Protocol for an independent patient data meta-analysis of prophylactic mesh placement for incisional hernia prevention after abdominal aortic aneurysm surgery: a collaborative European Hernia Society project (I-PREVENT-AAA)

Introduction Incisional hernia (IH) is a prevalent and potentially dangerous complication of abdominal surgery, especially in high-risk groups. Mesh reinforcement of the abdominal wall has been studied as a potential intervention to prevent IHs. Randomised controlled trials (RCTs) have demonstrated that prophylactic mesh reinforcement after abdominal surgery, in general, is effective and safe. In patients with abdominal aortic aneurysm (AAA), prophylactic mesh reinforcement after open repair has not yet been recommended in official guidelines, because of relatively small sample sizes in individual trials. Furthermore, the identification of subgroups that benefit most from prophylactic mesh placement requires larger patient numbers. Our primary aim is to evaluate the efficacy and effectiveness of the use of a prophylactic mesh after open AAA surgery to prevent IH by performing an individual patient data meta-analysis (IPDMA). Secondary aims include the evaluation of postoperative complications, pain and quality of life, and the identification of potential subgroups that benefit most from prophylactic mesh reinforcement. Methods and analysis We will conduct a systematic review to identify RCTs that study prophylactic mesh placement after open AAA surgery. Cochrane Central Register of Controlled Trials, MEDLINE Ovid, Embase, Web of Science Core Collection and Google Scholar will be searched from the date of inception onwards. RCTs must directly compare primary sutured closure with mesh closure in adult patients who undergo open AAA surgery. Lead authors of eligible studies will be asked to share individual participant data (IPD). The risk of bias (ROB) for each included study will be assessed using the Cochrane ROB tool. An IPDMA will be performed to evaluate the efficacy, with the IH rate as the primary outcome. Any signs of heterogeneity will be evaluated by Forest plots. Time-to-event analyses are performed using Cox regression analysis to evaluate risk factors. Ethics and dissemination No new data will be collected in this study. We will adhere to institutional, national and international regulations regarding the secure and confidential sharing of IPD, addressing ethics as indicated. We will disseminate findings via international conferences, open-source publications in peer-reviewed journals and summaries posted online. PROSPERO registration number CRD42022347881.


GENERAL COMMENTS
1.The primary aim is to evaluate the efficacy and effectiveness of the use of prophylactic mesh for patients who underwent post open abdominal aortic aneurysm surgery.What's outcome to measure the efficacy and effectiveness of the use of prophylactic mesh? 2. The secondary aims include evaluation of postoperative complications, pain, and quality of life.Please provide the clear definitions for each secondary outcome.That is, at which time point and how the postoperative complication, pain and quality of life will be measured or defined.3. Page 5, line 23.The authors say the primary outcome is the time to incisional hernia occurrence during long-term follow-up.Please define "long-term follow-up".4. Page 8, the section of treatment efficacy.I think this is mainly for studying the primary aim.Again, it is lack of detail of outcome.The authors mentioned they will report effect sized as relative risk with 95% CI.I assume the outcome is not time to long-term incisional hernia occurrence. 5. Please lay out the hypotheses for each study aims (primary and each secondary).6. Please describe statistical analysis approaches that will be used to address for each hypothesis (primary and each secondary) in sufficient detail.Author: We would first and foremost like to thank the reviewer for the clear comments on our manuscript.

REVIEWER
1.The primary aim is to evaluate the efficacy and effectiveness of the use of prophylactic mesh for patients who underwent post open abdominal aortic aneurysm surgery.What's outcome to measure the efficacy and effectiveness of the use of prophylactic mesh?Author response: The primary outcome parameter is incisional hernia rate, which we intend to determine at 2, 3 and 5 years after surgery.We have now more clearly formulated our primary outcome parameter in the paragraph 'Aims'.
2. The secondary aims include evaluation of postoperative complications, pain, and quality of life.Please provide the clear definitions for each secondary outcome.That is, at which time point and how the postoperative complication, pain and quality of life will be measured or defined.
Author response: We added clear outcome measures for the secondary outcomes, such as noting the types of rating scales that might have been used in the original trials for assessing the pain and quality of life of the patients.The time points at which we want to evaluate these secondary outcomes are 30 days, 6 months and 1 year postoperatively, which has been added to the revised manuscript in the paragraph 'Aims'.Of course, this will also depend on the availability of specific data on different postoperative time points in each of the included trials.
3. Page 5, line 23.The authors say the primary outcome is the time to incisional hernia occurrence during long-term follow-up.Please define "long-term follow-up".
Author response: We have extended the 'Aims' paragraph to include that we want to assess incisional hernia rate at 2, 3, and 5 years postoperatively.Again, this will also depend on the availability of these data in the included trials.
4. Page 8, the section of treatment efficacy.I think this is mainly for studying the primary aim.Again, it is lack of detail of outcome.The authors mentioned they will report effect sized as relative risk with 95% CI.I assume the outcome is not time to long-term incisional hernia occurrence.
Author response: Indeed, treatment efficacy will be determined using the primary outcome measure, which is IH rate.We removed 'time to long-term IH occurrence" from the manuscript, because the reviewer is correct that this is not the outcome of interest.We added more explanation in this section.Effect sizes from the Cox-regression models accounting for clustering on trial level, will be described with RRs.
5. Please lay out the hypotheses for each study aims (primary and each secondary).6. Please describe statistical analysis approaches that will be used to address for each hypothesis (primary and each secondary) in sufficient detail.
type of mesh implanted, imaging techniques used for the diagnosis of incisional hernia, etc. should be included.
GENERAL COMMENTSI think it is a very good idea to provide more scientific evidence for laparotomy wall closure techniques.As a tip, I think that certain technical characteristics such as mesh placement technique,