Mobile App-treatment of Mixed and Urgency Urinary Incontinence in Women

Urinary incontinence affects one fourth of adult women (1). It may reduce quality of life and costs for society are high. The most common type in women is stress urinary incontinence (SUI), i.e. leakage when coughing, sneezing or jumping. Urgency urinary incontinence (UUI) and mixed urinary incontinence (MUI), a combination of both stress and urgency UI, together adds up to nearly half of the cases of UI in women (1). Many women do not seek care, sometimes due to embarrassment (2). The recommended first line treatment for all three types of UI in women are pelvic floor muscle training (PFMT) and life style advices, leading to improvement or cure in two thirds of patients (3,4) . In addition, bladder training might be effective for UUI and MUI (3,4). Bladder training in combination with PFMT led to improvement or cure in one sixth of women with MUI (3). Previous research also suggest that psychological treatment could have a value for some women with UUI and MUI (5).

The investigators have previously demonstrated the efficacy of the mobile app Tät® for treatment of SUI (6). Apps have the potential to improve symptoms in many chronic conditions through self-management interventions (7).

The investigators have developed the mobile app Tät®II for women with UUI or MUI and the aim is to determine if this mobile app is effective for self-treatment.

Women are consecutively recruited via the website www.tät.nu (www.econtinence.se). The women answer an online screening questionnaire with automated response for initial screening of eligibility criteria. Informed consent and bladder diary are sent by ordinary post to the administrator of the study. After that, the women answer a web questionnaire including scoring instruments and finally a telephone interview is conducted by a urotherapist or a doctor. The purpose of this telephone interview is to confirm the clinical diagnosis of UUI or MUI, to ascertain that there are no alarm symptoms motivating examination in ordinary health care and to make sure that the woman is well informed about the study procedure.

After the telephone interview it is decided whether the woman is eligible for participation or not. If eligible, the interviewer send an e-mail to the study coordinator marked "Randomization". The order in which these e-mails arrive at the incoming mail box tat2.am@umu.se decide the order of randomization. An independent administrator has generated the allocation sequence and prepared 130 numbered opaque sealed envelopes (with assignment equally distributed between the two study groups). The study coordinator consecutively opens one envelope for each participant (in the order they arrived in the mailbox) and mark the number of the envelope on the coordinator list for the participant. The coordinator assigns an e-mail to the participant, with instructions for downloading the apps. If assigned to the treatment app group, a unique code is activated for each participant, which enables the participant to activate the complete app Tät®II including individual advices regarding self-care and recommended exercises based on the results from the questionnaire and the bladder diary. Two weeks after randomization, the activation status of the app is controlled and if it is not activated, the participants receive an e-mail asking whether they have experienced any technical problems with the app. In case of technical problems, they get instructions by e-mail or by telephone. After another week, a new review of the activation status is done and if the app still is not activated - participants are contacted via telephone.

Adverse events All participants are encouraged to report any adverse events that may occur during the study either by e-mail or by telephone. This information is included in the e-mail they get after allocation to treatment app or information app group. Questions about adverse events are also included in the follow-up questionnaire

14 weeks after randomization, the study coordinator will send both groups a web-based questionnaire with follow-up questions and scoring instruments and a bladder diary. The bladder diary is sent back by post. Non-responders will be reminded twice by e-mail (at 2 and 4 weeks) and once by telephone (at 6 weeks).

The participants in the information app group will receive an unique activating code to get access to the complete app with individual advices after this follow-up. The participants in the original information app group will be followed-up after another 14 weeks with the same follow-up questionnaire and a bladder diary and the same time frames for reminders. The results from this second follow-up in the original information app group will be compared with results from the first follow-up and serve as quality control for the original study. This design allows us to study long-term follow up results later.

Quality Assurance plan The study will be monitored according to Good Clinical Practice principles by study research nurse Agneta Lindberg at the local Clinical Research Centre of Region Jämtland Härjedalen to ascertain a proper procedure of conduction, recording and reporting data. The monitor will review study records, observe protocol procedures and the randomization process, and ensure that written informed consent has been correctly obtained. The first five participants-and after that one in ten randomly selected by the monitor- will be 100 % monitored as stated in the monitor plan. All study participants will be reviewed for informed consent procedure. According to the Medical Devices Directives (Meddevs 2.7/3) reporting and monitoring of adverse events and serious adverse events are not necessary when a CE-marked (Conformité Européenne) device is used in a study within its intended use covered by the CE-marking. The app Tät®II is used within its intended use covered by the CE-marking (Medical Product Agency, Sweden. Dnr:6.6.1-2016-97327, PID (Product identify number) 149104).

Data Dictionary, see primary and secondary outcomes

Plan for missing data The questionnaires will be web-based and every question will, if technically possible, be mandatory. However, should there for some reason be missing values, these will be replaced with the value corresponding to "no change", i.e. a missing value at follow-up will be replaced with the participant´s baseline value and a missing value at baseline will be replaced with the follow-up value. A missing answer in the PGI-I at follow-up will be assumed as "unchanged".

All data will be checked for out-of-range results, these will be treated as missing values.

Sample size calculation Based on results from the previous smartphone study and the findings of Albers-Heitner et al, improvements in the ICIQ UI SF of 2.5 points in the treatment app group and 0.9 points in the information app group are assumed. To detect this difference with 80% power, 2-side test and significance 0.05, a sample size of 49 is needed in each group. With an expected drop-out rate of 20%, approximately 60 participants are needed in each group. The investigators therefore aim to recruit 120 women aged 18 and older via the website www.tät.nu.

Statistical plan Intention-to-treat analysis will be performed on all outcome measures.

Baseline The two groups will be compared at baseline using Student´s t-test for continuous variables, Pearson Chi-Square test for categorical variables, and the Mann-Whitney U-test for ordinal variables. Baseline data will be compared for age, BMI, educational level, medication and for all primary and secondary outcomes that are measured at baseline.

Primary outcome The primary outcome is the difference between the groups in mean ICIQ UI SF score at follow-up and a linear mixed model analysis incorporating baseline data will be used.

Secondary outcomes

Comparison between groups:

For evaluating the difference between the groups in mean ICIQ LUTS qol score at follow-up, a linear mixed models analysis incorporating baseline data will be used.

For evaluating the difference between the groups regarding change of the median Incontinence Episode Frequency from baseline to follow-up, the Mann-Whitney U-test will be used.

To evaluate the difference between the groups in mean ICIQ-OAB score at follow-up, a linear mixed models analysis will be used incorporating baseline data.

To evaluate the difference between the groups in the mean score of the non-validated Incontinence Catastrophizing Scale (ICS) at follow-up, a linear mixed models analysis will be used incorporating baseline data.

For evaluating the difference between groups regarding change in usage of incontinence aids from baseline to follow-up, the Mann-Whitney U-test will be used.

The difference between the groups regarding PGI-I, a question on improvement only used at follow-up, will be analysed using the Mann-Whitney U-test.

Patient satisfaction. The proportion of participants that intend to seek more help after this first-line treatment will be analysed, this item will only be analysed in the treatment app group and no comparisons will be done.

Comparison within groups:

For comparison within the groups regarding the score on ICIQ LUTS qol, a paired t-test will be used.

For comparison within the groups regarding the IEF, a Wilcoxon signed-rank test will be used.

For comparison within the groups regarding the score on ICS, a paired t-test will be used For comparison within the groups regarding the score on ICIQ-OAB, a paired t-test will be used.

For comparison within the groups regarding the incontinence aid usage, a Wilcoxon signed-rank test will be used.