SeHCAT (tauroselcholic [75 selenium] acid) for diagnosing bile acid diarrhoea

Evidence on the effects of SeHCAT testing in Crohn's disease is very limited

4.3 The external assessment group's (EAG) systematic review on the clinical effectiveness of SeHCAT testing (see section 3) found only 1 study in people with Crohn's disease. The committee concluded that SeHCAT testing in this population could be useful but there is not enough data available to understand its benefits and harms. It recommended that further research is done to show the clinical effectiveness of SeHCAT testing in people with Crohn's disease (see sections 5.1 to 5.4).

Evidence on the effects of SeHCAT testing in people with primary bile acid diarrhoea is limited in quality

4.4 There were 9 new studies published since NICE's original guidance in 2012. So, 24 studies in total were available for the primary bile acid diarrhoea population. Most of these provided data on response to treatment after a positive test result. The committee noted that the populations in these studies did not reflect the people who would be seen in NHS clinical practice. This is because people with chronic diarrhoea in the NHS are likely to be offered tests to identify other conditions with similar symptoms first, before SeHCAT testing. The populations in the studies were not likely to have had faecal immunochemical tests and faecal calprotectin tests before SeHCAT because the studies pre-date their introduction. Also, the committee noted that the studies were often small and had methodological limitations. Most only described limited short-term outcomes. It recommended that further research is done to show the clinical effectiveness of SeHCAT testing in people with primary bile acid diarrhoea (see sections 5.1 to 5.4).

It is uncertain how SeHCAT test results affect decisions about treatment

4.5 The committee noted that although most studies described response to treatment after a positive SeHCAT test result, not everyone with a positive test result was offered bile acid sequestrants. Between 70% and 100% of people who had a positive SeHCAT test at a 15% threshold had bile acid sequestrants. The studies provided no information on how treatment decisions were made and it was unclear whether some people with negative test results would also get treatment. The committee concluded that research was needed to better understand how the test results affect treatment decisions (see section 5.1).

Outcomes for people with negative test results are not clear

4.6 The evidence described outcomes only for people who had a positive SeHCAT test result. The committee recognised that the potential benefits and harms of testing for people who had a negative test result are not clear. The clinical experts explained that in people who do not have bile acid diarrhoea, the synthetic bile acid in the SeHCAT capsule remains in the body for a long time. Although it contains a low level of radiation, the half-life of 75 selenium is almost 4 months. The committee noted that people with a negative test result retain some radiation in their body and it was unclear how these people might benefit from having the test. The committee concluded that although the radiation levels in SeHCAT are low and the test is safe, evidence from people with a negative test result is needed. This is to fully understand the benefits and harms of the SeHCAT test (see section 5.2).

The tolerability and effectiveness of different treatment options for bile acid diarrhoea are not clear

4.7 The committee noted that based on the evidence, it was not possible to estimate the effectiveness of the different bile acid sequestrants for treating bile acid diarrhoea. No evidence was found on the long-term effects of the bile acid sequestrants. It was unclear whether they have a sustained effect on bile acid diarrhoea and if they have any negative effects such as reducing vitamin absorption. The patient experts highlighted how important it is to better understand the tolerability of different bile acid sequestrants. The committee noted that many studies reported high rates of treatment discontinuation, but it was not clear whether the rates were the same for colestyramine and colesevelam. None of the studies used colestipol. The committee concluded that further research is needed to assess tolerability and effectiveness of the treatment options for bile acid diarrhoea (see section 5.3).

How severity of bile acid diarrhoea affects health-related quality of life is not clear

4.8 The committee noted that there was very limited evidence on the health-related quality of life of people with bile acid diarrhoea and whether treatment would improve this. The patient experts explained that the severity of symptoms and how much bile acid sequestrants improve symptoms may vary. The more severe the symptoms, the more effect treatment is likely to have. However, they explained that treatment is unlikely to completely resolve symptoms. This is because many people have flare-ups despite long-term treatment, especially when they have bile acid diarrhoea and irritable bowel syndrome. The committee noted that severe symptoms are more likely to be associated with reduced quality of life than less severe symptoms, but how much more likely is unknown. Further research on how severity of bile acid diarrhoea affects health-related quality of life and how this may change over time with and without treatment is needed (see section 5.4).

How SeHCAT testing affects clinical outcomes is uncertain

4.9 The committee considered the assumptions used in the economic model. It noted that, because of the lack of clinical outcome data, most of the model inputs were estimated based on expert opinion from a small group of clinicians. The clinical experts explained that they were not confident that their estimates captured the variability of bile acid diarrhoea seen in practice. The committee was not certain that the analyses presented had fully quantified the uncertainty caused by the lack of clinical outcome data. It concluded that the modelling should be considered exploratory.

Modelling the use of SeHCAT at a 15% threshold for a positive test result is appropriate

4.10 The EAG assumed that a threshold of 15% retention of SeHCAT would be used to define a positive test result in its model. The committee discussed whether this threshold was appropriate. The evidence was too limited to estimate how bile acid sequestrants might benefit people who have a positive test result at different SeHCAT thresholds. But it noted that in most studies a 15% threshold was used to define a positive SeHCAT test result. The clinical experts explained that the threshold used in practice varies. Treatment may also work for people with a positive test at higher thresholds, but 15% was a widely used and accepted threshold. The clinical experts noted that the 15% threshold was also supported by 2 recent surveys of SeHCAT use. The committee concluded that although the evidence did not allow the optimal threshold to be explored, it was reasonable to assume a 15% threshold in the model.

The resource impact of preventing colonoscopies when SeHCAT is used is captured in the analyses

4.11 Since NICE published the original guidance in 2012, the place of SeHCAT in the care pathway has changed. The EAG included the possibility of having a colonoscopy after SeHCAT testing in the model for people with suspected or diagnosed IBS-D or functional diarrhoea. The committee considered whether this reflected current practice and whether using SeHCAT could help reduce the number of colonoscopies done. The clinical experts explained that most colonoscopies are avoided because blood and stool tests are used to exclude inflammation before a SeHCAT test (see section 4.4). They noted that clinical practice varies but variation in the timing of colonoscopies (before or after SeHCAT testing) was adequately reflected in the modelling. The committee noted that the cost of colonoscopy was included in the model. It concluded that the resource impact of preventing colonoscopies was adequately captured. The committee questioned whether the model should also have included disutility associated with colonoscopy. The EAG explained that the disutility was not included because of a lack of data. But it noted that the model assumes colonoscopy occurs only in the 6 months immediately after a SeHCAT test. So, the committee concluded that it was unlikely that including a disutility for colonoscopy would change the overall conclusions of the cost-effectiveness analyses.

The model is unlikely to capture the full costs of providing SeHCAT testing

4.12 The committee discussed whether all the relevant costs involved in providing SeHCAT testing had been included in the model. The clinical experts explained that because the level of radioactivity in SeHCAT is low, other investigations using radioactivity could interfere with the test results. So, nuclear medicine departments cannot do other investigations when doing SeHCAT testing. The committee concluded that the cost of providing SeHCAT testing was unlikely to be fully captured in the model.

The model does not reflect the variable severity of bile acid diarrhoea

4.13 The long-term Markov model included a health state for people who have diarrhoea (because the treatment did not work) and a health state for people who do not have diarrhoea (because the treatment worked). The committee recalled its discussion on the severity of bile acid diarrhoea and how this could affect quality of life (see section 4.8). It concluded that the model did not capture the effects of variable diarrhoea severity and treatment response.

The relative value of SeHCAT testing may be overestimated in the model

4.14 The committee discussed whether it was appropriate to assume that response to bile acid sequestrants in the trial of treatment strategy was lower than in the SeHCAT strategy. This assumption was based on expert opinion. It recalled that the clinical experts highlighted that they were not confident of their answers to the questionnaire used to obtain values for the model. Assuming a lower probability of treatment response in the trial of treatment strategy would bias the model results towards SeHCAT and make it appear more cost effective. The committee concluded that using expert opinion without accounting for the discrepancies in treatment response for each of the strategies affected the internal validity of the model. As a result, this affected the comparison between the modelled strategies.

SeHCAT cannot be recommended for routine use in the NHS

4.15 The committee considered that there is an unmet clinical need for a test to diagnose bile acid diarrhoea. It recognised the value of having a diagnosis and access to treatment, but acknowledged that the evidence to support both the use of test and the treatment is highly uncertain. So, the full benefits and potential harms of widespread use of SeHCAT testing cannot be reliably quantified. There is no robust data to show the clinical utility of SeHCAT testing, that is:

Without this, SeHCAT's cost effectiveness cannot be adequately assessed. The committee concluded that it was unable to recommend the widespread use of SeHCAT testing. It encouraged further data collection to address the limitations in the evidence.