Quality of Life of Crohn's Disease Patients With Complex Perianal Fistulas: an Observational, Cross-sectional Study
Conditions: Crohn Disease, Rectal Fistula
Sponsor: Takeda

CLINICAL STUDY PROTOCOL 
NCT Number: 
Study Title: 
Study Number: 
NCT04876690 
Quality of Life of Crohn's Disease Patients With Complex Perianal 
Fistulas: an Observational, Cross-sectional Study 
IBD-5007
Protocol Version and Date: 
Version 1.0: 25-February-2021 
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Non-Interventional Study Protocol 
 
Title: 
Quality of life of Crohn’s disease patients with complex perianal fistulas: an 
observational, cross-sectional study (CONFLICT) 
 
 
Short title: 
Quality of life in patients with complex perianal fistulas (CONFLICT study) 
 
 
Study ID: 
IBD-5007 
 
 
Sponsor: 
Takeda Farmacêuticos Portugal 
Quinta da Fonte, Rua dos Malhões nº5, 
Edifício Q56 D. Pedro I, Piso 3 
Paço de Arcos 
2770-071, Lisboa 
Portugal 
Phone: +351 211 201 457 
 
 
Study phase: Medical Affairs, Post-Approval Company Sponsored (Observational) 
 
 
Date of version 1 of protocol: 25 Feb 2021 
 
 
 
 
 
 
 
 
 
 
 
 
CONFIDENTIAL PROPERTY OF TAKEDA 
This document is a confidential communication of Takeda. Acceptance of this document constitutes the 
agreement by the recipient that no information contained herein will be published or disclosed without written 
authorization from Takeda except to the extent necessary to obtain informed consent from those persons to 
whom the drug may be administered. Furthermore, the information is only meant for review and compliance by 
the recipient, his or her staff, and applicable institutional review committee and regulatory agencies to enable 
conduct of the study. 
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1 
Administrative information 
1.1 
Contacts 
A separate contact information list will be provided to each site. 
 
 
Issue 
Contact 
Serious adverse 
event and pregnancy 
reporting 
 
 
 
Responsible 
Medical Officer 
(carries overall 
responsibility for 
the conduct of the 
study) 
AE.PRT@takeda.com 
Paseo de la Castellana 95, Edificio Torre 
Europa – floor 22, 28046 Madrid (Spain) 
Tel: +34 917 14 99 00 
 
 
 
Takeda Farmacêuticos Portugal 
Quinta da Forte, Rua dos Malhões n.5, 
Edíficio Q56D, Pedro I, floor 3, Paço de 
Arcos, 2770-071, Lisbon (Portugal) 
Tel: 
 
 
 
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INVESTIGATOR SIGNATURE PAGE 
I confirm that I have read and that I understand this protocol and any other product information 
provided by the sponsor. I agree to conduct this study in accordance with the requirements of 
this protocol and also to protect the rights, safety, privacy, and well-being of study subjects in 
accordance with the following: 
 
- 
The ethical principles that have their origin in the Declaration of Helsinki. 
- 
International Conference on Harmonisation, E6 Good Clinical Practice: Consolidated 
Guideline. 
- 
All applicable laws and regulations, including, without limitation, data privacy laws 
and regulations. 
- 
Regulatory requirements for reporting serious adverse events as defined in this 
protocol. 
 
 
 
 
 
 
Signature of Investigator 
Date 
 
 
Investigator Name (print or type) 
 
 
Investigator’s Title 
 
 
Location of Facility (City, State/Provence) 
 
 
Location of Facility (Country) 
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STUDY SUMMARY 
 
Name of Sponsor(s): 
Takeda Farmacêuticos Portugal 
Compound/Product: 
Not applicable 
Title of Protocol: Quality of life of Crohn’s disease patients with complex perianal fistulas: an 
observational, cross-sectional study (CONFLICT) 
Study Number: IBD-5007 
Phase Not applicable 
Study Design: 
This is a national, observational, cross-sectional study primarily aimed at assessing the general Quality 
of Life (QoL) among Crohn’s disease (CD) patients with complex perianal fistulas (CPFs) in the 
Portuguese routine clinical practice. In addition to the cross-sectional design, the study will have a 
retrospective component to collect data on healthcare resource utilization and on the pharmacological 
and surgical treatments used for the management of CPFs in the three years prior to the inclusion visit. 
The study will be conducted in five Portuguese public hospitals experienced in the management of 
patients with CD. Gastroenterologists working at the participating hospitals will participate in the study 
as investigators. Eligible patients (i.e., meeting all inclusion criteria and no exclusion criteria) will be 
consecutively enrolled during routine medical appointments at the participating hospitals. 
Primary Objective: 
1) To assess the general QoL among CD patients with CPFs attending secondary care services in 
Portugal. 
Secondary Objectives: 
1) To assess the IBD-specific QoL among CD patients with CPFs. 
2) To assess the sexual function among CD patients with CPFs. 
3) To assess fecal incontinence among CD patients with CPFs. 
4) To assess the work productivity and activity impairment among CD patients with CPFs. 
5) To assess the healthcare resource utilization in CD patients with CPFs within the three years 
prior to the inclusion visit. 
6) To describe the sociodemographic, anthropometric, and clinical characteristics of CD patients 
with CPFs. 
7) To describe the pharmacological and surgical treatments used for the management of CPFs 
within the three years prior to the inclusion visit. 
8) To explore the association between general QoL and the sociodemographic, anthropometric, and 
clinical characteristics of CD patients with CPFs. 
Exploratory Objectives: 
1) To explore the association between IBD-specific QoL/sexual function and the 
sociodemographic, anthropometric, and clinical characteristics of CD patients with CPFs. 
Subject Population: 
Male and female CD patients aged 18 or older with CPF(s). 
Sample Size: 
80 eligible patients will be included in this study. 
Study Sites: 
Five Portuguese hospitals experienced in the 
management of CD patients. 
Duration of Study: 
Overall Study Duration (including ethics 
committees’ submissions): 11 months 
Enrolment period: 9 months 
Treatment/Follow-up: N/A 
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Criteria for Inclusion: 
1. Male or female patients aged 18 years or older at the inclusion visit. 
2. Patients diagnosed with CD. 
3. Presence of CPF(s), defined as ≥1 of the following criteria: 
o high intersphincteric, high transsphincteric, extrasphincteric, or suprasphincteric location; 
o ≥2 external openings; 
o associated collections. 
4. Patients attending routine gastroenterology appointments at the participating hospitals. 
5. Patients capable of understanding and complying with protocol requirements, in the investigators’ 
opinion. 
6. Patients or, when applicable, the patients’ legally acceptable representative, who signed and dated 
a written informed consent form and any required privacy authorization prior to the initiation of any 
study procedures. 
Criteria for Exclusion: 
1. Patients diagnosed with ulcerative colitis or indeterminate IBD. 
2. Patients with non-complex fistulas or with fistulas types other than perianal (e.g., rectovaginal). 
3. Patients currently participating in any interventional clinical trial. 
Endpoints/Outcomes and Measures 
Primary endpoint/outcome 
1) Meta-scores of the SF-12 questionnaire (physical component score [PCS-12] and mental 
component score [MCS-12]). 
Secondary endpoints/outcomes 
1) Short IBDQ (SIBDQ) questionnaire score. 
2) SQOL-M and SQOL-F questionnaire scores for male and female patients, respectively. 
3) Wexner score. 
4) Work Productivity and Activity Impairment (WPAI) questionnaire score. 
5) Outpatient visits (gastroenterology or other medical specialty), emergency room visit, 
hospitalizations (≥24 hours), and pharmacological and surgical treatments used for the 
management of CPFs within the three years prior to the inclusion visit. 
6) Patients’ sociodemographic, anthropometric and clinical characteristics. 
7) Pharmacological and surgical treatments used for the management of CPFs within the three 
years prior to the inclusion visit. 
8) Association between general QoL (PCS-12 and MCS-12) and the patients’ socio-demographic, 
anthropometric and clinical characteristics. 
Exploratory endpoint 
1) Association between IBD-specific QoL (SIBDQ score)/sexual function (SQOL-M and SQOL-F 
scores) and the patients’ socio-demographic, anthropometric and clinical characteristics. 
Statistical Considerations: 
Primary analysis 
The results obtained for each item of the SF-12 will be summarized in a frequency table, including 
counts (n) and percentages (%). The two resulting meta-scores – the physical health composite scale 
score and the mental health composite scale score – will be summarized by descriptive statistics, 
namely mean (with 95% confidence intervals), standard deviation, median, range (minimum and 
maximum values) and interquartile ranges. 
Secondary analyses 
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IBD-specific QoL, sexual function, fecal incontinence and impact on social/work activities and work 
productivity 
The results obtained for the remaining study questionnaires (SIBDQ, SQOL-M, SQOL-F, WPAI, and 
Wexner score) will be summarized as described for the primary analysis, with qualitative 
items/questions being summarized by counts (n) and percentages (%) and quantitative items/questions 
summarized by descriptive statistics, namely mean, standard deviation, median, range (minimum and 
maximum values) and interquartile ranges. 
Healthcare Resource Utilization 
Data on outpatient visits (number, medical specialty), emergency room visits (number), hospitalizations 
≥24 hours (number, length of stay, ICU admission, ICU length of stay), and pharmacological and 
surgical treatments used for CPF management (number) within the three years prior to the inclusion 
visit will be summarized descriptive statistics – namely mean, standard deviation, median, range 
(minimum and maximum) and interquartile ranges – or by absolute (n) and relative (%) frequencies, as 
applicable. Moreover, the number of patients with at least one outpatient visit, emergency room visit, 
and hospitalization ≥24 hours will be presented. 
Patients’ characteristics 
All patients sociodemographic, anthropometric and clinical characteristics will be summarized by 
descriptive statistics – namely mean, standard deviation, median, range (minimum and maximum) and 
interquartile ranges – or by absolute (n) and relative (%) frequencies, as applicable. 
Pharmacological treatments and surgeries for CPF 
The pharmacological and surgical treatments used for the management of CPF will be described by 
counts (n) and percentages (%). For each pharmacological treatment (antibiotics, monoclonal 
antibodies and immunosuppressants), patients will be divided into three categories (current users, past 
users, and non-users) considering the three years prior to the inclusion visit. Current combinations (i.e., 
combinations used by the patient at the inclusion visit) will be described by counts (n) and percentages 
(%). 
Factors associated with general QoL (SF-12) 
Associations between general QoL (for the two SF-12 meta-scores – PHC and MHC) and qualitative 
variables will be tested with the t-test for independent samples/ANOVA for two/three or more 
independent samples or with the Mann-Whitney/Kruskal-Wallis non-parametric tests, according to the 
assumption validations of the statistical test. Associations between general QoL (for PHC and MHC) 
and quantitative variables will be performed through Pearson correlation coefficient or Spearman 
correlation coefficient (in case the normality assumption is not verified). 
Moreover, linear multiple regressions will be used to explore the association between the dependent 
variable (PCS and MCS meta-scores of the SF-12) and independent variables of interest according to 
the bivariate analysis results. Regression coefficients (B) and 95% confidence intervals will be 
computed to measure the magnitude of these associations. 
Exploratory analyses 
The same methodology described above for factors associated with general QoL (SF-12) will be 
followed to explore the association between independent variables of interest and the following 
dependent variables: 
• 
IBD-specific QoL (SIBDQ score). 
• 
Sexual function (SQOL-M and SQOL-F scores for male and female patients, respectively). 
Sample Size Justification: 
The sample size was determined based on the study’s primary objective. To determine the sample 
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Table of Contents 
1 
Administrative information .................................................................................................... 2 
1.1 
Contacts ....................................................................................................................................... 2 
1.2 
Approval ...................................................................................................................................... 3 
INVESTIGATOR SIGNATURE PAGE ............................................................................................................ 4 
STUDY SUMMARY ................................................................................................................................... 5 
Table of Contents ........................................................................................................................... 9 
List of Abbreviations and Definition of Terms ................................................................................ 12 
2 
Introduction ........................................................................................................................... 13 
3 
Study Objective(s) and Endpoint(s)/Outcome(s) ..................................................................... 15 
3.1 
Objective(s) ................................................................................................................................ 15 
3.1.1 
Primary Objective .......................................................................................................................................... 15 
3.1.2 
Secondary Objective(s) .................................................................................................................................. 15 
3.1.3 
Exploratory Objective(s) ................................................................................................................................ 15 
3.2 
Endpoint(s)/Outcome(s) ............................................................................................................. 15 
3.2.1 
Primary Endpoint .......................................................................................................................................... 15 
3.2.2 
Secondary Endpoint(s) .................................................................................................................................. 16 
3.2.3 
Exploratory Endpoint(s) ................................................................................................................................ 16 
4 
Study Methods ...................................................................................................................... 17 
4.1 
Study Schedule ........................................................................................................................... 17 
4.2 
Study Design .............................................................................................................................. 17 
4.3 
Selection of Study Population ..................................................................................................... 19 
4.3.1 
Inclusion Criteria ........................................................................................................................................... 19 
4.3.2 
Exclusion Criteria ........................................................................................................................................... 20 
4.4 
Treatments................................................................................................................................. 20 
4.5 
Premature Termination or Suspension of Study or Study Site ...................................................... 21 
4.5.1 
Criteria for Premature Termination or Suspension of the Study ................................................................... 21 
4.5.2 
Criteria for Premature Termination or Suspension of Study Sites ................................................................. 21 
4.5.3 
Procedures for Premature Termination or Suspension of the Study or the Participation of Study Site(s) .... 21 
4.6 
Study Plan .................................................................................................................................. 21 
5 
Study Administrative Structure .............................................................................................. 27 
5.1 
Study Sites ................................................................................................................................. 27 
5.2 
Sponsor Personnel ..................................................................................................................... 27 
5.3 
Contract Research Organisation (CRO) ........................................................................................ 27 
6 
Ethics ..................................................................................................................................... 28 
6.1 
Ethical conduct of the Study ....................................................................................................... 28 
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6.2 
Independent Ethics Committee / Institutional Review Board and Authorities IEC/ IRB ................ 28 
6.3 
Authorities ................................................................................................................................. 29 
6.4 
Subject Information and Written Informed Consent ................................................................... 29 
7 
Safety Reporting .................................................................................................................... 31 
7.1 
Definitions ................................................................................................................................. 31 
7.2 
Safety events spontaneously notified to the investigator(s) or research team ............................. 33 
8 
Data Quality Control and Assurance ...................................................................................... 34 
8.1 
Quality Control ........................................................................................................................... 34 
8.2 
Audit from Quality Assurance Unit ............................................................................................. 34 
8.3 
Inspection by IRB/IEC or Competent Authority ........................................................................... 34 
8.4 
Data Management ..................................................................................................................... 34 
8.4.1 
Data Collection Tools and Flow ..................................................................................................................... 35 
9 
Statistical Methods and Determination of Sample Size .......................................................... 36 
9.1 
Statistical Analysis Plan .............................................................................................................. 36 
9.1.1 
General considerations ................................................................................................................................. 36 
9.1.2 
Primary analysis ............................................................................................................................................ 36 
9.1.3 
Secondary analyses ....................................................................................................................................... 37 
9.1.4 
Exploratory analyses ..................................................................................................................................... 40 
9.2 
Interim Analyses ........................................................................................................................ 41 
9.3 
Determination of Sample Size ..................................................................................................... 41 
10 
Reports .............................................................................................................................. 42 
11 
Publication, Disclosure, and Clinical Trial Registration Policy .............................................. 42 
12 
Archiving of Study Documentation ..................................................................................... 42 
13 
References ......................................................................................................................... 44 
14 
Appendices ......................................................................................................................... 46 
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APPENDICES 
1. SF-12 
 
2. SQOL-M 
 
3. SQOL-F 
 
4. Short Inflammatory Bowel Disease Questionnaire 
 
5. Work Productivity and Activity Impairment 
 
6. Wexner Score 
 
7. Perianal Disease Activity Index 
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List of Abbreviations and Definition of Terms 
 
 
AE: 
Adverse Event 
AE: 
Adverse Drug Reaction 
AGA: 
American Gastroenterological Association 
CA: 
Competent Authority 
CD: 
Crohn’s Disease 
CPF: 
Complex Perianal Fistula 
CRF: 
Case Report Form 
CRO: 
Contract Research Organisation 
GCP: 
Good Clinical Practice 
GPP: 
Good Pharmacoepidemiology Practices 
IBD: 
Inflammatory Bowel Disease 
IBDQ: 
Inflammatory Bowel Disease Questionnaire 
ICH: 
International Conference on Harmonisation 
IEC: 
Independent Ethics Committee 
IRB: 
Institutional Review Board 
LIFT: 
Ligation of the Intersphincteric fistula tract 
MCS: 
Mental Component Score 
PDAI: 
Perianal Disease Activity Index 
PCS: 
Physical Component Score 
QoL: 
Quality of Life 
SAE: 
Serious Adverse Event 
SAP: 
Statistical Analysis Plan 
SADR: 
Serious Adverse Drug Reaction 
TNF: 
Tumor Necrosis Factor 
WPAI: 
Work Productivity and Activity Impairment 
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2 
Introduction 
Crohn’s disease (CD) is a life-long chronic inflammatory condition of the gastrointestinal 
tract, resulting from an interaction between environmental and genetic factors (1,2). This 
disease is frequently complicated by fistulas, which may form between segments of the 
intestine and the skin or adjacent organs (e.g., bladder or vagina) (3). 
Fistulas may be classified as either simple or complex. According to the American 
Gastroenterological Association (AGA), a simple fistula is low (superficial or low 
intersphincteric or low transsphincteric origin of the fistula tract), has a single external 
opening, has no pain or fluctuation suggesting perianal abscess, and has no evidence of 
a rectovaginal fistula and anorectal stricture. A complex fistula is high (high 
intersphincteric or high transsphincteric or extrasphincteric or suprasphincteric origin of 
the fistula tract), may have multiple external openings, may be associated with the 
presence of pain or fluctuation to suggest a perianal abscess, and may be associated with 
the presence of a rectovaginal fistula, anorectal stricture or active rectal disease at 
endoscopy (4). Around 30% to 50% of CD patients present perianal fistulas (5), the 
majority of which (70-80%) are classified as complex (6,7). 
The symptoms and complications of perianal fistulas, such as pain, scarring, discharge, 
fecal incontinence, and sexual difficulties, may lead to a considerable deterioration of 
the patients’ Quality of Life (QoL) (5). Nonetheless, a recent systematic review showed 
that published studies on the QoL of CD patients with complex perianal fistulas (CPFs) 
are lacking in Europe (8). Indeed, only one study assessing QoL was identified, which 
showed that patients with perianal CD (84% of whom had complex anal fistulas) who 
underwent surgical treatment had significantly lower Inflammatory Bowel Disease 
Questionnaire (IBDQ) and physical health scores on the SF-12 in comparison with 
healthy controls. However, no differences in SF-12 mental health scores were observed 
(9). Similarly, only one study reporting data on the costs resulting from the management 
of CPF in CD patients was identified. This study, conducted in Spain, concluded that 
CD patients with fistulas account for a large part of the overall burden and economic 
costs of this disease (10). Accordingly, a study performed in the United States in 2008 
reported that direct costs were significantly higher among fistulizing CD patients versus 
those without fistulas ($35373 vs $15564 per patient per year, respectively; p<0.0001) 
(11). Still, as both these studies considered direct costs only, the total cost of CPF 
among patients with CD is expected to have been underestimated (8). Indirect costs, 
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such as those resulting from work absenteeism and sick leave, have rarely been 
considered in studies evaluating the burden of complex perianal CD (2). 
Though the burden of CPFs has seldom been studied, perianal disease (including 
fistulas, fissures, abscesses and stenosis) has been shown to significantly impact the 
QoL and sexual function of Inflammatory Bowel Disease (IBD) patients (12). Indeed, a 
study comparing IBD patients (including CD and ulcerative colitis) with and without 
perianal disease reported significantly lower SF-36 scores on all subscales – physical 
functioning, limitations due to physical health and emotional problems, energy/fatigue, 
emotional well-being, social functioning and general health – among the latter. 
Moreover, more than two-thirds of patients with perianal disease reported restriction of 
sexual activities (slight restriction [28%], moderate limitations [25%], marked 
limitations [12%], unable to engage in sexual activities [4%]). Patients with perianal 
disease were also more likely to report sick leave in the last 6 months and the influence 
of IBD on work productivity during the last 6 months was also significantly higher. 
Treatment of perianal fistulas is aimed at promoting long-term fistula healing while 
preserving continence and preventing diverting stomas (13). However, the currently available 
therapies rarely allow to achieve these goals, particularly among patients with complex 
fistulas (14). Available treatments for complex fistulas include antibiotics, 
immunosuppressants, monoclonal antibodies (Tumor Necrosis Factor [TNF]-inhibitors), and 
surgery (namely fistulotomy, advancement flap, ligation of the intersphincteric fistula tract 
[LIFT], fibrin glue, anal fistula plug, and seton placement) (4,15,16). Complex fistulas are 
specially challenging to treat as they are exceptionally refractory to conventional therapies 
(such as immunomodulators and antibiotics) and anti-TNFs (17–19). Additionally, only a 
small proportion of patients achieve long-term remission (20), with 60% to 70% relapsing 
after stopping treatment (21–23). 
Rationale 
 
As stated above, there is a lack of data regarding the burden of CPFs among patients 
with CD. To the best of our knowledge, no study assessing QoL, sexual function, and 
healthcare resource consumption in this population has been conducted and published in 
Portugal. The present study will aim at bridging this data gap, by evaluating and 
characterizing these dimensions in CD patients with CPFs attending routine clinical 
practice in Portugal. 
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3 
Study Objective(s) and Endpoint(s)/Outcome(s) 
3.1 
Objective(s) 
The aim of this study is to characterize the QoL (general and IBD-specific), sexual 
function, work productivity and activity impairment, and healthcare resource utilization 
among CD patients with CPFs attending secondary care services (gastroenterology 
appointments) in Portugal. 
 
3.1.1 Primary Objective 
1) To assess the general QoL among CD patients with CPFs attending secondary care 
services in Portugal. 
 
 
3.1.2 Secondary Objective(s) 
1) To assess the IBD-specific QoL among CD patients with CPFs. 
2) To assess the sexual function among CD patients with CPFs. 
3) To assess fecal incontinence among CD patients with CPFs. 
4) To assess the work productivity and activity impairment among CD patients with CPFs. 
5) To assess the healthcare resource utilization in CD patients with CPFs within the three 
years prior to the inclusion visit. 
6) To describe the sociodemographic, anthropometric, and clinical characteristics of CD 
patients with CPFs. 
7) To describe the pharmacological and surgical treatments used for the management of 
CPFs within the three years prior to the inclusion visit. 
8) To explore the association between general QoL and the sociodemographic, 
anthropometric, and clinical characteristics of CD patients with CPFs. 
 
3.1.3 Exploratory Objective(s) 
1) To explore the association between IBD-specific QoL/sexual function and the 
sociodemographic, anthropometric, and clinical characteristics of CD patients with CPFs. 
 
3.2 
Endpoint(s)/Outcome(s) 
3.2.1 Primary Endpoint 
1) Meta-scores of the SF-12 questionnaire (physical component score [PCS-12] and mental 
component score [MCS-12]). 
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3.2.2 Secondary Endpoint(s) 
1) Short IBDQ (SIBDQ) questionnaire score. 
2) SQOL-M and SQOL-F questionnaire scores for male and female patients, respectively. 
3) Wexner score. 
4) Work Productivity and Activity Impairment (WPAI) questionnaire score. 
5) Outpatient visits (gastroenterology or other medical specialty), emergency room visits, 
hospitalizations (≥24 hours), and pharmacological and surgical treatments used for the 
management of CPFs within the three years prior to the inclusion visit. 
6) Patients’ sociodemographic, anthropometric and clinical characteristics. 
7) Pharmacological and surgical treatments used for the management of CPFs within the 
three years prior to the inclusion visit. 
8) Association between general QoL (PCS-12 and MCS-12) and the patients’ socio- 
demographic, anthropometric and clinical characteristics. 
 
3.2.3 Exploratory Endpoint(s) 
1) Association between IBD-specific QoL (SIBDQ score)/sexual function (SQOL-M and 
SQOL-F scores) and the patients’ socio-demographic, anthropometric and clinical 
characteristics. 
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4 
Study Methods 
4.1 
Study Schedule 
Planned Start of the Study: April 2021 
 
Planned collection of first patient data (first patient first visit): April 2021 
Planned End of Study (last patient last visit): December 2021 
Date of database lock: February 2022 
 
 
The appointed Contract Research Organisation (CRO) will ensure that End-of-Study 
notification is submitted to the concerned authorities and IEC/IRB for each site and for the 
complete study, as locally required. 
Takeda Portugal will ensure that results are made publicly available as required by local 
authorities. 
Based on upcoming knowledge, the Takeda Portugal might choose to terminate the study 
prematurely. In such case study sites, IECs/IRBs and authorities will be informed promptly. 
 
4.2 
Study Design 
This is a national, observational, cross-sectional study primarily aimed at assessing the 
general QoL among CD patients with CPFs in the Portuguese routine clinical practice. 
In addition to the cross-sectional design, the study will have a retrospective component 
to collect data on healthcare resource utilization and on the pharmacological and 
surgical treatments used for the management of CPFs in the three years prior to the 
inclusion visit. 
This study is a ‘non-interventional study’ as defined in Directive 2001/20/EC and will 
follow the guidelines for GPP. This means that: 
 
• The assignment of a subject to a particular therapeutic strategy is not decided in 
advance by the study protocol but falls within current practice. 
• No additional diagnostic or monitoring procedures shall be applied to the patients. 
 
• Epidemiological methods shall be used for the analysis of collected data. 
 
The study will be conducted in five Portuguese public hospitals experienced in the 
management of patients with CD. Gastroenterologists working at the participating 
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hospitals will participate in the study as investigators. Eligible patients (i.e., meeting all 
inclusion criteria and no exclusion criteria) will be consecutively enrolled during routine 
medical appointments at the participating hospitals. These will include male and female 
CD patients aged 18 or older with CPF(s). Eligible patients will be invited to participate 
in the study until a total of 80 patients are enrolled (see Section 9.3). 
Data on the demographic, anthropometric and clinical characteristics of enrolled 
patients and on the pharmacological and surgical treatments used for CPF management 
will be collected based on medical records review and patient interviews during the 
inclusion visit. The interviews will aim to minimize the potential limitations associated 
with relying on medical records for data collection (see below in Limitations of the 
study design). Patient-reported questionnaires will be completed at this visit to 
characterize the patients’ general and IBD-specific QoL (SF-12 and SIBDQ, 
respectively), sexual function (SQOL-M and SQOL-F), work productivity and activity 
impairment (WPAI), fecal incontinence (Wexner score), and severity of CD involving 
the perianal area (perianal disease activity index [PDAI]). Information on healthcare 
resource utilization related with CPF management in the previous three years will be 
obtained retrospectively from the medical records. 
The patient recruitment and data collection will occur simultaneously, during an 
expected period of 9 months. This period may be extended to allow for the recruitment 
of the required study sample. 
 
 
Limitation of the study design 
 
Due to the observational design of this study and the reliance on medical records for 
data collection, there is the potential for incomplete or missing documentation, poorly 
recorded and absent information. Patient interviews will be conducted to minimize this 
limitation, by complementing/validating the medical records’ data. 
The consecutive inclusion of eligible patients during routine medical appointments at 
the study sites, as well as the fact that sites must keep a screening log documenting the 
reasons for non-eligibility of non-enrolled patients (see Section 4.3), is expected to 
minimize selection bias during the recruitment process. In turn, this is expected to 
contribute to an adequate representativeness of the study population, thus increasing the 
generalizability of the study results to the population of CD patients with CPFs being 
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followed and treated in the secondary care setting, in Portugal. 
 
One of the study PROs (Wexner score), which will be used to characterize the patients’ 
fecal incontinence, is not validated for Portuguese language (Portugal). A process of 
translation/back-translation will be carried out prior to using this score in the study. 
 
 
4.3 
Selection of Study Population 
Eligible patients include male and female CD patients aged 18 or older with CPF(s). A 
screening log will be kept at the study sites and will be updated as patients attend 
routine medical appointments. The date of signed informed consent (for included 
patients) and the reasons for non-enrolment (for excluded patients) should be 
documented in this log. 
 
4.3.1 Inclusion Criteria 
Subject eligibility is determined according to the following criteria prior to study 
inclusion: 
1. Male or female patients aged 18 years or older at the inclusion visit. 
 
2. Patients diagnosed with CD. 
 
3. Presence of CPF(s), defined as ≥1of the following criteria: 
 
o high intersphincteric, high transsphincteric, extrasphincteric, or 
suprasphincteric location; 
o 
≥2 external openings; 
o associated collections. 
4. Patients attending routine gastroenterology appointments at the participating 
hospitals. 
5. Patients capable of understanding and complying with protocol requirements, in 
the investigator’s opinion. 
 
6. Patients or, when applicable, the patients’ legally acceptable representative, who 
signed and dated a written informed consent form and any required privacy 
authorization prior to the initiation of any study procedures. 
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4.3.2 Exclusion Criteria 
Any patient who meets any of the following criteria will not qualify for study inclusion: 
 
1. Patients diagnosed with ulcerative colitis or indeterminate IBD. 
 
2. Patients with non-complex fistulas or with fistulas types other than perianal 
(e.g., rectovaginal). 
3. Patients currently participating in any interventional clinical trial. 
 
Patients should be included in the study only once. 
 
Data erroneously collected from patients for whom written consent is not available, 
will not be included in or will be deleted from the database. 
 
4.4 
Treatments 
Non-interventional/observational – no treatments/pharmacotherapy are instructed by the 
study protocol. 
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4.5 
Premature Termination or Suspension of Study or Study Site 
 
4.5.1 Criteria for Premature Termination or Suspension of the Study 
The study will be completed as planned unless there is a significant violation of 
Good Clinical Practice (GCP/GPV) that compromises the ability to achieve the 
primary study objectives. In this case, a temporary suspension or early termination 
of the study may be required. 
 
4.5.2 Criteria for Premature Termination or Suspension of Study Sites 
A study site may be terminated prematurely or suspended if the site (including the 
investigator) is found in significant violation of GCP/GPP, protocol, or contractual 
agreement, is unable to ensure adequate performance of the study, or as otherwise 
permitted by the contractual agreement. 
 
4.5.3 Procedures for Premature Termination or Suspension of the Study or the 
Participation of Study Site(s) 
In the event that Takeda Portugal, an IRB/ IEC or regulatory authority elects to 
terminate or suspend the study or the participation of a study site, a study-specific 
procedure for early termination or suspension will be provided by Takeda Portugal or 
by the appointed Contract Research Organisation (CRO); the procedure will be 
followed by applicable study sites during the course of termination or study suspension. 
 
4.6 
Study Plan 
The data to be collected for each enrolled patient is summarized in Table 1 and described 
below. 
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Table 1 – Overview of study data 
 
Inclusion visit 
Retrospective 
data collection 
Informed consent 
X 
Inclusion/exclusion criteria 
X 
Sociodemographic and anthropometric characteristics 
X 
Employment status 
X 
Smoking status 
X 
Date of CD diagnosis 
X 
Date of CPF diagnosis 
X 
Extraintestinal manifestations of CD 
X 
Montreal classification for CD 
X 
Harvey-Bradshaw Index (HBI) 
X 
Perianal disease activity index (PDAI) 
X 
Fistula characteristics 
X 
Other perianal lesions 
X 
Patient-reported questionnaires 
X 
Pharmacological and surgical treatments for CPF 
Xa 
Healthcare resource utilization 
Xa 
aWithin the three years prior to the inclusion visit 
 
 
Study variables 
 
The variables described below will be collected for each enrolled patient. 
 
 
Patient characteristics 
• Sociodemographic and anthropometric characteristics 
o Age 
o Sex 
o Height 
o Weight 
o BMI 
• Employment status 
o Employed 
 
o Unemployed 
 
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o Retired 
o Student 
o Other 
• Smoking status 
o Current 
o Former 
o Never 
• Date of CD diagnosis 
• Date of CPF diagnosis (for each CPF presented by the patient at the inclusion 
visit) 
 
Clinical characteristics 
• Extraintestinal manifestation of CD 
o Arthralgia 
o Arthritis 
o Aphthous stomatitis 
o Sacroiliitis 
o Episcleritis 
o Erythema nodosum 
o Psoriasis 
o Sclerosing cholangitis 
o Ankylosing spondylitis 
o Pyoderma gangrenosum 
o Uveitis 
o Arthrosis/osteoarthritis 
o Hepatitis 
o Other 
• CD characteristics 
o Montreal classification for CD 
- 
Age at onset 
 A1: at or below 16 years 
 A2: between 17 and 40 years 
 A3: above 40 years 
 
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- 
Disease location 
 L1 (terminal ileum) 
 L2 (colon) 
 L3 (ileocolon) 
 L4 (upper gastrointestinal [GI]) 
 L1 + L4 (terminal ileum + upper GI) 
 L2 + L4 (colon + upper GI) 
 L3 + L4 (ileocolon + upper GI) 
- 
Disease behavior 
 B1p (nonstricturing, nonpenetrating + perianal) 
 B2p (stricturing + perianal) 
 B3p (penetrating + perianal) 
o Disease activity (Harvey-Bradshaw Index [HBI]) 
• PDAI 
• Fistula characteristics (for each CPF presented by the patient at the inclusion 
visit) 
o Fistula type 
- 
High intersphincteric 
- 
High transsphincteric 
- 
Suprasphincteric 
- 
Extrasphincteric 
- 
Other 
o Number of internal fistula openings 
o Number of external fistula openings 
o Fistula position (midline vs. lateral) 
o Presence of seton (yes/no). If yes, date of seton placement 
• Other perianal lesions 
o Skin tags 
o Hemorrhoids 
o Anal fissure 
o Anal ulcer 
o Perianal abscess 
o Anorectal stricture 
 
o Cancer 
 
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o Other 
 
Study questionnaires 
The following patient-reported questionnaires will be completed by the patients at the 
inclusion visit: 
• SF-12 (for general QoL) 
• SIBDQ (for IBD-specific QoL) 
• SQOL-M and SQOL-F (for sexual function in male and female patients, 
respectively) 
• WPAI (for work productivity and activity impairment) 
• Wexner score 
 
Pharmacological and surgical treatments for CPF management 
At the inclusion visit, patients will be classified as treatment-naïve or treatment- 
experienced based on whether they have received any pharmacological treatment for 
CPF management since the diagnosis of this condition. Similarly, patients will be 
classified as surgery-naïve or patients who have underwent surgery for CPF 
management. 
Moreover, the pharmacological and surgical treatments used for the management of 
CPF within the three years prior to the inclusion visit will be recorded. The start and 
end dates (when applicable) for pharmacological treatments and the date of surgery for 
surgical procedures will be collected. 
• Pharmacological treatments 
 
o Antibiotics 
- 
Ciprofloxacin 
 
- 
Metronidazole 
 
- 
Other 
 
o Monoclonal antibodies 
- 
Infliximab 
 
- 
Adalimumab 
 
- 
Ustekinumab 
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- 
Vedolizumab 
 
- 
Other 
 
o Immunosuppressants 
- 
Azathioprine 
 
- 
Mercaptopurine 
 
- 
Other 
 
• Surgical treatments 
 
o Fistulotomy 
o Advancement flap 
o Ligation of the intersphincteric fistula tract (LIFT) 
o Fibrin glue 
o Anal fistula plug 
o Defunctioning stoma 
o Seton (cutting) 
o Seton (loose) 
o Other 
Healthcare resource utilization 
Data on healthcare resource utilization (HCRU) associated with CPF management 
within the three years prior to the inclusion visit will be collected. These data will 
include: 
• Gastroenterology and other medical specialty appointments for the management of 
CPF 
• Emergency room visits due to CPF 
 
• Hospitalizations (≥24 hours) due to CPF: 
 
o Date of admission 
o Date of hospital discharge 
o ICU admission (yes/no). If yes: date of ICU admission/discharge 
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5 
Study Administrative Structure 
5.1 
Study Sites 
The study is planned to be conducted in five Portuguese sites (public hospitals) 
experienced in the management of CD patients. Gastroenterologists working at the 
participating hospitals will be invited to participate in the study as investigators. 
Takeda Portugal or the appointed CRO will keep a record of the individuals responsible 
for each participating Study Site, the Site Responsibles. 
 
5.2 
Sponsor Personnel 
Takeda Portugal will keep a record of all relevant sponsor personnel. 
 
 
5.3 
Contract Research Organisation (CRO) 
A Contract Research Organisation (CRO) – CTI Clinical Trial & Consulting 
Services – will be responsible for the following tasks: 
• Start-up activities (including regulatory submissions) 
 
• Study monitoring 
 
• Data management 
 
• End of study notification 
 
• Statistical analysis 
 
• Final study report 
 
• Study publications 
 
The CRO will keep a record of all involved CRO personnel. 
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6 
Ethics 
This observational study will have no impact on the subject except for collection of informed 
consent to use the subject’s data and for the completion of five patient-reported 
questionnaires. Patient-reported questionnaires will be completed during a single routine 
medical appointment (inclusion visit) at the participating hospitals to minimize the impact on 
the patients’ routine clinical practice. The patient’s participation in the study will last the 
duration of the routine medical appointment only. 
 
6.1 
Ethical conduct of the Study 
This study will be conducted in accordance with the protocol, the current version of the 
Declaration of Helsinki, International Conference on Harmonisation E6 Good Clinical 
Practice, Good Pharmacoepidemiology Practices (GPP), ISPE GPP guideline and any local 
regulations. Special attention will be paid to data protection, considering the EU General 
Data Protection Regulation (95/46 EC) and applicable Portuguese legislation, namely law 
No. 58/2019. 
Takeda Portugal and/or the appointed CRO will ensure that the protocol, any amendments 
and the Subject Information Sheet/Informed Consent Form are submitted to the relevant 
Independent Ethics Committees (IECs)/Institutional Review Boards (IRBs) according to local 
requirements. 
Takeda Portugal is responsible for meeting the International Conference on Harmonisation 
(ICH) requirement for yearly updates to the IECs/IRBs, if applicable. 
 
6.2 
Independent Ethics Committee / Institutional Review Board and Authorities 
IEC/ IRB 
According to applicable regulations, the appointed CRO or the Site Study Responsible will: 
 
• notify or obtain approval from the relevant IEC/IRB of the protocol, any amendments 
and the Subject Information Sheet / Informed Consent Form 
The appointed CRO or the Study Responsible will submit required documents to the IEC / 
IRB, such as: 
• periodic updates on the progress of the study 
 
• notification of the end-of-study 
 
 
• 
a summary of the study results 
 
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Takeda Portugal or the appointed CRO will keep an updated list of all submission and 
approval dates of all documents submitted to the IEC / IRB and will provide the Site 
Responsible with a copy of this list. Copies of the documents will be distributed upon 
request. 
 
6.3 
Authorities 
Takeda Portugal or the appointed CRO will send required documents to the competent 
authority (CA) and/or other national or regional authorities. Takeda Portugal or the 
appointed CRO will keep an updated list of submission and approval dates and a copy of all 
documents submitted. 
 
6.4 
Subject Information and Written Informed Consent 
The Site Study Responsible must give the subject (and if applicable, parent or legal guardian) 
oral and written information about the study in a form that the subject (and if applicable, the 
parent or legal guardian) can understand, and obtain the subject’s (and if applicable, the 
subject’s assent and the parent’s or legal guardian’s) written consent before collection of 
identifiable subject information (hereinafter referred to as personal data). Before consenting, 
the subject (and if applicable, parent or legal guardian) must be left with ample time to 
consider and to pose questions. Since the study is observational the consent only concerns the 
data collection per se and is not consent to any interventional procedure or treatment. 
Moreover, as patient-reported questionnaires that are not part of routine clinical practice will 
be used, the ICF will briefly explain what each questionnaire is aimed at assessing and will 
clearly state that participation in the study is associated with the completion of such 
questionnaires. 
The subject must agree that Takeda Portugal personnel, appointed CRO personnel, or 
IEC/IRB or CA personnel (national or other) may require direct access to the subject’s data 
/ personal records which were collected, processed and stored in an anonymous form. 
 
The subject must agree that his / her data will be processed and stored in an anonymous form 
for evaluation of this study and any later overviews. Data may also be transferred in 
anonymous form to third parties, e.g., to other companies or authorities, that may be located 
in other countries with potentially different regulations for data. 
The subject and subject’s parent or legal guardian, if applicable, has the right to withdraw 
his/her consent at any time without prejudice. In the Informed Consent Form, it is stated that 
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if consent is withdrawn, any data collected before withdrawal of consent will be kept. One 
original signed Informed Consent Form must be kept at the study site, and one is provided to 
the subject and/or subject’s parent or legal guardian, as applicable. 
For details, see the Subject Information Sheet and Informed Consent Form. 
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7 
Safety Reporting 
This is an observational study, where patients will not receive any study medication. 
 
7.1 
Definitions 
Adverse Event 
An adverse event (AE) is any untoward medical occurrence in a subject administered a 
medicinal product and which does not necessarily have to have a causal relationship with this 
treatment. An AE can therefore be any unfavorable and unintended sign (including an 
abnormal laboratory finding), symptom, a new disease or worsening in severity or frequency 
of a concomitant disease, temporally associated with the use of a medicinal product, whether 
or not the event is considered causally related to the use of the product. 
Although abnormal laboratory values are typically not considered AEs, the following 
considerations may result in an abnormal laboratory value being considered an AE: 
 
• A laboratory test result that meets the criteria for an SAE 
• A laboratory test result that requires the subject/patient to receive specific corrective 
therapy 
• A laboratory abnormality that leads to discontinuation of therapy 
• A laboratory abnormality that the health care provider considers to be clinically significant 
 
Serious Adverse Events 
A Serious Adverse Event (SAE) is any untoward medical occurrence that at any dose: 
 
• Results in death. Note that death is an outcome of an event. The event(s) causing death 
should be recorded. 
• In the view of the Health care provider, places the subject/patient at immediate risk of 
death (a life threatening event); however, this does not include an event that, had it 
occurred in a more severe form, might have caused death 
• Requires inpatient hospitalization or prolongation of existing hospitalization 
• Results in persistent or significant disability/incapacity 
• Results in a congenital anomaly/birth defect 
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• An SAE may also be any other medically important event that, in the opinion of the Health 
care provider, may jeopardize the subject/patient or may require intervention to prevent 
one of the other outcomes listed in the definition above. (Examples of such medical events 
include allergic bronchospasm requiring intensive treatment in an emergency room or 
convulsions occurring at home that do not require an inpatient hospitalization.) 
 
 
Adverse Drug Reactions 
 
An adverse drug reaction (ADR) is an AE for which there is at least a reasonable suspicion of 
a causal relationship between an AE and a suspected medicinal product. 
 
 
Product Quality Issues 
 
A Product Quality Issue (PQI) refers to defects related to the safety, identity, strength, 
quality, or purity of the product or with the physical characteristics, packaging, labeling, or 
design of the product. 
 
 
Special Situation Reports 
 
A Special Situation Report (SSR) includes any of the following events: 
 
• Pregnancy: Any case in which a pregnancy patient is exposed to a Takeda Product or in 
which a female patient or female partner of a male patient becomes pregnant following 
treatment with Takeda Product. Exposure is considered either through maternal exposure 
or via semen following paternal exposure. 
• Breastfeeding: Infant exposure from breast milk 
• Overdose: All information of any accidental or intentional overdose 
• Drug abuse, misuse or medication error: All information on medicinal product abuse, 
misuse or medication error (potential or actual) 
• Suspected transmission of an infectious agent: Suspected (in the sense of confirmed or 
potential) transmission of an infectious agent by a medicinal product. 
• Lack of efficacy of Takeda Product 
• Accidental/Occupational exposure 
• Use outside the terms of the marketing authorization, also known as “off-label” 
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• Use of falsified medicinal product 
• Drug-drug interactions and drug-food interactions 
• Inadvertent or accidental exposure with or without an AE 
• Unintended benefit 
 
A SSR should be reported even if there is no associated AE. 
 
 
7.2 
Safety events spontaneously notified to the investigator(s) or research team 
If during the conduct of the study the investigator(s) or a member of the research team is 
spontaneously informed by a healthcare professional or patient of an SAE, AE, ADR, SSR or 
PQI where the event/issue pertains to a Takeda product (or unbranded generic), such 
information should be notified to the relevant Takeda Pharmacovigilance department within 
1 working day for fatal or life-threatening SAEs, within 4 calendar days for other SAEs, and 
within 7 calendar days for all other events. As such reports are spontaneously notified, 
causality of any adverse events should be assumed unless there is evidence to the contrary. 
 
Takeda Contact Information 
Spontaneous reports are notified to the local Pharmacovigilance department, according to the 
timelines described above from reception through the email address AE.PRT@takeda.com. 
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8 
Data Quality Control and Assurance 
8.1 
Quality Control 
Monitoring visits will be conducted during the study to ensure that all data have been 
accurately and completely recorded in the case report forms (CRFs). Electronic database 
entries will be compared against the source documents (e.g. hospital medical records). The 
study monitor should have direct access to all relevant source documents. The investigator 
should provide and monitor the access to this information and take the necessary measures to 
correct any data that is not completed as per the protocol. 
The investigator is responsible for ensuring that the study is conducted according to the study 
protocol and for recording any occurrence that may be considered as a protocol deviation. 
Study monitors should also record all protocol deviations identified. 
 
All study data will be entered in an electronic database. The database will have automatic 
controls in place to limit errors during the data entry process. 
 
8.2 
Audit from Quality Assurance Unit 
The Quality Assurance (QA) unit may audit the study to ensure that study procedures comply 
with the protocol and standard operating procedures, and that collected data is correct and 
complete. 
 
8.3 
Inspection by IRB/IEC or Competent Authority 
Representatives from IRB/IEC or CA may in rare cases wish to inspect the study on site. 
Upon receiving notification of such inspection, the Study Site Responsible must immediately 
contact Takeda Portugal and must make the records available as requested. 
 
8.4 
Data Management 
Data Management will be carried out by the contracted CRO (CTI) according to a Data 
Management Plan, which must be written and approved before the design of the study 
database is finalized. The data management provider should approve all data formats before 
the data collection tools are made available to the sites. 
If the written informed consent of a subject is known not to be available in spite of it being 
required, data for this subject is not entered into or is deleted from the database. 
If a subject is erroneously included in the study more than once only the data relating to the 
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first inclusion will be kept in the database and be available for analysis. Data from later 
inclusions will be transferred to the first dataset when relevant, i.e. if collected within the 
time frame of the first follow-up period. 
The current Standard Coding Instructions for coding of medical history, concomitant illness 
(MedDRA), and concomitant medication (WHO-Drug) must be followed. 
Each patient will receive a unique identification code that will be used to identify her/him 
throughout the data collection and statistical analysis, and that must be used on all study 
documentation related to that patient. Once assigned to a patient, the identification code will 
not be reused. The identification number will consist of five digits: the first two corresponding 
to the study site number and the last three a sequential number starting at 001). For instance, 
the identification number of the fourth subject of site 03 will be 03004. 
 
8.4.1 Data Collection Tools and Flow 
The Study Site will receive data collection tools (CRFs, access to electronic data capture, 
etc.) from Takeda Portugal or the appointed CRO. Whenever possible, complete data 
sets should be entered. Text field entries and any data collected on paper should be 
legible and follow the CRF completion guide. 
Following informed consent signature, the data required per protocol will be collected by the 
investigator or designee and entered in the study database. Study data will be collected based 
on medical records review, patient interviews and patient-reported questionnaires applied at 
the inclusion visit. 
The Study Site Responsible must sign off the complete data set for each subject, confirming 
the collected data. 
No adverse events will be collected or analyzed as part of this study as there are not safety 
endpoints. This non-interventional study is not designed to identify or quantify safety issues 
related in any way with Takeda products. Only SAEs, AEs, ADRs, SSRs and PQIs 
spontaneously reported to the investigator(s) or research team will be communicated to Takeda 
according to Section 7. 
When the database has been declared to be complete and accurate, it will be locked and made 
available for statistical analysis. Any changes to the database after this time can only be made 
after agreement from Takeda Portugal and must be documented. 
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9 
Statistical Methods and Determination of Sample Size 
Statistical analysis will be performed by the CRO’s biostatistics team according to a 
Statistical Analysis Plan (SAP) to be developed separately from the protocol. 
 
This section/the Statistical Analysis Plan describes the statistical analyses as foreseen at the 
time of planning the study. Any known deviations from the planned analyses, the reason for 
such deviations and all alternative / additional statistical analyses performed must be 
documented and described in subsequent study documents, namely the Statistical Report and 
Clinical Study Report. 
 
 
9.1 
Statistical Analysis Plan 
9.1.1 General considerations 
This study is observational and epidemiological methods will be employed for data analyses. 
 
All quantitative variables will be summarized using descriptive statistics, namely mean, 
standard deviation, median, range (minimum and maximum values) and interquartile ranges. 
All qualitative variables will be summarized by absolute (n) and relative (%) frequencies. The 
statistical analysis will be performed through frequency tables for qualitative variables and 
tables with descriptive statistics for quantitative variables. 
No imputation of missing data will be performed. Percentages will be calculated based on non- 
missing values. 
All eligible patients (i.e., meeting all inclusion criteria and no exclusion criteria) will be 
considered for the statistical analyses. 
All statistical procedures will be performed with the software SAS 9.4 or higher. 
For details of the statistical analyses please refer to the Statistical Analysis Plan. 
9.1.2 Primary analysis 
To characterize the patients’ general QoL, the results obtained for each item of the SF-12 will 
be summarized in a frequency table, including counts (n) and percentages (%). The two 
resulting meta-scores – the physical health composite scale score and the mental health 
composite scale score – will be summarized by descriptive statistics, namely mean (with 95% 
CI), standard deviation, median, range (minimum and maximum values) and interquartile 
ranges. 
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Ninety-five per cent CIs will be determined for the mean meta-scores of the SF-12 according 
to the following formula: 
 
 
 
9.1.3 Secondary analyses 
 
IBD-specific QoL 
 
mean ± 1.96 × standard deviation 
√n 
 
To characterize the patients’ IBD-specific QoL, the results obtained for each item of the 
SIBDQ and the overall score will be summarized will be summarized by descriptive statistics, 
namely mean, standard deviation, median, range (minimum and maximum values) and 
interquartile ranges. 
 
 
Sexual function 
 
The results obtained for each of the 11 items included in the SQOL-M questionnaire (for male 
patients) will be summarized in a frequency table, including counts (n) and percentages (%), 
and by descriptive statistics, namely mean, standard deviation, median, range (minimum and 
maximum values) and interquartile ranges. The overall score will also be summarized 
descriptively. 
The results obtained in each of the 18 items included in the SQOL-F (for female patients) will 
be summarized in a frequency table, including counts (n) and percentages (%), and by 
descriptive statistics, namely mean, standard deviation, median, range (minimum and 
maximum values) and interquartile ranges. The overall score will also be summarized 
descriptively. 
 
 
Fecal incontinence 
 
The results obtained for each of the five items of the Wexner score will be summarized in a 
frequency table, including counts (n) and percentages (%). The overall score will be 
summarized by descriptive statistics, namely mean, standard deviation, median, range 
(minimum and maximum values) and interquartile ranges. 
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Impact on social/work activities and work productivity 
 
Results from the first question of the WPAI will be summarized by counts (n) and percentages 
(%). Data on the remaining six questions will be summarized by descriptive statistics, namely 
mean, standard deviation, median, range (minimum and maximum values) and interquartile 
ranges. Moreover, the scores obtained for the four domains assessed by the WPAI – 
absenteeism (work time missed), presenteeism (impairment at work / reduced on-the-job 
effectiveness), work productivity loss and activity impairment – will be summarized 
descriptively. 
 
 
Healthcare Resource Utilization 
 
Data on outpatient visits (number, medical specialty), emergency room visits (number), 
hospitalizations ≥24 hours (number, length of stay, ICU admission, ICU length of stay), and 
pharmacological and surgical treatments used for CPF management (number) within the three 
years prior to the inclusion visit will be summarized descriptive statistics – namely mean, 
standard deviation, median, range (minimum and maximum) and interquartile ranges – or by 
absolute (n) and relative (%) frequencies, as applicable. 
Moreover, the number of patients with at least one outpatient visit, emergency room visit, and 
hospitalization ≥24 hours will be presented. 
 
 
Patients’ characteristics 
 
All patients sociodemographic, anthropometric and clinical characteristics described in Section 
4.6 will be summarized by descriptive statistics – namely mean, standard deviation, median, 
range (minimum and maximum) and interquartile ranges – or by absolute (n) and relative (%) 
frequencies, as applicable. The classification of patients as treatment- and/or surgery-naïve 
will also be presented by descriptive statistics. 
Patients will be divided into three categories based on the timing of CPF diagnosis in relation 
to the CD diagnosis: 
• Prior to CD diagnosis 
 
• At CD presentation (i.e., when CPF was diagnosed in the same year as CD) 
 
• During the course of the disease 
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Based on the HBI score, patients will be categorized into four categories: 
 
• Remission (score <5) 
 
• Mild activity (5-7) 
 
• Moderate activity (8-16) 
 
• Severe activity (>16) 
 
Based on the PDAI score, patients will be divided into two groups (24): 
 
• Inactive fistulizing disease (≤4) 
 
• Active fistulizing disease (>4) 
 
 
Pharmacological treatments and surgeries for CPF 
 
The pharmacological and surgical treatments used for the management of CPF (see Section 
4.6) will be described by counts (n) and percentages (%). 
For each pharmacological treatment (antibiotics, monoclonal antibodies and 
immunosuppressants), patients will be divided into three categories (current users, past users, 
and non-users) considering the three years prior to the inclusion visit. For instance, for 
immunosuppressants, the proportions of patients using these drugs at the inclusion visit, those 
who have used them within the last three years, and those who have not used them in this 
period will be summarized. 
Current combinations (i.e., combinations used by the patient at the inclusion visit) will be 
described by counts (n) and percentages (%). 
 
 
Factors associated with general QoL (SF-12) 
Bivariate analysis 
Comparisons of general QoL (for the two SF-12 meta-scores – PHC and MHC) and between 
groups defined based on qualitative variables, of patient characteristics, will be tested with the 
t-test for independent samples/ANOVA for two/three or more independent samples or with the 
Mann-Whitney/Kruskal-Wallis non-parametric tests, according to the assumption validations 
of the statistical test. The following qualitative variables will be considered for the bivariate 
analysis: sex, smoking status, employment status, extraintestinal manifestations of Crohn’s 
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disease, Montreal classification for CD disease (age at onset, disease location, and disease 
behavior), fistula type and position, CD disease activity (remission, mild activity, moderate 
activity, and severe activity), treatment-naïve (yes/no), surgery-naïve (yes/no), treatment- and 
surgery-naïve (yes/no), surgery for the management of CPFs within the three years prior to the 
inclusion visit (yes/no), type of surgery, and presence of seton, perianal abscess and anorectal 
stricture. 
Associations between general QoL (for PHC and MHC) and quantitative variables of patient 
characteristics, will be performed through Pearson correlation coefficient or Spearman 
correlation coefficient (in case the normality assumption is not verified). The following 
quantitative variables will be considered for the bivariate analysis: age, BMI, time since CD 
diagnosis, number of CPFs presented at the inclusion visit, time since CPF diagnosis (in 
patients with more than one CPF at the inclusion visit, the oldest date of diagnosis will be 
considered), PDAI score, number of internal and external fistula openings, time since seton 
placement, SIBDQ score, SQOL-M score (for male patients) and SQOL-F score (for female 
patients), and Wexner score. 
 
 
Linear multiple regressions 
 
Moreover, linear multiple regressions will be used to explore the association between the 
dependent variable (PCS and MCS meta-scores of the SF-12) and independent variables of 
interest according to the bivariate analysis results. Regression coefficients (B) and 95% 
confidence intervals will be computed to measure the magnitude of these associations. 
 
 
9.1.4 Exploratory analyses 
 
The same methodology described in Section 9.1.3 (for factors associated with general QoL 
[SF-12]) will be followed to explore the association between independent variables of interest 
and the following dependent variables: 
• IBD-specific QoL (SIBDQ score) 
 
• Sexual function (SQOL-M and SQOL-F scores for male and female patients, 
respectively) 
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9.2 
Interim Analyses 
No interim analyses are planned for this study. 
 
9.3 
Determination of Sample Size 
The sample size was determined based on the study’s primary objective – to assess the general 
QoL of CD patients with CPF. 
To determine the sample size, an expected standard deviation of the outcome (SF-12 score) is 
required. Ideally, a standard deviation of the SF-12 score assessed in CD patients with CPFs 
should be used. However, we found no studies in the literature reporting SF-12 scores 
exclusively for CD patients with CPFs. Alternatively, we used the data reported by a study that 
evaluated the QoL via SF-12 in CD patients (25). This study reported mean scores of 49.1 
(±10.2) and 49.6 (±10.6) for PCS-12 and MCS-12, respectively. 
Considering an expected standard deviation of 10.6 (the most conservative) based on the 
abovementioned study, a confidence level at 95% and a margin of error of approximately 2.3, 
a total of 80 patients should be included in the study to assess the general QoL via the SF-12 
questionnaire. The formula below was used for the sample size determination: 
 
 
 
 
 
Where: 
 
n = required sample size 
z2 × s2 
n = 
m2 
 
z = confidence level at 95% (standard value of 1.96) 
s = expected standard deviation 
m = margin of error 
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10 
Reports 
The Final Study Report should be available within one year from collection of the last data 
point, and the participating sites should be informed about the results when the report is 
finalized. 
 
 
11 
Publication, Disclosure, and Clinical Trial Registration Policy 
Takeda Portugal aims to have the results of this study published. 
 
Takeda Portugal has the right to use the data and results for regulatory purposes and for 
internal presentation within the company and to partners. 
Takeda may post the results of the study on ClinicalTrials.gov and/or other publicly 
accessible websites, as required by Takeda Policy/Standard, applicable laws and/or 
regulations. 
 
 
12 
Archiving of Study Documentation 
During the course of the study the Site Responsible must as a minimum file the below 
essential documents in the Study Site File: 
• Written agreement between Takeda Portugal or the appointed CRO and the Study 
Site. 
• The study protocol and any amendments 
 
• Signed and dated protocol agreement and amendment agreements, if any, with the 
original signature of the Site Responsible 
• Subject Information Sheet and Informed Consent Form in local language (notified to / 
approved by Independent Ethics Committees (IECs) / Institutional Review Boards (IRBs) 
as locally required), including the original signed Forms 
• The list of participating subjects 
 
• Written IEC / IRB approval / vote according to local regulations 
 
• The completed CRFs 
 
• The progress reports 
 
After final database lock the Site Responsible must as a minimum store the list of 
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participating subjects and the signed Informed Consent Forms on site for 5 years. The Site 
Responsible should store additional study documentation for a longer period of time as 
required by any local regulations and/or hospital requirement. 
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13 
References 
 
1. 
Gomollón F, Dignass A, Annese V, Tilg H, Van Assche G, Lindsay JO, et al. 3rd 
European Evidence-based Consensus on the Diagnosis and Management of Crohn’s 
Disease 2016: Part 1: Diagnosis and Medical Management. J Crohns Colitis. 2017 
Jan;11(1):3–25. 
 
2. 
Aguilera-Castro L, Ferre-Aracil C, Garcia-Garcia-de-Paredes A, Rodriguez-de-Santiago E, 
Lopez-Sanroman A. Management of complex perianal Crohn’s disease. Ann Gastroenterol 
Q Publ Hell Soc Gastroenterol. 2017;30(1):33–44. 
 
3. 
Gold SL, Cohen-Mekelburg S, Schneider Y, Steinlauf A. Perianal Fistulas in Patients With 
Crohn’s Disease, Part 1: Current Medical Management. Gastroenterol Hepatol. 2018 
Aug;14(8):470–81. 
 
4. 
American gastroenterological association medical position statement: perianal Crohn’s 
disease1. Gastroenterology. 2003 Nov 1;125(5):1503–7. 
 
5. 
Panés J, García-Olmo D, Van Assche G, Colombel JF, Reinisch W, Baumgart DC, et al. 
Long-term Efficacy and Safety of Stem Cell Therapy (Cx601) for Complex Perianal 
Fistulas in Patients With Crohn’s Disease. Gastroenterology. 2018;154(5):1334-1342.e4. 
 
6. 
Eglinton TW, Barclay ML, Gearry RB, Frizelle FA. The spectrum of perianal Crohn’s 
disease in a population-based cohort. Dis Colon Rectum. 2012 Jul;55(7):773–7. 
 
7. 
Bell SJ, Williams AB, Wiesel P, Wilkinson K, Cohen RCG, Kamm MA. The clinical 
course of fistulating Crohn’s disease. Aliment Pharmacol Ther. 2003 May 1;17(9):1145– 
51. 
 
8. 
Panes J, Reinisch W, Rupniewska E, Khan S, Forns J, Khalid JM, et al. Burden and 
outcomes for complex perianal fistulas in Crohn’s disease: Systematic review. World J 
Gastroenterol. 2018 Nov 14;24(42):4821–34. 
 
9. 
Riss S, Schwameis K, Mittlböck M, Pones M, Vogelsang H, Reinisch W, et al. Sexual 
function and quality of life after surgical treatment for anal fistulas in Crohn’s disease. 
Tech Coloproctology. 2013 Feb;17(1):89–94. 
 
10. Chaparro M, Zanotti C, Burgueño P, Vera I, Bermejo F, Marín-Jiménez I, et al. Health 
care costs of complex perianal fistula in Crohn’s disease. Dig Dis Sci. 2013 
Dec;58(12):3400–6. 
 
11. Cohen RD, Waters HC, Tang B, Rahman MI. Effects of fistula on healthcare costs and 
utilization for patients with Crohn’s disease treated in a managed care environment. 
Inflamm Bowel Dis. 2008 Dec;14(12):1707–14. 
 
12. Vollebregt PF, van Bodegraven AA, Markus‐de Kwaadsteniet TML, van der Horst D, 
Felt‐Bersma RJF. Impacts of perianal disease and faecal incontinence on quality of life 
and employment in 1092 patients with inflammatory bowel disease. Aliment Pharmacol 
Ther. 2018 May;47(9):1253–60. 
 
13. Gecse KB, Bemelman W, Kamm MA, Stoker J, Khanna R, Ng SC, et al. A global 
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consensus on the classification, diagnosis and multidisciplinary treatment of perianal 
fistulising Crohn’s disease. Gut. 2014 Sep;63(9):1381–92. 
 
14. Schwartz DA, Herdman CR. Review article: The medical treatment of Crohn’s perianal 
fistulas. Aliment Pharmacol Ther. 2004 May 1;19(9):953–67. 
 
15. Torres J, Bonovas S, Doherty G, Kucharzik T, Gisbert JP, Raine T, et al. ECCO 
Guidelines on Therapeutics in Crohn’s Disease: Medical Treatment. J Crohns Colitis. 
2020 Jan 1;14(1):4–22. 
 
16. Adamina M, Bonovas S, Raine T, Spinelli A, Warusavitarne J, Armuzzi A, et al. ECCO 
Guidelines on Therapeutics in Crohn’s Disease: Surgical Treatment. J Crohns Colitis. 
2020 Feb 10;14(2):155–68. 
 
17. Present DH, Rutgeerts P, Targan S, Hanauer SB, Mayer L, van Hogezand RA, et al. 
Infliximab for the treatment of fistulas in patients with Crohn’s disease. N Engl J Med. 
1999 May 6;340(18):1398–405. 
 
18. Sands BE, Anderson FH, Bernstein CN, Chey WY, Feagan BG, Fedorak RN, et al. 
Infliximab maintenance therapy for fistulizing Crohn’s disease. N Engl J Med. 2004 Feb 
26;350(9):876–85. 
 
19. Thia KT, Mahadevan U, Feagan BG, Wong C, Cockeram A, Bitton A, et al. Ciprofloxacin 
or metronidazole for the treatment of perianal fistulas in patients with Crohn’s disease: a 
randomized, double-blind, placebo-controlled pilot study. Inflamm Bowel Dis. 2009 
Jan;15(1):17–24. 
 
20. Molendijk I, Nuij VJAA, van der Meulen-de Jong AE, van der Woude CJ. Disappointing 
durable remission rates in complex Crohn’s disease fistula. Inflamm Bowel Dis. 2014 
Nov;20(11):2022–8. 
 
21. Domènech E, Hinojosa J, Nos P, Garcia-Planella E, Cabré E, Bernal I, et al. Clinical 
evolution of luminal and perianal Crohn’s disease after inducing remission with 
infliximab: how long should patients be treated? Aliment Pharmacol Ther. 2005 
Dec;22(11–12):1107–13. 
 
22. Goldstein ES, Marion JF, Present DH. 6-Mercaptopurine is effective in Crohn’s disease 
without concomitant steroids. Inflamm Bowel Dis. 2004 Mar;10(2):79–84. 
 
23. Korelitz BI, Present DH. Favorable effect of 6-mercaptopurine on fistulae of Crohn’s 
disease. Dig Dis Sci. 1985 Jan;30(1):58–64. 
 
24. Rencz F, Stalmeier PFM, Péntek M, Brodszky V, Ruzsa G, Gönczi L, et al. Patient and 
general population values for luminal and perianal fistulising Crohn’s disease health states. 
Eur J Health Econ HEPAC Health Econ Prev Care. 2019 Jun;20(Suppl 1):91–100. 
 
25. Christiansen LK, Lo B, Bendtsen F, Vind I, Vester-Andersen MK, Burisch J. Health- 
related quality of life in inflammatory bowel disease in a Danish population-based 
inception cohort. United Eur Gastroenterol J. 2019 Aug;7(7):942–54. 
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14 
Appendices 
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SQoL-M: 29/10/99 
1999, Pfizer Ltd, Ramsgate Rd, Sandwich, Kent, CT13 9NJ 
Portuguese (Portugal), May 2004 
Study Protocol Ver. 1, 25-FEB-2021 
Page 50 of 62 
 
 
 
2. SQOL-M 
 
Questionário sobre a Qualidade da Vida Sexual - Masculino 
(Portuguese version of the SQoL-M) 
 
 
Este questionário é composto por um conjunto de afirmações, cada uma sobre os 
pensamentos e sentimentos que eventualmente tenha em relação à sua vida 
sexual. A afirmação pode referir-se tanto a aspectos positivos como negativos da 
sua vida sexual. Este questionário destina-se a todos os homens, 
independentemente da sua escolha sexual. 
 
Pedimos-lhe que classifique cada afirmação de acordo com o quanto concorda ou 
discorda com a mesma, pondo um círculo à volta de uma das seis respostas 
possíveis. 
 
Ao responder a estas questões deve ter em conta as seguintes definições: 
 
Vida sexual: refere-se tanto às actividades sexuais físicas como à relação sexual 
emocional que tem com a sua parceira. 
 
Actividade sexual: inclui qualquer actividade que possa resultar em estimulação 
ou prazer sexual, por exemplo, relações sexuais, carícias, preliminares, 
masturbação (tanto auto-masturbação como a sua parceira a masturbá-lo a si) e 
sexo oral (ou seja, a sua parceira a fazer-lhe sexo oral). 
 
 
 
Normalmente a primeira resposta que lhe vem à cabeça é a melhor; por isso, não 
passe muito tempo com cada pergunta. 
 
Todas as suas respostas serão totalmente confidenciais 
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SQoL-M: 29/10/99 
1999, Pfizer Ltd, Ramsgate Rd, Sandwich, Kent, CT13 9NJ 
Portuguese (Portugal), May 2004 
Study Protocol Ver. 1, 25-FEB-2021 
Page 51 of 62 
 
 
 
 
 
 
 
 
Concordo 
completa- 
mente 
Concordo 
moderada- 
mente 
Concordo 
ligeiramente 
Discordo 
ligeira- 
mente 
Discordo 
moderada- 
mente 
Discordo 
completa- 
mente 
1. Quando penso na minha vida 
sexual, sinto-me frustrado. 
2. Quando penso na minha vida 
sexual, sinto-me deprimido. 
3. Quando penso na minha vida 
sexual, sinto-me menos homen. 
4. Perdi confiança em mim mesmo 
como parceiro sexual. 
5. Quando penso na minha vida 
sexual, sinto-me ansioso. 
6. Quando penso na minha vida 
sexual, sinto-me zangado. 
7. Preocupo-me com o futuro da 
minha vida sexual. 
8. Quando penso na minha vida 
sexual, sinto-me embaraçado. 
9. Quando penso na minha vida 
sexual, sinto-me culpado. 
10. Quando penso na minha vida 
sexual, preocupo-me que a minha 
parceira se sinta magoada ou 
rejeitada. 
11. Quando penso na minha vida 
sexual, sinto-me como se tivesse 
perdido algo. 
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3. SQOL-F 
 
 
 
 
 
QUESTIONARIO SOBRE A QUALIDADE DE VIDA SEXUAL • FEMININO © 
{SQol-F) 
 
 
Este questionario e composto por um conjunto de afirma96es, cada uma sobre os pensamentos e 
sentimentos que eventualmente tenha em relai;ao a sua vida sexual. A afirmai;ao pode referir-se 
tanto a aspectos positivos corrio negativos da sua vida sexual. Este questionario destina-se a todas 
as mulheres, independentemente da sua escolha sexual. 
 
 
Pedimos-lhe que classifique cada afirmai;ao de acordo com o quanto concorda ou discorda com a 
mesma, pondo um cfrculo a volta de urna das seis respostas possfveis. 
 
Ao responder a estas quest6es deve ter em conta as seguintes defini96es: 
 
 
Vida sexual: refere-se tanto as actividades sexuais fisicas como a relai;ao sexual emocional que tern 
com o seu companheiro. 
 
 
Actividade sexual: inclui qualquer actividade que possa resultar em estimula9ao ou prazer sexual, por 
exemplo, rela96es sexuais, carfcias, preliminares, masturba9ao (tanto auto-masturba9ao como o seu 
companheiro a masturba-la a si) e sexo oral (ou seja, o seu companheiro a fazer-lhe sexo oral). 
 
 
Normalmente a primeira resposta que lhe vem a cabei;a e a melhor; por isso, nao 
passe muito tempo com cada pergunta. 
 
Todas as suas respostas serao totalmente confidenciais 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
■ 
©1998, Pfizer Ltd, Ramsgate Rd, Sandwich, Kent, CT13 9NJ 
-
Draft 
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QUESTIONARIO SOBRE A QUALIDADE DE VIDA SEXUAL - FEMININO © (SQoL-F) 
D (1) Not Done 
1. Quando penso na minha vida 
sexual, e uma parte agradavel 
da minha vida 
 
2. Quando penso na minha vida 
sexual, sinto-me frustrada 
 
 
3. Quando penso na minha vida 
sexual, sinto-me deprimida 
 
 
 
4. Quando penso na minha vida 
sexual, sinto-me menos mulher 
 
 
 
5. Quando penso na minha vida 
sexual, sinto-me bem comigo 
pr6pria 
 
 
6. Perdi confianc;a em mim 
pr6pria como parceira sexual 
 
 
 
7. Quando penso na minha vida 
sexual, sinto-me ansiosa 
 
 
8. Quando penso na minha vida 
sexual, sinto-me zangada 
 
 
 
9. Quando penso na minha vida 
sexual, sinto-me pr6xima do 
meu companheiro 
■ 
©1998, Pfizer Ltd, Ramsgate Rd, Sandwich, Kent, CT13 9NJ 
-
Draft 
Concordo 
completa- 
mente 
Concordo 
moderada- 
mente 
Concordo 
ligeiramente 
Discordo 
ligeira- 
mente 
Discordo 
moderada- 
mente 
Discordo 
completa- 
mente 
Concordo 
cornpleta- 
mente 
Concordo 
moderada- 
mente 
Concordo 
ligeiramente 
Discordo 
ligeira- 
mente 
Discordo 
moderada- 
mente 
Discordo 
completa- 
mente 
Concordo 
completa- 
mente 
Concordo 
moderada- 
mente 
Concordo 
ligeiramente 
Discordo 
ligeira- 
mente 
Discordo 
moderada- 
mente 
Discordo 
completa- 
mente 
Concordo 
completa- 
mente 
Concordo 
moderada- 
mente 
Concordo 
ligeiramente 
Discordo 
ligeira- 
mente 
Discordo 
moderada- 
mente 
Discordo 
completa- 
mente 
Concordo 
completa- 
mente 
Concordo 
moderada- 
mente 
Concordo 
ligeiramente 
Discordo 
ligeira- 
mente 
Discordo 
moderada- 
mente 
Discordo 
completa- 
mente 
Concordo 
completa- 
mente 
Concordo 
moderada- 
mente 
Concordo 
ligeiramente 
Discordo 
ligeira- 
mente 
Discordo 
moderada- 
mente 
Discordo 
completa- 
mente 
Concordo 
completa- 
mente 
Concordo 
moderada- 
mente 
Concordo 
ligeiramente 
Discordo 
ligeira- 
mente 
Discordo 
moderada- 
mente 
Discordo 
completa- 
mente 
Concordo 
completa- 
mente 
Concordo 
moderada- 
mente 
Concordo 
ligeiramente 
Discordo 
ligeira- 
mente 
Discordo 
moderada- 
mente 
Discordo 
completa- 
mente 
Concordo 
completa- 
mente 
Concordo 
moderada- 
mente 
Concordo 
Iigeiramente 
Discordo 
ligeira- 
mente 
Discordo 
moderada- 
mente 
Discordo 
completa- 
mente 
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-
 
 
 
 
 
 
QUESTIONARIO SOBRE A QUALIDADE DE VIDA SEXUAL - FEMININO© (SQoL-F) 
 
10. Preocupo-me com o futuro da 
minha vida sexual 
 
 
11. Perdi o prazer na actividade 
sexual 
 
 
 
12. Quando penso na minha vida 
sexual, sinto-me embara9ada 
 
 
 
13. Quando penso na minha vida 
sexual, sinto que posso falar 
com o meu companheiro 
sobre assuntos sexuais 
 
14. Procuro evitar a actividade 
sexual 
 
 
 
15. Quando penso na minha vida 
sexual, sinto-me culpada 
 
 
 
16. Quando penso na minha vida 
sexual, preocupo-me que o 
meu companheiro se sinta 
magoado ou rejeitado 
 
17. Quando penso na minha vida 
sexual, sinto-me como se 
tivesse perdido algo 
 
18. Quando penso na minha vida 
sexual, estou satisfeita com a 
frequencia da actividade 
sexual 
■ 
©1998, Pfizer Ltd, Ramsgate Rd, Sandwich, Kent, CT13 9NJ 
 
 
 
 
 
 
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Study Protocol Ver. 1, 25-FEB-2021 
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4. SIBDQ  
QUESTIONÁRIO SOBRE A QUALIDADE DE VIDA NA 
DOENÇA INFLAMATÓRIA INTESTINAL (SIBDQ) 
 
 
Este questionário tem por objectivo avaliar como se tem sentido durante as últimas 2 
semanas. Perguntar-se-á quais são os seus sintomas como consequência da doença 
inflamatória intestinal, como se sente em geral e qual tem sido a sua disposição. 
 
 
1. 
Quantas vezes, durante as últimas 2 semanas, a sensação de fadiga ou cansaço e sentir-se 
enfraquecido têm sido para si um problema? Indique quantas vezes a fadiga ou o cansaço 
têm constituído para si um problema durante as últimas 2 semanas, escolhendo apenas uma 
resposta. 
 
1 SEMPRE 
2 QUASE SEMPRE 
3 UMA BOA PARTE DO TEMPO 
4 ALGUMAS VEZES 
5 POUCAS VEZES 
6 RARAMENTE 
7 NUNCA 
 
 
2. 
Quantas vezes, durante as últimas 2 semanas, teve de adiar ou desmarcar compromissos de 
ordem social devido ao problema intestinal? Assinale apenas uma resposta. 
 
1 SEMPRE 
2 QUASE SEMPRE 
3 UMA BOA PARTE DO TEMPO 
4 ALGUMAS VEZES 
5 POUCAS VEZES 
6 RARAMENTE 
7 NUNCA 
 
 
3. 
Qual o grau de dificuldade que teve, durante as últimas 2 semanas, em praticar desporto ou 
outras actividades de tempos livres que gostaria de ter realizado, em consequência do seu 
problema intestinal? Assinale apenas uma resposta. 
 
1 ENORME DIFICULDADE; ACTIVIDADES IMPOSSÍVEIS DE PRATICAR 
2 UMA GRANDE DIFICULDADE 
3 MUITA DIFICULDADE 
4 ALGUMA DIFICULDADE 
5 UM POUCO DE DIFICULDADE 
6 RARAMENTE SENTI DIFICULDADE 
7 SEM 
DIFICULDADE; 
O 
PROBLEMA 
INTESTINAL 
NÃO 
AFECTOU 
A 
ACTIVIDADE DESPORTIVA OU AS ACTIVIDADES DE TEMPOS LIVRES 
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4. 
Quantas vezes, durante as últimas 2 semanas, as dores no abdómen o perturbaram? 
Assinale apenas uma resposta. 
 
1 SEMPRE 
2 QUASE SEMPRE 
3 UMA BOA PARTE DO TEMPO 
4 ALGUMAS VEZES 
5 POUCAS VEZES 
6 RARAMENTE 
7 NUNCA 
 
 
5. 
Quantas vezes, durante as últimas 2 semanas, se sentiu deprimido ou desanimado? Assinale 
apenas uma resposta. 
 
1 SEMPRE 
2 QUASE SEMPRE 
3 UMA BOA PARTE DO TEMPO 
4 ALGUMAS VEZES 
5 POUCAS VEZES 
6 RARAMENTE 
7 NUNCA 
 
 
6. 
De um modo geral, quais os problemas que teve, durante as últimas 2 semanas, com a 
libertação de muitos gases intestinais? Assinale apenas uma resposta. 
 
1 ENORMES PROBLEMAS 
2 GRANDES PROBLEMAS 
3 BASTANTES PROBLEMAS 
4 ALGUNS PROBLEMAS 
5 POUCOS PROBLEMAS 
6 QUASE NENHUNS PROBLEMAS 
7 SEM PROBLEMAS 
 
 
7. 
De um modo geral, quais os problemas que teve, durante as últimas 2 semanas, para manter 
ou alcançar o peso desejado? Assinale apenas uma resposta. 
 
1 ENORMES PROBLEMAS 
2 GRANDES PROBLEMAS 
3 BASTANTES PROBLEMAS 
4 ALGUNS PROBLEMAS 
5 POUCOS PROBLEMAS 
6 QUASE NENHUNS PROBLEMAS 
7 SEM PROBLEMAS 
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Study Protocol Ver. 1, 25-FEB-2021 
Page 57 of 62 
 
 
 
 
 
 
8. 
Quantas vezes, durante as últimas 2 semanas, se sentiu descontraído e livre de tensão? 
Assinale apenas uma resposta. 
 
1 NUNCA 
2 RARAMENTE 
3 ALGUMAS VEZES 
4 UMA BOA PARTE DO TEMPO 
5 A MAIOR PARTE DO TEMPO 
6 QUASE SEMPRE 
7 SEMPRE 
 
 
9. 
Durante quanto tempo, nas últimas 2 semanas, sentiu a necessidade de ter de se deslocar à 
casa de banho apesar de ter os intestinos vazios? Assinale apenas uma resposta. 
 
1 SEMPRE 
2 QUASE SEMPRE 
3 UMA BOA PARTE DO TEMPO 
4 ALGUMAS VEZES 
5 POUCAS VEZES 
6 RARAMENTE 
7 NUNCA 
 
 
10. 
Durante quanto tempo, nas últimas 2 semanas, se sentiu irritado em consequência do seu 
problema intestinal? Assinale apenas uma resposta. 
 
1 SEMPRE 
2 QUASE SEMPRE 
3 UMA BOA PARTE DO TEMPO 
4 ALGUMAS VEZES 
5 POUCAS VEZES 
6 RARAMENTE 
7 NUNCA 
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5. WPAI 
 
 
 
 
 
 
 
WPAI:Fístulas Perianais Complexas 
Página 1 de 2 
Questionário sobre a Produtividade no Trabalho e Incapacidade de 
Realizar Actividades: 
Fístulas Perianais Complexas, V2.0 (WPAI:Fístulas Perianais 
Complexas) 
As perguntas seguintes referem-se ao efeito da(s) sua(s) fístula(s) perianal(ais) na sua 
capacidade de trabalhar e de realizar atividades normais. Preencha os espaços em branco ou 
assinale com um círculo um número, conforme indicado. 
1. Está empregado no momento (recebe salário)?  
NÃO 
 
SIM 
Se NÃO, assinale “NÃO” e passe para a pergunta 6. 
As próximas perguntas referem-se aos últimos sete dias, sem incluir o dia de hoje. 
2. Durante os últimos sete dias, quantas horas de trabalho perdeu devido aos problemas 
associados com a(s) sua(s) fístula(s) perianal(ais)? Inclua as horas perdidas com dias não 
trabalhados por estar doente, as vezes em que chegou mais tarde ao trabalho, que saiu mais 
cedo, etc., por causa da(s) fístula(s) perianal(ais). Não inclua as vezes que faltou ao trabalho 
para participar neste estudo. 
 
HORAS 
3. Durante os últimos sete dias, quantas horas de trabalho perdeu por qualquer outro motivo, 
como férias, feriados ou para participar neste estudo? 
 
HORAS 
4. Durante os últimos sete dias, quantas horas trabalhou efetivamente? 
 
HORAS (Se “0”, passe para a pergunta 6.) 
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5. Durante os últimos sete dias, até que ponto a(s) sua(s) fístula(s) perianal(ais) afetou(aram) a 
sua produtividade enquanto estava a trabalhar? 
 
Considere os dias em que ficou limitado em relação à quantidade ou ao tipo de trabalho que 
pôde realizar, os dias em que realizou muito menos do que gostaria ou os dias em que não 
conseguiu trabalhar de forma tão cuidadosa como o normal. Se a(s) fístula(s) perianal(ais) 
apenas afetou(aram) um pouco o seu trabalho, escolha um número baixo. Escolha um número 
alto se a(s) fístula(s) perianal(ais) afetou(aram) muito o seu trabalho. 
 
 
 
 
 
A(s) fístula(s) 
Considere apenas até que ponto a(s) fístula(s) perianal(ais) 
afetou(aram) a sua produtividade enquanto estava a trabalhar. 
 
A(s) fístulas(s) 
perianal(ais) não 
 
 perianal(ais) 
teve(tiveram) 
nenhum efeito 
sobre o meu 
trabalho 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 impediu-me(impedira 
m-me) 
completamente de 
realizar o meu 
trabalho 
COLOQUE UM CÍRCULO EM TORNO DE UM NÚMERO 
 
 
6. Durante os últimos sete dias, até que ponto a(s) fístula(s) perianal(ais) afetou(aram) a sua 
capacidade de realizar as suas atividades diárias normais não relacionadas com o trabalho? 
 
Atividades normais significam aquilo que faz habitualmente, como tarefas domésticas, fazer 
compras, cuidar das crianças, fazer exercício, estudar, etc. Considere as vezes em que ficou 
limitado em relação à quantidade ou ao tipo de atividades que pôde realizar e as vezes em que 
fez menos do que gostaria. Se a(s) fístula(s) perianal(ais) apenas afetou(aram) um pouco as 
suas atividades normais, escolha um número baixo. Escolha um número alto se a(s) fístula(s) 
perianal(ais) afetou(aram) muito as suas atividades. 
 
Considere apenas até que ponto a(s) fístula(s) perianal(ais) afetou(aram) a sua capacidade 
de realizar as suas atividades diárias normais, não relacionadas com o trabalho. 
A(s) fístula(s) 
perianal(ais) não 
A(s) fístula(s) 
 
 perianal(ais) 
teve(tiveram) 
nenhum efeito 
sobre as minhas 
atividades diárias 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 impediu-me 
(impediram-me) 
completamente de 
realizar as minhas 
atividades diárias 
COLOQUE UM CÍRCULO EM TORNO DE UM NÚMERO 
 
 
 
 
 
 
 
 
 
 
 
 
WPAI:Fístulas Perianais Complexas 
Página 2 de 2 
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6. Wexner score 
 
 
Escala de classificação de continência 
 
 
Tipo de 
 
Frequência 
 
 
incontinência 
Nunca 
Raramente 
Algumas vezes 
Frequentemente Sempre 
Sólida 
0 
1 
2 
3 
4 
Liquida 
0 
1 
2 
3 
4 
Gás 
0 
1 
2 
3 
4 
Uso de penso 
0 
1 
2 
3 
4 
Alteração do 
0 
1 
2 
3 
4 
 estilo de vida 
 
0-perfeito 
20-incontinência total 
 
Nunca=0 
Raramente=<1/mês 
Algumas vezes=<1/semana,>1/mês 
Frequentemente=<1/dia,>1/semana 
Sempre=>1/dia 
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Study Protocol Ver. 1, 25-FEB-2021 
Page 61 of 62 
 
 
7. PDAI 
Índice de Atividade da Doença de Crohn Perianal (Perianal Crohn’s Disease Activity Index, PDAI) 
Instruções para Índice de Atividade de Doença de Crohn Perianal (PDAI) 
A PDAI é uma escala que avalia a gravidade atual da doença de Crohn que envolve a área perianal. 
 
Os itens 1 a 3 são colocados diretamente ao doente. É pedido ao doente que "Por favor considere os 
seus sintomas perianais e não o estado de saúde geral ou outros sintomas relacionados com a doença 
de Crohn para o seguinte": 
 
 
Ao fazer a pergunta relativa à descarga perianal 
Para o item n.º 1 
Teve qualquer descarga da área perianal na última semana devido à qual tenha sujado a roupa 
interior ou por causa da qual tivesse de utilizar um penso para absorver? Podem ser-lhes apresentadas 
ou lidas as cinco opções de resposta. 
 
 
1. Atividade de doença perianal 
Descarga 
0 
Sem descarga 
1 
Descarga mínima de muco 
2 
Descarga moderada de muco ou purulenta 
3 
Descarga substancial 
4 
Mancha fecal muito evidente 
 
 
Para o item n.º 2, ao perguntar sobre a dor, deve relacionar-se especificamente com a dor perianal. 
 
Teve qualquer dor perianal e/ou restrição das suas atividades devido à dor à volta da zona 
perianal na última semana? Podem ser apresentadas ou lidas ao participante as cinco opções de 
resposta. 
 
 
2. Dor/restrição de atividades 
 
0 
Sem dor/sem restrição de atividades 
1 
Desconforto ligeiro, sem restrição 
2 
Desconforto moderado, com alguma limitação de atividade 
3 
Desconforto acentuado, limitação acentuada 
4 
Dor grave, limitação grave 
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Study Protocol Ver. 1, 25-FEB-2021 
Page 62 of 62 
 
 
 
 
Para o item n.º 3, deverá relacionar-se especificamente com a doença de Crohn perianal 
 
Teve alguma restrição na sua atividade sexual devido à sua doença de Crohn perianal na última 
semana? Podem ser apresentadas ou lidas ao participante as cinco opções de resposta. 
 
3. Restrição da atividade sexual 
 
0 
Sem restrição da atividade sexual 
1 
Restrição ligeira da atividade sexual 
2 
Limitação moderada da atividade sexual 
3 
Limitação acentuada da atividade sexual 
4 
Incapaz de se envolver em atividade sexual 
 
 
Os itens 4 e 5 devem ser preenchidos pelo médico prestador de cuidados de saúde após exame da área 
perianal. 
 
4. Tipo de doença perianal 
 
0 
Sem doença perianal/pólipos cutâneos 
1 
Fissura anal ou laceração da mucosa 
2 
<3 fístulas perianais 
3 
≥3 fístulas perianais 
4 
Ulceração ou fístulas do esfíncter anal com enfraquecimento significativo da pele 
 
5. Grau de endurecimento 
 
0 
Sem endurecimento 
1 
Endurecimento ligeiro 
2 
Endurecimento moderado 
3 
Endurecimento substancial 
4 
Flutuação/abcesso muito evidente 
 
 
Pontuação total:  
(soma das respostas 0-20) 
 
A pontuação PDAI é a soma das respostas para todos os 5 itens (intervalo 0-20); uma pontuação mais 
alta indica doença e restrição mais grave. Os dados sobre a validação do índice podem ser consultados 
no artigo abaixo: 
 
E. J. Irvine McMaster IBD Study Group. Usual therapy improves perianal Crohn's disease as measured 
by a new disease activity index. J Clin Gastroenterol. 1995 Jan;20(1):27-32 PMID: 7884173 
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