5.1 The committee discussed current practice in the NHS for monitoring the fluid status of people with chronic kidney disease who are having dialysis. It heard from clinical experts that target weights are set to determine how much fluid should be removed during a dialysis session. A person's target weight is usually set and adjusted based on clinical assessment, which takes into account the person's clinical history and any reported symptoms that may suggest fluid overload or dehydration. It heard that there is currently no standardised approach to clinical assessment of fluid status and that there is variation both in how it is done and also the frequency with which it occurs. The committee concluded that current practice for monitoring fluid status in people having dialysis is highly subjective and results in variation in practice both in and between centres.
5.2 The committee discussed the effect of fluid imbalances on the quality of life of a person having dialysis. It heard from a patient expert that the consequences of fluid overload can include oedema and difficulty breathing. In contrast, removing too much fluid during haemodialysis can lead to painful muscle cramps and hypotension, which can cause a person to faint during or shortly after dialysis sessions. It can also cause more prolonged side effects such as headaches and fatigue after a haemodialysis session. The committee heard from clinical experts that in the shorter term, fluid overload can result in hypertension whereas dehydration can lead to hypotension and decreased blood flow to organs, such as the heart and brain. The longer-term consequences of persistent or intermittent fluid overload and dehydration in adults can include cognitive decline, reduced residual renal function and major adverse cardiovascular events. In children, who often have dialysis as a bridge to a renal transplant, it may contribute to developmental delay and increase their risk of adverse cardiovascular events in later life, particularly if they go on to have dialysis as an adult after transplant failure. The committee concluded that technologies that aim to provide a more objective assessment of fluid status in people having dialysis may be a way of improving the quality of life for this population.
5.3 The committee reviewed the available evidence on the clinical effectiveness of using multiple frequency bioimpedance devices to guide fluid management in people with chronic kidney disease having dialysis. It noted that in total, 14 studies were included in the review, 6 of which were randomised controlled trials (RCTs). All of the studies reported data for the BCM – Body Composition Monitor device only, and 5 of the RCTs were noted to be at a high or uncertain risk of bias. No studies reported data for the InBody S10 or MultiScan 5000. The committee heard from clinical experts that the devices use different models to calculate how overhydrated or underhydrated a person is. Also, no data were available to determine the equivalence of fluid overload or target weight calculated by these devices and values calculated by the BCM – Body Composition Monitor; therefore clinical-outcome data from studies with the BCM – Body Composition Monitor could not be considered applicable to the other devices. The committee noted that without device-specific or equivalence data, the InBody S10 or MultiScan 5000 could not be considered further in this assessment.
5.4 The committee discussed the generalisability of data from the included studies to the NHS. It noted that none of the RCTs and 2 of the non-randomised studies (reported in 3 papers) were done in the UK. The committee heard from clinical experts that current practice varies widely between countries, particularly on whether fluid status is assessed by nursing or medical staff and how frequently assessments are done. It also noted that many of the studies did not give enough details to determine how standard clinical assessment was done, making it difficult to determine whether they were representative of UK practice. The committee therefore concluded that the effect estimates reported by the included studies may not be generalisable to clinical practice in England.
5.5 The committee discussed the evidence available on the effect of BCM – Body Composition Monitor-guided monitoring on mortality. The committee noted that the pooled-effect estimate (pooled hazard ratio 0.69; 95% confidence interval [CI] 0.23 to 2.08; p=0.51) of BCM – Body Composition Monitor-guided monitoring on mortality was not significant. It noted that the total number of mortality events in the 3 included studies was small (42 events) and that the methods used for randomisation were not adequate. It heard from clinical experts that these studies were not powered to show an effect on mortality because this is not the main aim of using the BCM device to guide fluid management. The committee concluded that there is likely to be substantial bias underlying the meta-analysis of mortality data and so there is great uncertainty about the pooled-effect estimate.
5.6 The committee discussed the effect of BCM – Body Composition Monitor-guided monitoring on intermediate outcomes such as blood pressure control and arterial stiffness. The committee noted that 3 RCTs reported data on arterial stiffness measured by pulse wave velocity and questioned the methods used to get the data. It heard from clinical experts that measurements of pulse wave velocity in these studies were carotid-femoral pulse wave velocity, which is not considered an appropriate surrogate for cardiac morbidity. The committee also noted that 2 of the studies included in the meta-analyses for blood pressure and arterial stiffness (Onofriescu et al. 2012 and 2014) seemed to have overlapping patient populations. When both of these studies are included in the meta-analyses, BCM– Body Composition Monitor-guided monitoring results in a statistically significant improvement in blood pressure (p=0.006) and arterial stiffness (p=0.04). If Onofriescu et al. (2012) is removed the effect is no longer statistically significant. The committee concluded that there was substantial uncertainty around the effect of BCM – Body Composition Monitor-guided monitoring on reducing arterial stiffness and blood pressure, and so on cardiovascular outcomes.
5.7 The committee considered the data available on the effect of BCM – Body Composition Monitor-guided monitoring on patient-reported adverse effects associated with dialysis. It noted that data from identified studies did not show a clear benefit to using the device. A patient expert commented that since their fluid levels had been monitored using the BCM – Body Composition Monitor device, they had experienced fewer side effects associated with fluid imbalance, and that if they have symptoms possibly related to dialysis a reading with the device can be used to check if they are because of fluid levels. The committee concluded that there is considerable uncertainty about the effect of BCM – Body Composition Monitor-guided monitoring on reducing the number of patient-reported adverse effects associated with fluid imbalance and dialysis.
5.8 The committee noted that the studies included reported data on the effect of fluid overload, but did not consider the effect of underhydration. It heard from a clinical expert that the BCM – Body Composition Monitor device may identify people, who have previously been identified as normally hydrated by clinical assessment, as underhydrated. Underhydration can lead to clotting in dialysis fistulas, muscle cramps and nausea. It heard that identifying people who are underhydrated, or preventing underhydration, could help to preserve residual renal function in people having dialysis. The committee concluded that more data is needed in this subgroup and noted that this will be collected in the National Institute for Health Research (NIHR) funded BISTRO trial (see section 5.17).
5.9 The committee discussed the likely effect of BCM – Body Composition Monitor-guided monitoring on peritoneal dialysis. The committee noted that most of the studies included in the clinical-effectiveness analyses reported data for haemodialysis. Only 1 RCT assessed use of the BCM – Body Composition Monitor device in people having peritoneal dialysis, and reported that BCM – Body Composition Monitor-guided monitoring reduced systolic blood pressure (mean difference −6.08 mm Hg; 95% CI −12.57 to 0.41) and absolute overhydration (−0.80 litres; 95% CI −1.32 to −0.28). The committee questioned whether BCM – Body Composition Monitor-guided monitoring could be expected to have a similar effect in both types of dialysis. The committee heard from clinical experts that the effect of BCM – Body Composition Monitor-guided monitoring for people on haemodialysis will not necessarily be the same for people having peritoneal dialysis because the pattern of fluid accumulation which occurs between sessions may be more pronounced with haemodialysis, which is done less often. Also, peritoneal dialysis may preserve residual renal function for longer, so any effect on this outcome could be more pronounced. The committee therefore concluded that there are insufficient data to determine the clinical effectiveness of BCM – Body Composition Monitor-guided monitoring for people having peritoneal dialysis.
5.10 The committee discussed the clinical effectiveness of BCM – Body Composition Monitor-guided monitoring in people under 18 years (that is, babies, children and young people). It noted that none of the identified studies assessed the use of the device in this group. The committee heard from clinical experts that because of physiological differences, and differences in comorbidities, between adults and babies, young people and children, the available data in adults cannot be considered applicable. It heard from clinical experts that a higher proportion of children who have dialysis have peritoneal dialysis rather than haemodialysis. The committee noted that any benefits or negative effects associated with managing fluids in children could influence outcomes and future treatments when they are adults, and so it is plausible that the effects of the BCM – Body Composition Monitor device may be greater in this population. The committee concluded that more data are needed on the clinical effectiveness of BCM – Body Composition Monitor-guided monitoring for people under 18 years having both haemodialysis and peritoneal dialysis.
5.11 The committee considered the results of the cost-effectiveness analyses for BCM – Body Composition Monitor-guided fluid monitoring. It noted that several scenarios had been modelled to investigate the uncertainties in estimates of effect on mortality and hospitalisation events that had been identified in the clinical-effectiveness review. The committee heard that the model was based on data from UK and European renal registries, supplemented with data from the clinical-effectiveness review. It heard from clinical experts that the baseline population risk data and clinical-effectiveness data reflected outcomes for adults only and concluded that the results of the cost-effectiveness analyses could not be considered applicable to children.
5.12 The committee questioned the impact of excluding the effect of prolonged underhydration, and related outcomes, from the model. It heard from the external assessment group that they had not been able to identify appropriate data sources for the prevalence of prolonged underhydration or its effect on mortality and hospitalisation rates. Also, data were not available to include an effect of BCM – Body Composition Monitor-guided monitoring on the incidence of prolonged underhydration or on the maintenance of residual renal function in the model. Clinical experts noted that this could either over- or underestimate the benefits of using the BCM – Body Composition Monitor, depending on whether its use increased or decreased the occurrence of prolonged underhydration. The committee concluded that the effect of BCM – Body Composition Monitor-guided monitoring on the incidence of prolonged underhydration, and associated outcomes such as residual renal function, is likely to be an important factor in assessing the cost effectiveness of the device and that, because of an absence of data, this has not been captured in the analyses.
5.13 The committee discussed the use of quality-of-life data in the model. It noted that the base-case model did not include an effect of BCM – Body Composition Monitor monitoring on quality of life, beyond its assumed effect on reducing mortality and hospitalisation events. The committee heard from clinical and patient experts that if using the BCM – Body Composition Monitor improved fluid management there would be reductions in dialysis-related side effects and improved recovery after dialysis, which would be of substantial benefit to patients. The committee concluded that, because of an absence of data, the effect of BCM – Body Composition Monitor-guided fluid management on quality of life had not been captured in the analyses.
5.14 The committee discussed the mortality estimates included in the model. It noted that the pooled-effect estimate from the clinical-effectiveness review showed no significant effect on this outcome (see section 5.5), but that BCM – Body Composition Monitor-guided monitoring was assumed to increase survival in the base-case scenarios. The committee considered that, based on the available evidence, it is uncertain whether BCM – Body Composition Monitor-guided monitoring has any effect on mortality. It also questioned whether this uncertainty had been captured in probabilistic analyses. The committee determined that the most plausible scenario modelled is further scenario 17, which assumes no difference in mortality between BCM – Body Composition Monitor-guided monitoring and clinical assessment alone. This scenario produced an incremental cost-effectiveness ratio (ICER) of about £20,000 per quality-adjusted life year (QALY) gained. The committee noted that this scenario results in very small QALY gains and so its ICER is sensitive to small changes in the non-fatal cardiovascular-event rate. Decreasing the effect of BCM – Body Composition Monitor-guided monitoring on this parameter by a small amount (changing the applied hazard ratio from 0.91 to 0.93) increased the ICER to over £40,000 per QALY. The committee concluded that the results of further scenario analysis 17 were the most plausible, but that there was considerable uncertainty about the results of this analysis, and whether they show that BCM – Body Composition Monitor-guided monitoring is a cost-effective intervention based on a reduction in cardiovascular-event rates alone.
5.15 The committee discussed the effect of including dialysis costs in the model. It noted that 2 sets of ICERs had been calculated, one with and one without dialysis costs. It noted that when dialysis costs are included, BCM – Body Composition Monitor-guided monitoring is unlikely to be considered cost effective, even if the device is provided at no cost. When dialysis costs are excluded the ICERs generally drop below £20,000 per QALY gained. The committee noted that despite the high costs of dialysis, these results were largely driven by the assumption that BCM – Body Composition Monitor-guided monitoring increases survival and therefore the duration of dialysis treatment. For scenarios which include a survival benefit, the committee concluded that it would be appropriate to exclude costs related to the extended period of survival because dialysis has been generally available in the health service for a long time and it has therefore already been accepted that the benefits gained by providing dialysis outweigh the cost of delivering the intervention.
5.16 The committee discussed the level of uncertainty in both the clinical- and cost-effectiveness analyses. It noted that there was considerable uncertainty about the effectiveness of BCM – Body Composition Monitor-guided monitoring to reduce the incidence of adverse outcomes, such as cardiovascular events. Also, no data were available for potentially important outcomes, such as residual renal function. Because of this uncertainty in clinical effectiveness, there was insufficient evidence to determine the cost effectiveness of the BCM – Body Composition Monitor at present with any certainty. However, the committee noted that exploratory cost-effectiveness analyses done for the BCM – Body Composition Monitor device suggested that it could be cost effective, although this was sensitive to small changes in the estimated effect of BCM – Body Composition Monitor-guided monitoring. The committee concluded that there was too much uncertainty at present to recommend the BCM – Body Composition Monitor for routine use, but wished to encourage further research (see section 6).
5.17 The committee considered ongoing research on the clinical effectiveness of multiple frequency bioimpedance devices. It noted that the multi-centre, UK-based BISTRO RCT funded by the NIHR and designed to assess the effectiveness of the BCM – Body Composition Monitor device for monitoring people over 18 years on haemodialysis, will begin recruitment in 2017. The trial is scheduled to report in 2020. The committee heard from clinical experts that the primary outcome will be loss of renal function and noted that the effect of BCM – Body Composition Monitor-guided monitoring on this outcome had not been included in cost-effectiveness analyses because of a lack of data (see section 5.12). The committee concluded that the BISTRO study is highly relevant to this assessment and data from this ongoing study are therefore likely to be important when the guidance is considered for updating in the future.
5.18 The committee noted that BCM – Body Composition Monitor-guided monitoring is routinely used alongside standard clinical assessment in about 25% of UK dialysis services for people with chronic kidney disease having dialysis. It heard from clinical experts that these centres have developed experience of the benefits and limitations of using the BCM – Body Composition Monitor device to help manage dialysis-related symptoms associated with fluid imbalance. The committee encouraged centres currently using the BCM – Body Composition Monitor device to continue using it and participate in relevant data collection and research.
5.19 The committee considered the feasibility of further research on the clinical effectiveness of BCM – Body Composition Monitor-guided fluid management in babies, children and young people having dialysis. It heard from clinical experts that this age group makes up less than 1% of the total population of people on dialysis, and that people in this group typically stay on dialysis for a relatively short period of time, until they have a renal transplant. Therefore multi-centre studies are likely to be needed to recruit enough participants to show an effect on clinical outcomes. In the shorter term, the committee wished to encourage paediatric renal services to collect and publish data on cognitive function and quality of life in patients having BCM– Body Composition Monitor-guided fluid management.
5.20 The committee noted that there were no data to determine the clinical effectiveness of the InBody S10 or MultiScan 5000 devices for guiding fluid management in people with chronic kidney disease who are having dialysis. The committee wished to encourage the companies to collect and publish data on both the validity of their device's underlying fluid model to calculate fluid overload and its associated clinical outcomes. The committee further noted the importance of validating the accuracy of all the multiple frequency bioimpedance devices included in this assessment for people with amputations, people for whom recommended electrode configurations cannot be used and people who are unable to assume recommended positioning for measurements to be made. Also, validation data may be important for people with extremes of body composition, and across different ethnicities, because normal ranges of lean or adipose tissue body composition may differ between ethnicities. It wished to encourage the publication of data on the validity of multiple frequency bioimpedance devices to calculate fluid overload and target weight in these groups.