BACKGROUND

The principal diagnosis/indication for this assessment is chronic diarrhoea due to bile acid malabsorption (BAM). Diarrhoea can be defined as the abnormal passage of loose or liquid stools more than three times daily and/or a daily stool weight > 200 g per day and is considered to be chronic if it persists for more than 4 weeks. The cause of chronic diarrhoea in adults is often difficult to ascertain and patients may undergo several investigations without a definitive cause being identified. BAM is one of several causes of chronic diarrhoea and results from failure to absorb bile acids (which are required for the absorption of dietary fats and sterols in the intestine) in the distal ileum.

OBJECTIVE

For people with chronic diarrhoea with unknown cause and in people with Crohn's disease and chronic diarrhoea with unknown cause (i.e. before resection): (1) What are the effects of selenium-75-homocholic acid taurine (SeHCAT) compared with no SeHCAT in terms of chronic diarrhoea, other health outcomes and costs? (2) What are the effects of bile acid sequestrants (BASs) compared with no BASs in people with a positive or negative SeHCAT test? (3) Does a positive or negative SeHCAT test predict improvement in terms of chronic diarrhoea, other health outcomes and costs?

DATA SOURCES

A systematic review was conducted to summarise the evidence on the clinical effectiveness of SeHCAT for the assessment of BAM and the measurement of bile acid pool loss. Search strategies were based on target condition and intervention, as recommended in the Centre for Reviews and Dissemination (CRD) guidance for undertaking reviews in health care and the Cochrane Handbook for Diagnostic Test Accuracy Reviews. The following databases were searched up to April 2012: MEDLINE; MEDLINE In-Process & Other Non-Indexed Citations; EMBASE; the Cochrane Databases; Database of Abstracts of Reviews of Effects; Health Technology Assessment (HTA) Database; and Science Citation Index. Research registers and conference proceedings were also searched.

REVIEW METHODS

Systematic review methods followed the principles outlined in the CRD guidance for undertaking reviews in health care and the National Institute for Health and Care Excellence (NICE) Diagnostic Assessment Programme interim methods statement. In the health economic analysis, the cost-effectiveness of SeHCAT for the assessment of BAM, in patients with chronic diarrhoea, was estimated in two different populations. The first is the population of patients with chronic diarrhoea with unknown cause and symptoms suggestive of diarrhoea-predominant irritable bowel syndrome (IBS-D) and the second population concerns patients with Crohn's disease without ileal resection with chronic diarrhoea. For each population, three models were combined: (1) a short-term decision tree that models the diagnostic pathway and initial response to treatment (first 6 months); (2) a long-term Markov model that estimates the lifetime costs and effects for patients initially receiving BAS; and (3) a long-term Markov model that estimates the lifetime costs and effects for patients initially receiving regular treatment (IBS-D treatment in the first population and Crohn's treatment in the second population). Incremental cost-effectiveness ratios were estimated as additional cost per additional responder in the short term (first 6 months) and per additional quality-adjusted life-year (QALY) in the long term (lifetime).

RESULTS

We found three studies assessing the relationship between the SeHCAT test and response to treatment with cholestyramine. However, the studies had small numbers of patients with unknown cause chronic diarrhoea, and they used different cut-offs to define BAM. For the short term (first 6 months), when trial of treatment is not considered as a comparator, the optimal choice depends on the willingness to pay for an additional responder. For lower values (between £1500 and £4600) the choice will be no SeHCAT in all scenarios; for higher values either SeHCAT 10% or SeHCAT 15% becomes cost-effective. For the lifetime perspective, the various scenarios showed widely differing results: in the threshold range of £20,000-30,000 per QALY gained we found as optimal choice either no SeHCAT, SeHCAT 5% (only IBS-D) or SeHCAT 15%. When trial of treatment is considered a comparator, the analysis showed that for the short term, trial of treatment is the optimal choice across a range of scenarios. For the lifetime perspective with trial of treatment, again the various scenarios show widely differing results. Depending on the scenario, in the threshold range of £20,000-30,000 per QALY gained, we found as optimal choice either trial of treatment, no SeHCAT or SeHCAT 15%.

CONCLUSIONS

In conclusion, the various analyses show that for both populations considerable decision uncertainty exists and that no firm conclusions can be formulated about which strategy is optimal. Standardisation of the definition of a positive SeHCAT test should be the first step in assessing the usefulness of this test. As there is no reference standard for the diagnosis of BAM and SeHCAT testing provides a continuous measure of metabolic function, diagnostic test accuracy (DTA) studies are not the most appropriate study design. However, in studies where all patients are tested with SeHCAT and all patients are treated with BASs, response to treatment can provide a surrogate reference standard; further DTA studies of this type may provide information on the ability of SeHCAT to predict response to BASs. A potentially more informative option would be multivariate regression modelling of treatment response (dependent variable), with SeHCAT result and other candidate clinical predictors as covariates. Such a study design could also inform the definition of a positive SeHCAT result.

STUDY REGISTRATION

The study is registered as PROSPERO CRD42012001911.

FUNDING

The National Institute for Health Research Health Technology Assessment programme.