3.1 Participants
Seven out of eight experts responded to the invitation. One of the potential participants could not be reached by phone or email. All of the experts who responded to our invitation participated in the study. Therefore, we achieved a high participation rate of 87.5%. Characteristics of study participants are shown in Table 3.
Table 3: Characteristics of the study participants
Characteristics
|
Options
|
Participants (n=7)
|
Gender
|
female
|
2
|
male
|
5
|
Age group
|
>59
|
2
|
50-59
|
2
|
40-49
|
2
|
30-39
|
1
|
Medical specialization
|
nephrology
|
1
|
neurology
|
1
|
immunology
|
1
|
pediatrics
|
2
|
internal medicine
|
1
|
psychiatry and neurology
|
1
|
Years of experience in the field of rare diseases
|
30
|
1
|
25
|
1
|
24
|
1
|
15
|
2
|
4
|
2
|
Prior experience with clinical decision support systems
|
yes
|
3
|
no
|
4
|
The participants were predominantly male (n=5) and the age range was wide. The study participants represented several different medical disciplines: nephrology (n=1), neurology (n=1), immunology (n=1), pediatrics (n=2), internal medicine (n=1) and a double qualification (neurology and psychiatry). Their experience with RDs ranged from 4 to 30 years, with an average of 16.7 years. Three of the seven study participants had prior experience with CDSSs.
3.2 Main themes by deductive category
In the following sections, the results are presented and organized by research questions and deductive categories. References for selected quotations are provided for each statement (see Additional file 4). We also provide exemplary quotes in each paragraph, abbreviated by “Q” and numbered in ascending order (e.g. Q1).
3.2.1 Relevant organizational conditions
Steps before a consultation with a patient
When asked to define the steps before a consultation with a patient at the center, the experts explained that medical or administrative center guides receive documents from the patients (e.g. via mail) or directly from the treating physician, typically private practitioners or doctors from other hospitals (Q1-Q3). One expert explained:
“The typical diagnostic route actually operates through our guides and coordinators, where the patients first report at the center and the center guides review the documents […]. And then the patients are referred directly to a B-center, where the patients are then seen or actually first examined by the center guide.” (Q1, translated from German)
One expert pointed out that patients referred from a university hospital are prioritized for a diagnosis (Q4).
After the center guides have inspected the documents, the patient case is assessed and a recommendation is made (Q5). One expert stated that an interdisciplinary case conference or discussion is part of the assessment of the patient case. In these conferences, physicians review and discuss cases together, and a decision is made as to whether or not the patient will be referred to a B-center (Q6).
Persons involved in the diagnostic process
The experts mentioned that administrative and medical center guides and various experts at the B-centers are involved in the diagnostic process (Q7-9). One expert stated:
“Once a month we have a case conference where we try to solve these patient cases. Every B-center is involved in this.” (Q8, translated from German)
Two experts gave examples of health professionals from different clinical specializations who are involved in the diagnostic process, for instance: neurology, pediatrics, general medicine, otorhinolaryngology, laboratory medicine, pulmonology and immunology (Q10-11, Q13-14).
One expert also pointed out that a specialist in psychosomatic medicine is part of their team, because some cases are not of somatic origin (Q12). Four experts explained that they perform interdisciplinary case discussions in their centers in order to analyze the patient cases (Q8, Q15-17). One of these experts indicated that in his center, large case discussions are organized in a kind of lecture. The goal is to discuss difficult patient cases to obtain further opinions (Q18).
Usage of clinical findings
Clinical findings are mainly used by the medical center guides, the experts at the B-centers, and also the specialists from the outpatient department (Q19-23). An expert stated:
“Then the patients are referred directly to a B-center, where the patients are then viewed or actually first examined by the center guide.” (Q19, translated from German)
Another explained:
“Either we see quite clearly that it is a rare movement disorder and then we would forward the documents very quickly to the appropriate B-center. And it doesn’t cost the center guide most of their time, rather the cases with a bundle of symptoms take a lot of time, which also have been clarified intensively.” (Q22, translated from German)
3.2.2 Clinical data for diagnosis of RDs
Clinical characteristics and findings of RDs
Regarding the relevant clinical features of RDs, two experts indicated that characteristics of RDs do not differ from common diseases and that no general symptoms could be reported. The overall combination of symptoms is important when an unusual symptom or patient history is described (Q24-25). One expert pointed out:
“Many of the characteristics of patients with rare diseases are common. It’s not that they all have rare symptoms, but they all have very common complaints.” (Q24, translated from German)
Another expert stated:
“It is certainly not possible to give generally valid symptoms, because any symptom that is present in a rare disease can also sometimes occur in a common disease. But it always depends on the overall constellation. […].” (Q25, translated from German)
One expert explained that clinical characteristics depended on the disease group. In immunology, for instance, the antibody constellation is important in connection with symptoms, whereas in movement disorders the actual movement disorder is essential in connection with genetics. The expert also pointed out that it would be difficult to apply a universal strategy because each disease group has a different blend of symptoms:
“Yes. That depends on the disease group. […]. In rare diseases I think it's difficult to find a universal strategy for all these diseases.” (Q26, translated from German)
For instance, in some cases neurological or psychological findings are important, whereas in pediatrics the morphology of the patient is likely to be important (Q27). One expert explained that many characteristics could not be depicted and are more or less coincidental: “Ultimately, many things cannot be depicted in this way, many things are more or less coincidental.” (Q28, translated from German)
One expert suggested that a patient's family tree is an indication for the diagnosis, and the phenotype increases the likelihood of the diagnosis of a certain disease (Q29-30). On the other hand, two experts mentioned that there are also diseases that are phenotypically very different, such as immunodeficiencies or psychiatric diseases (Q31). Mental illnesses, for example, have high phenotypic variability. One expert described a family in which different family members had each developed different mental illnesses as a result of a RD (e.g. depression or schizophrenia) (Q32).
Additionally, one expert also regarded the patient’s own description of their symptoms to be important (Q33).
Relevance of findings
One expert explained that certain findings or measurements are required for the diagnosis of certain diseases, while the same findings are completely irrelevant for other diseases:
“[…].The findings I need for this are completely different. For one of them I need a lactate value. And for another, I'm not interested in the lactate value at all.” (Q34, translated from German)
For example, the laboratory and imaging data, clinical symptoms and genetics are of interest to internists:
“As an internist, one naturally always likes to look at the laboratory values. Are there any abnormalities in the laboratory or any abnormalities in imaging? What symptoms does the patient report? These are the central pre-diagnostics. […].” (Q35, translated from German)
For another expert, the epidemiology of the patient, e.g. age, sex and origin, is also of interest. One expert indicated that the travel anamnesis is also relevant in order to exclude rare infectious diseases (Q36).
Patient documentation
Five experts explained that they prepare a summary letter containing the most important findings and examinations regarding the patient (Q37-41). One expert stated:
“We summarize. That’s what the center guides do. They compile a summary letter of what they saw there.” (Q37, translated from German)
Another expert stated:
“[…] we send the patients a doctor's letter. The letter tries to represent the essential findings structured […] in terms of comprehensibility and arranged according to symptom groups. Then the letter is sent back.” (Q38, translated from German)
One RDC uses a standardized questionnaire containing the findings and the results of the case conference (Q42). Another RDC also documents whether exome sequencing would be indicated (Q43). In addition, this center continuously documents suspicious diagnoses in their electronic health record system (EHR) (Q44-45).
One expert pointed out that the documentation is stored in a separate database and not in their EHR. Additionally, patients’ demographic data are also documented there (Q46-47).
Another expert explained that documentation of chronic immunodeficiencies is performed in more detail, including medication, demographic data, diagnoses and diagnosis criteria (Q48-49).
3.2.3 Appropriate user group for a CDSS for RDs
Use of software tools for diagnostic support
When asked whether software tools are used for diagnostic support in their centers, two experts mentioned using the internet and medical databases such as Medline, Online Mendelian Inheritance in Man (OMIM) and Orphanet (Q50-51). OMIM is a database which contains descriptions of human genes and their relationship to phenotypes [38]. Orphanet is an organization which provides a database including information about RDs [39]. Three experts did not specify which software tools are used (Q52-54). One expert stated:
“We have never used FindZebra. But apart from that we try to use tools, although I cannot tell you exactly what my colleagues use.” (Q52, translated from German)
One expert cited Phenomizer, ADA, Isabel Healthcare and FindZebra as software tools for diagnostic support in their center:
“On the one hand there are the special tools, of course, like FindZebra or Phenomizer, but we also strongly refer to Isabel Healthcare for example, which is more general. We can also access ADA.” (Q55, translated from German)
With Phenomizer it is possible to measure the similarity between phenotypes and genetic diseases. The software suggests a disease based on the entered phenotypes [40]. FindZebra is a search engine for RDs and which finds related articles for entered patient characteristics, querying selected databases such as Orphanet, Wikipedia or Medline [41]. Isabel Healthcare is a web-based diagnostic support system that provides a weighted list of differential diagnoses based on entered symptoms [22]. ADA DX is a software with the potential to recognize RDs in their early stages [25].
One expert mentioned that there are currently no satisfactory software solutions to support diagnosis (Q56).
Users of a clinical decision support system
The experts considered medical center guides as well as the specialists in B-centers to be the likely future users of DISERDIS (Q57-61). One expert explained:
“Who? Definitely the doctors.” (Q57, translated from German)
Another expert stated:
“Well, at the first level definitely the center guide, but at the second level the specialists in the B-centers.” (Q60, translated from German)
One expert cautioned that administrative center guides should not be considered as users because they don't have the necessary medical training to evaluate the patients (Q62). Another expert pointed out that the use of the system could depend on the quality of the CDSS. If the system was accurate enough, the center guide could use it. However, if the system required additional expert knowledge, the expert in the B-center would be a more suitable user (Q63).
Another aspect mentioned was that DISERDIS should also be used outside the centers, elsewhere in the clinic (Q64). One expert also suggested that users should be divided into two groups: those who filled in data entry forms (e.g. coding professionals) and medical center guides who follow the recommendations of the CDSS (Q65).