Evidence strengths and limitations

Evidence strengths and limitations

No randomised controlled trials were identified that compared colesevelam with placebo or other treatments (such as colestyramine or colestipol) in people with bile acid malabsorption.

Odunsi-Shiyanbade et al. (2010) was a small RCT in 24 women with diarrhoea-predominant irritable bowel syndrome. Only 4 women had evidence of bile acid malabsorption and results for these women were not reported separately. Therefore, the results of the study cannot be applied directly to the population considered in this evidence summary. In addition, the study included women only and the results may not be generalisable to men.

Although it was randomised, controlled and blinded, and allocation was concealed and follow-up complete, the study has other limitations. Firstly, it was small and therefore may not have had the statistical power to show a true difference between colesevelam and placebo, should one exist. In addition, follow-up was short term (only 12–14 days).

It is unclear whether differences in baseline characteristics between the groups were statistically significant and may have biased the results. For example, mean fasting serum 7-hydroxy-4-cholesten-3-one (7C4, an indirect measure of bile acid synthesis that is used to screen for bile acid malabsorption) was higher in the placebo group (38.2 nanograms/ml compared with 31.8 nanograms/ml in the colesevelam group). Similarly, of the 4 women with bile acid malabsorption (7C4 61 nanograms/ml or more), 3 were in the placebo group and 1 was in the colesevelam group. However, the study authors report that there were no clinically important differences in 7C4 levels in the 2 groups.

Wedlake et al. (2009) was a review of the electronic patient records of 45 people with a diagnosis of cancer and symptoms of bile acid malabsorption for 3 months or more. Most were women (n=37). Although data on gastrointestinal symptoms had been recorded prospectively, the study had a retrospective design, which poses a risk of inaccurate recording of findings. In addition, it was uncontrolled and unblinded and reported results from a single centre. All people had completed treatment for cancer or were undergoing treatment for ongoing or relapsed cancer and the results might not be generalisable to other populations. In addition, some people had more than one condition that may have caused their symptoms; some were prescribed other medicines in addition to colesevelam; and some may have benefited from changes in diet.

Puleston et al. (2005) was a small case series of 5 people, reported in a letter. This study also had a retrospective design and was uncontrolled and unblinded.

The authors of all studies note that their findings warrant further investigation in properly powered prospective double-blind controlled trials.