The epidemiology, management and impact of surgical wounds healing by secondary intention: a research programme including the SWHSI feasibility RCT

Article history

The research reported in this issue of the journal was funded by PGfAR as project number RP-PG-0609-10171. The contractual start date was in June 2011. The final report began editorial review in May 2017 and was accepted for publication in May 2019. As the funder, the PGfAR programme agreed the research questions and study designs in advance with the investigators. The authors have been wholly responsible for all data collection, analysis and interpretation, and for writing up their work. The PGfAR editors and production house have tried to ensure the accuracy of the authors’ report and would like to thank the reviewers for their constructive comments on the final report document. However, they do not accept liability for damages or losses arising from material published in this report.

Declared competing interests of authors

Karl Claxton reports personal fees from F. Hoffmann-La Roche Ltd (Basel, Switzerland) and personal fees from HERON (Parexcel, Walton, MA, USA), outside the submitted work. Nicky Cullum reports non-financial support from Kinetic Concepts, Inc. (KCI; San Antonio, TX, USA), outside the submitted work. David Torgerson reports grants from the National Institute for Health Research (NIHR), outside the submitted work, and is director of a clinical trial unit funded by NIHR. Nicky Welton reports grants from NIHR, during the conduct of the study, and she is principal investigator for a research grant jointly funded by the Medical Research Council and Pfizer Inc. (New York, NY, USA), outside the submitted work.

Copyright statement

© Queen’s Printer and Controller of HMSO 2020. This work was produced by Chetter et al. under the terms of a commissioning contract issued by the Secretary of State for Health and Social Care. This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed, the full report) may be included in professional journals provided that suitable acknowledgement is made and the reproduction is not associated with any form of advertising. Applications for commercial reproduction should be addressed to: NIHR Journals Library, National Institute for Health Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK.

2020 Queen’s Printer and Controller of HMSO

Introduction

More than 10 million surgical operations are conducted every year in the NHS, with the majority of these involving a wound created by surgical incision. 1 Most incised surgical wounds heal by primary intention, when the wound edges are closely apposed and sutured, clipped or glued together. However, not all surgical wounds heal in this way; some wounds are left open after surgery and heal from the bottom up by the formation of granulation tissue (known as healing by secondary intention). The surgical wounds healing by secondary intention (SWHSIs) may be planned (e.g. after significant tissue loss for which primary closure is not possible, or in the presence of infection). Alternatively, healing by secondary intention may be unplanned when a primarily closed wound opens or ‘dehisces’ (full or partial separation of wound edges). These SWHSIs, also called ‘open surgical wounds’, may remain open for many months, are prone to infection, may prolong hospital stays, and necessitate further hospital admissions and surgeries (delayed primary closure) or skin grafting,2 all adversely affecting patients’ quality of life and incurring substantial NHS costs.

Prevalence of SWHSIs

Although SWHSIs are thought to be relatively common, when we planned this research there were few national or international data regarding their epidemiology. Two published studies estimated that SWHSIs constituted approximately 28% of all prevalent surgical wounds. 3,4 From data collected in Hull and East Yorkshire, UK, Srinivasaiah et al. 4 reported 136 open surgical wounds and 74 dehisced surgical wounds, from a total population of 590,000 (a point prevalence of 0.36/1000 population). Further UK cross-sectional data from Bradford, UK, reported 111 wounds that were classed by the study authors as open surgical wounds and a further 88 that were classed by the study authors as having broken down post surgery. 3 However, the size of the underlying population and, hence, point prevalence for these wounds was not reported. A population-based estimate of the prevalence of SWHSIs alongside in-depth investigation of their origin, natural history, typical treatments and impact on patients and health services was needed.

Details of patient and wound characteristics

Previous research on wound prevalence by Vowden and Vowden3 and Srinivasaiah et al. 4 focused on all wounds, rather than specific wound types. To the best of our knowledge, when we began this research, there was no high-quality information (national or international) describing patients with a SWHSI (age, sex, comorbidities, concomitant medications, surgical speciality); wound characteristics (site, size location, aetiology, whether or not the wounds were planned to be left open before surgery, frequency of wound infection); SWHSI treatments or healing rates in general and for specific patient groups (e.g. those with diabetes mellitus). Robust time to healing data were also limited and reports frequently presented inaccurately analysed data. 5–10 The generalisability of the existing research was also limited, as many trials reported time to healing rates in relation to subpopulations of SWHSI patients and treatments: one trial5 of perineal wounds and foam dressing, two trials7,8 of pilonidal sinus wounds and silastic foam dressing, and one trial10 of below-knee amputation wounds and plaster cast with silicone sleeve or elastic compression. The lack of systematic data describing SWHSIs and their treatment and outcomes was matched by a lack of knowledge about the impact of SWHSIs on patients’ quality of life or daily functioning, as well as the impact of these wounds on the use of health-care resources. This, in combination, made it almost impossible to assess the impact of SWHSIs and their treatments on patients, or to plan new research studies to assess the clinical effectiveness and cost-effectiveness of potential new or alternative treatments or interventions.

The treatment of SWHSIs

Management of SWHSIs often involves daily or more frequent dressing changes, sometimes with packing of the wound cavity. Many different dressing options are available, from simple dressings such as gauze (which can be painful to remove) to more modern options such as foam, hydrocolloid and alginate dressings. Wounds may also be treated by debridement (the removal of foreign material and devitalised tissue) or by skin grafting. When this research was conceived, the type and frequency of treatments being used for SWHSIs was not known. Randomised controlled trials (RCTs) in SWHSI patients are infrequent and often poorly designed, underpowered, utilise surrogate outcomes and often report limited or incorrectly analysed healing data, making interpretation of these data incredibly difficult. For example, a multicentre RCT comparing the effects of zinc oxide with placebo mesh on secondary-healing pilonidal wounds was underpowered, recruiting only 64 participants (n = 33 zinc and n = 31 placebo), and although it did not detect a difference in median healing times (54 days, interquartile range 42–71 days for zinc; 62 days, interquartile range 55–82 days for placebo; p = 0.32), this may have been due to the lack of power. In the same study, fewer postoperative antibiotics (a surrogate marker of wound infection) were prescribed in the zinc oxide group (n = 3) than in the placebo group (n = 12) (p = 0.005). 11

In terms of evidence of effectiveness of different treatment options, Vermeulen et al. 12 explored the relative effects of dressings and topical agents for SWHSIs in a systematic review. They found only 13 RCTs, all of which were small, of poor quality and often conducted > 10 years previously. There was no evidence to indicate that the choice of dressing or topical treatment offered any benefit in terms of wound healing time, but the data were sparse. A systematic review, conducted to inform National Institute for Health and Care Excellence (NICE) clinical guidelines on surgical site infection, investigated the effects of topical antiseptics and antibiotics (including impregnated dressings) on the risk of wound infection in SWHSIs. 13 The four included studies were small and provided generally uncertain evidence on a range of uncommon treatment options. The guidelines recommend that chlorinated lime and boric acid [Edinburgh University Solution of Lime (EUSOL)] and gauze, moist cotton gauze or mercuric antiseptic solutions should not be used to prevent surgical site infection in the management of SWHSIs. 13

Increasingly, more advanced and costly wound treatments have been extensively adopted into clinical practice, with inadequate supporting evidence. One example is negative-pressure wound therapy (NPWT), a device that applies a carefully controlled negative pressure (or vacuum) to the dressing, moving tissue fluid away from the treated wound area into a disposable canister. 14 The canister is removed and replaced either when it becomes full or at least once per week. The device is generally used as part of the SWHSI treatment pathway, rather than to the point of healing, and can be administered and removed by both nurses and surgeons.

Cost of treating SWHSIs

Surgical wounds healing by secondary intention can be large and may produce a significant volume of exudate, which can be difficult to manage, and frequent, time-consuming, dressing changes are common. In addition, SWHSIs must also be protected from infection and trauma during healing. It has been suggested that SWHSIs are at high risk of postoperative infection, with the wound providing an ideal environment for bacterial proliferation, which may be associated with delayed healing. 15 These factors, and the possible need for further surgery, suggest that the costs of treating patients with SWHSIs could be substantial. The lack of available epidemiological evidence in relation to SWHSIs had, however, made it difficult to ascertain the health and social care costs of treating these wounds.

SWHSIs: the patients’ perspective

The lack of systematic data describing SWHSIs, their treatment and outcomes was matched by a scarcity of knowledge about the impact of SWHSIs on patients’ quality of life. Little was known regarding patients’ perspectives and experiences of living with a SWHSI, or their views, expectations and concerns regarding management and outcomes.

SWHSIs: the clinicians’ perspective

A variety of clinicians, including surgeons, tissue viability nurses and general practice nurses, are all commonly involved in the management of patients with SWHSIs. As previously stated, there is a dearth of high-level evidence to guide the management of these patients, particularly regarding the clinical effectiveness and cost-effectiveness of different treatments or interventions. Greater clarity is required regarding assessment of these wounds and the factors that influence management decisions.

Summary

In summary, this research programme was undertaken recognising that SWHSIs may be common and costly but that there was a need for further exploration of the extent, nature, outcomes and impact of these wounds. The lack of international epidemiological data regarding these patients seriously impairs the development of new research studies in this area. There was also huge uncertainty regarding SWHSI management. Options ranged from inexpensive simple dressings to the more complex and costly NPWT, but accurate data regarding the frequency of use of specific treatments was non-existent. In addition, all treatment options for SWHSIs lacked robust, supportive evidence bases in terms of clinical effectiveness and cost-effectiveness, and the impact on patients’ quality of life. As a result, clinicians and patients were uninformed about how to care for SWHSIs and, specifically, which treatment options were most effective and offered the best value for money. The need for research to fill these evidence gaps was also highlighted by the NICE guidance. 13

Given the number of treatment options available, it is important that patients, carers and health professionals are involved in trial design, including the selection of significant outcome measures, and that research is conducted through sufficiently powered trials to detect significant differences in healing rates between treatments. However, the enormous cost of conducting the trials required to fill the evidence gaps means that a rush to undertake such studies, before obtaining additional key intelligence, would be hugely inefficient. There were several important unknowns: information about the natural history and epidemiology of SWHSIs; which treatments were being used most commonly and, thus, should be evaluated; whether or not the decision uncertainty associated with various treatments justifies an expensive trial; and whether or not a trial is feasible. In addition, little was known about which outcomes matter to patients with SWHSIs and what the desirable treatment characteristics are from the perspective of the staff treating them. We have undertaken research to generate vital data regarding an important, costly and hugely under-researched health problem. The research findings will aid in planning service delivery and future research, including economic modelling and primary studies.

Workstream 1

Workstream 1 aimed to describe the number, characteristics, current treatments, impacts and health outcomes of patients with SWHSIs. This was achieved using an initial prevalence survey and a subsequent inception cohort of patients with a SWHSI to collect naturalistic data regarding treatments used, rates of healing, adverse events and quality-of-life changes.

Workstream 2

Workstream 2 aimed to use all available research data to estimate the cost-effectiveness of current treatments for SWHSIs, as identified in workstream 1, and was completed using evidence synthesis and decision-analytic modelling. If assessments of cost-effectiveness suggested that there was decision uncertainty (i.e. uncertainty about which treatment offers best value to the NHS), we would extend analyses to assess whether or not investment in future research on treatments for SWHSIs was likely to be worthwhile and, if so, what research would offer best value for money.

Workstream 3

Workstream 3 aimed to determine the impact of SWHSIs on patients, specifically their perspectives and experiences of living with a SWHSI, of wound management and relevant wound outcomes. In addition, this workstream aimed to determine NHS professionals’ views about SWHSI treatments and important outcomes to measure treatment effects. This was achieved through qualitative interviews with both patients and NHS professionals.

Workstream 4

Workstream 4 aimed to determine the feasibility of conducting further primary research on SWHSIs through a pilot, feasibility RCT.

This synopsis describes the results of our findings from all four workstreams. Publications arising from this research programme are listed in the Acknowledgements.

Cross-sectional survey

Cohort study

Results

A total of 396 patients were recruited to the cohort study from primary and acute care settings in Yorkshire, UK, with 393 participants included in data analysis (three patients were found to be ineligible following recruitment and so were excluded from the analysis). Just over half of participants were male (n = 222, 56.5%), participants had a median age of 55 (range 19–95) years and 69.5% of the study population were classed as overweight or obese (31.3% and 38.17%, respectively). Current smokers made up 28.5% of participants (i.e. were currently smoking or had quit within the last year).

The most common comorbidities we observed were cardiovascular disease (n = 151, 38.4%), followed by diabetes mellitus (n = 103, 26.2%) and peripheral vascular disease (n = 57, 14.5%). The majority of participants had no previous history of SWHSIs (n = 93, 72.0%) and had only one SWHSI (n = 358, 91.0%), and their surgical wound had been planned to heal by secondary intention (n = 236, 60.1%). The median area of the reference SWHSI at baseline was 6 cm² (range 0.01–1200 cm²). SWHSI location varied; however, the most common sites were the abdomen (n = 132, 33.6%), foot (n = 59, 15.0%) and leg (n = 58, 14.8%), linking the commonly represented surgical specialities of colorectal (n = 136, 39.7%) and vascular (n = 82, 20.9%). At baseline, 164 patients (41.7%) were receiving hydrofibre dressings and 89 patients (22.7%) were receiving NPWT. Further details of baseline demographics (patient, wound and surgery) and treatments received are presented in Tables 4–7.

TABLE 4 - Cohort patient baseline characteristics

BMI, body mass index; NSAID, non-steroidal anti-inflammatory drug; SD, standard deviation.

N is less than total sample: 107 patients without associated comorbidity.

N is less than total sample: 121 patients did not report medication use.

Variable	Patients (N = 393)
Age (years), median (range)	55.0 (19.0–95.3)
Sex, n (%)
Male	222 (56.5)
Female	171 (43.5)
BMI (kg/m2), mean (SD)	28.9 (6.6)
History of SWHSI, n (%)
Yes	93 (23.7)
No	283 (72.0)
Do not know	17 (4.3)
Tobacco use, n (%)
None in last 10 years	219 (55.7)
None current, but in last 10 years	62 (15.8)
Current (less than one pack/day) or quit in last year	84 (21.4)
Current (more than one pack/day)	28 (7.1)
Baseline comorbidities	Patients (N = 286), n (%)a
Cardiovascular disease	151 (38.4)
Diabetes mellitus	103 (26.2)
Airways (e.g. asthma)	69 (17.6)
Arthritis	65 (16.5)
Peripheral vascular disease	57 (14.5)
Cancer	51 (13.0)
Orthopaedic (e.g. fractures)	27 (6.9)
Stroke	20 (5.1)
Autoimmune	19 (4.8)
Neurological	11 (2.8)
Other	31 (7.9)
Medications used	Patients (N = 272), n (%)b
Anticoagulants/antiplatelets	196 (49.9)
Vasodilator	111 (28.2)
NSAIDs	66 (16.8)
Corticosteroids	11 (2.8)
Immunosuppressant	9 (2.3)
Cytotoxic	5 (1.3)

TABLE 5 - Cohort wound baseline characteristics

GP, general practitioner.

Variable	Patients (N = 393)
Number of SWHSIs, median (range)	1 (1–6)
Area (cm2), median (range)	6 (0.01–1200)
SWHSI location, n (%)
Abdomen	132 (33.6)
Foot	59 (15.0)
Leg	58 (14.8)
Perianal	34 (8.7)
Back	19 (4.8)
Natal cleft	16 (4.1)
Buttocks	16 (4.1)
Breast	7 (1.8)
Arm	5 (1.3)
Perineum	5 (1.3)
Head	3 (0.8)
Hand	2 (0.5)
Neck	2 (0.5)
Missing	35 (8.9)
Aetiology, n (%)
Planned	236 (60.0)
Dehisced	141 (35.9)
Surgically opened	16 (4.1)
Tissue involvement, n (%)
Full thickness	235 (59.8)
Muscle, tendon or bone exposed	120 (30.5)
Organ exposed	1 (0.3)
Unsure	35 (8.9)
Missing	2 (0.5)
Infection at baseline, n (%)
Yes	79 (20.1)
No	314 (79.9)
Antibiotics used, n (%)
Yes	182 (46.3)
No	211 (53.7)
Dressing, n (%)
Hydrofibre/spun hydrocolloid	164 (41.7)
Other	129 (32.8)
Wound contact	114 (29.0)
NPWT	89 (22.7)
Foam	36 (9.2)
Alginate	27 (6.9)
Silver containing	23 (5.9)
Iodine	19 (4.8)
Soft polymer	19 (4.8)
Hydrocolloid	10 (2.5)
Superabsorbent	7 (1.8)
Cavity foam	4 (1.0)
Hydrogel	1 (0.3)
Silver sulfadiazine	1 (0.3)
Treatment environment, n (%)
Hospital inpatient	229 (58.3)
Home	88 (22.4)
GP	55 (14.0)
Hospital outpatient	11 (2.8)
Other	8 (2.0)
Missing	2 (0.5)

TABLE 6 - Surgery baseline characteristics

GI, gastrointestinal.

Variable	Patients (N = 393), n (%)
Subspecialty
Colorectal	156 (39.7)
Vascular	82 (20.9)
Other	50 (12.7)
Plastics	33 (8.4)
Orthopaedic	17 (4.3)
Obstetrics and gynaecology	13 (3.3)
Surgical debridement	11 (2.8)
Upper GI tract	7 (1.8)
Urology	7 (1.8)
Cardiothoracic	7 (1.8)
Neurosurgery	3 (0.8)
Thoracic	3 (0.8)
Breast	2 (0.5)
Trauma	1 (0.3)
Oral and maxillofacial	1 (0.3)
Surgery type
Emergency	236 (60.1)
Elective	135 (34.4)
Missing	22 (5.6)
Contamination level
Dirty	247 (62.9)
Contaminated	65 (16.5)
Clean-contaminated	51 (13.0)
Clean	26 (6.6)
Missing	4 (1.0)

TABLE 7 - Cohort treatment dressings received at any time

Values exceed total N due to multiple dressing changes and reasons throughout follow-up.

Treatment dressings received (at any time)	Patients (N = 393), n (%)a
Hydrofibre	259 (65.9)
Basic wound contact dressing	212 (53.9)
Other	196 (49.9)
NPWT	115 (29.3)
Foam	113 (28.8)
Silver-containing dressing	89 (22.7)
Soft polymer dressing	73 (18.6)
Iodine-containing dressing	71 (18.1)
Alginate dressing	49 (12.5)
Hydrogel	23 (5.9)
Hydrocolloid	22 (5.6)
Superabsorbent	21 (5.3)
Cavity	12 (3.1)
Polyhexamethylene biguanide dressing	8 (2.0)

The mean length of participant follow-up was 499 days [standard deviation (SD) 127.4 days], with a range of 13–651 days (median 528 days). Sixty-six participants (16.8%) were not followed up for the entire study duration (31 withdrew, 29 died and six were lost to follow-up). When the reference SWHSI was situated on a limb, this was amputated for 3.3% of participants (n = 13), of whom 61.5% had experienced an infection during follow-up (n = 8) and 76.9% had diabetes mellitus (n = 10). Infections were experienced by 32.1% of study participants (n = 126). Hospital admissions were reported for 97 participants (24.7%), of which 66 participants (68.0%) returned to the operating theatre. Thirty-six cases (38.1%) of hospital admissions were related to SWHSIs.

Data indicated that the reference SWHSI healed for 81.4% of participants (n = 320) during the study. Agreement between patient self-report and nurse assessment of healing status verification was relatively high (77.8% at 6 months and 74.2% at 12 months). Disagreements were present for four participants: three patients had healing confirmed during a visit but paperwork was not completed to this effect and one participant was not healed at the verification visit but healed shortly afterwards. The median time to healing for all cohort participants was 86 (95% CI 75 to 103) days, as presented in Figure 2. When we assessed time to healing against baseline participant and wound characteristics in a Cox proportional hazards model, baseline wound area above median (p < 0.01) and surgical wound contamination level as determined at the point of surgery (p = 0.04) were significant predictors of prolonged time to healing (see Appendix 4). Infection at any point was also found to be a significant predictor of prolonged time to healing (p < 0.01).

FIGURE 2.

Cohort study: Kaplan–Meier curve of time to healing in days.

The most commonly received treatment throughout the study was hydrofibre dressings, with 65.9% (n = 259) of participants receiving this treatment at least once. Nearly one-third (n = 115, 29.3%) of participants received NPWT at some point during the study.

Health utility scores captured by the EuroQol-5 Dimensions (EQ-5D) measure22 (in which 0 = death and 1 = perfect health) were a mean of 0.5 (SD 0.4) at baseline, increasing to a mean of 0.6 (SD 0.4) at 6 months and 0.6 (SD 0.4) at 12 months. Further details are provided in Table 8.

TABLE 8 - Cohort EQ-5D utility scores by time point and healing status

Time point	Overall	Healing status		p-value
		Healed	Not healed
Baseline, n	383	311	72
Mean (SD)	0.5 (0.4)	0.5 (0.37)	0.4 (0.42)	0.07
3 months, n	258	223	35
Mean (SD)	0.6 (0.4)	0.6 (0.38)	0.6 (0.33)	0.58
6 months, n	219	191	28
Mean (SD)	0.6 (0.4)	0.6 (0.37)	0.5 (0.34)	0.08
12 months, n	185	166	19
Mean (SD)	0.6 (0.4)	0.6 (0.35)	0.6 (0.38)	0.31

Pain, measured as BPI scores for pain severity (in which 0 = no pain and 10 = pain as bad as you can imagine) and pain interference (in which 0 = does not interfere and 10 = completely interferes)23 reduced slightly over time. Mean pain severity reduced from 3.7 (SD 2.54) at baseline to 3.0 (SD 3.0) by 15 months; similarly, mean pain interference scores reduced from 4.2 (SD 2.54) at baseline to 3.1 (SD 3.17) at 15 months. Further details are provided in Table 9.

TABLE 9 - Cohort BPI scores by time point and healing status

Time point	BPI
	Pain severity				Interference
	Overall	Healing status		p-value	Overall	Healing status		p-value
		Healed	Not healed			Healed	Not healed
Baseline, n	385	313	72		390	318	72
Mean (SD)	3.7 (2.54)	3.6 (2.53)	4.0 (2.53)	0.28	4.2 (3.12)	4.2 (3.14)	4.4 (3.05)	0.63
3 months, n	257	220	37		260	223	37
Mean (SD)	3.3 (2.63)	3.3 (2.70)	3.4 (2.17)	0.83	3.8 (3.12)	3.7 (3.13)	4.3 (3.08)	0.30
6 months, n	210	182	28		214	186	28
Mean (SD)	3.4 (2.67)	3.3 (2.71)	3.9 (2.38)	0.22	3.8 (3.18)	3.7 (3.20)	4.6 (2.97)	0.13
12 months, n	179	161	18		179	161	18
Mean (SD)	3.4 (2.66)	3.3 (2.70)	4.0 (2.32)	0.29	3.6 (3.18)	3.5 (3.20)	4.3 (2.97)	0.36

Quality of life was measured using the SF-12 and presented as SF-12 physical component scores (PCSs) and mental component scores (MCSs). 21 At baseline, the mean PCS was 33.1 (SD 10.7) and the mean MCS was 42.2 (SD 12.35). At 15 months’ follow-up, the mean PCS was 40.8 (SD 13.46) and the mean MCS was 48.3 (SD 10.73). Further details are provided in Table 10. A linear mixed model, adjusting for duration of SWHSI, baseline SWHSI area, location, participant age and baseline SF-12 subscale score, found follow-up time point, baseline score, age and SWHSI duration to be significant predictors of PCS (p < 0.001 in all cases) and MCS (p = 0.03 for time point and p < 0.01 for age, baseline score and SWHSI duration).

TABLE 10 - Cohort SF-12 PCS and MCS by time point

Time point	SF-12 dimensions (overall population)
	PCS	MCS
Baseline, n	390	390
Mean (SD)	33.1 (10.17)	42.2 (12.35)
3 months, n	255	255
Mean (SD)	37.7 (13.15)	45.1 (11.69)
6 months, n	223	223
Mean (SD)	39.2 (12.91)	45.1 (12.13)
9 months, n	210	210
Mean (SD)	39.4 (12.89)	46.4 (11.28)
12 months, n	187	187
Mean (SD)	38.8 (13.11)	47.2 (11.58)
15 months, n	147	147
Mean (SD)	40.8 (13.46)	48.3 (10.73)
18 months, n	78	78
Mean (SD)	39.4 (13.52)	47.3 (11.12)

Objectives

• To estimate the cost-effectiveness of NPWT compared with wound dressings for the healing of SWHSIs, using cohort data from workstream 1.

• To assess whether or not investment in further research on treatments for SWHSIs is likely to be worthwhile.

Methods

In this workstream, we evaluated if, after adjustment, NPWT was clinically effective and cost-effective when compared with standard dressings. For clinical effectiveness, we used wound healing as the outcome; for cost-effectiveness, we quantified the impact of differences in time to healing on quality-adjusted life-years (QALYs). This approach assumed that no mortality differences existed and, thus, any improvements in health-related quality of life (HRQoL) were associated with accelerated time to healing only. We also noted that any additional HRQoL improvements that may have arisen from treatment (independent of healing status) were expected to be transient and not to have a significant impact on HRQoL (which is a multidimensional concept that includes domains related to physical, mental, emotional and social functioning). For this reason, such effects were not considered here.

We hypothesised that NPWT could be cost-effective by reducing healing time, improving HRQoL and reducing treatment costs (via reduced healing time). We envisaged that if the total costs of treatment were higher with NPWT than for comparator treatments, NPWT would only be cost-effective if the incremental costs to QALY gains fell below the standard NICE £20,000–30,000 per QALY threshold.

Specifically, the cost-effectiveness analysis used cost per QALY gained as the cost-effectiveness outcome. A 1 year time horizon was considered and a NHS perspective was adopted. Formally, we aimed to quantify the impact of NPWT in expected time to healing. The difference in QALYs between the interventions was derived from the expected time to healing and the EQ-5D index score while healed/unhealed, the latter estimated using the multilevel model (described in supplementary material in Appendix 5). Incremental disease costs were calculated in an analogous way to incremental QALYs, making use of the cost estimates derived in the multilevel two-part modelling approach (see Appendix 5). Treatment-related costs considered that patients received some form of treatment up to healing. The daily costs associated with the ‘non-NPWT’ group were based on average costs of dressings in participants who had received other treatments and were calculated by multiplying this cost by the difference in time to healing. For patients receiving NPWT, an average daily cost of NPWT was applied to the mean time on NPWT treatment in the cohort study. In the remaining time, patients were assumed to use dressings, with a daily cost equal to patients in the ‘non-NPWT’ group.

The cohort data were analysed for evidence regarding the various aspects of treatment and wound healing, including the impact of treatment (NPWT vs. dressings) on the time to healing and the impact of this SWHSI healing on disease-specific costs and HRQoL, as is presented in Figure 3. To estimate the effect of treatment on healing, we attempted to control the confounding (and selection bias) inherent when using observational data in this context. We adjusted for observed confounding (i.e. for characteristics observed within the cohort study sample that determine time to healing and may have differed between the groups). We also attempted to account for any potential confounding from unobserved sources.

FIGURE 3.

Time to healing: descriptive Kaplan–Meier curve. Reproduced with permission from Saramago et al. 28 This is an Open Access article distributed in accordance with the terms of the Creative Commons Attribution (CC BY 4.0) license, which permits others to distribute, remix, adapt and build upon this work, for commercial use, provided the original work is properly cited. See: http://creativecommons.org/licenses/by/4.0/. The figure includes minor additions and formatting changes to the original figure.

Reproduced with permission from Saramago et al. 28 This is an Open Access article distributed in accordance with the terms of the Creative Commons Attribution (CC BY 4.0) license, which permits others to distribute, remix, adapt and build upon this work, for commercial use, provided the original work is properly cited. See: http://creativecommons.org/licenses/by/4.0/. The figure includes minor additions and formatting changes to the original figure.

Health-related quality of life was assessed in the cohort study using the EQ-5D index score, obtained through a self-reported questionnaire, comprising five domains (mobility, self-care, usual activities, pain and discomfort, and anxiety and depression). 22 Participants were also asked to complete a resource use questionnaire quarterly. This questionnaire was developed for this study to allow costing of NHS resources specifically attributable to the SWHSIs and included collection of number of contacts with general practitioners (GPs), nurses and doctors in NHS institutions or the patient’s home, as well as the number of nights spent as an inpatient between study follow-up time points. The costing used national sources and 2014 prices. 29

Analyses required the application of econometric models to the cohort data. A Bayesian approach to inferences was utilised, computed using Markov chain Monte Carlo simulation, using WinBUGS version 1.4.3 (Medical Research Council Biostatistics Unit, Cambridge, UK). 30

Results

Conclusions

This work compared the clinical effectiveness and cost-effectiveness of NPWT in healing of SWHSIs, relative to dressings, using advanced methods of adjustment for the potential selection effects expected with observational data. The published paper from this stream of work (see Appendix 5) covers methodological aspects of this research; thus, here we aimed to discuss the clinical implications of our results.

Results show that NPWT users in the cohort took longer to heal and this result (which did not reach conventional levels of statistical significance) sustains even after adjustment for differences in potential prognostic factors between the groups. A number of limitations of the data and methods of analyses were also tested (e.g. alternative assumptions on censoring), with none leading to different conclusions. Across all analyses, treatment with NPWT for SWHSIs was not clinically effective or cost-effective and there was little uncertainty over this result. Our treatment effect findings are derived from modelling of observational data and our results (and our interpretation of these) assume that inferences obtained (after adjustment) are unbiased. However, even extensive adjustment of observational data does not negate the potential for unresolved confounding to affect the results and the risk of this can reduce confidence in conclusions drawn from observational data. Definitive evidence from a RCT may be the only way to overcome this lack of confidence.

It is also important to emphasise that we evaluated the causal effects of NPWT on the healing of SWHSIs. Wound infection at baseline was explored in our analyses and was not found to be associated with either treatment allocation or wound healing. However, NPWT may have further direct effects on HRQoL (independent of healing), for example in prevention of wound infection or assisting with wound management. These other effects are likely to be less significant in magnitude and in duration, as NPWT is typically used for only a short duration of time. If future research further explores the effectiveness of NPWT on infection (prevention or treatment), it is important that this research is designed to also explore effects on healing.

There are other important clinical conclusions to be drawn from our analyses. First, patients treated with NPWT in the cohort study differ from those who were not; that is, there was significant selection into treatment with NPWT in the cohort study. Trying to understand how clinicians allocate treatment with NPWT was, however, difficult. Wound area, level of tissue involvement and being an inpatient (rather than outpatient) seemed to have contributed to decisions on whether or not to use NPWT, but do not fully explain these treatment decisions.

Second, in adjusting for selection effects, it was important to consider relevant predictors of healing. However, given the absence of epidemiological research, there was no a priori evidence on what could predict healing in this patient group. The associations found within our work used a predefined process of model selection and indicated that being an inpatient (rather than outpatient) and having a history of a SWHSI may be relevant prognostic characteristics for healing. However, the sample of patients included in the cohort was very heterogeneous. For example, there was a range of anatomical sites for SWHSIs, with the most frequent being the abdomen (33.6%) and foot and leg wounds (30%); there was an approximately equal share of dehisced versus planned open wounds (60% vs. 40%, respectively) and an approximately equal share of wounds with superficial versus deeper tissue involvement (59% with skin involvement only vs. 41% with skin and subcutaneous tissue involvement). If determinants of healing differed across different subpopulations, then a more homogeneous sample would have meant that it was easier to identify these.

Third, our analyses of the cohort data suggest the existence of a subpopulation of ‘hard-to-heal’ patients: time to healing for those who healed (mean 99 days) was very different from the mean follow-up for those who did not heal (mean 416 days). Those who did not heal within follow-up also differed from those who did and our explorations indicate that BMI and foot wound location are associated with a lower probability of healing. Further research could continue to explore characteristics of ‘hard-to-heal’ patients who present with the biggest burden of disease and thus have a larger capacity to benefit from treatments.

Finally, our research also suggests that individuals with a history of SWHSIs treated with NPWT are expected to take even longer to heal than those who did not have a history of SWHSIs. Although we are not clear of the clinical plausibility of such an effect, future research on NPWT could explore the evidence for such treatment effect interaction.

The findings from this workstream have informed the final phase of work in our research programme: a pilot, feasibility RCT assessing NPWT compared with standard dressings.

Objectives

To explore, using qualitative interviews:

• patients’ perspectives and experiences of living with a SWHSI and to elicit their views regarding management and desirable outcomes

• NHS professionals’ views and experiences concerning treatment choices for SWHSIs.

Methods

The purpose of this qualitative research was to explore the daily, lived experiences of patients with a SWHSI and to understand health-care professionals’ perspectives of managing these wounds. The topic guide developed for use with patients (see Appendix 9) comprised a few key questions to encourage in-depth exploration of how a SWHSI might affect every aspect of patients’ lives. Patient advisors were asked to comment on the content and clarity of the patient topic guide prior to its use. During interview, individual patients were encouraged to identify and speak freely about any issue related to their SWHSI that affected them. The clinicians’ topic guide (see Appendix 10) similarly encouraged clinicians to fully express their own perspectives, with the topic guide acting as a flexible tool to guide the discussion.

Patients and clinicians were recruited from both acute and community nursing services in two settings in the north of England: one was a large city with an economically and ethnically diverse population and high levels of deprivation and the other was a smaller city, also with high levels of deprivation and ethnic diversity.

Patients were eligible to participate if they had a surgical wound considered to be healing by secondary intention by the referring clinician, were aged ≥ 18 years and able to give informed consent. Patients were purposively sampled to include those who had SWHSIs that were slow to heal or non-healing, and to ensure representation across sex, age, duration of wound and surgical discipline (e.g. general, vascular, orthopaedic surgery). We aimed for ethnic diversity within the patient sample and for a range of patients from both acute and community treatment settings. Potentially eligible patients were identified and approached regarding study participation by a member of their usual health-care team. Clinicians were purposively sampled from among those with responsibility for caring for patients with SWHSIs, and a range of clinicians from community and acute settings were selected for participation.

The backgrounds of the two researchers involved in the study differed: one was a registered nurse with extensive experience of applied health services research, whereas the other had a background in social sciences research. The two researchers, who were co-located in the same office, held regular, informal meetings during data collection to discuss any differences and ensure consistency of approach. No significant differences were identified in the data collected by the two individuals.

Semistructured interviews were conducted in patients’ homes and at the clinicians’ place of work. Interviews with patients lasted approximately 1 hour (interviews with surgeons ranged from 30 to 45 minutes and those with nurses ranged from 60 to 75 minutes). All interviews were audio-recorded and fully transcribed before being analysed for thematic content using the ‘framework’ approach (see Appendix 11). 41 Interviews continued until no new information was forthcoming. 42 After familiarisation with the data set and initial identification of themes, a coding framework was developed to allow for linkage between participants and their responses and comparison across the full data set. This coding framework was modified during the initial phases of data analysis to accommodate new responses from patients. Interpretation relied on the abilities of the analysts to determine meaning, salience and connection. 43 The input of patient advisors was sought during the analytic process and advisors were asked to contribute to reflections on the meaning and interpretation of the data arising from the interviews.

The study received research ethics approval from Yorkshire and the Humber – Leeds Central Research Ethics Committee (reference 11/YH/0313) and written, informed consent was obtained from all patients prior to participation in the interviews.

Results

Conclusions

To the best of our knowledge, this is the first study investigating patients’ and clinicians’ views about the management and treatment of SWHSIs, and patients’ experiences of living with this condition. Findings from our study therefore lay the groundwork for further research in this important aspect of health care about which so little is known. For example, understanding more about what matters to patients helps to ensure that appropriate outcomes are captured in future trials.

Patients’ initial reactions to their SWHSIs were of shock and disbelief, and the visual reminder following surgery of a ‘violated’ body intensified these feelings, particularly for patients with large abdominal cavity wounds. Having a SWHSI had a substantial impact on daily living and this impact was particularly important for those patients with children or in employment, who constitute a younger demographic than seen in previous wound research associated with other wound types. As healing progressed, patients were concerned with both their own reaction to the wound and the reactions of others. The long healing process for many patients, characterised by a reduced quality of life and a constant need for treatment and care, concurs with previous evidence in relation to patients with other wound types or ulceration. 46–53 It is worth emphasising, however, that SWHSI patients are typically much younger than patients with leg or pressure ulcers and frequently have major caring and employment responsibilities: Cullum et al. 27 reported a mean age of 79.65 (SD 11.32) years for venous leg ulcer patients, a difference of 25 years when compared with the mean age observed in workstream 1 [54.1 (SD 18.2) years]. Wound care experiences among patients varied greatly, but most patients were willing to try any treatment that promised healing. Understanding the ‘lived experience’ of patients is crucial for clinicians to provide effective management and improve patient quality of life. Establishing a therapeutic relationship and listening to patient concerns is vital to meeting patient’s physical, emotional and psychosocial needs during the wound healing process. The provision of additional information for patients in relation to the rationale of treatment choices is also an important element for consideration with regards future treatment delivery.

Clinicians had varying levels of knowledge in relation to wound care treatment options. Nurses were frequently responsible for dressing choice decisions, made on the basis of wound condition, clinical experience and recommendations. A treatment frequently favoured by clinicians was NPWT. The lack of robust evidence for this treatment option was noted by several of the study clinicians; however, for many, individual experiences of its use were deemed to sufficiently demonstrate the effectiveness of this treatment. 14

The use of purposive sampling enabled us to obtain a diverse range of views from both patients and clinicians. It is noted, however, that only a limited number of interviews were conducted with clinicians. Therefore, further research may be warranted to build on these findings.

Generalisability in qualitative research involves thinking through what kind of relationship the study findings have with other populations and settings, and unpacking exactly what inferences can be drawn from the data analysis. 41 Our study yielded ‘rich’ data that captured a wide-ranging, yet in-depth, picture of significant issues relating to patients’ and clinicians’ views and experiences of SWHSIs. The study findings, therefore, promote and enhance understanding of the impact of a SWHSI on patients’ lives, as well as describing the challenges faced by clinicians in managing these wounds, thereby adding to the evidence base by ‘sensitising’ readers, including the research community, to new ways of thinking about SWHSIs. Our study findings may be considered transferable to the ‘parent populations’ of patients with SWHSIs and the clinicians looking after them; however, decisions concerning broader extrapolation of the findings must take into account any study-specific contextual factors that may limit applicability. 41

Objectives

• To test the methods and feasibility of a full RCT of NPWT compared with usual care (no NPWT) for SWHSI.

• Specifically, to determine:

  • likely recruitment rate, including potential participants’ willingness to be randomised and if this depends on wound location and other factors

  • clinicians’ willingness and ability to recruit and randomise participants

  • testing of inclusion and exclusion criteria

  • fitness for purpose of data collection methods, including across and between care settings

  • ability of sites and clinicians to supply NPWT to participants in a timely fashion, irrespective of care settings, and assess any training requirements

  • ability of community staff to manage participants randomised to NPWT

  • suitability of method of outcome ascertainment

  • adequacy of duration of follow-up

  • rates of withdrawal from treatment, response rates to questionnaires, attrition from the trial and likely rates of missing data for outcomes

  • other methodological issues, including feasibility of blinded outcome assessment and whether or not trial documentation is acceptable to NHS nurses collecting data

  • feasibility of collecting data for and conducting of economic analyses in a larger trial (through exploratory analyses).

Methods

The pilot, feasibility RCT was conducted over a 10-month period (20 November 2015 to 30 September 2016: recruitment 20 November 2015 to 30 June 2016 and follow-up 20 February 2016 to 30 September 2016) in acute and community settings at three study sites in Leeds and Hull, Yorkshire, UK. Prior to study activity commencing, approval was obtained from Yorkshire and the Humber – Leeds East Research Ethics Committee (reference 15-YH-0307) and from the associated NHS trusts.

Patients were eligible for inclusion if they were aged ≥ 18 years and able to give full informed consent; were receiving care from Hull and East Yorkshire Hospitals NHS Trust (now Hull University Teaching Hospitals NHS Trust), Leeds Teaching Hospitals NHS Trust or Leeds Community Healthcare NHS Trust; had a SWHSI that could be reasonably treated with NPWT and wound dressings; had a SWHSI that was considered ready for NPWT (i.e. minimum 80% viable tissue or thin layer of slough requiring no further debridement); and were receiving adequate nutrition (as assessed by the senior nurse responsible for nursing care). Patients were ineligible for inclusion if they had limited life expectancy; active systemic infection; inadequate haemostasis or risk of bleeding; chronic wounds (e.g. pressure or foot ulcers) that were non-surgical in origin but had been surgically debrided; or had wound characteristics that precluded the use of NPWT (e.g. unclear undermining, necrotic or malignant tissue, eschar, exposed blood vessels, organs, anastomotic sites or nerves). Patients were also excluded if they had previously been or were currently receiving NPWT on their SWHSIs (including applications while in theatre for the surgery resulting in the SWHSI), if the wound was located where a vacuum seal could not be obtained, if they had participated in a research study in the previous 4 weeks, or if they were unwilling to have wound photographs taken.

Health-care professionals initially identified and screened patients for eligibility. Those meeting eligibility criteria were approached with further details of the study by a clinical or research nurse (subject to patient consent to approach), prior to study consent being obtained. As the main aim of this study was to determine the feasibility of conducting a larger trial, rather than to detect a treatment effect, a formal sample size calculation was not required. We aimed to randomise 50 patients over a 7-month recruitment period.

Baseline data were collected, including participant, surgery and wound information, wound dimensions (measurements and wound tracing) and a photograph, pain assessment [using a visual analogue scale (VAS) and the BPI]23 and quality-of-life data (SF-12 and EQ-5D-3L). 21,22 As this was a feasibility trial, a primary outcome was not defined; rather, a range of feasibility (e.g. recruitment rate, time to intervention delivery) and clinical (e.g. time to wound healing) outcomes were collected to inform a future definitive trial. Participants were followed up for a maximum of 3 months, unless they withdrew consent, died or became lost to follow-up. Clinical outcomes were collected prospectively on a weekly to fortnightly basis at follow-up assessment visits conducted by the research nurses, including wound dimensions and photographs, healing status [defined as ‘complete epithelial cover in the absence of a scab (eschar)’], infection, hospital admission, return to operating theatre and treatment changes. Participants also completed self-report postal questionnaires (EQ-5D-3L,22 BPI,23 SF-1221 and resource use and pain via a VAS) at 2 weeks, 1 month and 3 months post randomisation. When consent was provided, participants were also contacted by text message on a weekly basis and asked to provide a numeric rating of their wound pain in the previous week. When participants failed to respond, one further message was sent before text message data collection discontinued. When participants’ wounds were reported to have healed during the study, text messaging data collection ceased at the point of wound healing.

Information concerning acceptability of study participation was collected from participants using Likert scales. Data relating to acceptability of documentation and training requirements for NPWT were initially collected from research nurses, using a Likert scale. Qualitative interviews were then completed with the research nurses to ascertain additional information regarding acceptability of the study processes, documentation and delivery.

Participants were allocated (1 : 1) to the intervention (NPWT) or usual care (no NPWT), using random permuted blocks, with stratification by wound area (< 28 cm², ≥ 28 cm²). Allocations were concealed through a central randomisation service at the University of York.

The study intervention (NPWT) was delivered using NPWT devices that were in use in the acute and community services in Hull and Leeds, which included V.A.C^® (KCI Medical Asia Pte Ltd, Singapore), Renasys^® (Smith & Nephew, London, UK) and PICO^® (Smith & Nephew, London, UK) devices. The NPWT treatment delivery (e.g. device type, pressure cycles, dressing change and canister emptying frequency, application and removal of the device and treatment duration) was as per the standard practice at the time to ensure that the pragmatic nature of the pilot feasibility study was maximised. This was therefore decided by the clinical care team in conjunction with the participant and nurse, with the only stipulation for NPWT being that use must be clinically appropriate.

The control group participants received usual care (wound dressings, no NPWT), with dressing type and frequency of change left to the discretion of the clinical care team. As there is no evidence to suggest that any one dressing is more clinically effective or cost-effective than another,12 types of dressings were not stipulated for the trial.

Owing to the nature of the intervention, it was not possible to blind participants or health-care professionals to trial treatment; however, the feasibility of blinded outcome assessment of healing was assessed within the trial using study photographs. Initially, it was proposed that blinded review of healing would be completed for every participant photograph obtained, but this was reduced during the study to review of only the final photograph, due to time and resource constraints. Assessment of blinding to treatment allocation was conducted through review of photographs taken at the week 1 follow-up.

Data analysis was conducted using Stata, using the principles of intention to treat and two-sided statistical tests at the 5% significance level, when appropriate. Summary statistics for all variables were generated by trial arm and overall. Time to healing was defined as the number of days from randomisation to date of healing. Data were right censored at the date of the final assessment visit for participants not deemed to have healed. Time to healing was assessed using Kaplan–Meier curves, recognising that the study was not powered to detect a treatment effect. A Cox proportional hazards regression was used to investigate the impact of covariates (contamination level of surgery, wound infection, wound size, SWHSI history and location). Cost-effectiveness was explored using total mean resource use costs and mean QALYs per trial arm.

To understand improvements to trial processes, to support research nurses in conducting a larger RCT in this area, qualitative interviews with eight research nurses were completed. Interviews were audio-recorded and fully transcribed before being analysed for thematic content using a ‘framework’ approach. 41,58 Interpretation of the findings enabled linkage between individual nurses and their responses to account for variation between the type of study site (acute or community).

Prior to analysis, wound tracings were measured using Mouseyes software (R Taylor, Manchester, UK) to obtain perimeter and area estimates. 59 Both adjusted (length × width × Π)60 and unadjusted (length × width) wound area (cm²) measurements were calculated using ruler measurements obtained at clinical follow-up visits.

Results

Recruitment and participation

Recruitment to the study commenced on 20 November 2015 and continued until 30 June 2016. Delays in study set up, beyond the control of the research team, had an impact on recruitment rate in the early stages of the trial; there was only one recruiting site active until the two remaining sites were opened to recruitment in February and March 2016, respectively. The overall target recruitment rate for the study was seven participants per month and, following successful opening of all three recruitment sites, the study achieved this target in the final 4 months of recruitment (Figure 4). The flow of participants through the trial is shown in Figure 5.

FIGURE 4.

Cumulative target and actual participant recruitment.

FIGURE 5.

Pilot feasibility RCT: Consolidated Standards of Reporting Trials (CONSORT) flow diagram. a, Reasons not mutually exclusive.

Of 248 patients screened for eligibility, 75.0% (n = 186) were ineligible (including one participant found to be randomised in error). The most common reason for ineligibility was that the patient was receiving or had previously received NPWT on their current SWHSI (45/248, 18.1%), had NPWT applied while in theatre (n = 7/248, 2.8%) or both (24/248, 9.7%). Twenty-two participants were eligible but did not wish to consent to study participation; the most common reason for declination was not wishing to receive NPWT (5/22, 22.7%). Reasons for ineligibility were largely distributed across the observed wound locations, with the exception of ‘receiving inadequate nutrition’, which was only reported for five patients with abdominal wounds, and ‘presence of exposed vessels or organs’, which was reported for 11 abdominal and two leg wounds only.

Forty-one of the 248 screened patients (16.5%) were randomised to the pilot feasibility RCT, with 40 participants included in the study analyses (one patient was found to be ineligible following randomisation and so was withdrawn from study data collection and analysis). Of those correctly randomised, 19 out of 40 patients (47.5%) were allocated to NPWT and 21 out of 40 patients (52.5%) were allocated to usual care.

The mean age of participants was 57.8 (SD 14.4) years and just over half (n = 22, 55.0%) were male. Participants were, on average, overweight [mean BMI 29.1 (SD 5.7) kg/m²], 60% (n = 24) were diabetic and 10 (25.0%) reported being a current smoker. The most common location of the wounds in recruited participants was the foot (n = 24, 60.0%), of which 19 out of 24 (79.2%) were due to toe or foot amputation, two (8.3%) were due to incision and drainage, two (8.3%) occurred following debridement (of amputation site, n = 1; of non-chronic ulcer, n = 1) and the cause of the remaining foot wound was unknown. Usual-care participants had their wound for a median of 12 days and over one-third (8/21, 38.1%) had a wound infection at baseline. NPWT participants had their wound for a median of 7 days and 26.3% (5/19) of participants had a wound infection at baseline. Baseline characteristics are summarised in Table 18.

TABLE 18 - Pilot feasibility RCT: baseline characteristics of randomised participants by treatment group

Totals for NPWT, usual care and overall total were N = 18, N = 21 and N = 39 for this category.

Variable	Treatment group		Total (N = 40)
	NPWT (N = 19)	Usual care (N = 21)
Age (years)
Mean (SD)	58.8 (15.1)	56.9 (13.9)	57.8 (14.4)
Median (minimum, maximum)	62 (33, 88)	55 (35, 86)	58.5 (33, 88)
Sex, n (%)
Male	11 (57.9)	11 (52.4)	22 (55.0)
Female	8 (42.1)	10 (47.6)	18 (45.0)
BMI (kg/m2)
Mean (SD)	29.2 (5.6)	29.0 (6.0)	29.1 (5.7)
Median (minimum, maximum)	28.6 (20.9, 39.9)	29.3 (13.7, 39.9)	28.7 (13.7, 39.9)
Diabetic, n (%)
Yes	12 (63.2)	12 (57.1)	24 (60.0)
Peripheral vascular disease, n (%)
Yes	7 (36.8)	7 (33.3)	14 (35.0)
Tobacco use, n (%)
None	13 (68.4)	10 (47.6)	23 (57.5)
Ex-smoker	1 (5.3)	6 (28.6)	7 (17.5)
Current (less than or equal to one pack a day)	2 (10.5)	4 (19.1)	6 (15.0)
Current (more than one pack a day)	3 (15.8)	1 (4.8)	4 (10.0)
History of SWHSI, n (%)
Yes	5 (26.3)	5 (23.8)	10 (25.0)
No	11 (57.9)	15 (71.4)	26 (65.0)
Do not know	3 (15.8)	1 (4.8)	4 (10.0)
Wound area (cm2)
< 28 cm2, n (%)	10 (52.6)	11 (52.4)	21 (52.5)
≥ 28 cm2, n (%)	9 (47.4)	10 (47.6)	19 (47.5)
Median (minimum, maximum)	18.2 (0.2, 122.5)	20.4 (2.3, 93.2)	19.3 (0.2, 122.5)
Wound duration (days)
Median (minimum, maximum)	7 (0, 27)	12 (1, 142)	7 (0, 142)
Wound infected, n (%)
Yes	5 (26.3)	8 (38.1)	13 (32.5)
No	14 (73.7)	13 (61.9)	27 (67.5)
Wound location, n (%)
Foot	11 (57.9)	13 (61.9)	24 (60.0)
Abdomen	3 (15.8)	3 (14.3)	6 (15.0)
Leg	3 (15.8)	1 (4.8)	4 (10.0)
Breast	1 (5.3)	1 (4.8)	2 (5.0)
Groin	0 (0.0)	2 (9.5)	2 (5.0)
Buttocks	0 (0.0)	1 (4.8)	1 (2.5)
Perianal area	1 (5.3)	0 (0.0)	1 (2.5)
Type of surgery, n (%)a
Elective	12 (66.7)	18 (85.7)	30 (76.9)
Emergency	6 (33.3)	3 (14.3)	9 (23.1)
Contamination level of surgery, n (%)
Clean	6 (31.6)	2 (9.5)	8 (20.0)
Clean/contaminated	9 (47.4)	12 (57.1)	21 (52.5)
Contaminated	4 (21.1)	7 (33.3)	11 (27.5)

Clinical outcomes

Healing

Participants were followed for a median of 84 days after randomisation (range 13 to 105 days) to assess wound healing. During the study, 10 wounds (of 40, 25.0%) were deemed to have healed based on assessment at weekly follow-up [six in the NPWT group (31.8%) and four in the usual-care group (19.1%)]. Time to healing was summarised using Kaplan–Meier curves (Figure 6). Adjusted Cox proportional hazards models indicated that wound size (p = 0.03) and duration of wound (p < 0.001) were predictors of time to wound healing, with smaller and longer duration of wounds associated with increased time to healing (see Appendix 13).

FIGURE 6.

Pilot feasibility RCT: Kaplan–Meier curve – time from randomisation to healing.

Infection

During the trial, 17 participants (NPWT, n = 6, 31.6%; usual care, n = 11, 52.4%) experienced an infection. Of these, nine experienced infection at baseline only (NPWT, n = 3, 15.8%; usual care, n = 6, 28.6%), four during follow-up only (NPWT, n = 1, 5.3%; usual care, n = 3, 14.3%) and four both at baseline and during follow-up (NPWT, n = 2, 10.5%; usual care, n = 2, 9.5%).

Hospitalisation

Participants in the NPWT group spent a median of 29 nights in hospital during the trial and participants in the usual-care group spent a median of 10 nights in hospital.

There were five reported hospitalisations during the trial, all of which were associated with serious adverse events (as Adverse events). In four instances (of five, 80.0%) the participants were subsequently discharged and in one instance (20.0%) the participant was withdrawn from the study (due to amputation) and subsequently died, and so further information regarding hospital discharge was not collected.

Conclusions

This pilot, feasibility RCT provides invaluable information on the feasibility of conducting a large-scale trial of NPWT for treatment of SWHSIs and identifies areas of key consideration in the planning of future research.

What do we now know about the SWHSI patient population?

This research programme emerged from clinical uncertainty about the best way of managing SWHSIs. To the best of our knowledge, there has been very little previous research on open surgical wounds, and what small amount there has been has focused only on dehisced surgical wounds;64,65 we have now shown that these constitute approximately half of all SWHSIs. We have studied both dehisced surgical wounds and those intentionally left open after surgery because they present similar challenges for clinical management. We planned this research at a time (2009) when the use of a costly intervention, NPWT, was increasing; however, access to it varied hugely, based on clinical setting, local policies and resources. Prior to this research, little was known about the frequency of SWHSIs, the characteristics of the patients who experience them and longer-term outcomes. Without basic information about the frequency and prognosis of a health condition and how patients are affected by it, it is impossible to plan research on treatments. 66 Initially, we undertook a cross-sectional survey of the prevalence of treated SWHSIs, which had the dual purpose of deriving the first population-based estimate of prevalence, as well as identifying where and when SWHSIs occurred, to aid the planning of an inception cohort. The cross-sectional survey (conducted in 2012) was anonymised, completed away from the patient and did not require consent in order to optimise data capture. To the best of our knowledge, this survey provides the first estimate of the prevalence of treated SWHSIs, which we estimate at 4.1 per 10,000 of the population (95% CI 3.5 to 4.7). 16 There are several things worth noting about this estimate: the prevalence is similar to best estimates of the UK prevalence of leg ulcers (4.4 per 10,000),27 almost half of SWHSIs (48%) were planned (before surgery) to be left open, the wounds had been present for a median of 28 days, the patients were mainly receiving care in primary and community care settings and 93% of patients were receiving wound dressings (6% had NPWT). Colorectal surgery was the most frequent type of surgery to precede the SWHSI, although plastic surgery and vascular surgery were also common.

This survey, although rather basic in design (lacking independent case ascertainment, for example, due to resourcing), provided crucial intelligence for planning the cohort study. Our median time from surgery to wound breakdown (in those whose wounds were not intentionally left open) of 9 days accords with previous studies of dehiscence. 64,67

Our inception cohort collected data from 393 patients with SWHSIs and, to the best of our knowledge, is the first detailed analysis of this patient population, their wound treatments and healing trajectories. A notable difference between this and the cross-sectional survey (apart from the longitudinal follow-up) was the requirement for informed consent, which may have influenced participation. In total, 57% of the cohort were men, the overall median age was 55 years, 70% of the cohort were overweight or obese (higher than the 2015 national average of 63%)68 and 29% were smokers or had quit in the last 12 months (compared with 19% of the adult population in Great Britain). 69 Common comorbidities were cardiovascular disease (in 38%), diabetes mellitus (in 26%) and peripheral vascular disease (in 14.5%). The wounds of 60% of the cohort participants were planned to be left open before surgery, higher than for the cross-sectional survey in which 48% were planned. This probably reflects the relative ease of recruitment of participants to the cohort, when it was known in advance that their wound would be open after surgery.

Our research illustrates, for the first time, the heterogeneous nature of the population of people with SWHSIs and of their wounds. Although it was anticipated that SWHSIs would stem from a range of surgical specialties, the distribution of SWHSI sites is noteworthy (34% abdominal, 15% feet, 15% leg) and anatomical site is very likely to influence the impact of the wound on quality of life (if it influences mobility or ability to drive, for example). The clinical specialty under whose auspices the preceding surgery took place was most commonly colorectal (40%), but also commonly vascular (21%). This information is vital to the planning of future research to ensure that the studies are carried out in the populations most affected. Moreover, these subpopulations of people with SWHSIs are likely to demonstrate very different healing trajectories from one another (an open wound on the foot in somebody with peripheral vascular disease and/or diabetes mellitus is likely to heal differently from a partially dehisced abdominal wound post appendectomy). Those conducting future trials in this area will need to make decisions about trading off ease of recruitment of a heterogeneous population (with consequent ‘noisy’ healing data) with recruitment from smaller, focused patient populations. This is illustrated by our pilot trial, to which we recruited 40 eligible participants, 60% of whom had a SWHSI on the foot (compared with 15% in the cohort study). The nature of those recruited to the pilot trial meant that the time to healing was much longer than for the cohort study and far fewer healing events were observed (only 25% healed), despite the 90-day follow-up period. The reasons for the excess of patients with foot wounds in the pilot trial are unclear, but it is likely that they were more readily recruited for some reason. It is possible that the current enthusiasm for NPWT as a treatment for SWHSIs meant that some health professionals were not in equipoise and were unwilling to randomise, thus making it difficult to recruit specific patient subgroups.

Future trials will therefore need to be carefully planned, with a desired population in mind and appropriate targeted recruitment. The cohort study time to healing data will be invaluable to the planning of new research, particularly in relation to appropriate follow-up time frames.

Exploratory analysis of predictors of healing within the cohort identified larger-area surgical wound contamination classification (as judged at the point of surgery)70 and infection at any time point as predictors of slower healing. The median time to healing of 86 (95% CI 75 to 103) days is very similar to that for venous leg ulcers (84 days in typical venous ulcer patients in a recent trial). 71 The typical healing trajectory for people with a SWHSI is not smooth, with episodes of infection and hospital readmission commonplace. The relatively young age of SWHSI patients compared with other patient groups with chronic wounds (e.g. leg and pressure ulcers) is particularly noteworthy. The wide-ranging impact on quality of life was detectable using the generic EQ-5D and SF-12 instruments, and was both physical and mental. 21,22 We heard directly from the patients themselves of the often devastating impact on their lives. Patients often felt isolated and confined to the home with disruption of working and caring responsibilities, causing feelings of dependency and burden. There were frequently financial impacts of the SWHSIs on the person and their family. To the best of our knowledge, the cost to the NHS of a SWHSI had not previously been estimated. We estimated that the mean cost of a SWHSI to health services was £1060 before the inclusion of treatment costs. Use of NPWT was estimated to cost, on average, an additional £1323 per month and use of dressings was estimated to cost, on average, an additional £441 per month.

What do we now know about treating SWHSIs?

Prior to this research, we had no information about treatments that were being used for SWHSIs. From our research we have learned that SWHSI treatments fall into three main categories: dressings, NPWT and further surgery. We observed a plethora of treatments being used for SWHSIs; however, hydrofibre dressings were the most commonly used (66% of patients received these at some time), alongside a high use of NPWT. Although the cross-sectional survey identified NPWT use in only 6% of patients, the cohort study indicated that a much larger proportion (29%) were treated with NPWT at some time.

Dressings are the cornerstone of treatment for complex wounds and there are many categories available, ranging from simple, basic wound contact dressings to ‘advanced’ dressings containing ingredients such as silver. 29 However, the evidence for the effectiveness of specific dressings and NPWT for SWHSIs is sparse and of low quality. 12 The most recent systematic review of the effects of dressings for open surgical wounds highlighted the paucity of evidence and a review of the effects of NPWT on open surgical wounds (search date June 2015) similarly concluded that there is currently no rigorous evidence available and therefore the benefits and harms are unclear. 14 There is an increasing amount of research regarding NPWT for the primary prevention of surgical site infections in closed surgical wounds; however, its effects in this context also remain unclear. 72,73 There is some evidence of potential benefit of NPWT for foot wounds in diabetes mellitus; however, this evidence is of low certainty due to its low quality. 31

We planned to construct a cost-effectiveness model for NPWT compared with dressings for open surgical wounds using a combination of published and cohort study data. We were unable to populate this model with published data as there were no data reporting time to healing as an outcome in RCTs of NPWT in this patient population. Using the cohort data alone to compare the effects of NPWT and dressings on time to healing effectiveness, and after using different approaches to adjust for confounding, we concluded that NPWT is less effective and more costly than wound dressings for SWHSIs. We had originally intended to conduct a value of information analysis to determine the potential impact of uncertainty on the decision regarding NPWT to treat SWHSIs. This analysis would assess the health and cost implications of the wrong decision being made and thus inform investments in future research to mitigate these uncertainties. However, our analyses showed that uncertainty around the decision not to use NPWT was very small. Even with the use of advanced adjustment techniques, such as those applied here, observational data may still affect the conclusions. Meta-analyses comparing the findings of RCTs and cohorts designed to answer the same clinical question give an OR of 1.04 (95% CI 0.89 to 1.21), highlighting the potential for agreement between the designs and the associated uncertainty. 74 The current economic evaluation uses all available evidence on the clinical effectiveness and cost-effectiveness of NPWT; thus, we argue that it should be seriously considered. However, the potential for unresolved confounding may limit confidence in the associated conclusions and therefore this may lead to justified calls for definitive RCT evidence to be obtained.

Interviews with patients and health professionals provided further insights into the use of, and views about, treatments for SWHSIs. The wide range of dressings used and inconsistency of use was noted by patients. Sharp, sometimes painful, debridement of SWHSIs was also reported by patients, despite the lack of high-quality evidence to support its use. 75 However, debridement was not measured explicitly as a treatment in the cohort study, so further data are needed on how widespread sharp debridement is as a treatment for SWHSIs. Finally, although our study participants generally viewed NPWT as an effective treatment, they reported various drawbacks, including pain during dressing changes. Some study participants reported feeling too embarrassed to go outside the home with NPWT in situ, due to the bulky appearance of the equipment and their fears that the exudate and odour might be detected by other people. Nurses’ varying levels of expertise in use of NPWT appeared to provoke anxiety in patients. These findings mirror those from other small qualitative interview studies with patients receiving NPWT. 76–78

What do we now know about living with a SWHSI?

The interviews with patients, together with the cohort HRQoL data, show the devastating effect that open surgical wounds can have on those affected. For those who did not expect to have an open wound after surgery, there were feelings of shock, fear and anxiety; these are feelings akin to those reported by people who have undergone life-changing trauma. 79 Significantly, the presence of an open wound resulted in the withdrawal of many people from normal employment, leisure and social activities. During interviews, participants indicated that their physical and mental resources had become depleted through the dominance of the wound in their lives.

We note the low baseline mean SF-12 PCSs and MCSs for SWHSI patients [mean PCS 33.1 (SD 10.17); mean MCS 42.2 (SD 12.35)]. These values, for people who have recently undergone surgery and who have an open wound, are lower than the mean PCS reported for an, on average, older venous leg ulcer population [mean PCS 38.4 (SD 11.2); mean MCS 48.6 (SD 12.0)],71 and are also lower than mean scores for other patient groups, such as those with coronary heart disease and arthritis. 80,81 However, the SWHSI cohort mean scores are similar to postoperative SF-12 data from 85 participants with mainly closed wounds [mean PCS 35.1 (SD 7.8); mean MCS 43.5 (SD 12.4) 30 days post surgery]. 82 Thus, it is difficult to separate the impact of surgery from the impact of an open wound on HRQoL. In the SWHSI cohort, we noted a significant improvement over time in both PCS and MCS, suggesting that the SF-12 is responsive to changes in HRQoL in this population. Improved quality of life was likely to be the result of recovery from surgery, changes in the underlying condition the surgery aimed to ameliorate or resolve and wound healing. The baseline EQ-5D index score was found to be, on average, 0.43 (SD 0.45). Modelling results indicated that wound healing was associated with a small (but statistically significant) increase in EQ-5D index score (mean 0.055, SE 0.02). This level of improvement is smaller than what has been detected for the healing of other wound types,71 but this may be due to different estimation methods. This value is also within the range of minimal clinically important differences evaluated across a wide range of conditions. 83,84

Although baseline HRQoL was relatively poor in this SWHSI cohort, pain severity and interference scores of 4 (SD 3) (measured using the BPI)23 were indicative of relatively mild pain when compared with, for example, the mean pain severity score of 7.0 (SD 1.8) and pain interference score of 7.6 (SD 2.0) reported in 440 patients with known chronic, non-malignant pain. 85 In addition, for the SWHSI cohort, mean pain scores reduced, on average, by only 1 point, to 3 points, by 15 months, follow-up. In interviews, some patients discussed pain and its impact, but it did not seem to be a key topic of concern and was not an obvious source for the overall poor HRQoL observed in those with a SWHSI.

Our findings, from exploring living with a SWHSI with patients, illuminate the significance of psychosocial effects, due to diminished sense of self, inability to fulfil social roles and obligations, and curtailment of normal social activities, especially when patients’ hopes for healing are not met. Our study also highlights the impact of financial pressures on younger patients whose wound rendered them unfit for work, and their concerns about consequences for their family and implications for employment in the longer term.

From a patient perspective, the aspiration for complete wound healing was a major focus of all those interviewed. Healing was largely linked to return to some semblance of life prior to surgery, and was considered a sign that the body was returning to ‘normality’. This focus on healing as a key outcome agrees with previous findings from interviews with 33 patients with a range of complex wounds, including leg ulcers, foot ulcers and surgical wounds. 27 Here, most people, again, said that being healed or ‘cured’ was their main goal, as did eight participants with complex wounds who, when responding to the question ‘what did you most want from treatment?’, reported that they most wanted the wound to heal. 46

Health professionals’ management of patient expectations is crucial to the patient experience. We know from our cohort study that, although the median time to healing was around 3 months, some people would live with a SWHSI for significantly longer than this. We heard how comments from health-care professionals regarding healing and the condition of their wound had profound impacts on patients. Positive feedback was a boost for morale and sustained the patient’s hope for healing, whereas negative remarks adversely affected the patient’s general outlook. Conflicting information led to feelings of confusion and consternation in patients. Even quite casual remarks from health-care professionals could have a profound impact, which has been noted in other recent research on patients with complex wounds. 86 Patients’ expectations for wound healing may often appear unrealistic, yet clinicians need to manage these expectations within a framework that allows patients some measure of hope for healing, while avoiding the arousal of ‘false hope’, which may result in feelings of disappointment, disillusionment and distrust, which undermine professional–patient relationships. 46 Open, non-healing wounds that endure, such as SWHSIs, are associated with the ‘forever healing’ process, characterised by a constant need for treatment and care and a diminished quality of life, as described in patients with venous, diabetic and pressure ulceration. 47–51,53,87 This is challenging for clinicians, who must communicate uncertainty regarding wound progress and likely treatment outcomes without raising false hope or inducing a ‘spiral of hopelessness’ in patients. 51

Given the severity of impact that these wounds have on patients’ well-being, it is not clear whether or not psychological interventions may be useful in helping patients with hard-to-heal wounds to accept and adapt to their non-healing wound. Our findings also point to the need for improvements in communication with health-care professionals concerning the slow healing processes associated with SWHSIs; further research is required to investigate how, when and by whom information should be conveyed to patients with these types of wounds. Study (nurse) participants also highlighted the need for patients to receive written, as well as verbal, information, including information about signs and symptoms of infection and what action to take should these occur.

Strengths of the research

A key strength of this research is the new information that has been captured and reported on this SWHSI patient population. Prior to this research, we did not know the prevalence of SWHSIs, the surgeries involved, how many SWHSIs were planned compared with how many formed spontaneously, how costly these wounds are to the health service, how best to treat these wounds and how best we might direct future research on SWHSIs. There was also an absence of rigorous data regarding SWHSI management in the UK, how long they took to heal and what the impact of these wounds is on patients and their families. This research has provided this information for one geographical area of the UK (Yorkshire and the Humber).

We present data and conclusions that address many of the uncertainties that were faced at the start of the work, which we aimed to address using the methodologies described here. This work should provide a solid foundation for the design and planning of further research in the field.

We have employed robust epidemiological, analytical and qualitative methodologies, as required. By conducting an inception cohort study (as opposed to a prevalence cohort study), we were able to obtain accurate estimates of time to event data on outcomes for this SWHSI patient group; we also obtained a full picture of treatments received over the natural history of the wound. Although a prevalence cohort would have allowed higher recruitment figures, it would have provided far less clarity on crucial outcomes, such as time to healing. We were unable to rely on retrospective extraction of routinely collected data on wound treatments and outcomes, as systematically collected data, especially in the community, are limited. Thus, obtaining robust data, such as we have, requires data collection to be embedded in an appropriately designed primary study from the inception of the wound.

Limitations of the research

Our cohort study was conducted in only two centres in the UK and we therefore acknowledge that practice may vary across different centres and that the prevalence rates observed may not reflect those observed across the UK.

We have noted previously that the generalisability of findings of the cohort study may have been reduced by the need for consent, which removes some of the patient group from the study group. Our cross-sectional survey findings reassured us, however, as there were no major differences in key demographic features, although more wounds in cohort participants were planned to be left open before surgery. Those patients treated with NPWT in the cohort study were found to differ from those who were not, therefore indicating potential treatment selection. Interviews with clinicians helped to explore how NPWT may be allocated; however, this did not provide a definitive explanation for treatment decisions.

The nature of the cross-sectional survey may have resulted in some cases of SWHSIs not being reported, resulting in an underestimation of treated SWHSI prevalence. The number of responses received was as we expected, and so we are confident that the number of missed wounds was low and not systematic, probably due to publicity of the survey and support provided for nurses to complete study activity.

Within the cohort study, 73 wounds (18.6%) did not heal by the end of the study follow-up period. Time to healing was used as the primary outcome, given that this is an important and recommended outcome in wounds research. However, when using this outcome, it is acknowledged that there will inevitably be some participants who do not heal by the end of the follow-up time point. We acknowledge that the lack of healing data for these participants may have had an impact on the robustness of the findings; however, we expect this to be minimal, given the small number of participants this affected.

To meet the objective of our research programme, we opted to take a broad approach and collected data on a wide range of SWHSIs. This means that we have captured data on the heterogeneity of the wound type, but this also results in more limited data with which to investigate subgroups of SWHSIs in more detail, and this may be the focus of future work.

We present findings on the relative treatment effects of NPWT using observational data, given that there was a lack of RCT data available on relative effects of NPWT on SWHSIs. It is widely acknowledged that experimental data with groups formed by randomisation provide the least biased estimates of treatment effects. We implemented use of advanced adjustment approaches to try and reduce bias as much as possible, for both known (e.g. factors identified as prognostic for wound healing such as wound size, previous wound history or level of tissue involvement) and unknown confounders. However, even with adjustment, there is still the potential for unresolved confounding to affect the results and reduces confidence in them, leading to calls for definitive evidence from a RCT.

The relative treatment effects of NPWT were evaluated only on the healing of SWHSIs and so could not account for other direct effects on HRQoL (e.g. wound management). Again, these limitations may benefit from further assessment in a RCT.

The qualitative interviews conducted as part of this research programme identified a diverse range of views from both patients and clinicians. It is, however, noted that only a limited number of interviews were conducted with both clinicians (12 clinicians comprising seven nurses and five surgeons) and patients, which may limit the conclusions drawn. Interviews with both patients and clinicians continued until data saturation was achieved, thus ensuring comprehensive data. Further qualitative research may, however, be warranted to build on these findings.

Implications for practice

Findings from this research indicate that SWHSIs are relatively common, at least within the Yorkshire and the Humber region, UK (4.1 per 10,000 population), and such wounds frequently arise following colorectal, plastic or vascular surgery.

Data suggest that wounds will demonstrate different healing trajectories. Wounds with a large surface area, contaminated wounds (at the point of surgery) and infection at any time were found to predict slow healing. Furthermore, wound location and patient comorbidity may have an impact on wound healing trajectory.

This research has identified the vast range of treatments in use for SWHSIs and has identified increasing use of NPWT as a treatment during the wound healing pathway (rising from 6% to 29% over the course of approximately 3 years). Despite increasing use of this treatment within the NHS, RCT evidence supporting the use of this treatment for SWHSIs is sparse and of low quality. Our results indicate that NPWT has a negative impact on healing and is not cost-effective. However, as our results are based solely on observational data and, even after thorough adjustment, there may be unresolved confounding, the potential for which may limit confidence in the research findings.

Implications for research

This research signals the importance of, scope of, feasibility of and opportunity for further research on SWHSIs. As is the case across the wound care field, there are few good data on the prognostic factors for healing and on which factors may be amenable to treatment to promote better outcomes. NPWT, as with other medical devices in wound care, has been adopted widely, with relatively little evidence to support its use. If decision-makers and funders call for definitive evidence derived from a RCT, the design of such a RCT would need to be carefully considered, based on data presented here. The overall population of those with SWHSIs is too heterogeneous for inclusion into a single trial and we would suggest that future research should focus on specific groups. Although people with open surgical wounds after colorectal surgery formed our largest subpopulation, careful engagement with colorectal surgeons and patients would be required for a full trial in this patient population given the difficulties and barriers outlined in the pilot trial.

Careful consideration also needs to be given to the outcomes measured in a full trial. We focused in this research on healing, and maintain, based on the findings of patient interviews, that this is a key outcome for future research. However, it is important to note that if NPWT is not cost-effective for healing, it may still offer worthwhile advantages for patients and health services, which need to be balanced against disbenefits and costs. Impacts of NPWT on outcomes such as infection and reoperation should also be considered, as should patients’ view of the treatment. The type of patient group recruited and the outcomes of interest will all influence the duration of follow-up of any planned study.

In terms of how NPWT is evaluated, investigators must carefully consider the level of pragmatism that will be employed in any future trial. 88 There is a range of NPWT machines available for use, including those that use gauze dressings, foam dressings, single-use machines and repeat-use devices. There is no good evidence of any differences in the clinical effectiveness or cost-effectiveness of different machines, thus the trial design choice of whether to mandate use of a specific machine or allow sites to use their current NPWT provision will be down to the investigator. Although use of a single device will reduce the ‘noise’ in an evaluation, it is likely to limit the appeal of involvement to potential sites, as well as the potential generalisability of data. Thus, a pragmatic approach will arguably reflect effectiveness findings as they might be seen in the NHS and also make a large study more feasible. The same is true in terms of NPWT usage protocols (e.g. levels of pressure and cycle length), as well as how NPWT is used as part of the treatment pathway. The more prescriptive a future study is, the less pragmatic and feasible it may become but there would be less ‘noise’ in the findings.

Similar intervention issues also need to be considered in terms of the comparator in any future study. We know that SWHSI patients receive multiple dressings and there is no high-quality evidence that one dressing type is better than another for SWHSIs or any other complex wound type. 89 Use of a specific dressing type, such as hydrofibre, could be explored in a trial, but large deviations from use of a single dressing over the duration of a patient’s SWHSI would be expected.

Blinded outcome assessment is crucial for studies with subjective outcomes, such as healing and infection. 90 We have demonstrated here that blinded outcome assessment in a NPWT trial in people with SWHSIs is possible, but protocols and equipment that ensure high-quality images are required. We also note the importance of taking photographs beyond the point at which the unblinded investigator considers a wound healed, so that a later healing date can be recorded by a blinded assessor should they disagree with the unblinded assessment.

Careful consideration should be given to use of data collection via text message in future trials investigating treatments for SWHSIs. Although this method has been identified as a simple, inexpensive, valid and acceptable method of data collection in previous studies,91–93 our pilot, feasibility RCT suggested that data collection via text messaging was more successful in younger patients (respondents were, on average, almost 10 years younger than non-respondents). Other studies, which have successfully used text messaging for data collection have also included younger populations ranging from 22.0 (SD 1.47) years93 to 44.0 (SD 13.4) years of age. 91 Future trials of SWHSI treatments should therefore consider the demographics of the target patient population prior to inclusion of such methods, to ensure that if utilised, data collection is likely to be successful and so provide sufficient data for analysis.

Questions for future research

We consider key research questions raised by this programme of research to be:

• Which treatments are clinically effective and cost-effective for SWHSIs for all patients or for particular patient subgroups?

• Can particular prognostic factors predict time to healing of SWHSIs?

• Do psychosocial interventions have the potential to improve quality of life in people with hard-to-heal SWHSIs?

• What are the current care pathways for people with SWHSIs, how do they vary nationally and can they be optimised to improve efficiencies and outcomes?

• Is the development of evidence-based practice guidelines for the management of SWHSI patients possible, in order to benefit and inform patients, clinicians and NHS commissioning?

Contributions of authors

Ian Chetter (Professor, Vascular Surgery) was the chief investigator; led the research programme and chaired the Programme Management Group; and led workstreams 1 and 4.

Catherine Arundel (Research Fellow, Health Research and Trials) contributed to the design, conduct, analysis, interpretation and reporting of workstream 4.

Kerry Bell (Statistician, Health Research and Trials) undertook the statistical analysis and interpretation for workstream 1.

Hannah Buckley (Statistician, Health Research and Trials) undertook the statistical analysis and interpretation and advised on conduct for workstream 1, and advised on the design, conduct and statistical analysis for workstream 4.

Karl Claxton (Professor, Economics) oversaw all aspects of workstream 2 (design, conduct, analysis, interpretation and reporting).

Belen Corbacho Martin (Health Economist, Health Research and Trials) undertook the economic analysis and interpretation for workstream 4.

Nicky Cullum (Professor, Nursing) contributed to the conception, design, conduct, analysis and reporting of all workstreams and provided input to the programme management and strategy.

Jo Dumville (Senior Lecturer, Health Sciences) contributed to the design, conduct, analysis and reporting of all workstreams.

Caroline Fairhurst (Statistician, Health Research and Trials) undertook the statistical analysis for workstream 4.

Eileen Henderson (Assistant to Medical Director, NHS Needs) ensured that all workstreams met NHS needs and were relevant to NHS decision uncertainty.

Karen Lamb (Research Co-ordinator, Wound Research) contributed to the design and conduct of workstream 1 and the design, conduct, analysis and reporting of workstream 4.

Judith Long (Project Manager, Vascular Surgery Research) led and undertook qualitative data collection, analysis and reporting for workstream 4.

Dorothy McCaughan (Research Fellow, Health Research) led and undertook qualitative data collection, analysis and reporting for workstream 3.

Elizabeth McGinnis (Research Fellow, Wound Research) contributed to the design, conduct, analysis and reporting of workstreams 1 and 4.

Angela Oswald (Tissue Viability Matron, Wound Care and Research) provided clinical leadership and expertise in relation to NPWT.

Pedro Saramago Goncalves (Research Fellow, Health Economics) undertook the analyses in workstream 2 and contributed to the design, conduct, interpretation and reporting of workstream 2.

Laura Sheard (Senior Research Fellow, Health Research) undertook qualitative data collection and analysis for workstream 3.

Marta O Soares (Senior Research Fellow, Health Economics) supervised all aspects of workstream 2 (design, conduct, analysis, interpretation and reporting) and contributed to the design, conduct, analysis and reporting of workstreams 1 and 4.

Nikki Stubbs (Clinical Pathway Lead, Wound Research) contributed to the design, conduct, analysis and reporting of workstreams 1 and 4.

David Torgerson (Professor, Health Research and Trials) contributed to the management of the programme of work and the design, conduct, analysis, interpretation and reporting of workstreams 1 and 4.

Nicky Welton (Reader, Statistics and Health Economic Modelling) oversaw the design, interpretation and reporting of the analyses in workstream 2.

Publications

Data-sharing statement

All data requests should be submitted to the corresponding author for consideration. Access to anonymised data may be granted following review.

Patient data

This work uses data provided by patients and collected by the NHS as part of their care and support. Using patient data is vital to improve health and care for everyone. There is huge potential to make better use of information from people’s patient records, to understand more about disease, develop new treatments, monitor safety, and plan NHS services. Patient data should be kept safe and secure, to protect everyone’s privacy, and it’s important that there are safeguards to make sure that it is stored and used responsibly. Everyone should be able to find out about how patient data are used. #datasaveslives You can find out more about the background to this citation here: https://understandingpatientdata.org.uk/data-citation.

Disclaimers

This report presents independent research funded by the National Institute for Health Research (NIHR). The views and opinions expressed by authors in this publication are those of the authors and do not necessarily reflect those of the NHS, the NIHR, CCF, NETSCC, PGfAR or the Department of Health and Social Care. If there are verbatim quotations included in this publication the views and opinions expressed by the interviewees are those of the interviewees and do not necessarily reflect those of the authors, those of the NHS, the NIHR, NETSCC, the PGfAR programme or the Department of Health and Social Care.

Search strategy: dressings

We searched the following electronic databases:

• Cochrane Wounds Group Specialised Register (date range searched: inception to 10 January 2012)

• Cochrane Central Register of Controlled Trials (date range searched: inception to The Cochrane Library, 2012, Issue 1)

• Ovid MEDLINE (date range searched: 1946 to 10 January 2012)

• Ovid EMBASE (date range searched: 1974 to 10 January 2012)

• EBSCOhost Cumulative Index to Nursing and Allied Health Literature (CINAHL) (date range searched: 1982 to 10 January 2012).

Date searched: 10 January 2012.

Search strategy: cohort studies

We searched the following electronic databases:

• Ovid MEDLINE (date range searched: 1946 to 31 December 2013)

• Ovid EMBASE (date range searched: 1974 to 31 December 2013)

• EBSCOhost CINAHL (date range searched: 1982 to 31 December 2013).

Date searched: 31 December 2013.

Search strategy: economic and health utility studies

We searched the following electronic databases:

• Ovid MEDLINE (date range searched: 1946 to 31 December 2013)

• Ovid EMBASE (date range searched: 1974 to 31 December 2013)

• EBSCOhost CINAHL (date range searched: 1982 to 31 December 2013)

• NHS Economic Evaluation Database (date range searched: inception to 2013, Issue 12).

Date searched: 31 December 2013.