Multi-criteria decision analysis (MCDA) could potentially solve current methodological difficulties in the appraisal of orphan drugs. Areas covered: We provide an overview of the existing evidence regarding the use of MCDA in the appraisal of orphan drugs worldwide. Three databases (Pubmed, Embase, Web of Science) were searched for English, French and German literature published between January 2000 and April 2017. Full-text articles were supplemented with conference abstracts. A total of seven articles and six abstracts were identified. Expert commentary: The literature suggests that MCDA is increasingly being used in the context of appraising orphan drugs. It has shown itself to be a flexible approach with the potential to assist in decision-making regarding reimbursement for orphan drugs. However, further research regarding its application must be conducted.

Evidence is produced to show that the sennosides are probably breakdown products from primary glycosidal compounds occurring in the crude drug. Carefully prepared extracts have been shown to contain these primary compounds and one such compound has been isolated in a pure form. Biological and chemical assays show it is about 50 per cent more active than the sennosides and the relation of this fact to the explanation of the total activity of senna is discussed.

Sm,-The letter by Vickers in the August issue of this Journal (1961) has stimulated us to report the isolation of five anthracene glycosides from senna since our report of the separation of an active primary glycoside (Fairbairn, Friedmann and Ryan, 1958).This has been isolated from Alexandrian senna pod and appears to be similar to that reported by Vickers. We have shown it to be a rhein-monoglucoside by chemical analysis. Ultra-violet absorption measurements indicate that the compound is identical with synthetic rhein-8-glucoside, prepared from authentic rhein anthrone-8-glucoside by aerial oxidation in sodium borate solution at pH 9.2, and differs from a sample of synthetic rhein-1-glucoside, kindly supplied by Dr. A. C. Bellaart. Our experience is that the glucoside isolated by us is not readily decomposed by sodium bicarbonate solution with the formation of rhein, which does not accord with the inference that can be drawn from Vickers' letter.Rhein-8-diglucoside. A second glycoside isolated has been shown to be rhein-8-diglucoside. This glycoside, is much more soluble in water than the 1or 8-monoglucosides. It can be converted into the 8-monoglucoside by treatment with 0 . 1~ hydrochloric acid at room temperature.Rhein anthrone-8-glucoside, which is virtually half a sennoside molecule, was also found by us to be present in senna pod. This has been identified by hydrolysis to rhein anthrone, which was characterised spectroscopically, and by the formation of a green compound (Amax 640 mp) with p-nitrosodimethylaniline in pyridine (Tsukida and Suzuki, 1954). The conversion of rhein anthrone-8-

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