Design and management considerations for control groups in hybrid effectiveness-implementation trials: Narrative review & case studies.

Hybrid effectiveness-implementation studies allow researchers to combine study of a clinical intervention's effectiveness with study of its implementation with the aim of accelerating the translation of evidence into practice. However, there currently exists limited guidance on how to design and manage such hybrid studies. This is particularly true for studies that include a comparison/control arm that, by design, receives less implementation support than the intervention arm. Lack of such guidance can present a challenge for researchers both in setting up but also in effectively managing participating sites in such trials. This paper uses a narrative review of the literature (Phase 1 of the research) and comparative case study of three studies (Phase 2 of the research) to identify common themes related to study design and management. Based on these, we comment and reflect on: (1) the balance that needs to be struck between fidelity to the study design and tailoring to emerging requests from participating sites as part of the research process, and (2) the modifications to the implementation strategies being evaluated. Hybrid trial teams should carefully consider the impact of design selection, trial management decisions, and any modifications to implementation processes and/or support on the delivery of a controlled evaluation. The rationale for these choices should be systematically reported to fill the gap in the literature.

Economic evaluation of the OSAC randomised controlled trial: oral corticosteroids for non-asthmatic adults with acute lower respiratory tract infection in primary care.

OBJECTIVE: To estimate the costs and outcomes associated with treating non-asthmatic adults (nor suffering from other lung-disease) presenting to primary care with acute lower respiratory tract infection (ALRTI) with oral corticosteroids compared with placebo. DESIGN: Cost-consequence analysis alongside a randomised controlled trial. Perspectives included the healthcare provider, patients and productivity losses associated with time off work. SETTING: Fifty-four National Health Service (NHS) general practices in England. PARTICIPANTS: 398 adults attending NHS primary practices with ALRTI but no asthma or other chronic lung disease, followed up for 28 days. INTERVENTIONS: 2× 20 mg oral prednisolone per day for 5 days versus matching placebo tablets. OUTCOME MEASURES: Quality-adjusted life years using the 5-level EuroQol-5D version measured weekly; duration and severity of symptom. Direct and indirect resources related to the disease and its treatment were also collected. Outcomes were measured for the 28-day follow-up. RESULTS: 198 (50%) patients received the intervention (prednisolone) and 200 (50%) received placebo. NHS costs were dominated by primary care contacts, higher with placebo than with prednisolone (£13.11 vs £10.38) but without evidence of a difference (95% CI £3.05 to £8.52). The trial medication cost of £1.96 per patient would have been recouped in prescription charges of £4.30 per patient overall (55% participants would have paid £7.85), giving an overall mean 'profit' to the NHS of £7.00 (95% CI £0.50 to £17.08) per patient. There was a quality adjusted life years gain of 0.03 (95% CI 0.01 to 0.05) equating to half a day of perfect health favouring the prednisolone patients; there was no difference in duration of cough or severity of symptoms. CONCLUSIONS: The use of prednisolone for non-asthmatic adults with ALRTI, provided small gains in quality of life and cost savings driven by prescription charges. Considering the results of the economic evaluation and possible side effects of corticosteroids, the short-term benefits may not outweigh the long-term harms. TRIAL REGISTRATION NUMBERS: EudraCT 2012-000851-15 and ISRCTN57309858; Pre-results.

What are patients' preferences for revision surgery after periprosthetic joint infection? A discrete choice experiment.

OBJECTIVES: Understanding patients' preferences for treatment is crucial to provision of good care and shared decisions, especially when more than one treatment option exists for a given condition. One such condition is infection of the area around the prosthesis after hip replacement, which affects between 0.4% and 3% of patients. There is more than one treatment option for this major complication, and our study aimed to assess the value that patients place on aspects of revision surgery for periprosthetic hip infection. DESIGN: We identified four attributes of revision surgery for periprosthetic hip infection. Using a discrete choice experiment (DCE), we measured the value placed on each attribute by 57 people who had undergone either one-stage or two-stage revision surgery for infection. SETTING: The DCE was conducted with participants from nine National Health Service hospitals in the UK. PARTICIPANTS: Adults who had undergone revision surgery for periprosthetic hip infection (N=57). RESULTS: Overall, the strongest preference was for a surgical option that resulted in no restrictions on engaging in valued activities after a new hip is fitted (ß=0.7). Less valued but still important attributes included a shorter time taken from the start of treatment to return to normal activities (6 months; ß=0.3), few or no side effects from antibiotics (ß=0.2), and having only one operation (ß=0.2). CONCLUSIONS: The results highlight that people who have had revision surgery for periprosthetic hip infection most value aspects of care that affect their ability to engage in normal everyday activities. These were the most important characteristics in decisions about revision surgery.

Parents' preferences for nursery care when children are unwell: a discrete choice experiment.

BACKGROUND: Pre-school children's daycare is associated with increased incidence of respiratory and diarrhoeal illnesses. While the incidence might be reduced if all unwell children were kept at home, parental employment pressures make this difficult when children are marginally unwell. METHODS: A discrete choice experiment (DCE) was conducted to identify what aspects of daycare policy and provision would affect parents' decisions to keep marginally unwell children home. Prior qualitative research informed parameter choice. The DCE was accompanied by a best-worst scaling task examining preferences for four modifiable aspects of care: swapping unused daycare sessions, reimbursing unused sessions, daycare paracetamol policy and presence of a 'quiet room'. RESULTS: Paracetamol guidelines and the presence of a quiet room had the strongest predicted influence on parents' decision-making. Conditional on assumptions about the set-up of the daycare, introducing a 'no paracetamol' policy would result in a fall from 62 to 25% in mean predicted probabilities of a parent sending a marginally unwell child to nursery, while introducing a quiet room would increase the mean probability from 34 to 53%. CONCLUSIONS: Daycare policy, particularly the use of paracetamol prior to attendance, could impact parents' decisions to send unwell children to daycare, potentially influencing the transmission of children's infectious illness.

Risk of obstetric anal sphincter injury in women having a vaginal birth after a previous caesarean section: A population-based cohort study.

OBJECTIVE: Caesarean section is increasing in prevalence and with it the proportion of women going into their next pregnancy with a scar on their uterus. For women considering vaginal birth after caesarean (VBAC), accurate information about the associated risks is required. STUDY DESIGN: The cohort comprised 192,057 women who had a vaginal delivery of a singleton, term, cephalic infant between the 1st April 2013 and the 31st March 2014 in England: 182,064 women who were having their first baby, and 9993 women who were having a second baby after a previous caesarean delivery. Their risk of an obstetric anal sphincter injury (OASI) was compared using a mixed-effects logistic regression model, adjusting for maternal age, use of instrument, episiotomy, prolonged labour, shoulder dystocia, and demographic factors. RESULTS: The OASI rate was 5.0% in primiparous women, 5.8% in secondiparous women undergoing VBAC after previous elective caesarean, and 7.6% in secondiparous women undergoing VBAC after previous emergency caesarean. Women having a VBAC for their second baby following an emergency caesarean section in their first delivery had a higher rate of OASI than primiparous women (adjusted OR 1.31; 95% CI: 1.20, 1.43), For women with a previous elective delivery, the rates are similar to those for primiparous women. CONCLUSION: Women having a VBAC after emergency caesarean have a higher rate of OASI than primiparous women. This is important in the counselling of women considering VBAC.

The views of the general public on prioritising vaccination programmes against childhood diseases: A qualitative study.

BACKGROUND: Decisions regarding which vaccines are funded in the United Kingdom (UK) are increasingly informed by cost-effectiveness analyses. Such analyses use Quality Adjusted Life Years (QALYs) as a measure of effectiveness and assume that QALYs are equal regardless of where and in whom they occur in the population. However, there is increasing debate about whether this QALY approach is appropriate and whether societal preferences for childhood vaccinations should be used to help inform childhood immunisation policy. OBJECTIVE: To gauge the general public's preferences for prioritising certain characteristics of childhood vaccination, to help inform future policy making decisions in the UK. DESIGN: Qualitative design using individual face-to-face interviews, with data analysed using an inductive thematic framework approach. SETTING: Two counties in England, UK. POPULATION: Adult members of the general public were recruited using the Bristol and South Gloucestershire open electoral registers, using gender and deprivation quotas for each area. PARTICIPANTS: 21 members of the public participated in qualitative interviews. RESULTS: The qualitative research identified three major themes and several key attributes that influences participant's opinions about priority setting for childhood vaccinations: (1) population segment (i.e. age group, carer impact and social group), (2) vaccine preventable diseases preferences (i.e. disease severity, disease incidence and declining infection) and (3) risks and benefits associated with childhood vaccinations (i.e. vaccine associated side-effects, herd protection and peace of mind). CONCLUSION: Evidence from this qualitative study suggests that some members of the UK general public have more nuanced views than the health-maximisation approach when considering how childhood vaccines should be prioritised. This is not necessarily captured by the current economic approaches for assessing the benefits from childhood vaccinations in the UK, but is an important area for future research to ensure appropriate decision making.

Effect of Oral Prednisolone on Symptom Duration and Severity in Nonasthmatic Adults With Acute Lower Respiratory Tract Infection: A Randomized Clinical Trial.

Importance: Acute lower respiratory tract infection is common and often treated inappropriately in primary care with antibiotics. Corticosteroids are increasingly used but without sufficient evidence. Objective: To assess the effects of oral corticosteroids for acute lower respiratory tract infection in adults without asthma. Design, Setting, and Participants: Multicenter, placebo-controlled, randomized trial (July 2013 to final follow-up October 2014) conducted in 54 family practices in England among 401 adults with acute cough and at least 1 lower respiratory tract symptom not requiring immediate antibiotic treatment and with no history of chronic pulmonary disease or use of asthma medication in the past 5 years. Interventions: Two 20-mg prednisolone tablets (n = 199) or matched placebo (n = 202) once daily for 5 days. Main Outcomes and Measures: The primary outcomes were duration of moderately bad or worse cough (0 to 28 days; minimal clinically important difference, 3.79 days) and mean severity of symptoms on days 2 to 4 (scored from 0 [not affected] to 6 [as bad as it could be]; minimal clinically important difference, 1.66 units). Secondary outcomes were duration and severity of acute lower respiratory tract infection symptoms, duration of abnormal peak flow, antibiotic use, and adverse events. Results: Among 401 randomized patients, 2 withdrew immediately after randomization, and 1 duplicate patient was identified. Among the 398 patients with baseline data (mean age, 47 [SD, 16.0] years; 63% women; 17% smokers; 77% phlegm; 70% shortness of breath; 47% wheezing; 46% chest pain; 42% abnormal peak flow), 334 (84%) provided cough duration and 369 (93%) symptom severity data. Median cough duration was 5 days (interquartile range [IQR], 3-8 days) in the prednisolone group and 5 days (IQR, 3-10 days) in the placebo group (adjusted hazard ratio, 1.11; 95% CI, 0.89-1.39; P = .36 at an α = .05). Mean symptom severity was 1.99 points in the prednisolone group and 2.16 points in the placebo group (adjusted difference, -0.20; 95% CI, -0.40 to 0.00; P = .05 at an α = .001). No significant treatment effects were observed for duration or severity of other acute lower respiratory tract infection symptoms, duration of abnormal peak flow, antibiotic use, or nonserious adverse events. There were no serious adverse events. Conclusions and Relevance: Oral corticosteroids should not be used for acute lower respiratory tract infection symptoms in adults without asthma because they do not reduce symptom duration or severity. Trial Registration: ISRCTN.com Identifier: ISRCTN57309858.

One-stage or two-stage revision surgery for prosthetic hip joint infection--the INFORM trial: a study protocol for a randomised controlled trial.

BACKGROUND: Periprosthetic joint infection (PJI) affects approximately 1% of patients following total hip replacement (THR) and often results in severe physical and emotional suffering. Current surgical treatment options are debridement, antibiotics and implant retention; revision THR; excision of the joint and amputation. Revision surgery can be done as either a one-stage or two-stage operation. Both types of surgery are well-established practice in the NHS and result in similar rates of re-infection, but little is known about the impact of these treatments from the patient's perspective. The main aim of this randomised controlled trial is to determine whether there is a difference in patient-reported outcome measures 18 months after randomisation for one-stage or two-stage revision surgery. METHODS/DESIGN: INFORM (INFection ORthopaedic Management) is an open, two-arm, multi-centre, randomised, superiority trial. We aim to randomise 148 patients with eligible PJI of the hip from approximately seven secondary care NHS orthopaedic units from across England and Wales. Patients will be randomised via a web-based system to receive either a one-stage revision or a two-stage revision THR. Blinding is not possible due to the nature of the intervention. All patients will be followed up for 18 months. The primary outcome is the WOMAC Index, which assesses hip pain, function and stiffness, collected by questionnaire at 18 months. Secondary outcomes include the following: cost-effectiveness, complications, re-infection rates, objective hip function assessment and quality of life. A nested qualitative study will explore patients' and surgeons' experiences, including their views about trial participation and randomisation. DISCUSSION: INFORM is the first ever randomised trial to compare two widely accepted surgical interventions for the treatment of PJI: one-stage and two-stage revision THR. The results of the trial will benefit patients in the future as the main focus is on patient-reported outcomes: pain, function and wellbeing in the long term. Patients state that these outcomes are more important than those that are clinically derived (such as re-infection) and have been commonly used in previous non-randomised studies. Results from the INFORM trial will also benefit clinicians and NHS managers by enabling the comparison of these key interventions in terms of patients' complication rates, health and social resource use and their overall cost-effectiveness. TRIAL REGISTRATION: Current controlled trials ISRCTN10956306 (registered on 29 January 2015); UKCRN ID 18159.

Factors influencing parents' decision-making when sending children with respiratory tract infections to nursery.

BACKGROUND: Many families rely on formal day care provision, which can be problematic when children are unwell. Attendance in these circumstances may impact on the transmission of infections in both day care and the wider community. METHODS: Thirty-one semi-structured interviews were conducted to investigate how parents make decisions about nursery care when children are unwell. Topics for discussion included: illness attitudes, current practice during childhood illness and potential nursery policy changes that could affect decision-making. RESULTS: A combination of illness perceptions and external factors affected decision-making. Parents: (i) considered the severity of respiratory and non-respiratory symptoms differently, and stated that while most other contagious illnesses required nursery exclusion, coughs/colds did not; (ii) said decisions were not solely based on nursery policy, but on practical challenges such as work absences, financial penalties and alternative care availability; (iii) identified modifiable nursery policy factors that could potentially help parents keep unwell children at home, potentially reducing transmission of infectious illness. CONCLUSIONS: Decision-making is a complex interaction between the child's illness, personal circumstance and nursery policy. Improving our understanding of the modifiable aspects of nursery policies and the extent to which these factors affect decision-making could inform the design and implementation of interventions to reduce the transmission of infectious illness and the associated burden on NHS services.

Cost-effectiveness of cognitive-behavioural therapy as an adjunct to pharmacotherapy for treatment-resistant depression in primary care: economic evaluation of the CoBalT Trial.

BACKGROUND: Depression is expensive to treat, but providing ineffective treatment is more expensive. Such is the case for many patients who do not respond to antidepressant medication. AIMS: To assess the cost-effectiveness of cognitive-behavioural therapy (CBT) plus usual care for primary care patients with treatment-resistant depression compared with usual care alone. METHOD: Economic evaluation at 12 months alongside a randomised controlled trial. Cost-effectiveness assessed using a cost-consequences framework comparing cost to the health and social care provider, patients and society, with a range of outcomes. Cost-utility analysis comparing health and social care costs with quality-adjusted life-years (QALYs). RESULTS: The mean cost of CBT per participant was £910. The difference in QALY gain between the groups was 0.057, equivalent to 21 days a year of good health. The incremental cost-effectiveness ratio was £14 911 (representing a 74% probability of the intervention being cost-effective at the National Institute of Health and Care Excellence threshold of £20 000 per QALY). Loss of earnings and productivity costs were substantial but there was no evidence of a difference between intervention and control groups. CONCLUSIONS: The addition of CBT to usual care is cost-effective in patients who have not responded to antidepressants. Primary care physicians should therefore be encouraged to refer such individuals for CBT.

Bristol girls dance project feasibility study: using a pilot economic evaluation to inform design of a full trial.

BACKGROUND: There is currently little guidance for pilot trial economic evaluation where health outcomes and costs are influenced by a range of wider determinants and factors. OBJECTIVES: This article presents the findings of a pilot economic evaluation study running alongside the Bristol Girls Dance Project (BGDP) feasibility study. DESIGN: 3-arm, cluster randomised, controlled pilot trial and economic evaluation. 7 schools (n=210) from the Bristol and greater Bristol area, UK were randomly allocated to the intervention arm 3 schools (n=90) and the control arm 4 schools (n=120). INTERVENTION: Girls aged 11-12 years with parental consent were provided with two, 90 min dance sessions per week for 9 weeks at school facilities. ECONOMIC OUTCOME MEASURES: Programme costs and girls' preferences for attributes of dance and preferences for competing leisure time activities were measured. RESULTS: The mainstream average cost of the BGDP programme (not including research, control and dance teacher training costs) per school was $2126.40, £1329 and €1555 and per participant was $70.90, £44.31 and €51.84 in 2010-2011 prices. Discrete choice experiment (DCE) methods are acceptable to girls of this age indicating time available for other leisure activities on dance class days is the attribute girls valued most and 2 h leisure time remaining preferred to 3 h. CONCLUSIONS: This pilot study indicates that providing full cost data for a future trial of the BGDP programme is feasible and practical. There is no evidence from preference data to support adjustment to intervention design. A future economic evaluation is likely to be successful utilising the resource use checklist developed. The importance of categorising separately resources used to develop, prepare, deliver and maintain the programme to estimate mainstream costs accurately is demonstrated.

Are multidisciplinary teams in secondary care cost-effective? A systematic review of the literature.

OBJECTIVE: To investigate the cost effectiveness of management of patients within the context of a multidisciplinary team (MDT) meeting in cancer and non-cancer teams in secondary care. DESIGN: Systematic review. DATA SOURCES: EMBASE, MEDLINE, NHS EED, CINAHL, EconLit, Cochrane Library, and NHS HMIC. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Randomised controlled trials (RCTs), cohort, case-control, before and after and cross-sectional study designs including an economic evaluation of management decisions made in any disease in secondary care within the context of an MDT meeting. DATA EXTRACTION: Two independent reviewers extracted data and assessed methodological quality using the Consensus on Health Economic Criteria (CHEC-list). MDTs were defined by evidence of two characteristics: decision making requiring a minimum of two disciplines; and regular meetings to discuss diagnosis, treatment and/or patient management, occurring at a physical location or by teleconferencing. Studies that reported on the costs of administering, preparing for, and attending MDT meetings and/or the subsequent direct medical costs of care, non-medical costs, or indirect costs, and any health outcomes that were relevant to the disease being investigated were included and classified as cancer or non-cancer MDTs. RESULTS: Fifteen studies (11 RCTs in non-cancer care, 2 cohort studies in cancer and non-cancer care, and 2 before and after studies in cancer and non cancer care) were identified, all with a high risk of bias. Twelve papers reported the frequency of meetings which varied from daily to three monthly and all reported the number of disciplines included (mean 5, range 2 to 9). The results from all studies showed mixed effects; a high degree of heterogeneity prevented a meta-analysis of findings; and none of the studies reported how the potential savings of MDT working may offset the costs of administering, preparing for, and attending MDT meetings. CONCLUSIONS: Current evidence is insufficient to determine whether MDT working is cost-effective or not in secondary care. Further studies aimed at understanding the key aspects of MDT working that lead to cost-effective cancer and non-cancer care are required.

Women and their partners' preferences for Down's syndrome screening tests: a discrete choice experiment.

OBJECTIVES: This study aimed to determine quantitatively the attributes of such screening tests that couples placed most value on. METHODS: A stated preference discrete choice experiment was conducted among a sample of pregnant women and their male partners. One four-level attribute (cost) and three two-level attributes (detection rate, gestation and time to wait for results) were used to generate eight hypothetical pairs of tests. RESULTS: A total of 103 participants fully completed the questionnaire (63 women, 40 men). Overall, the sample was most concerned with test cost. However, latent class analysis showed three groups of participants whose concern for attributes differed, with cost, detection rate and delay in receiving results being the most important to each. Willingness to pay calculations showed that participants who were most concerned with detection rate were prepared to pay more than four times the amount than those most cost-sensitive would pay for the 'best test' option as compared with the 'worst test'. CONCLUSIONS: Overall, couples were sensitive to the price of the screening test, but explicit subgroups are also shown that would pay large amounts for improvements in other attributes, particularly detection rates. This could provide important information to policymakers and practitioners in antenatal care, specifically in relation to the trade-offs made when couples decide about antenatal screening tests.

A qualitative investigation of the decision-making process of couples considering prenatal screening for Down syndrome.

OBJECTIVE: The aim of this study was to investigate how couples regard screening information and how they make subsequent decisions about undergoing prenatal screening for Down syndrome. METHODS: Twenty semi-structured interviews were conducted to explore aspects of the decision-making process. Interviews were digitally recorded and transcribed verbatim, and data were analysed using the framework approach. RESULTS: Couples reported a strong desire for a joint but ultimately private decision-making process and saw the main role of their midwife as an information provider. Considerable confusion existed over which screening tests were available via the National Health Service and which were offered privately. Provision of experiential information regarding both subsequent diagnostic tests and the experience of living with Down syndrome would have been beneficial. CONCLUSION: This study shows that couples would benefit from receiving experiential information when they are deciding about Down syndrome screening. Future research should be conducted to establish what form such information should take, the most helpful means to provide such information, and whether such information would also be useful in other contexts where people need to make decisions whether to undergo screening.