Rehabilitation of older patients: day hospital compared to rehabilitation at home. A randomised controlled trial

Article history

The research reported in this issue of the journal was commissioned by the HTA programme as project number 97/26/01. The contractual start date was in September 2002. The draft report began editorial review in December 2007 and was accepted for publication in January 2009. As the funder, by devising a commissioning brief, the HTA programme specified the research question and study design. The authors have been wholly responsible for all data collection, analysis and interpretation, and for writing up their work. The HTA editors and publisher have tried to ensure the accuracy of the authors’ report and would like to thank the referees for their constructive comments on the draft document. However, they do not accept liability for damages or losses arising from material published in this report.

Declared competing interests of authors

None

Copyright statement

© 2009 Queen’s Printer and Controller of HMSO. This monograph may be freely reproduced for the purposes of private research and study and 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: NETSCC, Health Technology Assessment, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK

2009 Queen’s Printer and Controller of HMSO

An ageing population

Population demography is an important driving factor in changing the emphasis of health service delivery from acute care in hospitals to community care for long-term conditions. Over the last 35 years the UK population aged over 65 years has grown by 31%, from 7.4 million to 9.7 million, whilst the population aged under 16 years has declined by 19%, from 14.2 million to 11.5 million. More recently, population ageing is reflected in the growth of the oldest old. The largest percentage growth in population in the year to mid-2006 was at ages 85 years and over (5.9%). The number of people aged 85 years and over grew by 69,000 in the year to 2006, reaching a record 1.2 million. Current population projections suggest that the number of centenarians in England and Wales will increase at an annual average rate of 6% a year to four times the current number, reaching almost 40,000 by mid-2031. 1 These projections, sometimes referred to as the ‘demographic imperative’, imply a need to respond by adapting existing services, introducing new ones and perhaps abandoning old ones to meet the evolving health and social care needs of an ageing population.

Assessment and rehabilitation

One of the key concepts in quality care for older people is the need for comprehensive assessment and a rehabilitative approach to care management. Traditionally this approach to care has been available in day hospitals, but it is increasingly being made available in the community (or at least elements of it are) – closer to or actually in the recipient’s own home. In this context the day hospital may be regarded as an outpatient service, which is provided in a clinical setting and which does not require residence in the clinical institution to receive the service. The day hospital building may be provided in a hospital setting (e.g. on a teaching or district general hospital site) or closer to the patient’s home (e.g. on a community hospital or rehabilitation unit site).

The day hospital has long been regarded as a central resource in medicine for older people and identified as a totem of good practice in health care for older people. The so-called ‘geriatric day hospital’ evolved from modest beginnings in the 1950s in Oxfordshire and rapidly became an essential component for the emerging departments of geriatric medicine. Literature descriptions of the work of day hospitals emphasised the importance of rehabilitation as a core component of day hospital work. Further facets described included medical, nursing and remedial treatments and elements of social care within an ambulatory care setting. More recently, the role of the day hospital as a provider of specialised multidisciplinary clinical assessment, admission avoidance and subacute care and investigation has been proposed. 2 In the UK the activities of day hospitals are seen primarily as alternatives to community-based rehabilitation or hospital inpatient care. 3 A survey of health authorities and trusts in England and Wales4 showed that, of 345 trusts in England, 209 (61%) provided day hospitals, 193 (56%) provided outpatient rehabilitation and 120 (36%) provided community-based rehabilitation teams. The vast majority of day hospitals (195, 96%) had been established before 1993. In contrast, the majority of community rehabilitation teams (52%) had been established since 1993.

Over 10 years ago the National Audit Office5 encouraged NHS executives to ‘review the availability of research on the cost-effectiveness of care provided by day hospitals and encourage further research if appropriate’. The Public Accounts Committee6 of the House of Commons has also acknowledged the lack of ‘research evidence indicating unequivocally that in terms of clinical effectiveness and cost-effectiveness there was a case for day hospitals against other services’.

Policy context

More recently a number of developments in the UK health and social care environment have highlighted the need for a more complete understanding of the influence of rehabilitation setting on costs and outcomes of care. Policy responses to the demographic imperative, and other concerns about the nature, quality and value of national health-care provision, have underlined a shifting emphasis from acute, hospital-based care to ambulatory, preventive and community-based care.

For example, in the UK, recent policy initiatives have emphasised joined-up working between health and social care. 2,7 Primary care organisations, which are now responsible for commissioning health care, are encouraged to partner with social services. Joint working between health-care and local government organisations is encouraged and supported by financial flexibilities introduced in the Health Act 1999. In some areas this has led to the formation of care trusts, which manage both health and social care services in a locality.

During this period the concept of intermediate care was introduced in the NHS Plan8 and National Service Framework for Older People. 9 The framework identifies the range of community-based services that should be used to prevent hospital admission where possible and to provide active rehabilitation in the community following discharge from hospital. The concept arose from concerns about the unnecessary use of acute hospital inpatient care to meet the needs of older people. 10

Much of the policy focus has been around changing the delivery of acute care. This is illustrated in measures such as the time spent in the accident and emergency department becoming performance indicators and the introduction of the Community Care (Delayed Discharges etc.) Act,11 which introduced a system of reimbursement for delayed transfers of care, to encourage coordination between acute health and community social care to reduce delayed transfers of care from hospital into the community.

The ‘bed-blocking’ older person, trapped in inpatient care and consuming precious health-care resources, continues to provide a powerful image to drive change in the way that acute care services are provided, and most importantly in their relationship to home-based services and in the development of services to provide recuperation and rehabilitation in the home.

More recently the National Service Framework for Long-term Conditions has defined a number of quality requirements for services for people with long-term conditions. 12 The framework focuses on neurological conditions, but the principles apply to other specific long-term conditions and to people of all ages, including older people. Older people have specific assessment and rehabilitation needs related to complex co-morbidity and age-related functional deficits and, as much as any other group with long-term conditions, respond to early and specialist rehabilitation (quality requirement 4) in hospital or other specialist settings to meet their continuing and changing needs, and community rehabilitation and support (quality requirement 5) to additionally increase their independence and help them live as they wish.

The 2006 White Paper Our Health, Our Care, Our Say13 described a future in which resources will be shifted to provide more care outside hospital and in the home, which it is expected will be accompanied by a shift of resources into community health and social services and which emphasises preventive care and care ‘closer to home’. This intention is accompanied by a clear commitment to shifting resources into preventive and community services and residential and home-based support for older people and people with long-term conditions. This agenda has a clear implication for the ‘place of care’ for services in health and social care in the future, which will be community- and home-based wherever possible.

The following extract from Hansard (Box 1) illustrates the current nature of the changes that are taking place in the health and social care system in the UK and provides a picture of the policy backdrop against which recent research into ‘place of care’ for rehabilitation (including the studies described in this document) is taking place. Clearly, the evolving policy and service landscape places value on appropriate and specialist rehabilitation services, together with community provision, close to the patient’s own home when feasible and appropriate. When placed in this context, an RCT of day hospital compared with home-based rehabilitation is seen to address key policy issues at the interface between hospital and community-based services for older people.

Research challenges

Although the changing policy landscape provides an incentive to inform decision-making in this area, it provides for a rapidly changing background of provision, including a major shift in emphasis between hospital and community-based care, which has added considerably to the research challenges of developing useful comparative analyses between hospital-based and home-based services.

In addition to the general challenges to ‘place of care’ research occasioned by the rapidly changing policy and practice landscape referred to above, there are some specific challenges to developing meaningful comparative analyses of day hospital rehabilitation and home-based care:

• There is no systematic typology of day hospitals against which to compare the structure of individual units. Day hospitals provide a wide range of services, from social day care to medical assessment and treatment. 14,15 Different day hospitals provide different mixes of services16 according to local needs, facilities and the availability of complementary services. Such variations in the level of structure of day hospitals reduce the potential for generalisation of studies of effectiveness/cost-effectiveness conducted in a single unit.

• There are a variety of objectives of care, ranging from active rehabilitation to social care, which leads to a broad case mix. For example, there is wide variation in physical and psychological disability among patients attending for each of the several objectives of care17,18 and a range of professional perceptions of the reasons for attending. 19

• Defining appropriate outcomes of day hospital care may also be problematic. Measurement at the levels of health and dependency20,21 has not yet been shown to be appropriate or sensitive to change in this population. Measures of patients’ and carers’ satisfaction with the service may be useful,22 as may approaches that measure the attainment of relevant goals. 23

• The measurement of the costs of day hospital care is not straightforward. 22 Day hospitals are frequently not budget centres in their own right and transport (a significant component of day hospital costs) may not be costed separately or consistently between units. 24 Costs of community-based alternatives to day hospital care will fall upon a variety of agencies, all of which would have to be taken into account in comparative economic studies.

Research question

Against this background of rapidly changing service provision and the research and measurement challenges, we have attempted to perform a randomised controlled trial (RCT) of day hospital versus home-based rehabilitation with health economic analysis to test the following specific hypotheses:

1. older people and their informal carers are not disadvantaged by home-based rehabilitation relative to day hospital rehabilitation

2. home-based rehabilitation is less costly.

The research question was identified in the Health Technology Assessment programme’s process for identifying evidence gaps25 and prioritising research. 26

Review of previous studies of day hospital services for older people

Although there are already RCTs of day hospital services in the literature, few have provided detailed evidence of costs and outcomes to inform decision-making about the provision of rehabilitation services for older people with respect to place of care. A Cochrane review published in 199927 included 12 RCTs in which day hospital attendance was evaluated against comprehensive elderly care (five trials28–32), domiciliary care (four trials33–36) or no comprehensive care (three trials37–39). Overall, 2867 subjects were included and the review examined 22 individual day hospitals in both postacute and subacute care. The authors concluded that, compared with patients receiving neither comprehensive care nor domiciliary rehabilitation, patients attending day hospitals had less functional deterioration and institutional care and a small reduction in average hospital bed use. However, the studies that addressed the question of best place of care, by comparing the provision of active treatment in the community, showed that day hospitals offer little advantage for patient outcome over other forms of comprehensive medical services. The review included studies performed over a 35-year period and trials designed to answer questions about the setting for rehabilitation for stroke care, or alternative settings for care usually provided in inpatient units, outpatient units and nursing homes.

Review methods

We have brought our view of the literature up to date by developing a previous review of the best place of care for older people after acute and during subacute illness, which included papers published between 1988 and 1999 and included analysis of day hospital rehabilitation and community rehabilitation. 40 Guidelines from the NHS Centre for Reviews and Dissemination41 were used as a methodological framework. Search strategies and methods have previously been described in detail42 and results published in part elsewhere. 40

We updated the review on day hospital rehabilitation by repeating the literature searches using the same strategies and databases as before, first in 2004 and subsequently in 2007. Study selection and data extraction used the same process of title and abstract review, selection of potentially relevant studies and review of selected studies against defined quality and relevance criteria. The update was carried out in two stages: for the update from 1999 to 2004 papers were included after a process of dual observer review, selecting papers on the basis of design (randomised and pseudo-randomised trials), the comparison being made (place of care) and the inclusion of subjects over 65 years; for the final update to June 2007 these processes were carried out by a single observer (SGP). Trials and quasi-randomised studies that compared day hospital care with an alternative setting for assessment and rehabilitation were eligible for inclusion.

Literature review results

Mortality

The data from the studies seem to support the notion that day hospital patients are neither more nor less likely to die as a consequence of receiving their care in this setting. However, the data might also suggest a disadvantage for day hospital patients over time. Pooled data for 6-month (Figure 1) and 12-month (Figure 2) follow-up [odds ratio (OR) 1.33, 95% confidence interval (CI) 0.96 to 1.84] and for all final follow-up (Figure 3), regardless of when that was (OR 1.22, 95% CI 0.92 to 1.63), again suggest a slightly poorer outcome for day hospital patients, but the differences do not reach statistical significance.

FIGURE 1.

Mortality at 6 months.

FIGURE 2.

Mortality at 12 months.

FIGURE 3.

Mortality at final follow-up combined.

Conclusion

Overall this review reveals a paucity of comparable studies in which the day hospital is evaluated as a setting for rehabilitation and compared with realistic alternatives for twenty-first century practice, such as community-based rehabilitation. Although the evidence base for day hospitals contains relatively large numbers of observations, these observations have been made over a period of five decades and with widely differing comparator interventions. None of the excluded trials compared day hospital rehabilitation with rehabilitation in the home, with the exception of the DOMINO study36 in which patients were not randomised to day hospital care but to a ‘care of the elderly stratum’ in which they could receive day hospital care but mostly did not (about one-third of subjects in this stratum received day hospital care). Included trials have compared rehabilitation or some other intervention in the day hospital with comparator interventions such as inpatient hospital care, specialist neurological care, nursing home treatment or outpatient follow-up. In the Huntingdon community rehabilitation trial35 patients received their rehabilitation in a day hospital or in a local authority day centre – a non-clinical institutional setting – rather than in their own homes. Given the significant methodological challenges that research into day hospitals presents, it is perhaps not surprising that the development of alternatives to the day hospital as settings for rehabilitation has proceeded in the absence of evidence of their relative costs or effectiveness, leaving day hospitals in service but increasingly unsure of their role.

Equally, the literature review has found evidence to support the view that home-based rehabilitation teams have not been systematically evaluated in comparison with day hospitals as a setting for rehabilitation in ambulatory care.

The hypotheses (older people and their informal carers are not disadvantaged by home-based rehabilitation relative to day hospital rehabilitation, and home-based rehabilitation is less costly) remain hypotheses that have not been fully evaluated in well-constructed RCTs, and in policy terms the research question – which is about cost-effective provision of rehabilitation services for older people and people with long-term conditions – remains one in which there is current interest for policy- and decision-makers in the NHS.

Introduction

In preparation for an RCT of home-based rehabilitation versus day hospital rehabilitation we carried out a survey of NHS trusts in England.

Objectives

Our principal aim in conducting this survey was to establish the scope of provision of home-based and day hospital rehabilitation services to support the development and conduct of a pragmatic RCT, conducted in multiple centres in England and including health economic analysis (ISRCTN71801032),48 with the aim of providing valuable information on which to base future decisions about day hospital and home-based rehabilitation services.

The objectives of the survey were to:

• discover the scope of service provision in home-based and day hospital rehabilitation for older people in England

• identify potential trial sites for an RCT.

Potential trial sites would already be running both home-based and day hospital rehabilitation services, would express interest in participating as a trial site in an RCT of these services and, ideally, would be able to predict a degree of stability in local service provision over the proposed duration of the trial.

Methods

We carried out a postal survey of NHS trusts in England during 2003. All trusts in England were identified by contacting each of the 28 strategic health authorities for a list of their primary care and hospital trusts. When this information was difficult to obtain, the Department of Health website was consulted. All trusts were sent an initial questionnaire that asked whether or not they provided home-based and/or day hospital rehabilitation for elderly patients. The trusts that replied then received a second questionnaire asking for more detail about type of service and staffing.

Results

Of the 534 potentially relevant trusts identified, 31 were found to no longer exist and 23 reported the survey as being irrelevant to their services (e.g. trusts dealing exclusively in the care of children or ambulance services). Of the remaining 489 trusts, 400 returned completed initial questionnaires and 372 (76%) contained complete and relevant responses (Table 12).

Of these, 324 (87%) trusts reported providing rehabilitation services, 184 (46%) reported the provision of both home-based rehabilitation and day hospital rehabilitation, 80 (20%) provided home-based rehabilitation but not day hospital rehabilitation and 61 (15%) day hospital rehabilitation but not home-based rehabilitation. Trusts providing rehabilitation services were sent a second questionnaire and 200 replies (62%) were received. The results of these replies for each service type are shown in Table 13, and a comparison of the results between trusts providing both day hospital and home-based rehabilitation services and those providing only one or the other setting for rehabilitation services is shown in Table 14.

Discussion

This survey served the dual purpose of providing a snapshot of the scope of provision of home-based and day hospital rehabilitation services for older people and providing a sampling frame for the systematic identification of potential sites for an RCT.

In both settings trusts reported providing functional assessment and rehabilitation. Services in both settings were usually provided with physiotherapy, occupational therapy and nursing staff. Medical staffing was significantly less likely in the community-based services, and day hospitals were very much more likely to provide medical or specialised medical services [such as Parkinson’s disease, falls, and transient ischaemic attack (TIA) clinics] and nursing procedures. Home-based services were more likely to be provided by community practitioners (GP and nurse) and be time limited in nature (i.e. restricted to a specific number of weeks’ service provision) (see Table 13).

It was possible that trusts reporting only one or other type of service would provide more comprehensive services in a single setting than trusts in which services were provided in both settings. Accordingly the data were analysed by both service type and whether the responding trust provided only day hospital or rehabilitation services or both. This analysis (see Table 14) showed that the differences between home-based and day hospital-based services were broadly similar, whether or not the responding trust provided both types of service.

A project about the best place of care for older people (HTA project reference 96/43/014) carried out a national survey of services for older people in England during 1988. This survey was more comprehensive in the range of services about which it gathered information than that reported here, but it included questions that may be directly comparable with the questions asked in the present questionnaire. The 1998 survey asked, ‘Do you provide day hospital services for older people?’, and in 2003 we asked, ‘Does your trust provide day hospital rehabilitation services for elderly people?’. The 1998 survey asked, ‘Do you provide community-based rehabilitation teams for older people?’, and we asked, ‘Does your trust provide a home-based rehabilitation service for older people?’.

A comparison of the results of these two survey questionnaires is summarised in Table 15. This suggests an increase in the provision of home-based rehabilitation services, which appear to have been provided in parallel with day hospital rehabilitation services – the proportion of trusts reporting day hospital rehabilitation services remained static during the period of comparison. Although the methods and the questions are not identical, and therefore this result could be explained by the slightly different emphases of the questions about home-based rehabilitation, it does suggest that NHS services managers, over the period of the two surveys, were actively taking the sort of decision about the provision of rehabilitation services for older people that our RCT was designed to inform. Further, the range of provision of day hospital and home-based rehabilitation services identified in this survey implies that, when the survey was performed, clinicians were making pragmatic decisions about the settings in which to provide rehabilitation for older people, which was being delivered by a variety of practitioners in different settings.

This sense of heterogeneity in provision, and in delivery of services, reveals that rehabilitation for older people is far from being a standardised service and may be taken to suggest ongoing uncertainty about the preferred setting for rehabilitation. It certainly implies that decisions about the settings for rehabilitation were still current at the time of starting the RCT described later in this report.

Marked heterogeneity of services contains implications for the design of an RCT and led us to suggest that the number of sites involved in the RCT needed, if possible, to be higher than the three originally anticipated, to allow a broader representation of services.

Furthermore, heterogeneity and rapid service development and changes suggest that observational studies would be of value alongside an RCT to provide a clearer picture of the local and national context within which the trial was taking place.

In summary, when this research was commissioned, the research question was selected as being of national importance by the NIHR Evaluation, Trials and Studies Coordinating Centre (NETSCC). Survey work carried out before commencing the trial indicated that providers and commissioners were actively deciding to provide both types of service, and a systematic literature review indicated that the research question(s) had not already been answered.

Introduction

This chapter has been written to follow the revised Consolidated Standards for Reporting Trials (CONSORT) framework49 for reporting an RCT. The background and supporting literature review are presented in Chapter 1 of this report. A national survey of NHS trusts in England carried out to identify potential trial sites in 2003 is presented in Chapter 2.

Essential conclusions from the literature evidence and national survey data were that:

1. there is insufficient comparative evidence to inform choices on service development and the treatment of individual patients between day hospital and home-based rehabilitation

2. in the changing landscape of NHS provision both types of service are being provided by NHS managers (as evidenced by an increase in the proportion of trusts providing both service types between 1998 and 2003) and chosen between by NHS clinicians who are utilising the different service models for the benefits of their clients.

Objectives and hypotheses

We have designed and implemented a pragmatic RCT to compare home-based rehabilitation with day hospital rehabilitation. Rehabilitation itself, in a variety of forms and settings, is supported by evidence of effective practice,50 suggesting that both day hospital and home-based rehabilitation are capable of providing benefit. However, a detailed comparison of costs between home-based and day hospital rehabilitation has not previously been available. This trial was conducted to test the following hypotheses:

1. older people and their informal carers are not disadvantaged by home-based rehabilitation relative to day hospital rehabilitation

2. home-based rehabilitation is less costly.

Trial design and methods

Statistical methods

Approach to missing data

Missing questionnaire items

For the statistical analyses of the questionnaire data, missing responses were replaced with the individual’s mean relevant subscale score for the corresponding item, providing that the participant responded to at least half of the items within the subscale. In practice, only the NEADL scale had missing data – about 1% of data were missing for this scale, mainly because one of the questions was only partially relevant to some participants.

Data missing because of loss to follow-up

To conform to ITT principles, outcome scores missing because of loss to follow-up were imputed using the last observation carried forward (LOCF) method as prespecified in the analysis plan. Figure 4 illustrates this methodology.

FIGURE 4.

Example of the last observation carried forward method for EQ-5D_index scores.

All three methods (observed case, ITT with LOCF imputation and MMRM) were compared.

Health economic analysis

Data processing

Results

Flow of participants through the study: CONSORT diagram

Recruitment began at the first site in March 2005 and ended in October 2006, at which point four sites were randomising patients into the trial. Of the 907 participants assessed for eligibility, 89 were randomised and allocated to treatment, of whom 84 (42 in each treatment arm) received either home-based or day hospital rehabilitation (Figure 5).

FIGURE 5.

Flow of patients through the study.

Of the 472 patients who were considered ineligible to take part in the study, 272 (58%) were excluded as they were referred to the service for assessment by a single discipline. These subjects were therefore, by definition, not referred for multidisciplinary rehabilitation and were therefore not eligible for randomisation. Of the rest, the majority were excluded for local service-specific reasons. For example, 143 (30%) were excluded because of having a diagnosis of either motor neurone disease or Parkinson’s disease at sites at which location-specific services had been established for these specific diagnoses.

The levels of ineligibility, exclusion and refusal led to lower than expected levels of recruitment into the trial, which eventually left us unable to meet recruitment targets resulting in closure of recruitment before the target sample size had been achieved.

We therefore developed and proposed an exit strategy that limited follow-up to 6 months for subjects already randomised before October 2006, so that data collection would finish by the end of April 2007. This meant that the 12-month follow-up was sacrificed for some subjects to achieve a timely end to the project. The strategy anticipated that about 90 subjects would be randomised and that 6-month follow-up data would be available on about 85% of randomised participants.

The CONSORT diagram (Figure 5) shows that five patients were lost from the home-based rehabilitation group before the start of the intervention. Therefore, although 89 were randomised to the intervention (allocated), only 84 actually received an intervention. The reasons for loss to follow-up post treatment allocation are given in Table 26. At the 6-month follow-up, 33 patients in the home-based rehabilitation arm (79%) and 32 in the day hospital rehabilitation arm (76%) were available for analyses.

TABLE 26 - Reasons for loss to follow-up post treatment allocation

Lost before	Study arm
	Day hospital (n = 42)	Home (n = 47)
Receiving intervention	Total (remaining): 0 (42)	Withdrew : 2; deceased: 1; unknown: 2 Total (remaining): 5 (42)
3-month follow-up	Withdrew: 4; too ill: 1; deceased: 1; interview missed but subject not lost to follow-up: 1 Total (remaining): 6 (36) (35 interviewed)	Withdrew: 3; deceased: 1; unable to locate patient: 1 Total (remaining): 5 (37)
6-month follow-up	Deceased: 3 Total (remaining): 3 (33)	Deceased: 1; withdrew: 2; unable to complete: 1; unknown: 1 Total (remaining): 5 (32)
12-month follow-up	Deceased: 2; withdrew: 2; unable to complete: 12 Total (remaining): 16 (17)	Unable to complete: 6 Total (remaining): 6 (26)

Interview-based outcomes

Analysis of outcomes using observed case data set

The following analyses were conducted on all patients for whom data were available at each follow-up point.

Primary outcome: NEADL total score at 6 months

Mean total NEADL scores for day hospital rehabilitation and home-based rehabilitation are given in Table 33, which suggests that home-based rehabilitation was slightly favoured on this outcome.

TABLE 33 - Summary of patient outcomes at 6 months

DHR, day hospital rehabilitation; HBR, home-based rehabilitation.

Outcome	Possible range (worst to best)	DHR (n = 33), mean (SD)	HBR (n = 32), mean (SD)
NEADL total score	0 to 66	30.78 (15.01)	32.11 (16.89)
EQ-5Dindex	–0.59 to 1.00	0.56 (0.23)	0.59 (0.32)
EQ-5Dvas	0 to 100	58.67 (16.08)	59.84 (19.48)
HADS anxiety	12 to 0	6.06 (4.67)	5.56 (4.15)
HADS depression	12 to 0	6.67 (3.05)	5.97 (4.16)

To assess this apparent difference between the two treatment arms, an ANCOVA was conducted providing a mean estimated difference between the two groups after adjusting for baseline scores on the same outcome (Table 34). This method allows preintervention differences in morbidity to be taken into account, increasing the statistical power of the comparison. Mean adjusted total NEADL scores at 6 months were estimated to be around two points lower in the home-based care group (a difference of 3%) but as the 95% confidence interval around this estimate includes zero, it is concluded that this difference is not statistically significant. The ‘true’ difference between home-based rehabilitation and day hospital rehabilitation in terms of the NEADL total score can therefore be said (with 95% confidence) to lie between 6.9 points in favour of home-based care and 2.6 points in favour of day hospital care.

TABLE 34 - Mean estimated difference in outcomes at 6 months adjusted for baseline scores by analysis of covariance

Outcome	Mean estimated difference adjusted for baseline	Lower 95% CI	Upper 95% CI	p-value
NEADL total score	–2.139	–6.870	2.592	0.370
EQ-5Dindex	0.023	–0.114	0.161	0.735
EQ-5Dvas	–1.601	–8.809	5.607	0.659
HADS anxiety	–0.578	–2.409	1.253	0.530
HADS depression	1.033	–0.441	2.507	0.166

Secondary outcomes 1: NEADL subscales at 6 months

Mean scores from the four NEADL subscales plus the kitchen/domestic composite scale (household) were almost identical between the two treatment groups at 6 months, with a general tendency to be slightly worse in the day hospital group (Table 35). Mean estimated differences after adjusting for baseline scores are presented in Table 36.

TABLE 35 - NEADL subscale scores at 6 months

DHR, day hospital rehabilitation; HBR, home-based rehabilitation.

Subscale	Possible range (worst to best)	DHR (n = 33), mean (SD)	HBR (n = 32), mean (SD)
Mobility	0 to 24	7.30 (5.16)	8.19 (6.19)
Kitchen	0 to 20	10.76 (4.31)	10.34 (5.07)
Domestic	0 to 20	5.21 (4.52)	5.91 (5.04)
Leisure	0 to 24	7.51 (3.79)	7.68 (3.31)
Household (composite)	0 to 40	15.97 (7.94)	16.25 (9.28)

TABLE 36 - Mean estimated difference in NEADL subscale scores at 6 months adjusted for baseline

Subscale	Mean estimated difference adjusted for baseline	Lower 95% CI	Upper 95% CI	p-value
Mobility	–0.58	–2.59	1.42	0.564
Kitchen	–0.40	–1.90	1.11	0.601
Domestic	–0.91	–2.31	0.49	0.198
Leisure	–0.11	–1.41	1.20	0.872
Household (composite)	–1.38	–3.88	1.12	0.273

Secondary outcomes 2: total NEADL scores at 3 and 12 months’ follow-up

In addition to the primary end point of 6 months, group mean total NEADL scores for cases available at 3 months and at 12 months were also compared (Table 37). Estimated differences between each treatment group, after adjusting for baseline scores, favoured home-based care at 3 months but day hospital care at 12 months; however, neither result was statistically significant (3 months: estimate –2.79, 95% CI –7.84 to 1.90, p = 0.228; 12 months: estimate 1.39, 95% CI –6.11 to 8.88, p = 0.710).

TABLE 37 - Mean NEADL total scores at 3 and 12 months’ follow-up

DHR, day hospital rehabilitation; HBR, home-based rehabilitation.

		Group
		DHR	HBR
3 months	Group size	35	37
	Mean score (SD)	31.69 (14.68)	31.05 (17.23)
12 months	Group size	17	26
	Mean score (SD)	31.61 (15.36)	28.06 (17.50)

Secondary outcomes 3: health-related quality of life and psychological well-being of patients at 6 months

Health-related quality of life, as measured by the EQ-5D, was similar in each group, in terms of both VAS ratings and the weighted health state index (Table 38). The proportions of patients who classified themselves as experiencing a problem in one of the five domains of HRQoL contained within the EQ-5D were also compared (Figure 6). In general, the results suggest that a smaller proportion of patients experienced HRQoL difficulties in the home-based rehabilitation group, particularly with respect to the anxiety/depression scale.

TABLE 38 - Odds ratios for the likelihood of experiencing an HRQoL difficulty at 6 months, adjusting for baseline proportions by multiple logistic regression

General model: ln(p/(1–p)) = χ + β₁(randomisation group) + β₂(baseline proportion).

EQ-5D domain	Adjusted odds ratioa	95% CI for odds ratio		p-value
		Lower	Upper
Mobility	1.16	0.24	5.51	0.852
Usual activities	0.33	0.09	1.23	0.100
Self-care	0.65	0.22	1.89	0.431
Pain/discomfort	2.18	0.64	7.41	0.212
Anxiety/depression	0.34	0.11	1.05	0.060

FIGURE 6.

Percentages of patients experiencing problems in each of the EQ-5D domains at 6 months.

Statistical comparison of the proportions in Figure 6 was conducted using multiple logistic regression to take into account interindividual differences in HRQoL difficulties before the start of rehabilitation. The resulting statistic is the odds ratio, which in this instance provides a measure of how much more (or less) likely are patients in home-based care to have experienced HRQoL difficulties relative to patients who received rehabilitation at day hospital. An odds ratio of 1 indicates that patients are equally likely to experience difficulties in both groups. Health-related quality of life problems related to anxiety/depression appeared less common in the home-based rehabilitation group; however, as the 95% confidence intervals for the estimated odds ratios given in Table 38 all include 1, we conclude that there were no differences in HRQoL between the two groups at 6 months.

Mean scores on the HADS anxiety and depression scales were similar in each group at 6 months (Table 33) and did not differ significantly in analyses adjusted for baseline scores on these scales (Table 34). Using a clinical ‘caseness’ criteria threshold of 8, 39.4% and 31.3% of those in day hospital and home-based rehabilitation groups, respectively, were classified as having an increased likelihood of clinical anxiety. An increased likelihood of clinical depression was observed for 36.4% of day hospital cases and 37.5% of home-based care cases. Odds ratios for the likelihood of being considered a clinical case of anxiety or depression, adjusted for baseline proportions, are given in Table 39.

TABLE 39 - Odds ratios for the likelihood of being classified as a clinical case of anxiety or depression at 6 months, adjusting for baseline proportions by multiple logistic regression

General model: ln(p/(1–p)) = χ + β₁(randomisation group) + β₂(baseline proportion).

HADS domain	Adjusted odds ratioa	95% CI for odds ratio		p-value
		Lower	Upper
Anxiety	1.22	0.376	3.97	0.739
Depression	0.86	0.29	2.60	0.793

Summary of questionnaire-based outcomes at 6 months

Figure 7 provides a summary of the effect of place of care on the principal interview-based outcomes. Estimated differences between day hospital-based rehabilitation and home-based rehabilitation for each outcome (± 95% confidence intervals), after adjusting for baseline scores, were expressed as a percentage using respective scale ranges as denominators. The two shaded areas in Figure 7 provide 5% and 10% ‘non-inferiority margins’. Non-inferiority for home-based care, for a given outcome, is inferred when the 95% confidence interval is contained within this shaded area. Thus, we may conclude that after 6 months’ follow-up home-based care is not inferior to day hospital-based care in respect of all outcomes with the exception of HADS anxiety. There is insufficient evidence to reject the null hypothesis for this outcome as the estimated range of possible values falls outside of 10% in favour of hospital-based care. It is also noted, however, that the confidence intervals around the mean total NEADL and HADS depression scores include values higher than 10% in favour of home-based care.

FIGURE 7.

Effect of place of care on patient outcomes at 6 months.

Secondary outcomes 4: health-related quality of life and psychological well-being at 3 and 12 months

Mean EQ-5D_index scores were better for day hospital patients than for home-based care patients at the 3-month follow-up (Table 40). The estimated difference between groups in this outcome, after adjustment for baseline scores, was 0.122 (95% CI 0.002 to 0.242) and was significant at the 5% level (Table 41). There were no other differences in outcomes at 3 months, although a marginally statistically significant difference in depression scores on the HADS was observed in favour of home-based care (p = 0.056).

TABLE 40 - Health-related quality of life and psychological well-being of patients at 3 months

DHR, day hospital rehabilitation; HBR, home-based rehabilitation.

Outcome	Possible range (worst to best)	DHR (n = 35), mean (SD)	HBR (n = 37), mean (SD)
EQ-5Dindex	–0.59 to 1.00	0.61 (0.21)	0.51 (0.32)
EQ-5Dvas	0 to 100	56.54 (15.51)	57.70 (17.73)
HADS anxiety	12 to 0	6.83 (4.16)	5.65 (3.96)
HADS depression	12 to 0	6.83 (3.28)	5.81 (4.01)

TABLE 41 - Mean estimated difference in outcomes at 3 months adjusted for baseline scores by analysis of covariance

Outcome	Mean estimated difference adjusted for baseline	Lower 95% CI	Upper 95% CI	p-value
EQ-5Dindex	0.122	0.002	0.242	0.047
EQ-5Dvas	–2.559	–9.371	4.254	0.456
HADS anxiety	0.047	–1.466	1.559	0.951
HADS depression	1.374	–0.039	2.786	0.056

Health-related quality of life and psychological well-being outcomes were both similar between the two groups of patients who were able to be followed up at 12 months (Table 42). The observed difference in HADS anxiety scores is probably explained by differences between the two groups at baseline and was not statistically significant following ANCOVA (Table 43).

TABLE 42 - Health-related quality of life and psychological well-being of patients at 12 months

DHR, day hospital rehabilitation; HBR, home-based rehabilitation.

Outcome	Possible range (worst to best)	DHR (n = 17), mean (SD)	HBR (n = 26), mean (SD)
EQ-5Dindex	–0.59 to 1.00	0.55 (0.35)	0.51 (0.33)
EQ-5Dvas	0 to 100	58.71 (15.94)	53.08 (18.61)
HADS anxiety	12 to 0	7.24 (4.51)	5.27 (4.59)
HADS depression	12 to 0	6.76 (3.78)	7.27 (4.76)

TABLE 43 - Mean estimated difference in outcomes at 12 months adjusted for baseline scores by analysis of covariance

Outcome	Mean estimated difference adjusted for baseline	Lower 95% CI	Upper 95% CI	p-value
EQ-5Dindex	0.147	–0.051	0.345	0.141
EQ-5Dvas	6.315	–3.184	15.815	0.187
HADS anxiety	0.223	–1.906	2.351	0.834
HADS depression	–0.167	–2.423	2.089	0.882

Secondary outcomes 5: therapist-rated outcomes

Median ratings for the four TOMs dimensions at the end of rehabilitation were 4.0 (‘mild impairment’) or better with similar scores seen between groups on the four TOMs dimensions (Table 44). A formal test of the differences between the two treatment groups on discharge did not reveal any statistically significant findings (Table 45).

TABLE 44 - Discharge TOMs ratings

DHR, day hospital rehabilitation; HBR, home-based rehabilitation.

For the impairment scale there were two individuals from the HBR group whose data were missing. Group sizes were thus 15 and 29 for the DHR and HBR groups respectively.

Dimension	Statistic	DHR (n = 15)	HBR (n = 31)
Impairmenta	Median (min.–max.)	4.0 (1.0–4.5)	4.0 (1.0–5.0)
Activity	Median (min.–max.)	4.0 (0.0–5.0)	4.0 (1.0–5.0)
Social participation	Median (min.–max.)	4.5 (1.0–5.0)	4.0 (2.0–5.0)
Well-being	Median (min.–max.)	4.0 (2.0–5.0)	4.0 (3.0–5.0)

TABLE 45 - Test of differences between groups on discharge TOMs scores

	Impairment	Activity	Social participation	Well-being
Mann–Whitney U test	188.50	211.50	199.00	218.00
p-value	0.455	0.613	0.421	0.718

Changes in therapist-rated outcomes between treatment groups for the subset of patients for whom data were available are compared in Table 46. Focusing on patients who improved between initial and discharge assessment (Figure 8), there was a greater proportion of patients with a positive direction of change in the day hospital group on all aspects of the TOMs rating scale with the exception of social participation. However, if deterioration in TOMs rating is considered, a smaller proportion of patients in the home care group were seen to have a negative direction of change following rehabilitation.

TABLE 46 - Changes in TOMs ratings between initial and discharge assessment

DHR, day hospital rehabilitation; HBR, home-based rehabilitation.

For the impairment scale there were two individuals from the HBR group whose data were missing. Group sizes were thus 15 and 29 for the DHR and HBR groups respectively.

Dimension	Direction of change	DHR (n = 15)	HBR (n = 31)
Impairmenta	Negative	1 (6.7%)	1 (3.4%)
	Sustained	6 (40%)	14 (48.3%)
	Positive	8 (53.3%)	14 (48.3%)
Activity	Negative	2 (13.3%)	0
	Sustained	4 (26.7%)	14 (45.2%)
	Positive	9 (60%)	17 (54.8%)
Social participation	Negative	2 (13.3%)	0
	Sustained	4 (26.7%)	11 (35.5%)
	Positive	9 (60%)	20 (64.5%)
Well-being	Negative	0	0
	Sustained	6 (40%)	17 (54.8%)
	Positive	9 (60%)	14 (45.2%)

FIGURE 8.

Percentage of those who improved between baseline and discharge assessment by randomisation group.

Secondary outcomes 6: carer psychological health at 3, 6 and 12 months

In both treatment groups, 23 of the 42 (55%) patients who provided baseline data had carers (55%), the psychological well-being of whom was measured using the GHQ-30 at 3, 6 and 12 months. Mean GHQ-30 scores for the carers who completed this questionnaire at each follow-up point are given in Table 47. There was no evidence of any differences in the psychological health of carers of day hospital patients and home-based patients at any of the three follow-up points.

TABLE 47 - Mean carer GHQ-30 scores at each follow-up point

DHR, day hospital rehabilitation; HBR, home-based rehabilitation.

Follow-up point	Group size		GHQ-30 total score, mean (SD)		Mean difference	Lower 95% CI	Upper 95% CI	p-value
	DHR	HBR	DHR	HBR
3 months	23	23	33.91 (16.40)	35.96 (13.21)	–2.04	–10.89	6.80	0.644
6 months	20	21	34.45 (14.08)	35.33 (16.92)	–0.883	–10.75	8.979	0.857
12 months	13	18	31.54 (9.95)	31.78 (4.60)	–0.239	–8.73	8.251	0.954

Secondary outcomes 7: hospital admissions during the 12-month follow-up period

The frequency of hospital admissions for both sets of patients over the 12-month follow-up period is shown in Table 48. Fewer patients in the home-based care group were admitted to hospital on any occasion over the observation period (43% versus 52%); however, this difference was not statistically significant (OR 0.75, 95% CI 0.62 to 3.47, p = 0.383). For those patients who had at least one hospital admission (22 in the day hospital rehabilitation group and 18 in the home-based rehabilitation group), the mean total length of stay was greater for the day hospital group (mean difference 9.3 days, 95% CI –12.5 to 31.1 days) but, as the confidence interval indicates, this difference was not statistically significant. The mean duration of stay per visit was similar (day hospital rehabilitation 15.8 days versus home-based rehabilitation 16.4 days, p = 0.936).

TABLE 48 - Frequency of hospital admissions during the 12-month follow-up period

DHR, day hospital rehabilitation; HBR, home-based rehabilitation.

Number of admissions	DHR (n = 42)	HBR (n = 42)	Total
None	20 (47.62%)	24 (57.14%)	44 (52.38%)
One	11 (26.19%)	14 (33.33%)	25 (29.76%)
Two	7 (16.67%)	1 (2.38%)	8 (9.52%)
Three	4 (9.52%)	3 (7.14%)	7 (8.33%)

As hospital admission data were in the form of counts, a Poisson regression model was also fitted. The number of admissions over the 12-month follow-up period was not affected by place of care in this model (exp^β = 0.68, 95% CI 0.41 to 1.12, p = 0.130).

Changes in principal outcomes during the 6 months’ follow-up

In total, 32 patients in each arm of the study provided outcome data at all three follow-up points up to 6 months. To examine the extent to which outcomes changed over this period, and whether they did so in a different way depending upon which group is considered (an ‘interaction effect’), a repeated measures ANOVA model was formed for the five main outcome variables. Means plots for the five outcomes are given in Figure 9 and the resulting p-values for these models are shown in Table 49. The p-values for the three effects may be interpreted as follows:

1. between-group effect – looks for a significant difference in mean outcome scores between the two groups, ignoring any changes over the course of the study

2. follow-up point effect (within-group effect) – looks for a significant difference in mean outcome over the 6-month follow-up period, ignoring any differences between the groups

3. group × follow-up point interaction (interaction effect) – examines whether any changes that occur over the 6-month follow-up period do so in a consistent manner across both groups.

FIGURE 9.

Effect of place of care on patient outcomes at baseline, 3 and 6 months.

TABLE 49 - p-values for repeated measures analysis of variance (see Figure 9)

Outcome	Group effect	Follow-up effect	Interaction
NEADL total	0.898	0.877	0.410
EQ-5Dindex	0.815	0.677	0.002
EQ-5Dvas	0.954	0.217	0.956
HADS anxiety	0.180	0.001	0.219
HADS depression	0.725	0.017	0.225

There was no evidence of change in either NEADL total scores nor EQ-5D measures over the 6-month follow-up period; however, both HADS scales saw statistically significant improvements, with most of this seen between baseline and 3 months. Although there was clear evidence of an interaction for the EQ-5D_index outcome, neither main effect reached statistical significance.

ITT analyses with LOCF imputation for missing data due to loss to follow-up

Mean total NEADL scores at 6 months along with those for the other main patient outcomes after replacement of missing data due to loss to follow-up by the LOCF method are shown in Table 50, and estimated differences in group means following adjustment for baseline scores are given in Table 51. A statistically significant difference in outcome was observed for HADS depression, which was estimated to be 1.4 points better in the home-based rehabilitation group. Although no other statistically significant findings were observed, Figure 10 shows that, consistent with the non-LOCF data set, one confidence interval fell outside of the 10% non-inferiority margin – HADS anxiety.

TABLE 50 - Summary of patient outcomes at 6 months following LOCF imputation

DHR, day hospital rehabilitation; HBR, home-based rehabilitation.

Outcome	Possible range (worst to best)	DHR (n = 42), mean (SD)	HBR (n = 42), mean (SD)
NEADL total score	0 to 66	28.34 (15.33)	29.23 (16.66)
EQ-5Dindex	–0.59 to 1.00	0.51 (0.26)	0.52 (0.34)
EQ-5Dvas	0 to 100	56.93 (16.28)	58.23 (18.27)
HADS anxiety	12 to 0	6.12 (4.48)	5.59 (3.83)
HADS depression	12 to 0	7.24 (3.53)	6.07 (3.94)

TABLE 51 - Mean estimated difference in outcomes at 6 months adjusted for baseline scores by analysis of covariance (LOCF imputation)

Outcome	Mean estimated difference adjusted for baseline	Lower 95% CI	Upper 95% CI	p-value
NEADL total score	–3.222	–7.687	1.243	0.155
EQ-5Dindex	0.011	–0.109	0.131	0.857
EQ-5Dvas	–2.937	–8.991	3.117	0.337
HADS anxiety	–0.347	–1.843	1.160	0.648
HADS depression	1.357	0.050	2.663	0.042

FIGURE 10.

Summary of the effect of place of care on patient outcomes at 6 months (LOCF data set).

Comparison between observed case, LOCF and MMRM estimates of differences between rehabilitation groups at 6 months

Estimated differences in 6-month patient outcomes (± 95% CI) obtained from the observed case and LOCF data sets are compared in Table 52, along with the estimates provided by the MMRM analysis. These estimates are compared graphically in Figure 11 for the primary outcome measures and in Appendix 2 for secondary measures (see Figures 29–31). For the NEADL (total) outcome it can be seen that the estimated mean effect of place of rehabilitation is larger when derived from the LOCF imputed data set and from the MMRM analysis. Importantly, however, the confidence interval relevant to the non-inferiority range (shown in the shaded area) is similar for each of the three methods and the general conclusion reached from the primary analysis data set remains. Inferences made for the EQ-5D_index, HADS anxiety and HADS depression using data from the observed case data set are similarly reinforced by the supplementary analyses.

TABLE 52 - Comparison between estimated group differences derived from the observed case (primary analysis) and ITT (LOCF) data sets, and those using all available data (MMRM)

Unable to obtain estimate because of limitations of the data set.

Outcome	Estimated value	Observed case data set	LOCF data set	MMRM analysis
NEADL total score	Mean difference	–2.139	–3.222	–4.150
	Upper 95% CI	2.592	1.243	1.784
	Lower 95% CI	–6.870	–7.687	–10.083
EQ-5Dindex	Mean difference	0.023	0.011	0.161
	Upper 95% CI	0.161	0.131	0.329
	Lower 95% CI	–0.114	–0.109	–0.007
EQ-5Dvas	Mean difference	–1.601	–2.937	a
	Upper 95% CI	5.607	3.117	a
	Lower 95% CI	–8.809	-8.991	a
HADS anxiety	Mean difference	–0.578	–0.347	–0.213
	Upper 95% CI	1.253	1.160	1.968
	Lower 95% CI	–2.409	–1.843	–2.393
HADS depression	Mean difference	1.033	1.357	2.280
	Upper 95% CI	2.507	2.663	4.374
	Lower 95% CI	–0.441	0.050	0.185

FIGURE 11.

Estimated difference in NEADL total scores at 6 months between day hospital rehabilitation and home-based rehabilitation using different statistical approaches. Direction of effect same as in Figure 10.

Analysis of costs

Breakdown of costs

Table 54 provides a breakdown of the unadjusted costs accumulated by patients in each arm at 7 and 13 months. As previously discussed there was considerable variation in follow-up times for administration of the economic questionnaires, hence the analysis presented here excludes data when the time interval for the questionnaire varied by more than 16% from the intended analysis point. In practice, nine economic questionnaires were excluded because they fell outside the range 179–247 days, and one economic questionnaire was excluded because it fell outside the range 332–458 days. It should be stressed that apart from these exclusions the data have not been adjusted for variations in follow-up times. Statistical analysis and inference were not attempted before adjusting for discrepancies in follow-up times. The data are provided as an illustration of the contributions of different components to overall costs.

TABLE 54 - Unadjusted costs at 7 and 13 months after randomisation, broken down by category

LA, local authority.

		Ancillary NHS costs	Residential/day care	Private expenses	Home care NHS/LA	Informal care	Rehabilitation cost	Inpatient costs	Total private	Total public	Total
7 Months
Day hospital	Entries	28	28	28	28	28	26	32	28	27	27
	Mean	£1197	£206	£424	£218	£6824	£2803	£1280	£7248	£4043	£11,376
	Median	£788	£0	£82	£0	£1278	£3006	£0	£1469	£3718	£7504
Hospital at home	Entries	28	28	28	28	28	28	33	28	27	27
	Mean	£1626	£101	£306	£3299	£8543	£310	£1003	£8849	£5996	£14,412
	Median	£861	£0	£83	£0	£3090	£231	£0	£3686	£1331	£7870
Hospital at home excl. 3607	Entries	27	27	27	27	27	27	32	27	26	26
	Mean	£1662	£93	£317	£733	£7516	£309	£1005	£7833	£3347	£10,691
	Median	£867	£0	£93	£0	£2596	£190	£0	£3609	£1281	£6522
13 Months
Day hospital	Entries	16	16	16	16	16	27	32	16	16	16
	Mean	£1993	£936	£2534	£935	£13,652	£1847	£1478	£16,186	£7902	£24,088
	Median	£1589	£0	£227	£0	£2526	£2039	£0	£3120	£4018	£11,405
Hospital at home	Entries	26	26	26	26	26	29	33	26	26	26
	Mean	£2750	£1311	£732	£4855	£14,201	£326	£1320	£14,933	£9982	£24,916
	Median	£1704	£0	£185	£0	£4236	£268	£0	£4504	£2968	£18,218
Hospital at home excl. 3607	Entries	25	25	25	25	25	28	32	25	25	25
	Mean	£2815	£1059	£583	£1183	£12,727	£326	£1332	£13,310	£6113	£19,423
	Median	£1888	£0	£160	£0	£4032	£194	£0	£4343	£2928	£17,400

The cost data for all patients with three or four economic questionnaires and a rehabilitation log (56 patients) are plotted in Figures 12 and 13. The graphs present costs against the time interval at follow-up for each patient with data at 7 months and at 13 months. Patient 3607 stands out in both plots as having accumulated the highest costs at both follow-up intervals.

FIGURE 12.

Total public sector costs plotted for each patient after 7 and 13 months.

FIGURE 13.

Total costs plotted for each patient 7 and 13 months after randomisation.

The median number of entries on the rehabilitation logs is approximately twice as large for patients in the day hospitals (median 18) as for home-based rehabilitation patients (median 9.5). The difference is statistically significant (Mann–Whitney U test, p = 0.001). Although this may simply reflect a more segmented approach to rehabilitative care for the group in the day hospitals, it is possible that illness severity was higher in this group or that the rehabilitation logs did not capture all of the care package for patients rehabilitated at home.

Ancillary care includes primary care, outpatient visits, tests and investigations, ambulance use, home adaptations/equipment, and all home visits by professionals not directly involved in the rehabilitative care (psychologists, etc). Residential/day care covers residential accommodation, sitting services and day care centres (not day hospital rehabilitation). Home care is the cost of care assistance provided at home by the NHS or local authority. Private expenses are all patient costs including drugs, transport, meals on wheels, private treatment and care costs. Informal care is the total unpaid care assistance received by the patient, valued at £8/hour. The rehabilitation cost is the cost of the direct rehabilitative care package provided as home-based rehabilitation or in the day hospital, which includes staff costs, overheads and transport costs. Inpatient costs record the cost of all inpatient stays during the follow-up period (213 and 395 days), valued at £187 per day (UCHSC 2006).

Sensitivity analysis

Much of the recorded resource use for rehabilitating patients consists of formal and informal care. The contribution of informal carers was quite considerable and a detailed examination of the consequences of the valuation of this input was undertaken. Table 56 compares mean and median total costs, with an hour of informal care valued at £0, £4, £8, £12 and £16. Although changing the value of informal care has a very large impact on total mean and median costs, its impact on the relative differences between the two groups is small. The exception to this is the median cost for the home-based rehabilitation group when informal care is valued at £0. Nevertheless Mann–Whitney U tests suggest the differences are not statistically significant, even with informal care ignored.

TABLE 56 - Total care costs at 213 and 395 days with the value of informal care varied from £0 to £16

DHR, day hospital rehabilitation; HBR, home-based rehabilitation.

		Care valued at £0			Care valued at £4			Care valued at £8			Care valued at £12			Care valued at £16
		DHR	HBR	p-value	DHR	HBR	p-value	DHR	HBR	p-value	DHR	HBR	p-value	DHR	HBR	p-value
213 Days
All data	Mean	£4484	£6464		£7293	£10,397		£10,102	£14,330		£12,910	£18,263		£15,719	£22,196
	Median	£3151	£1585	0.20	£4720	£5592	0.77	£5948	£7679	0.76	£6213	£9,766	0.60	£6,797	£11,854	0.66
	Entries	21	25		21	25		21	25		21	25		21	25
Excluding patient 3607	Mean	£4484	£3677		£7293	£7034		£10,102	£10,390		£12,910	£13,747		£15,719	£17,103
	Median	£3151	£1444	0.12	£4720	£4747	0.59	£5948	£6531	0.58	£6213	£8,524	0.43	£6,797	£10,518	0.49
	Entries	21	24		21	24		21	24		21	24		21	24
395 Days
All data	Mean	£8207	£10,699		£16,010	£18,402		£23,812	£26,105		£31,615	£33,808		£39,417	£41,511
	Median	£4850	£2882	0.49	£7767	£14,344	0.92	£9,842	£18,432	0.95	£11,445	£20,954	1.00	£13,048	£22,766	1.00
	Entries	13	23		13	23		13	23		13	23		13	23
Excluding patient 3607	Mean	£8207	£6229		£16,010	£13,140		£23,812	£20,052		£31,615	£26,964		£39,417	£33,876
	Median	£4850	£2815	0.35	£7767	£13,295	0.75	£9842	£17,707	0.77	£11,445	£20,588	0.85	£13,048	£22,389	0.82
	Entries	13	22		13	22		13	22		13	22		13	22

A large component of the direct rehabilitative costs in day hospitals comprises the hospital overheads and the cost of patient transport to and from the hospital. Clearly estimation of these costs will have an impact on any differences in costs between home-based rehabilitation and day hospital care. In the main analysis centre-specific day hospital overhead estimates were applied to each day hospital patient’s cost. The vast majority of day hospital cases originated from Chippenham and North Tyneside, both of which had overhead estimates that were below average for the four sites in the trial. Replacing the site-specific overhead estimates with the mean overheads of £68.50 marginally increased mean and median costs in the day hospital rehabilitation group, but any differences between the two arms remained non-significant at 5%. A further analysis of overhead and patient transport costs was undertaken in which the total overhead and transport costs attributed to a patient for each day’s attendance at the day hospital was varied between £120 and £250. The results are presented in Figure 14. It is evident that mean costs for the day hospital rehabilitation group lie between mean costs for the home-based rehabilitation group with and without the exclusion of the most expensive patient in that group.

FIGURE 14.

Sensitivity analysis examining the effect of changing hospital overheads/transport costs.

Although medians might be regarded as a better measure of location for non-symmetrically distributed data, means are a better indicator of volume costs. Hence, mean costs may be more useful than median costs for decision-makers. Means are susceptible to outliers, and exclusion of patient 3607 from the home-based rehabilitation group has a large impact. Mean public sector and total costs are reduced with most now falling below mean values for the day hospital rehabilitation group. Figures 12 and 13 illustrate the spread of the data. Although patient 3607 incurs the highest costs at 7 and 13 months in both figures, it is not clear that this patient is an outlier. The data spread, particularly in the home-based rehabilitation arm, is considerable, and we would expect it to be right skewed. It is possible that costs in the home-based rehabilitation arm are artificially inflated by the inclusion of this particularly resource-intensive patient, but there appears to be no clear basis for exclusion. It is conceivable that resource-intensive patients might be particularly expensive to treat at home.

The breakdown of costs in Table 54 illustrates the significant burden rehabilitating patients place on carers. Direct rehabilitative care costs do appear to be much lower for patients rehabilitated at home, but given the small numbers of patients in the day hospital rehabilitation arm with data at 12 months (395 days) it might be unwise to search the data looking for significant differences in the breakdown of costs. Nevertheless the data suggest the possibility that costs incurred in the direct rehabilitative care of day hospital rehabilitation patients are being displaced into other areas such as primary care for the home-based rehabilitation patients. The analysis of resource use in Table 53 also suggests an increased burden in primary care for home-based rehabilitation patients.

The total costs in the study include informal care and the contribution of voluntary care was very large. It is possible that the economic questionnaires overestimated the contribution of friends and relatives who may not have been fully occupied with care duties during the time periods given. The methodology to value this care is contentious. 80 A value of £8 an hour was chosen in the base case, which is similar to the average hourly wage of a local authority home care worker (£7.30, UCHSC 2006). A strict replacement cost approach would have substituted the unit cost of an hour of home care provided by the local authority (£16, UCHSC 2006). 81 An opportunity cost approach would require the estimation of the value of the opportunities forgone in providing care82 (often taken as the subject’s wage rate.) This is not easy to establish for retired carers, but is unlikely to be zero. Ignoring these costs is tantamount to assuming that the carer’s time is valued at zero, which is unlikely to be consistent with any of the proposed valuation methods. The sensitivity analysis demonstrates that informal care has a sizeable impact on total costs, but little impact on the relative cost differences between the two arms. In the absence of informal care costs (care valued at £0) there remain no statistically significant differences between costs in the two trial arms.

The efficiency of day hospitals is likely to be a key consideration in the analysis of cost differences between day hospital rehabilitation and home-based rehabilitation. The reference cost submissions from the four trial sites suggest significant variation in the efficiency of day hospital provision. The reference cost submissions include therapeutic staff whereas these costs were netted out when calculating overhead costs. Consequently it is unclear what the national average day hospital overheads are. The mean overheads of £68.50 for the four sites may well be typical. Addition of patient transport costs to the mean overheads suggests that overheads and transport costs for day hospital patients are typically around £170 per day. The impact of these costs on cost differences between day hospital rehabilitation and home-based rehabilitation is illustrated in Figure 14. Median public sector costs are lower for the home-based rehabilitation patients, and Mann–Whitney U tests suggest that the differences are approaching statistical significance at high values for overheads/transport. However, the mean public sector costs are higher for the home-based rehabilitation patients before patient 3607 is excluded. This would suggest that, although ‘typical’ public sector costs are lower in the home-based rehabilitation arm, volume costs are higher. Although more seriously ill patients are likely to accrue a greater number of day hospital attendances, there may be some efficiencies to be gained by transporting them to the treatment centre. In contrast, the rehabilitative costs of treatment at the patient’s home may be more linearly dependent on the number of contacts with professionals. We would expect this to manifest itself as a larger spread of costs for the home-based rehabilitation patients, and Figure 12 supports this. A larger spread in combination with the skewed nature of costs may be responsible for the different inferences drawn from the mean and median data.

The impact of varying the overhead/transport costs on total costs is less ambiguous (Figure 14). Mean and median total costs for the day hospital rehabilitation patients are generally lower although none of the differences approaches statistical significance.

Theoretically, analysis of the 12-month follow-up data (at 395 days) is preferable to analysis of the 6-month follow-up data (at 213 days) as not all patients have been discharged from formal rehabilitation at 213 days. However, the limited data at 395 days reduce the power of the analysis. Analysis of mean costs paints a different picture to the analysis of median costs. Mean total and public sector costs are higher in the home-based rehabilitation group than in the day hospital rehabilitation group. Median public sector costs are lower in the home-based rehabilitation group but median total costs remain higher. It should be highlighted that none of these differences is statistically significant, hence we must conclude that the analysis of costs does not provide sufficient evidence to determine whether home-based rehabilitation is less costly than rehabilitation at day hospitals.

Implications for practice

• Compared with day hospital rehabilitation, providing rehabilitation in patients’ own homes confers no particular disadvantage for patients and carers.

• Our results are consistent with the non-inferiority of home-based rehabilitation compared with day hospital rehabilitation.

• The cost of providing home-based rehabilitation does not appear to be significantly different from that of providing rehabilitation in a day hospital.

• Rehabilitation providers and purchasers need to consider the place of care in the light of local needs, to provide the benefits of both kinds of services.

Taking account of the limitations of this study, the findings provide useable new information to inform decisions on the provision of rehabilitation services for older people in local areas. Our findings suggest that patients receiving rehabilitation in their own homes are not disadvantaged and that the cost of providing home-based rehabilitation is not significantly different from that of providing rehabilitation in a day hospital. This concurs with the literature evidence about alternatives to day hospital care, which shows that provided an active and comprehensive alternative is provided in the community then there is no particular disadvantage for patients and carers. This point is of course vital when decisions are being made about which services to provide in which setting.

It is clear that we have not shown that either setting for rehabilitation offers decisive advantages over the other. We have also shown that costs are probably fairly similar. However, it is also apparent that home-based and day hospital rehabilitation teams tend to offer somewhat different mixes of clinical skills and services, and that many referrals are made outside of even the relatively unrestricted inclusion criteria for this trial.

In considering the implications for future research we can see that it was ambitious to attempt a definitive trial of day hospital versus home-based rehabilitation in essentially unselected older people with rehabilitation needs. We believe that the approach was correct but acknowledge that the challenges we experienced in recruiting sites and subjects resulted in disappointingly low levels of participation in the trial.

Implications for research

• Future research in this area should examine syndrome- or condition-specific approaches to providing for the needs of older people in ambulatory care.

• Further attempts to address issues of cost-effectiveness and place of care in elderly rehabilitation research should focus more on the cost-effective use of specific day hospital services, rather than on whether they compete with community care settings.

• The development and assessment of approaches and instruments for measuring outcomes for older people in receipt of rehabilitation in ambulatory care remains a justifiable focus for future research and development.

• Rather than comparing these settings for efficacy, future research might focus on identifying those services that are better provided in one or other setting, and will take account of the current commissioning environment that explicitly supports choice in the provision of health services for patients.

The reasons for referral for rehabilitation fell into a small number of categories (stroke, falls, mobility assessment). Each of these is likely to be associated with differences in processes, costs and outcomes and this may well have been reflected in the wide range of costs that were observed. This suggests that future research may need to focus on condition- or syndrome-specific questions in establishing the effectiveness of services provided in day hospitals.

Day hospitals have a long tradition of providing specialist services for older people, including rehabilitation, but there has been little previous and no recent research on their use as a setting for rehabilitation. Overhead calculations suggested a significant difference in costs in the four day hospitals studied. This, together with rapid change in the service infrastructure and environment, may mean that further attempts to address issues of cost-effectiveness and place of care in elderly rehabilitation research should focus more on the cost-effective use of specific day hospital services (such as falls and mobility assessment services), rather than on whether they compete with community care settings.

We have not demonstrated equivalence of effect between the two settings; rather our results are consistent with the non-inferiority of home-based rehabilitation compared with day hospital rehabilitation. More research would be required to provide a definitive answer to this question; however, the large numbers of subjects whose needs were met outside of the clinical pathways leading to recruitment and randomisation suggests that local service providers may already be directing older people to home-based or day hospital services according to local custom, practice and patterns of service provision, adding further weight to the assertion that future research in this area will need to examine these syndrome- or condition-specific approaches to providing for the needs of older people in ambulatory care.

Choice of primary outcome measure for future studies in this area is of key importance. Despite some evidence of responsiveness in similar patient populations, the NEADL scale did not prove sufficiently responsive for use as a primary outcome measure. Other approaches are suggested by the fact that some of the psychosocial domains were apparently responsive to change in this clinical setting, and the use of goal-oriented, patient-focused measurement of outcome using TOMs has shown some promise. Therefore the development and assessment of approaches and instruments for measuring outcomes for older people in receipt of rehabilitation in ambulatory care remains a justifiable focus for future research and development.

Although the results of the literature review, national survey of NHS trusts and this small RCT taken together can be informative for local providers, purchasers, commissioners and other stakeholders in relation to rehabilitation for older people, local decisions will need to be made in the context of local service delivery infrastructure and development needs. Therefore, in deciding about the settings in which to provide rehabilitation services, stakeholders will need to consider the benefits of home-based rehabilitation and ambulatory support provided in day hospitals in the light of local needs, to provide the benefits of both kinds of services.

Contribution of authors

Stuart Parker (Professor, Health Care for Older People), John Bond (Professor, Social Gerontology and Health Services Research), Carol Jagger (Professor, Epidemiology), Pam Enderby (Professor, Rehabilitation), Richard Curless (Consultant, Geriatric Medicine), Allesandra Vanoli (Senior Research Associate, Health Economics) and Cam Donaldson (Professor, Health Economics) were involved in the conception and design of the project, acquisition analysis and interpretation of data. Kate Fryer (Research Associate) was involved in conception and design, and with Sarah Forster (Research Associate) and Derek Ross (Research Associate) had responsibility for data acquisition and project management. Alex John (Research Fellow) assisted in data acquisition analysis and interpretation, project management and TOMs training. Chris Dyer (Consultant, Geriatric Medicine), Thein Wynn (Consultant, Geriatric Medicine) and Richard Curless assisted in the acquisition of data as clinicians in the randomising sites. Mark Pennington (Research Associate, Health Economics) performed the health economic analysis with Cam Donaldson. Cindy Cooper (Director, Clinical Trials Research Unit), Steven Julious (Senior Lecturer, Medical Statistics), Tim Chater (Database Manager) and Phillip Oliver (Medical Statistician) assisted in the validation, analysis and interpretation of data. Phillip Oliver performed the statistical analyses with Steven Julious.

All authors reviewed drafts of the manuscript for critical intellectual content and gave their approval to the final version.

Disclaimers

The views expressed in this publication are those of the authors and not necessarily those of the HTA programme or the Department of Health.

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    By Lloyd Jones M, Hummel S, Bansback N, Orr B, Seymour M.

26. Comparison of the effectiveness of inhaler devices in asthma and chronic obstructive airways disease: a systematic review of the literature.

    By Brocklebank D, Ram F, Wright J, Barry P, Cates C, Davies L, et al.

27. The cost-effectiveness of magnetic resonance imaging for investigation of the knee joint.

    By Bryan S, Weatherburn G, Bungay H, Hatrick C, Salas C, Parry D, et al.

28. A rapid and systematic review of the clinical effectiveness and cost-effectiveness of topotecan for ovarian cancer.

    By Forbes C, Shirran L, Bagnall A-M, Duffy S, ter Riet G.

29. Superseded by a report published in a later volume.

30. The role of radiography in primary care patients with low back pain of at least 6 weeks duration: a randomised (unblinded) controlled trial.

    By Kendrick D, Fielding K, Bentley E, Miller P, Kerslake R, Pringle M.

31. Design and use of questionnaires: a review of best practice applicable to surveys of health service staff and patients.

    By McColl E, Jacoby A, Thomas L, Soutter J, Bamford C, Steen N, et al.

32. A rapid and systematic review of the clinical effectiveness and cost-effectiveness of paclitaxel, docetaxel, gemcitabine and vinorelbine in non-small-cell lung cancer.

    By Clegg A, Scott DA, Sidhu M, Hewitson P, Waugh N.

33. Subgroup analyses in randomised controlled trials: quantifying the risks of false-positives and false-negatives.

    By Brookes ST, Whitley E, Peters TJ, Mulheran PA, Egger M, Davey Smith G.

34. Depot antipsychotic medication in the treatment of patients with schizophrenia: (1) Meta-review; (2) Patient and nurse attitudes.

    By David AS, Adams C.

35. A systematic review of controlled trials of the effectiveness and cost-effectiveness of brief psychological treatments for depression.

    By Churchill R, Hunot V, Corney R, Knapp M, McGuire H, Tylee A, et al.

36. Cost analysis of child health surveillance.

    By Sanderson D, Wright D, Acton C, Duree D.

1. A study of the methods used to select review criteria for clinical audit.

   By Hearnshaw H, Harker R, Cheater F, Baker R, Grimshaw G.

2. Fludarabine as second-line therapy for B cell chronic lymphocytic leukaemia: a technology assessment.

   By Hyde C, Wake B, Bryan S, Barton P, Fry-Smith A, Davenport C, et al.

3. Rituximab as third-line treatment for refractory or recurrent Stage III or IV follicular non-Hodgkin’s lymphoma: a systematic review and economic evaluation.

   By Wake B, Hyde C, Bryan S, Barton P, Song F, Fry-Smith A, et al.

4. A systematic review of discharge arrangements for older people.

   By Parker SG, Peet SM, McPherson A, Cannaby AM, Baker R, Wilson A, et al.

5. The clinical effectiveness and cost-effectiveness of inhaler devices used in the routine management of chronic asthma in older children: a systematic review and economic evaluation.

   By Peters J, Stevenson M, Beverley C, Lim J, Smith S.

6. The clinical effectiveness and cost-effectiveness of sibutramine in the management of obesity: a technology assessment.

   By O’Meara S, Riemsma R, Shirran L, Mather L, ter Riet G.

7. The cost-effectiveness of magnetic resonance angiography for carotid artery stenosis and peripheral vascular disease: a systematic review.

   By Berry E, Kelly S, Westwood ME, Davies LM, Gough MJ, Bamford JM, et al.

8. Promoting physical activity in South Asian Muslim women through ‘exercise on prescription’.

   By Carroll B, Ali N, Azam N.

9. Zanamivir for the treatment of influenza in adults: a systematic review and economic evaluation.

   By Burls A, Clark W, Stewart T, Preston C, Bryan S, Jefferson T, et al.

10. A review of the natural history and epidemiology of multiple sclerosis: implications for resource allocation and health economic models.

    By Richards RG, Sampson FC, Beard SM, Tappenden P.

11. Screening for gestational diabetes: a systematic review and economic evaluation.

    By Scott DA, Loveman E, McIntyre L, Waugh N.

12. The clinical effectiveness and cost-effectiveness of surgery for people with morbid obesity: a systematic review and economic evaluation.

    By Clegg AJ, Colquitt J, Sidhu MK, Royle P, Loveman E, Walker A.

13. The clinical effectiveness of trastuzumab for breast cancer: a systematic review.

    By Lewis R, Bagnall A-M, Forbes C, Shirran E, Duffy S, Kleijnen J, et al.

14. The clinical effectiveness and cost-effectiveness of vinorelbine for breast cancer: a systematic review and economic evaluation.

    By Lewis R, Bagnall A-M, King S, Woolacott N, Forbes C, Shirran L, et al.

15. A systematic review of the effectiveness and cost-effectiveness of metal-on-metal hip resurfacing arthroplasty for treatment of hip disease.

    By Vale L, Wyness L, McCormack K, McKenzie L, Brazzelli M, Stearns SC.

16. The clinical effectiveness and cost-effectiveness of bupropion and nicotine replacement therapy for smoking cessation: a systematic review and economic evaluation.

    By Woolacott NF, Jones L, Forbes CA, Mather LC, Sowden AJ, Song FJ, et al.

17. A systematic review of effectiveness and economic evaluation of new drug treatments for juvenile idiopathic arthritis: etanercept.

    By Cummins C, Connock M, Fry-Smith A, Burls A.

18. Clinical effectiveness and cost-effectiveness of growth hormone in children: a systematic review and economic evaluation.

    By Bryant J, Cave C, Mihaylova B, Chase D, McIntyre L, Gerard K, et al.

19. Clinical effectiveness and cost-effectiveness of growth hormone in adults in relation to impact on quality of life: a systematic review and economic evaluation.

    By Bryant J, Loveman E, Chase D, Mihaylova B, Cave C, Gerard K, et al.

20. Clinical medication review by a pharmacist of patients on repeat prescriptions in general practice: a randomised controlled trial.

    By Zermansky AG, Petty DR, Raynor DK, Lowe CJ, Freementle N, Vail A.

21. The effectiveness of infliximab and etanercept for the treatment of rheumatoid arthritis: a systematic review and economic evaluation.

    By Jobanputra P, Barton P, Bryan S, Burls A.

22. A systematic review and economic evaluation of computerised cognitive behaviour therapy for depression and anxiety.

    By Kaltenthaler E, Shackley P, Stevens K, Beverley C, Parry G, Chilcott J.

23. A systematic review and economic evaluation of pegylated liposomal doxorubicin hydrochloride for ovarian cancer.

    By Forbes C, Wilby J, Richardson G, Sculpher M, Mather L, Reimsma R.

24. A systematic review of the effectiveness of interventions based on a stages-of-change approach to promote individual behaviour change.

    By Riemsma RP, Pattenden J, Bridle C, Sowden AJ, Mather L, Watt IS, et al.

25. A systematic review update of the clinical effectiveness and cost-effectiveness of glycoprotein IIb/IIIa antagonists.

    By Robinson M, Ginnelly L, Sculpher M, Jones L, Riemsma R, Palmer S, et al.

26. A systematic review of the effectiveness, cost-effectiveness and barriers to implementation of thrombolytic and neuroprotective therapy for acute ischaemic stroke in the NHS.

    By Sandercock P, Berge E, Dennis M, Forbes J, Hand P, Kwan J, et al.

27. A randomised controlled crossover trial of nurse practitioner versus doctor-led outpatient care in a bronchiectasis clinic.

    By Caine N, Sharples LD, Hollingworth W, French J, Keogan M, Exley A, et al.

28. Clinical effectiveness and cost – consequences of selective serotonin reuptake inhibitors in the treatment of sex offenders.

    By Adi Y, Ashcroft D, Browne K, Beech A, Fry-Smith A, Hyde C.

29. Treatment of established osteoporosis: a systematic review and cost–utility analysis.

    By Kanis JA, Brazier JE, Stevenson M, Calvert NW, Lloyd Jones M.

30. Which anaesthetic agents are cost-effective in day surgery? Literature review, national survey of practice and randomised controlled trial.

    By Elliott RA Payne K, Moore JK, Davies LM, Harper NJN, St Leger AS, et al.

31. Screening for hepatitis C among injecting drug users and in genitourinary medicine clinics: systematic reviews of effectiveness, modelling study and national survey of current practice.

    By Stein K, Dalziel K, Walker A, McIntyre L, Jenkins B, Horne J, et al.

32. The measurement of satisfaction with healthcare: implications for practice from a systematic review of the literature.

    By Crow R, Gage H, Hampson S, Hart J, Kimber A, Storey L, et al.

33. The effectiveness and cost-effectiveness of imatinib in chronic myeloid leukaemia: a systematic review.

    By Garside R, Round A, Dalziel K, Stein K, Royle R.

34. A comparative study of hypertonic saline, daily and alternate-day rhDNase in children with cystic fibrosis.

    By Suri R, Wallis C, Bush A, Thompson S, Normand C, Flather M, et al.

35. A systematic review of the costs and effectiveness of different models of paediatric home care.

    By Parker G, Bhakta P, Lovett CA, Paisley S, Olsen R, Turner D, et al.

1. How important are comprehensive literature searches and the assessment of trial quality in systematic reviews? Empirical study.

   By Egger M, Jüni P, Bartlett C, Holenstein F, Sterne J.

2. Systematic review of the effectiveness and cost-effectiveness, and economic evaluation, of home versus hospital or satellite unit haemodialysis for people with end-stage renal failure.

   By Mowatt G, Vale L, Perez J, Wyness L, Fraser C, MacLeod A, et al.

3. Systematic review and economic evaluation of the effectiveness of infliximab for the treatment of Crohn’s disease.

   By Clark W, Raftery J, Barton P, Song F, Fry-Smith A, Burls A.

4. A review of the clinical effectiveness and cost-effectiveness of routine anti-D prophylaxis for pregnant women who are rhesus negative.

   By Chilcott J, Lloyd Jones M, Wight J, Forman K, Wray J, Beverley C, et al.

5. Systematic review and evaluation of the use of tumour markers in paediatric oncology: Ewing’s sarcoma and neuroblastoma.

   By Riley RD, Burchill SA, Abrams KR, Heney D, Lambert PC, Jones DR, et al.

6. The cost-effectiveness of screening for Helicobacter pylori to reduce mortality and morbidity from gastric cancer and peptic ulcer disease: a discrete-event simulation model.

   By Roderick P, Davies R, Raftery J, Crabbe D, Pearce R, Bhandari P, et al.

7. The clinical effectiveness and cost-effectiveness of routine dental checks: a systematic review and economic evaluation.

   By Davenport C, Elley K, Salas C, Taylor-Weetman CL, Fry-Smith A, Bryan S, et al.

8. A multicentre randomised controlled trial assessing the costs and benefits of using structured information and analysis of women’s preferences in the management of menorrhagia.

   By Kennedy ADM, Sculpher MJ, Coulter A, Dwyer N, Rees M, Horsley S, et al.

9. Clinical effectiveness and cost–utility of photodynamic therapy for wet age-related macular degeneration: a systematic review and economic evaluation.

   By Meads C, Salas C, Roberts T, Moore D, Fry-Smith A, Hyde C.

10. Evaluation of molecular tests for prenatal diagnosis of chromosome abnormalities.

    By Grimshaw GM, Szczepura A, Hultén M, MacDonald F, Nevin NC, Sutton F, et al.

11. First and second trimester antenatal screening for Down’s syndrome: the results of the Serum, Urine and Ultrasound Screening Study (SURUSS).

    By Wald NJ, Rodeck C, Hackshaw AK, Walters J, Chitty L, Mackinson AM.

12. The effectiveness and cost-effectiveness of ultrasound locating devices for central venous access: a systematic review and economic evaluation.

    By Calvert N, Hind D, McWilliams RG, Thomas SM, Beverley C, Davidson A.

13. A systematic review of atypical antipsychotics in schizophrenia.

    By Bagnall A-M, Jones L, Lewis R, Ginnelly L, Glanville J, Torgerson D, et al.

14. Prostate Testing for Cancer and Treatment (ProtecT) feasibility study.

    By Donovan J, Hamdy F, Neal D, Peters T, Oliver S, Brindle L, et al.

15. Early thrombolysis for the treatment of acute myocardial infarction: a systematic review and economic evaluation.

    By Boland A, Dundar Y, Bagust A, Haycox A, Hill R, Mujica Mota R, et al.

16. Screening for fragile X syndrome: a literature review and modelling.

    By Song FJ, Barton P, Sleightholme V, Yao GL, Fry-Smith A.

17. Systematic review of endoscopic sinus surgery for nasal polyps.

    By Dalziel K, Stein K, Round A, Garside R, Royle P.

18. Towards efficient guidelines: how to monitor guideline use in primary care.

    By Hutchinson A, McIntosh A, Cox S, Gilbert C.

19. Effectiveness and cost-effectiveness of acute hospital-based spinal cord injuries services: systematic review.

    By Bagnall A-M, Jones L, Richardson G, Duffy S, Riemsma R.

20. Prioritisation of health technology assessment. The PATHS model: methods and case studies.

    By Townsend J, Buxton M, Harper G.

21. Systematic review of the clinical effectiveness and cost-effectiveness of tension-free vaginal tape for treatment of urinary stress incontinence.

    By Cody J, Wyness L, Wallace S, Glazener C, Kilonzo M, Stearns S, et al.

22. The clinical and cost-effectiveness of patient education models for diabetes: a systematic review and economic evaluation.

    By Loveman E, Cave C, Green C, Royle P, Dunn N, Waugh N.

23. The role of modelling in prioritising and planning clinical trials.

    By Chilcott J, Brennan A, Booth A, Karnon J, Tappenden P.

24. Cost–benefit evaluation of routine influenza immunisation in people 65–74 years of age.

    By Allsup S, Gosney M, Haycox A, Regan M.

25. The clinical and cost-effectiveness of pulsatile machine perfusion versus cold storage of kidneys for transplantation retrieved from heart-beating and non-heart-beating donors.

    By Wight J, Chilcott J, Holmes M, Brewer N.

26. Can randomised trials rely on existing electronic data? A feasibility study to explore the value of routine data in health technology assessment.

    By Williams JG, Cheung WY, Cohen DR, Hutchings HA, Longo MF, Russell IT.

27. Evaluating non-randomised intervention studies.

    By Deeks JJ, Dinnes J, D’Amico R, Sowden AJ, Sakarovitch C, Song F, et al.

28. A randomised controlled trial to assess the impact of a package comprising a patient-orientated, evidence-based self- help guidebook and patient-centred consultations on disease management and satisfaction in inflammatory bowel disease.

    By Kennedy A, Nelson E, Reeves D, Richardson G, Roberts C, Robinson A, et al.

29. The effectiveness of diagnostic tests for the assessment of shoulder pain due to soft tissue disorders: a systematic review.

    By Dinnes J, Loveman E, McIntyre L, Waugh N.

30. The value of digital imaging in diabetic retinopathy.

    By Sharp PF, Olson J, Strachan F, Hipwell J, Ludbrook A, O’Donnell M, et al.

31. Lowering blood pressure to prevent myocardial infarction and stroke: a new preventive strategy.

    By Law M, Wald N, Morris J.

32. Clinical and cost-effectiveness of capecitabine and tegafur with uracil for the treatment of metastatic colorectal cancer: systematic review and economic evaluation.

    By Ward S, Kaltenthaler E, Cowan J, Brewer N.

33. Clinical and cost-effectiveness of new and emerging technologies for early localised prostate cancer: a systematic review.

    By Hummel S, Paisley S, Morgan A, Currie E, Brewer N.

34. Literature searching for clinical and cost-effectiveness studies used in health technology assessment reports carried out for the National Institute for Clinical Excellence appraisal system.

    By Royle P, Waugh N.

35. Systematic review and economic decision modelling for the prevention and treatment of influenza A and B.

    By Turner D, Wailoo A, Nicholson K, Cooper N, Sutton A, Abrams K.

36. A randomised controlled trial to evaluate the clinical and cost-effectiveness of Hickman line insertions in adult cancer patients by nurses.

    By Boland A, Haycox A, Bagust A, Fitzsimmons L.

37. Redesigning postnatal care: a randomised controlled trial of protocol-based midwifery-led care focused on individual women’s physical and psychological health needs.

    By MacArthur C, Winter HR, Bick DE, Lilford RJ, Lancashire RJ, Knowles H, et al.

38. Estimating implied rates of discount in healthcare decision-making.

    By West RR, McNabb R, Thompson AGH, Sheldon TA, Grimley Evans J.

39. Systematic review of isolation policies in the hospital management of methicillin-resistant Staphylococcus aureus: a review of the literature with epidemiological and economic modelling.

    By Cooper BS, Stone SP, Kibbler CC, Cookson BD, Roberts JA, Medley GF, et al.

40. Treatments for spasticity and pain in multiple sclerosis: a systematic review.

    By Beard S, Hunn A, Wight J.

41. The inclusion of reports of randomised trials published in languages other than English in systematic reviews.

    By Moher D, Pham B, Lawson ML, Klassen TP.

42. The impact of screening on future health-promoting behaviours and health beliefs: a systematic review.

    By Bankhead CR, Brett J, Bukach C, Webster P, Stewart-Brown S, Munafo M, et al.

1. What is the best imaging strategy for acute stroke?

   By Wardlaw JM, Keir SL, Seymour J, Lewis S, Sandercock PAG, Dennis MS, et al.

2. Systematic review and modelling of the investigation of acute and chronic chest pain presenting in primary care.

   By Mant J, McManus RJ, Oakes RAL, Delaney BC, Barton PM, Deeks JJ, et al.

3. The effectiveness and cost-effectiveness of microwave and thermal balloon endometrial ablation for heavy menstrual bleeding: a systematic review and economic modelling.

   By Garside R, Stein K, Wyatt K, Round A, Price A.

4. A systematic review of the role of bisphosphonates in metastatic disease.

   By Ross JR, Saunders Y, Edmonds PM, Patel S, Wonderling D, Normand C, et al.

5. Systematic review of the clinical effectiveness and cost-effectiveness of capecitabine (Xeloda^®) for locally advanced and/or metastatic breast cancer.

   By Jones L, Hawkins N, Westwood M, Wright K, Richardson G, Riemsma R.

6. Effectiveness and efficiency of guideline dissemination and implementation strategies.

   By Grimshaw JM, Thomas RE, MacLennan G, Fraser C, Ramsay CR, Vale L, et al.

7. Clinical effectiveness and costs of the Sugarbaker procedure for the treatment of pseudomyxoma peritonei.

   By Bryant J, Clegg AJ, Sidhu MK, Brodin H, Royle P, Davidson P.

8. Psychological treatment for insomnia in the regulation of long-term hypnotic drug use.

   By Morgan K, Dixon S, Mathers N, Thompson J, Tomeny M.

9. Improving the evaluation of therapeutic interventions in multiple sclerosis: development of a patient-based measure of outcome.

   By Hobart JC, Riazi A, Lamping DL, Fitzpatrick R, Thompson AJ.

10. A systematic review and economic evaluation of magnetic resonance cholangiopancreatography compared with diagnostic endoscopic retrograde cholangiopancreatography.

    By Kaltenthaler E, Bravo Vergel Y, Chilcott J, Thomas S, Blakeborough T, Walters SJ, et al.

11. The use of modelling to evaluate new drugs for patients with a chronic condition: the case of antibodies against tumour necrosis factor in rheumatoid arthritis.

    By Barton P, Jobanputra P, Wilson J, Bryan S, Burls A.

12. Clinical effectiveness and cost-effectiveness of neonatal screening for inborn errors of metabolism using tandem mass spectrometry: a systematic review.

    By Pandor A, Eastham J, Beverley C, Chilcott J, Paisley S.

13. Clinical effectiveness and cost-effectiveness of pioglitazone and rosiglitazone in the treatment of type 2 diabetes: a systematic review and economic evaluation.

    By Czoski-Murray C, Warren E, Chilcott J, Beverley C, Psyllaki MA, Cowan J.

14. Routine examination of the newborn: the EMREN study. Evaluation of an extension of the midwife role including a randomised controlled trial of appropriately trained midwives and paediatric senior house officers.

    By Townsend J, Wolke D, Hayes J, Davé S, Rogers C, Bloomfield L, et al.

15. Involving consumers in research and development agenda setting for the NHS: developing an evidence-based approach.

    By Oliver S, Clarke-Jones L, Rees R, Milne R, Buchanan P, Gabbay J, et al.

16. A multi-centre randomised controlled trial of minimally invasive direct coronary bypass grafting versus percutaneous transluminal coronary angioplasty with stenting for proximal stenosis of the left anterior descending coronary artery.

    By Reeves BC, Angelini GD, Bryan AJ, Taylor FC, Cripps T, Spyt TJ, et al.

17. Does early magnetic resonance imaging influence management or improve outcome in patients referred to secondary care with low back pain? A pragmatic randomised controlled trial.

    By Gilbert FJ, Grant AM, Gillan MGC, Vale L, Scott NW, Campbell MK, et al.

18. The clinical and cost-effectiveness of anakinra for the treatment of rheumatoid arthritis in adults: a systematic review and economic analysis.

    By Clark W, Jobanputra P, Barton P, Burls A.

19. A rapid and systematic review and economic evaluation of the clinical and cost-effectiveness of newer drugs for treatment of mania associated with bipolar affective disorder.

    By Bridle C, Palmer S, Bagnall A-M, Darba J, Duffy S, Sculpher M, et al.

20. Liquid-based cytology in cervical screening: an updated rapid and systematic review and economic analysis.

    By Karnon J, Peters J, Platt J, Chilcott J, McGoogan E, Brewer N.

21. Systematic review of the long-term effects and economic consequences of treatments for obesity and implications for health improvement.

    By Avenell A, Broom J, Brown TJ, Poobalan A, Aucott L, Stearns SC, et al.

22. Autoantibody testing in children with newly diagnosed type 1 diabetes mellitus.

    By Dretzke J, Cummins C, Sandercock J, Fry-Smith A, Barrett T, Burls A.

23. Clinical effectiveness and cost-effectiveness of prehospital intravenous fluids in trauma patients.

    By Dretzke J, Sandercock J, Bayliss S, Burls A.

24. Newer hypnotic drugs for the short-term management of insomnia: a systematic review and economic evaluation.

    By Dündar Y, Boland A, Strobl J, Dodd S, Haycox A, Bagust A, et al.

25. Development and validation of methods for assessing the quality of diagnostic accuracy studies.

    By Whiting P, Rutjes AWS, Dinnes J, Reitsma JB, Bossuyt PMM, Kleijnen J.

26. EVALUATE hysterectomy trial: a multicentre randomised trial comparing abdominal, vaginal and laparoscopic methods of hysterectomy.

    By Garry R, Fountain J, Brown J, Manca A, Mason S, Sculpher M, et al.

27. Methods for expected value of information analysis in complex health economic models: developments on the health economics of interferon-β and glatiramer acetate for multiple sclerosis.

    By Tappenden P, Chilcott JB, Eggington S, Oakley J, McCabe C.

28. Effectiveness and cost-effectiveness of imatinib for first-line treatment of chronic myeloid leukaemia in chronic phase: a systematic review and economic analysis.

    By Dalziel K, Round A, Stein K, Garside R, Price A.

29. VenUS I: a randomised controlled trial of two types of bandage for treating venous leg ulcers.

    By Iglesias C, Nelson EA, Cullum NA, Torgerson DJ, on behalf of the VenUS Team.

30. Systematic review of the effectiveness and cost-effectiveness, and economic evaluation, of myocardial perfusion scintigraphy for the diagnosis and management of angina and myocardial infarction.

    By Mowatt G, Vale L, Brazzelli M, Hernandez R, Murray A, Scott N, et al.

31. A pilot study on the use of decision theory and value of information analysis as part of the NHS Health Technology Assessment programme.

    By Claxton K, Ginnelly L, Sculpher M, Philips Z, Palmer S.

32. The Social Support and Family Health Study: a randomised controlled trial and economic evaluation of two alternative forms of postnatal support for mothers living in disadvantaged inner-city areas.

    By Wiggins M, Oakley A, Roberts I, Turner H, Rajan L, Austerberry H, et al.

33. Psychosocial aspects of genetic screening of pregnant women and newborns: a systematic review.

    By Green JM, Hewison J, Bekker HL, Bryant, Cuckle HS.

34. Evaluation of abnormal uterine bleeding: comparison of three outpatient procedures within cohorts defined by age and menopausal status.

    By Critchley HOD, Warner P, Lee AJ, Brechin S, Guise J, Graham B.

35. Coronary artery stents: a rapid systematic review and economic evaluation.

    By Hill R, Bagust A, Bakhai A, Dickson R, Dündar Y, Haycox A, et al.

36. Review of guidelines for good practice in decision-analytic modelling in health technology assessment.

    By Philips Z, Ginnelly L, Sculpher M, Claxton K, Golder S, Riemsma R, et al.

37. Rituximab (MabThera^®) for aggressive non-Hodgkin’s lymphoma: systematic review and economic evaluation.

    By Knight C, Hind D, Brewer N, Abbott V.

38. Clinical effectiveness and cost-effectiveness of clopidogrel and modified-release dipyridamole in the secondary prevention of occlusive vascular events: a systematic review and economic evaluation.

    By Jones L, Griffin S, Palmer S, Main C, Orton V, Sculpher M, et al.

39. Pegylated interferon α-2a and -2b in combination with ribavirin in the treatment of chronic hepatitis C: a systematic review and economic evaluation.

    By Shepherd J, Brodin H, Cave C, Waugh N, Price A, Gabbay J.

40. Clopidogrel used in combination with aspirin compared with aspirin alone in the treatment of non-ST-segment- elevation acute coronary syndromes: a systematic review and economic evaluation.

    By Main C, Palmer S, Griffin S, Jones L, Orton V, Sculpher M, et al.

41. Provision, uptake and cost of cardiac rehabilitation programmes: improving services to under-represented groups.

    By Beswick AD, Rees K, Griebsch I, Taylor FC, Burke M, West RR, et al.

42. Involving South Asian patients in clinical trials.

    By Hussain-Gambles M, Leese B, Atkin K, Brown J, Mason S, Tovey P.

43. Clinical and cost-effectiveness of continuous subcutaneous insulin infusion for diabetes.

    By Colquitt JL, Green C, Sidhu MK, Hartwell D, Waugh N.

44. Identification and assessment of ongoing trials in health technology assessment reviews.

    By Song FJ, Fry-Smith A, Davenport C, Bayliss S, Adi Y, Wilson JS, et al.

45. Systematic review and economic evaluation of a long-acting insulin analogue, insulin glargine

    By Warren E, Weatherley-Jones E, Chilcott J, Beverley C.

46. Supplementation of a home-based exercise programme with a class-based programme for people with osteoarthritis of the knees: a randomised controlled trial and health economic analysis.

    By McCarthy CJ, Mills PM, Pullen R, Richardson G, Hawkins N, Roberts CR, et al.

47. Clinical and cost-effectiveness of once-daily versus more frequent use of same potency topical corticosteroids for atopic eczema: a systematic review and economic evaluation.

    By Green C, Colquitt JL, Kirby J, Davidson P, Payne E.

48. Acupuncture of chronic headache disorders in primary care: randomised controlled trial and economic analysis.

    By Vickers AJ, Rees RW, Zollman CE, McCarney R, Smith CM, Ellis N, et al.

49. Generalisability in economic evaluation studies in healthcare: a review and case studies.

    By Sculpher MJ, Pang FS, Manca A, Drummond MF, Golder S, Urdahl H, et al.

50. Virtual outreach: a randomised controlled trial and economic evaluation of joint teleconferenced medical consultations.

    By Wallace P, Barber J, Clayton W, Currell R, Fleming K, Garner P, et al.

1. Randomised controlled multiple treatment comparison to provide a cost-effectiveness rationale for the selection of antimicrobial therapy in acne.

   By Ozolins M, Eady EA, Avery A, Cunliffe WJ, O’Neill C, Simpson NB, et al.

2. Do the findings of case series studies vary significantly according to methodological characteristics?

   By Dalziel K, Round A, Stein K, Garside R, Castelnuovo E, Payne L.

3. Improving the referral process for familial breast cancer genetic counselling: findings of three randomised controlled trials of two interventions.

   By Wilson BJ, Torrance N, Mollison J, Wordsworth S, Gray JR, Haites NE, et al.

4. Randomised evaluation of alternative electrosurgical modalities to treat bladder outflow obstruction in men with benign prostatic hyperplasia.

   By Fowler C, McAllister W, Plail R, Karim O, Yang Q.

5. A pragmatic randomised controlled trial of the cost-effectiveness of palliative therapies for patients with inoperable oesophageal cancer.

   By Shenfine J, McNamee P, Steen N, Bond J, Griffin SM.

6. Impact of computer-aided detection prompts on the sensitivity and specificity of screening mammography.

   By Taylor P, Champness J, Given- Wilson R, Johnston K, Potts H.

7. Issues in data monitoring and interim analysis of trials.

   By Grant AM, Altman DG, Babiker AB, Campbell MK, Clemens FJ, Darbyshire JH, et al.

8. Lay public’s understanding of equipoise and randomisation in randomised controlled trials.

   By Robinson EJ, Kerr CEP, Stevens AJ, Lilford RJ, Braunholtz DA, Edwards SJ, et al.

9. Clinical and cost-effectiveness of electroconvulsive therapy for depressive illness, schizophrenia, catatonia and mania: systematic reviews and economic modelling studies.

   By Greenhalgh J, Knight C, Hind D, Beverley C, Walters S.

10. Measurement of health-related quality of life for people with dementia: development of a new instrument (DEMQOL) and an evaluation of current methodology.

    By Smith SC, Lamping DL, Banerjee S, Harwood R, Foley B, Smith P, et al.

11. Clinical effectiveness and cost-effectiveness of drotrecogin alfa (activated) (Xigris^®) for the treatment of severe sepsis in adults: a systematic review and economic evaluation.

    By Green C, Dinnes J, Takeda A, Shepherd J, Hartwell D, Cave C, et al.

12. A methodological review of how heterogeneity has been examined in systematic reviews of diagnostic test accuracy.

    By Dinnes J, Deeks J, Kirby J, Roderick P.

13. Cervical screening programmes: can automation help? Evidence from systematic reviews, an economic analysis and a simulation modelling exercise applied to the UK.

    By Willis BH, Barton P, Pearmain P, Bryan S, Hyde C.

14. Laparoscopic surgery for inguinal hernia repair: systematic review of effectiveness and economic evaluation.

    By McCormack K, Wake B, Perez J, Fraser C, Cook J, McIntosh E, et al.

15. Clinical effectiveness, tolerability and cost-effectiveness of newer drugs for epilepsy in adults: a systematic review and economic evaluation.

    By Wilby J, Kainth A, Hawkins N, Epstein D, McIntosh H, McDaid C, et al.

16. A randomised controlled trial to compare the cost-effectiveness of tricyclic antidepressants, selective serotonin reuptake inhibitors and lofepramine.

    By Peveler R, Kendrick T, Buxton M, Longworth L, Baldwin D, Moore M, et al.

17. Clinical effectiveness and cost-effectiveness of immediate angioplasty for acute myocardial infarction: systematic review and economic evaluation.

    By Hartwell D, Colquitt J, Loveman E, Clegg AJ, Brodin H, Waugh N, et al.

18. A randomised controlled comparison of alternative strategies in stroke care.

    By Kalra L, Evans A, Perez I, Knapp M, Swift C, Donaldson N.

19. The investigation and analysis of critical incidents and adverse events in healthcare.

    By Woloshynowych M, Rogers S, Taylor-Adams S, Vincent C.

20. Potential use of routine databases in health technology assessment.

    By Raftery J, Roderick P, Stevens A.

21. Clinical and cost-effectiveness of newer immunosuppressive regimens in renal transplantation: a systematic review and modelling study.

    By Woodroffe R, Yao GL, Meads C, Bayliss S, Ready A, Raftery J, et al.

22. A systematic review and economic evaluation of alendronate, etidronate, risedronate, raloxifene and teriparatide for the prevention and treatment of postmenopausal osteoporosis.

    By Stevenson M, Lloyd Jones M, De Nigris E, Brewer N, Davis S, Oakley J.

23. A systematic review to examine the impact of psycho-educational interventions on health outcomes and costs in adults and children with difficult asthma.

    By Smith JR, Mugford M, Holland R, Candy B, Noble MJ, Harrison BDW, et al.

24. An evaluation of the costs, effectiveness and quality of renal replacement therapy provision in renal satellite units in England and Wales.

    By Roderick P, Nicholson T, Armitage A, Mehta R, Mullee M, Gerard K, et al.

25. Imatinib for the treatment of patients with unresectable and/or metastatic gastrointestinal stromal tumours: systematic review and economic evaluation.

    By Wilson J, Connock M, Song F, Yao G, Fry-Smith A, Raftery J, et al.

26. Indirect comparisons of competing interventions.

    By Glenny AM, Altman DG, Song F, Sakarovitch C, Deeks JJ, D’Amico R, et al.

27. Cost-effectiveness of alternative strategies for the initial medical management of non-ST elevation acute coronary syndrome: systematic review and decision-analytical modelling.

    By Robinson M, Palmer S, Sculpher M, Philips Z, Ginnelly L, Bowens A, et al.

28. Outcomes of electrically stimulated gracilis neosphincter surgery.

    By Tillin T, Chambers M, Feldman R.

29. The effectiveness and cost-effectiveness of pimecrolimus and tacrolimus for atopic eczema: a systematic review and economic evaluation.

    By Garside R, Stein K, Castelnuovo E, Pitt M, Ashcroft D, Dimmock P, et al.

30. Systematic review on urine albumin testing for early detection of diabetic complications.

    By Newman DJ, Mattock MB, Dawnay ABS, Kerry S, McGuire A, Yaqoob M, et al.

31. Randomised controlled trial of the cost-effectiveness of water-based therapy for lower limb osteoarthritis.

    By Cochrane T, Davey RC, Matthes Edwards SM.

32. Longer term clinical and economic benefits of offering acupuncture care to patients with chronic low back pain.

    By Thomas KJ, MacPherson H, Ratcliffe J, Thorpe L, Brazier J, Campbell M, et al.

33. Cost-effectiveness and safety of epidural steroids in the management of sciatica.

    By Price C, Arden N, Coglan L, Rogers P.

34. The British Rheumatoid Outcome Study Group (BROSG) randomised controlled trial to compare the effectiveness and cost-effectiveness of aggressive versus symptomatic therapy in established rheumatoid arthritis.

    By Symmons D, Tricker K, Roberts C, Davies L, Dawes P, Scott DL.

35. Conceptual framework and systematic review of the effects of participants’ and professionals’ preferences in randomised controlled trials.

    By King M, Nazareth I, Lampe F, Bower P, Chandler M, Morou M, et al.

36. The clinical and cost-effectiveness of implantable cardioverter defibrillators: a systematic review.

    By Bryant J, Brodin H, Loveman E, Payne E, Clegg A.

37. A trial of problem-solving by community mental health nurses for anxiety, depression and life difficulties among general practice patients. The CPN-GP study.

    By Kendrick T, Simons L, Mynors-Wallis L, Gray A, Lathlean J, Pickering R, et al.

38. The causes and effects of socio-demographic exclusions from clinical trials.

    By Bartlett C, Doyal L, Ebrahim S, Davey P, Bachmann M, Egger M, et al.

39. Is hydrotherapy cost-effective? A randomised controlled trial of combined hydrotherapy programmes compared with physiotherapy land techniques in children with juvenile idiopathic arthritis.

    By Epps H, Ginnelly L, Utley M, Southwood T, Gallivan S, Sculpher M, et al.

40. A randomised controlled trial and cost-effectiveness study of systematic screening (targeted and total population screening) versus routine practice for the detection of atrial fibrillation in people aged 65 and over. The SAFE study.

    By Hobbs FDR, Fitzmaurice DA, Mant J, Murray E, Jowett S, Bryan S, et al.

41. Displaced intracapsular hip fractures in fit, older people: a randomised comparison of reduction and fixation, bipolar hemiarthroplasty and total hip arthroplasty.

    By Keating JF, Grant A, Masson M, Scott NW, Forbes JF.

42. Long-term outcome of cognitive behaviour therapy clinical trials in central Scotland.

    By Durham RC, Chambers JA, Power KG, Sharp DM, Macdonald RR, Major KA, et al.

43. The effectiveness and cost-effectiveness of dual-chamber pacemakers compared with single-chamber pacemakers for bradycardia due to atrioventricular block or sick sinus syndrome: systematic review and economic evaluation.

    By Castelnuovo E, Stein K, Pitt M, Garside R, Payne E.

44. Newborn screening for congenital heart defects: a systematic review and cost-effectiveness analysis.

    By Knowles R, Griebsch I, Dezateux C, Brown J, Bull C, Wren C.

45. The clinical and cost-effectiveness of left ventricular assist devices for end-stage heart failure: a systematic review and economic evaluation.

    By Clegg AJ, Scott DA, Loveman E, Colquitt J, Hutchinson J, Royle P, et al.

46. The effectiveness of the Heidelberg Retina Tomograph and laser diagnostic glaucoma scanning system (GDx) in detecting and monitoring glaucoma.

    By Kwartz AJ, Henson DB, Harper RA, Spencer AF, McLeod D.

47. Clinical and cost-effectiveness of autologous chondrocyte implantation for cartilage defects in knee joints: systematic review and economic evaluation.

    By Clar C, Cummins E, McIntyre L, Thomas S, Lamb J, Bain L, et al.

48. Systematic review of effectiveness of different treatments for childhood retinoblastoma.

    By McDaid C, Hartley S, Bagnall A-M, Ritchie G, Light K, Riemsma R.

49. Towards evidence-based guidelines for the prevention of venous thromboembolism: systematic reviews of mechanical methods, oral anticoagulation, dextran and regional anaesthesia as thromboprophylaxis.

    By Roderick P, Ferris G, Wilson K, Halls H, Jackson D, Collins R, et al.

50. The effectiveness and cost-effectiveness of parent training/education programmes for the treatment of conduct disorder, including oppositional defiant disorder, in children.

    By Dretzke J, Frew E, Davenport C, Barlow J, Stewart-Brown S, Sandercock J, et al.

1. The clinical and cost-effectiveness of donepezil, rivastigmine, galantamine and memantine for Alzheimer’s disease.

   By Loveman E, Green C, Kirby J, Takeda A, Picot J, Payne E, et al.

2. FOOD: a multicentre randomised trial evaluating feeding policies in patients admitted to hospital with a recent stroke.

   By Dennis M, Lewis S, Cranswick G, Forbes J.

3. The clinical effectiveness and cost-effectiveness of computed tomography screening for lung cancer: systematic reviews.

   By Black C, Bagust A, Boland A, Walker S, McLeod C, De Verteuil R, et al.

4. A systematic review of the effectiveness and cost-effectiveness of neuroimaging assessments used to visualise the seizure focus in people with refractory epilepsy being considered for surgery.

   By Whiting P, Gupta R, Burch J, Mujica Mota RE, Wright K, Marson A, et al.

5. Comparison of conference abstracts and presentations with full-text articles in the health technology assessments of rapidly evolving technologies.

   By Dundar Y, Dodd S, Dickson R, Walley T, Haycox A, Williamson PR.

6. Systematic review and evaluation of methods of assessing urinary incontinence.

   By Martin JL, Williams KS, Abrams KR, Turner DA, Sutton AJ, Chapple C, et al.

7. The clinical effectiveness and cost-effectiveness of newer drugs for children with epilepsy. A systematic review.

   By Connock M, Frew E, Evans B-W, Bryan S, Cummins C, Fry-Smith A, et al.

8. Surveillance of Barrett’s oesophagus: exploring the uncertainty through systematic review, expert workshop and economic modelling.

   By Garside R, Pitt M, Somerville M, Stein K, Price A, Gilbert N.

9. Topotecan, pegylated liposomal doxorubicin hydrochloride and paclitaxel for second-line or subsequent treatment of advanced ovarian cancer: a systematic review and economic evaluation.

   By Main C, Bojke L, Griffin S, Norman G, Barbieri M, Mather L, et al.

10. Evaluation of molecular techniques in prediction and diagnosis of cytomegalovirus disease in immunocompromised patients.

    By Szczepura A, Westmoreland D, Vinogradova Y, Fox J, Clark M.

11. Screening for thrombophilia in high-risk situations: systematic review and cost-effectiveness analysis. The Thrombosis: Risk and Economic Assessment of Thrombophilia Screening (TREATS) study.

    By Wu O, Robertson L, Twaddle S, Lowe GDO, Clark P, Greaves M, et al.

12. A series of systematic reviews to inform a decision analysis for sampling and treating infected diabetic foot ulcers.

    By Nelson EA, O’Meara S, Craig D, Iglesias C, Golder S, Dalton J, et al.

13. Randomised clinical trial, observational study and assessment of cost-effectiveness of the treatment of varicose veins (REACTIV trial).

    By Michaels JA, Campbell WB, Brazier JE, MacIntyre JB, Palfreyman SJ, Ratcliffe J, et al.

14. The cost-effectiveness of screening for oral cancer in primary care.

    By Speight PM, Palmer S, Moles DR, Downer MC, Smith DH, Henriksson M, et al.

15. Measurement of the clinical and cost-effectiveness of non-invasive diagnostic testing strategies for deep vein thrombosis.

    By Goodacre S, Sampson F, Stevenson M, Wailoo A, Sutton A, Thomas S, et al.

16. Systematic review of the effectiveness and cost-effectiveness of HealOzone^® for the treatment of occlusal pit/fissure caries and root caries.

    By Brazzelli M, McKenzie L, Fielding S, Fraser C, Clarkson J, Kilonzo M, et al.

17. Randomised controlled trials of conventional antipsychotic versus new atypical drugs, and new atypical drugs versus clozapine, in people with schizophrenia responding poorly to, or intolerant of, current drug treatment.

    By Lewis SW, Davies L, Jones PB, Barnes TRE, Murray RM, Kerwin R, et al.

18. Diagnostic tests and algorithms used in the investigation of haematuria: systematic reviews and economic evaluation.

    By Rodgers M, Nixon J, Hempel S, Aho T, Kelly J, Neal D, et al.

19. Cognitive behavioural therapy in addition to antispasmodic therapy for irritable bowel syndrome in primary care: randomised controlled trial.

    By Kennedy TM, Chalder T, McCrone P, Darnley S, Knapp M, Jones RH, et al.

20. A systematic review of the clinical effectiveness and cost-effectiveness of enzyme replacement therapies for Fabry’s disease and mucopolysaccharidosis type 1.

    By Connock M, Juarez-Garcia A, Frew E, Mans A, Dretzke J, Fry-Smith A, et al.

21. Health benefits of antiviral therapy for mild chronic hepatitis C: randomised controlled trial and economic evaluation.

    By Wright M, Grieve R, Roberts J, Main J, Thomas HC, on behalf of the UK Mild Hepatitis C Trial Investigators.

22. Pressure relieving support surfaces: a randomised evaluation.

    By Nixon J, Nelson EA, Cranny G, Iglesias CP, Hawkins K, Cullum NA, et al.

23. A systematic review and economic model of the effectiveness and cost-effectiveness of methylphenidate, dexamfetamine and atomoxetine for the treatment of attention deficit hyperactivity disorder in children and adolescents.

    By King S, Griffin S, Hodges Z, Weatherly H, Asseburg C, Richardson G, et al.

24. The clinical effectiveness and cost-effectiveness of enzyme replacement therapy for Gaucher’s disease: a systematic review.

    By Connock M, Burls A, Frew E, Fry-Smith A, Juarez-Garcia A, McCabe C, et al.

25. Effectiveness and cost-effectiveness of salicylic acid and cryotherapy for cutaneous warts. An economic decision model.

    By Thomas KS, Keogh-Brown MR, Chalmers JR, Fordham RJ, Holland RC, Armstrong SJ, et al.

26. A systematic literature review of the effectiveness of non-pharmacological interventions to prevent wandering in dementia and evaluation of the ethical implications and acceptability of their use.

    By Robinson L, Hutchings D, Corner L, Beyer F, Dickinson H, Vanoli A, et al.

27. A review of the evidence on the effects and costs of implantable cardioverter defibrillator therapy in different patient groups, and modelling of cost-effectiveness and cost–utility for these groups in a UK context.

    By Buxton M, Caine N, Chase D, Connelly D, Grace A, Jackson C, et al.

28. Adefovir dipivoxil and pegylated interferon alfa-2a for the treatment of chronic hepatitis B: a systematic review and economic evaluation.

    By Shepherd J, Jones J, Takeda A, Davidson P, Price A.

29. An evaluation of the clinical and cost-effectiveness of pulmonary artery catheters in patient management in intensive care: a systematic review and a randomised controlled trial.

    By Harvey S, Stevens K, Harrison D, Young D, Brampton W, McCabe C, et al.

30. Accurate, practical and cost-effective assessment of carotid stenosis in the UK.

    By Wardlaw JM, Chappell FM, Stevenson M, De Nigris E, Thomas S, Gillard J, et al.

31. Etanercept and infliximab for the treatment of psoriatic arthritis: a systematic review and economic evaluation.

    By Woolacott N, Bravo Vergel Y, Hawkins N, Kainth A, Khadjesari Z, Misso K, et al.

32. The cost-effectiveness of testing for hepatitis C in former injecting drug users.

    By Castelnuovo E, Thompson-Coon J, Pitt M, Cramp M, Siebert U, Price A, et al.

33. Computerised cognitive behaviour therapy for depression and anxiety update: a systematic review and economic evaluation.

    By Kaltenthaler E, Brazier J, De Nigris E, Tumur I, Ferriter M, Beverley C, et al.

34. Cost-effectiveness of using prognostic information to select women with breast cancer for adjuvant systemic therapy.

    By Williams C, Brunskill S, Altman D, Briggs A, Campbell H, Clarke M, et al.

35. Psychological therapies including dialectical behaviour therapy for borderline personality disorder: a systematic review and preliminary economic evaluation.

    By Brazier J, Tumur I, Holmes M, Ferriter M, Parry G, Dent-Brown K, et al.

36. Clinical effectiveness and cost-effectiveness of tests for the diagnosis and investigation of urinary tract infection in children: a systematic review and economic model.

    By Whiting P, Westwood M, Bojke L, Palmer S, Richardson G, Cooper J, et al.

37. Cognitive behavioural therapy in chronic fatigue syndrome: a randomised controlled trial of an outpatient group programme.

    By O’Dowd H, Gladwell P, Rogers CA, Hollinghurst S, Gregory A.

38. A comparison of the cost-effectiveness of five strategies for the prevention of nonsteroidal anti-inflammatory drug-induced gastrointestinal toxicity: a systematic review with economic modelling.

    By Brown TJ, Hooper L, Elliott RA, Payne K, Webb R, Roberts C, et al.

39. The effectiveness and cost-effectiveness of computed tomography screening for coronary artery disease: systematic review.

    By Waugh N, Black C, Walker S, McIntyre L, Cummins E, Hillis G.

40. What are the clinical outcome and cost-effectiveness of endoscopy undertaken by nurses when compared with doctors? A Multi-Institution Nurse Endoscopy Trial (MINuET).

    By Williams J, Russell I, Durai D, Cheung W-Y, Farrin A, Bloor K, et al.

41. The clinical and cost-effectiveness of oxaliplatin and capecitabine for the adjuvant treatment of colon cancer: systematic review and economic evaluation.

    By Pandor A, Eggington S, Paisley S, Tappenden P, Sutcliffe P.

42. A systematic review of the effectiveness of adalimumab, etanercept and infliximab for the treatment of rheumatoid arthritis in adults and an economic evaluation of their cost-effectiveness.

    By Chen Y-F, Jobanputra P, Barton P, Jowett S, Bryan S, Clark W, et al.

43. Telemedicine in dermatology: a randomised controlled trial.

    By Bowns IR, Collins K, Walters SJ, McDonagh AJG.

44. Cost-effectiveness of cell salvage and alternative methods of minimising perioperative allogeneic blood transfusion: a systematic review and economic model.

    By Davies L, Brown TJ, Haynes S, Payne K, Elliott RA, McCollum C.

45. Clinical effectiveness and cost-effectiveness of laparoscopic surgery for colorectal cancer: systematic reviews and economic evaluation.

    By Murray A, Lourenco T, de Verteuil R, Hernandez R, Fraser C, McKinley A, et al.

46. Etanercept and efalizumab for the treatment of psoriasis: a systematic review.

    By Woolacott N, Hawkins N, Mason A, Kainth A, Khadjesari Z, Bravo Vergel Y, et al.

47. Systematic reviews of clinical decision tools for acute abdominal pain.

    By Liu JLY, Wyatt JC, Deeks JJ, Clamp S, Keen J, Verde P, et al.

48. Evaluation of the ventricular assist device programme in the UK.

    By Sharples L, Buxton M, Caine N, Cafferty F, Demiris N, Dyer M, et al.

49. A systematic review and economic model of the clinical and cost-effectiveness of immunosuppressive therapy for renal transplantation in children.

    By Yao G, Albon E, Adi Y, Milford D, Bayliss S, Ready A, et al.

50. Amniocentesis results: investigation of anxiety. The ARIA trial.

    By Hewison J, Nixon J, Fountain J, Cocks K, Jones C, Mason G, et al.

1. Pemetrexed disodium for the treatment of malignant pleural mesothelioma: a systematic review and economic evaluation.

   By Dundar Y, Bagust A, Dickson R, Dodd S, Green J, Haycox A, et al.

2. A systematic review and economic model of the clinical effectiveness and cost-effectiveness of docetaxel in combination with prednisone or prednisolone for the treatment of hormone-refractory metastatic prostate cancer.

   By Collins R, Fenwick E, Trowman R, Perard R, Norman G, Light K, et al.

3. A systematic review of rapid diagnostic tests for the detection of tuberculosis infection.

   By Dinnes J, Deeks J, Kunst H, Gibson A, Cummins E, Waugh N, et al.

4. The clinical effectiveness and cost-effectiveness of strontium ranelate for the prevention of osteoporotic fragility fractures in postmenopausal women.

   By Stevenson M, Davis S, Lloyd-Jones M, Beverley C.

5. A systematic review of quantitative and qualitative research on the role and effectiveness of written information available to patients about individual medicines.

   By Raynor DK, Blenkinsopp A, Knapp P, Grime J, Nicolson DJ, Pollock K, et al.

6. Oral naltrexone as a treatment for relapse prevention in formerly opioid-dependent drug users: a systematic review and economic evaluation.

   By Adi Y, Juarez-Garcia A, Wang D, Jowett S, Frew E, Day E, et al.

7. Glucocorticoid-induced osteoporosis: a systematic review and cost–utility analysis.

   By Kanis JA, Stevenson M, McCloskey EV, Davis S, Lloyd-Jones M.

8. Epidemiological, social, diagnostic and economic evaluation of population screening for genital chlamydial infection.

   By Low N, McCarthy A, Macleod J, Salisbury C, Campbell R, Roberts TE, et al.

9. Methadone and buprenorphine for the management of opioid dependence: a systematic review and economic evaluation.

   By Connock M, Juarez-Garcia A, Jowett S, Frew E, Liu Z, Taylor RJ, et al.

10. Exercise Evaluation Randomised Trial (EXERT): a randomised trial comparing GP referral for leisure centre-based exercise, community-based walking and advice only.

    By Isaacs AJ, Critchley JA, See Tai S, Buckingham K, Westley D, Harridge SDR, et al.

11. Interferon alfa (pegylated and non-pegylated) and ribavirin for the treatment of mild chronic hepatitis C: a systematic review and economic evaluation.

    By Shepherd J, Jones J, Hartwell D, Davidson P, Price A, Waugh N.

12. Systematic review and economic evaluation of bevacizumab and cetuximab for the treatment of metastatic colorectal cancer.

    By Tappenden P, Jones R, Paisley S, Carroll C.

13. A systematic review and economic evaluation of epoetin alfa, epoetin beta and darbepoetin alfa in anaemia associated with cancer, especially that attributable to cancer treatment.

    By Wilson J, Yao GL, Raftery J, Bohlius J, Brunskill S, Sandercock J, et al.

14. A systematic review and economic evaluation of statins for the prevention of coronary events.

    By Ward S, Lloyd Jones M, Pandor A, Holmes M, Ara R, Ryan A, et al.

15. A systematic review of the effectiveness and cost-effectiveness of different models of community-based respite care for frail older people and their carers.

    By Mason A, Weatherly H, Spilsbury K, Arksey H, Golder S, Adamson J, et al.

16. Additional therapy for young children with spastic cerebral palsy: a randomised controlled trial.

    By Weindling AM, Cunningham CC, Glenn SM, Edwards RT, Reeves DJ.

17. Screening for type 2 diabetes: literature review and economic modelling.

    By Waugh N, Scotland G, McNamee P, Gillett M, Brennan A, Goyder E, et al.

18. The effectiveness and cost-effectiveness of cinacalcet for secondary hyperparathyroidism in end-stage renal disease patients on dialysis: a systematic review and economic evaluation.

    By Garside R, Pitt M, Anderson R, Mealing S, Roome C, Snaith A, et al.

19. The clinical effectiveness and cost-effectiveness of gemcitabine for metastatic breast cancer: a systematic review and economic evaluation.

    By Takeda AL, Jones J, Loveman E, Tan SC, Clegg AJ.

20. A systematic review of duplex ultrasound, magnetic resonance angiography and computed tomography angiography for the diagnosis and assessment of symptomatic, lower limb peripheral arterial disease.

    By Collins R, Cranny G, Burch J, Aguiar-Ibáñez R, Craig D, Wright K, et al.

21. The clinical effectiveness and cost-effectiveness of treatments for children with idiopathic steroid-resistant nephrotic syndrome: a systematic review.

    By Colquitt JL, Kirby J, Green C, Cooper K, Trompeter RS.

22. A systematic review of the routine monitoring of growth in children of primary school age to identify growth-related conditions.

    By Fayter D, Nixon J, Hartley S, Rithalia A, Butler G, Rudolf M, et al.

23. Systematic review of the effectiveness of preventing and treating Staphylococcus aureus carriage in reducing peritoneal catheter-related infections.

    By McCormack K, Rabindranath K, Kilonzo M, Vale L, Fraser C, McIntyre L, et al.

24. The clinical effectiveness and cost of repetitive transcranial magnetic stimulation versus electroconvulsive therapy in severe depression: a multicentre pragmatic randomised controlled trial and economic analysis.

    By McLoughlin DM, Mogg A, Eranti S, Pluck G, Purvis R, Edwards D, et al.

25. A randomised controlled trial and economic evaluation of direct versus indirect and individual versus group modes of speech and language therapy for children with primary language impairment.

    By Boyle J, McCartney E, Forbes J, O’Hare A.

26. Hormonal therapies for early breast cancer: systematic review and economic evaluation.

    By Hind D, Ward S, De Nigris E, Simpson E, Carroll C, Wyld L.

27. Cardioprotection against the toxic effects of anthracyclines given to children with cancer: a systematic review.

    By Bryant J, Picot J, Levitt G, Sullivan I, Baxter L, Clegg A.

28. Adalimumab, etanercept and infliximab for the treatment of ankylosing spondylitis: a systematic review and economic evaluation.

    By McLeod C, Bagust A, Boland A, Dagenais P, Dickson R, Dundar Y, et al.

29. Prenatal screening and treatment strategies to prevent group B streptococcal and other bacterial infections in early infancy: cost-effectiveness and expected value of information analyses.

    By Colbourn T, Asseburg C, Bojke L, Philips Z, Claxton K, Ades AE, et al.

30. Clinical effectiveness and cost-effectiveness of bone morphogenetic proteins in the non-healing of fractures and spinal fusion: a systematic review.

    By Garrison KR, Donell S, Ryder J, Shemilt I, Mugford M, Harvey I, et al.

31. A randomised controlled trial of postoperative radiotherapy following breast-conserving surgery in a minimum-risk older population. The PRIME trial.

    By Prescott RJ, Kunkler IH, Williams LJ, King CC, Jack W, van der Pol M, et al.

32. Current practice, accuracy, effectiveness and cost-effectiveness of the school entry hearing screen.

    By Bamford J, Fortnum H, Bristow K, Smith J, Vamvakas G, Davies L, et al.

33. The clinical effectiveness and cost-effectiveness of inhaled insulin in diabetes mellitus: a systematic review and economic evaluation.

    By Black C, Cummins E, Royle P, Philip S, Waugh N.

34. Surveillance of cirrhosis for hepatocellular carcinoma: systematic review and economic analysis.

    By Thompson Coon J, Rogers G, Hewson P, Wright D, Anderson R, Cramp M, et al.

35. The Birmingham Rehabilitation Uptake Maximisation Study (BRUM). Homebased compared with hospital-based cardiac rehabilitation in a multi-ethnic population: cost-effectiveness and patient adherence.

    By Jolly K, Taylor R, Lip GYH, Greenfield S, Raftery J, Mant J, et al.

36. A systematic review of the clinical, public health and cost-effectiveness of rapid diagnostic tests for the detection and identification of bacterial intestinal pathogens in faeces and food.

    By Abubakar I, Irvine L, Aldus CF, Wyatt GM, Fordham R, Schelenz S, et al.

37. A randomised controlled trial examining the longer-term outcomes of standard versus new antiepileptic drugs. The SANAD trial.

    By Marson AG, Appleton R, Baker GA, Chadwick DW, Doughty J, Eaton B, et al.

38. Clinical effectiveness and cost-effectiveness of different models of managing long-term oral anti-coagulation therapy: a systematic review and economic modelling.

    By Connock M, Stevens C, Fry-Smith A, Jowett S, Fitzmaurice D, Moore D, et al.

39. A systematic review and economic model of the clinical effectiveness and cost-effectiveness of interventions for preventing relapse in people with bipolar disorder.

    By Soares-Weiser K, Bravo Vergel Y, Beynon S, Dunn G, Barbieri M, Duffy S, et al.

40. Taxanes for the adjuvant treatment of early breast cancer: systematic review and economic evaluation.

    By Ward S, Simpson E, Davis S, Hind D, Rees A, Wilkinson A.

41. The clinical effectiveness and cost-effectiveness of screening for open angle glaucoma: a systematic review and economic evaluation.

    By Burr JM, Mowatt G, Hernández R, Siddiqui MAR, Cook J, Lourenco T, et al.

42. Acceptability, benefit and costs of early screening for hearing disability: a study of potential screening tests and models.

    By Davis A, Smith P, Ferguson M, Stephens D, Gianopoulos I.

43. Contamination in trials of educational interventions.

    By Keogh-Brown MR, Bachmann MO, Shepstone L, Hewitt C, Howe A, Ramsay CR, et al.

44. Overview of the clinical effectiveness of positron emission tomography imaging in selected cancers.

    By Facey K, Bradbury I, Laking G, Payne E.

45. The effectiveness and cost-effectiveness of carmustine implants and temozolomide for the treatment of newly diagnosed high-grade glioma: a systematic review and economic evaluation.

    By Garside R, Pitt M, Anderson R, Rogers G, Dyer M, Mealing S, et al.

46. Drug-eluting stents: a systematic review and economic evaluation.

    By Hill RA, Boland A, Dickson R, Dündar Y, Haycox A, McLeod C, et al.

47. The clinical effectiveness and cost-effectiveness of cardiac resynchronisation (biventricular pacing) for heart failure: systematic review and economic model.

    By Fox M, Mealing S, Anderson R, Dean J, Stein K, Price A, et al.

48. Recruitment to randomised trials: strategies for trial enrolment and participation study. The STEPS study.

    By Campbell MK, Snowdon C, Francis D, Elbourne D, McDonald AM, Knight R, et al.

49. Cost-effectiveness of functional cardiac testing in the diagnosis and management of coronary artery disease: a randomised controlled trial. The CECaT trial.

    By Sharples L, Hughes V, Crean A, Dyer M, Buxton M, Goldsmith K, et al.

50. Evaluation of diagnostic tests when there is no gold standard. A review of methods.

    By Rutjes AWS, Reitsma JB, Coomarasamy A, Khan KS, Bossuyt PMM.

51. Systematic reviews of the clinical effectiveness and cost-effectiveness of proton pump inhibitors in acute upper gastrointestinal bleeding.

    By Leontiadis GI, Sreedharan A, Dorward S, Barton P, Delaney B, Howden CW, et al.

52. A review and critique of modelling in prioritising and designing screening programmes.

    By Karnon J, Goyder E, Tappenden P, McPhie S, Towers I, Brazier J, et al.

53. An assessment of the impact of the NHS Health Technology Assessment Programme.

    By Hanney S, Buxton M, Green C, Coulson D, Raftery J.