Question

Key questions 1-6

Fitzgibbons, Giobbie-Hurder, Gibbs, Dunlop, Reda, McCarthy, Neumayer, Barkun, Hoehn, Murphy, Sarosi, Syme, Thompson, Wang, Jonasson

Watchful waiting vs repair of inguinal hernia in minimally symptomatic men, a RCT

Several articles :

JAMA 2006, Watchful waiting vs repair of inguinal hernia in minimally symptomatic men, a RCT

JACS 2006, Tension-free repair vs watchful waiting for men with asymptomatic or minimally symptomatic inguinal hernias : a cost-effectiveness analysis

Annals of Surgery 2013, Long-term results of a RCT of a nonoperative strategy (watchful waiting) for men with minimally symptomatic inguinal hernia

Study type/ evidence level

Study details/ limitations

Patients characteristics

Interventions

Study type: RCT

Evidence level: ++++

Countries: USA

Centres: 5

Setting:

Funding source:

Dropout rates:

Study limitations:

Total nr pts: 720

Patients characteristics: men with minimally symptomatic inguinal hernias

Inclusion criteria: men, aged 18 years or older, presenting with asymptomatic or minimally symptomatic hernia

Exclusion criteria: undetectable hernia, local or systemic infection, ASA>3

Watchful waiting compared to surgical repair (standard open tension-free repair)

Notes

Aim: to compare pain and the physical component score (PCS) of the Short Form-36 Version 2 survey at 2 years

FU at 3 and 6 months and annually

Outcome measures/ results

Primary outcomes:

Pain and discomfort interfering with usual activities at 2 years and change in PCS from baseline to 2 years

Secondary outcomes:

Complications, patient-reported pain, functional status, activity levels and satisfaction with care

First results 2006:

- primary intention-to-treat outcomes were similar at 2 years for watchful waiting vs surgical repair; 23% of patients assigned to watchful waiting crossed over operation, usual because of hernia-related pain; one WW-patient experienced acute hernia incarceration (0.3%); a second had acute incarceration with bowel obstruction

- at 2 years, WW was a cost-effective treatment option for men with minimal or no hernia symptoms

Long-term results: 81 of 254 men (31.9%) crossed over to surgical repair before the end of the original study with a median follow-up of 3.2 (range: 2-4.5) years. The estimated cumulative crossover rate with a maximum follow-up of 11.5 years, was 68%, usually (54,1%) because of pain. Men older than 65 year crossed over at a higher rate than younger men.

Conclusion long-term: men who present with an inguinal hernia even when minimally symptomatic should be counselled that although WW is a reasonable and safe strategy, symptoms will likely progress and an operation will be needed eventually.

Physical component SF-36: Mean 2-year PCS change from baseline was not significantly different: watchfulwaiting patients improved by 0.29 points (of 100) and surgical repair patients improved by 0.13 points (difference, 0.16; 95% confidence interval, −1.2 to 1.5)

Question

Key questions 1-6

O’Dwyer, Norrie, Alani, Walker, Duffy, Horgan

Observation or operation for patients with an asymptomatic inguinal hernia

Several articles :

Annals of Surgery 2006, Observation or operation for patients with an asymptomatic inguinal hernia

British Journal of Surgery 2011, Long-term follow-up of patients with a painless inguinal hernia from a randomized clinical trial

Study type/ evidence level

Study details/ limitations

Patients characteristics

Interventions

Study type: RCT

Evidence level: ++++

Countries: UK

Centres: 1

Setting:

Funding source:

Dropout rates:

Study limitations:

Total nr pts: 160

Patients characteristics: men with minimally symptomatic inguinal hernias

Inclusion criteria: men, aged 55 years or older, inguinal hernia that was reducible on lying down or with minimal applied pressure, no pain at rest or movement

Exclusion criteria: patients unfit for local anesthetic repair, irreducible hernia

Wait-and-see compared to surgical repair (tension-free mesh repair under local or general anesthesia)

Notes

Aim: to compare operation with a wait-and-see policy in patients with an asymptomatic hernia

FU at 6 months and annually

Outcome measures/ results

SF-36, disability assessed with Barthel index, VAS pain score

Primary endpoint:

Pain and general health status at 6 months and at 1 year

Other outcomes: costs to health service and rate of operation for a new symptom or complication

First results 2006:

At 12 months no significant differences between the groups in VAS score; number of patients recording pain on moving and number taking regular analgesia similar; rate of crossover from observation to operation 23 patients at a median follow-up of 574 days; 3 serious hernia-related adverse events in observation group compared to none in operation group

Long-term results: crossover rate from observation to operation at 1 year 16%, at 5 years 54% and at 7.5 years 72%; main reason for crossover was pain in 33 men and acute hernia in 2

Conclusion long-term: most patients with a painless inguinal hernia develop symptoms over time. Surgical repair is recommended for medically fit patients with a painless inguinal hernia.

SF-36 12 months: Mean difference of 7 (95% CI, 0 to 14;P 0.039) in favour of surgery.

Study reference

Study characteristics

Patient characteristics ²

Intervention (I)

Comparison / control (C) ³

Follow-up

Outcome measures and effect size ⁴

Comments

De Goede 2018

Type of study: RCT

Setting: 29 community and academic centers in The Netherlands, and 2 Belgian centers

Countries: The Netherlands, Belgium

Source of funding:

Netherlands Organisation for Health Research and Development (ZonMW), Erasmus Medical Center Efficiency Research Grant, and the Foundation ‘‘Stichting Physico Therapeutisch Instituut.’’ Investigators received no financial incentives from the funding sources.

Inclusion criteria:

Men aged 50 years and older with a mildly symptomatic or asymptomatic inguinal hernia (pain/discomfort score 1 or 0) were eligible for inclusion.

An inguinal hernia was confirmed on physical examination. Confirmation of the diagnosis with the use of ultrasonography was optional, not mandatory.

Exclusion criteria:

Bilateral, scrotal, or femoral hernia, or those classified as ASA class 4. Men with a first recurrent inguinal hernia were not excluded.

N total at baseline:

Elective repair: 258

Watchful waiting: 270

Important prognostic factors²:

Baseline characteristics and hernia details were balanced between the 2 groups.

The mean age of the population was 65.1 years (SD 8.3) and the mean body mass index (BMI) was 24.9 kg/m2 (SD 2.7).

Stratified factors at randomisation men aged 50-65 years or 65 years and older, participating centers, and duration of inguinal hernia present at baseline.

Describe intervention (elective repair):

Patients assigned to surgery underwent repair as soon as possible after randomization (preferably within 4–8 weeks).

Surgery was performed at the surgical department of the involved center. In consultation of the patient, the surgeon determined the operation technique used for inguinal hernia repair. This study allowed surgeons to use different operation techniques

Most surgeons performed Lichtenstein open tension-free repairs: 176 out of 226 repairs (77.9%) in patients who were assigned to elective repair, and 69 out of 99 repairs (69.7%) in patients assigned to watchful waiting and crossed to surgery

Describe control (watchful waiting):

Patients who were randomly assigned to watchful waiting were given written instructions to recognize a hernia com- plication (incarceration or strangulation) after randomization.

Length of follow-up:

Patients in both treatment groups were invited for follow-up at 3, 12, 24, and 36 months at the outpatient clinic of each participating center.

During these follow-up visits conducted by independent trial coordinators, patients underwent physical examination.

Loss-to-follow-up:

Intervention (elective repair): n=24 (9,3%); Reasons: 21 patients withdrew consent immediately after randomization and 3 patients did not meet the inclusion criteria (1 patient with a femoral hernia, 1 with a bilateral hernia, and 1 patient with a lipoma)

Control (watchful waiting): n=8 (3,0%); Reasons: 4 patients withdrew consent and 4 patients did not meet the inclusion criteria (1 patient with a femoral hernia, 1 with a lipoma, and 2 patients who were excluded because they were younger than 50 years of age).

Incomplete outcome data:

Not applicable.

Time to event was calculated from the date of randomization until an event occurred; patients were considered censored if they died, were lost to follow-up, or completed follow-up without any event, with a maximum of 36 months (length of the study period).

Outcome measures and effect size (include 95%CI and p-value if available) ⁵:

Primary endpoint was the mean difference in a 4-point pain/discomfort score at 24 months of follow-up (differences between watchful waiting 0.58 vs elective repair 0.35):

-0.23 (95% CI -0.32 to -0.14

Symptoms (T=24 months):

4-point pain/discomfort score (MD): -0.23 (-0.37; 0.09); p 0.001

Quality of life (T=24 months):

VAS score rating (MD): 1.43 (-1.78; 3.63); p 0.203

EQ-5D: 0.04 (0.01; 0.07) 0.009

SF-36 PCS scores 1.77 (0.53; 3.02) 0.005

SF-36 MCS scores -0.98

(-2.16; 0.21); p 0.106

Costs: Not reported.

Adverse events (T=36 months: % hernia complication (incarceration or strangulation):

In the watchful waiting group, 93 patients (35,4%) eventually underwent elective surgery and 6 patients (2, 3%) received emergent surgery for strangulation/incarceration. No bowel resection had to be performed due to a prolonged state of ischemia.

Pragmatic trial approach

Trial registration: the Dutch Trial Registry, ID number: NTR629.

The INCA trial was an investigator-initiated trial and the funders had no role in study design, conducting of the study, data collection, data analysis, data interpretation, or writing of the report.

Patti 2014

Type of study: prospective comparative cohort

Setting: Department of Surgical and Oncological Sciences, University of Palermo

Countries: Italy

Source of funding: Not reported

Inclusion criteria:

Male patients aging over 75 years affected by minimally symptomatic inguinal hernia were included. Hernioplasty was suggest for all patients.

Exclusion criteria: Hernia recurrence, the presence of a large umbilical hernia, hepatic cirrhosis and advanced neoplastic.

N total at baseline:

Elective hernioplasty: 25

Patients refusing hernioplasty: 15

Important prognostic factors²:

Patients of both groups were similar for age, anesthesiologic risk according to ASA grading, Barthel and Charlson Index, type of hernia according to Nhyus classification and side of hernia.

Describe intervention (surgery):

All hernioplasties were performed after short-term antibiotic prophylaxis with 2 gm i.v. Ceftazidime one hour before surgery. In all patients hernioplasty was carried out under local anesthesia using a mixture of 40 ml 1% mepivacaine and 20 ml 0.5% bupivacaine plus 2 ml sodium bicarbonate. All patients received a tension-free Lichtenstein hernioplasty using an high density polypropylene mesh. All operations were performed by the same surgical staff.

Describe control (refusing hernioplasty):

Follow-up after 6 months. All patients were, even though, one of them underwent emergency hernioplasty due to hernia strangulation.

Length of follow-up:

6 months.

Loss-to-follow-up:

None.

Incomplete outcome data:

None.

Outcome measures and effect size (include 95%CI and p-value if available) ⁵:

The SF-36 questionnaire (BP, VT, PF, and GH) and PCS and MCS scores was administered to all patients at the time of enrolment and 6 months after.

Symptoms (6 months):

Not applicable.

Quality of life:

T=0: no significant differences between the two groups as regards all domains of SF-36 and MCS and PCS scores (data not shown).

T=6 months

No comparisons between groups were made, only within the groups compared to baseline. Results were presented in Figures, without numerical reporting in text.

SF-36 scores (surgery):

In patients underwent hernioplasty, all eight domains of SF-36 resulted significantly improved . This increase was more evident for BP, VT, PF, and GH.

MCS/PCS scores (surgery):

In the same way MCS and PCS scores significantly increased as compared to preoperative values.

SF-36 scores (refused surgery):

The eight domains of SF-36 resulted unmodified at 6 months in comparison to baseline.

MCS/PCS scores (refused surgery):

MCS and PCS values did not show any significant modifications.

Costs: Not applicable.

Adverse events: % hernia complication (incarceration or strangulation):

Refusing surgical operation: 1 underwent emergency hernioplasty due to hernia strangulation.

Elective hernioplasty: all patients were alive, no hernia recurrence was observed and no patients claimed pain.

Study reference

(first author, publication year)

Describe method of randomisation¹

Bias due to inadequate concealment of allocation?²

(unlikely/likely/unclear)

Bias due to inadequate blinding of participants to treatment allocation?³

(unlikely/likely/unclear)

Bias due to inadequate blinding of care providers to treatment allocation?³

(unlikely/likely/unclear)

Bias due to inadequate blinding of outcome assessors to treatment allocation?³

(unlikely/likely/unclear)

Bias due to selective outcome reporting on basis of the results?⁴

(unlikely/likely/unclear)

Bias due to loss to follow-up?⁵

(unlikely/likely/unclear)

Bias due to violation of

intention to treat analysis?⁶

(unlikely/likely/unclear)

De Goede 2018

Stratified block randomisation using computer software.

Detailed information on the randomization procedure, data collected during follow-up, and ethical considerations and monitoring can be found in the Supplementary Appendix II (http://links.lww.com/SLA/B210). ⁷

Unlikely, stratified block randomisation using computer software and patient registered in online database.

Likely, study participants could not be blinded as study design compares surgery vs waiting when primary outcome is subjective.

Unclear, care providers could not be blinded as study design compares surgery vs waiting, but unclear whether they provided different care.

Unlikely, independent trial coordinators conducted the follow-up visits at 3, 12, 24, and 36 months. However, the primary outcome is subjective.

Unlikely, all outcomes mentioned in the NTR ⁸ are reported in this publication, except for medical and non-medical costs.

Unlikely, reasons reported; n=21 (elective surgery) withdrew consent immediately after randomization and n=3 patients did not meet the inclusion criteria; n= 4 patients withdrew consent (watchful waiting) and 4 patients did not meet the inclusion criteria.

Unlikely, participants are kept in the intervention groups to which they were randomized, regardless of the intervention they actually received (8 crossed to watchful waiting and 99 crossed to surgery, reasons were given) .

Patti 2014

No randomisation, prospective comparative cohorts.

Likely, no randomisation. However, patients of both groups were similar for age, anesthesiologic risk according to ASA grading, Barthel and Charlson Index, type of hernia according to Nhyus classification and side of hernia.

Likely, study participants could not be blinded as study design compares surgery vs waiting when primary outcome is subjective.

Unclear, care providers could not be blinded as study design compares surgery vs waiting, but unclear whether they provided different care.

Likely, because of lack of blinding and subjective outcomes.

Unlikely, all outcomes mentioned are reported.

Unlikely, no drop-outs.

Likely, in patients who refused hernioplasty the comparison was limited to 14 subjects because one patient underwent emergency hernioplasty after two months (=per protocol analysis). And no comparisons made between the two groups, but only within the groups compared to baseline.

Fitzgibbons 2006

Stratified block randomisation using computer software.

Stratification by the presence of primary or recurrent hernia, unilateral or bilateral hernia, and study site.

Random block sizes of 2, 4, or 6.

Unlikely, stratified block randomisation using computer software and patients randomization and assignment at a site remote from trial location (Veterans Administration (VA) Cooperative Studies Program Coordinating Center, Hines, Ill.).

Likely, study participants could not be blinded as study design compares surgery vs waiting when primary outcome is subjective (pain and discomfort interfering with usual activities).

Unclear, care providers could not be blinded as study design compares surgery vs waiting, but unclear whether they provided different care.

Unlikely, all site investigators were blinded to interim outcome comparisons until all patients had undergone their final evaluation.

Unlikely, all outcomes measures mentioned in the methods are reported.

Unlikely, very few patients (7 and 11 in the watchful-waiting and surgical repair groups).

Unlikely, participants were kept in the intervention groups to which they were randomized, regardless of the intervention they actually received (62 crossed to watchful waiting and 85 crossed to surgery).

O’Dwyer 2006

Randomization method not described.

Unclear, although mentioned: “There is a tendency for the operation group to have slightly worse SF-36 scores at baseline consistently across all components, with slightly larger hernias, which have been endured for slightly longer. These differences are due to chance”.

Likely, study participants could not be blinded as study design compares surgery vs waiting when primary outcome is subjective (pain and general health status).

Unclear, care providers could not be blinded as study design compares surgery vs waiting, but unclear whether they provided different care.

Unclear, blinding of outcome assessors not reported.

Unlikely, all outcomes measures mentioned in the methods are reported.

Unlikely, 2 lost to follow-up in watchful waiting group.

Unlikely, participants were kept in the intervention groups to which they were randomized, regardless of the intervention they actually received (5 did not undergo surgery, and 23 crossed from watchful waiting to surgery (reasons were given).

- candidate number

2019

- NTR Number

NTR629

- ISRCTN

ISRCTN31866667

- Date ISRCTN created

- date ISRCTN requested

4-jul-2006

- Date Registered NTR

15-mrt-2006

- Secondary IDs

N/A 

- Public Title

INguinal hernia: operative or Conservative Approach (INCA TRIAL)?

- Scientific Title

INguinal hernia: operative or Conservative Approach (INCA TRIAL)?

- ACRONYM

INCA trial

- hypothesis

Non-inferiority hypothesis: observation is not inferior to operation with respect to the mean of pain and discomfort during 3 years follow-up.

- Healt Condition(s) or Problem(s) studied

Hernia inguinal

- Inclusion criteria

1. Unilateral inguinal hernia;
2. Males;
3. Medial or lateral inguinal hernia;
4. Age >= 50 years;
5. Description I or II of pain or discomfort interfering with daily activity;
6. Primary or recurrent inguinal hernia;
7. Informed consent (addendum V).

- Exclusion criteria

1. Gender: female;
2. Bilateral inguinal hernia;
3. Femoral hernia;
4. Description III or IV of pain or discomfort interfering with daily activity;
5. Acute hernia complication (bowel obstruction, incarceration, strangulation, peritonitis or perforation);
6. Patient classified as American Society of Anaesthesiologist Class 4 or Class 5;
7. Scrotal hernia (cannot be corrected laparoscopically);
8. Patient is unable to speak Dutch;
9. Physical activity: patient travels regularly during which professional medical help is not always accessible.

- mec approval received

yes

- multicenter trial

yes

- randomised

yes

- masking/blinding

None

- control

Not applicable

- group

Parallel

- Type

2 or more arms, randomized

- Studytype

intervention

- planned startdate

1-mrt-2006

- planned closingdate

1-mrt-2011

- Target number of participants

800

- Interventions

Operative correction of the inguinal hernia or observative management.

- Primary outcome

The mean of 4 pain/discomfort scores during a follow-up period of 3 years.

- Secondary outcome

The Quality Adjusted Life Years (QALY) with quality weights measured with the EuroQol and in a sensitivity analysis with a transformed SF-36 utility weight, medical and non-medical costs and the event-free survival at 3 years.

- Timepoints

N/A

- Trial web site

N/A

- status

open: patient inclusion

- CONTACT FOR PUBLIC QUERIES

Prof. Dr. J.F. Lange

- CONTACT for SCIENTIFIC QUERIES

Drs. A.R. Wijsmuller

- Sponsor/Initiator

Erasmus Medical Center, Department of Surgery

- Funding
(Source(s) of Monetary or mATerial Support)

ZON-MW, The Netherlands Organization for Health Research and Development, Stichting Physico Therapeutisch Instituut, Erasmus Medical Center, Department of Surgery

- Publications

N/A

- Brief summary

The presence of an inguinal hernia is an indication for an elective herniorraphy if no contra-indications are present. However, life expectancy is equal for surgical and observational management. Additionally, recent studies indicate that there is a high incidence of chronic postoperative pain after inguinal hernia surgery.
The primary objective of this multicentre study is to investigate whether abstaining from operation is a better alternative to surgical treatment in male inguinal hernia patients. The target sample of 800 men will be randomly assigned to either surgical or observational non-surgical management. The outcomes of the study are pain/discomfort, quality of life, event-free survival and costs.
To determine whether there is any difference in the mean of pain/discomfort scores (4 point scale, 0-3) during follow-up with 0,15 points and a power of 80%, the required sample size in each group is 400 patients. With the help of a Student's t-test a non-inferiority hypothesis will be tested. The hypothesis states that both groups have had the same mean pain/discomfort scores.
The secondary objective is to investigate whether a non-surgical approach is cost-effective compared to current practice (hernia operation). The third objective is a comparison of the event-free survivorship functions of both groups. The fourth objective is an evaluation of the baseline risk factors in the not-operated group with respect to their ability to predict which type of patients will require surgery during the follow-up period.

- Main changes (audit trail)

- RECORD

15-mrt-2006 - 6-mei-2008

Certainty assessment

№ of patients

Effect

Certainty

Importance

№ of studies

Study design

Risk of Bias

Inconsistency

Indirectness

Imprecision

Other considerations

Elective surgery

Watchful waiting

Relative
(95% CI)

Absolute
(95% CI)

Symptoms (follow up: range 3 months to 36 months; assessed with: various methods (VAS/4-points pain discomfort list)

3

randomised trials

serious ^a

not serious

not serious ^b

serious ^c

none

No differences were found between surgery and watchful waiting after one year of follow-up measured and no difference in the percentage of participants with pain or discomfort after two years of follow-up. There was a statistical significant and clinical relevant difference on the 4-point pain discomfort list after two years (-0.23 points difference (95% CI -0.32-0.14)) in favor of elective surgery in men of 50 years and older with a mildly symptomatic or asymptomatic inguinal hernia, but the VAS score rating was not significantly different between both groups 1.43 (-1.78; 3.63)

⨁⨁◯◯
LOW

CRITICAL

Quality of life (follow up: 24 months; assessed with: SF-36 PCS and MCS, and EQ-5D)

4

randomised trials and non-randomised study

serious ^a

not serious

serious ^d

serious ^e

none

Significant differences were found between surgery and watchful waiting for outcome measurements SF-36 (PCS) after one (study 1) and two years (study 2) in favour of surgery. The effects were not considered as clinically relevant. For VAS and EQ-5D no differences were found.

⨁◯◯◯
VERY LOW

CRITICAL

Complications/adverse events (eg. Incarceration) (short term)

4

randomised trials and non-randomised study

serious ^a

not serious

not serious

not serious

none

In three RCTs and one non-randomised study the percentage of emergent surgery for strangulation/incarceration was lower than 2,5%.

⨁⨁⨁◯
MODERATE

CRITICAL

Complications/adverse events (long term)

2

randomised trials

serious ^a

not serious

not serieous

serious ^e

none

Most men with asymptomatic or minimal symptomatic inguinal hernia develop symptoms and require surgical treatment mostly due to pain (72% of patients form watchful waiting group develop symptoms in 7.5 years).

⨁⨁◯◯
LOW

CRITICAL