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Halphen M.,Norgine Ltd | Heresbach D.,Center Hospitalier Of Cannes | Gruss H.-J.,Witten/Herdecke University | Belsey J.,JB Medical Ltd
Gastrointestinal Endoscopy | Year: 2013

Background: Variations in bowel cleansing quality before colonoscopy can cause confounding of results within clinical trials and inappropriate treatment decisions in clinical practice. A new tool - the Harefield Cleaning Scale - has been developed, which addresses the limitations of existing scales. Objective: Validation exercise for the new cleansing scale. Design: Retrospective validation study. Setting: Various colonoscopy units in France. Patients: Patients who had a total of 337 colonoscopies recorded. Intervention: Video-recorded colonoscopy. Main Outcome Measurements: Comparisons of 2 scoring systems to assess direct correlation, interrater reliability, internal consistency, and test-retest reliability, based on assessment of video recordings from 337 colonoscopies. Results: Correlation analysis for expert scores by using the 2 scales yielded a Spearman correlation coefficient of 0.833. Similarly, the comparison of the segmental sum score revealed a Spearman correlation coefficient of -0.778. Cross-tabulation for successful colon cleansing was 92.88% versus unsuccessful colon cleansing in 7.12%. Reliability assessment indicated an acceptable internal consistency with a Cronbach alpha coefficient of 0.81. Test-retest reliability demonstrated an overall agreement of 0.639 (kappa statistic). Receiver operating characteristic analysis versus Aronchick Scale scores yielded an area under the curve of 0.945, with sensitivity of 99% and specificity of 83% at the optimum score cut-off point. Limitations: Test-retest reliability was assessed by using a different patient population to the other measures. There were insufficient patient numbers to assess performance by using adenoma detection rate. Conclusion: This validation analysis has demonstrated that the Harefield Cleansing Scale is a robust, reliable, and consistent tool that has the potential to improve the effective standardization of bowel preparation assessment in both clinical and research practice. © 2013 American Society for Gastrointestinal Endoscopy.

Gruss H.-J.,Witten/Herdecke University | Cockett A.,Norgine Ltd | Leicester R.J.,St. Georges Hospital
Journal of Medical Economics | Year: 2012

Objective: With the availability of several bowel cleansing agents, physicians and hospitals performing colonoscopies will often base their choice of cleansing agent purely on acquisition cost. Therefore, an easy to use budget impact model has been developed and established as a tool to compare total colon preparation costs between different established bowel cleansing agents. Methods: The model was programmed in Excel and designed as a questionnaire evaluating information on treatment costs for a range of established bowel cleansing products. The sum of costs is based on National Health Service reference costs for bowel cleansing products. Estimations are made for savings achievable when using a 2-litre polyethylene glycol with ascorbate components solution (PEGASC) in place of other bowel cleansing solutions. Test data were entered into the model to confirm validity and sensitivity. The model was then applied to a set of audit cost data from a major hospital colonoscopy unit in the UK. Results: Descriptive analysis of the test data showed that the main cost drivers in the colonoscopy process are the procedure costs and costs for bed days rather than drug acquisition costs, irrespective of the cleansing agent. Audit data from a colonoscopy unit in the UK confirmed the finding with a saving of £107,000 per year in favour of PEGASC when compared to sodium picosulphate with magnesium citrate solution (NaPicMgCit). For every patient group the model calculated overall cost savings. This was irrespective of the higher drug expenditure associated with the use of PEGASC for bowel preparation. Savings were mainly realized through reduced costs for repeat colonoscopy procedures and associated costs, such as inpatient length of stay. Conclusions: The budget impact model demonstrated that the primary cost driver was the procedure cost for colonoscopy. Savings can be realized through the use of PEGASC despite higher drug acquisition costs relative to the comparator products. From a global hospital funding perspective, the acquisition costs of bowel preparations should not be used as the primary reason to select the preferred treatment agent, but should be part of the consideration, with an emphasis on the clinical outcome. © 2012 Informa UK Ltd All rights reserved.

Gruss H.J.,ICON Clinical Research | Pediconi C.,Norgine Ltd | Jacobs A.,Dianthus Medical Ltd.
Colorectal Disease | Year: 2014

Aims: NRL001 is a highly specific α1-adrenoceptor agonist currently under evaluation for the treatment of faecal incontinence caused by a weak internal anal sphincter. The aim of this meta-analysis was to quantify the effect of NRL001 on cardiovascular parameters including heart rate, blood pressure and QT interval. Methods: Data from the four Phase I healthy volunteer studies SUM (NCT00857467), SURD (NCT01099670), SUSD (NCT00850590) and SAGE (NCT01099683) were pooled and analyses were performed on individual subject data. Mixed effects regression analysis was used to determine the effect of NRL001 on heart rate, blood pressure and QT intervals. A multivariate statistical model was used to determine the effect of covariates on heart rate. Results: Subjects given NRL001 experienced a dose related decrease in heart rate of up to 9.48 bpm compared with subjects in the placebo arms. No statistically significant evidence for a threshold effect was found. There was no clear evidence of dose effect of NRL001 on blood pressure. QT interval increased in all NRL001 subject as expected; QTCF also showed a statistically significant increase. However, QTCB was shortened with no significant treatment effect. Conclusions: NRL001 was found to have a dose-dependent effect on heart rate; however clinically-relevant bradycardia was not reported, indicating the decrease in heart rate was not of clinical significance. Furthermore, no clinically-significant drug effect on blood pressure or mean arterial pressure was observed. QT intervals were affected by changes in heart rate. However, trends were dependant on the correction factor used. No consistent QT effect was observed, but a thorough QTC study will be required to confirm the effects of rectally applied NRL001. © 2014 The Association of Coloproctology of Great Britain and Ireland.

Belsey J.D.,JB Medical Ltd | Geraint M.,Norgine Ltd | Dixon T.A.,JB Medical Ltd
International Journal of Clinical Practice | Year: 2010

It is unclear how polyethylene glycol (PEG) laxatives compare with other classes of laxative in terms of efficacy. To assess efficacy of PEG vs. placebo and active comparators in adults with non-organic constipation. Text Word searches were carried out on MEDLINE, EMBASE, CINAHL, Cochrane Central Register of Clinical Trials and Google Scholar databases covering the period January 1970 to October 2009. Search terms were (constipation) AND (randomised OR randomized) AND (PEG OR polyethylene OR macrogol OR movicol OR idrolax OR miralax OR transipeg OR forlax OR colyte OR golytely OR isocolan OR nulytely) NOT colonoscopy. Only published randomised controlled trials, with a parallel-group or cross-over design, comparing oral PEG with placebo or a comparator laxative in adults with a history of non-organic constipation, were included. The frequency of defaecation in each arm, on completion of the protocol-defined treatment duration was extracted. All pooled analyses were based on random effect models. Of the 20 qualifying studies, 10 were vs. placebo, seven were vs. lactulose, and four were vs. other agents. One study compared PEG, placebo and lactulose. PEG treatment resulted in a highly significant increase in defaecations/week over placebo (all studies: additional 1.98 stools/week; p = 0.0003, high-quality studies: additional 2.34 stools/week; p = 0.0001) and over lactulose (all studies: additional 1 stool/week; p = 0.0017, high-quality studies: additional 1.65 stools/week; p = 0.021). This meta analysis is the only quantitative statistical analysis to have been published in the field. PEG was found to be a more effective laxative than lactulose in adult patients with constipation. © 2010 Blackwell Publishing Ltd.

Bell D.,Bio Kinetic Europe Ltd | Pediconi C.,Norgine Ltd | Jacobs A.,Dianthus Medical Ltd.
Colorectal Disease | Year: 2014

Aims: The application of α-adrenoceptor agonists can improve faecal incontinence symptoms. The aim of this study was to investigate the pharmacokinetic and systemic effects of NRL001 administered as different strengths in 1 or 2 g suppositories. Methods: This randomised, double-blind, placebo controlled study included 48 healthy subjects. Group 1 consisted of two cohorts of 12 subjects administered either four single doses of 1 or 2 g rectal suppository with either 5, 7.5 or 10 mg NRL001, or matching placebo. Group 2 consisted of two cohorts of 12 subjects administered either four single doses of 1 or 2 g rectal suppository with either 10, 12.5 or 15 mg NRL001, or matching placebo. Doses were given in an escalating manner with placebo at a random position within the sequence. Results: Tmax was at ~4.5 h post-dose for all NRL001 doses. Median AUC0-tz, AUC0-∞ and Cmax increased with increasing dose for both suppository sizes. The estimate of ratios of geometric means comparing 2 g with 1 g suppository, and regression analysis for dose proportionality, was close to 1 for the variables AUC0-tz, AUC0-∞ and Cmax (P > 0.05). For both suppository sizes, 20-min mean pulse rate was significantly decreased compared with placebo with all doses (P < 0.05). Blood pressure decreased overall. There were 144 adverse events (AEs) and no serious AEs reported during the study. All AEs were mild in severity. Conclusions: The regression analysis concluded that the doses were dose proportional. © 2014 The Association of Coloproctology of Great Britain and Ireland.

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