LETTERS TO THE EDITOR Re: Balaban et al.—Low Volume Bowel Preparation for Colonoscopy: Randomized Endoscopist-Blinded Trial of Liquid Sodium Phosphate Versus Tablet Sodium Phosphate

TO THE EDITOR: In their recent article, Balaban et al. (1) conclude that liquid sodium phosphate (Fleet Phosph-Soda, C.B. Fleet, Lynchburg, VA) is better tolerated and more effective at colon cleansing than sodium phosphate tablets (Visicol, InKine Pharmaceutical, Blue Bell, PA). We at InKine believe that this study, which was performed at a single center and supported by C.B. Fleet, might have had several serious methodologic flaws and that the report has a critical factual omission. First, the article indicates that 23.2% of the patients screened for the study declined to participate because of “a request not to take the tablets. ” This number is grossly inconsistent with the roughly 3% of patients who have declined a tablet colon preparation in our studies (unpublished data). The fact that so many subjects rejected a tablet preparation out of hand in the Balaban study strongly suggests that this therapeutic option was presented to study patients in a negatively biased manner, which would tend to distort and invalidate the subsequent testing of patient attitudes about the preparation. Similar bias against the tablet is suggested by the virtually identical mean scores of the Likert scale for taste (3.0 0.75 for the liquid vs 3.0 0.62 for the tablets). This scale ranged from 1 to 5, for “very poor” to “very good,” respectively. In our studies, 71% of patients found that Visicol (a hard, tightly compressed tablet) was tasteless (unpublished data). The very salty taste of the Fleet product is difficult to mask with any beverage. It is unexpected that study patients would rate a virtually tasteless tablet (taken with any clear liquid) to be equivalent in taste to a sodium phosphate solution. The data for taste suggest that most patients in both study groups rated the taste of the preparation as “3”; perhaps the wording of the scale encouraged this result–few would rate any preparation as tasting “good” or “very good. ” The authors state that seizures have been reported with sodium phosphate tablets but not with the liquid, citing a published report by U.S. Food and Drug Administration (FDA) authors and an online FDA “Science Backgrounder. ” However, another FDA “Science Backgrounder” (dated July 27, 2002) that is not cited by the authors indicates that liquid sodium phosphate has been associated with seizures in published reports (2). PEG colon preparations have likewise been associated with seizures and fatalities (3). Finally, the article indicates that this study was performed with the original formulation of Visicol tablets, which contained the common, insoluble tablet binder microcrystalline cellulose (MCC). MCC might be visible during colonoscopy, requiring suctioning. Unlike stool, MCC is generally easy to suction. It appears that MCC contributed to the grading of “stool” in the colons of patients taking the tablets, because there was no other way to rate MCC in the instrument used in this study. The article correctly states that the currently marketed formulation of Visicol contains less MCC than the original one; in fact, it contains less than one half the amount of MCC in the formulation used in the Balaban study. Also, data published by Rex et al. indicate that a reduced tablet regimen (28 or 32 old formulation tablets, compared with the 40-tablet regimen used by Balaban) produces very good colon cleansing and that fewer tablets are associated with less visible MCC (4). Notably, the old formulation of Visicol at a dose of 40 tablets was equivalent to the leading PEG preparation in colon cleansing and was much better tolerated in two identical, randomized, investigator-blinded, multicenter studies involving 845 patients undergoing colonoscopy (5). We believe that the current formulation of Visicol, with less MCC, results in even better colon cleansing than the old formulation.