R Hernández

Systematic review of the clinical effectiveness and cost-effectiveness of oesophageal Doppler monitoring in critically ill and high-risk surgical patients

OBJECTIVES To assess the effectiveness and cost-effectiveness of oesophageal Doppler monitoring (ODM) compared with conventional clinical assessment and other methods of monitoring cardiovascular function. DATA SOURCES Electronic databases and relevant websites from 1990 to May 2007 were searched. REVIEW METHODS This review was based on a systematic review conducted by the US Agency for Healthcare Research and Quality (AHRQ), supplemented by evidence from any additional studies identified. Comparator interventions for effectiveness were standard care, pulmonary artery catheters (PACs), pulse contour analysis monitoring and lithium or thermodilution cardiac monitoring. Data were extracted on mortality, length of stay overall and in critical care, complications and quality of life. The economic assessment evaluated strategies involving ODM compared with standard care, PACs, pulse contour analysis monitoring and lithium or thermodilution cardiac monitoring. RESULTS The AHRQ report contained eight RCTs and was judged to be of high quality overall. Four comparisons were reported: ODM plus central venous pressure (CVP) monitoring plus conventional assessment vs CVP monitoring plus conventional assessment during surgery; ODM plus conventional assessment vs CVP monitoring plus conventional assessment during surgery; ODM plus conventional assessment vs conventional assessment during surgery; and ODM plus CVP monitoring plus conventional assessment vs CVP monitoring plus conventional assessment postoperatively. Five studies compared ODM plus CVP monitoring plus conventional assessment with CVP monitoring plus conventional assessment during surgery. There were fewer deaths [Peto odds ratio (OR) 0.13, 95% CI 0.02-0.96], fewer major complications (Peto OR 0.12, 95% CI 0.04-0.31), fewer total complications (fixed-effects OR 0.43, 95% CI 0.26-0.71) and shorter length of stay (pooled estimate not presented, 95% CI -2.21 to -0.57) in the ODM group. The results of the meta-analysis of mortality should be treated with caution owing to the low number of events and low overall number of patients in the combined totals. Three studies compared ODM plus conventional assessment with conventional assessment during surgery. There was no evidence of a difference in mortality (fixed-effects OR 0.81, 95% CI 0.23-2.77). Length of hospital stay was shorter in all three studies in the ODM group. Two studies compared ODM plus CVP monitoring plus conventional assessment vs CVP monitoring plus conventional assessment in critically ill patients. The patient groups were quite different (cardiac surgery and major trauma) and neither study, nor a meta-analysis, showed a statistically significant difference in mortality (fixed-effects OR 0.84, 95% CI 0.41-1.70). Fewer patients in the ODM group experienced complications (OR 0.49, 95% CI 0.30-0.81) and both studies reported a statistically significant shorter median length of hospital stay in that group. No economic evaluations that met the inclusion criteria were identified from the existing literature so a series of balance sheets was constructed. The results show that ODM strategies are likely to be cost-effective. CONCLUSIONS More formal economic evaluation would allow better use of the available data. All identified studies were conducted in unconscious patients. However, further research is needed to evaluate new ODM probes that may be tolerated by awake patients. Given the paucity of the existing economic evidence base, any further primary research should include an economic evaluation or should provide data suitable for use in an economic model.

A randomised controlled trial of the use of aciclovir and/or prednisolone for the early treatment of Bell’s palsy: the BELLS study

OBJECTIVE To determine whether oral prednisolone or aciclovir, used separately or in combination, early in the course of Bells palsy, improves the chances of recovery at 3 and 9 months. DESIGN A 2 x 2 factorial randomised double-blind trial. Patients were randomly assigned to treatment by an automated telephone service using a permuted block randomisation technique with block sizes of four or eight, and no stratification. SETTING Mainland Scotland, with referrals mainly from general practice to 17 hospital trial sites. PARTICIPANTS Adults (aged 16 years or older) with unilateral facial nerve weakness of no identifiable cause presenting to primary care, the emergency department or NHS24 within 72 hours of symptom onset. INTERVENTIONS Patients were randomised to receive active preparations or placebo for 10 days: (1) prednisolone (50 mg per day, 2 x 25-mg capsules) and aciclovir (2000 mg per day, 5 x 400-mg capsules); (2) prednisolone and placebo (lactose, indistinguishable); (3) aciclovir and placebo; and (4) placebo and placebo. OUTCOME MEASURES The primary outcome was recovery of facial function assessed by the House-Brackmann scale. Secondary outcomes included health status, pain, self-perceived appearance and cost-effectiveness. RESULTS Final outcomes were available for 496 patients, balanced for gender; mean age 44 years; initial facial paralysis moderate to severe. One half of patients initiated treatment within 24 hours of onset of symptoms, one-third within 24-48 hours and the remainder within 48-72 hours. Of the completed patients, 357 had recovered by 3 months and 80 at 9 months, leaving 59 with a residual deficit. There were significant differences in complete recovery at 3 months between the prednisolone comparison groups (83.0% for prednisolone, 63.6% for no prednisolone, a difference of + 19.4%; 95% confidence interval (CI): + 11.7% to + 27.1%, p < 0.001). The number needed to treat (NNT) in order to achieve one additional complete recovery was 6 (95% CI: 4 to 9). There was no significant difference between the aciclovir comparison groups (71.2% for aciclovir and 75.7% for no aciclovir). Nine-month assessments of patients recovered were 94.4% for prednisolone compared with 81.6% for no prednisolone, a difference of + 12.8% (95% CI: + 7.2% to + 18.4%, p < 0.001); the NNT was 8 (95% CI: 6 to 14). Proportions recovered at 9 months were 85.4% for aciclovir and 90.8% for no aciclovir, a difference of -5.3%. There was no significant prednisolone-aciclovir interaction at 3 months or at 9 months. Outcome differences by individual treatment (the four-arm model) showed significant differences. At 3 months the recovery rate was 86.3% in the prednisolone treatment group, 79.7% in the aciclovir-prednisolone group, 64.7% in the placebo group and 62.5% in the aciclovir group. At 9 months the recovery rates were respectively 96.1%, 92.7%, 85.3% and 78.1%. The increase in recovery rate conferred by the addition of prednisolone (both for prednisolone over placebo and for aciclovir-prednisolone over aciclovir) is highly statistically significant (p < 0.001). There were no significant differences in secondary measures apart from Health Utilities Index Mark 3 (HUI3) at 9 months in those treated with prednisolone. CONCLUSIONS This study provided robust evidence to support the early use of oral prednisolone in Bells palsy as an effective treatment which may be considered cost-effective. Treatment with aciclovir, either alone or with steroids, had no effect on outcome.

The Clinical Effectiveness and Cost-Effectiveness of Different Surveillance Mammography Regimens After the Treatment for Primary Breast Cancer: Systematic Reviews, Registry Database Analyses and Economic Evaluation

BACKGROUND Following primary breast cancer treatment, the early detection of ipsilateral breast tumour recurrence (IBTR) or ipsilateral secondary cancer in the treated breast and detection of new primary cancers in the contralateral breast is beneficial for survival. Surveillance mammography is used to detect these cancers, but the optimal frequency of surveillance and the length of follow-up are unclear. OBJECTIVES To identify feasible management strategies for surveillance and follow-up of women after treatment for primary breast cancer in a UK setting, and to determine the effectiveness and cost-effectiveness of differing regimens. METHODS A survey of UK breast surgeons and radiologists to identify current surveillance mammography regimens and inform feasible alternatives; two discrete systematic reviews of evidence published from 1990 to mid 2009 to determine (i) the clinical effectiveness and cost-effectiveness of differing surveillance mammography regimens for patient health outcomes and (ii) the test performance of surveillance mammography in the detection of IBTR and metachronous contralateral breast cancer (MCBC); statistical analysis of individual patient data (West Midlands Cancer Intelligence Unit Breast Cancer Registry and Edinburgh data sets); and economic modelling using the systematic reviews results, existing data sets, and focused searches for specific data analysis to determine the effectiveness and cost-utility of differing surveillance regimens. RESULTS The majority of survey respondents initiate surveillance mammography 12 months after breast-conserving surgery (BCS) (87%) or mastectomy (79%). Annual surveillance mammography was most commonly reported for women after BCS or after mastectomy (72% and 53%, respectively). Most (74%) discharge women from surveillance mammography, most frequently 10 years after surgery. The majority (82%) discharge from clinical follow-up, most frequently at 5 years. Combining initiation, frequency and duration of surveillance mammography resulted in 54 differing surveillance regimens for women after BCS and 56 for women following mastectomy. The eight studies included in the clinical effectiveness systematic review suggest surveillance mammography offers a survival benefit compared with a surveillance regimen that does not include surveillance mammography. Nine studies were included in the test performance systematic review. For routine IBTR detection, surveillance mammography sensitivity ranged from 64% to 67% and specificity ranged from 85% to 97%. For magnetic resonance imaging (MRI), sensitivity ranged from 86% to 100% and specificity was 93%. For non-routine IBTR detection, sensitivity and specificity for surveillance mammography ranged from 50% to 83% and from 57% to 75%, respectively, and for MRI from 93% to 100% and from 88% to 96%, respectively. For routine MCBC detection, one study reported sensitivity of 67% and specificity of 50% for both surveillance mammography and MRI, although this was a highly select population. Data set analysis showed that IBTR has an adverse effect on survival. Furthermore, women experiencing a second tumour measuring >20 mm in diameter were at a significantly greater risk of death than those with no recurrence or those whose tumour was <10 mm in diameter. In the base-case analysis, the strategy with the highest net benefit, and most likely to be considered cost-effective, was surveillance mammography alone, provided every 12 months at a societal willingness to pay for a quality-adjusted life-year of either £20,000 or £30,000. The incremental cost-effectiveness ratio for surveillance mammography alone every 12 months compared with no surveillance was £4727. LIMITATIONS Few studies met the review inclusion criteria and none of the studies was a randomised controlled trial. The limited and variable nature of the data available precluded any quantitative analysis. There was no useable evidence contained in the Breast Cancer Registry database to assess the effectiveness of surveillance mammography directly. The results of the economic model should be considered exploratory and interpreted with caution given the paucity of data available to inform the economic model. CONCLUSIONS Surveillance is likely to improve survival and patients should gain maximum benefit through optimal use of resources, with those women with a greater likelihood of developing IBTR or MCBC being offered more comprehensive and more frequent surveillance. Further evidence is required to make a robust and informed judgement on the effectiveness of surveillance mammography and follow-up. The utility of national data sets could be improved and there is a need for high-quality, direct head-to-head studies comparing the diagnostic accuracy of tests used in the surveillance population. FUNDING The National Institute for Health Research Health Technology Assessment programme.

Discrete Choice Experiments

Discrete choice experiments (DCEs) were introduced into health economics in the early 1990s to ensure a person-centred approach to economic evaluation. While economic evaluation had focused on clinical outcomes, using measures such as quality-adjusted life years (QALYs), DCEs valued broader aspects of care, including how the care is delivered and non-health outcomes. DCEs are an attribute-based measure of value. They can be used to address a range of questions faced by decision-makers, including valuing patient experiences alongside clinical outcomes, valuing health states and predicting uptake/acceptability of new services. DCEs provide potentially useful information within a health technology assessment (HTA) decision-making context—what characteristics (attributes) are important, how important these are, trade-offs between characteristics, monetary measures of value and predictions of take-up rates and acceptability of interventions/medicines/services. This chapter provides an introduction to DCEs, summarising the method and discussing how they can inform the HTA process. The method is illustrated using a DCE within a HTA looking at surveillance of ocular hypertension. We discuss methodological challenges within a HTA context and areas for future research.

Romiplostim for the treatment of chronic immune or idiopathic thrombocytopenic purpura: a single technology appraisal.

This paper presents a summary of the evidence review group (ERG) report into the clinical and cost-effectiveness of romiplostim for the treatment of adults with chronic immune or idiopathic thrombocytopenic purpura (ITP) based upon a review of the manufacturers submission to the National Institute for Health and Clinical Excellence (NICE) as part of the single technology appraisal (STA) process. The submissions evidence came from two relatively high-quality randomised controlled trials (RCTs). The ERG found no evidence that any important data were missed or that data extraction was inaccurate. In both RCTs more patients in the romiplostim than in the placebo group achieved a durable platelet response [non-splenectomised patients: romiplostim 25/41 (61%), placebo 1/21 (5%), odds ratio (OR) 24.45, 95% confidence interval (CI) 3.34 to 179.18; splenectomised patients: romiplostim 16/42 (38%), placebo 0/21 (0%), OR 8.5 (95% CI 1.15 to 372)] and an overall platelet response [non-splenectomised patients: romiplostim 36/41 (88%), placebo 3/21 (14%), OR 34.74, 95% CI 7.77 to 155.38; splenectomised patients: romiplostim 33/42 (79%), placebo 0/21 (0%), OR 16.6 (95% CI 2.37 to 706]. The difference in mean period with a platelet response was 13.9 weeks (95% CI 10.5 to 17.4) in favour of romiplostim in the RCT of non-splectomised patients and 12.1 weeks (95% CI 8.7 to 15.6) in favour of romiplostim in the RCT of splectomised patients. The manufacturers economic model evaluated the cost-effectiveness of romiplostim compared with standard care. The ERG had concerns about the way the decision problem was addressed in the economic model and about the non-adjustment of findings for confounding factors. In non-splenectomised patients, using romiplostim as a first option treatment, the base-case incremental cost-effectiveness ratio (ICER) was 14,840 pounds per quality-adjusted life-year (QALY). In splenectomised patients the ICER was 14,655 pounds per QALY. Additional sensitivity analyses performed by the ERG identified two issues of importance: whether individuals entered the model on watch and rescue or on active therapy in the comparator arm (ICER 21,674 pounds per QALY for non-splenectomised patients, 29,771 pounds per QALY for splenectomised patients); whether it was assumed that any unused medicine would be wasted. Combining all of the separate sensitivity analyses, and assuming that watch and rescue was not the first-line treatment, increased the ICERs further (non-splenectomised 37,290 pounds per QALY; splenectomised 131,017 pounds per QALY). In conclusion, the manufacturers submission and additional work conducted by the ERG suggest that romiplostim has short-term efficacy for the treatment of ITP, but there is no robust evidence on long-term effectiveness or cost-effectiveness of romiplostim compared with relevant comparators.

Optical Coherence Tomography for the Monitoring of Neovascular Age-Related Macular Degeneration: A Systematic Review

TOPIC To compare the accuracy of optical coherence tomography (OCT) with alternative tests for monitoring neovascular age-related macular degeneration (nAMD) and detecting disease activity among eyes previously treated for this condition. CLINICAL RELEVANCE Traditionally, fundus fluorescein angiography (FFA) has been considered the reference standard to detect nAMD activity, but FFA is costly and invasive. Replacement of FFA by OCT can be justified if there is a substantial agreement between tests. METHODS Systematic review and meta-analysis. The index test was OCT. The comparator tests were visual acuity, clinical evaluation (slit lamp), Amsler chart, color fundus photographs, infrared reflectance, red-free images and blue reflectance, fundus autofluorescence imaging, indocyanine green angiography (ICGA), preferential hyperacuity perimetry, and microperimetry. We searched the following databases: MEDLINE, MEDLINE In-Process, EMBASE, Biosis, Science Citation Index, the Cochrane Library, Database of Abstracts of Reviews of Effects, MEDION, and the Health Technology Assessment database. The last literature search was conducted in March 2013. We used the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) to assess risk of bias. RESULTS We included 8 studies involving more than 400 participants. Seven reported the performance of OCT (3 time-domain [TD] OCT, 3 spectral-domain [SD] OCT, 1 both types) and 1 reported the performance of ICGA in the detection of nAMD activity. We did not find studies directly comparing tests in the same population. The pooled sensitivity and specificity of TD OCT and SD OCT for detecting active nAMD was 85% (95% confidence interval [CI], 72%-93%) and 48% (95% CI, 30%-67%), respectively. One study reported ICGA with sensitivity of 75.9% and specificity of 88.0% for the detection of active nAMD. Half of the studies were considered to have a high risk of bias. CONCLUSIONS There is substantial disagreement between OCT and FFA findings in detecting active disease in patients with nAMD who are being monitored. Both methods may be needed to monitor patients comprehensively with nAMD.

Screening for open angle glaucoma: Systematic Review of Cost-effectiveness Studies

PurposeTo systematically review current evidence on the cost-effectiveness of screening strategies for open angle glaucoma (OAG). Materials and MethodsStudies that reported both costs and outcomes of alternative screening strategies for OAG were identified by a highly sensitive search of electronic databases (eg, MEDLINE, EMBASE, NHS EED, HTA Database), last search December 2005. Data on costs regarding cases and years of visual impairment prevented, cases of blindness prevented, and cases of OAG detected were extracted. Incremental cost-effectiveness ratios were calculated using data provided in the included studies. ResultsFour studies met the inclusion criteria. The latest of these was published in 1997. The screening tests and treatments reported in these studies are now not considered to be best practice. Furthermore, data were not reported in sufficient detail to reinterpret the results of the studies in terms of a common outcome measure. Finally, these studies suffered from methodologic weaknesses that further limit their usefulness for decision making. ConclusionsCurrently, there is insufficient economic evidence on which to base recommendations regarding screening for OAG. New technologies, potentially suitable as screening devices, and new treatments are available. Further research, both in terms of economic models and conduct of clinical trials with concurrent economic evaluation, may help inform policy makers regarding cost-effectiveness and acceptability of screening for OAG.

Systematic review of economic evaluations of laparoscopic surgery for colorectal cancer.

Objective  Colorectal cancer is one of the most common cancers and the standard surgical treatment for this cancer is open resection (OS), but laparoscopic surgery (LS) may be an alternative treatment. In 2000, a Health Technology Assessment (HTA) review found little evidence on costs and cost‐effectiveness in comparing the two methods. The evidence base has since expanded and this study systematically reviews the economic evaluations on the subject published since 2000.

Optical coherence tomography for the diagnosis, monitoring and guiding of treatment for neovascular age-related macular degeneration: a systematic review and economic evaluation.

BACKGROUND Age-related macular degeneration is the most common cause of sight impairment in the UK. In neovascular age-related macular degeneration (nAMD), vision worsens rapidly (over weeks) due to abnormal blood vessels developing that leak fluid and blood at the macula. OBJECTIVES To determine the optimal role of optical coherence tomography (OCT) in diagnosing people newly presenting with suspected nAMD and monitoring those previously diagnosed with the disease. DATA SOURCES Databases searched: MEDLINE (1946 to March 2013), MEDLINE In-Process & Other Non-Indexed Citations (March 2013), EMBASE (1988 to March 2013), Biosciences Information Service (1995 to March 2013), Science Citation Index (1995 to March 2013), The Cochrane Library (Issue 2 2013), Database of Abstracts of Reviews of Effects (inception to March 2013), Medion (inception to March 2013), Health Technology Assessment database (inception to March 2013). REVIEW METHODS Types of studies: direct/indirect studies reporting diagnostic outcomes. INDEX TEST time domain optical coherence tomography (TD-OCT) or spectral domain optical coherence tomography (SD-OCT). COMPARATORS clinical evaluation, visual acuity, Amsler grid, colour fundus photographs, infrared reflectance, red-free images/blue reflectance, fundus autofluorescence imaging, indocyanine green angiography, preferential hyperacuity perimetry, microperimetry. Reference standard: fundus fluorescein angiography (FFA). Risk of bias was assessed using quality assessment of diagnostic accuracy studies, version 2. Meta-analysis models were fitted using hierarchical summary receiver operating characteristic curves. A Markov model was developed (65-year-old cohort, nAMD prevalence 70%), with nine strategies for diagnosis and/or monitoring, and cost-utility analysis conducted. NHS and Personal Social Services perspective was adopted. Costs (2011/12 prices) and quality-adjusted life-years (QALYs) were discounted (3.5%). Deterministic and probabilistic sensitivity analyses were performed. RESULTS In pooled estimates of diagnostic studies (all TD-OCT), sensitivity and specificity [95% confidence interval (CI)] was 88% (46% to 98%) and 78% (64% to 88%) respectively. For monitoring, the pooled sensitivity and specificity (95% CI) was 85% (72% to 93%) and 48% (30% to 67%) respectively. The FFA for diagnosis and nurse-technician-led monitoring strategy had the lowest cost (£ 39,769; QALYs 10.473) and dominated all others except FFA for diagnosis and ophthalmologist-led monitoring (£ 44,649; QALYs 10.575; incremental cost-effectiveness ratio £ 47,768). The least costly strategy had a 46.4% probability of being cost-effective at £ 30,000 willingness-to-pay threshold. LIMITATIONS Very few studies provided sufficient information for inclusion in meta-analyses. Only a few studies reported other tests; for some tests no studies were identified. The modelling was hampered by a lack of data on the diagnostic accuracy of strategies involving several tests. CONCLUSIONS Based on a small body of evidence of variable quality, OCT had high sensitivity and moderate specificity for diagnosis, and relatively high sensitivity but low specificity for monitoring. Strategies involving OCT alone for diagnosis and/or monitoring were unlikely to be cost-effective. Further research is required on (i) the performance of SD-OCT compared with FFA, especially for monitoring but also for diagnosis; (ii) the performance of strategies involving combinations/sequences of tests, for diagnosis and monitoring; (iii) the likelihood of active and inactive nAMD becoming inactive or active respectively; and (iv) assessment of treatment-associated utility weights (e.g. decrements), through a preference-based study. STUDY REGISTRATION This study is registered as PROSPERO CRD42012001930. FUNDING The National Institute for Health Research Health Technology Assessment programme.

Developing the clinical components of a complex intervention for a glaucoma screening trial: a mixed methods study

Background Glaucoma is a leading cause of avoidable blindness worldwide. Open angle glaucoma is the most common type of glaucoma. No randomised controlled trials have been conducted evaluating the effectiveness of glaucoma screening for reducing sight loss. It is unclear what the most appropriate intervention to be evaluated in any glaucoma screening trial would be. The purpose of this study was to develop the clinical components of an intervention for evaluation in a glaucoma (open angle) screening trial that would be feasible and acceptable in a UK eye-care service. Methods A mixed-methods study, based on the Medical Research Council (MRC) framework for complex interventions, integrating qualitative (semi-structured interviews with 46 UK eye-care providers, policy makers and health service commissioners), and quantitative (economic modelling) methods. Interview data were synthesised and used to revise the screening interventions compared within an existing economic model. Results The qualitative data indicated broad based support for a glaucoma screening trial to take place in primary care, using ophthalmic trained technical assistants supported by optometry input. The precise location should be tailored to local circumstances. There was variability in opinion around the choice of screening test and target population. Integrating the interview findings with cost-effectiveness criteria reduced 189 potential components to a two test intervention including either optic nerve photography or screening mode perimetry (a measure of visual field sensitivity) with or without tonometry (a measure of intraocular pressure). It would be more cost-effective, and thus acceptable in a policy context, to target screening for open angle glaucoma to those at highest risk but for both practicality and equity arguments the optimal strategy was screening a general population cohort beginning at age forty. Conclusions Interventions for screening for open angle glaucoma that would be feasible from a service delivery perspective were identified. Integration within an economic modelling framework explicitly highlighted the trade-off between cost-effectiveness, feasibility and equity. This study exemplifies the MRC recommendation to integrate qualitative and quantitative methods in developing complex interventions. The next step in the development pathway should encompass the views of service users.BackgroundGlaucoma is a leading cause of avoidable blindness worldwide. Open angle glaucoma is the most common type of glaucoma. No randomised controlled trials have been conducted evaluating the effectiveness of glaucoma screening for reducing sight loss. It is unclear what the most appropriate intervention to be evaluated in any glaucoma screening trial would be. The purpose of this study was to develop the clinical components of an intervention for evaluation in a glaucoma (open angle) screening trial that would be feasible and acceptable in a UK eye-care service.MethodsA mixed-methods study, based on the Medical Research Council (MRC) framework for complex interventions, integrating qualitative (semi-structured interviews with 46 UK eye-care providers, policy makers and health service commissioners), and quantitative (economic modelling) methods. Interview data were synthesised and used to revise the screening interventions compared within an existing economic model.ResultsThe qualitative data indicated broad based support for a glaucoma screening trial to take place in primary care, using ophthalmic trained technical assistants supported by optometry input. The precise location should be tailored to local circumstances. There was variability in opinion around the choice of screening test and target population. Integrating the interview findings with cost-effectiveness criteria reduced 189 potential components to a two test intervention including either optic nerve photography or screening mode perimetry (a measure of visual field sensitivity) with or without tonometry (a measure of intraocular pressure). It would be more cost-effective, and thus acceptable in a policy context, to target screening for open angle glaucoma to those at highest risk but for both practicality and equity arguments the optimal strategy was screening a general population cohort beginning at age forty.ConclusionsInterventions for screening for open angle glaucoma that would be feasible from a service delivery perspective were identified. Integration within an economic modelling framework explicitly highlighted the trade-off between cost-effectiveness, feasibility and equity. This study exemplifies the MRC recommendation to integrate qualitative and quantitative methods in developing complex interventions. The next step in the development pathway should encompass the views of service users.