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

Article history

The research reported in this issue of the journal was commissioned and funded by the HTA Programme on behalf of NICE as project number 07/20/01. The protocol was agreed in April 2007. The assessment report began editorial review in August 2007 and was accepted for publication in June 2008. 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: NCCHTA, Alpha House, Enterprise Road, Southampton Science Park, Chilworth, Southampton SO16 7NS, UK.

2009 Queen’s Printer and Controller of HMSO

Description of health problem

Optimal management of cardiac output, fluid balance and haemodynamic status has long been considered key to improving outcome in critically ill patients and in high-risk patients undergoing major surgery. Traditionally, pulmonary artery catheters (PACs) have been used to monitor cardiac output and haemodynamic status to guide treatment. A recent Health Technology Assessment (HTA) Programme-funded study demonstrated that PAC insertion and management of critically ill patients using the variables monitored by PACs fails to confer an outcome benefit. 1 Further studies have also cast doubt on the value of PACs in high-risk major surgery. 2 This, coupled with concerns related to procedural complications associated with the insertion and use of the PAC, along with the development of less invasive cardiac output monitors in clinical practice, has resulted in a global decline in the usage of the PAC in recent years.

Less invasive technologies to monitor cardiac output and other haemodynamic variables include oesophageal Doppler monitoring (ODM), transoesophageal echocardiography, transthoracic impedance, carbon dioxide elimination and systems based upon pulse contour analysis and dye dilution methods.

Oesophageal Doppler monitoring measures blood flow velocity in the descending thoracic aorta using a flexible probe inserted into the patient’s oesophagus with an ultrasound transducer at its tip. The information is combined with an estimate of aortic cross-sectional area (derived from a nomogram based on the patient’s age, height and weight) and an estimate of the fraction of the cardiac output perfusing the upper body, allowing continuous monitoring of cardiac output and haemodynamic status. ODM is a relatively simple procedure requiring no calibration and minimal training and has a good safety profile. The probe itself is uncomfortable and often poorly tolerated by awake patients, therefore patients monitored with ODM generally need to be adequately sedated or anaesthetised. While this is often undertaken in patients requiring such monitoring, it does tend to limit the use of the probes to an operating theatre, high dependency unit (HDU) or intensive care unit (ICU) environment. Newer, softer probes designed to be tolerated in awake patients have been developed, but at present are not widely available.

Although described as continuously monitoring, the ODM probes often need to be refocused prior to each measurement, so they are normally used to make frequent, repeated measurements rather than to provide a beat-by-beat measure of stroke volume.

Transoesophageal echocardiography allows direct assessment of the heart’s structure and function. It can also be used to derive cardiac output by measuring the Doppler shift in the reflected ultrasound beam to determine blood velocity and by direct measurement of the cross-sectional area of the aorta. It has several limitations as a technique: the probe is large and expensive; patients require considerable amounts of sedation or an anaesthetic to tolerate it; and a highly-skilled, highly-trained operator is required to operate the probe, as without one continuous monitoring of cardiac function is impossible.

Pulse contour analysis devices employ algorithms to calculate cardiac output from analysis of the arterial pressure/time waveform, and so require the presence of an indwelling arterial catheter (often present anyway in the targeted populations). There are several types of device available, but all require initial calibration with another measure of cardiac output which may be by means of either a transpulmonary thermodilution or lithium dilution technique. Systems using thermodilution to calibrate also require the presence of a central venous catheter, with its associated hazards. While lithium dilution calibration does not require the presence of a central venous catheter, the lithium used to calibrate the system can interact with muscle relaxant drugs used in anaesthesia. Therefore, care needs to be taken regarding timing of calibration. Pulse contour devices, while requiring calibration and taking slightly longer to set up than ODM, do have the advantage that they can be tolerated by awake patients.

Proponents of the use of cardiac output monitoring to guide fluid replacement and pharmacological treatment suggest this allows optimisation of the patient’s haemodynamic status, helping to maintain adequate tissue perfusion. This, in turn, prevents overt or occult organ damage which hinders the patient’s recovery. Thus, monitoring has the potential to reduce mortality, complications, lengths of stay in critical care facilities and overall hospital stays, all of which could result in savings in health-care costs.

Approximately 3 million surgical operations are conducted in the UK annually, with an overall hospital mortality rate of 0.8–1.0%. 3 The National Confidential Enquiry into Patient Outcome and Deaths (NCEPOD) reports that there were over 20,000 deaths following surgery in England, Wales and Northern Ireland alone in 2003. 4 Therefore, any improvement in morbidity and mortality for these patient groups would markedly improve important patient outcomes for large groups of patients as well as significantly improving utilisation of health-care resources.

Current service provision

In the NHS, variation in practice exists with regard to haemodynamic optimisation and patient monitoring during the perioperative period and in critical care environments. Inevitably, the lack of published national guidelines or frameworks in this area contributes to these differences. The only published statement from the National Institute for Health and Clinical Excellence (NICE) with regard to ODM to date has been as part of NICE’s Interventional Procedures (IP) Programme, relating only to safety and efficacy. 5 ODM was not felt to fall within the IP Programme’s remit as it is considered standard clinical practice with risks and benefits that are sufficiently well known.

Within the NHS the ODM that is most widely used is the CardioQ™ device (Deltex Medical, Chichester, UK). There are CardioQ monitors in around two-thirds of the 300 or so NHS hospitals that regularly undertake moderate or major surgery within the UK. The probes are single use, and several types exist which can be used to monitor for periods of from 6 hours to 10 days. Currently the CardioQ is used to monitor around 25,000 patients each year within the NHS. While it is difficult to state accurately the categories of patients in whom the ODM probes are being used, information from the manufacturer suggests that approximately one-third are used in intensive care, one-third intraoperatively (theatre only) and one-third throughout the perioperative period (although given the large number of potential patients their use overall remains infrequent).

Given the large number of operations carried out within the NHS each year (in excess of 2 million) and the relatively small number of cardiac output monitors, many patients receive what might be termed conventional clinical assessment. The recent Agency for Health Care Research and Quality (ARHQ) report6 defined this as follows:

Conventional clinical assessment usually refers to non-invasive assessment of various clinical markers. In some institutions, fluid management may be based only on assessment of hemodynamic variables such as heart rate, systolic blood pressure and urinary output, with no measure of blood flow or CVP.

Such a definition would seem to be applicable to the NHS (although considerable variation in actual practice throughout the NHS might be expected).

Description of technology under assessment

Oesophageal Doppler monitoring was first described by Side and Gosling in the early 1970s and since then there have been significant advances in the technology and its clinical use. ODM is currently used in a variety of clinical settings, most commonly in critical care environments and in patients undergoing surgery (particularly patients with significant co-morbidity or those undergoing major surgery with a high incidence of blood loss and/or significant fluid shifts.) ODM allows continuous monitoring of a patient’s haemodynamic variables and, more importantly, allows the display of trends in these variables. This allows the clinician to titrate intravenous fluids and inotropic drugs to optimise tissue perfusion and oxygen delivery. The length of time this monitoring is required depends on the individual clinical situation. Upon completion of ODM the probe is simply removed.

The procedure measures blood velocity in the descending thoracic aorta using a flexible probe inserted into the patient’s oesophagus via the mouth or nose. The tip of the probe contains a transducer which transmits an ultrasound beam. The tip is advanced to mid-thoracic level and rotated to direct the ultrasound beam towards the descending aorta, allowing measurement of blood velocity using the Doppler frequency shift in the reflected ultrasound. This information is combined with an estimate of aortic cross-sectional area (derived from a nomogram based on the patient’s age, height and weight) and upper body blood flow, allowing haemodynamic variables such as cardiac output, stroke volume and systolic flow time to be continuously measured. In addition, if other variables such as central venous pressure (CVP) and blood pressure are known, derived variables such as systemic vascular resistance can be calculated.

The probe and monitor are simple to use, and a period of training in groups of no more than 12 patients has been shown to be sufficient to ensure reliable measurements of cardiac output. 7 Generally speaking, the probe can be inserted and a clear signal can be obtained within a few minutes.

Oesophageal Doppler monitoring has been shown to have a high validity (no bias and high clinical agreement) for monitoring changes in cardiac output during the management of critically ill patients in both operating rooms and ICUs. 8 Good correlation also exists when comparing cardiac output measurements derived from ODM and PACs by means of thermodilution. 7,9–11

Contraindications to insertion of ODM probes include patients under 16 years of age (special alternative probes and equipment are necessary for these patients), severe bleeding diathesis, facial trauma, oesophageal abnormalities such as varices, stents, strictures, carcinoma or oesophagitis and recent oesophageal or upper airway surgery. The presence of arrhythmias, severe aortic valve disease or a thoracic aortic aneurysm or the use of an intra-aortic balloon counterpulsation device, while not absolute contraindications to inserting the probe, may lead to difficulty in obtaining an accurate waveform and meaningful information.

Care needs to be taken in interpreting the data in certain other clinical situations as ODM makes the assumption that a constant proportion of the cardiac output enters the descending aorta, which is not always the case. Redistribution of blood flow between the ascending and descending aorta may occur during cross clamping of the aorta and with acute haemorrhage, where more of the cardiac output may be selectively diverted to coronary and cerebral circulation as opposed to the descending aorta. In addition, the presence of a sympathetic block to the lower body (such as that caused by epidural or spinal anaesthesia/analgesia) may lead to an overestimation of cardiac output.

Although there are no reported major complications resulting directly from the use of the ODM probe, a small number of minor complications have been reported in the literature, such as minor oral trauma and inadvertent tracheal placement of the probe. 6

Aim and objectives of this review

Given this uncertainty about the role of cardiac output monitoring, the aim of this review was to assess the effectiveness and cost-effectiveness of one particular type of monitoring, ODM, when used for monitoring cardiac function in comparison with (a) standard care (i.e. no cardiac output monitor perioperatively) among critically ill patients and patients undergoing major surgery, and (b) other methods of monitoring heart function (such as PAC or pulse contour monitoring devices) in critically ill patients or in patients undergoing major surgery.

As described in subsequent chapters, the analysis focused on outcomes of most importance to patients (e.g. mortality, length of hospitalisation, length of stay in critical care and complication rates). Cost-effectiveness was assessed from the perspective of the NHS and personal social services.

In the following two sections, the place of cardiac output monitoring in the pathways of care of both patients undergoing major surgery and critically ill patients is briefly described.

Use of cardiac output monitoring among patients undergoing major surgery

Cardiac output monitoring systems are used in operating theatres across all the major surgical specialties. They tend to be used predominantly for surgery of moderate to major severity, often in patients with significant co-morbidity or where significant blood loss or fluid shifts may be anticipated, as a consequence of either the patient’s underlying condition or their anticipated surgery. However, not every patient undergoing major surgery will need to have their cardiac output monitored; generally they will be assessed preoperatively and the need for cardiac output monitoring will be determined by the anaesthetist based upon the clinical assessment, taking into account surgical factors and patient factors including co-morbidities (Figures 1 and 2). The anaesthetist may also be guided by the results of preoperative cardiac testing such as stress echocardiography or radionuclide cardiography (such tests are likely to be performed regardless of whether the use of ODM is an option). 12 Although the decision to use cardiac output monitoring is usually made preoperatively, occasionally factors encountered during surgery may lead to a decision to adopt monitoring during the intraoperative period, and this may continue into the postoperative period. Monitoring of surgical patients typically finishes at the end of the surgery.

FIGURE 1.

Pre-surgery assessment of patient.

FIGURE 2.

Decision regarding use of cardiac output monitoring system.

Use of cardiac output monitoring among critically ill patients

Patients requiring treatment in an ICU (level 3 care) or an HDU (level 2 care), by definition, need a higher level of care and monitoring than that available in general wards (level 1 care) (based on the Department of Health classification system). The decision to utilise these higher levels of care may be affected by a number of factors including patients’ underlying surgical condition, their co-morbidities and the nature of surgery performed. In these complicated patients, haemodynamic function is frequently disturbed owing to a combination of the patient’s existing disease(s) interacting with acute haemodynamic instability caused by surgery, anaesthesia, acute blood loss and fluid shifts. These complex interactions are not always apparent or easily interpretable using conventional clinical assessment and monitoring alone. In such patients, in addition to helping to guide and monitor operative fluid therapy, haemodynamic monitoring may also assist in differentiating between varying aetiologies of haemodynamic instability including hypovolaemia, sepsis and cardiogenic causes of tissue hypoperfusion or shock. This is important as the treatment for each of these pathologies is different. Among critically ill patients, monitoring would typically continue until there is a resolution of cardiovascular instability, which will be based on a broader clinical assessment.

Methods for reviewing effectiveness (Aberdeen TAR group)

Results

Number of studies identified

The results of the searches are summarised in Table 1 and Figure 3. The numbers retrieved from the searches in CINAHL, Science Citation Index (SCI), BIOSIS and CENTRAL include only the additional reports found after excluding those identified from the MEDLINE/EMBASE multifile search. A total of 663 reports were identified, of which 42 were selected for full assessment. As well as the AHRQ review,6 10 reports met inclusion criteria; eight of which had already been identified in the AHRQ review.

TABLE 1 - Search results

Database	Number retrieved	Number selected for assessment
MEDLINE/EMBASE/MEDLINE In Process multifile search (after deduplication in Ovid)	444	15
CINAHL	4	0
SCI	69	6
BIOSIS	74	2
CENTRAL	15	5
National Research Register	32	8
Current Controlled Trials	10	2
Clinical Trials	1	1
DARE	5	2
HTA Database	6	0
Cochrane Database of Systematic Reviews	3	1
Total retrieved	663	42

FIGURE 3.

Flow diagram outlining the screening process.

Assessment of effectiveness

ODM during surgery

ODM plus CVP plus conventional clinical assessment versus CVP plus conventional clinical assessment

The only data available for this comparison came from the AHRQ report, from five studies involving 453 patients. The type of surgery performed included elective bowel surgery,17,21,24 elective cardiac surgery20 and elective general, urological or gynaecological surgery. 18

Mortality

All five studies reported that no deaths occurred during surgery in either the ODM or the control group. Three studies17,20,21 reported one death each in the control group (1/28; 1/30; 1/52, respectively) within 30 days following surgery, and one study24 reported one death in the control group (1/64) within 60 days following surgery. However, the AHRQ report stated that the between-group differences were not statistically significant.

Figure 4 shows a meta-analysis (Peto method) undertaken by the Aberdeen group of the five studies reporting mortality. This shows that ODM was associated with statistically significantly fewer deaths compared with control (OR 0.13, 95% CI 0.02–0.96). In this analysis the study by Mythen and colleagues,20 which investigated elective cardiac surgery patients, has also been included and, even though the study is small, it exhibits a similar trend to that observed in the other studies. The meta-analysis results should be interpreted with caution because of the low number of events and the overall low number of patients in the combined totals.

FIGURE 4.

Meta-analysis of studies reporting mortality (Aberdeen TAR group).

Major complications

Three of five studies reported major complications,17,20,21 which were generally defined as life threatening or requiring intensive or high-dependency care. The type of complications reported included severe tachyarrhythmias17 and chest infection, multiple organ failure, respiratory failure, cerebrovascular accident and paralytic ileus. 20 All three studies showed a statistically significant difference in major complications that favoured the ODM groups (all of the major complications occurred in the control groups). The AHRQ report stated that the ORs [Peto method; (95% CI)] for the three studies were –2.08 (–3.72 to –0.44),21 –2.19 (–4.01 to –0.37)17 and –2.19 (–3.86 to –0.51). 20 Although a meta-analysis was undertaken, the AHRQ report did not present a pooled estimate of effect size on the grounds that only three of the five studies (i.e. less than 80%) reported separate data on major complications. The 95% CI around the pooled estimate was 0.04–0.31, indicating that ODM was associated with statistically significantly fewer major complications.

Figure 5 shows a meta-analysis (Peto method) undertaken by the Aberdeen group of the three studies reporting major complications, with the pooled estimate showing that ODM was associated with statistically significantly fewer major complications (OR 0.12, 95% CI 0.04–0.31). It is again worth noting that the data relating to use of ODM in cardiac surgery patients20 are similar to those from the other studies reporting outcomes conducted on non-cardiac patients.

FIGURE 5.

Meta-analysis of studies reporting major complications (Aberdeen TAR group).

Total complications

Four studies reported total complications. 17,18,21,24 The AHRQ report stated that two studies showed a statistically significant difference, indicating fewer total complications in the ODM group (OR 0.23, 95% CI 0.10–0.54;18 OR 0.41, 95% CI 0.20–0.8424). The other two studies also showed fewer complications in the ODM group, without reaching statistical significance (OR 0.44, 95% CI 0.13–1.54;17 OR 0.47, 95% CI 0.20–1.0721). Gan and colleagues18 reported the total number of complications rather than the number of patients with complications. Although a random-effects meta-analysis was undertaken, the AHRQ report did not present a pooled estimate of effect on the grounds that the studies reported complications somewhat differently (patients versus events). The 95% CI around the pooled estimate was –1.43 to –0.57, indicating that ODM was associated with statistically significantly fewer total complications.

Figure 6 shows a meta-analysis undertaken by the Aberdeen group of the three studies that reported the number of patients in each group who experienced complications. The pooled estimate shows that ODM was associated with statistically significantly fewer total complications (OR 0.43, 95% CI 0.26–0.71).

FIGURE 6.

Meta-analysis of studies reporting total number of patients with complications (Aberdeen TAR group).

Length of hospital stay

All five studies reported this outcome. The AHRQ report stated that four studies reported a statistically significant reduction in length of stay (based on either medians or means) associated with ODM, with a median of 6 versus 7 days, p = 0.03;18 7 (IQR 3–35) versus 9 (IQR 4–45) days, p = 0.005;21 10 (IQR 5.75) versus 11.5 (IQR 4.75) days, p = 0.03;24 and a mean of 6.4 (range 5–9) versus 10.1 (range 5–48) days, p = 0.01. 20 The fifth study, by Conway and colleagues,17 reported a median of 12 (range 7–103) days for the ODM group versus 11 (range 7–30) days for the control group (p-value not reported). Table 5 shows the length of hospital stay for the five studies.

TABLE 5 - Length of hospital stay (days)

IQR, interquartile range; NR, not reported; SD, standard deviation.

The report stated that in the study by Conway and colleagues17 one patient in the ODM group remained in hospital for 103 days, not because of complications but because a social/community placement could not be found.

Source: AHRQ report. 6

Study	n	Measure	ODM group	Control group	p-value
aConway 200217	57	Mean (SD) Median (range)	18.7 (20.2) 12 (7–103)	12.7 (6.0) 11 (7–30)	NR NR
Gan 200218	100	Mean (SD) Median	5 (3) 6	7 (3) 7	NR 0.03
Mythen 199520	60	Mean (range)	6.4 (5–9)	10.1 (5–48)	0.01
Noblett 200621	103	Median (IQR)	7 (3–35)	9 (4–45)	0.005
Wakeling 200524	128	Median (IQR)	10 (5.75)	11.5 (4.75)	0.03

The AHRQ used a conservative method to impute effect sizes from the median, range and sample size when possible and conducted a random-effects meta-analysis. An overall pooled estimate was not presented on the grounds that three of the five studies reporting this outcome did not present data that allowed a precise effect size to be calculated. However the 95% CI was presented; this was –2.21 to –0.57 days, indicating that ODM was associated with a statistically significantly shorter length of hospital stay.

Although the data should be treated extremely cautiously, Figure 7 shows a meta-analysis undertaken by the Aberdeen group of the two studies reporting means and standard deviations for length of hospital stay. The pooled estimate shows that ODM was associated with a statistically significantly shorter length of hospital stay (WMD –1.82, 95% CI –2.98 to –0.65). There is evidence of heterogeneity which may be caused by differences between the two study population groups, although much of the difference in the mean length of stay in the Conway study was caused by one patient in the ODM group (see footnote, Table 5). As this meta-analysis includes only one of the four studies favouring ODM it might be argued that the estimate is slightly biased against ODM.

FIGURE 7.

Meta-analysis of length of hospital stay (Aberdeen TAR group).

Overall, the data available for length of stay suggest that this may be shorter in the ODM group, although the precise magnitude of the difference is uncertain. However, the data from the Aberdeen meta-analysis also suggest that the type of patient may also be important.

ODM plus conventional clinical assessment versus CVP plus conventional clinical assessment

Again, the only data for this comparison came from the AHRQ report. 6 One study, by Venn and colleagues,23 compared ODM plus conventional assessment (n = 30) with CVP monitoring plus conventional assessment (n = 31) in patients undergoing surgery for hip fracture repair (this study also included conventional assessment alone (n = 29) as a comparator, see below).

Mortality

The AHRQ report stated that although there were fewer deaths in the ODM group (3/30) compared with the control group (6/31), the difference was not statistically significant (p = 0.30).

Major complications

Venn and colleagues23 did not report major complications separately from total complications.

Total complications

There were 46.7% (14/30) complications in the ODM plus conventional assessment group compared with 51.6% (16/31) in the CVP monitoring plus conventional assessment group. The AHRQ report6 stated that the difference in the rate of total complications (comprising mostly infections and cardiovascular events) favoured the ODM group without being statistically significant (OR 0.82, 95% CI 0.30–2.25). In terms of the number of patients experiencing complications, 33.3% (10/30) patients in the ODM group experienced complications compared with 45.2% (14/31) patients in the CVP monitoring group, again favouring the ODM group but without reaching statistical significance (OR 0.61, 95% CI 0.21–1.72).

Length of hospital stay

The AHRQ report6 stated that the difference in the mean length of hospital stay between the ODM and CVP monitoring groups was not statistically significant (13.5 versus 13.3 days, respectively, p = 0.96).

ODM plus conventional clinical assessment versus conventional clinical assessment

The AHRQ report6 included two studies that reported this comparison, involving 99 patients undergoing surgery for hip fracture repair. 22,23 An additional study to those included by the AHRQ report was identified. This was a poster by Dodd and colleagues26 involving 40 patients undergoing colorectal surgery.

Mortality

The AHRQ report stated that both studies reported that no deaths occurred during surgery. Venn and colleagues23 reported that three (3/30) deaths occurred in the ODM group and two (2/29) occurred in the control group within 30 days following surgery, while Sinclair and colleagues22 reported that one (1/20) death occurred in the control group during this period. Sinclair and colleagues22 reported a further two deaths [one (1/20) in the ODM group and one in the control group] after this period and within 3 months following surgery. In terms of total mortality rates, the AHRQ report stated that neither study showed a statistically significant difference between the two treatment groups.

The additional study by Dodd and colleagues26 reported hospital mortality of one (1/20) death in the ODM group and two (2/20) deaths in the control group.

Figure 8 shows a meta-analysis of studies reporting mortality undertaken by the Aberdeen group, including the additional study by Dodd and colleagues,26 with the pooled estimate failing to reach statistical significance and with confidence intervals sufficiently wide to include clinically important differences favouring either intervention (OR 0.81, 95% 0.23–2.77).

FIGURE 8.

Meta-analysis of studies reporting mortality (Aberdeen TAR group).

Major complications

Sinclair and colleagues22 did not report complications and Venn and colleagues23 did not report major complications separately from total complications. The additional study by Dodd and colleagues26 did not report major complications.

Total complications

The AHRQ report stated that in the study by Venn and colleagues,23 the ODM group experienced statistically significantly fewer complications (46.7%, 14/30) than the control group (79.3%, 23/29) (OR 0.23, 95% CI 0.07–0.72). However, in terms of the number of patients experiencing complications, the difference between the ODM group (33.3%, 10/30) and the control group (55.2%, 16/29) was not statistically significant and the confidence interval was sufficiently wide to contain clinically important differences favouring either intervention (OR 0.41, 95% CI 0.14–1.16).

The additional study by Dodd and colleagues26 did not report total complications.

Length of hospital stay

The AHRQ report stated that both studies reported a shorter length of stay for the ODM group. Sinclair and colleagues22 reported a statistically significantly shorter length of stay for the ODM group compared with the control group, with a median of 11 (range 3–23) days versus 20 (range 5–220) days, p < 0.05. In the study by Venn and colleagues,23 although the ODM group experienced a shorter length of stay (mean 13.5 days, 95% CI 10.9–17.5) compared with the control group (mean 17.5 days, 95% CI 13.9–24.4) the difference was not statistically significant (p = 0.31). Table 6 shows the length of hospital stay. In a random-effects meta-analysis undertaken by the AHRQ report, the pooled mean difference was statistically significant in favour of patients receiving ODM (mean difference –6.76, 95% CI –11.83 to –1.68).

TABLE 6 - Length of hospital stay (days)

NR, not reported.

Data are for number of days until medically fit for discharge.

Study	n	Measure	ODM group	Control group	p-value
aDodd 200426	40	Median (range)	8 (5–34)	9 (5–27)	NR
Sinclair 199722	40	Median (range)	11 (3–23)	20 (5–220)	< 0.05
Venn 200223	90	Mean (95% CI)	13.5 (10.9–17.5)	17.5 (13.9–24.4)	0.31

The additional study by Dodd and colleagues26 reported a shorter median (range) length of stay of 8 (5–34) days for the ODM group compared with 9 (5– 27) days for the control group, in terms of the number of days until medically fit for discharge. However, Dodd and colleagues26 reported a longer median length of stay in the HDU of 3 (2–10) days for the ODM group (n = 7) compared with 2 (2–10) days for the control group (n = 5).

ODM among critically ill patients

ODM plus CVP plus conventional clinical assessment versus CVP plus conventional clinical assessment

The AHRQ report included one study19 that reported this comparison in 174 patients admitted to cardiac intensive care following cardiac surgery, with the intervention group allocated to a fluid replacement algorithm guided by ODM during the first 4 hours after admission to cardiac intensive care. An additional study by Chytra and colleagues25 was identified, involving 162 multiple-trauma patients admitted to an ICU following surgery, with the intervention group allocated to a fluid replacement algorithm guided by ODM during the first 12 hours after admission to the ICU.

Mortality

The AHRQ report stated that in the study by McKendry and colleagues19 there were more deaths in the ODM group (4/89) compared with the control group (2/85) although the difference was not statistically significant (p = 0.43). Chytra and colleagues25 reported fewer deaths in the ODM group (13/80) compared with the control group (18/82). Although the groups of patients included in the two studies might be considered very different, a meta-analysis was undertaken by the Aberdeen group of the studies reporting mortality (Figure 9). The OR for each study individually was not statistically significant, with the confidence intervals being sufficiently wide to include clinically important differences favouring either intervention. The pooled estimate also failed to reach statistical significance (OR 0.84, 95% CI 0.41–1.70). The results of the meta-analysis should be interpreted with caution owing to the very different types of patient included in the two studies.

FIGURE 9.

Meta-analysis of studies reporting mortality (Aberdeen TAR group).

Major complications

Although McKendry and colleagues19 stated that there was a trend towards fewer major postoperative complications and deaths in the ODM group, major complications were not reported separately from total complications. The additional study by Chytra and colleagues25 also did not report major complications separately.

Total complications

The AHRQ report stated that although fewer patients in the ODM group (19.1%, 17/89) experienced complications compared with the control group (30.6%, 26/85), the difference was not statistically significant (p = 0.08). In the additional study by Chytra and colleagues,25 fewer patients in the ODM group (18.8%, 15/80) experienced infectious complications compared with the control group (34.1%, 28/82), with the difference being statistically significant (p = 0.032). Figure 10 shows a meta-analysis undertaken by the Aberdeen group of the studies reporting the number of patients with complications, with ODM being associated with statistically significantly fewer complications (OR 0.49, 95% CI 0.30–0.81). Again caution must be exercised when interpreting this meta-analysis as the patient groups in the two studies were different.

FIGURE 10.

Meta-analysis of studies reporting total number of patients with complications (Aberdeen TAR group).

Length of hospital stay

The AHRQ report6 stated that there was a statistically significantly shorter median length of stay in the ODM group (7 days, range not reported) compared with the control group (9 days, range not reported), p = 0.02. The mean length of stay was also shorter in the ODM group (11.4 days) compared with the control group (13.9 days), p-value not reported. In the additional study by Chytra and colleagues25 there was a statistically significantly shorter median length of stay in the ODM group (14 days, IQR 8.25–21) compared with the control group (17.5 days, IQR 11–29), p = 0.045. Table 7 shows the length of hospital stay.

TABLE 7 - Length of hospital stay (days)

IQR, interquartile range; NR, not reported.

Study	n	Measure	ODM group	Control group	p-value
Chytra 200725	162	Median (IQR)	14 (8.25–21)	17.5 (11–29)	0.045
McKendry 200419	174	Mean	11.4	13.9	NR
		Median	7	9	0.02

Chytra and colleagues25 also reported a statistically significantly shorter ICU median length of stay in the ODM group (7 days, IQR 6–11) compared with the control group (8.5 days, IQR 6–16), p = 0.031.

Summary

The evidence on ODM presented in this chapter is based on the AHRQ report,6 supplemented by two additional studies that were identified. 25,26 The eight RCTs17–24 included in the AHRQ report and the two additional RCTs25,26 reported the use of ODM in patients during surgery or among critically ill patients. The four outcomes reported by the AHRQ report were mortality, major complications, total complications and length of hospital stay. None of the studies reported quality of life data. None of the studies reported results for patients with sepsis compared with those without sepsis.

The AHRQ report used an ECRI 25-question scale to assess the quality of the included studies. This scale was also applied to the additional studies that were identified. In the AHRQ report, for all comparisons reported by more than one study, the median quality score fell within the range ≥ 8.5 to 10.0, a quality rating of ‘high’ for this evidence base. The additional study by Dodd and colleagues26 also received a quality rating of ‘high’, while the study by Chytra and colleagues25 fell within the range > 6.7 but ≤ 8.4 and received a quality rating of ‘moderate’.

The AHRQ report scored 5 (minor bias) on a scale of 1 (extensive flaws) to 7 (minimal flaws) on the Oxman and Guyatt checklist14,15 for assessing the methodological quality of systematic reviews.

Five studies involving 453 patients reported ODM plus CVP monitoring plus conventional assessment versus CVP monitoring plus conventional assessment during surgery. 17,18,20,21,24 The AHRQ report did not pool mortality data. In meta-analyses undertaken by the Aberdeen group, pooled estimates showed statistically significantly fewer deaths in the ODM group (Peto OR 0.13, 95% CI 0.02–0.96) and a statistically significant reduction in the incidence of major complications (Peto OR 0.12, 95% CI 0.04–0.31) and total complications (fixed-effects OR 0.43, 95% CI 0.26–0.71). However, as noted above, as the number of deaths was low and the total combined sample size was modest, the pooled estimate for mortality should be interpreted with caution. In four of five studies reporting length of hospital stay, there was a statistically significant difference in favour of ODM, with a median of 6 versus 7 days, p = 0.03,18 7 (IQR 3–35) versus 9 (IQR 4–45) days, p = 0.005,21 10 (IQR 5.75) versus 11.5 (IQR 4.75) days, p = 0.03,24 and a mean of 6.4 (range 5–9) versus 10.1 (range 5–48) days, p = 0.01. 20 A random-effects meta-analysis undertaken by the AHRQ report showed a statistically significantly shorter length of hospital stay in favour of the ODM group (pooled estimate not presented, 95% CI –2.21 to –0.57). One of the studies included in this comparison considered the use of ODM among elective cardiac surgery patients. 20 This group of patients might be considered to be different from patients undergoing other forms of surgery. Nevertheless, the results from this study were consistent with the results of the others.

Only Venn and colleagues23 reported ODM plus conventional assessment versus CVP monitoring plus conventional assessment during surgery, in a study involving 61 patients. Although the outcomes reported favoured the ODM group, none were statistically significant and confidence intervals were sufficiently wide to include clinically important differences favouring either treatment.

Two studies22,23 included in the AHRQ report and one additional study26 involving a total of 139 patients reported ODM plus conventional assessment versus conventional assessment during surgery. None of the studies showed a statistically significant difference in mortality, and in a meta-analysis of the three studies undertaken by the Aberdeen group, the pooled estimate was not statistically significant (fixed-effects OR 0.81, 95% CI 0.23–2.77). None of the studies reported the outcome of major complications. Only Venn and colleagues23 reported total complications, with the AHRQ report stating that there was a statistically significant difference in favour of the ODM group in terms of the number of complications (OR 0.23, 95% CI 0.07–0.72) but not in terms of the number of patients experiencing complications (0.41, 95% CI 0.14–1.16).

One study19 included in the AHRQ report and one additional study25 involving a total of 336 patients reported ODM plus CVP monitoring plus conventional assessment versus CVP monitoring plus conventional assessment among critically ill patients. Neither study showed a statistically significant difference in mortality, and in a meta-analysis undertaken by the Aberdeen group, the pooled estimate was not statistically significant (fixed-effects OR 0.84, 95% CI 0.41–1.70). There may be some concerns that the patient groups included in the two studies were very different, so this pooled estimate should be treated with caution. Neither study reported the outcome of major complications. In a meta-analysis undertaken by the Aberdeen group of total complications, the two studies showed a similar trend and the pooled estimate showed that statistically significantly fewer patients in the ODM group experienced this outcome (OR 0.49, 95% CI 0.30–0.81). In terms of length of hospital stay, the AHRQ report6 stated that in the study by McKendry and colleagues19 there was a statistically significantly shorter median length of stay in the ODM group compared with the control group (7 versus 9 days, p = 0.02), and the study by Chytra and colleagues25 also reported a statistically significantly shorter median length of stay in favour of the ODM group compared with the control group (14 versus 17.5 days, p = 0.045).

In terms of ODM-related complications, five studies17,21,22,23,25 reported that none occurred, while the remaining five18,19,20,24,26 made no mention of ODM-related complications.

Methods

Results

Balance sheet

As described above, no economic evaluations that met the inclusion criteria were found from the systematic search of the literature. It was, therefore, not possible to provide any comment on the comparative costs and/or effects of ODM in comparison with relevant comparators. To give an idea of the impact that regular use of ODM might have on the NHS in terms of costs and effects, a series of balance sheets were drawn up. The balance sheet presents the differences between interventions, in terms of resource use and natural and clinical measures of effectiveness. Such an approach serves to highlight the choices and trade-offs between the various monitoring modalities. Nonetheless, any decision based on the balance sheet approach is made using an implicit (rather than an explicit) synthesis of the available data.

Recent evidence on the cost-effectiveness of alternatives to ODM

Although no data were identified that were relevant to a comparison of ODM, a previous HTA monograph reported findings from a systematic review and RCT of the effectiveness and cost-effectiveness of PAC in patient management in intensive care. 1 Within the trial, 55 (10.9%) patients in the PAC group and 179 (35.2%) patients in the control group received transoesophageal Doppler monitoring. However, no separate results were presented for these patients. The HTA suggests that PAC was unlikely to be cost-effective for this group of patients. The HTA also provided an indication of the cost drivers, i.e. the major determinants of the differences in cost between the interventions compared. It is likely that the costs of ODM compared with the costs of no ODM will be driven by similar factors, primarily length of stay differences. The trial reported in the HTA found that for the financial year 2002–3, the cost per day in an ICU was £1353. Thus, if the addition of ODM to high-risk surgical and critically ill hospitalised patients does lead to a significant reduction in length of ICU stay, it is likely to have a large impact on cost. Other things being equal, if the costs of equipment and staffing associated with ODM per patient were to be less than £310 [a conservative estimate based on data from Information Servicers Division (ISD) Scotland]29 regular ODM use is likely to be cost saving, especially if we take into account the cost information supplied by the manufacturer (Ewan Phillips, Deltex Medical, July 2007, personal communication).

Summary

This chapter presents the overall evidence currently available on the cost-effectiveness of ODM compared with relevant comparators in the management of critically ill hospitalised patients and high-risk surgical patients, based on a systematic review of the literature. No economic evaluations that met inclusion criteria were identified and little extra knowledge of the cost-effectiveness of ODM relative to the various strategies could be ascertained.

In order to explore the choices and trade-offs of the various monitoring modalities, a balance sheet was presented for each strategy for which evidence was available from the review of effectiveness. Some evidence indicates that ODM might be expected to be more efficient than not using ODM but any judgement depends upon the strategies compared. Further information for the critically ill hospitalised patient group compared with high-risk surgical patients is required owing to the sparse data on this patient group. The trade-offs highlighted by the balance sheets could be further informed by more formal consideration of the balance of probabilities in terms of which strategy is or is not likely to be cost-effective.

In terms of effectiveness, it should be noted that no comparisons of ODM with thermodilution or PAC methods were found and that, therefore, such comparisons are not included in this review or on the balance sheet.

An economic model for ODM

Drummond and colleagues defined economic evaluation as the ‘comparative analysis of alternative courses of action in terms of both their costs and consequences,’ ideally over the remaining lifetime of the patient. 30 Economic evaluations are an important aid to decision-making because (a) a systematic analysis makes it easier to identify clearly the relevant alternatives; (b) such an approach makes explicit the viewpoint of the analysis; and (c) without some attempt at measurement, the uncertainty surrounding orders of magnitude can be critical.

Moreover, there are certain characteristics that an economic model should have in order to be a sound basis for decision-making. Among these is that it should include all the relevant alternatives for comparison and should allow for appropriate information to be taken into account within the evaluation. The model can be thought of as describing the pathways of care that a patient may follow in situations where ODM is and is not used. A potential model structure should consider strategies that include no cardiac monitoring, alone or in combination with technologies such as pulse contour analysis monitoring, lithium dilution cardiac monitors (i.e. LiDCO monitor), and thermodilution cardiac monitors (i.e. PiCCO monitor), as comparators for strategies that include ODM. A similar model structure could be outlined for the use of ODM within hospital critical care.

By clearly structuring the decision problem it is possible to highlight the data that are needed to fully inform any decision. However, it is possible that decisions might be reasonably made without all these data. In subsequent sections we explore how the data that are currently available can be used more fully to inform judgements on cost-effectiveness.

Cost of ODM

In this section data provided by a manufacturer, Deltex Medical, as well as data from public sources have been used to estimate the extra (incremental) costs associated with ODM. Table 13 shows the annual total cost of ODM assuming a 5-year lifetime for the monitor. The costs of ODM are based on data provided by Deltex Medical (Ewan Phillips, Deltex Medical, August 2007, personal communication).

The cost of the probes varies from £60 for a 6-hour oral/nasal Doppler probe for use intraoperatively or perioperatively to £121 for a 10-day sterilised oral Doppler probe for use in critical care. Information from the manufacturer indicated that the use of more than one probe by a patient was rare. Therefore, it was assumed that the number of probes used per monitor per year is similar to the number of patients receiving ODM per year. However, this will depend upon the initial selection of the probe and the prior clinical judgement as to how the patient will respond. Given the nature of the patient groups it might be expected that the use of more than one probe would be more common among critically ill than surgical patients.

It is unclear how many patients might use a monitor per year (i.e. how intensively the equipment is used) and what would be the optimal use rate in a potential steady state. For instance, the average length of stay in an ICU in Scotland’s hospitals is 4.7 days31 (for an HDU it is 3.2 days). This does not mean, however, that a particular monitor would be used, on average, every 5 days as this would imply a full-time usage assumption for this equipment. Moreover, patients receiving critical care (within either an ICU or an HDU) who require ODM might not be representative of the whole population of patients receiving critical care, and their length of stay may be higher or lower than the average. Given the absence of data on the length of use of ODM, a simple assumption can be made about the number of patients who might be treated with a single monitor within a given year. For illustrative purposes, in this exercise three usage rates per monitor per year have been considered (36, 125 and 500) to explore the impact of different levels of intensity of use (Table 14). These figures result from an assumption of 250 days of usage of equipment per year and different numbers of patients treated (i.e. one patient every 7 days, one patient every 2 days and two patients per day, respectively).

Table 15 shows estimations of the total cost for ODM equipment and probe per patient. Based on the assumptions stated above and according to the probe used the total equipment cost can range from around £66 to £214 per patient.

When estimating costs of a procedure it would be usual to include other categories of cost such as the staff time involved. However, the marginal staff cost of using ODM may be minimal as the staff required to interpret the outputs of the monitor will be there anyway. Furthermore, the time it takes to insert the probe and obtain the initial readings is also minimal (e.g. about 5 minutes; Dr Gordon Houston, July 2007, personal communication). Other direct costs associated with the procedure, such as ultrasound gel or other disposal materials, are negligible. As indicated in Chapter 4, one category of costs not included in these analyses is the cost of treatments incurred as a result of monitoring. The net effect and magnitude of these costs is uncertain.

Further estimation of the implications for cost-effectiveness

This section explores the cost-effectiveness of ODM for the different comparisons presented in Chapters 3 and 4. The analyses focused on two outcomes: mortality and length of hospital stay. Worst- and best-case scenarios for the use of ODM were constructed for each comparison. These scenarios differed in terms of the cost of ODM equipment (e.g. £214 for worst-case and £66 for best-case scenario, as reported in Table 15), and the cost attached to any reduction in the length of stay due to ODM. For the worst-case scenario this was taken to be equal to £310 per day (corresponding to the cost of a day in a general medical ward) and for the best-case scenario the cost used was £1680 per day, which corresponds to the cost of a day in an ICU. 31 Finally, the mean length of survival per additional survivor was taken to be 1 year for the worst-case scenario and 5 years for the best-case scenario. These numbers help to illustrate the trade-offs that might be faced.

Results are presented in terms of QALYs. For these calculations a quality of life weight [as measured by the European Quality of Life-5 Dimensions (EQ-5D) scale] at 12 months of 0.66 was used. This estimate is based on quality of life of ICU survivors at 12 months (lower than the 0.88 score that might be estimated for the general population32).

Finally, in order to allow for the statistical imprecision surrounding estimates of the differences in mean length of stay and survival, normal and lognormal distributions, respectively, were used to describe the uncertainty in these parameters. The data required to construct these distributions were the estimated confidence intervals reported in Chapter 3 and, as such, the same limitations as stated in Chapters 3 and 4 apply to this economic evaluation exercise.

High-risk surgical patients

ODM plus CVP plus conventional clinical assessment versus CVP plus conventional clinical assessment for high-risk surgical patients

Table 9 shows a balance sheet for the ODM plus CVP monitoring plus conventional clinical assessment versus CVP monitoring plus conventional clinical assessment comparison for high-risk surgical patients. In favour of ODM it shows reduction in mortality (OR 0.13, 95% CI 0.02–0.96), reduction in major complications (OR 0.12, 95% CI 0.04–0.31), reduction in total complications (OR 0.43, 95% CI 0.26–0.71) and reduction in length of hospital stay (WMD –1.82, 95% CI –2.98 to –0.65). Conversely, favouring the non-use of ODM there are the additional costs for ODM and potentially increased management costs for survivors due to a lower mortality rate in the ODM group. With the cost calculations obtained for ODM in the previous section and focusing on the reduction in mortality, it is possible to illustrate the extent of the increment in health-care costs and QALYs per additional survivor before ODM would not be considered cost-effective at a £30,000 per QALY threshold. 33

Figure 11 shows the results for ODM plus CVP monitoring plus conventional clinical assessment versus CVP monitoring plus conventional clinical assessment for high-risk surgical patients. The probabilistic sensitivity analysis was based on 1000 iterations of a Monte Carlo analysis. The black line represents the £30,000 cost per QALY threshold and the circles on the right and below this line are iterations of the model that indicate that the use of ODM would be cost-effective. The more circles there are to the right of and below the line the more likely it is that the use of ODM would be cost-effective. The white circle in the middle of the black circle ‘cloud’ is the incremental cost-effectiveness based on the point estimates for each of the parameters used in assessing cost-effectiveness.

FIGURE 11.

Incremental cost-effectiveness plane – best-case ODM scenario: ODM + CVP + conventional clinical assessment vs CVP + conventional clinical assessment for high-risk surgical patients.

It can be seen in Figure 11 that a great majority of the points lie within the second quadrant; this indicates that using ODM together with CVP monitoring and conventional clinical assessment seems to be more effective and less costly than using only CVP monitoring and conventional clinical assessment. A similar result can be observed in Figure 12 for the worst-case ODM scenario. Note that the cloud appears truncated on the right because of our assumption of a 1- or 5-year increment to length of life for additional survivors.

FIGURE 12.

Incremental cost-effectiveness plane – worst-case ODM scenario: ODM + CVP + conventional clinical assessment vs CVP + conventional clinical assessment for high-risk surgical patients.

Figures 13 and 14 show the average extra cost per additional survivor that would need to be incurred before ODM would no longer be considered cost-effective. In terms of Figures 11 and 12 this is equivalent to moving the circles upward and crossing the £30,000 threshold. For the best-case scenario this mean that the extra cost per additional survivor would be £4441 (95% CI £2151–£6732) and for the worst-case scenario the extra cost per additional survivor would be £642 (95% CI £225–£1060).

FIGURE 13.

Histogram: extra NHS survival costs for ODM to stop being considered cost-effective – best-case ODM scenario: ODM + CVP + conventional clinical assessment vs CVP + conventional clinical assessment for high-risk surgical patients.

FIGURE 14.

Histogram: extra NHS survival costs for ODM to stop being considered cost-effective – worst-case ODM scenario: ODM + CVP + conventional clinical assessment vs CVP + conventional clinical assessment for high-risk surgical patients.

Caution should be taken when reading these results as calculations did not take into account the other issues favouring ODM (e.g. the reductions in complications that the calculations assume are fully captured by the reductions in length of stay and increases in survival). The incorporation of all these factors into a full economic model might give a better idea of the likelihood of ODM being cost-effective.

Further analysis was undertaken using data from the AHRQ report on the difference in length of hospital stay. These data are more conservative than those used above. A lognormal distribution was attached to these data using the 95% CI, i.e. –2.21 to –0.57 days. The other data used in this model are the same as those used for the worst-case model presented above.

The great majority of points from the probabilistic sensitivity analysis lie in the second quadrant, where using ODM together with CVP monitoring and conventional clinical assessment seems to be more effective and less costly than using only CVP monitoring and conventional clinical assessment (Figure 15). However, should the mean incremental cost per additional survivor be £448 or more (95% CI £117–£779) then the ODM-based strategy would no longer be considered cost-effective (Figure 16).

FIGURE 15.

Incremental cost-effectiveness plane – sensitivity analysis using AHRQ meta-analysis on length of stay: ODM + CVP + conventional clinical assessment vs CVP + conventional clinical assessment for high-risk surgical patients.

FIGURE 16.

Histogram: extra NHS survival costs for ODM to stop being considered cost-effective – sensitivity analysis using AHRQ meta-analysis on length of stay: ODM + CVP + conventional clinical assessment vs CVP + conventional clinical assessment for high-risk surgical patients.

ODM plus conventional clinical assessment versus CVP plus conventional clinical assessment for high-risk surgical patients

Unfortunately, there are no feasible exercises for this comparison as there are no data on which calculations could be based. This means that it is not possible to provide any sensible estimates of the incremental costs and benefits of ODM for this clinical scenario.

ODM plus conventional clinical assessment versus conventional clinical assessment for high-risk surgical patients

Table 11 shows the balance sheet for this comparison. In favour of ODM a reduction in length of hospital stay (OR –6.76, 95% CI –11.83 to –1.68) can be observed. The difference in mortality is not statistically significant as the confidence intervals are sufficiently wide to favour any of the comparators (OR 0.81, 95% CI 0.23–2.77). The same analyses as used previously were undertaken in this case.

Figures 17 and 18 show the results for best- and worst-case ODM scenarios, respectively. In both these figures more than half of the iterations from the Monte Carlo simulation are in the second quadrant (i.e. ODM is more effective and less costly); therefore, no matter how much the decision-maker would value a QALY gained, these results will always favour the ODM strategy. The remainder of the iterations are mainly in the third quadrant, where ODM is both less costly and less effective. Consequently, cost-effectiveness for these results will depend on how much society values the QALY gain from not using ODM. For the £30,000 threshold (black line), in the majority of these iterations the use of ODM would be considered cost-effective (i.e. the circles are to the right of and below the threshold line).

FIGURE 17.

Incremental cost-effectiveness plane – best-case ODM scenario: ODM + conventional clinical assessment vs conventional clinical assessment for high-risk surgical patients.

FIGURE 18.

Incremental cost-effectiveness plane – worst-case ODM scenario: ODM + conventional clinical assessment vs conventional clinical assessment for high-risk surgical patients.

Figures 19 and 20 show the histograms for the average extra cost per additional survivor that would need to be incurred before ODM would no longer be considered cost-effective for the best- and worst-case scenarios, respectively. For the best-case scenario a mean extra cost of £11,588 (95% CI –£2529 to £25,705) is needed for ODM to stop being considered cost-effective, while a mean extra cost of £1879 (95% CI –£920 to £4678) would be required for the worst-case scenario.

FIGURE 19.

Histogram: extra NHS survival costs for ODM to stop being considered cost-effective – best-case ODM scenario: ODM + conventional clinical assessment vs conventional clinical assessment for high-risk surgical patients.

FIGURE 20.

Histogram: extra NHS survival costs for ODM to stop being considered cost-effective – worst-case ODM scenario: ODM + conventional clinical assessment vs conventional clinical assessment for high-risk surgical patients

Critically ill patients

ODM plus CVP plus conventional clinical assessment versus CVP plus conventional clinical assessment for critically ill hospitalised patients

Table 12 shows the balance sheet for ODM plus conventional clinical assessment versus CVP monitoring plus conventional clinical assessment for critically ill hospitalised patients. In favour of ODM the reduction in total complications (OR 0.49, 95% CI 0.30–0.81) and the reduction in length of stay (1–2 days less) were stated; while there was no statistically significant difference in mortality (OR 0.84, 95% CI 0.41–1.70) and it was not possible to measure the effects on other outcomes.

Figures 21 and 22 show the results of the probabilistic analyses for the best- and worst-case scenarios, respectively. The variability in the cost results comes from the uncertainty in the length of stay estimation. As there were no data to attach a probability distribution to this parameter, an assumption about the difference in length of stay was made. Differences of 2 days and 1 day in length of stay in favour of ODM were assumed for the best- and worst-case scenarios, respectively (it is for this reason that there is almost no variability in incremental cost in the probabilistic analysis). There is variability in QALYs, however, as estimates of the differences in mortality were available.

FIGURE 21.

Incremental cost-effectiveness plane – best-case ODM scenario: ODM + CVP + conventional clinical assessment vs CVP + conventional clinical assessment for critically ill patients.

FIGURE 22.

Incremental cost-effectiveness plane – worst-case ODM scenario: ODM + CVP + conventional clinical assessment vs CVP + conventional clinical assessment for critically ill patients.

Almost 70% of the Monte Carlo simulation iterations lie within the second quadrant (i.e. ODM is more effective and less costly). The remaining 30% of the results lie in the third quadrant (i.e. ODM is less effective and less costly). Therefore, the decision as to whether they are cost-effective is independent of the threshold. For the best-case scenario for ODM the probability of being cost-effective at a £30,000 threshold is 90% (80% for worst-case ODM scenario).

Figures 23 and 24 show the histograms for the average extra cost per additional survivor that would need to be incurred before ODM would no longer be considered cost-effective for the best- and worst-case scenarios, respectively. For the former, a mean additional cost of £4978 (95% CI –£2655 to £12,611) would be needed for ODM to stop being considered cost-effective; while for the latter, a mean additional cost of £364 (95% CI –£1271 to £1998) would be needed for ODM to stop being considered cost-effective.

FIGURE 23.

Histogram: extra NHS survival costs for ODM to stop being considered cost-effective – best-case ODM scenario: ODM + CVP + conventional clinical assessment vs CVP + conventional clinical assessment for critically ill patients.

FIGURE 24.

Histogram: extra NHS survival costs for ODM to stop being considered cost-effective – worst-case ODM scenario: ODM + CVP + conventional clinical assessment vs CVP + conventional clinical assessment for critically ill patients.

Summary

This chapter explored the cost-effectiveness of ODM and thus expanded upon the work presented in previous chapters. However, it was not possible to obtain quantitative results for all four comparisons for which balance sheets were produced in Chapter 4 and for those where it was possible, results should be interpreted with caution as the results presented in this chapter are subject to the same caveats as those noted in earlier chapters.

For high-risk patients we obtained quantitative results for ODM plus CVP monitoring plus conventional clinical assessment versus CVP monitoring plus conventional clinical assessment and for ODM plus conventional clinical assessment versus conventional clinical assessment. For critically ill hospitalised patients we obtained quantitative results for ODM plus CVP monitoring plus conventional clinical assessment versus CVP monitoring plus conventional clinical assessment only. No quantitative results were obtained for ODM plus conventional clinical assessment versus CVP monitoring plus conventional clinical assessment for high-risk surgical patients.

All the comparisons exploring the strategies that involved the use of ODM seem to have a reasonable chance of being considered cost-effective given the assumptions that we have made. However, these results seem to be heavily dependent on the mean cost for the NHS of treating those extra survivors and on the cost of treatments incurred because of monitoring. The threshold value that these costs would need to reach before ODM might not be considered cost-effective ranged from £581 to £11,600 depending on the comparison and the underlying assumptions. It is not clear from this current work whether or not costs of this magnitude are likely to exist in practice.

There are further limitations to these analyses; the main one, perhaps, being the partial modelling approach adopted here. The analyses did not take into account other factors presented within the balance sheets. This would not affect every comparison in the same way. For instance, factors such as the reduction in major and total complications are definitely in favour of ODM (i.e. higher quality of life for those not having these major complications) for the ODM plus CVP monitoring plus conventional clinical assessment within surgery comparison. Therefore, including these into a full economic model would improve the cost-effectiveness of ODM (however, part of the effect of complications within the model should have been reflected within length of stay differences). For the other comparisons it is unclear what the effect would be of including these additional factors into an economic model.

Finally, as stated earlier in this report, the cost-effectiveness of any strategy depends on the alternative strategies with which it is being compared. For this reason, a full economic model should include all the relevant alternatives; these are all the potential relevant pathways of care that include and do not include ODM, as well as current practice.

Statement of principal findings

Strengths and limitations

The strengths of this review include the fact that the AHRQ report upon which it is based is a high-quality study (scored as 5, ‘minor bias’ on the Oxman and Guyatt systematic review checklist). Also, an additional two studies were identified to add to the evidence base of the eight studies included in the AHRQ review. In addition, all included studies were RCTs, which are less prone to bias than non-randomised study designs, and the outcomes assessed were all patient related.

As noted above there may be some concerns about combining data relating to cardiac surgery patients with data relating to non-cardiac surgery patients. In terms of the use of ODM during surgery the results from both groups of patients are broadly consistent. However, it is less clear whether it is appropriate to combine the data from the two studies identified that considered using ODM among critically ill patients, as the patient groups in these two studies are different.

In terms of limitations, both the AHRQ report and this review excluded non-English language studies. Of the eight studies included in the AHRQ report and the two additional studies identified, five involved fewer than 100 patients. Only 2 of the 10 studies assessed ODM in critical illness. The AHRQ review’s outcomes were broadly similar to those included in the original protocol for this review, with the exception of quality of life, which the AHRQ report did not include as an outcome. However, none of the included studies assessing ODM during surgery or postoperatively reported quality of life data.

A limitation of the technology noted by Chytra and colleagues was that in their study of ODM during critical illness it was difficult to keep the Doppler probe in the correct position without frequent adjustments during the 12-hour period that it was being assessed in the ICU. 25 The authors also found the 12-hour study protocol to be time consuming and noted that it would not have been feasible without the co-operation of nursing staff. Gan and colleagues stated that there was a learning curve to achieve placement of the probe to capture the maximal signal. 18 A study by Lefrant and colleagues recommended a period of training involving no more than 12 patients to ensure reliability of cardiac output measurements by ODM. 7

Other reviews of fluid optimisation interventions have been published that reported patient-related outcomes. A Cochrane review by Price and colleagues51 included RCTs comparing a fluid optimisation intervention with normal practice or with another fluid optimisation intervention in patients undergoing surgery to repair proximal femoral fracture. The review included two studies, by Sinclair and colleagues22 and Venn and colleagues,23 both of which are included in the AHRQ report. The Cochrane review concluded that invasive methods of fluid optimisation during surgery may shorten hospital stay but that their effects on other important, patient-centred, longer-term outcomes are uncertain. 51

A review by Bundgaard-Nielsen and colleagues52 assessed the influence of goal-directed therapy on postoperative outcome. Nine studies met the inclusion criteria; the eight reporting ODM were those included in the AHRQ report and the ninth was a study by Pearse and colleagues53 comparing LiDCO with CVP monitoring. Pearse and colleagues53 concluded that goal-directed therapy reduces hospital stay, postoperative nausea and vomiting and complications, and facilitates faster gastrointestinal functional recovery.

With regard to the cost-effectiveness data the primary limitation is the lack of existing studies, which restricts the analysis of cost-effectiveness. Nevertheless, merely by organising the available data some reasonably firm conclusions could be drawn and the choices and trade-offs could be highlighted. Any judgements that utilise these data should consider the pros and cons for the use of ODM as well as the importance of the considerable uncertainty surrounding the estimates of relative effectiveness. Currently, these judgements must be based on the implicit valuation of these factors, but a more explicit consideration could be provided by using the available data within a modelling exercise. Such an exercise was explored and involved the more formal consideration of costs and partially incorporated the best available evidence on effectiveness. The added value of such work might be seen as limited for some comparisons, such as ODM plus CVP monitoring and conventional clinical assessment versus plus CVP monitoring and conventional clinical assessment, where conclusions could potentially be reached already. The modelling exercise incorporated some of the uncertainty around effectiveness estimates and shed some light on the extent to which the use of ODM might be considered cost-effective. A full economic model might serve further to inform the decision-making process by entirely incorporating other factors (e.g. number of major and/or total complications) for all the relevant alternatives, and not only employing those pairwise comparisons considered in the partial modelling exercises. Cardiac monitoring can be used in a variety of patient groups. It is possible that the cost-effectiveness (and the effectiveness) may differ between these groups. An indication for this is the evidence of heterogeneity identified in Figure 7.

Uncertainties

In terms of the type of patients considered to be suitable for ODM-guided fluid administration during surgery, the AHRQ report stated that its conclusions applied only to patients undergoing surgical procedures with an expected substantial blood loss or fluid shifts requiring fluid replacement. The types of surgery performed in the seven AHRQ and one additional study assessing ODM during surgery included moderate- to high-risk procedures such as elective bowel surgery, hip fracture repair surgery, elective cardiac surgery, elective general, urological or gynaecological surgery, and major general abdominal surgery.

The optimal period of ODM-guided fluid administration once patients have been admitted to critical care following surgery is unclear. McKendry and colleagues19 applied ODM-guided fluid administration for a period of 4 hours after patients were admitted to cardiac intensive care after cardiac surgery, while Chytra and colleagues25 monitored multiple-trauma patients with major blood loss for a period of 12 hours following admission to the ICU.

All of the included studies involved unconscious patients, as ODM technologies currently in practice are unsuitable for use in postoperative awake patients. Although an ODM probe is now manufactured for per-nasal passage in awake patients it has yet to be fully evaluated and no additional studies using such a probe were identified that met our inclusion criteria.

In terms of cost-effectiveness, limited data are currently available. While it may be possible to draw some sensible conclusions about the use of ODM, additional research may be useful both in terms of using the available data more fully in an economic modelling exercise and to fill gaps in the primary research evidence.

Other relevant factors

Potentially relevant studies identified from a search of the National Research Register are listed in Appendix 9. The largest of the ongoing studies is a French multicentre study (Cholley) that is scheduled to run from April 2007 to April 2010. This study was also mentioned in the AHRQ report. The aim of the study is to assess whether intraoperative fluid supplementation to improve tissue perfusion can reduce the incidence of postoperative complications in elderly patients with hip fracture. The study design is described as randomised, double-blind and placebo controlled. The primary end point is to demonstrate that colloid titration, guided using oesophageal Doppler estimation of stroke volume, during the surgical repair of hip fracture reduces the incidence of postoperative complications. Secondary end points include (a) delay to walking without help; (b) increased number of days ‘out of hospital’ at 3 months after the fracture; and (c) mortality at 1 year. The protocol for the study indicated that 19 centres would be participating and that the aim was to recruit 800 patients. This will be the largest study of ODM during surgery to date and its results should add substantially to the existing evidence base.

Implications for practice

Recommendations for research

Contribution of authors

Graham Mowatt completed the review of effectiveness. Gordon Houston drafted the background chapter and along with Brian Cuthbertson provided advice and commented on drafts of the review. Rodolfo Hernández drafted the decision problem and conducted the economic evaluation. Robyn de Verteuil conducted the review of economic evaluations. Cynthia Fraser developed and ran the search strategies and was responsible for obtaining papers and for reference management. Luke Vale led the review team.

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.

Health Technology Assessment reports published to date

1. Home parenteral nutrition: a systematic review.

   By Richards DM, Deeks JJ, Sheldon TA, Shaffer JL.

2. Diagnosis, management and screening of early localised prostate cancer.

   A review by Selley S, Donovan J, Faulkner A, Coast J, Gillatt D.

3. The diagnosis, management, treatment and costs of prostate cancer in England and Wales.

   A review by Chamberlain J, Melia J, Moss S, Brown J.

4. Screening for fragile X syndrome.

   A review by Murray J, Cuckle H, Taylor G, Hewison J.

5. A review of near patient testing in primary care.

   By Hobbs FDR, Delaney BC, Fitzmaurice DA, Wilson S, Hyde CJ, Thorpe GH, et al.

6. Systematic review of outpatient services for chronic pain control.

   By McQuay HJ, Moore RA, Eccleston C, Morley S, de C Williams AC.

7. Neonatal screening for inborn errors of metabolism: cost, yield and outcome.

   A review by Pollitt RJ, Green A, McCabe CJ, Booth A, Cooper NJ, Leonard JV, et al.

8. Preschool vision screening.

   A review by Snowdon SK, Stewart-Brown SL.

9. Implications of socio-cultural contexts for the ethics of clinical trials.

   A review by Ashcroft RE, Chadwick DW, Clark SRL, Edwards RHT, Frith L, Hutton JL.

10. A critical review of the role of neonatal hearing screening in the detection of congenital hearing impairment.

    By Davis A, Bamford J, Wilson I, Ramkalawan T, Forshaw M, Wright S.

11. Newborn screening for inborn errors of metabolism: a systematic review.

    By Seymour CA, Thomason MJ, Chalmers RA, Addison GM, Bain MD, Cockburn F, et al.

12. Routine preoperative testing: a systematic review of the evidence.

    By Munro J, Booth A, Nicholl J.

13. Systematic review of the effectiveness of laxatives in the elderly.

    By Petticrew M, Watt I, Sheldon T.

14. When and how to assess fast-changing technologies: a comparative study of medical applications of four generic technologies.

    A review by Mowatt G, Bower DJ, Brebner JA, Cairns JA, Grant AM, McKee L.

1. Antenatal screening for Down’s syndrome.

   A review by Wald NJ, Kennard A, Hackshaw A, McGuire A.

2. Screening for ovarian cancer: a systematic review.

   By Bell R, Petticrew M, Luengo S, Sheldon TA.

3. Consensus development methods, and their use in clinical guideline development.

   A review by Murphy MK, Black NA, Lamping DL, McKee CM, Sanderson CFB, Askham J, et al.

4. A cost–utility analysis of interferon beta for multiple sclerosis.

   By Parkin D, McNamee P, Jacoby A, Miller P, Thomas S, Bates D.

5. Effectiveness and efficiency of methods of dialysis therapy for end-stage renal disease: systematic reviews.

   By MacLeod A, Grant A, Donaldson C, Khan I, Campbell M, Daly C, et al.

6. Effectiveness of hip prostheses in primary total hip replacement: a critical review of evidence and an economic model.

   By Faulkner A, Kennedy LG, Baxter K, Donovan J, Wilkinson M, Bevan G.

7. Antimicrobial prophylaxis in colorectal surgery: a systematic review of randomised controlled trials.

   By Song F, Glenny AM.

8. Bone marrow and peripheral blood stem cell transplantation for malignancy.

   A review by Johnson PWM, Simnett SJ, Sweetenham JW, Morgan GJ, Stewart LA.

9. Screening for speech and language delay: a systematic review of the literature.

   By Law J, Boyle J, Harris F, Harkness A, Nye C.

10. Resource allocation for chronic stable angina: a systematic review of effectiveness, costs and cost-effectiveness of alternative interventions.

    By Sculpher MJ, Petticrew M, Kelland JL, Elliott RA, Holdright DR, Buxton MJ.

11. Detection, adherence and control of hypertension for the prevention of stroke: a systematic review.

    By Ebrahim S.

12. Postoperative analgesia and vomiting, with special reference to day-case surgery: a systematic review.

    By McQuay HJ, Moore RA.

13. Choosing between randomised and nonrandomised studies: a systematic review.

    By Britton A, McKee M, Black N, McPherson K, Sanderson C, Bain C.

14. Evaluating patient-based outcome measures for use in clinical trials.

    A review by Fitzpatrick R, Davey C, Buxton MJ, Jones DR.

15. Ethical issues in the design and conduct of randomised controlled trials.

    A review by Edwards SJL, Lilford RJ, Braunholtz DA, Jackson JC, Hewison J, Thornton J.

16. Qualitative research methods in health technology assessment: a review of the literature.

    By Murphy E, Dingwall R, Greatbatch D, Parker S, Watson P.

17. The costs and benefits of paramedic skills in pre-hospital trauma care.

    By Nicholl J, Hughes S, Dixon S, Turner J, Yates D.

18. Systematic review of endoscopic ultrasound in gastro-oesophageal cancer.

    By Harris KM, Kelly S, Berry E, Hutton J, Roderick P, Cullingworth J, et al.

19. Systematic reviews of trials and other studies.

    By Sutton AJ, Abrams KR, Jones DR, Sheldon TA, Song F.

20. Primary total hip replacement surgery: a systematic review of outcomes and modelling of cost-effectiveness associated with different prostheses.

    A review by Fitzpatrick R, Shortall E, Sculpher M, Murray D, Morris R, Lodge M, et al.

1. Informed decision making: an annotated bibliography and systematic review.

   By Bekker H, Thornton JG, Airey CM, Connelly JB, Hewison J, Robinson MB, et al.

2. Handling uncertainty when performing economic evaluation of healthcare interventions.

   A review by Briggs AH, Gray AM.

3. The role of expectancies in the placebo effect and their use in the delivery of health care: a systematic review.

   By Crow R, Gage H, Hampson S, Hart J, Kimber A, Thomas H.

4. A randomised controlled trial of different approaches to universal antenatal HIV testing: uptake and acceptability. Annex: Antenatal HIV testing – assessment of a routine voluntary approach.

   By Simpson WM, Johnstone FD, Boyd FM, Goldberg DJ, Hart GJ, Gormley SM, et al.

5. Methods for evaluating area-wide and organisation-based interventions in health and health care: a systematic review.

   By Ukoumunne OC, Gulliford MC, Chinn S, Sterne JAC, Burney PGJ.

6. Assessing the costs of healthcare technologies in clinical trials.

   A review by Johnston K, Buxton MJ, Jones DR, Fitzpatrick R.

7. Cooperatives and their primary care emergency centres: organisation and impact.

   By Hallam L, Henthorne K.

8. Screening for cystic fibrosis.

   A review by Murray J, Cuckle H, Taylor G, Littlewood J, Hewison J.

9. A review of the use of health status measures in economic evaluation.

   By Brazier J, Deverill M, Green C, Harper R, Booth A.

10. Methods for the analysis of quality-of-life and survival data in health technology assessment.

    A review by Billingham LJ, Abrams KR, Jones DR.

11. Antenatal and neonatal haemoglobinopathy screening in the UK: review and economic analysis.

    By Zeuner D, Ades AE, Karnon J, Brown J, Dezateux C, Anionwu EN.

12. Assessing the quality of reports of randomised trials: implications for the conduct of meta-analyses.

    A review by Moher D, Cook DJ, Jadad AR, Tugwell P, Moher M, Jones A, et al.

13. ‘Early warning systems’ for identifying new healthcare technologies.

    By Robert G, Stevens A, Gabbay J.

14. A systematic review of the role of human papillomavirus testing within a cervical screening programme.

    By Cuzick J, Sasieni P, Davies P, Adams J, Normand C, Frater A, et al.

15. Near patient testing in diabetes clinics: appraising the costs and outcomes.

    By Grieve R, Beech R, Vincent J, Mazurkiewicz J.

16. Positron emission tomography: establishing priorities for health technology assessment.

    A review by Robert G, Milne R.

17. The debridement of chronic wounds: a systematic review.

    By Bradley M, Cullum N, Sheldon T.

18. Systematic reviews of wound care management: (2) Dressings and topical agents used in the healing of chronic wounds.

    By Bradley M, Cullum N, Nelson EA, Petticrew M, Sheldon T, Torgerson D.

19. A systematic literature review of spiral and electron beam computed tomography: with particular reference to clinical applications in hepatic lesions, pulmonary embolus and coronary artery disease.

    By Berry E, Kelly S, Hutton J, Harris KM, Roderick P, Boyce JC, et al.

20. What role for statins? A review and economic model.

    By Ebrahim S, Davey Smith G, McCabe C, Payne N, Pickin M, Sheldon TA, et al.

21. Factors that limit the quality, number and progress of randomised controlled trials.

    A review by Prescott RJ, Counsell CE, Gillespie WJ, Grant AM, Russell IT, Kiauka S, et al.

22. Antimicrobial prophylaxis in total hip replacement: a systematic review.

    By Glenny AM, Song F.

23. Health promoting schools and health promotion in schools: two systematic reviews.

    By Lister-Sharp D, Chapman S, Stewart-Brown S, Sowden A.

24. Economic evaluation of a primary care-based education programme for patients with osteoarthritis of the knee.

    A review by Lord J, Victor C, Littlejohns P, Ross FM, Axford JS.

1. The estimation of marginal time preference in a UK-wide sample (TEMPUS) project.

   A review by Cairns JA, van der Pol MM.

2. Geriatric rehabilitation following fractures in older people: a systematic review.

   By Cameron I, Crotty M, Currie C, Finnegan T, Gillespie L, Gillespie W, et al.

3. Screening for sickle cell disease and thalassaemia: a systematic review with supplementary research.

   By Davies SC, Cronin E, Gill M, Greengross P, Hickman M, Normand C.

4. Community provision of hearing aids and related audiology services.

   A review by Reeves DJ, Alborz A, Hickson FS, Bamford JM.

5. False-negative results in screening programmes: systematic review of impact and implications.

   By Petticrew MP, Sowden AJ, Lister-Sharp D, Wright K.

6. Costs and benefits of community postnatal support workers: a randomised controlled trial.

   By Morrell CJ, Spiby H, Stewart P, Walters S, Morgan A.

7. Implantable contraceptives (subdermal implants and hormonally impregnated intrauterine systems) versus other forms of reversible contraceptives: two systematic reviews to assess relative effectiveness, acceptability, tolerability and cost-effectiveness.

   By French RS, Cowan FM, Mansour DJA, Morris S, Procter T, Hughes D, et al.

8. An introduction to statistical methods for health technology assessment.

   A review by White SJ, Ashby D, Brown PJ.

9. Disease-modifying drugs for multiple sclerosis: a rapid and systematic review.

   By Clegg A, Bryant J, Milne R.

10. Publication and related biases.

    A review by Song F, Eastwood AJ, Gilbody S, Duley L, Sutton AJ.

11. Cost and outcome implications of the organisation of vascular services.

    By Michaels J, Brazier J, Palfreyman S, Shackley P, Slack R.

12. Monitoring blood glucose control in diabetes mellitus: a systematic review.

    By Coster S, Gulliford MC, Seed PT, Powrie JK, Swaminathan R.

13. The effectiveness of domiciliary health visiting: a systematic review of international studies and a selective review of the British literature.

    By Elkan R, Kendrick D, Hewitt M, Robinson JJA, Tolley K, Blair M, et al.

14. The determinants of screening uptake and interventions for increasing uptake: a systematic review.

    By Jepson R, Clegg A, Forbes C, Lewis R, Sowden A, Kleijnen J.

15. The effectiveness and cost-effectiveness of prophylactic removal of wisdom teeth.

    A rapid review by Song F, O’Meara S, Wilson P, Golder S, Kleijnen J.

16. Ultrasound screening in pregnancy: a systematic review of the clinical effectiveness, cost-effectiveness and women’s views.

    By Bricker L, Garcia J, Henderson J, Mugford M, Neilson J, Roberts T, et al.

17. A rapid and systematic review of the effectiveness and cost-effectiveness of the taxanes used in the treatment of advanced breast and ovarian cancer.

    By Lister-Sharp D, McDonagh MS, Khan KS, Kleijnen J.

18. Liquid-based cytology in cervical screening: a rapid and systematic review.

    By Payne N, Chilcott J, McGoogan E.

19. Randomised controlled trial of non-directive counselling, cognitive–behaviour therapy and usual general practitioner care in the management of depression as well as mixed anxiety and depression in primary care.

    By King M, Sibbald B, Ward E, Bower P, Lloyd M, Gabbay M, et al.

20. Routine referral for radiography of patients presenting with low back pain: is patients’ outcome influenced by GPs’ referral for plain radiography?

    By Kerry S, Hilton S, Patel S, Dundas D, Rink E, Lord J.

21. Systematic reviews of wound care management: (3) antimicrobial agents for chronic wounds; (4) diabetic foot ulceration.

    By O’Meara S, Cullum N, Majid M, Sheldon T.

22. Using routine data to complement and enhance the results of randomised controlled trials.

    By Lewsey JD, Leyland AH, Murray GD, Boddy FA.

23. Coronary artery stents in the treatment of ischaemic heart disease: a rapid and systematic review.

    By Meads C, Cummins C, Jolly K, Stevens A, Burls A, Hyde C.

24. Outcome measures for adult critical care: a systematic review.

    By Hayes JA, Black NA, Jenkinson C, Young JD, Rowan KM, Daly K, et al.

25. A systematic review to evaluate the effectiveness of interventions to promote the initiation of breastfeeding.

    By Fairbank L, O’Meara S, Renfrew MJ, Woolridge M, Sowden AJ, Lister-Sharp D.

26. Implantable cardioverter defibrillators: arrhythmias. A rapid and systematic review.

    By Parkes J, Bryant J, Milne R.

27. Treatments for fatigue in multiple sclerosis: a rapid and systematic review.

    By Brañas P, Jordan R, Fry-Smith A, Burls A, Hyde C.

28. Early asthma prophylaxis, natural history, skeletal development and economy (EASE): a pilot randomised controlled trial.

    By Baxter-Jones ADG, Helms PJ, Russell G, Grant A, Ross S, Cairns JA, et al.

29. Screening for hypercholesterolaemia versus case finding for familial hypercholesterolaemia: a systematic review and cost-effectiveness analysis.

    By Marks D, Wonderling D, Thorogood M, Lambert H, Humphries SE, Neil HAW.

30. A rapid and systematic review of the clinical effectiveness and cost-effectiveness of glycoprotein IIb/IIIa antagonists in the medical management of unstable angina.

    By McDonagh MS, Bachmann LM, Golder S, Kleijnen J, ter Riet G.

31. A randomised controlled trial of prehospital intravenous fluid replacement therapy in serious trauma.

    By Turner J, Nicholl J, Webber L, Cox H, Dixon S, Yates D.

32. Intrathecal pumps for giving opioids in chronic pain: a systematic review.

    By Williams JE, Louw G, Towlerton G.

33. Combination therapy (interferon alfa and ribavirin) in the treatment of chronic hepatitis C: a rapid and systematic review.

    By Shepherd J, Waugh N, Hewitson P.

34. A systematic review of comparisons of effect sizes derived from randomised and non-randomised studies.

    By MacLehose RR, Reeves BC, Harvey IM, Sheldon TA, Russell IT, Black AMS.

35. Intravascular ultrasound-guided interventions in coronary artery disease: a systematic literature review, with decision-analytic modelling, of outcomes and cost-effectiveness.

    By Berry E, Kelly S, Hutton J, Lindsay HSJ, Blaxill JM, Evans JA, et al.

36. A randomised controlled trial to evaluate the effectiveness and cost-effectiveness of counselling patients with chronic depression.

    By Simpson S, Corney R, Fitzgerald P, Beecham J.

37. Systematic review of treatments for atopic eczema.

    By Hoare C, Li Wan Po A, Williams H.

38. Bayesian methods in health technology assessment: a review.

    By Spiegelhalter DJ, Myles JP, Jones DR, Abrams KR.

39. The management of dyspepsia: a systematic review.

    By Delaney B, Moayyedi P, Deeks J, Innes M, Soo S, Barton P, et al.

40. A systematic review of treatments for severe psoriasis.

    By Griffiths CEM, Clark CM, Chalmers RJG, Li Wan Po A, Williams HC.

1. Clinical and cost-effectiveness of donepezil, rivastigmine and galantamine for Alzheimer’s disease: a rapid and systematic review.

   By Clegg A, Bryant J, Nicholson T, McIntyre L, De Broe S, Gerard K, et al.

2. The clinical effectiveness and cost-effectiveness of riluzole for motor neurone disease: a rapid and systematic review.

   By Stewart A, Sandercock J, Bryan S, Hyde C, Barton PM, Fry-Smith A, et al.

3. Equity and the economic evaluation of healthcare.

   By Sassi F, Archard L, Le Grand J.

4. Quality-of-life measures in chronic diseases of childhood.

   By Eiser C, Morse R.

5. Eliciting public preferences for healthcare: a systematic review of techniques.

   By Ryan M, Scott DA, Reeves C, Bate A, van Teijlingen ER, Russell EM, et al.

6. General health status measures for people with cognitive impairment: learning disability and acquired brain injury.

   By Riemsma RP, Forbes CA, Glanville JM, Eastwood AJ, Kleijnen J.

7. An assessment of screening strategies for fragile X syndrome in the UK.

   By Pembrey ME, Barnicoat AJ, Carmichael B, Bobrow M, Turner G.

8. Issues in methodological research: perspectives from researchers and commissioners.

   By Lilford RJ, Richardson A, Stevens A, Fitzpatrick R, Edwards S, Rock F, et al.

9. Systematic reviews of wound care management: (5) beds; (6) compression; (7) laser therapy, therapeutic ultrasound, electrotherapy and electromagnetic therapy.

   By Cullum N, Nelson EA, Flemming K, Sheldon T.

10. Effects of educational and psychosocial interventions for adolescents with diabetes mellitus: a systematic review.

    By Hampson SE, Skinner TC, Hart J, Storey L, Gage H, Foxcroft D, et al.

11. Effectiveness of autologous chondrocyte transplantation for hyaline cartilage defects in knees: a rapid and systematic review.

    By Jobanputra P, Parry D, Fry-Smith A, Burls A.

12. Statistical assessment of the learning curves of health technologies.

    By Ramsay CR, Grant AM, Wallace SA, Garthwaite PH, Monk AF, Russell IT.

13. The effectiveness and cost-effectiveness of temozolomide for the treatment of recurrent malignant glioma: a rapid and systematic review.

    By Dinnes J, Cave C, Huang S, Major K, Milne R.

14. A rapid and systematic review of the clinical effectiveness and cost-effectiveness of debriding agents in treating surgical wounds healing by secondary intention.

    By Lewis R, Whiting P, ter Riet G, O’Meara S, Glanville J.

15. Home treatment for mental health problems: a systematic review.

    By Burns T, Knapp M, Catty J, Healey A, Henderson J, Watt H, et al.

16. How to develop cost-conscious guidelines.

    By Eccles M, Mason J.

17. The role of specialist nurses in multiple sclerosis: a rapid and systematic review.

    By De Broe S, Christopher F, Waugh N.

18. A rapid and systematic review of the clinical effectiveness and cost-effectiveness of orlistat in the management of obesity.

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

19. The clinical effectiveness and cost-effectiveness of pioglitazone for type 2 diabetes mellitus: a rapid and systematic review.

    By Chilcott J, Wight J, Lloyd Jones M, Tappenden P.

20. Extended scope of nursing practice: a multicentre randomised controlled trial of appropriately trained nurses and preregistration house officers in preoperative assessment in elective general surgery.

    By Kinley H, Czoski-Murray C, George S, McCabe C, Primrose J, Reilly C, et al.

21. Systematic reviews of the effectiveness of day care for people with severe mental disorders: (1) Acute day hospital versus admission; (2) Vocational rehabilitation; (3) Day hospital versus outpatient care.

    By Marshall M, Crowther R, Almaraz- Serrano A, Creed F, Sledge W, Kluiter H, et al.

22. The measurement and monitoring of surgical adverse events.

    By Bruce J, Russell EM, Mollison J, Krukowski ZH.

23. Action research: a systematic review and guidance for assessment.

    By Waterman H, Tillen D, Dickson R, de Koning K.

24. A rapid and systematic review of the clinical effectiveness and cost-effectiveness of gemcitabine for the treatment of pancreatic cancer.

    By Ward S, Morris E, Bansback N, Calvert N, Crellin A, Forman D, et al.

25. A rapid and systematic review of the evidence for the clinical effectiveness and cost-effectiveness of irinotecan, oxaliplatin and raltitrexed for the treatment of advanced colorectal cancer.

    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.

1. A systematic review and economic model of switching from nonglycopeptide to glycopeptide antibiotic prophylaxis for surgery.

   By Cranny G, Elliott R, Weatherly H, Chambers D, Hawkins N, Myers L, et al.

2. ‘Cut down to quit’ with nicotine replacement therapies in smoking cessation: a systematic review of effectiveness and economic analysis.

   By Wang D, Connock M, Barton P, Fry-Smith A, Aveyard P, Moore D.

3. A systematic review of the effectiveness of strategies for reducing fracture risk in children with juvenile idiopathic arthritis with additional data on long-term risk of fracture and cost of disease management.

   By Thornton J, Ashcroft D, O’Neill T, Elliott R, Adams J, Roberts C, et al.

4. Does befriending by trained lay workers improve psychological well-being and quality of life for carers of people with dementia, and at what cost? A randomised controlled trial.

   By Charlesworth G, Shepstone L, Wilson E, Thalanany M, Mugford M, Poland F.

5. A multi-centre retrospective cohort study comparing the efficacy, safety and cost-effectiveness of hysterectomy and uterine artery embolisation for the treatment of symptomatic uterine fibroids. The HOPEFUL study.

   By Hirst A, Dutton S, Wu O, Briggs A, Edwards C, Waldenmaier L, et al.

6. Methods of prediction and prevention of pre-eclampsia: systematic reviews of accuracy and effectiveness literature with economic modelling.

   By Meads CA, Cnossen JS, Meher S, Juarez-Garcia A, ter Riet G, Duley L, et al.

7. The use of economic evaluations in NHS decision-making: a review and empirical investigation.

   By Williams I, McIver S, Moore D, Bryan S.

8. Stapled haemorrhoidectomy (haemorrhoidopexy) for the treatment of haemorrhoids: a systematic review and economic evaluation.

   By Burch J, Epstein D, Baba-Akbari A, Weatherly H, Fox D, Golder S, et al.

9. The clinical effectiveness of diabetes education models for Type 2 diabetes: a systematic review.

   By Loveman E, Frampton GK, Clegg AJ.

10. Payment to healthcare professionals for patient recruitment to trials: systematic review and qualitative study.

    By Raftery J, Bryant J, Powell J, Kerr C, Hawker S.

11. Cyclooxygenase-2 selective non-steroidal anti-inflammatory drugs (etodolac, meloxicam, celecoxib, rofecoxib, etoricoxib, valdecoxib and lumiracoxib) for osteoarthritis and rheumatoid arthritis: a systematic review and economic evaluation.

    By Chen Y-F, Jobanputra P, Barton P, Bryan S, Fry-Smith A, Harris G, et al.

12. The clinical effectiveness and cost-effectiveness of central venous catheters treated with anti-infective agents in preventing bloodstream infections: a systematic review and economic evaluation.

    By Hockenhull JC, Dwan K, Boland A, Smith G, Bagust A, Dundar Y, et al.

13. Stepped treatment of older adults on laxatives. The STOOL trial.

    By Mihaylov S, Stark C, McColl E, Steen N, Vanoli A, Rubin G, et al.

14. A randomised controlled trial of cognitive behaviour therapy in adolescents with major depression treated by selective serotonin reuptake inhibitors. The ADAPT trial.

    By Goodyer IM, Dubicka B, Wilkinson P, Kelvin R, Roberts C, Byford S, et al.

15. The use of irinotecan, oxaliplatin and raltitrexed for the treatment of advanced colorectal cancer: systematic review and economic evaluation.

    By Hind D, Tappenden P, Tumur I, Eggington E, Sutcliffe P, Ryan A.

16. Ranibizumab and pegaptanib for the treatment of age-related macular degeneration: a systematic review and economic evaluation.

    By Colquitt JL, Jones J, Tan SC, Takeda A, Clegg AJ, Price A.

17. Systematic review of the clinical effectiveness and cost-effectiveness of 64-slice or higher computed tomography angiography as an alternative to invasive coronary angiography in the investigation of coronary artery disease.

    By Mowatt G, Cummins E, Waugh N, Walker S, Cook J, Jia X, et al.

18. Structural neuroimaging in psychosis: a systematic review and economic evaluation.

    By Albon E, Tsourapas A, Frew E, Davenport C, Oyebode F, Bayliss S, et al.

19. Systematic review and economic analysis of the comparative effectiveness of different inhaled corticosteroids and their usage with long-acting beta₂ agonists for the treatment of chronic asthma in adults and children aged 12 years and over.

    By Shepherd J, Rogers G, Anderson R, Main C, Thompson-Coon J, Hartwell D, et al.

20. Systematic review and economic analysis of the comparative effectiveness of different inhaled corticosteroids and their usage with long-acting beta₂ agonists for the treatment of chronic asthma in children under the age of 12 years.

    By Main C, Shepherd J, Anderson R, Rogers G, Thompson-Coon J, Liu Z, et al.

21. Ezetimibe for the treatment of hypercholesterolaemia: a systematic review and economic evaluation.

    By Ara R, Tumur I, Pandor A, Duenas A, Williams R, Wilkinson A, et al.

22. Topical or oral ibuprofen for chronic knee pain in older people. The TOIB study.

    By Underwood M, Ashby D, Carnes D, Castelnuovo E, Cross P, Harding G, et al.

23. A prospective randomised comparison of minor surgery in primary and secondary care. The MiSTIC trial.

    By George S, Pockney P, Primrose J, Smith H, Little P, Kinley H, et al.

24. A review and critical appraisal of measures of therapist–patient interactions in mental health settings.

    By Cahill J, Barkham M, Hardy G, Gilbody S, Richards D, Bower P, et al.

25. The clinical effectiveness and cost-effectiveness of screening programmes for amblyopia and strabismus in children up to the age of 4–5 years: a systematic review and economic evaluation.

    By Carlton J, Karnon J, Czoski-Murray C, Smith KJ, Marr J.

26. A systematic review of the clinical effectiveness and cost-effectiveness and economic modelling of minimal incision total hip replacement approaches in the management of arthritic disease of the hip.

    By de Verteuil R, Imamura M, Zhu S, Glazener C, Fraser C, Munro N, et al.

27. A preliminary model-based assessment of the cost–utility of a screening programme for early age-related macular degeneration.

    By Karnon J, Czoski-Murray C, Smith K, Brand C, Chakravarthy U, Davis S, et al.

28. Intravenous magnesium sulphate and sotalol for prevention of atrial fibrillation after coronary artery bypass surgery: a systematic review and economic evaluation.

    By Shepherd J, Jones J, Frampton GK, Tanajewski L, Turner D, Price A.

29. Absorbent products for urinary/faecal incontinence: a comparative evaluation of key product categories.

    By Fader M, Cottenden A, Getliffe K, Gage H, Clarke-O’Neill S, Jamieson K, et al.

30. A systematic review of repetitive functional task practice with modelling of resource use, costs and effectiveness.

    By French B, Leathley M, Sutton C, McAdam J, Thomas L, Forster A, et al.

31. The effectiveness and cost-effectivness of minimal access surgery amongst people with gastro-oesophageal reflux disease – a UK collaborative study. The reflux trial.

    By Grant A, Wileman S, Ramsay C, Bojke L, Epstein D, Sculpher M, et al.

32. Time to full publication of studies of anti-cancer medicines for breast cancer and the potential for publication bias: a short systematic review.

    By Takeda A, Loveman E, Harris P, Hartwell D, Welch K.

33. Performance of screening tests for child physical abuse in accident and emergency departments.

    By Woodman J, Pitt M, Wentz R, Taylor B, Hodes D, Gilbert RE.

34. Curative catheter ablation in atrial fibrillation and typical atrial flutter: systematic review and economic evaluation.

    By Rodgers M, McKenna C, Palmer S, Chambers D, Van Hout S, Golder S, et al.

35. Systematic review and economic modelling of effectiveness and cost utility of surgical treatments for men with benign prostatic enlargement.

    By Lourenco T, Armstrong N, N’Dow J, Nabi G, Deverill M, Pickard R, et al.

36. Immunoprophylaxis against respiratory syncytial virus (RSV) with palivizumab in children: a systematic review and economic evaluation.

    By Wang D, Cummins C, Bayliss S, Sandercock J, Burls A.

1. Deferasirox for the treatment of iron overload associated with regular blood transfusions (transfusional haemosiderosis) in patients suffering with chronic anaemia: a systematic review and economic evaluation.

   By McLeod C, Fleeman N, Kirkham J, Bagust A, Boland A, Chu P, et al.

2. Thrombophilia testing in people with venous thromboembolism: systematic review and cost-effectiveness analysis.

   By Simpson EL, Stevenson MD, Rawdin A, Papaioannou D.

3. Surgical procedures and non-surgical devices for the management of non-apnoeic snoring: a systematic review of clinical effects and associated treatment costs.

   By Main C, Liu Z, Welch K, Weiner G, Quentin Jones S, Stein K.

4. Continuous positive airway pressure devices for the treatment of obstructive sleep apnoea–hypopnoea syndrome: a systematic review and economic analysis.

   By McDaid C, Griffin S, Weatherly H, Durée K, van der Burgt M, van Hout S, Akers J, et al.

5. Use of classical and novel biomarkers as prognostic risk factors for localised prostate cancer: a systematic review.

   By Sutcliffe P, Hummel S, Simpson E, Young T, Rees A, Wilkinson A, et al.

6. The harmful health effects of recreational ecstasy: a systematic review of observational evidence.

   By Rogers G, Elston J, Garside R, Roome C, Taylor R, Younger P, et al.

Health Technology Assessment Programme

1. Director, NIHR HTA Programme, Professor of Clinical Pharmacology, University of Liverpool

2. Director, Medical Care Research Unit, University of Sheffield