Original Title: Efectividad y seguridad de la irrigación transanal en adultos con disfunción intestinal

Authors' objectives: To analyze the efficacy and safety of TAI in adult patients with BD.

Authors' results and conclusions: RESULTS: The systematic search allowed us to identify a SR published in 2021, that met the objective of our study, so it was decided to complete and update this SR, finding 2 new studies. The primary objective of the SR was to study the effect of TAI on bowel function in adult patients with: a) NBD, b) LARS, and c) Faecal incontinence and chronic constipation of any origin. It included 27 studies (3 RCTs, 1 non-randomised CE and 23 observational studies) with a total of 1435 subjects. The primary outcome was the effect of TAI on bowel function obtained especially from Patient-Reported Outcome Measures (PROMs). The main secondary outcomes were quality of life, dropout rate and AE. Of the two updated studies, the first aimed to investigate the efficacy and safety of TAI with Navina Smart® and the second to assess the satisfaction, safety, perception and adherence to Navina Smart® treatment in patients dissatisfied with previous TAI treatments. Both studies are prospective multicentre uncontrolled studies involving adult patients with NBD. The first study included 84 patients with data collection at baseline (visit 1) and at 3 months (visit 2), and the second study included 28 patients with a followup time of 4 weeks. Regarding the effectiveness of TAI, the SR included 11 studies of patients with NBD (1 RCT, 8 prospective cohort studies, 1 retrospective and 1 cross-sectional), with 308 patients and follow-up time between 3 and 112 weeks. To assess bowel function the studies used the NBD score, the Cleveland Clinic Constipation Score (CCCS), the Cleveland Clinic Incontinence Score (CCIS), the Mark's Faecal Incontinence Grading System score (FIGS) and Likert scales. Of the 11 studies, 6 found significant improvement in bowel function. The RCT evaluated TAI versus conservative treatment and found improvement in CCCS and FIGS scores (p<0.001), but not in NBD. One study found that the mean bowel care time was significantly decreased in patients with TAI (p=0.04). In relation to quality of life, the RCT found significant differences in favour of TAI using the American Society of Colon and Rectal Surgeons Faecal Incontinence Score (FIQLS) with the coping/behaviour and embarrassment subscales (p<0.05), but not for the lifestyle and depression/self-perception subscales. The drop-out rate from TAI treatment ranged from 0% to 66%. The quality of the studies was considered excellent (1 study), good (6 studies), fair (2 studies), and poor (2 studies). Regarding LARS, the SR evaluated 5 studies (1 RCT and 4 prospective cohort studies) which included 96 patients. Follow-up time ranged from 6 to 12 months in 3 studies, and 2 studies collected medians of 1.6 years and 29 months. The following scales were used to assess bowel function: William's incontinence score, CCIS, LARS score, Memorial Sloan Kettering Cancer Center Bowel Function Instrument (MSKCC BFI), FIGS, and Obstructed Defaecation Syndrome (ODS) score. Of the 5 studies, 3 found significant improvement in bowel function (p<0.05). The RCT found improvement in bowel function according to LARS score and FIGS, but not in ODS. In regards to quality of life, 1 study found significant improvement using SF-36; 1 study showed improvement in the mental component but not the physical component of the same scale and improvement in all domains of the FIQLS (p<0.001); and another study observed improvement in global health status scores using the EORTCQLQ-C30 questionnaire. The dropout rate from TAI treatment ranged from 0% to 23%. Study quality was good in 3 studies, fair in 1 study and poor in another study. For the group of patients with faecal incontinence and constipation, the SR included 10 studies with a total of 1012 cases (1 non-randomised clinical trial, 7 prospective cohorts, 1 cross-sectional and 1 retrospective). Followup time ranged from 1.5 to 12 months in 4 studies, with a median between 1.06 and 8.5 years in 2 studies and a median between 7.6 and 18 months in 4 studies. To assess bowel function the studies used, among others, the CCIS score, CCCS, Park's scale, ODS, and FIQLS. Of the 10 studies, 2 found significant improvement in bowel function (p<0.05); 1 study found no improvement in faecal incontinence among patients who continued TAI treatment versus those who discontinued, using the FIQLS score. In relation to quality of life, 3 studies found improvement in TAI-treated patients, 1 study according to the SF-36 and FIQLS scales (p=0.012), 1 study in one of the SF-36 components (p=0.01), and 1 study according to an 11-point Likert scale (p<0.001); 1 study found no improvement in quality of life in patients who successfully responded to TAI treatment versus those who did not respond successfully. The dropout rate ranged from 8% to 57%. The methodological quality of the studies was assessed as good in 7 studies, fair in 1 study and poor in 2 studies. Of the 2 updated studies, the first found that the NBD score ranged from 17.75±4.87 at visit 1 (baseline) to 9.94±5.26 at visit 2 (3 months); (p<0.0001). Mean bowel care time went from 73.5±61.9 minutes at visit 1 to 46.4±20.5 minutes at visit 2; (p=0.0007); satisfaction with bowel management on a 5-point scale (higher value higher satisfaction), ranged from 1.85±0.78 at visit 1 to 3.67±0.98, at visit 2; (p<0.0001). The dropout rate from TAI treatment was 6%. The second study found that 79% of patients were able to use the Navina Samrt® device independently and 7% needed assistance. Of the 11 patients dissatisfied with the TAI system they were using at the start of the study, 8 patients were satisfied with the Navina Smart® system at the end of the study. Of the total number of patients, 67% were satisfied with the Navina Smart® treatment. Fifty-four percent considered the system practical compared to 33% who did not. Regarding safety of TAI treatment, the SR found that 2 studies, out of 11 studies in patients with NBD, reported AEs in a proportion of between 29% and 36% of cases. The most frequent AEs were abdominal pain, sweating/swelling, malaise, headache and perianal/anorectal pain. One of these studies reported 3 serious events, but no major findings. In patients with LARS, 2 of the 5 studies reported the presence of AEs in a proportion of between 29% and 62% of patients. AEs included abdominal cramps, mild rectal bleeding, leakage after irrigation, nausea and insertion pain. In patients with faecal incontinence and constipation, 5 of the 10 studies reported AEs in a proportion between 22% and 59% of patients. AEs included abdominal cramps, leakage of irrigation fluid, abdominal distention, anorectal pain, chills, nausea, dizziness or sweating. Of the 2 updated studies, the first reported AEs in 11 of the 84 patients who started the study (13%). Of these, 4 were device-related and mild, and 7 AEs were possibly device-related and mild in all but 1 severe case. Ninety-seven device deficiencies were reported, the most frequent being related to the electronic control unit (78%) and the rectal catheter (22%). The second study found that patients reported no device-related AE's. The methodological quality assessment of the SR, according to the AMSTAR-2 instrument, resulted in a medium confidence level; and that of the two updated studies, according to the MINORS instrument for nonrandomised studies, scored 8 and 7 (16 being the ideal score for noncomparative studies). Regarding economic aspects of TAI, 3 cost-effectiveness studies of TAI were found, 2 of them using the Peristeen® Anal Irrigation system, and one without specifying the TAI system in patients with NBD. The results showed that TAI treatment could reduce costs compared to standard bowel care, with robust sensitivity studies. The estimates made had limitations and the studies were not independent. In relation to organisational, ethical, social, legal or implementation aspects of TAI, no studies analysing these aspects were found. However, the evaluated studies do note the importance of Informed Consent, and the need for training and support for patients undergoing TAI treatment. CONCLUSIONS: This report studies the efficacy and safety of TAI in the treatment of adult patients with bowel dysfunction and finds that TAI is used in a variety of clinical conditions, although most studies focus on ID of neurogenic origin. There are different TAI systems on the market, but the most widely used is the Peristeen® transanal irrigation system. Recent studies use new developments such as the Navina Smart® system that allows electronic regulation of irrigation, although information on its results is still limited. In relation to treatment effectiveness, most studies found that TAI improves BD, regardless of the cause. However, the evidence is limited, with few comparative studies, short follow-up time, and methodological quality that could be improved. Treatment drop-out is one of the main problems associated with TAI. The outcome study of TAI treatment is a complex process. The different clinical conditions treated, together with the variable and intimate nature of the symptoms, makes evidence difficult to obtain. Different tools are used to measure bowel function, most of which are selfreported, but not all of which are validated. In relation to the safety of treatment, studies find that side effects are frequent, regardless of the clinical condition treated, but most are mild. However, it is difficult to assess the relationship between TAI treatment and adverse events. The studies show no cases of intestinal perforation. The economic studies found analyse the cost-effectiveness of TAI in patients with NBD and estimate that the costs associated with the treatment would be lower than those of standard bowel care. However, the studies have methodological weaknesses and the results should be refined in future studies. The present report has limitations. Most of the studies included patients who did not drop out of treatment, so the results of TAI may not be extrapolable; furthermore, treated patients may be more severe, as TAI is often used as a second line of treatment. Results are closely related to the search strategy used, and there may be publication bias with more studies favouring treatment. Further research on TAI is essential. Long-term prospective studies with well-defined inclusion criteria and validated outcome measures, with analysis of results in subgroups of patients, would be of great interest. Well-designed, independent economic studies to help understand the costeffectiveness of the different TAI systems available would be very useful.

Authors' methods: A systematic review (SR) of the scientific literature was conducted. The identification of studies was done through a search of the following databases: Medline, EMBASE, Cochrane Database of Systematic Reviews, DARE (Database of Abstracts of Reviews of Effects), Health Technology Assessment (HTA) Database and NHS-EED (National Health System Economic Evaluation Database) Centre for Reviews and Dissemination (CRD) and national and international Health Technology Assessment Agency databases such as NICE, CADTH or INAHTA. The search strategy for study identification was adapted to each database using free and controlled terminology. We searched the Internet and clinical trials databases such as ClinicalTrials.gov and International Clinical Trials Registry Platform (ICTRP). A manual review of the bibliographic references of the documents found was also carried out. The search strategy did not include restrictions by study size or language. The bibliographic manager EndNote v.12 was used. Inclusion criteria were: randomised controlled clinical trials (RCTs), SRs and/or meta-analyses, cohort studies, case-control studies, case series, health technology assessment reports, or Clinical Practice Guidelines, published until 20 May 2021 without language restriction, involving men and women ≥18 years old, with BD of any cause and undergoing treatment with TAI. Narrative reviews, conference publications and letters to the editor; and duplicate or outdated studies were excluded. As outcome measures we collected: -Effectiveness measures in terms of: improvement of bowel function; improvement of bowel care (time spent on bowel care, need for other treatments...); -Quality of life measured with different scales; -Dropout rate from treatment; -Any other measures considered in the studies; -Safety measures in terms of AEs or complications associated with treatment; technical failures of the devices; - Economic, organisational, social, ethical, legal or implementation aspects of the technology. The identification, selection and review of studies were carried out by two reviewers in a comprehensive and independent manner. The search identified a recent SR (February 2021) of high quality with the same objective as our study, so it was decided to complete and update the SR found to provide new scientific evidence. To this end, a new literature search was conducted, replicating the search strategy used in the SR, including studies up to 24 May 2021. Data collection included information on study characteristics, patient and intervention characteristics, and outcome measures in relation to effectiveness and safety. The methodological quality of the SR was assessed using the AMSTAR-2 instrument,RoB-2 for randomized studies and MINORS (Methodological Index for Non-Randomized Studies) instrument for nonrandomised studies. Finally, the internal quality of the report was assessed using the Red Española de Evaluación de Tecnologías Sanitarias y Prestaciones del Sistema Nacional de Salud (RedETES) checklist and an external review by an independent clinical specialist.

Project Status: Completed

Year Published: 2022

URL for published report: https://redets.sanidad.gob.es/productos/buscarProductos.do?metodo=detalle&id=1099

Requestor: Spanish Ministry of Health

English language abstract: An English language summary is available

Publication Type: Not Assigned

Country: Spain

Organisation Name: Agencia de Evaluacion de Tecnologias Sanitarias

Contact Address: Instituto de Salud "Carlos III", Calle Sinesio Delgado 6, Pabellon 4, 28029 Madrid, Spain. Tel: +34 9 1 822 2005; Fax: +34 9 1 387 7841;

Contact Name: Luis M. Sánchez Gómez

Contact Email: luism.sanchez@isciii.es

Copyright: <p>Agencia de Evaluacion</p>