TREATgermany: German National Clinical Registry: Treatment and Medical Care of Patients With Moderate-to-severe Atopic Dermatitis
Conditions: Moderate-to-severe Atopic Dermatitis
Sponsor: Technische Universität Dresden

German National Clinical registry TREATgermany 
Prof. Dr. J. Schmitt, Faculty of Medicine Carl Gustav Carus TU Dresden 
1 
 
Study protocol 
 
 
 German National Clinical registry: Treatment 
and medical care of patients with moderate-to-
severe Atopic Dermatitis  
 
 
TREATgermany 
Version 4.3, September 2021 
English Version 
 
Project management 
 
Prof. Dr. med. Jochen Schmitt, MPH  
(coordinating study lead) 
Center for Evidence-Based Healthcare (ZEGV), 
Faculty of Medicine Carl Gustav Carus TU Dresden, Germany 
 
Prof. Dr. med. Thomas Werfel 
Division of Immunodermatology and Allergy Research, Department of Dermatology and  
Allergy Hannover Medical School, Germany 
 
Prof Dr. med. Stephan Weidinger 
Department of Dermatology and Allergy, University Hospital Schleswig-Holstein, Campus 
Kiel, Germany 
 
In kooperation with the German Dermatological Society 
 
CONFIDENTIAL 
The informations in this study protocol must be kept strictly confidential. They only serves to inform the study 
physician, study personal, the ethics committee, the authorities and patients. This study protocol may not be 
disclosed to third parties without the consent of the study authorities.

German National Clinical registry TREATgermany 
Prof. Dr. J. Schmitt, Faculty of Medicine Carl Gustav Carus TU Dresden 
2 
 
CONTENTS 
 
List of abbreviations 
4 
Participants and institutions 
5 
Synopsis (german) 
7 
Synopsis (english) 
16 
Visit plan 
22 
1. INTRODUCTION 
24 
1.1 
Atopic dermatitis 
24 
1.2 
Treatment of atopic dermatitis 
25 
1.3 
The TREAZeczema registry 
25 
1.4 
The European registry network TREAT 
26 
2 
STUDY OBJECTIVES 
27 
3 
STUDY DESCRIPTION 
28 
3.1 
Study design 
28 
3.2 
Institutions involved 
28 
3.3 
Scientific-strategic advisory board 
28 
4 
PATIENT POPULATION 
30 
4.1 
Number of patients 
30 
4.2 
Inclusion and exclusion criteria 
30 
5 
STUDY DESIGN 
31 
5.1 
Selection of patients, round 1 (baseline) 
31 
5.2 
Follow-up visits 
32 
5.3 
Interim visits 
32 
5.4 
Withdrawal of patients and drop-outs 
32 
5.5 
Optional module „Biobanking and Bioanalytics“ 
32 
6 
DOCUMENTATION / DATA MANAGEMENT 
34 
6.1 
Data entry forms 
34 
6.2 
Assessment tools 
36 
6.3 
Adverse drug reactions (ADR) and regulations applying to pharmacovigilance 
40 
7 
STATISTICS 
42 
8 
REPORTING 
43 
9 
ETHICAL, LEGAL AND ADMINISTRATIVE ASPECTS 
43 
10 
SIGNATURES 
45 
11 
REFERENCES 
46 

German National Clinical registry TREATgermany 
Prof. Dr. J. Schmitt, Faculty of Medicine Carl Gustav Carus TU Dresden 
3 
 
Appendix 
Appendix 1: U.K. Working Party’s Diagnostic Criteria (1994) 
 
Appendix 2: SCORAD-Index 
 
Appendix 3: Dermatology Life Quality Index (DLQI) 
 
Appendix 4: Investigator’s Global Assessment (IGA)/Patient’s Global Assessment (PGA)  
Appendix 5: Work Limitations Questionnaire (WLQ) 
 
Appendix 6: EuroQoL (EQ-5D) 
 
Appendix 7: Patient-oriented eczema measure (POEM) 
 
Appendix 8: Center for Epidemiological Studies – Depression Scale (CES-D) 
 
Appendix 9: Patient Benefit Index (PBI) 
Appendix 10: Fatigue Severity Scale (FSS) 
Appendix 11: Eczema Area Severity Index (EASI) 
Appendix 12: Children's Dermatology Life Quality Index (cDLQI) 
Appendix 13: Patient Oriented Eczema Measure (POEM) for children 
Appendix 14: Strengths and Difficulties Questionnaire (SDQ) 
Appendix 15: KINDL 
Appendix 16: Children's Sleep Habits Questionnaire (CSHQ) 
Appendix 17: Sleep Self Report – DE (SSR-DE, for children from 7-12 years) 
Appendix 18: Mood and Feelings Questionnaire (MFQ) at the example of adolescence 
Appendix 19: SOP “Publikationsvereinbarung und Datenanforderung” 
 
 

German National Clinical registry TREATgermany 
Prof. Dr. J. Schmitt, Faculty of Medicine Carl Gustav Carus TU Dresden 
4 
 
List of abbreviations 
 
AD 
Atopic Dermatitis 
ADR 
Adverse Drug Reaction 
BSA 
Body Surface Area 
cDLQL 
Children's Dermatology Life Quality Index 
CES-D 
Center for Epidemiological Studies – Depression  
CSHQ 
Children's Sleep Habits Questionnaire 
DLQI 
Dermatology Life Quality Index 
EASI 
Eczema Area Severity Index 
EQ-5D  
EuroQoL 
FSS 
Fatigue Severity Scale 
IGA  
Investigator Global Assessment 
IVIG 
Intravenous immune globulin 
MFQ 
Mood and Feelings Questionnaire 
MTX 
Methotrexat 
NRS 
Numeric Rating Scale 
oSCORAD  
objective SCORAD 
PGA  
Patient Global Assessment 
POEM 
Patient-oriented eczema measure 
QALY 
Quality adjusted life years 
QoL 
Quality of Life 
SCORAD 
Severity Scoring Of Atopic Dermatitis  
SDQ 
Strengths and Difficulties Questionnaire 
SSR 
Sleep Self Report 
VAS 
Visuelle Analogue Scale 
WLQ 
Work Limitation Questionnaire  
 

German National Clinical registry TREATgermany 
Prof. Dr. J. Schmitt, Faculty of Medicine Carl Gustav Carus TU Dresden 
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Participants and institutions 
 
 
Project management: 
Prof. Dr. med. Jochen Schmitt, MPH  
(coordinating study lead) 
Center for Evidence-Based Healthcare (ZEGV), 
Faculty of Medicine Carl Gustav Carus TU 
Dresden, Germany 
 
Prof. Dr. med. Thomas Werfel 
Division of Immunodermatology and Allergy 
Research, Department of Dermatology and  
Allergy Hannover Medical School, Germany 
 
Prof Dr. med. Stephan Weidinger 
Department of Dermatology and Allergy, University 
Hospital Schleswig-Holstein, Campus Kiel, 
Germany 
Study coordination: 
Dr. Eva Haufe 
Center for Evidence-Based Healthcare (ZEGV), 
Faculty of Medicine Carl Gustav Carus TU 
Dresden, Germany 
Dermatological center support 
Dr. med. Annice Heratizadeh 
Department of Dermatology and  
Allergy Hannover Medical School, Germany 
 
Dr. med. Susanne Abraham 
Clinic for Dermatology, University Allergy Center, 
Universiy Hospital Carl Gustav Carus TU Dresden, 
Germany 
Center support,  
Optional Module Bioanalytics 
Inken Harder M.Sc. 
Department of Dermatology and Allergy, University 
Hospital Schleswig-Holstein, Campus Kiel, 
Germany 
Documentation / Quality management: 
Center for Evidence-Based Healthcare (ZEGV), 
Faculty of Medicine Carl Gustav Carus TU 
Dresden, Germany 
 
Biometrics/ Statistics: 
Center for Evidence-Based Healthcare (ZEGV), 
Faculty of Medicine Carl Gustav Carus TU 
Dresden, Germany 
 
Responsible authority for koordination, 
quality assurance, data management und 
data analysis: 
Center for Evidence-Based Healthcare (ZEGV), 
Faculty of Medicine Carl Gustav Carus TU 
Dresden, Germany 
 
Survey locations: 
 
Dermatological clinics and practices in 
Germany, pediatric practices specialized in 
allergology / atopic dermatitis 
Scientific-strategic advisory board: 
 
The scientific-strategic advisory board 
consists of  at least 8 voting members and is 
to contribute scientific, clinical, 
methodological and strategic expertise to the 
Members with voting rights: 
 
Prof. Dr. med. Andreas Wollenberg, LMU Munich 
(ETFAD) 
 
 

German National Clinical registry TREATgermany 
Prof. Dr. J. Schmitt, Faculty of Medicine Carl Gustav Carus TU Dresden 
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register. Unanimous recommendations of the 
Expert Advisory Board are sought, otherwise 
a simple majority applies. 
 
 
Sponsors of the Registry (e.g. 
pharmaceutical manufacturers, foundations, 
etc.) are granted the right to nominate up to 
2 guests for the advisory board who have an 
advisory function but are not entitled to vote. 
The nomination of additional persons with 
guest status is reserved for the study 
directors. 
Prof. Carsten Flohr (King‘s College London)  
 
Prof. Dr. Christian Apfelbacher (University 
Magdeburg) 
 
Two representative of the German Dermatological 
Society (Deutschen Dermatologische Gesellschaft 
(DDG)). 
 
One representative of the Professional Association 
of German Dermatologists (Berufsverband der 
Deutschen Dermatologen (BVDD)). 
 
Two representatives of the German Society for 
Allergology and Clinical Immunology (DGAKI) 
 
 
  
 

German National Clinical registry TREATgermany 
Prof. Dr. J. Schmitt, Faculty of Medicine Carl Gustav Carus TU Dresden 
16 
 
Synopsis (english)  
 
Title 
German National Clinical registry: Treatment and medical care of 
patients with moderate-to-severe Atopic Dermatitis. 
Acronym 
TREATgermany 
Study lead 
Prof. Dr. Jochen Schmitt (Dresden) (coordinating study lead) 
Prof. Dr. Thomas Werfel (Hannover) 
Prof. Dr. Stephan Weidinger (Kiel) 
Study design 
Prospective multicenter registry for patients with moderate-to-severe 
atopic dermatitis  
Background 
- Atopic dermatitis (AD) constitutes significant burden to patients, 
families, and healthcare systems. [1-3]  
- About 60% of all patients with AD are adults. [4] However, the 
prevalence and incidence is significantly higher in childhood and 
adolescence. 
- Some children, adolescents and adults with moderate-to-severe 
AD cannot be sufficiently controlled with topical treatments alone 
and require intermittent or continuous treatment with systemic 
immunomodulating therapies or UV-therapy. [5] 
- Systematic reviews and meta-analyses [6-9] indicate that 
although several different interventions for moderate-to-severe 
AD have been investigated in clinical trials, therapy 
recommendations are currently only possible for dupilumab (from 
6 years of age) [10-12], Baricitinib (from 18 years of age) [13, 14], 
and for the short-term use of cyclosporine A. 
- Methodological limitations in the majority of trials on conventional 
immunosuppressive therapies, such as the use of non-validated 
outcomes that are not relevant to patients, prevent evidence-
based clinical decision making. [15-17]  
- Pharmaceutical treatment of patients suffering from AD is diverse 
and frequently not in line with the current guidelines (for example 
S2-guideline in Germany). [18] 
- Systemic antiinflammatory and immunemodulatory therapies 
include several conventional immunosuppressive therapies such 
as glucocorticosteroids, cyclosporine A (CSA), methotrexate 
(MTX), or azathioprine (AZA). [6-9] Further, dupilumab became 
the first biologic medication approved for the treatment of 
moderate-to-severe AD for adult patients in 2018, in 2019 the 
approval was expanded for adolescents (from 12 years of age), 
and in 2020 for children (from 6 years of age). [10-12] Since 
2020, baricitinib has also been approved for the treatment of 
moderate-to-severe AD for adult patients. [13, 14] In 2021, 
tralokinumab for adults [19, 20] and upadacitinib from the age of 
12 years [21, 22] were also approved for the treatment of 
moderat-to-severe AD.  
- Large head-to-head trials are missing so that long-term 
effectiveness of systemic interventions for moderate-to-severe 
AD is speculative. [6]  
- In this situation, clincial registries can provide valuable 
information for evidence-based clinical decision making. 
 

German National Clinical registry TREATgermany 
Prof. Dr. J. Schmitt, Faculty of Medicine Carl Gustav Carus TU Dresden 
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Background (cont) 
The German AD registry 
- 
In 2011, the German Registry “TREATeczema” was initiated by 
Prof. Schmitt (Dredsen) and Prof. Werfel (Hannover) to 
investigate treatment and medical care of adult patients with 
severe AD in Germany in routine care.  
- 
TREATeczema stimulated initiatives in other European countries  
that currently plan to establish the prospective investigation of 
clinical cohorts with AD. 
- 
The experiences with the German AD-registry from the past 4 
years also highlight the necessity for some important 
modifications to increase the acceptance, implications, and 
recruitement in clinical care.  
- 
These modifications include:   
o Expansion to patients with moderate-to-severe AD, as 
these patients are also potential candidates for systemic 
treatment.  
o Observation for more than 36 months.  
o Separation of the coordinating register center 
(responsible for data management, quality assurance, 
data storage and data analysis) from the recuiting 
centers.  
o Increase of the acceptance of the registry for patients 
and physicians by offering financial compensation and 
electronic data collection software. 
 
Extension of TREATgermany to children and adolescents is 
necessary as  
- 
moderate-to-severe AD is frequent in this age group, but the 
effectiveness of existing topical and systemic agents in the 
routine care setting on clinical severity, patient-reported 
outcomes, and the course of AD and associated atopic and non-
atopic comorbidities over time is still poorly understood  
- 
it is unclear how many children and adolescents cannot be 
effectively controlled with the avoidance of trigger factors, 
patient education, and topical anti-inflammatory treatment alone 
(i.e. how many children would require systemic therapy given 
safe and effective treatment is approved) 
- 
innovative agents will become available for these age groups 
within the next years and reference data will be necessary to 
evaluate their effectiveness and indication criteria 
- 
adequate evidence regarding patient needs in children and 
adolescents with moderate-to-severe AD is urgently needed to 
provide value-based healthcare for this vulnerable patient group 
- 
Best-practice models of transition from adolescent to adult care 
of patients with moderate-to-severe AD do not exist yet, but 
constitute a prerequisite for the establishment of efficient patient 
care 
 
- 
The different European AD-registry initiatives also require the 
coordination in terms of data assessment to enable pooled 
international comparisons. Based on these grounds the 
European registry network (TREAT) was initiated. It is lead by 
Prof. Schmitt, Prof. Flohr (UK), Prof. Spuls (Netherlands), PD Dr. 
Apfelbacher (Magdeburg, Germany) and Prof. Irvine (Ireland). 
The contributing national registries remain formally independent.  
 

German National Clinical registry TREATgermany 
Prof. Dr. J. Schmitt, Faculty of Medicine Carl Gustav Carus TU Dresden 
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- 
TREATgermany emerges from the previous German AD-
registry TREATeczema. It includes all the necessary 
modifications outlined above and is part of the European registry 
family TREAT.  
 
Objectives 
 
Establishment of a national evidence-based clinical registry and 
research network with the following objectives: 
  
- Characterization of medical care and pharmaceutical therapies 
adults suffering from moderate-to-severe AD. The perspective of the 
patient (utility, treatment goals, quality of life, and treatment 
satisfaction), sequence of treatments, and change of treatments will 
be a primary focus.  
 
- Investigation of comparative effectiveness, tolerability and safety of 
systemic therapies for moderate-to-severe AD. 
 
- Developement of a platform for further investigations, such as 
pragmatic clinical trials, epidemiologic studies, outcomes research, 
immunologic and molecular research (given approval of responsible 
ethics commission). 
  
Study sites: 
 
Coordinating register center responsible for data management, 
quality assurance, data storage and data analysis: ZEGV Dresden   
 
Recruitment sites: All dermatological hospitals, outpatient 
dermatologists, and general physicians with focus on AD in 
Germany are invited to participate as recruitment sites.  
 
We aim to involve at least 40 recruitment sites in TREATgermany 
for adult patients and 30 recruitment sites for children and 
adolescents. The enrolment of children/adolescents and adults in a 
centre is possible. 
 
The protagonists of TREATgermany and the German national AD 
patient education network AGNES “Arbeitsgemeinschaft 
Neurodermitisschulung” cooperate very well. AGNES includes eight 
academies that are responsible for the standardized education of 
dermatologists and pediatricians, nurses, nutritionists and 
psychologists. These professionals form training teams that are 
active in 120 education centers in Germany. In the past year, about 
3,000 patients (children, adolescents and parents) were 
successfully trained in self-management, coping and treatment of 
AD according to the AGNES curriculum.   
The use of the well established, preexisting AGNES network for 
recruitment and follow up of children and adolescents with 
moderate-to-severe AD for inclusion in TREATgermany will ensure 
high feasibility, quality, and representativeness of recruitment into 
the registry.  
  
 
Number of patients 
included: 
Within the first 6 years we aim to include at least 800 adult patients 
with follow-up of at least 36 Months and up to 2025 600 
children/adolescents with follow-up of 3 years in the registry. 

German National Clinical registry TREATgermany 
Prof. Dr. J. Schmitt, Faculty of Medicine Carl Gustav Carus TU Dresden 
19 
 
Inclusion criteria: 
- AD according to the UK working party diagnostic criteria [23, 24]  
- Moderate-to-severe AD 
o objective SCORAD > 20 [25]  or 
o currently antiinflammatory systemic treatment for AD 
or 
o Z.n. antiinflammatory systemic treatment for AD 
within past 24 months 
 
Patients who have been enrolled into the previous AD-registry 
TREATeczema may be enrolled into TREATgermany following 
informed consent if they meet the above inclusion criteria.  
 
Study procedures  
 
- No study related intervention will be performed 
- Included patients will be prospectively followed for at least 24 
months. A maximum duration of follow-up is not intended.  
- During the observation period standardized study visits are 
performed to prospectively document patient characteristics, 
clinical data, patient-reported outcomes, physicians‘ reasons for 
treatment decisions, and satisfaction with treatment.  
- The first study visit is scheduled at patient inclusion (Baseline-
visite; V1). The second and third study visit are scheduled 3 and 
6 months after baseline, respectively. (V2 after 3 months, V3 after 
6 months). Thereafter, study visits are scheduled after 3 months 
(if a new systemic treatment was initiated) or after 6 months (in 
case no new systemic treatment was prescribed). 
- 
Adolescent patients who reach the age of 18 years will be 
followed through transition of care into adulthood after informed 
consent and further followed through the adult patient part of 
TREATgermany. 
 
Duration 
- TREATgermany for adults: follow up until 01/2023 
- TREATgermany for children/adolescents: 01/2020 to 12/2025 

German National Clinical registry TREATgermany 
Prof. Dr. J. Schmitt, Faculty of Medicine Carl Gustav Carus TU Dresden 
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Data assessment  
- Prospective electronic documentation of disease course and 
severity, medical care and pharmaceutical treatment of AD. 
- Pseudomized data will be stored at the registry center (ZEGV 
Dresden). 
- Completion patient and physician report form by paper and pencil 
will be possible upon request. In this case the completed study 
forms will be sent to the ZEGV Dresden.  
- Study assessments include: 
- 
A physician report form to document patient history and 
clinical parameters such as the objective severity of clinical 
signs, affected body regions, physician’s global assessment 
of disease severity, course of disease and medical treatment 
of AD including adverse events. 
- 
Important comorbidities are recorded in the case of inclusion 
and change, sociodemographic parameters in the case of 
inclusion and at biennial intervals.A patient report from to 
assess important subjective parameters, patient reported 
outcomes such as symptoms, quality of life, treatment 
satisfaction, patient’s assessment of global disease severity 
including %BSA, totally/partial well-controlled weeks, 
sickness absence due to AD and visits to healthcare 
professionals. 
- 
A customized patient report for children/adolescents to 
assess important subjective parameters, patient-/caregiver-
reported outcomes such as AD symptoms, quality of life, 
sleeping disorders, treatment satisfaction, patient’s 
assessment of global disease severity, totally/partial well-
controlled weeks, drug adherence, days absent at school, 
mental health problems (Strengths and Difficulties 
Questionnaire), AD family impact, parental work limitations 
and absenteeism due to child’s AD, visits to healthcare 
professionals.  
 
 
- Data from patients who have been previously enrolled in 
TREATeczema (about 80 patients) may be transferred into 
TREATgermany following informed consent. 
  
- 
Participation in the optional Biospecimen Database, 
Biorepository and Molecular Analysis requires separate 
informed consent. 
  

German National Clinical registry TREATgermany 
Prof. Dr. J. Schmitt, Faculty of Medicine Carl Gustav Carus TU Dresden 
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Outcomes: 
Target parameters to evaluate the effectiveness of AD treatment 
include according to the recommendations of the HOME initiative 
[17, 26, 27]: 
- 
objective clinical severity (EASI, oSCORAD) [25, 28] 
- 
disease symptoms (POEM, POEM for children) [29], severity 
of pruritus and sleeping problems (VAS) [30] 
- 
flares and level of disease control over time [31]  
- 
health-related quality of life (DLQI, cDLQI) [32]  
 
Adverse events and reasons for withdrawals will be documented for 
both adults and children and adolescents by recruiting sites.  
  
Patient/caregiver and physician treatment satisfaction and 
physicians’ reasons for the choice of specific interventions will be 
assessed.  
 
Data analysis 
Descriptive and exploratory data analyses will be performed at least 
once per year by the ZEGV Dresden.  
 
 
Recruiting sites will receive aggregated annual results from all 
patients included in the registry and all patients recruited at their 
recruitment site.  
 
Ethics and legal aspects: The study will be conducted in consistency with the declaration of 
Helsinki, data protection laws, and professional regulations.  
 
Prerequirement for study initiation is approval by the ethics 
commission of the Medical Faculty Carl Gustav Carus Dresden and 
the ethics commissions of the participating recruitment sites. 
 
Inclusion of patients is only possible following informed consent.  
 

German National Clinical registry TREATgermany 
Prof. Dr. J. Schmitt, Faculty of Medicine Carl Gustav Carus TU Dresden 
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Visit plan 
 
Visit 
 
V1 
 
Baseline 
 
V2 
 
3 months 
after  
baseline 
V3  
 
6 months 
after  
baseline 
V4-n 
 
At intervals 
of 3 or 6 
months* 
Time frame 
 
±2 weeks 
±2 weeks 
±2 weeks 
Clarification / Declaration of consent 
X 
 
 
 
Inclusion / exclusion criteria 
X 
 
 
 
Physician questionnaire 
Demographic information 
X 
 
 
 
Anamnesis/ medical history 
X 
X 
X 
X 
Physical examination 
X 
X 
X 
X 
Therapy (prescribed / actual) 
X 
X 
X 
X 
Clinical signs (obj. SCORAD and EASI) 
X 
X 
X 
X 
Affected parts of the body 
X 
X 
X 
X 
Investigator’s Global Assessment (IGA) 
X 
X 
X 
X 
Reasons for therapy choice 
X 
X 
X 
X 
Physician satisfaction with treatment (VAS) 
X 
X 
X 
X 
Adverse drug reactions (AE/SAE) 
X 
X 
X 
X 
Optional add-on module Bioanalytics (after 
prior separate consent) 
X 
(X)$ 
(X)$ 
(X)$ 
Patient questionnaire 
Compliance with atopic dermatits treatment 
 
 
 
 
Patient’s Global Assessment (PGA)  
X 
X 
X 
X 
Dermatology Life Quality Index (DLQI, 
cDLQI) 
X 
X 
X 
X 
Symptoms of atopic dermatitis (POEM, 
POEM for children, NRS pruritus, pain and 
sleep disturbance) 
X 
X 
X 
X 
Center for Epidemiological Studies – 
Depression Scale (CES-D) 
X 
X 
X 
X 
Strengths and Difficulties Questionnaire for 
Children (SDQ2-4, SDQ4-17, SDQ11-17 
(self-report)) 
X 
X 
X 
X 
Children's Sleep Habits Questionnaire 
(CSHQ-DE) 
X 
X 
X 
X 
Fatigue (FSS) 
X 
X 
X 
X 

German National Clinical registry TREATgermany 
Prof. Dr. J. Schmitt, Faculty of Medicine Carl Gustav Carus TU Dresden 
23 
 
Work Limitations Questionnaire (WLQ) / 
School Life Quality (as part of the KINDL) 
X 
X 
X 
X 
Sick leave due to atopic dermatitis/ receiving 
medical treatment 
X 
X 
X 
X 
School sick leave / parents’ sick leave due to 
atopic dermatitis/receicing medial treatment 
X 
X 
X 
X 
Benefit / Aim (PBI) 
X 
X 
X 
X 
Generic quality of life EuroQoL (EQ-5D) / 
KINDL for children and adolescents 
X 
X 
X 
X 
Patient satisfaction (NRS) 
X 
X 
X 
X 
Mood and Feelings Questionnaire (MFQ) 
self-reported for adolescents / parents‘ report 
X 
X 
X 
X 
Sleep Self Report (SSR-DE) 
X 
X 
X 
X 
Recap of atopic eczema (RECAP) 
X 
X 
X 
X 
 
* 3 months between visits if a new systemic therapy has been initiated, otherwise 6 months  
$ for the change of the anti-inflammatory system therapy of atopic dermatitis 
 

German National Clinical registry TREATgermany 
Prof. Dr. J. Schmitt, Faculty of Medicine Carl Gustav Carus TU Dresden 
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1. INTRODUCTION 
 
1.1 Atopic dermatitis 
Atopic dermatitis (synonyms: atopic eczema) is a chronic or chronic-relapsing, non-contagious 
inflammatory skin disease. [3] The UK Working Party definition of atopic dermatitis (see 
Appendix 1)  is itchy skin plus three or more of the following features: (i) onset under the age 
of 2 y; (ii) a history of flexural involvement; (iii) a history of asthma or hayfever (or a history of 
atopic disease in siblings and parents if the child is under 4 y); (iv) a history of generally dry 
skin in the last year; and (v) visible flexural dermatitis. [33] The prevalence of atopic dermatitis 
in western industrialized nations is up to 10-20% in infancy and 5-10% in adulthood. [34-37]  
 
Despite the greater prevalence in infancy, approximately 60% of all patients with atopic 
dermatitis are adults. [4] Among adults under dermatological care atopic dermatitis is the fourth 
most common diagnosis. [4] About 60% of the adults with atopic dermatitis are in outpatient 
dermatological care. About 40% of the patients are treated by general practitioners, and the 
implementation of a consultation fee has led to a further drop of the percentage of patients in 
dermatological care. [38] Despite the high prevalence and the socio-medical significance, 
medical care patterns for atopic dermatitis in adulthood are insufficiently known.  
 
In a large number of patients signs and symptoms of the disease cause a profound and 
multifaceted impact on the quality of life and professional performance. [39-41] Physicians 
often misjudge the treatment goals of their patients with atopic dermatitis. [42] Due to allergic 
[43], mental [44, 45], and somatic comorbidities [46], the intractable itch, and the associated 
sleep impairment [47], the quality of life and performance in professional life of patients with 
atopic dermatitis and their relatives is significantly impaired. [1, 48] Both affected patients and 
the general population perceive uncontrolled atopic dermatitis as having a comparably large 
impact on health as e.g. angina pectoris, chronic anxiety disorder or rheumatoid arthritis. [49] 
Due to the high direct and indirect medical costs and the association with multiple comorbidities 
[44, 50-54], atopic dermatitis has a tremendous economic and socio-medical relevance. [1, 39, 
55]  
 
In children and adolescents, only little is known about the effectiveness of existing topical and 
systemic therapeutics in routine care in terms of clinical severity, patient-reported outcomes 
and AD progression as well as associated atopical and non-atopical comorbidities over time. 
In addition, it is unclear how many children and adolescents cannot be effectively controlled 
by avoiding trigger factors, patient education and topical anti-inflammatory treatment alone (i.e. 
how many children would need systemic therapy if safe and effective treatment is given). 

German National Clinical registry TREATgermany 
Prof. Dr. J. Schmitt, Faculty of Medicine Carl Gustav Carus TU Dresden 
25 
 
Innovative therapeutics will also be available for these age groups within the next few years, 
so reference data are required to evaluate their effectiveness and indication criteria. 
Best-practice models for the transition from adolescent to adult care of patients with moderate-
to-severe AD do not yet exist, but they are a prerequisite for establishing efficient patient care. 
 
 
 
1.2 Treatment of atopic dermatitis 
Despite numerous new insights on the pathogenesis of atopic dermatitis, no causal treatment 
is currently available. [3] AD management aims to improve symptoms and establish long-term 
disease control by avoidance of individual trigger factors, skin barrier restoration through 
moisturizer use, and a step-up/step-down approach aimed at reducing inflammation. [35] The 
choice of anti-inflammatory therapy is largely based on AD severity/activity; mild AD can 
usually be controlled with topical treatments; more severe disease may require phototherapy 
and/or systemic immunomodulatory therapy. [5]  
 
An analysis of routine medical care health insurance suggested that 10 to 15% of all patients 
with atopic dermatitis were treated systemically within a 2-year observation period from 2003 
to 2004. [4] Despite insufficient trial evidence [7, 56], systemic steroids were the most 
frequently used systemic therapeutics. In contrast, ciclosporin and other systemic therapies 
such as azathioprine, MTX and mycophenolate mofetil were rarely used in clinical practice [4], 
despite available evidence for their efficacy from clinical studies. [6, 8, 57] Many important 
questions about healthcare delivery and medical care for patients with moderate-to-severe 
atopic dermatitis are still unknown. This includes reasons for or against using (a specific) 
systemic therapy, their clinical benefit, and physician and patient satisfaction.  
Further important gaps in research concerning the medicinal treatment in patients with 
moderate-to-severe atopic dermatitis are, among other things, the following: 
 
- 
Studies on the effectiveness and patient safety of treatments under real-life conditions  
- 
Long-term observations  
- 
Physicians’ reasons to prescribe or not prescribe systemic therapies to children / 
adolescents / adults with severe AD 
- 
the transition in the care of children / adolescents during the transition into adulthood 
- 
Health economic evaluations 
- 
Patients' preference and decision studies. 
 
 
 
1.3 The TREAZeczema registry 
Against this background the registry TREATeczema for adults with severe atopic dermatitis 
was planned and established in Germany by Prof. Schmitt, Prof. Werfel and Prof. Weidinger 

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in 2011. Until October 2014 in total 78 patients (average age 39 years, 61% male) were 
included at five study centres. A high demand of outpatient and inpatient services by the 
patients included in the registry was noted. The most frequently administered systemic 
treatment was cyclosporine, which also showed the greatest clinical effectivity (EASI-50 
response rate 51%; EASI-75 response rate 34% after a 12-week treatment period). 
Azathioprine, MTX, oral prednisolone, mycophenolate mofetil, alitretinoin and leflunomide had 
been prescribed to single patients only.  
Based on the experiences from TREATeczema, it became apparent that important 
modifications are necessary in order to increase patients’ and physicians’ willingness to 
participate and to improve the registry’s validity.  
These modifications/amendments included:   
- 
Expansion to “moderate-to-severe AD” in order to include all patients eligible for 
systemic therapy 
- 
Extension of the observation period, preferably without a time limit, to examine long-
term outcomes  
- 
Separation of coordination, data management, quality assurance, data repository and 
analysis from recruitment centres (according to DNVF-Methoden-Memorandum 
registry) [58]  
- 
Reimbursement of study centers and provision of electronic data capturing toold to 
increase motivation of investigators 
  
 
 
1.4 The European registry network TREAT 
The German registry of atopic dermatitis TREATeczema was the first atopic dermatitis registry 
worldwide and served as a role model for similar initiatives in other European countries. In 
order to ensure collaboration and coordination of different national registries being planned 
and established, the International TREAT Registry Taskforce (treat-registry-taskforce.org) as 
an umbrella was established. The task force is coordinated by Prof. Schmitt (GER), Prof. Flohr 
(UK), Prof. Spuls (NL), Prof. Apfelbacher (GER) and Prof. Irvine (Ireland). The individual 
national registries remain independent, but are closely aligned in terms of outcome 
assessments. 
 
 

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2 
STUDY OBJECTIVES 
 
TREATgermany is based on the registry TREATeczema and part of the European registry 
family TREAT. The main aim of TREATgermany is the development and expansion of a 
nationwide clinical academic registry for patients with moderate-to-severe atopic dermatitis 
and to characterize healthcare delivery patterns, to investigate the comparative effectiveness, 
tolerability and safety of available systemic therapies, and to gain insights into physicians’ and 
patients’ treatment goals and satisfaction. 
 
TREATgermany has 3 main aims: 
 
1. Healthcare research 
To characterize patients with moderate-to-severe atopic dermatitis and their medical care. 
Special consideration is given to the patients’ perspective (e.g., disease burden, treatment 
goals, quality of life), reasons for the use of specific systemic therapies, changes and sequence 
of therapies, use of medical services, use of alternative treatment methods, satisfaction with 
applied treatments from the perspective of both the physician and the patient, impact of 
comorbidities, influence of atopic dermatitis on productivity/ performance at school and cost of 
illness. 
 
2. Effectiveness research, evidence-based medicine  
To investigate the comparative effectiveness, tolerability and safety of available systemic of 
treatment options for moderate-to-severe atopic dermatitis. 
 
3. Creation of a platform for basic and clinical research 
To provide a platform for clinical, epidemiological, and molecular research.  
 
 

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3 
STUDY DESCRIPTION 
 
3.1 Study design 
TREATgermany is a non-interventional study (observational study), which is performed as 
prospective cohort study in form of a clinical registry. 
Data are collected during routine care for patients with moderate-to-severe atopic dermatitis 
without any further intervention or direct comparison of different therapies (e.g. cross-over). It 
is non-clinical study according to § 40-42 AMG. 
 
3.2 Institutions involved 
Coordinating registry centers are the Zentrum für Evidenzbasierte Gesundheitsversorgung 
(ZEGV) of the Medizinischen Fakultät Carl Gustav Carus der TU Dresden, the Department of 
Dermatology and Allergy of the University Hospital Schleswig-Holstein, Campus Kiel as well 
as the Department of Dermatology and Allergy at the University Medical School Hannover. 
The ZEGV is responsible for clinical data management, storage, analysis and reporting. 
 
Recruitment centers: Every dermatology clinic, dermatology office and primary care provider 
with a specific focus on allergology / AD (pediatricians and GP office) in Germany can 
participate in the registry. The goal is to have at least 40 recruitment centers for adult patients 
and 30 recruitment centers for children and adolescents. The recruitment of children / 
adolescents and adults in the same center is possible. In order to ensure that observations are 
representative for the German healthcare system, a mix of tertiary care/specialised centers 
(e.g.  university and hospital-based dermatology and allergy departments) and office-based 
dermatology centers should be achieved. Participating centers will be asked to include as 
many (consecutive) patients as possible. Participating centers will also be offered opportunities 
for scientific cooperation. For every patient included and observed for at least 3 years an 
incentive of 250 Euros will be provided. 
 
3.3 Scientific-strategic advisory board 
The scientific-strategic advisory board supports the principal investigators in all scientific and 
strategic concerns, helps with the recruitment of new centers, can propose and comment on 
analyses, and propose modifications of data acquisition.  
The scientific-strategic advisory board must be composed of 6 full members with a voting right 
and guests members without the right to vote. 
Full members are: Prof. Carsten Flohr (King‘s College London) will act as international expert. 
Prof. Flohr is building up a registry for atopic dermatitis in UK and is one of the coordinators of 
the European registry-network TREAT. Prof. Christian Apfelbacher (University of Magdeburg) 

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is an expert in health care and epidemiological research, and has built up the CARPE registry 
on hand eczema. Prof. Zink is head of the German Rheumatism Research Center Berlin and 
the RABBIT-Registry for arthritis. The German Dermatological Society (DDG) will nominate 
two experts and the Professional Association of German Dermatologists (BVDD) is invited to 
nominate one expert for the advisory board. 3 members to be appointed shall act as 
representatives of office-based dermatology. Unanimous recommendations of the expert 
advisory board are aimed at, otherwise the simple majority applies.  
 
In addition to the 6 full members, every sponsor of the registry (e.g. pharma companies, 
foundations, etc.) are granted the right to nominate up to 2 guest members. The nomination of 
further persons with guest status is reserved for the coordinators of the registry. 
 
The composition of the scientific-strategic advisory board shall comprise excellent clinical, 
methodological and strategic expertise. 
 
 

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4 
PATIENT POPULATION 
 
4.1 Number of patients 
The goal is to include at least 800 patients in the registry within 6 years after initiation (realized 
in April 2016). 
 
4.2 Inclusion and exclusion criteria 
The following inclusion criteria must be met for a patient to be included in the registry: 
 
- 
Confirmed diagnosis of atopic dermatitis [23, 24] 
- 
Moderate-to-severe atopic dermatitis 
o Objective SCORAD > 20 [25] and/or 
o Current systemic therapy of atopic dermatitis and/or 
o Systemic therapy for atopic dermatitis within the past 24 months 
 
Patients who were already included in the previous registry (TREATeczema) can be included 
in the TREATgermany registry after they have been informed and given their consent, if they 
meet the inclusion criteria. 
 
 

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5 
STUDY DESIGN 
 
There is no study-related intervention. Enrolled patients are observed for a period of at least 
24 months without a predetermined maximum observation period. During the observation 
period, study visits take place at intervals of 3 or 6 months (see visit plan).  
 
5.1 
Selection of patients, round 1 (baseline) 
Prior to enrollment, patients will receive appropriate information about the purpose of the study, 
its design and procedures, and possible risks and benefits of participation. The information 
about the study is provided personally by the treating physician and in a written form by the 
patient information/parent information. Only after all questions of the patient/parents have been 
clarified, the patient/parents will be asked to sign two copies of the consent form, one of which 
will be provided to the patient/parents. Patients who meet the inclusion criteria will be enrolled 
into the study after having provided written consent. The consent of the underage participants 
is renewed when the age limit of 7 or 12 years is exceeded, the consent is obtained when they 
reach the age of majority. 
 
Physician questionnaire: During the baseline visit, a detailed medical history, a physical 
examination (using established tools such as the SCORAD, EASI, investigator’s global 
assessment (IGA), etc.), a photo documentation (typical lesion and distribution patterns of the 
skin changes in the extremities and trunk) as well as the documentation of the prescribed 
therapies and the reasons/motivation for therapy decisions are performed. Potential adverse 
drug reactions of atopic dermatitis therapies are recorded. 
 
Patient questionnaire for adults: Patients are asked to fill in the patient questionnaire, which 
captures socio-demographic information, history of the disease, current treatment (and 
compliance), quality of life impairment (DLQI, EuroQoL), and symptoms (POEM, NRS itching 
and sleep disorders), the course of atopic dermatitis, occupational limitations due to atopic 
dermatitis (WLQ), depressive symptoms (CES-D), fatigue (FSS), therapy goals/benefits (PBI) 
and treatment satisfaction are assessed. 
 
Patient questionnaire for children/adolescents: Parents or children/adolescents (from the 
appropriate age) are asked to fill out the patient questionnaire completely, including information 
on socio-demographic characteristics, disease history, actual therapy (compliance), quality of 
life (cDLQI, KINDLR), symptoms (POEM for children, NRS pruritus and sleep disturbances), 
course of AD (including degree of disease control), school restrictions due to AD (partial scale 
of the KINDLR), strengths and weaknesses (SDQ2-4, SDQ4-17, SDQ11-17 (self-reported) for 

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children and adolescents), sleep quality (CSHQ for children and adolescents), therapy goals/ 
benefits and satisfaction with treatment. In addition, there is the recording of absence from 
school due to AD and the inability of the parents to work due to their childrens’ AD as well as 
due to receiving medical treatments/number of doctor visits. 
 
5.2 
Follow-up visits 
The second and third visitis take place every 3 months according to the baseline (V2: after 3 
months, V3: after 6 months).  
Thereafter, the intervals between visits depend on newly initiated systemic therapies. If a new 
system therapy has been initiated during a visit, the next visit will take place after 3 months. If 
no new system therapy was prescribed, the next visit is after 6 months. 
 
At each follow-up visit, the physician documents the clinical examination findings (objective 
SCORAD, EASI, global severity of disease, affected body parts), the prescribed therapy 
including the rationale for the prescription, as well as reasons for a change or continuation of 
therapy and possible adverse drug reactions (ADR). 
The patient questionnaire for follow-up visits is similar to the questionnaire for the baseline visit 
(see visit schedule).   
 
5.3 
Interim visits 
Interim visits can be made between the regular study visits if the attending physician considers 
this necessary. Reasons for interim visits can be e.g. relapses of disease, the occurrence of 
adverse events due to atopic dermatitis treatment, inpatient stays due to atopic dermatitis or 
the change of the anti-inflammatory systemic therapy. Doctor and patient questionnaires of the 
interim visits correspond to those of the follow-up visits (see 5.2). 
 
 
5.4 
Withdrawal of patients and drop-outs 
Patients can withdraw from the study at any time at their own request, without giving any 
reason and without consequences for their future treatment. 
 
 
5.5 
Optional module „Biobanking and Bioanalytics“ 
Atopic dermatitis is a disease that typically occurs in infancy, but can sometimes only manifest 
itself later. In some of the affected children, for unclear reasons, the typical symptoms 
spontaneously subside in the course of childhood, although they may recur later, while others 
suffer from chronic, persistent courses. Some children with AD also develop atopical and 
affective comorbidities. Although the disease can take a variety of long-term courses, its 
determinants are largely not understood and cannot currently be predicted either clinically or 
by laboratory methods. [59] To date, no markers exist that predict the course of the disease or 

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Prof. Dr. J. Schmitt, Faculty of Medicine Carl Gustav Carus TU Dresden 
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the development of comorbidities and thus could be used to control treatment or preventive 
measures. 
The influence of certain treatments on molecular mechanisms in terms of disease modification 
is also insufficient and has been studied especially in adults, although children and adolescents 
represent the largest group of patients. Furthermore, the few available molecular studies on 
children with AD indicate that other mechanisms than in adulthood may determine the disease 
activity and the perpetuation of the inflammation and that therefore other sensible target 
structures for drug therapies [60] might exist. For these reasons, molecular studies on children 
and adults are of outstanding importance. 
 
In order to answer further scientific questions, from all registry patients who give their informed 
consent, biological samples are systematically collected at baseline and at final visit (blood 
and stool), and at initiation of a new systemic therapy (blood – no more than 5 ml from children 
up to 11 years old / no more than 19 ml from adolescents from 12-17 years / no more than 20 
ml from adults older than 18 years- and skin swabs -only adults-).   
The blood (no more than 20 ml) and skin samples are used to isolate genetic material (DNA 
and RNA). The genetic material is used to identify genetic factors involved in the development, 
course and response to therapy of AD.Whole-genome sequencing is currently not planned, 
but should not be ruled out in the future. Additionally, the transcriptome and proteome are to 
be analysed. Furthermore, non-invasive skin swabs are sampled for microbiome analysis and 
skin flakes for are sampled for skin physiology analysis.  This minimally invasive collection of 
biosamples, which can be carried out with minimal stress as part of routine blood sampling, 
and whose processing, as shown in the patient information, does not result in any individual 
benefit. 
All biosamples are stored pseudonymized and until further notice at the biobank of the 
Laboratory for Molecular Dermatology in Kiel (Prof. Dr. Stephan Weidinger) separately from 
the phenotypic data (held at the ZEGV Dresden). In compliance with data protection 
regulations, pseudonymised data from biomaterial and from medical examinations or surveys 
collected within the context of this registry are matched for research purposes. Accompanying 
molecular analyzes could lead to an enormous gain in knowledge and help to make better 
disease prediction and targeted prevention recommendations. This data is then anonymised. 
Individual backtracking of results from molecular analysis is not possible and not planned. 
Participation in the additional module is voluntary and requires a separate explanation of its 
purpose, procedure, possible risks and advantages personally by the treating doctor and in 
writing by means of a separate patient information. Non-participation in the additional module 
"Bioanalytics" in no way affects the main study. 
 

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6 
DOCUMENTATION / DATA MANAGEMENT 
 
It is the physician's responsibility to ensure that the study is conducted in compliance with all 
legal requirements and that the data are correctly recorded in the corresponding data entry 
forms. 
 
All data generated in the course of this study (including anamnesis, concomitant diseases, 
experimental data, results of examinations and adverse events) must be recorded in the data 
entry forms by appropriately authorized persons. This also applies to data from patients who 
were excluded from the study. It must be ensured that all persons involved in the trial can be 
identified. 
 
The data collection is pseudonymised. The physician documents the participation of patients 
on a special identification list in order to ensure that a patient can be identified after the study 
has been completed. In addition, the participation of the patient in this study should be noted 
in the patient record. An assignment list of patient name and pseudonym remains in the 
recruiting office. In the physician and patient questionnaires, the data are entered in 
pseudonym form. Only pseudonymised data is sent to the registry office. 
 
 
6.1 Data entry forms 
All patient data and examination results are entered into the data entry forms (physicians and 
patient questionnaires) specially created for these studies. The data is primarily collected 
electronically. 
 
Technical implementation 
With REDcap (database including mobile survey module) the patient enters his data directly 
using an iPad. The physician works browser-based on a desktop PC. The corresponding 
questionnaire for the patient is generated on the iPad using a QR code from the attending 
physician’s entry system. This ensures that the patient does not see any further data apart 
from the questionnaire to be processed by him (neither his own previously entered data, nor 
treatment data of the physician or data of other patients). 
This recording system was developed in direct cooperation with the KKS Dresden. The KKS 
has a REDCap license that TREATgermany can use on a contractual basis. The entries in the 
data entry system are immediately checked for completeness and plausibility and, if 
necessary, corrected with the help of automatic feedback or help instructions. The medical 
study staff has an up-to-date view of all entries at all times and can check them for 
completeness and quality. The management of the digital questionnaires as well as the 

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administration of access authorizations, study centers and involved personnel is carried out by 
the administrative area at the KKS Dresden (responsible administrator: Ms. Katja Wendrich). 
The REDCap database for TREATgermany is also hosted at KKS. A corresponding contract 
was concluded between the registry center and the KKS for this purpose. No data is stored on 
the mobile devices. The pseudonymized data is transmitted directly to the REDCap database 
via WLAN. At the end of the study, the database will be closed after all entries have been 
entered and queries have been clarified. This process is documented. 
 
Data protection and security 
The entries in the data acquisition system are immediately checked for completeness and 
plausibility and, if necessary, corrected with the help of automatic feedback or help instructions. 
The medical study staff has an up-to-date view of all entries at all times and can check them 
for completeness and quality. The management of the digital questionnaires as well as the 
administration of access authorizations, study centers and involved personnel is carried out by 
the administrative area at the KKS Dresden (responsible administrator: Ms. Katja Wendrich). 
The KKS also hosts the REDCap database for TREATgermany (and manages the 
corresponding server). A corresponding contract was concluded between the registry office 
and the KKS for this purpose. The mobile devices are the property of the medical faculty of the 
TU Dresden, whose IT division is responsible for the mobile device management. No data is 
stored on these devices. The pseudonymized data is transmitted directly to the REDCap 
database via WLAN. The WLAN is end-user specific.  
Alternatively, it is possible to fill out the physician and patient questionnaires using a paper and 
pencil version of the physician and patient questionnaires. In this case the completed original 
pages (without names or initials) are sent to the data center at ZEGV Dresden, a copy remains 
at the study centre and is stored there according to the legal requirements.  
The physician ensures that all patient data are entered into the study documents immediately, 
legibly, completely, correctly and in accordance with the patient files. In case of incomplete or 
implausible data, the registry office at ZEGV Dresden will contact the respective recruitment 
centre.  
At the end of the study, the database is closed after all entries have been made and the queries 
have been clarified. This process is documented. 
 

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6.2 Assessment tools 
 
SCORAD (see Appendix 2) 
The SCORAD was introduced in 1993 by the European Task Force on Atopic Dermatitis and 
is today a common and sufficiently validated assessment tool for the severity classification of 
atopic dermatitis. [15, 30, 61] 
The SCORAD is calculated according to a formula that takes into account objective criteria 
(body surface area manifestation (BSA) and intensity of typical skin conditions) and subjective 
complaints of the patient (itching and insomnia, on a VAS scale). The minimum SCORAD is 0, 
the maximum SCORAD 103 points. [62-64] 
In 1997, the European Task Force on Atopic Dermatitis also introduced the so-called objective 
SCORAD (oSCORAD), which does not take into account itching and insomnia, as these 
subjective symptoms are subject to the greatest variability. 
The maximum oSCORAD is 83, the minimum 0 points. The task force proposes to use the 
oSCORAD as inclusion criterion for studies and defines: mild AD as oSCORAD < 15, moderate 
AD as oSCORAD 15-40 and severe AD with an oSCORAD > 40 points. [25] 
 
Dermatology Life Quality Index (DLQI) (see Appendix 3) 
The Dermatological Quality of Life Index (DLQI), developed by Finlay and Kahn in 1994, is a 
widely used, well validated and practicable instrument in clinical routine, which has proven its 
worth in measuring the quality of life (QoL) in dermatology [32, 41, 65] The questionnaire 
records the QoL of the last 7 days and consists of 10 questions each, which can be evaluated 
as an overall score or assigned to the following 6 dimensions: symptoms, daily life, 
leisure/sport, work/school, social life/relationship and treatment. For each question, 0 to 3 
points are given, whereby 3 points indicate the greatest possible impairment of the QoL in the 
queried area. A validated German translation is available. The DLQI is a validated instrument 
which is very often used to assess the dermatological QoL in patients with AD. [41, 65-67] 
 
Assessment of global disease severity by physician (IGA) and patient (PGA) (see 
Appendix 4) 
Charman et al. recommend that in studies, in addition to a complex, symptom-related score 
system such as SCORAD and the recording of QoL, a global, basic assessment of the severity 
of the disease or its modification by both the patient and the physician should always be 
performed. As a static, six-degree assessment instrument, the Investigator's Global 
Assessment (IGA) is a frequent target criterion of clinical studies. Severity levels 0 (healed) to 
5 (very severe) are defined exclusively by the intensity of an average skin change, the intensity 

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of which is not taken into account. The Patient's Global Assessment (PGA) is a target criterion 
corresponding to the IGA, in which the patient himself makes the assessment. [68] 
 
Work Limitations Questionnaire (WLQ) (see Appendix 5) 
The WLQ measures valid and reliable the productivity at the workplace within the past 2 weeks. 
Altogether 4 dimensions of productivity at the workplace (presenteeism) are recorded: Time 
management, physical resilience, mental resilience, performance at work. The WLQ is 
validated against actual productivity, so that a monetary amount can be assigned to loss of 
productivity. This makes the WLQ ideally suited for pharmacoeconomic analyses from a social 
perspective. A German translation is available. [69-73] 
 
EuroQoL (EQ-5D) (see Appendix 6) 
The EuroQoL is a well validated instrument for measuring the general health-related quality of 
life impairment. The results of the EuroQoL have been validated against utility values 
determined by the time-tradeoff method. On the basis of multiple time-delayed measurements 
of morbidity using EuroQoL, lost quality of adjusted life years (QALY) can be calculated. Thus, 
EuroQoL is ideally suited for the measurement of morbidity in cost-effectiveness analyses. [74, 
75] 
 
Patient-oriented eczema measure (POEM) for adults and children (see Appendix 7 and 
Appendix 13) 
POEM is a well validated instrument to measure the typical symptoms of patients with AD. [15, 
29] The patient himself evaluates the frequency of occurrence and severity of 7 symptoms 
(such as itching and burning of the skin) within the last week, each according to a 5-point Likert 
scale. The maximum POEM score is 28 points. The POEM measures the symptoms relevant 
to the patient and correlates well with the DLQI and PGA. 
 
Center for Epidemiological Studies Depression Scale (CES-D) (see Appendix 8) 
The CES-D scale is a scale for measuring depressive symptomatology in the general 
population and is considered a useful tool for epidemiological studies on depression. The items 
on the scale are the symptoms that are associated with depression and that have already 
proven to be validated. [76, 77] 
 
Patient Benefit Index (PBI) (see Appendix 9) 
The PBI is a validated instrument introduced in the dermatology department of M. Augustin for 
the determination of specific, individual patient goals in the current treatment of the skin 
disease. [78, 79] A total of 23 possible treatment goals are evaluated on an importance scale 

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from 0 ("not at all") to 5 ("very"). In the respective follow-up visit, the degree to which the goals 
have been achieved is also assessed on a scale from 0 ("not at all") to 5 ("very") based on the 
23 previously prioritized treatment goals. In a retrospective cohort study, the PBI was used in 
about 1600 patients with AD. [78, 79] 
 
Fatigue Severity Scale (see Appendix 10) 
The FSS is a widely used, well validated tool for recording fatigue symptoms over the past 
week using 9 items. A validated German translation is available. [80, 81] Fatigue in patients 
with AD has not yet been sufficiently investigated. However, it is known from other chronic 
inflammatory diseases (psoriasis, MS) that fatigue is frequent, can cause relevant limitations 
in patients and can be treated by effective therapy of the underlying disease. [82] 
 
Eczema Area Severity Index (EASI) (see Appendix 11) 
The Eczema Area Severity Index (EASI) [28, 83] is a very well validated [61] and widely used 
instrument in clinical studies to measure the objective severity of AD based on the intensity 
and extent of typical skin lesions on a scale of 0 to 72. The HOME Initiative recommends the 
use of the EASI as a core outcome instrument in all AD studies. [27] The particular use of the 
tool is to highlight changes in the severity of the disease over the course of treatment. [28] 
 
Children's Dermatology Life Quality Index (cDLQI) (see Appendix 12) 
This is the analogue of the Dermatology Life Quality Index (DLQI) for adults. Skin diseases 
can lead to severe impairment of quality of life and handicaps in children. The measurement 
of the impact of skin diseases on quality of life is necessary to facilitate clinical decision-
making, for clinical research, for the examination of pediatric care and for political reasons, in 
order to deliver arguments for more resources for the care of children with skin diseases. 
Measures for adults are unsuitable because the life of children is very different from that of 
adults. [84] 
 
Strengths and Difficulties Questionnaire (SDQ-Deu) (see Appendix 14) 
The Strengths and Difficulties Questionnaire (SDQ) is a practicable and economical diagnostic 
tool for the quantification of behavioral aspects in children and in the developmental 
framework. Particular attention is paid to the balanced proportion of positively formulated 
behavioral aspects in the self-assessment and external assessment of children and 
adolescents. The following questionnaire versions are available: Questionnaires for parents of 
3 and 4 or 4-16 year olds and for self-assessment for 11-17 year olds. The following five scales 
are addressed: emotional problems, behavior problems, hyperactivity, behavior problems with 
peers, prosocial behaviour. [85] 

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Questionnaire on the quality of life of children and adolescents (KINDL) (see Appendix 
15) 
The KINDLR is a generic instrument for recording health-related quality of life in children and 
adolescents from 3 years of age. The KINDLR has been translated into numerous languages 
and used in numerous national and international studies. The representative study KiGGS on 
the health of children and adolescents in Germany - initiated by the Robert Koch Institute (RKI) 
- provides standard values. With 24 questions, the KINDLR is a short, methodically tested and 
flexible instrument. There are three versions of the KINDLR for different ages and levels of 
development. In addition, a self-survey and a third-party survey are offered for each age 
version of the KINDLR. 
In principle, the KINDLR follows a cross-disease (generic) approach and can therefore be used 
to record the quality of life in both healthy and sick children. In addition, the KINDLR offers 
various modules that can be used in addition to the main instrument. One of these modules 
aims to record the quality of life in connection with chronic illnesses or longer hospital stays. 
Further modules record the disease or complaint-specific quality of life in selected complaints 
(adiposity, bronchial asthma, diabetes, epilepsy, cancer, AD and spina bifida). [86] 
 
Children's Sleep Habits Questionnaire (CSHQ-DE) (see Appendix 16) 
The CSHQ is a retrospective screening questionnaire for parents of children of preschool and 
elementary school age, which has already been used in a number of studies to determine 
children's sleep behavior. It can also be used for orientation in younger children. [87] 
 
Sleep Self Report – DE (SSR) (see Appendix 17) 
The German version of the Sleep Self Report (SSR) is a screening tool for physically and 
mentally healthy children to record sleep behavior in self-assessment for children between 7 
and 12 years of age. It records the sleep behavior from the child's point of view and thus 
enables a direct comparison between self-judgment and that of others. In addition, his items 
meet the ICSD criteria for sleep disorders. [88] 
 
Mood and Feelings Questionnaire (MFQ) (see Appendix 18) 
A questionnaire for recording depressive symptoms in children and adolescents, which 
enables a comparison between self-reported information and information provided by parents 
or other attachment figures. [89] 
 
 

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Prof. Dr. J. Schmitt, Faculty of Medicine Carl Gustav Carus TU Dresden 
40 
 
6.3 Adverse drug reactions (ADR) and regulations applying to 
pharmacovigilance 
 
 
Definition: Adverse drug reactions (ADR) are any harmful and unindented response to a 
medicinal product which is intended to be applied to humans. More precisely an ADR are 
deemed to occur if the causal link between medicinal product and the incident can not be 
excluded with complete certainty. ADR are regardless of the medical products´s intentional 
purpose. Thus, by definition, results from e.g. overdosage, abuse, improper use, application 
errors or application in pregnancy and lactation period are excluded. 
ADR or the clinical suspicion of ADR by patients or medical professionals in the treatment of 
atopic dermatitis are supposed to be identified and reported according to the current legal 
regulations.  
The type of ADR (signs, symptoms or disease, preferably diagnosis), its onset and recovery, 
its intensity (mild = tolerable, moderate = influence on daily activities, severe = daily activities/ 
work not possible), the suspected link to the systemic treatmend of AD, the measures or acts 
to restore, correct or modify the subjects health or well-being and the events outcome should 
be recorded. 
 
A suspected case of a serious unexpected adverse reaction is according to the Directive 
2001/20/EG supposed to be labeld as a Suspected Unexpected Serious Adverse Reaction 
(SUSAR). If the serious ADR does not appear on the appropriate professional information it is 
defined as unexpected. The physician in charge is supposed to report the Suspected 
Unexpected Serious Adverse Reaction immediately, but at the latest within 15 days, to the 
responsible regulatory authorities, the physicians behind the clinical registry and the registry´s 
head office. The physician in charge is supposed to report every Suspected Unexpected 
Serious Adverse Reaction leading to death or has been life-threatening, immediate, but at 
the latest within 7 days, the responsible regulatory authorities (BfArM), the participating 
physicians, die director of studies and the coordination registry center (ZEGV). The director of 
the registry is suposed to inform all participating physicians about the event. 
5 
 
 
The participating physicians report on ADR which are suspected to be associated with a 
medical product of a pharmaceutical company founding the registry pseudonymised to the 
study director. 
 
The registry is financed through Sanofi-Aventis Deutschland GmbH. The study director has to 
forward the report to the corresponding department of Sanofi-Aventis Deutschland GmbH or 

German National Clinical registry TREATgermany 
Prof. Dr. J. Schmitt, Faculty of Medicine Carl Gustav Carus TU Dresden 
41 
 
rather the sponsoring company. The participating doctor agrees to give access to the findings 
of additional examinations concerning ADR (e.g. results of autopsy, hospital report, consultant 
report). The study director is responsible for esthablishing the contact between the 
corresponding department of Sanofi-Aventis Deutschland GmbH (or rather the sponsoring 
company) and the reporting physician. A detailed list of the relevant products of Sanofi-Aventis 
(or rather the sponsoring company) is provided for the participating physicians. 
 
 

German National Clinical registry TREATgermany 
Prof. Dr. J. Schmitt, Faculty of Medicine Carl Gustav Carus TU Dresden 
42 
 
 
7 
STATISTICS 
The data is checked for plausibility. Data analysis is performed descriptively and exploratively. 
Measured values are calculated by t-Test and/or Mann-Whitney-U-Test and frequencies by 
Chi-Quadrat-Test and/or by exact Fisher-Test. In order to answer complex questions 
multivariate regression- und variance-analytical methods are additionally used. The analysis 
are performed by the ZEGV Dresden at least annualy. Recruitment centres obtain the annual 
analysis on all patients of the registry and on the particular centre.  
 
No confirmatory analysis are planned due to the non-interventional character of the study 
(observational study). The inclusion of at least 600 patients is planned to picture the medical 
supply of adults with moderate-to-severe AD adequately. 
Consistent with the recommendations of the HOME Initiative [17, 26, 27] the key target figures 
in the analysis of the efficacy of the AD treatment include the following scores: 
 
- 
Objective severity of clinical signs of AD (EASI, objective SCORAD) [25, 28] 
- 
Symptoms (POEM, POEM for children) [29], severity of itch and sleep disturbances 
(VAS) [30]  
- 
Flare-ups and the course of disease [31]  
- 
Quality of life (DLQI, cDLQI) [32]  
 
To assess the needed number of patients to evaluate the comparative effectiveness of 
systemic treatments in adults with moderate-to-severe AD a calculation by „detectable 
alternative“ for various scenarios was made. Based on the assumption of an oSCORAD-50 
Response Rate of 50% (viz. 50% of the treated patients show an improvement of at least 50% 
in oSCORAD) during therapy (e.g. CSA) a difference in the oSCORAD-50 Response Rate of 
27%, 19% or rather 14% can be demonstrated with a power of 80% and 5% significance level 
n=50, n=100 more specifically n=200 patients per treatment group. (PS Power and Sample 
Size Calculations Version 2.1.30) 

German National Clinical registry TREATgermany 
Prof. Dr. J. Schmitt, Faculty of Medicine Carl Gustav Carus TU Dresden 
43 
 
8 
REPORTING 
The collected data serve exclusively academic purposes. The intention is to publish the 
collected data in scientific journals with broad readership and additionally present the results 
understandable for laymen in publications and/or public lectures. Data protection concerning 
the patient´s and the participating physician´s data applies to all publications.  
 
 
9 
ETHICAL, LEGAL AND ADMINISTRATIVE ASPECTS 
The investigation is conducted in accordance to the Declaration of Helsinki and the 
professional code of the responsible federal states Medical Associations in the version curent 
of any time. 
 
Patient´s participation in the investiagtion is voluntary. The consent for participation can be 
withdrawn at any time without justification or disadvantages concerning the further necessary 
medical care. Prior to study participation patients will be informed in written and spoken form  
on the nature and scope of the investigation, in particular on the health benefits and potential 
risks. The patients´agreement is documented by the signed consent. In the case of withdrawal 
from the investigation the data already acquired will not be deleted. The patient has to be 
informed concerning this matter prior to study inclusion.  
To verify the diagnosis AD clinical fotographs are used on top of the epidemiological criteria of 
the UK Working Party (see Appendix 1). [24] By means of the photographs the members of 
the steering committee/ scientific board check the correctness of the diagnosis. Given the fact, 
that in adulthood e.g. a cutaneaos T cell lymphoma can be misjudged as an AD the photo 
documentation is essential. The documentation of the clinical finding is done at baseline and 
incudes photographs of characteristic lesions and the distribution patterns on extremities and 
trunk. Patients will be informed about the purpose of the photo documentation. In the event of 
rejection, participation in the investigation will still be possible.  
 
Prior to study initiation the study plan is submitted for appraisal to the ethics committee of the 
Medical faculty Dresden. Without the approval in written form the recruitment process of 
patients/subjects will not be started. Necessary requirement to conduct the study at the 
recruitment sites is an approval of the responsible ethics committee. 
 
The patients´name and any other confidential information will be handled in strict adherence 
to medical secrecy, the European Data Protection Regulation and the Federal Data Protection 
Act (Bundesdatenschutzgesetz, BDSG).  
 

German National Clinical registry TREATgermany 
Prof. Dr. J. Schmitt, Faculty of Medicine Carl Gustav Carus TU Dresden 
44 
 
In general, it is thus the intension that within the registry TREATgermany and within the 
additional registry „Bioanalytics“ the collected data are exchanged in encrypted form between 
the headquarter of the registry, the operator of the biobank and the coordination centres (Clinic 
for Dermatology, Venerology and Allergology at the Universitätsklinikum Schleswig-Holstein, 
Campus Kiel and Clinic for Dermatology, Venerology and Allergology at the Medizinischen 
Hochschule Hannover) to investigate scientific questions concerning AD and are transmitted 
to uncommercial collaboration partners. For this purpose the patient´s approval will be 
obtained. The disclosure of the research data to uncommercial collaboration partners is based 
on contractual arrangements and is characterised by the SOP „Publikationsvereinbarung und 
Datenanforderung“ (Appendix 19). 
 
 

German National Clinical registry TREATgermany 
Prof. Dr. J. Schmitt, Faculty of Medicine Carl Gustav Carus TU Dresden 
45 
 
10 
SIGNATURES 
 
 
PD Dr. med. J. Schmitt 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
________________________________________ 
 
 
 
 
 
 
 
 
Dresden, 15.09.2021 
 
 
 
 
Prof. Dr. med. T. Werfel 
 
 
  
 
 
________________________________________ 
 
 
 
 
 
 
 
 
Hannover, 17.09.2021 
 
 
 
Prof. Dr. med. S. Weidigner 
 
 
  
 
 
________________________________________ 
 
 
 
 
 
 
 
 
Kiel, 21.09.2021 
 
 
Physician 
I hereby confirm that I have read and understood the present study protocol and accept it in 
all parts. I undertake to ensure that the patients brought into the study by my centre are treated, 
observed and documented according to the provisions of this protocol. 
 
 
Name 
 
 
 
 
 
 
 
 
Ort, Datum 
 
 
 
 
 
 
 
 
 Unterschrift 
 

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Prof. Dr. J. Schmitt, Faculty of Medicine Carl Gustav Carus TU Dresden 
46 
 
 
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