PROSPERO International prospective register of systematic reviews The effect of probiotics on functional constipation: a systematic review of randomised controlled trials EIRINI DIMIDI, STEPHANOS CHRISTODOULIDES, KONSTANTINOS FRAGKOS, MARK SCOTT, KEVIN WHELAN Citation EIRINI DIMIDI, STEPHANOS CHRISTODOULIDES, KONSTANTINOS FRAGKOS, MARK SCOTT, KEVIN WHELAN. The effect of probiotics on functional constipation: a systematic review of randomised controlled trials. PROSPERO 2013:CRD42013004799 Available from http://www.crd.york.ac.uk/prospero_rebranding/display_record.asp?id=crd42013004799 Review question(s) To assess the effect of probiotics on stool output, symptoms and gut transit time in adults with functional constipation via a systematic review of randomised controlled trials. Searches Information sources: The Cochrane Central Register of Controlled Trials (CENTRAL) MEDLINE from 1946 EMBASE from 1946 WEB OF SCIENCE from 1900 There are no language, publication or date restrictions. Supplementary approaches will be carried out to identify possibly eligible studies, these will include: hand searching of conference abstracts from the following conferences; o Digestive Disease Week (Gastroenterology) from 2000-2013. o British Society of Gastroenterology (Gut) from 2000-2013. o American Society for Parenteral and Enteral Nutrition (J Parent Enteral Nutr) from 2000-2013. o European Society for Clinical Nutrition and Metabolism (Clin Nutr; Clin Nutr Supp, e-spen) from 2002-2012. o British Dietetic Association (Journal of Human Nutrition and Dietetics) from 2002-2012. o British Association for Parenteral and Enteral Nutrition (Proc Nutr Soc, e-spen) from 2000-2011. o Association of Coloproctology of Great Britain and Ireland (Colorect Dis) from 2000-2013. o Association of American Colon and Rectal Surgeons (Dis Colon Rectum) from 2000-2013. scanning reference lists of eligible papers and relevant review papers; contacting authors of eligible papers and relevant review papers and consultation with experts in the field. Search Page: 1 / 6
We will use the following search terms to search all databases: Population: 1. constipation; 2. functional constipation; 3. primary constipation; 4. chronic constipation; 5. idiopathic constipation; 6. irritable bowel syndrome; 7. IBS-C; 8. adults; 9. elderly; Intervention: 10. probiotics; 11. lactobacillus; 12. bifidobacterium; 13. Lactobacillus acidophilus; 14. Lactobacillus casei; 15. Lactobacillus rhamnosus; 16. Bifidus bulgaricus; 17. Bifidobacterium lactis; 18. Bifidobacterium animalis; 19. bifidobacteria; 20. Saccharomyces boulardii; 21. Escherichia Coli Nissle; 22. microbial cell preparations; 23. Fermented milk; Study design 24. Randomised controlled trial; 25. Trial; Page: 2 / 6
26. Clinical trial; 27. (1-9) AND (10-23) AND (24-27). Types of study to be included Only randomised controlled trials will be included. Condition or domain being studied Functional constipation, primary constipation, idiopathic constipation, chronic constipation, constipation-predominant irritable bowel syndrome (IBS-C). Participants/ population Trials will be included if they recruited adult participants (18 years old and over), with functional constipation, primary constipation, chronic constipation or IBS-C. Studies that included participants with other gastrointestinal diseases, druginduced constipation or constipation secondary to other diseases/morbidities will be excluded. Only studies which were undertaken in a community or outpatient setting will be included. There are no other restrictions for age, gender or ethnicity. Intervention(s), exposure(s) Trials will be included if their intervention includes any strains/dose/treatment regime of probiotics alone. Probiotics may come in tablet, powder, capsule, softgel, fermented milk or fortified food forms (as long as the control group is such that the effect of the probiotic alone can be isolated). Trials that used synbiotics as an intervention will be excluded, as will trials of probiotics in conjunction with any other intervention (e.g. dietary modification, laxative medication). Comparator(s)/ control Trials will be included only if they use placebo as a control. Trials that use fermented milks or fortified food forms as an intervention, and use a comparator such as food or drink which act as a control group will also be eligible. Studies which contain multiple study arms will be included only as long as the probiotic and placebo arm can be isolated. Outcome(s) Primary outcomes Stool frequency (using a bowel diary or stool collection) Stool consistency (using Bristol scale or other stool chart or objective measure) Stool weight (using weighing scales for a total stool collection) Gastrointestinal symptoms (e.g. bloating, straining, sense of incomplete evacuation etc) (using bowel diary, visual analogues scales, Likert scale) Whole gut transit time Colonic transit time Secondary outcomes Adverse effects Compliance Data extraction, (selection and coding) Selections of studies: two reviewers (ED, SC) will independently screen the citations, titles and abstracts of all publications found by the search strategies. Eligibility assessment will be performed in a blinded standardised manner. To avoid location bias, all articles found by the search will be sought through inter-library loan and other means. For trials that appeared to be eligible after initial screening, full articles will be read to examine their eligibility based on the pre-defined inclusion criteria. Reasons for exclusion of screened trials will be documented. Page: 3 / 6
Data extraction and management: A standard extraction form will be developed to record data for participant characteristics, study design, type of intervention, comparator group and type of outcome measures, for each included study. Data will be also collected related to the trials methodological quality such as assessment of allocation concealment, blinding, intention to treat analysis and selective reporting. Information on conflict of interests of the authors and source of funding will be also extracted. Whether results are duplicated in other articles from the same research group will be assessed. In such cases, the article with the most complete dataset will be included in the systematic review. Data extraction will be undertaken independently by two reviewers. A third member of the team (KW) will resolve any disagreements. Missing data: Authors of a study in which there is missing information or reported data inconsistencies will be contacted, as necessary. Where data cannot be obtained or used, we will specify this. Risk of bias (quality) assessment Two reviewers (ED, SC) will independently assess the risk of bias for each individual study using the Cochrane risk of bias tool as recommended in the PRISMA statement. Authors will be contacted for additional information regarding their methods or results. The quality of eligible trials will be assessed based on a table of risk of bias as suggested by the Cochrane Handbook. This will include study design, randomisation schedule, allocation concealment, participants and/or observer blinding, data collectors, complete outcome data and selective outcome reporting. Information about intention to treat analysis and issues of conflict of interests will also be collected. Judgements about risk of bias related to each domain will be categorised as low, high or unclear, according to criteria described in the Cochrane Handbook. Strategy for data synthesis Recommendation of the Cochrane Handbook for devising the strategy for data synthesis and analysis will be followed. If there is sufficient homogeneity between the trials, data will be pooled to create a meta-analysis. I-squared will be used to determine heterogeneity. A quantitative synthesis will be used if the included studies are sufficiently homogenous. Analysis of subgroups or subsets If a meta-analysis is feasible, a subgroup analysis will be carried out with the different types of constipation (functional constipation versus IBS-C), as well as with the different age groups (adults versus elderly). If feasible, a subgroup analysis will be undertaken with the different types of probiotic genus and species. Dissemination plans A paper will be submitted to a leading nutrition or gastroenterology journal and an abstract will be submitted to relevant conferences. Contact details for further information EIRINI DIMIDI Diabetes and Nutritional Sciences 4.103 Franklin Wilkins Building 150 Stamford Street London, SE1 9NH United Kingdom eirini.dimidi@kcl.ac.uk Page: 4 / 6
Organisational affiliation of the review King's College London http://www.kcl.ac.uk/index.aspx Review team Miss EIRINI DIMIDI, King's College London Mr STEPHANOS CHRISTODOULIDES, Queen Mary University of London Dr KONSTANTINOS FRAGKOS, University College London Dr MARK SCOTT, Queen Mary University of London Professor KEVIN WHELAN, King's College London Details of any existing review of the same topic by the same authors None Anticipated or actual start date 01 August 2013 Anticipated completion date 01 July 2014 Funding sources/sponsors None Conflicts of interest None known Language English Country England Subject index terms status Subject indexing assigned by CRD Subject index terms Aged; Fatigue; Humans; Questionnaires; Self Report Stage of review Completed but not published Date of registration in PROSPERO 09 September 2013 Date of publication of this revision 27 June 2014 DOI 10.15124/CRD42013004799 Stage of review at time of this submission Started Completed Preliminary searches Yes Yes Piloting of the study selection process Yes Yes Page: 5 / 6
Powered by TCPDF (www.tcpdf.org) Formal screening of search results against eligibility criteria Yes Yes Data extraction Yes Yes Risk of bias (quality) assessment Yes Yes Data analysis Yes Yes PROSPERO International prospective register of systematic reviews The information in this record has been provided by the named contact for this review. CRD has accepted this information in good faith and registered the review in PROSPERO. CRD bears no responsibility or liability for the content of this registration record, any associated files or external websites. Page: 6 / 6