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Effective Health Care Program

Comparative Effectiveness of Surgical Options for Inguinal Hernia

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On August 9, 2011, two amendments were made to this protocol. To view these amendments, please see the section titled “Summary of Protocol Amendments.”

Background and Objectives for the Systematic Review

Inguinal Hernia

An inguinal hernia is a protrusion of abdominal contents into the inguinal canal through an abdominal wall defect. A direct inguinal hernia protrudes through the deep inguinal ring, whereas an indirect inguinal hernia protrudes through the internal inguinal ring and may descend through the inguinal canal. Direct hernias typically develop only in adulthood and are more likely to recur than indirect hernias.1 If the hernia is severe enough to restrict blood supply to the intestine, it is termed a strangulated hernia, and immediate corrective surgery is necessary. Most inguinal hernias, however, are less dangerous, and elective surgery is often performed to correct the defect. Symptoms include abdominal pain and a lump in the groin area, which is most easily palpable during a cough. Some inguinal hernias, however, are asymptomatic.2

The lifetime rate of inguinal hernia is 25 percent in males and 2 percent in females.3 The risk of inguinal hernia increases with age, and the annual incidence is around 50 percent by the age of 75.4 Approximately two-thirds of inguinal hernias are indirect, and one-third are direct.3 Approximately 10 percent of cases are bilateral.5 Recurrence occurs in approximately 1 percent to 5 percent of cases.6

In children, the incidence ranges from 0.8 percent to 4.4 percent.7 It is 10 times more common in boys and also more common in infants born before 32 weeks gestation (13% prevalence) and infants weighing less than 1,000 grams at birth (30% prevalence).7 As in adults, about 10 percent of cases involve bilateral hernia.8

Numerous classification systems have been proposed for groin hernias.9 One commonly used system was introduced by Nyhus in 1993.10 This system employs several clinical factors including direct/indirect, degree of enlargement of the internal inguinal ring, and degree of posterior wall weakness. Specifically, it comprises six types of increasing severity: 1) indirect inguinal hernia with a normal internal ring; 2) indirect inguinal hernia with an enlarged internal ring; 3a) direct inguinal hernia; 3b) indirect inguinal hernia causing posterior wall weakness; 3c) femoral hernia; and 4) recurrent hernia.10 (This review will not involve femoral hernias due to the different patient populations and pertinent treatments.) Stoppa 11 proposed that aggravating factors such as obesity or abdominal distension should upgrade the patient by one Nyhus level.11 Higher severity generally means a higher risk of recurrence, and an appropriate classification may support the management approach.

Surgical Repair of Inguinal Hernia

Surgical repair of hernias is the most commonly performed general surgical procedure in the United States.12 In 2003, an estimated 770,000 surgical repairs of inguinal hernia were performed.12 These repairs are typically performed on an outpatient basis (87% in 1996).12 Such a large volume of procedures suggests that even modest improvements in patient outcomes would have a substantial impact on population health.13

The primary goals of surgery include preventing recurrence of the hernia, returning the patient to normal activities quickly, and minimizing postsurgical discomfort and the adverse effects of surgery. The various surgeries present different constellations of benefits and risks, which presents some clinical uncertainty in the choice among approaches. Balancing these factors is a difficult yet critical process in an effort to make the best possible medical decisions.

Some patients with inguinal hernias may not be in pain or limited in any way by the hernia. For these patients, surgery may not be necessary. One of the key questions (KQs) in the evidence review will be a comparison between surgical and nonsurgical approaches to the management of pain-free inguinal hernias.

Surgical procedures for inguinal hernia repair generally fall into three categories: open repair without the use of mesh (i.e., sutured), open repair with a mesh, and laparoscopic repair with a mesh. Within each of these categories, several specific procedures have been employed. Until the 1980s, open suture repair was the standard; however, the resulting tension along the suture line yielded relatively high rates of recurrence and patient discomfort. Nonsutured “tension-free” surgical mesh gained in popularity, and many specific open procedures were used, such as Lichtenstein repair and mesh plug repair. One author estimated that in 2003, 93 percent of groin hernia repairs involved the use of a mesh, and of these, about three-fourths of these repairs involved either a Lichtenstein repair or mesh plug.12 Thus, the most important relevant questions about current hernia repair all involve comparisons between different mesh-based approaches.

Almost all surgical procedures in adults involved the use of a synthetic mesh to cover the defect. However, mesh is not recommended for use in pediatric inguinal hernia due to concerns about the risk of inflammatory reactions, damage to the vas deferens and/or testes, and infertility.7

More recently, two laparoscopic approaches using a mesh—transabdominal preperitoneal repair and totally extraperitoneal repair—have seen increased use.14 Laparoscopic approaches have the potential for shortening recovery time and reducing some postoperative morbidities.15 They also may be associated with longer operation times and a relatively long learning curve. Totally extraperitoneal repair was introduced after transabdominal preperitoneal repair due to concerns about a possible increased risk of internal organ damage within the peritoneum.

Previous research has shown that the repair of a recurrent inguinal hernia is subject to a greater risk of additional recurrence.16 Further, bilateral inguinal hernia is subject to a greater recurrence risk than unilateral inguinal hernia.17 These increased risks may be due to certain anatomical difficulties that complicate the surgical approach in these types of patients.18 Some clinicians have suggested that laparoscopic approaches are better suited to recurrent and bilateral hernias, and in KQ 2 (see below) we delineate separate comparisons for primary, bilateral, and recurrent hernia.

Specific aspects about mesh repair that may influence outcomes are the type of mesh (e.g., lightweight or heavyweight), whether mesh fixation is used, and if so, whether fixation is accomplished with sutures or glue. These mesh-specific issues are covered by specific KQs (see Key Questions below).

Different procedures often require different methods for anesthesia. Some forms of open mesh repair can be performed with local anesthesia, whereas laparoscopic techniques such as transabdominal preperitoneal repair often require general anesthesia.19 Two key postsurgical morbidities are surgical site infection20 and chronic pain.21 Sanabria et al.20 found that without prophylactic antibiotics, surgical site infections occurred in 2.9 percent of patients having undergone mesh repair, as compared to only 1.4 percent among those who received prophylactic antibiotics. Regarding chronic pain, Nienjuis et al.21 estimated that pain lasting beyond 3 months postoperatively occurs in 11 percent of patients undergoing mesh repair.

In terms of settings, most hernia surgeries are performed not in specialized hernia centers, but rather by general surgeons who also perform many other types of surgeries.19 It is generally recognized that the surgical repair of inguinal hernia is a highly specialized skill, and patients receiving care from more-experienced surgeons may be better than patients receiving care from less-experienced surgeons. The evidence review will specifically examine evidence on the association between surgical experience and hernia recurrence (see Key Questions below).

Given the clinical uncertainty, a systematic review of the existing evidence on comparative effectiveness will help inform important medical decisions about surgical options for inguinal hernia. The findings of the review may impact clinical decisions by patients and surgeons, treatment recommendations by professional societies, purchasing decisions by hospitals, and coverage decisions by payers.

The Key Questions

Ten initial KQs had been posted for public comment on the Web site of the Effective Health Care Program from October 25, 2010, to November 22, 2010. Several changes were made to the KQs based on input from Key Informants and public comment.

Initially there had been two KQs pertaining to nonmesh procedures, but given the relative rarity of such procedures in current clinical practice, as well as the existence of other substantive issues that are more important to address (i.e., open mesh vs. laparoscopic mesh in bilateral hernia or recurrent hernia), we removed these two questions. Instead, we chose to expand the question comparing open and laparoscopic mesh procedures to specifically address three separate populations: primary hernia, bilateral hernia, and recurrent hernia. Also, a previous KQ had combined type-of-mesh comparisons and type-of-fixation-method questions, and we decided to separate these into two KQs.

The final list of KQs is below. The subsequent table (Table 1) clarifies the scope of each KQ using the PICOTS format (Patients, Interventions, Comparisons, Outcomes, Timing, and Settings).

Among adults with pain-free primary inguinal hernias:

Question 1

Does hernia repair differ from watchful waiting in patient-oriented effectiveness outcomes and/or adverse events?

Among adults with painful inguinal hernias without incarceration/strangulation:

Question 2

Does open hernia repair with a mesh differ from laparoscopic hernia repair with a mesh in patient-oriented effectiveness outcomes and/or adverse events?

  1. For primary hernias?
  2. For bilateral hernias?
  3. For recurrent hernias?

Question 3

Do different open mesh-based repair procedures (e.g., Lichtenstein repair, mesh plug) differ in patient-oriented effectiveness outcomes and/or adverse events?

Question 4

Do different laparoscopic mesh-based repair procedures (e.g., transabdominal preperitoneal repair, totally extraperitoneal repair) differ in patient-oriented effectiveness outcomes and/or adverse events?

Question 5

Do different mesh products (lightweight, heavyweight) differ in patient-oriented effectiveness outcomes and/or adverse events?

Question 6

Do different mesh-fixation methods (e.g., no fixation, sutures, glue) differ in patient-oriented effectiveness outcomes and/or adverse events?

Question 7

For each type of laparoscopic mesh repair, what is the association between surgical experience and hernia recurrence?

Among pediatric patients (age 21 years or younger):

Question 8

For a possible contralateral hernia, does same-operation repair/exploration differ from watchful waiting in patient-oriented effectiveness outcomes and/or adverse events?

Question 9

Does open hernia repair without a mesh differ from laparoscopic hernia repair without a mesh in patient-oriented effectiveness outcomes and/or adverse events?

Table 1. Scope of Key Questions: Patients, Interventions, Comparators, Outcomes, Timing, and Settings

For each KQ, the table below depicts the population(s), intervention(s), comparator(s), outcome(s), timing, and setting.

  Key Question
  1 2a 2b 2c 3 4 5 6 7 8 9
Patient-oriented effectiveness outcomes include: hernia recurrence, hospital visits, length of hospital stay, office visits, return to daily activities, return to work, quality of life, and patient satisfaction. Adverse events include any unintended effects such as chronic pain, infection, small-bowel perforation, hematoma, et cetera. We did not examine certain surrogate outcomes, namely operation time and the rate of conversion from laparoscopic (LAP) to open surgery, .because of their reduced importance in addressing the Key Questions.
Age Adults Pediatric
patients
Condition Inguinal hernia without
incarceration/strangulation
Possible
contra-
lateral
inguinal hernia
without incarc-
eration/
strangu-
lation
Inguinal
hernia
without incarc-
eration/
strangu-
lation
Pain status Pain-
free
Painful Pain-
free
or
painful
Unilateral or bilateral Unila-
teral
or
bilat-
eral
Bilat-
eral
Unilateral or bilateral
Primary or recurrent Prim-
ary
Prim-
ary or recurr-
ent
Recu-
rrent
Primary or recurrent
Intervention Watch-
ful waiting
Open
mesh
Open mesh
var-
iant 1
LAP
mesh
var-
iant 1
Mesh
var-
iant 1
Fixa-
tion variant 1
LAP mesh,
with diffe-
rent levels
of surgi-
cal exper-
ience

Watch-
ful
waiting

Open
no
mesh
Comparator Any surgery LAP
mesh
Open mesh
var-
iant 2
LAP
mesh
var-
iant 2
Mesh
var-
iant 2
Fixa-
tion variant 2
Surg-
ical explor-
ation
or
repair
LAP
no
mesh
Outcomes Patient-oriented effectiveness outcomes and adverse events
(see list of outcomes at the bottom of this table)
Time points

For hernia recurrence, quality of life, and patient satisfaction, we will include followup data of at least 6 months+ on at least 50% of enrolled patients will be included. For other outcomes, we will include any time point for which data were reported on at least 50% of enrolled patients.

Any time point for which data were reported on at least 50% of enrolled patients.

Setting Any setting

Analytic Framework

The analytic framework is intended to show out the nine Key Questions fit within the general scope of inguinal hernia management. It is divided into four columns vertically, reading from left to right as Populations, Interventions, Surrogate Outcomes, and Patient-Oriented Outcomes. The Populations column lists the different types of patient populations of interest, including adults with pain-free primary inguinal hernia (Key Question 1), adults with painful inguinal hernia without strangulation (Key Questions 2 through 7), pediatric patients with possible contralateral hernia (Key Question 8), and pediatric patients with primary inguinal hernia (Key Question 9). Each of these populations has a relevant choice between interventions. For adults with pain-free primary inguinal hernia, it is the choice between watchful waiting and surgery; for adults with painful inguinal hernia without strangulation, it is the choice between different types of surgery; for pediatric patients with possible contralateral hernia, it is the choice between watchful waiting and surgery; for pediatric patients with primary inguinal hernia it is the choice between open surgery and laparoscopic surgery. These intervention choices are represented in the second column, labeled Interventions. Key Questions 2 through 7 for adults, as well as Key Question 9 for pediatric patients, are represented in this column. Key Question 2 involves comparisons between open mesh surgery and laparoscopic mesh surgery, and has three sub-questions (for primary, bilateral, and recurrent hernia). Key Question 3 involves comparisons within the group of open mesh procedures (and therefore the number appears within the box for open mesh), and Key Question 4 involves comparisons within the group of laparoscopic mesh procedures (and therefore the number appears within the box for laparoscopic mesh). Key Questions 5 (comparison among meshes) and 6 (comparisons among fixation methods) each appear in both the box for open mesh and the box for laparoscopic mesh because they apply to both sets. Key Question 7 only applies to the latter however, as it involves the relationship between surgical experience with laparoscopic repair and hernia recurrence. The third column lists two surrogate outcomes, operation time and conversion to open. These outcomes are measured during or soon after surgery, and are of less importance than the ones listed in the final column, Patient-Oriented Outcomes. These latter outcomes include all of the outcomes to be examined in this review, including hernia recurrence, hospital visits, length of hospital stay, office visits, return to daily activities, return to work, quality of life, patient satisfaction, and adverse events.

Methods

A. Criteria for Inclusion/Exclusion of Studies in the Review

The inclusion criteria are listed below in separate categories pertaining to 1) publication type, 2) study design, 3) patient characteristics, 4) treatment characteristics, and 5) data.

  1. Publication criteria
    1. Publication must be a full article; abstracts alone will not be included, because they do not include sufficient details about experimental methods to permit an evaluation of study design and conduct and they also may only contain a subset of the measured outcomes.22,23 Abstracts of randomized studies that did not subsequently appear as full articles will be flagged for possible evidence of publication bias.
    2. To capture the most relevant data, we will include studies published on or after January 1, 1990. Studies published before 1990 likely describe procedures no longer being used commonly or outcomes that are not likely to be predictive of current outcomes. For our evidence searches, we anticipate that the last search will be conducted on April 1, 2011, and an updated search will be conducted while the report is under review.
    3. To avoid double-counting of patients, when several reports of overlapping patients are available, only outcome data from the report with the largest number of patients will be included. We will include the data when a smaller report provides data on an outcome that was not provided by the largest report.
    4. Studies must be published in English. Moher et al. have demonstrated that exclusion of non–English-language studies from meta-analyses has little impact on the conclusions drawn.24 Juni et al. found that non-English studies typically were of lower methodological quality and that excluding them had little effect on effect-size estimates in the majority of meta-analyses they examined.25 Although we recognize that in some situations exclusion of non-English studies could lead to bias, we believe that the few instances in which this may occur do not justify the time and cost typically necessary for translation of studies to identify those of acceptable quality for inclusion in our review.24,25 Due to the prevalence of non–English-language studies of inguinal hernia repair, however, we will examine the English abstracts of these studies in an attempt to assess the degree of bias resulting from their exclusion.
  2. Study design criteria
    1. For questions comparing interventions (i.e., all KQs except KQ 7 on surgical experience), the study must either randomize patients to treatments or use an analytic method to address selection bias, such as baseline matching on multiple characteristics, propensity scoring, or other analytic approach. Studies with large differences at baseline between groups (regardless of whether they were randomized), or entailed confounding by indication, will be excluded. Studies comparing meshes or mesh-fixation methods must not confound results by differences in surgical procedures for inserting the mesh. For KQ 7 on surgical experience, a control group will not be required; however, the study must provide data on the relation between surgical experience and outcomes. The definition of surgical experience must be specific to laparoscopic mesh hernia repair, not simply a measure of general experience such as surgeon age.
    2. Study can be prospective or retrospective, but retrospective studies must use consecutive enrollment (or enrollment of a random sample of eligible participants).
    3. The treatments being compared must be administered during the same time period, so that any observed difference between treatment outcomes are not attributable to differential time frames.
  3. Patient criteria
    1. To be included for a given KQ, the study must have provided data for which at least 85 percent of the patients had the condition specified in the KQ. For example, for KQ 2a, we only included data points for which at least 85 percent of the patients were adults with painful primary inguinal hernia without incarceration/strangulation.
    2. We used a flexible definition of “adulthood”; we defined “adults” as anyone aged 18 years or older and we defined the “pediatric population” as anyone aged 21 years or younger. This means that studies enrolling those aged 18–20 years could have been included as either an adult study or a pediatric study, depending on the average age of those enrolled.
  4. Treatment criteria
    1. The study must provide sufficient information about the treatments for one to determine that the data address one of the KQs.
    2. The study must not describe a specialized and novel hernia repair that has not been widely practiced by other surgeons. This is to maintain the focus of the report on the most common types of repair.
    3. The hernia repair must not be performed simultaneously with another operation (e.g., prostatectomy). Surgical complications of combined operations make it difficult to isolate aspects of the hernia repair itself.
  5. Data criteria
    1. The study must report data on at least one of the included outcomes for at least one of the KQs.
    2. Outcome data must not rely on retrospective recall (e.g., in an interview long after the procedure had been performed) because such outcomes may not accurately reflect patients’ experiences.
    3. For some outcomes in the adult population, we will include data points at least 6 months after treatment (hernia recurrence, quality of life, and patient satisfaction). For all other outcomes (and in the pediatric population), there will be no minimum followup.
    4. We will include data points capturing at least 10 patients with the condition of interest who represented at least 50 percent of eligible enrolled patients.

B. Searching for the Evidence: Literature Search Strategies for Identification of Relevant Studies To Answer the Key Questions

Literature searches will be performed by Medical Librarians within the Evidence-based Practice Center (EPC) Information Center, and will follow established systematic search protocols. The searches will be led by the Director of Health Technology Assessment/EPC Information Center.

Consistent with our evidence-based searching protocol, for all KQs, we will search the following databases on the OVID SP platform using the one-search and deduplication features: MEDLINE, PreMEDLINE, and Embase. The Cochrane Library (including the Central Register of Controlled Trials, the Cochrane Database of Methodology Reviews, and the Cochrane Database of Systematic Reviews), the Database of Abstracts of Reviews of Effects, the Health Technology Assessment Database, and the United Kingdom National Health Service Economic Evaluation Database will also be searched for unique reviews, trials, economic analyses, and technology assessments.

Search terms will be identified by: 1) reviewing relevant systematic reviews on similar topics that are identified by members of the research staff, 2) reviewing how other relevant studies are indexed, their subject heading terms, and their keywords, and 3) reviewing MeSH and EMTREE indexes for relevant and appropriate terms. After reviewing these, a combination of subject headings and keywords will be identified. Search strategies will be developed using these terms. Once developed, search strategies will be reviewed by senior research analyst(s) and the Director of the Health Technology Assessment/EPC Information Center. Per the request of technical staff, no limits on language will be applied by the search—as recommended on page 9 of the Relevo and Balshem chapter in the Methods Guide for Comparative Effectiveness Reviews (hereafter, Methods Guide)26—and search dates have been established as 1990–2011. A study-design filter will be applied to retrieve systematic reviews and clinical trials.

Literature search results will initially be reviewed by the Medical Librarian. Using the KQs and inclusion/exclusion criteria identified by Senior Research Analyst(s), the Medical Librarian will assess relevancy and retrieve results. Feedback from the Senior Research Analyst(s) and the Director of the Health Technology Assessment/EPC Information Center—including details regarding gaps in the search strategy, as well as articles (identified by the Senior Research Analyst[s]) not retrieved by the searches—will be integrated into the search strategy using key terms and subject headings. The updated strategy will be re-run in all identified databases. Additional results will be scanned, and their relevancy will be assessed by the Medical Librarians. New results will be downloaded and forwarded to Senior Research Analyst(s) for review. Hand searches of reference lists in identified articles will also be reviewed for possible inclusion. The search will be updated during the peer-review period of the draft report.

Articles will be reviewed first at the abstract level by a single person, and any articles possibly meeting the inclusion criteria for at least one KQ will be obtained for full review. A randomly selected 10 percent of the articles excluded at the abstract level will be screened by a second person to ensure that no articles are excluded inappropriately. If this process reveals any studies that the team agrees were mistakenly excluded, then all of the other articles excluded at the abstract level will be screened by a second person.

Full articles meeting the inclusion criteria will be retained for abstraction of information on general study characteristics, patient characteristics, treatment characteristics, risk-of-bias items, and outcome data (see next section). Separately for each person who screened full articles, we will randomly select 10 percent of the articles excluded at the full-article level and have them screened by a second person to ensure that no articles are excluded inappropriately. If this process reveals any studies that the team agrees were mistakenly excluded, then all of the other articles excluded at the full-article level will be screened by a second person.

C. Data Abstraction and Data Management

We plan to extract study information into spreadsheets in Microsoft Excel. An initial period of pilot testing will enhance accuracy, which will be assessed by three team members. After the initial period of pilot testing for data abstraction, we will do single-reviewer abstraction of data. A randomly selected 10 percent of the abstracted data points will be abstracted by a second person (separately for each person who abstracted data). Also, due to the possibility of subjective interpretation, the risk-of-bias items will be judged in duplicate, and discrepancies will be resolved with discussion. The overall categories of information to be obtained from each study will include:

  • General study characteristics. Author, publication year, country, study design, dates of patient enrollment, length of follow-up, funding source, and which KQ(s) the study addressed.
  • Patient characteristics. Number of enrolled patients, age, sex, hernia type(s), presurgical pain level, presurgical quality-of-life scores, presurgical functional activity scores, unilateral/bilateral, primary/recurrent, prior hernia repairs, and hernia classification (e.g., Nyhus classification,10 if used).
  • Treatment characteristics. Procedure category, specific procedure, specific mesh (if applicable), fixation method (if applicable), number of surgeons performing the procedures in the study, surgeons’ prior experience with the repair procedures performed, surgical setting (i.e., specialized hernia center or general surgery), and type of anesthesia.
  • Risk-of-bias items. See the next section.
  • Outcome data. Study methods of followup for data collection will be extracted, as well as the time point(s) of evaluation. For each included outcome, we will extract the number of patients contributing data to each included time point. We will extract the numerical data necessary for us to compute an effect size and its standard error for all included outcomes for each study. These may include means, standard deviations, counts, proportions, results of authors’ statistical tests, or other statistical details, depending on what is reported.

Multiple publications of the same study (e.g., publications reporting subgroups, other outcomes, or longer followup) will be identified by examining author affiliations, study designs, enrollment criteria, and enrollment dates.

D. Assessment of Methodological Risk-of-Bias of Individual Studies

As stated above, due to the possibility of subjective interpretation, this step will be performed by two extractors for each study, and discrepancies will be resolved by consensus. We will assess the risk-of-bias (i.e., internal validity) separately for each outcome and each time point of each study. The reason for outcome specificity is that some subjective outcomes are more susceptible to bias than other outcomes. The reason for time-point specificity is that longer followup often results in attrition or right-censoring, which may yield patients who are somewhat different than the full set of enrolled patients and also may introduce a systematic difference between the groups being compared.

For all studies with control groups (regardless of whether patients were randomly assigned to groups), we will assess risk-of-bias using the items in the table below. All but one of these items were selected from a pool of items typically used by this EPC for technology assessments. The last question (on surgeon’s prior number of procedures) was devised specifically for this project. Each of these items will be answered as “Yes,” “No,” or “Not reported.”

Item Comments
Were patients randomly assigned to the study’s groups?  
Was there concealment of group allocation?  
For nonrandomized trials, did the study employ any other methods to enhance group comparability? All included studies will have a “Yes” for this question, because non-randomized studies are required to use an analytic control to address selection bias.
Was the process of assigning patients to groups made independently from physician and patient preference?  
Did patients in different study groups have similar levels of performance on the outcome of interest at the time they were assigned to groups? This will only be used for outcomes that have a baseline measure (e.g., quality-of-life).
Were the study groups comparable for all other important factors at the time they were assigned to groups?  
Was the comparison of interest prospectively planned?  
If patients received ancillary treatment(s), was there a ≤5% difference between groups in the proportion of patients receiving each specific ancillary treatment? If ancillary treatments differed substantially between groups, then the study will be excluded.
Were the two groups treated concurrently? All included studies will have a “Yes” for this question, because it is a requirement for inclusion.
Were those who assessed the patient’s outcomes blinded to the group to which the patients were assigned?  
Was the outcome measure of interest objective and was it objectively measured?
  • The following will always be considered objective outcomes: adverse events, hospital stay, office visits, and hospital visits.
  • The following will always be considered subjective outcomes: return to work, return to daily activities, quality of life (QOL), functional status (FCT), and patient satisfaction.
  • For hernia recurrence, we will consider it objective if the patient was physically assessed by a clinician for recurrence. If instead the recurrence assessment is based on patient report, this will be considered subjective.
Was there ≤15% difference in the length of followup for the two groups? This item will only be used for the following outcomes: hernia recurrence, adverse events, QOL, FCT, office visits, and hospital visits.
Did ≥85% of enrolled patients provide data at the time point of interest?  
Was there a ≤15% difference between groups in the percentage of patients provided data at the time point of interest?  
For questions comparing two procedures, did the two groups’ surgeons have similar numbers of prior operations performing the procedure they performed in the study?  

Note that funding source is not listed as a risk-of-bias item. This is because funding source is an indirect measure of risk-of-bias and also because we will consider it at a later stage in the assessment of the strength of evidence, specifically when assessing the possibility of publication bias or selective outcome-reporting bias (see the section below entitled Grading the Evidence for Each Key Question).

We will categorize each study as “Low,” “Medium,” or “High” risk-of-bias using the following method:

  • In order to be considered low risk-of-bias, the study must meet ALL of the following conditions:
    • Randomized (item 1).
    • Concealment of allocation (item 2) OR blinded outcome assessors (item 10) OR both.
    • Good baseline comparability for both outcome (item 5) and other patient characteristics (item 6).
    • Good baseline comparability on surgeons’ number of prior operations performing the compared procedures (item 15).
    • If NOT blinded outcome assessors (item 10) (or NR blinded outcome assessors), then it was an objective outcome (item 11).
    • ≤15 percent difference in length of followup between groups (item12).
    • ≥85 percent of enrolled patients provided data to this time point (item 13).
    • ≤15 percent difference in data provision rates to this time point (item 14).
  • In order to be considered high risk-of-bias, the study must meet AT LEAST TWO of the following criteria:
    • Process of assigning patients to groups NOT made independently from physician and patient preference (item 4)
    • Not good baseline comparability for either the outcome (item 5) or other patient characteristics (item 6)
    • Retrospective (item 7)
    • Difference in ancillary treatments ≥5 percent (item 8)
    • Not a blinded outcome assessor (item 10) AND a subjective outcome (item 11)
  • In order to be considered Medium risk-of-bias, the study neither meets the criteria for low risk-of-bias nor the criteria for high risk-of-bias.

E. Data Synthesis

We plan to perform meta-analysis wherever appropriate and possible. This decision will depend on the judged clinical homogeneity of the different study populations, cointerventions, and outcomes, as well as what is reported by those studies. Subgroup analyses may be performed based on key identified aspects of the studies, such as the specific procedure (e.g., transabdominal preperitoneal repair or totally extraperitoneal repair), the specific mesh (e.g., lightweight or heavyweight), or study design (e.g., randomization or not).

For each outcome in the review, an important consideration is the smallest difference between groups that can still be considered clinically significant (MCSD or minimum clinically significant difference). This definition aids interpretation in two main ways: 1) to determine whether a statistically significant difference is clearly clinically significant and 2) to determine whether a statistically nonsignificant difference is small enough to exclude the possibility of a clinically significant difference. Ideally, the MCSD is decided for each outcome before the results of the studies are known.

After hernia repair, a key outcome is hernia recurrence; for this outcome, we define the MCSD as 3 percentage points (e.g., 1% vs. 4% for two separate treatments). This was based on statements in two multicenter trials (the U.S. Department of Veterans Affairs trial 27 and the Medical Research Council trial28) that such a difference is clinically meaningful. For other anticipated outcomes, we used the following approaches concerning the definitions of minimum clinical significance:

  • Length of hospital stay. 1 day difference between groups.
  • Number of hospital visits/number of office visits. 20 percent difference between groups (e.g., means of 5 visits and 4 visits).
  • Time to return to daily activities/return to work. If reported as a continuous measure, 1 week difference between groups. If reported as a dichotomous measure, no a-priori definition; we may need to consult with the Technical Expert Panel (TEP) to determine the MCSD.
  • Quality of life. 5 percent of the range of the scale (e.g., 5 points on the SF-36, which ranges from 0–100).
  • Patient satisfaction. No a-priori definition used, because it is not clear how studies will report this outcome; we may need to consult with the TEP to determine the MCSD.
  • Pain. If reported as a continuous measure, 20 percent of the range of the scale (e.g., 20 points on the Visual Analog Scale (VAS), which ranges from 0–100).29 If reported as a dichotomous measure, we will not set an a priori definition; we may need to consult with the TEP to determine the MCSD.
  • Other adverse events. No a-priori definition; we may need to consult with the TEP to determine different MCSDs for different adverse events.

If meta-analysis is deemed appropriate and possible for a given comparison and a given outcome, we will compute effect sizes and standard errors using standard methods and will perform DerSimonian and Laird random-effects meta-analysis30 using Comprehensive Meta-Analysis (CMA) software (Biostat Inc., Englewood, NJ).31

For rare events (rates <1%), we will use either the Peto or Mantel-Haenszel odds ratios, as recommended on page 8 of the Methods Guide chapter, Conducting Quantitative Synthesis When Comparing Medical Interventions,32 and supported by the simulation studies of Sweeting et al.33 and Bradburn et al.34

To best interpret the findings, we will define the MSCD for each outcome using information in the hernia literature, general information on that outcome, input from the TEP, and/or standards suggested by Cohen.35 This will help determine whether the between-groups difference is clinically significant or whether a statistically nonsignificant finding is sufficiently precise to rule out the possibility of a clinically significant difference.

To measure heterogeneity, we will use I2 and tau. Both are used because I2 can increase simply by increasing the numbers of patients in the studies (whereas tau is a more direct measure of heterogeneity),36 but tau is more difficult to interpret because its scale is different for different effect sizes. Heterogeneity measures will be used to determine whether a meta-regression will be attempted. If heterogeneity is present and there are at least five studies, we will perform a meta-regression in an attempt to explain the heterogeneity. To control for spurious findings, meta-regressions will employ the permutation test37 in the Stata software (Stata Corporation, College Station, TX).38

In determining the factors that may explain heterogeneity, we plan to focus primarily on meta-regressions to study-level predictors, rather than patient-level predictors, because the latter are subject to the ecological fallacy, as suggested in the Methods Guide chapter entitled Conducting Quantitative Synthesis When Comparing Medical Interventions.32 However, given their importance in this context, we may use some aggregated patient-level variables and plan to interpret these results with caution. Examples of predictors to be included are surgical setting (specialized hernia center or not), number of prior procedures performed by the study’s surgeons, country of origin, mean age, percentage of patients with bilateral hernia, percentage of patients with recurrent hernia, and risk-of-bias variables such as randomization to groups and baseline group comparability.

The final report will present findings in the following manner, organized by KQ. First, if the evidence permits an answer to the KQ, this answer will be stated first, in boldface, along with the rating of the evidence supporting that conclusion. If the evidence is insufficient to answer the question, this will be stated first. The outcomes will be presented in the following order: hernia recurrence, hospital visits, length of hospital stay, office visits, return to daily activities, return to work, quality of life, patient satisfaction, and adverse events (which include effects such as chronic pain after surgery, infection, etc.). If space constraints require a prioritization of these outcomes, the priority list will include four outcomes: hernia recurrence, quality of life, patient satisfaction, and adverse events. However, full results of all included outcomes will be available in appendices.

F. Grading the Evidence for Each Key Question

We will implement the rating system described by Owens et al.39 (also part of the Methods Guide40) and will use many of the principles described by Treadwell et al.41 This will involve a rating for confidence in the conclusion about the direction of the effect. Each evidence rating will be “High,” “Moderate,” “Low,” or “Insufficient,” and the process for combining domain scores into an overall rating will be systematic, thereby precluding the need for duplication of effort (as noted by Owens et al.39). A rating of “Insufficient” will apply to evidence bases that involve no studies or where the evidence does not support a conclusion (e.g., when the uncertainty is so high that the evidence cannot discriminate among conflicting conclusions). We will be fully transparent about the process that produces the ratings, so that readers can replicate the process or use the individual domains to arrive at their own overall ratings.

Owens et al.39 describe eight domains to be considered: risk-of-bias, consistency, directness, precision, magnitude of effect, publication bias, dose-response association, and all plausible confounders would reduce the effect. Judgments concerning applicability are not included in the rating of the strength of evidence (but see the next section on how we will assess applicability in this report).

We plan to provide evidence ratings for hernia recurrence, quality of life, patient satisfaction, and adverse events. Depending on time constraints of the review, we may grade additional outcomes as well. For the question on the association between surgical experience and hernia recurrence, no grading system yet exists for grading this type of evidence (i.e., on association), therefore we do not plan to rate that evidence.

G. Assessing the Applicability of the Evidence for Each Key Question

The applicability of the evidence involves five aspects: 1) patients, 2) interventions, 3) comparisons, 4) outcomes, and 5) settings. In order to define optimally the target population, we will search for any large population-based studies conducted of patients receiving treatment in the United States. The typical interventions, comparisons, outcomes (e.g., typical hernia-recurrence rates), and settings of care will also be used to more clearly specify the most applicable study characteristics (i.e., most typical of hernia care in the United States). A large portion of the inguinal hernia literature has been conducted outside the United States, and this literature may have limited applicability because other countries may differ from the United States in any of the five aspects listed above.

Regarding patients, this report has three general target populations: 1) adults with a pain-free inguinal hernia not strangulated/incarcerated; 2) adults with a painful inguinal hernia not strangulated/incarcerated; and 3) pediatric patients with an inguinal hernia not strangulated/incarcerated. We hope to define this more precisely with respect to adult ages, pediatric ages, and specific types of inguinal hernia (i.e., direct or indirect). For interventions and comparisons, a key consideration is the prior experience of the surgeons performing the procedures. If the surgeons performing the procedures had more prior experience with those procedures than typical surgeons in clinical practice, this would limit the applicability of the findings. For outcomes, if the study reported hernia-recurrence rates that were much different from typical rates (e.g., 10% instead of 2%), the between-group comparison (e.g., 8% vs. 12%) may be inapplicable to typical practice. Finally, regarding settings, if the study settings were atypical (e.g., the study surgeons practiced in specialized hernia care centers), the findings may also be inapplicable.

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Definition of Terms

I2: This is a measure of heterogeneity, ranging from 0% to 100%, in which higher values suggesting greater heterogeneity. See Higgins and Thompson42 for more details.

Tau: This is a measure of heterogeneity indicating the standard deviation of the effect sizes; it is on the scale of the effect size. For example, in a meta-analysis of log odds ratio, tau is on the scale of the log odds ratio. See Rucker et al.36 for more details.

Summary of Protocol Amendments

August 9, 2011

Section

Protocol Deviation

Rationale

IV. E.

The protocol had stated that the minimum clinically significant difference (MCSD) for the outcome return to daily activities is one week. We propose to change it to one day.

The typical length of time before returning to daily activities after inguinal hernia surgery is about 10 days. This relatively short period of time suggests that shortening it by just 1 day would be considered important to patients and/or clinicians. Thus we propose setting the MCSD at one day for this outcome. Nothing in the literature clearly indicates what practicing clinicians consider the MCSD after hernia repair, so this is based on the consensus of the research team.

IV. E.

The protocol had stated that the minimum clinically significant difference (MCSD for the outcome return to work is one week. We propose to change it to one day.

Same points as above, except for return to work.

  1. Review of Key Questions
    For all EPC reviews, key questions were reviewed and refined as needed by the EPC with input from Key Informants and the Technical Expert Panel (TEP) to assure that the questions are specific and explicit about what information is being reviewed. In addition, for Comparative Effectiveness reviews, the key questions were posted for public comment and finalized by the EPC after review of the comments.
  2. Key Informants
    Key Informants are the end users of research, including patients and caregivers, practicing clinicians, relevant professional and consumer organizations, purchasers of health care, and others with experience in making health care decisions. Within the EPC program, the Key Informant role is to provide input into identifying the Key Questions for research that will inform healthcare decisions. The EPC solicits input from Key Informants when developing questions for systematic review or when identifying high priority research gaps and needed new research. Key Informants are not involved in analyzing the evidence or writing the report and have not reviewed the report, except as given the opportunity to do so through the public review mechanism.

    Key Informants must disclose any financial conflicts of interest greater than $10,000 and any other relevant business or professional conflicts of interest. Because of their role as end-users, individuals are invited to serve as Key Informants and those who present with potential conflicts may be retained. The TOO and the EPC work to balance, manage, or mitigate any potential conflicts of interest identified.

  3. Technical Experts
    Technical Experts comprise a multi-disciplinary group of clinical, content, and methodologic experts who provide input in defining populations, interventions, comparisons, or outcomes as well as identifying particular studies or databases to search. They are selected to provide broad expertise and perspectives specific to the topic under development. Divergent and conflicted opinions are common and perceived as health scientific discourse that results in a thoughtful, relevant systematic review. Therefore study questions, design and/or methodological approaches do not necessarily represent the views of individual technical and content experts. Technical Experts provide information to the EPC to identify literature search strategies and recommend approaches to specific issues as requested by the EPC. Technical Experts do not do analysis of any kind nor contribute to the writing of the report and have not reviewed the report, except as given the opportunity to do so through the public review mechanism.

    Technical Experts must disclose any financial conflicts of interest greater than $10,000 and any other relevant business or professional conflicts of interest. Because of their unique clinical or content expertise, individuals are invited to serve as Technical Experts and those who present with potential conflicts may be retained. The TOO and the EPC work to balance, manage, or mitigate any potential conflicts of interest identified.

  4. Peer Reviewers
    Peer reviewers are invited to provide written comments on the draft report based on their clinical, content, or methodologic expertise. Peer review comments on the preliminary draft of the report are considered by the EPC in preparation of the final draft of the report. Peer reviewers do not participate in writing or editing of the final report or other products. The synthesis of the scientific literature presented in the final report does not necessarily represent the views of individual reviewers. The dispositions of the peer review comments are documented and will, for CERs and Technical briefs, be published three months after the publication of the Evidence report.

    Potential Reviewers must disclose any financial conflicts of interest greater than $10,000 and any other relevant business or professional conflicts of interest. Invited Peer Reviewers may not have any financial conflict of interest greater than $10,000. Peer reviewers who disclose potential business or professional conflicts of interest may submit comments on draft reports through the public comment mechanism.