronic pain over a 1-year time horizon, finding a strong impact of pain on cost-effectiveness. McCormack and colleagues who modelled a decision to perform hernia repairs using laparoscopic or open mesh procedures also drew similar conclusions. 13 McCormack and colleagues found recurrence to be an important factor. While our model includes a health state for recurrence, variation in recurrence data within the model had minimal impact on overall results, owing to the current low recurrence rate after hernia repairs. 7,36,86 Our findings are consistent with a number of existing studies, all of which find chronic pain to be an important driver of outcomes following primary inguinal hernia repair. 15,17,20

In our model, in all but two extreme scenario analyses, the conclusion of dominance remained unbroken. The first scenario analysis, where both the RR of chronic pain and the risk of recurrence were assumed equal to the upper end of their 95% CI, generated an ICER of £15,109 per QALY gained. However, the results were surrounded by considerable uncertainty. Despite the low likelihood of such an extreme scenario analysis, the point estimate of the ICER remains favourable to the open preperitoneal mesh repair. The second scenario analysis, where the surgical cost of open preperitoneal mesh repair was assumed to be 20% greater than that of the Lichtenstein mesh repair, generated an ICER of £1778 per QALY gained. This scenario can be regarded as plausible, especially in an early post recommendation phase when surgeons would be required to progress along a learning curve, which may generate short-run additional costs. However, even when cost of surgery is increased by 20%, the open preperitoneal approach remains likely to be cost-effective with a probability of cost-effectiveness of 94% at a WTP of £20,000 per QALY gained. The cost of open preperitoneal surgery would need to be 59% greater than that of the Lichtenstein surgery to change the overall cost-effectiveness conclusions.

The lack of baseline, relative effect size or utility data for hernia repair in different age groups hampered the possibility to estimate cost-effectiveness for different age subgroups reliably. However, there was no obvious reason to believe that costs of the two surgical procedures would differ by age, and utility values were adjusted to reflect population norms in the base-case analysis. Furthermore, there were no data available to model the cost-effectiveness of the different techniques used to perform open preperitoneal mesh repairs.

Clinical effectiveness

This assessment has been conducted according to current methodological standards and is the most up to date and complete evidence base assessing the effects of open preperitoneal mesh repair versus Lichtenstein repair for the treatment of primary inguinal hernia. We need to acknowledge, however, some potential limitations.

The meta-analyses results demonstrated evidence of statistical heterogeneity between included trials. For binary outcomes we used a random-effects model as the primary meta-analysis method, except when events were rare, when we used the recommended Peto approach. Although we observed a trend in favour of the open preperitoneal approach, CIs for treatment effects were wide and most results were not statistically significant at the conventional 5% level. Varying differences in the way outcomes were assessed and reported were observed across trials. In particular, considerable variation existed among included trials with regard to: (1) the definition of chronic pain and the use of measurement scales after surgery; (2) the definition of ‘work and normal activities’; (3) the time of follow-up assessments and study duration; (4) characteristics of the hernia defect (high-risk and low-risk hernias); (5) type of open preperitoneal techniques and type of mesh (soft mesh, mesh with memory ring, single layer, double layer); and (6) surgeon’s expertise.

The assessment of pain (acute and chronic) is quite challenging as ‘pain’ is essentially a subjective outcome and the tools for its measurement are variable and not straightforward. The majority of included studies used a VAS, which is considered a valid tool for measuring pain after inguinal hernia repair (IASP). However, the VAS has the limitation to measure pain only as one-dimension score, while pain is a more complex phenomenon. Moreover, the exact significance of scores higher than 0 may be difficult to capture or interpret. The observed variation in the rates of chronic pain between trials can be partly explained by the way trial investigators described chronic pain. Chronic pain was (1) defined according to the definition of the IASP including a VAS score above 0 which lasts for more than 3 months, (2) defined as a VAS score between 3 and 1061 or (3) not defined at all. Moreover, as chronic pain may be triggered by the position of the mesh and the type of mesh fixation, different type of techniques used for inguinal hernia repair as well as the surgeon’s expertise may have contributed to the observed differences between trials. Two trials,56,59 both conducted in the Netherlands, reported an unusual high incidence of chronic pain (13% and 40%, respectively) and persistent numbness (51% and 25%, respectively) after Lichtenstein repair. It is possible, but we have no information to confirm this, that the pain was the result of nerve damage, which is more likely to occur after Lichtenstein repair than after open preperitoneal repair.

Time of follow-up assessments varied among included trials, which made it challenging to combine outcome data reliably. Furthermore, we could not assess long-term complications and recurrences as the majority of trials were of relatively short duration (mean 17 months).

We were not able to quantify the impact of the potential risk of bias on the observed estimates of effects. Overall, only two trials were judged at low risk of bias,52,56 whereas remaining trials were judged at high or unclear risk of bias because of inadequate randomisation methods, blinding procedures (lack of participants and/or outcome assessors blinding) or reporting. We contacted the authors of trials who did not report important methodological details but did not receive any further information.

The open preperitoneal approach (e.g. Kugel, TIPP) may require more cranial incision than the Lichtenstein approach and outcome assessors may recognise the shape of the performed incision even when they are blinded to the surgical methods. However, the main outcome of interest for this assessment, ‘chronic pain’, was self-reported by participants and it is unlikely they were able to identify the type of hernia repair from the surgical incision. Therefore, two trials52,59 that blinded participants but reported a difference in the shape of the surgical incisions were judged to be at low risk of bias of detection bias.

As all included trials were conducted outside the UK, there is some uncertainty on whether or not the results of this assessment are applicable to a UK setting.

Cost-effectiveness

The cost-effectiveness results were broadly robust to a range of sensitivity analyses undertaken, and there is a high degree of confidence that the open preperitoneal approach is cost-effective compared with the Lichtenstein approach. Although, we used the best available evidence to populate our economic model, our results are subject to a number of assumptions and uncertainties. Most of these uncertainties impact on the magnitude of cost savings or QALY gains for open preperitoneal repair, however, do not change the overall conclusions and recommendations.

There were no data available to explore the cost-effectiveness of different types of open preperitoneal techniques (e.g. Kugel, TIPP repair). While we can conclude, with a high degree of confidence, that the open preperitoneal approach is cost-effective for the treatment of inguinal hernia, we are not in the position to make any claims on the most appropriate or preferred open preperitoneal technique. Different techniques may contribute to substantial differences in outcomes and costs. The economic model failed to account for such differences between techniques.

With regard to the surgical cost of the two interventions, we could not identify secondary procedure codes from HRG data to develop individual costs for the open preperitoneal approach compared with the Lichtenstein approach. All procedures mapped to the same code and were, therefore, assumed to have equal cost in the economic model. While the assumption of similar treatment costs would remain the same, the value of these costs might not truly represent opportunity costs of the procedures, especially given that procedure codes may include the higher cost of laparoscopic procedures. Although the model may overestimate the cost of open hernia repairs, the error would have no impact on the marginal analysis because of the assumption of costs equivalence across all open mesh techniques. Data related to time to discharge from hospital show no difference between procedures, and clinical expert opinion indicates almost identical surgical procedures. The main difference between surgical approaches appears to be the exact placement of the mesh. Thus, it is likely that the performed sensitivity analyses account for any differences in the costs of performing the surgical procedures in clinical practice.

Another factor that might contribute to surgical costs in the UK is the current limited clinical expertise in performing the open preperitoneal mesh repair. The majority of UK surgeons (96%) prefer the standard Lichtenstein approach. 16 Consequently, if the open preperitoneal mesh repair were to be recommended, there would be significant training costs to take into consideration as surgeons would be expected to progress along a learning curve until they acquire expertise and confidence with the new technique. In the short term, this may add an additional cost burden to the NHS for the open preperitoneal approach. However, it is likely that any additional cost would be offset by a reduction in the costs of treating postoperative complications, such as chronic pain and recurrences.

A number of assumptions were made regarding the structure and the relevant data to populate the economic model. We assumed that a patient could have a maximum of two hernia recurrences before they entered either a ‘well’ health state or died of natural causes. This assumption mirrors that made previously by McCormack and colleagues. 13 We also assumed that no pain or numbness occurred after a recurrence as the modelling of such health states was beyond the scope of this assessment, given that the differences would probably be because of the recurrence operation and not to the index procedure. Sensitivity analyses, which explored the impact of imputing similar rates of pain and numbness as for the primary procedure, did not alter our conclusions.

We further assumed that recurrence procedures would be carried out using the same technique as for the index procedure. This assumption had a limited impact on cost-effectiveness results, given that all procedures were assumed to generate the same surgical cost. Again, modelling the decision on the most appropriate procedure to treat recurrences was beyond the scope of the review.

A further concern relates to the quantity and quality of data available to populate the economic model, especially for chronic pain and numbness after hernia repair. The model was developed to detail the progression of pain or numbness over time. However, data were not available from included trials to populate the model at all the time points of interest (3 months, 1 year and 5 years after surgery). The heterogeneity observed between trials adds uncertainty to the baseline data used in the model. This is particularly problematic for pain and numbness that were measured inconsistently across trials. Nevertheless, in all cases we have managed to apply baseline data for a single treatment strategy, namely the Lichtenstein repair arm of appropriate RCTs. To limit the heterogeneity impact as much as possible, where possible, we have selected trials that reported similar measures of pain over time.

None of the included trials from which baseline data were sourced, detailed the treatment strategy used to manage chronic pain. It was therefore unclear whether pain reduction over time was owing to any treatment at all, to self-medication, to conservative pharmacotherapy or to more aggressive treatment approaches (see Achelrod and Stargardt,36 for example). The incremental costs (i.e. the magnitude of cost saving to the NHS) predicted by the economic model are highly sensitive to the cost of treatment for chronic pain. There is a lack of evidence in the literature to identify appropriate treatment strategies for chronic pain after hernia repair. However, it is reasonable to assume an initial conservative treatment approach that may move towards a more aggressive treatment, if chronic pain persists over time. Uncertainties in the preferred treatment approach used in UK clinical practice together with a lack of data to link treatment to pain outcomes weaken the economic model projections of the magnitude of incremental costs and outcomes. It is reasonable to assume, for example, that minor pain would require no treatment, whereas more serious pain (e.g. a VAS score of 7 and above) would require a more aggressive approach. The lack of appropriate data to stratify pain according to severity is an important limitation, which may add uncertainty to the modelled chronic pain costs and outcomes. The base-case economic model follows a conservative treatment approach as this approach is more likely to reflect UK clinical practice and less likely to overstate cost-effectiveness findings. However, alternative treatment strategies, from minor or no treatment to more aggressive approaches, may also be applied. We used evidence from the available literature36 to identify a more aggressive treatment approach and thus range the cost of treatment from no treatment (assumed cost per cycle = £0) to aggressive (cost per cycle = £855.98). The variation in the costs applied allows for a range of plausible treatment approaches for chronic pain. The assumed modelled cost of chronic pain does not impact on the probability of cost-effectiveness, but the magnitude of cost savings to the NHS varies substantially.

Quality-adjusted life-years calculated for the base-case economic analysis were based on utility weights calculated from a single UK study,27 which raises some concerns with regard to generalisability. Furthermore, for health states where data from the UK MRC study were not available, we assumed that early postoperative complications and recurrences would have an impact similar to that of chronic pain in the base-case analysis. This assumption generated some uncertainty in QALY estimates. We explored alternative data sources for incidence of recurrence, using assumptions about reported PROMs data, and imputed a less severe health-state utility of numbness for all complications as sensitivity analyses. While different utility weights for the model generated different QALY estimates, none altered the cost-effectiveness conclusions.

NHS budgetary impact

At present, the majority of open mesh repairs for inguinal hernia performed in the UK are based on the standard Lichtenstein approach with very few, if any, based on the open preperitoneal approach. The results of our assessment and our economic evaluation, however, showed better patient outcomes after open preperitoneal mesh repair over the longer term and hence potential cost savings. The budgetary impact of increasing the use of the open preperitoneal approach in the UK clinical setting is dependent on the clinical effectiveness of the open preperitoneal mesh approach compared with the Lichtenstein mesh approach as well as on the number of open mesh procedures for primary inguinal hernias performed annually and the likely proportion of procedures that might be conducted using the preperitoneal approach. As such, the budgetary impact projections should be interpreted as explanatory. The cost savings to the NHS are heavily dependent on the willingness of surgeons to change current routine practice and their confidence in the open preperitoneal mesh repair. Data from the HES show that out of 65,759 primary inguinal hernia repairs carried out in England during the period 2012/13, 61,280 (93%) were open procedures based on the use of prosthetic materials (e.g. mesh). 1 The 2010 NICE implementation uptake report35 on laparoscopic surgery for inguinal hernia repair indicated that 16.36% of all primary repairs were performed using laparoscopy. Based on the 2012/13 hospital activity level and assuming that the rates of laparoscopic hernia repair remain unchanged from the 2010 NICE uptake report, we can reasonably infer that 10,758 primary mesh procedures were likely to be conducted using a laparoscopic approach, while the remaining 50,522 were likely to be conducted using an open mesh approach (probably the Lichtenstein approach, as nearly all open mesh repairs in the UK are performed using the standard Lichtenstein technique). 16

Figure 20 outlines the projected annual cost savings to the NHS for various uptake rates of open preperitoneal mesh repair. The projected cost savings are informed by the base-case economic model projections of average cost savings of £256 for every case completed as open preperitoneal mesh repair rather than Lichtenstein mesh repair.

FIGURE 20.

Annual impact on NHS England budgets of performing open procedures using open preperitoneal technique.

If all cases were to be transferred to the open preperitoneal approach, the cost savings to the NHS in England alone would be substantial, amounting to a maximum of £12.93M per year. It is worth noting that these estimates are based on projections from the economic model, which is informed by an uncertain evidence base. Further work would be required to re-estimate budgetary impacts once more conclusive data on clinical effectiveness are available.

In Scotland, 8068 inguinal hernia repairs were completed in 2012/13. 87 Assuming that 92% of hernia repairs were for a primary hernia (as in England),1 7423 repairs were performed for the treatment of primary hernias. In Scotland, the proportion of completed laparoscopic surgeries appears to be slightly lower than in England. Data from 2007/8 indicate that only 13% of all inguinal hernia repairs were completed using laparoscopic surgery. 46 Therefore, considering the assumptions outlined above, the estimated number of procedures to which the economic model result applies is 6374 per annum. Figure 21 reproduces a similar assessment of budget impact for NHS Scotland.

FIGURE 21.

Annual impact on NHS Scotland budgets of performing open procedures using open preperitoneal technique.

As the magnitude of cost savings are sensitive to a number of factors outlined throughout our economic evaluation, the estimated cost savings to the NHS should be considered in light of the uncertainty around some parameters in the economic model. Factors such as additional training costs of moving to the open preperitoneal approach could reduce the magnitude of NHS cost savings in the early post recommendation phase. The true cost savings will depend in part on how easily change of routine practice could be achieved and how quickly surgeons could progress along a learning curve. It is likely that any additional costs for open preperitoneal mesh repair owing to development of the surgeon’s skills and training would be short term and would be more than offset by the projected cost savings over the longer period. It is likely that any change in practice would take place over an extended period of time and any additional training costs would be expected to be staggered over time.

There is no guidance regarding the preferred method for open preperitoneal mesh repair. Owing to a lack of suitable data, the systematic review of clinical evidence and the economic model assessed different open preperitoneal mesh techniques together as one single analysis. It is feasible to assume that different approaches may generate different cost estimates and further research is required to identify the most efficient open preperitoneal mesh technique in order to optimise the use of current NHS resources.

Previous NICE guidance34 recommends the use of laparoscopic repairs, even though more costly, because of a lower incidence of chronic pain and an earlier return to normal activities compared with open mesh repair. The open preperitoneal mesh repair allows patients to return to work and normal activities earlier and potentially improves pain outcomes. Further research is required to determine any potential trade-offs between the laparoscopic approach and the open preperitoneal approach and establish if cost savings could be enhanced further without adverse consequences for patients.

Impact on patients and their families

Patients having an open preperitoneal mesh repair returned to normal activities (including work) around 1.5 days earlier than those in the Lichtenstein mesh repair groups (mean difference –1.49 days, 95% CI –2.78 to –0.20 days). The earlier resumption of daily and working activities is likely to be of benefit to patients, their families (with a potentially reduced burden of care) and to the society more generally. We also observed a trend towards a lower incidence of postoperative pain, recurrences and complications even though results were not statistically significant at the conventional 5% level of confidence. These findings may translate into reduced requirements for oral analgesics in the immediate postoperative period. With early return to normal activities patients reduce their time off work after hernia surgery. Therefore, the open preperitoneal mesh repair can be associated with a reduction in lost wages as well as a reduction in lost productivity because of absence from work.

Hospital Episode Statistics show that 34,147 out of 61,280 (56%) of all primary inguinal hernia repairs using mesh were performed in people of working age (age 18–64 years). 1 Applying this information to the estimated number of total open repairs outlined above, 28,292 people treated with open mesh repair would be of working age in England. Applying a standard average hourly unit tariff for working time in the UK of £12.80 per hour88 to the estimated difference in return to normal activities, the average cost saving from reduction in lost wages is £19.07 per additional open mesh repair conducted using an open preperitoneal approach (95% CI £2.56 to £35.58). Figure 22 presents the cost savings from a reduction in lost wages in England per annum for different implementation rates of open preperitoneal mesh repair. If all repairs were performed using the open preperitoneal approach instead of the Lichtenstein approach, the estimated cost savings from a reduction in lost wages in England is £539,528 annually (95% CI £72,428 to £1,006,629). Figure 23 shows the projected cost savings from a reduction in lost wages for different uptake rates in Scotland.

FIGURE 22.

Annual impact on reduction in lost wages from open preperitoneal mesh repair in England.

FIGURE 23.

Annual impact on reduction in lost wages from open preperitoneal mesh repair in Scotland.

If all repairs were performed using the open preperitoneal approach instead of the Lichtenstein approach, estimated cost savings from a reduction in lost wages in Scotland is £68,061 annually (95% CI £9137 to £126,985).

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