Overview and details of the selected research

Out of the 1,660 articles, 402 articles were identified through PubMed, 929 articles were from EMBASE, 88 articles were from Cochrane Central, 15 articles were from Web of Science, and 226 articles were from CINHAL. 115 articles satisfied the eligibility criteria and were selected for analysis in this review. The characteristics of the selected studies in terms of six specific domains are summarized in Table 2. These domains were selected for analysis as they were considered the most useful categories for answering the questions under investigation in this review as they relate to RD stakeholders’ by firstly, identifying stakeholders’ key characteristics including the nature of their stake i.e., their relationship to RD’s, the nature of the studies various focuses in terms of identifying specific stakeholder issues, which countries these studies are being conducted in, types of study and study focus over the review’s specified timescale.

Table 2 Characteristics of the 115 selected studiesTrends in academic interest related to RD

The number of studies on RD stakeholders has steadily increased over the years during the time period reviewed, with a notable, more rapid increase since 2015 (Fig. 2). In 2015, the number of studies doubled from the previous year, when only five studies were conducted. The cut-off date of the literature search in May 2020 and consequently, results indicate a lower number of publications in that year.

Fig. 2

Publication year of the 115 selected studies

Additionally, it was observed that multiple jurisdictions have participated in international studies on RD. Study locations were categorized into six continents and analyzed based on the countries (Fig. 3, Additional file 1: Table S3). Across the 115 selected articles, Europe and North America were most commonly featured in RD research accounting for 93 articles (Table 1, Additional file 1: Table S3). Europe was selected as the exclusive study location in 45 articles, making it the region where the majority of the research in this area was conducted (39.1%). Fifty-two articles (45.2%) examined countries in North America where 13 (11.3%) focused on Canada and 39 (33.9%) focused on the US. Fifteen studies focused on the areas in Asia and Oceania, and only one study included both the regions. No single study was focused on Africa exclusively, but two studies included several countries in Africa (1.7%). The number of studies focused on two or more regions has increased over time, with 14 studies (12.2%) conducted since 2012, suggesting that international collaboration and joint research are becoming more common in areas of research related to RD. Europe has been the most involved in intercontinental studies, participating in 12 out of 14 studies (10.4%). North America was the second most involved continent, participating in 9 studies (10.3%). These two continents were the focus of 8 studies (7.0%). Europe and Asia collaborated in 4 articles (4.6%), and only 1 article featured South America (1.1%).

Fig. 3

Study locations of the 115 selected studies

Study participants

For this analysis, RD stakeholders were categorized into three groups and studies were categorized by the stakeholder participant (Fig. 4, Additional file 1: Table S4).

Group 1: Patients, parents, caregivers, or patient organizations. This group was the most involved in RD research, with 87 articles (75.7%) including them as study participants compared with other RD stakeholders (Table 1).

Patients and patient support groups: 41 studies (35.7%) included only patients or patient support groups.

Families or caregivers: 18 studies (15.7%) included only families or caregivers.

Both patients and families or caregivers: 18 studies (15.7%) included both patients and families or caregivers.

Group 2: Healthcare professionals (HCPs). This group included specialists from specific medical disciplines, general practitioners (GPs), and other healthcare professionals (HCPs). 18 articles (20.7%) included HCPs as study participants.

Specialists: Nine articles included specialists from specific medical disciplines, such as neurology, pediatrics, genetics, oncology, obstetrics, and pulmonology.

GPs: Four articles included only GPs.

Other HCPs: Two articles included nurses, dentists, or healthcare managers.

Group 3: The public. This group included university students, social support practitioners, and research fund providers. Seven studies (8.1%) included only the public, while six studies included them along with patients, caregivers, or healthcare professionals.

Fig. 4

Stakeholders of the 115 selected articles

Types of RD

The types of RD in the 115 selected studies were analyzed in accordance with the International Classification of Diseases–11 Mortality and Morbidity Statistics (ICD-11 MMS). Unspecified RD were the most common among the selected articles in the review, accounting for 46 of the 115 articles (40.0%) (Table 1). Endocrine, nutritional, and metabolic diseases (stem code #05) were examined in 20 articles, being the most studied types of diseases with specific codes (17.4%). Neurological diseases (stem code #08) were exclusively examined in 11 articles (9.6%). Ten articles studied diseases labeled as developmental anomalies (stem code #20), including diseases such as Poland’s syndrome and Rett’s syndrome (8.7%). Autoimmune disorders (stem code #04) were studied in eight articles (7.0%). Five articles covered diseases related to blood or blood-forming organs, with four articles concentrating on hemophilia and one on thrombocytopenic purpura (4.3%). Two articles each focused on the visual system (stem code #09), circulatory system (stem code #11), skin (stem code #14), musculoskeletal system or connective tissue (stem code #15). Rare tumors (stem code #02) and genitourinary diseases (stem code #16) were investigated in only one study, respectively. The type of tumor included was not stated; however, nephrotic syndrome was the singular type of disease under the genitourinary disease category. Five articles investigated more than one disease, while endocrine, nutritional, and metabolic diseases were included in all of them (4.3%).

Study topics

The majority of the studies included in the review were concerned with stakeholders’ experiences of RD (n = 74/115, 64.3%, Additional file 1: Table S4). A total of 24 studies examined the opinions of various stakeholders, with nine studies exploring knowledge level or education history (7.8%), and eight studies focusing on the prevalence of these diseases (7.0%). The remaining studies were focused on stakeholders’ feelings on diverse and various issues such as treatment preferences, access to information and funding (see Supplementary 4 for detailed breakdown of topic details).

Topics related to experiences with RD were selected as a research subject for more than half of Group 1 (n = 58/77, 75.3%) and Group 2 studies (n = 10/18, 55.6%), followed by the opinions of the stakeholders and their knowledge (n = 5/18, 27.8%, respectively). Questions concerning funding were most commonly surveyed in studies investigating Group 3 participants exclusively (n = 6/7, 85.7%). According to selected articles using questionnaires, four out of six of these studies inquired about the general public’s opinions on the use of governmental funding for RD (Additional file 1: Table S4).

Approximately 60% of the studies surveying participants from both Groups 1 and 2 investigated relevant stakeholders’ various opinions on patient engagement, diagnosis, treatment, or research priorities (n = 4/7, 57.1%), whereas the remaining studies investigated experiences of the diagnosis and treatment processes or QoL issues (n = 37/86, 42.9%). One article studied individuals from both Groups 1 and 3 surveyed their opinions on RD treatment, and two other studies involved participants from Groups 1, 2, and 3 and explored their experiences as far as the accessibility of information relevant to RD. Participants from Groups 2 and 3 were also asked about prevalence (n = 1/3, 33.3%) and their knowledge (n = 2/3, 66.7%) of RD.

In addition to this quantitative analysis, surveys from 36 articles were included in a thematic analysis for in-depth investigation. The number of times specific topics were included in the survey questionnaires was investigated. As questionnaires may cover many topics as well as the same topic multiple times, the total frequencies of each topic-category appearing in questionnaires will necessarily exceed the total number of articles reviewed.

A total of 23 studies out of 36 included Group 1 participants as the study subjects (Fig. 5). The topic-category “experience” appeared in the survey questions a total of 230 times. Questions asking about the experience with the HCPs were mentioned 76 times, thereby accounting for the most frequent question topic among the 23 studies. Questions related to physical experiences (such as illness symptoms, transportation, or movement difficulties), psychological experiences (such as stress coping and QoL), and social experiences in various environments were asked 39, 33, and 33 times, respectively. Questions concerning the opinions of patients, families, or caregivers appeared 40 times. Survey participants who were living with RD were also asked their opinions on engagement 12 times. Their perspectives of participation in RD research were mentioned across five questions, their opinions on patient organizations appeared in four questions, and their perceptions of data sharing were queried two times.

Fig. 5

Thematic analysis of Group 1 studies (n = 23). The area of each box represents the details and frequency count of the questionnaires by categories of experience, opinions, and knowledge in the Group 1 studies

Questionnaires from 12 articles that surveyed Group 2 participants were also included in thematic analysis (Fig. 6). Questions about their experiences appeared 71 times, while the questions relating to their knowledge and opinions on RD were asked 35 and 34 times, respectively. Participants from Group 2 were asked to assess the level of their own knowledge of RD five times. Additionally, they were asked whether they were aware of the treatment and diagnosis guidelines four times.

Fig. 6

Thematic analysis of Group 2 studies (n = 12). The area of each box represents the details and frequency count of the questionnaires by categories of experience, opinions, and knowledge in the Group 2 studies

For the five Group 3 studies whose questionnaires could be accessed, public opinions were the most explored topic (Fig. 7). Opinions on the use of public funds for activity related to RD were asked seven times.

Fig. 7

Thematic analysis of Group 3 studies (n = 5). The area of each box represents the details and frequency count of the questionnaires by categories of experience, opinions, and knowledge in the Group 3 studies

Study methodologies

The dominant study methodology was the quantitative research method, which was used in 114 of the 115 selected articles (99.1%, Table 3, Additional file 1: Table S6). 89 studies adopted quantitative methods as exclusive methodologies in their studies (77.4%), while 80 articles used simple questionnaires to study various stakeholders, and nine articles selected diverse quantitative methodologies, such as Discrete Choice Experiments, 36-Item Short-Form Health Survey (SF-36), Acceptance of Illness Scale (AIS), Parental Needs Scale for RD (PNS-RD) (7.8%). On the other hand, 25 studies used both quantitative and qualitative methods for their research (21.7%), while questionnaire methodology was predominantly used as a joint method in 22 articles (19.1%). The interview research method was most aligned with questionnaires and was employed in 11 studies (9.6%). Literature review methodology was used in combination with questionnaires, discrete choice experiments, or the Delphi technique in eight studies (7.0%). Questionnaire methods were also sometimes combined with discussion methods (0.9%) and patient record analysis (0.9%), respectively. Only one study selected a qualitative research method—discussion—as the sole study method (0.9%).

Table 3 Study methodologies employed in the 115 selected articles