Dual Guidance Structure for Evaluation of Patients With Unclear Diagnosis in Centers for Rare Diseases (ZSE-DUO)

Duale Lotsenstruktur Zur Abklärung Unklarer Diagnosen in Zentren für Seltene Erkrankungen

In people suffering from a rare disease the diagnostic process and the confirmation of a final diagnosis is often ongoing for many years. Factors contributing to delayed diagnosis include the limited knowledge of health care professionals about rare diseases and their symptoms but also a psychiatric or psychosomatic (co-)morbidity obscuring the symptoms of the rare disease. The project ZSE-DUO will evaluate whether a combination of an expert in somatic medicine and a psychiatric/psychosomatic specialist will increase the rate of assured diagnoses in patients approaching a center of rare diseases (primary outcome), accelerate the process until a diagnosis is made, reduce the costs of diagnosing a patient, and lead to a higher satisfaction of patients and health care professionals. Furthermore, the project will evaluate whether the use of psychosomatic screening tools at registration of a patient in a center for rare diseases will help to guide the diagnostic process. Two cohorts of 682 patients each will be sequentially recruited over 9 plus 9 months: the Control group cohort (CG based on somatic expertise) and the Experimental group cohort (EG combined psychosomatic/somatic expertise Included will be persons from the age of at least 12 years presenting with symptoms and signs which are not explained by current diagnoses (as judged by the patient's primary care physician and a specialized physician at the center for rare diseases ZSE evaluating the medical records). Patients will be recruited from 11 German Centers for Rare Diseases associated with University hospitals in the cities of Aachen, Bochum, Frankfurt, Hannover, Magdeburg, Mainz, Münster, Regensburg, Tübingen, Ulm and Würzburg. Recruitment will be supported by a collaboration with the German patient organization representing many rare disease organizations ACHSE e.V. and a collaboration with the insurance companies Techniker Krankenkasse, IKK gesund plus and AOK Hessen who also provide data on costs of care. Data collection and analysis will be coordinated and performed by the Institute for Clinical Epidemiology and Biometry at the University of Würzburg, the Institute for Epidemiology, Social Medicine and Science of Health Care Systems in Hannover, and the Department of Medical Psychology in Hamburg. The project is funded by the Innovationsfond of the Federal Joint Committee in Germany.

Study Overview

• Status: Completed
• Conditions: Rare Diseases; Orphan Diseases
• Intervention / Treatment: Other: dual expert guidance structure

• Study Type: Interventional
• Enrollment (Actual): 1379
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Germany
  • Aachen, Germany, 52074
    • Center for Rare Diseases ZSEA, University Hospital
  • Bochum, Germany, 44791
    • Center for Rare Diseases CeSER, St. Josef Hospital
  • Bochum, Germany, 44791
    • LWL-Universitätsklinikum der Ruhr-Universität
  • Frankfurt, Germany, 60590
    • Center for Rare Diseases FRZSE, UNiversity Hospital
  • Hannover, Germany, 30625
    • Center for Rare Diseases, Hannover Medical School
  • Magdeburg, Germany
    • Center for Rare Diseases MKSE, Otto von Guericke University
  • Mainz, Germany, 55131
    • Center for Rare Diseases, Medical Center
  • Muenster, Germany, 48149
    • Center for Rare Diseases, University Hospital
  • Regensburg, Germany, 93053
    • Center for Rare Diseases ZSER, University Hospital
  • Tuebingen, Germany, 72076
    • Center for Rare Diseases, University Hospital
  • Ulm, Germany, 89075
    • Center for Rare Diseases, University Hospital
  • Bavaria
    • Würzburg, Bavaria, Germany, 97080
      • Center for Rare Diseases ZESE, University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• first contact with the Center for Rare Diseases for unclear diagnosis
• suspicion of a rare disease but no established diagnosis
• attending the Center for Rare Diseases as an outpatient
• written informed consent

Exclusion Criteria:

• age <12 years
• incomplete medical records including summary letters, imaging studies, blood tests etc.
• pre-diagnosed disease(s) explaining all symptoms

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Health Services Research
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Usual care; Standard evaluation process for patients approaching a center for rare diseases with an unclear diagnosis. The process includes the evaluation of complete medical records byan experienced physician, an outpatient visit to the center, and case discussion between experts. The process may also include an inpatient stay, a local case conference and a case conference between centers for rare diseases from different cities
Experimental: New Innovative Care; The innovative evaluation process includes the additional involvement of a psychiatrists/psychosomatic expert in all of the processes described for the usual care arm plus the option to use telemedicine in the process of evaluation in addition to outpatient and inpatient visits and to transfer the patient back into standard care (i.e., primary care physician, rehabilitation, psychological/psychosomatic specialized care, etc.)	Other: dual expert guidance structure; Two medical experts, one somatic specialist and one psychiatrist/psychosomatic specialist see all medical records and the patients together

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Diagnoses made	The number of diagnoses explaining the symptomatology of the patient made during the evaluation process	12 months after signing the consent form

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to diagnosis	The time it takes to make a diagnosis	12 months after signing the consent form
Patient satisfaction with diagnostic process using ZUF-8	The patients' satisfaction with the diagnostic process is assessed in the total sample with the questionnaire ZUF-8 (Fragebogen zur Patientenzufriedenheit - patient satisfaction questionnaire) and in a randomly selected subsample of about 40 patients by structured telephone interviews.	12 months after signing the consent form
Costs of the diagnostic process	estimated costs from first contact with the center for rare diseases until a diagnosis explaining the symptoms has been established	up to 12 months after signing the consent from
Patients' quality of life using EQ-5D and SF12 (or KIDSCREEN-10 for children)	Change in the patients' quality of life as assessed with the Quality of life questionnaires EQ-5D from the EuroQoL Group in all patients and Short Form 12 (SF-12) in patients 16 years and older. In patients younger than 16 years, the health-related quality of life questionnaire for children and adolescents KIDSCREEN-10 is used.	12 months after signing the consent from
Physician satisfaction with new form of care using new questionnaire	The satisfaction of physicians working in the Centers fro Rare Diseases with the new form of care compared to standard care will be assessed by a newly developed questionnaire administered to all physicians involved in patient care in the 11 centers. For the development of the questionnaire, 3 focus groups of 10 physicians each will be questioned.	30 months after the project start (end of the intervention period)
Value of screening instruments for psychiatric-psychosomatic (co-)morbidities	Performance of screening tools to identify patients with psychiatric-psychosomatic comorbidities against the judgement of a psychiatrist/psychosomatic expert seeing the patient (intervention group only)	30 months after the project start (end of intervention period)

Collaborators and Investigators

• Sponsor: Wuerzburg University Hospital
• Collaborators: Hannover Medical School; Goethe University; University Hospital Tuebingen; Universitätsklinikum Hamburg-Eppendorf; University of Wuerzburg; University Hospital Ulm; Otto-von-Guericke University Magdeburg; University Hospital Regensburg; University Hospital, Aachen; St. Josef Hospital Bochum; Techniker Krankenkasse; University Medical Center Mainz; AOK Hessen; Allianz Chronischer Seltener Erkrankungen ACHSE e.V.; IKK gesund plus; LWL-Universitätsklinikum der Ruhr-Universität Bochum; Universität Münster

Publications and helpful links

General Publications

• Schippers C, Volk D, de Zwaan M, Deckert J, Dieris-Hirche J, Herpertz S, Schulz JB, Hebestreit H; ZSE-DUO Arbeitsgruppe. [ZSE-DUO - dual guidance structure at the centre for rare diseases]. Inn Med (Heidelb). 2022 Jul;63(7):791-797. doi: 10.1007/s00108-022-01350-8. Epub 2022 Jun 2. German.
• Hebestreit H, Zeidler C, Schippers C, de Zwaan M, Deckert J, Heuschmann P, Krauth C, Bullinger M, Berger A, Berneburg M, Brandstetter L, Deibele A, Dieris-Hirche J, Graessner H, Gundel H, Herpertz S, Heuft G, Lapstich AM, Lucke T, Maisch T, Mundlos C, Petermann-Meyer A, Muller S, Ott S, Pfister L, Quitmann J, Romanos M, Rutsch F, Schaubert K, Schubert K, Schulz JB, Schweiger S, Tuscher O, Ungethum K, Wagner TOF, Haas K; ZSE-DUO working group. Dual guidance structure for evaluation of patients with unclear diagnosis in centers for rare diseases (ZSE-DUO): study protocol for a controlled multi-center cohort study. Orphanet J Rare Dis. 2022 Feb 14;17(1):47. doi: 10.1186/s13023-022-02176-1.
• Hebestreit H, Lapstich AM, Brandstetter L, Krauth C, Deckert J, Haas K, Pfister L, Witt S, Schippers C, Dieris-Hirche J, Maisch T, Tuscher O, Barlescu L, Berger A, Berneburg M, Britz V, Deibele A, Graessner H, Gundel H, Heuft G, Lucke T, Mundlos C, Quitmann J, Rutsch F, Schubert K, Schulz JB, Schweiger S, Zeidler C, Zeltner L, de Zwaan M; ZSE-DUO Working Group. Effect of the addition of a mental health specialist for evaluation of undiagnosed patients in centres for rare diseases (ZSE-DUO): a prospective, controlled trial with a two-phase cohort design. EClinicalMedicine. 2023 Oct 6;65:102260. doi: 10.1016/j.eclinm.2023.102260. eCollection 2023 Nov.
• Witt S, Kristensen K, Blomeke J, Hebestreit H, Wocker M, Pfister L, Bullinger M, Tuscher O, Deckert J, Graessner H, Lapstich AM, Zwaan M, Mundlos C, Quitmann JH. [Quality of Life and Experienced Distress of Patients Suspected of having a Rare (Chronic) Health Condition - Initial Findings from the ZSE-DUO Study]. Psychother Psychosom Med Psychol. 2023 Jan;73(1):9-15. doi: 10.1055/a-1814-3998. Epub 2022 Jul 6. German.

Study record dates

Study Major Dates

• Study Start (Actual): October 15, 2018
• Primary Completion (Actual): January 31, 2022
• Study Completion (Actual): September 30, 2022

Study Registration Dates

• First Submitted: May 23, 2018
• First Submitted That Met QC Criteria: June 19, 2018
• First Posted (Actual): June 20, 2018

Study Record Updates

• Last Update Posted (Actual): December 13, 2023
• Last Update Submitted That Met QC Criteria: December 6, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: psychosomatic; unclear diagnosis
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Rare Diseases
• Other Study ID Numbers: ZSE-DUO_V1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No