Prophylactic mesh reinforcement of stomas: a cost-effectiveness meta-analysis of randomised controlled trials

Background Previous meta-analyses of randomised controlled trials (RCTs) have suggested a reduction in parastomal hernias (PSH) with prophylactic mesh. However, concerns persist regarding variably supportive evidence and cost. We performed an updated systematic review and meta-analysis to inform a novel cost-effectiveness analysis. Methods The PubMed, EMBASE and Cochrane Centre Register of Controlled Trials databases were searched (February 2018). We included RCTs assessing mesh reinforcement during stoma formation. We assessed PSH rates, subsequent repair, complications and operative time. Odds ratios (OR) and numbers needed to treat (NNT) were generated on intention to treat (ITT) and per protocol (PP) bases. These then informed cost analysis using 2017 UK/USA reimbursement rates and stoma care costs. Results Eleven RCTs were included. Four hundred fifty-three patients were randomised to mesh (PP 412), with 454 controls (PP 413). Six studies used synthetic meshes, three composite and two biological (91.7% colostomies; 3.64% ileostomies, 4.63% not specified). Reductions were seen in the number of hernias detected clinically and on computed tomography scan. For the former, ITT OR was 0.23 (95% confidence interval 0.11–0.51; p = 0.0003; n = 11); NNT 4.17 (2.56–10.0), with fewer subsequent repairs: OR 0.29 (0.13–0.64; p = 0.002; n = 7; NNT16.7 (10.0–33.3). Reductions persisted for synthetic and composite meshes. Operative time was similar, with zero incidence of mesh infection/fistulation, and fewer peristomal complications. Synthetic mesh demonstrated a favourable cost profile, with composite approximately cost neutral, and biological incurring net costs. Conclusions Reinforcing elective stomas with mesh (primarily synthetic) reduces subsequent PSH rates, complications, repairs and saves money. We recommend that future RCTs compare mesh subtypes, techniques, and applicability to emergency stomas.


Introduction
Parastomal hernias (PSH) remain common, occurring in 6% of patients with loop ileostomies and almost half with end colostomies, and can profoundly affect quality of life, impair productivity and generate substantial healthcare costs [1].
Mesh PSH repair was originally described in 1997 [1] and is generally accepted as the most effective method. However, a number of recent randomised controlled trials (RCTs) have variably suggested that reinforcing stomas prophylactically with mesh reduces the risk of PSH. Consequent systematic reviews and meta-analyses have supported this position [2], and also variably suggested risk of complications to be minimal, addressing one of two major reservations towards widespread acceptance and change in practice, beyond heterogeneity of the evidence base. However, none have addressed the second: financial cost. We aimed to perform an updated systematic review and meta-analysis, informing a cost-effectiveness analysis.

Literature search
We searched the PubMed, EMBASE and Cochrane Centre Register of Controlled Trials databases up to 9 February 2018, in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses and Meta-analysis Of Observational Studies in Epidemiology guidelines using the following search term: (mesh OR hernia) AND (stoma OR parastomal OR colostomy OR ileostomy) AND (randomised OR controlled OR trial). Bibliographies of retrieved articles were searched. Two authors (JMF and CPJW) screened articles independently.

Inclusion and exclusion criteria
We included English language RCTs randomising patients undergoing stoma formation (loop/end ileostomy/colostomy) to mesh reinforcement (synthetic/composite/biological) or not.

Endpoints
Primary outcomes were development of PSH (clinically and/ or radiologically detected, as defined in individual studies) and subsequent repair. These were then used to inform a cost-effectiveness analysis. Our secondary outcomes were complications (as defined by individual studies) and operating time [3].

Data collection
Data were extracted independently (JMF and CPJW). We contacted one study's authors to clarify ITT and PP results [4].

Assessment of bias and evidence quality
Bias was assessed using the Cochrane Collaboration 'Risk of bias' tool [5], with recommendations stratified using GRADE [6].

Meta-analysis and other statistical analysis
Meta-analysis was performed using RevMan v5.2 (The Cochrane Collaboration); additional analyses using R v3.02 (R Core Team). Heterogeneity was quantified by I 2 and Chisquare. Odds ratios (OR), absolute risk reduction (ARR) and 95% confidence intervals (CI) were calculated used random effects when I 2 > 50%. Both intention to treat (ITT; patients randomised to treatment arms, irrespective of subsequent protocol violations), and per protocol (PP; only patients receiving treatment and follow-up as stipulated) analyses were performed. Funnel plots were inspected for asymmetry. Perceived publication bias was corrected using the 'trim and fill' method [7]. p < 0.05 was considered significant. Sensitivity analyses were conducted.

Cost-effectiveness analysis
We performed a two-tiered analysis. The first (most conservative) comprised the cost of elective PSH repair and mesh. The second tier included additive stoma care for patients with a PSH per year for 2 years (typical follow-up of included RCTs). This was estimated by assuming PSH resulted in 25% more frequent leakage with a commensurate increase in cost of appliances and care (£3024.80-4315/$3932.5-5609.50) [8,9,10].

Evidence quality
Overall, quality ranged from very low to moderate (

Cost analysis
Routine use of synthetic mesh would save money (

Discussion
In the most up-to-date meta-analysis of 11 RCTs involving 907 patients, we found reinforcing elective stomas with prophylactic mesh reduced the incidence of subsequent PSH and repair. There was no significant increase in operative time, with substantial cost savings for synthetic meshes, and fewer peristomal complications. The evidence was less clear (and of lower quality) for composite and biological meshes, with the extra cost of the latter seeming to subsume potential savings. These findings agree with recent meta-analyses [2]. However, none have assessed costs, anecdotally perceived to be significant and hence a barrier to changes in practice. As such we believe our findings are novel, and provide context to the evolving evidence base. This notwithstanding, we acknowledge a number of limitations, beyond those of constituent study heterogeneity, bias and methodology. We used GRADE recommendations to provide context, but we were unable to perform meaningful meta-regression on the basis of individual study quality. Similarly, we were unable to compare stoma types, other than analysis of end colostomy.
Ours is also the first meta-analysis to include the recent publication by Odensten et al. [3]. This was notable both as the largest study to date, with relatively little bias and its finding of a lack of effect. The reasons for this are unclear; however, the rates of PSH in both arms of the trial were high, at approximately 30%.
Our cost analysis was by necessity constrained by the very limited data available regarding cost to patients, and projections by length of study follow-up. It is very likely that our estimates are conservative: NNT would likely reduce further with time, and we could not reliably account for significant additional costs, including the economic costs to patients who develop hernias (for example time off work) beyond stoma care. Furthermore, it is likely that commensurate  benefits in quality of life would be seen beyond the financial, but these areas have received little attention in the literature. We recommend that these be explored in the next generation of RCTs and furthermore, that these compare mesh types and reinforcement approach. However, perhaps most pressing is whether reinforcement is of benefit in patients undergoing emergency stomas, particularly a Hartmann's procedure. A substantial proportion of these patients never undergo reversal, whilst they are perhaps most vulnerable to the consequences of PSH.

Conclusions
We found that reinforcing stomas with mesh reduces subsequent PSH rates, repair and complications, and should be considered routinely. Synthetic mesh has the best evidence profile and results in potentially substantial cost savings. The additional cost of composite and biological mesh does not yet appear to confer any additional benefit.

Compliance with ethical standards
Conflict of interest The authors declare that they have no conflict of interest.
Ethical approval This article does not contain any studies with human participants or animals performed by any of the authors.
Informed consent As a meta-analysis of published data formal consent was not required.
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