Prospective Registry for Patients Undergoing Surgery for Male Stress Urinary Incontinence

STATISTICS

1. Number of Participants: Investigators anticipate to recruit 1000 patients from at least 25-30 European Centers and prospectively collect data from 100 - 200 patients per year. Statistical analysis will be performed on the total number of participants. Based on the available literature, we anticipate an average cure rate of 50% for AUS and for male slings an average cure rate of 65% at the end of study. With an estimated sample size of 700 patients treated with Artificial Urethral Sphincter (AUS) and 300 patients with a male sling, and taking into account an attrition rate of 10-15%, we will be able to detect a 50% cure rate with 6% on either side of the 95% Confidence Interval for AUS (proportion 0,50 with 95% Confidence Intervals: 0,44-0,56) and a 65% cure rate for patients treated with male slings (proportion 0,65 with 95% Confidence Intervals: 0,57-0,74).
2. Statistical Analysis:

No adjustment procedures or imputations of missing data will take place.

2.1 Patient characteristics: Patient characteristics as age, weight, length, etc. will be summarized using descriptive statistics - the number of patients with non-missing data, mean, standard deviation, median, minimum and maximum will be presented for continuous outcomes, and the number and percentage of patients in each category will be presented for categorical outcomes. A subgroup analysis by Device subtype will be carried out.

2.2 Primary endpoint analyses: Cure rate will be the main endpoint of the study, and is defined as urinary continence with no need for use of pads or the use of 1 light security pad. The cure rate after 10 years of study follow up will be calculated together with its 95% Confidence Intervals, for the total patient group as well as for each device subtype.

2.3 Secondary endpoints analyses: Time being Incontinence-free will be a secondary endpoint of the study, and is defined as the interval from the date of regaining continence after surgery to the date of incontinence. Continence is defined as no pad use or one light security pad per 24 hours use. Patients who die will be censored at time of death. Overall time being incontinence-free will be presented using the Kaplan-Meier curve, for the total patient group as well as for each device subtype.

Time being revision-free will be another endpoint of the study, and is defined as the interval from the date of surgery to the date of revision. Patients who die will be censored at time of death. Overall time being revision-free will be presented using the Kaplan-Meier curve, for the total patient group as well as for each device subtype.

The results of questionnaires ICIQ Male LUTS Questionnaire SF and EQ-5D-5L will be analysed comparing baseline with 12 weeks post-surgery and the yearly follow up results for the whole group and for the device subgroups. Further, complications (and SADE's), pain and symptoms during and post-surgery and other post-operative data will be evaluated in the device subgroups.

2.4 Prognostic factors: Univariable and multivariable analysis will be carried out to identify clinical and surgical variables that correlate with (in)continence or revisions for each of the device subtypes.

STUDY CONDUCT CONSIDERATIONS

A research co-coordinator will be available in each center for obtaining Ethics Committees (ECs) approval and to deliver logistics of patient screening, follow-up visits, data collection and data entry into the electronic Case Report Form (eCRF).

1. Regulatory and Ethical Considerations: Prior to initiation of a study site, the research co-coordinator will obtain approval from the appropriate regulatory agency and ECs to conduct the study in accordance with applicable country-specific regulatory requirements. The study will be conducted in accordance with applicable subject privacy requirements.
2. Recruitment and Consent:

A patient information sheet and consent form will be available and translated in the local language. This form will state that data will be processed anonymously and handled according to local data protection laws. In case a patient is eligible, the physician will verbally inform the patient about this registry and its purpose. The patient will also receive a written patient information sheet in the local language explaining the registry. The patient will be given ample opportunity to ask any questions he might have. The patient will be given as much time as needed to consider his participation in this registry. If a patient agrees to participate, the informed consent form will be signed prior to registration of the patient data.

ADMINISTRATIVE ASPECTS AND PUBLICATION

1. Handling and Storage of Data and Documents: All items as described in the protocol will be entered into an eCRF. The physician will guarantee that all team members or other persons involved in the center will respect the confidentiality of any information concerning the registry patients. All parties involved in this registry will maintain strict confidentiality to assure that neither the person nor the family privacy of a patient participating in the registry is violated. Likewise, the appropriate measures shall be taken to avoid the access of non-authorized persons to the registry data. Data will be made anonymous and extracts of the anonymized data will be accessible for reporting and statistical analyses. The processing of the personal data on the patients taking part in this registry, and in particular regarding data concerning consent, shall comply with the local law on the privacy and with the European Directive on the Privacy of data (95/46/EC).
2. Site Audit: Site audits will be conducted by the European Association of Urology Foundation for Urological Research (EAU RF) or another designated third party in approximately 5-10% of the sites. To avoid fraud, spot check monitoring and source data verification will be conducted to identify if a patient really exists and if the data entered in the database is retrieved from real patient files and has been transferred correctly.
3. Project Database: For the purpose of the study, the data will be stored in a central database held by ESFFU under the umbrella of EAU RF. The investigator or a qualified employee will enter all relevant patient data into a web based electronic Data Capture system. Data checks, programmed in the data capture system, use predefined rules for range or consistency with other data fields in the registry. Data will also be checked for accuracy and correctness by data-managers of the EAU RF according to internal procedures. The site will be capable of modifying the data to assure accuracy with source documentation. At the end of the study, EAU RF will archive the study data in accordance with internal procedures. Specific instructions for use of the eCRF system will be included in the training material provided to the investigational site.
4. Amendments: Amendments are changes made to the registry protocol. Amendments will be notified or submitted for approval to the Ethical Committee (EC) as required according to local law.
5. Annual Progress Report: According to local requirements, the sponsor will submit a summary of the progress of the registry to the participating physicians and research coordinators for submission to the local ECs (if required) in each country once a year. Information will be provided on the date of inclusion of the first patient, numbers of patients included and numbers of patients that have completed the registry, issues, and amendments.
6. End of Registry Report: According to local requirements, the sponsor or physician will notify the Competent Authority (CA), the Central Ethical Committee (CEC) and local ECs of the end of the study. The registry will end after such decision is taken by ESFFU and EAU RF. In case the registry is ended, the sponsor or physician will notify the CA/CEC and local ECs (if required), including the reasons for the premature termination. Within one year after the end of the registry, the sponsor will submit a final registry report with the results of the registry, including any publications/abstracts of the registry, to the CA/CEC and local EC (if required).
7. Steering Committee:

A Steering Committee was assembled, consisting of urologist key opinion leaders in the field of reconstructive surgery and physicians/scientists with clinical and methodological expertise. The Steering Committee is responsible for the assignment of National Coordinators. Each participating country has one National Coordinator who has been selected by the Steering Committee. The Steering Committee will convene once or twice a year.