Results of a PREM to measure the rare disease patients’ caregivers experience: A Spanish cross-sectional study

Objective To measure the experience of the person suffering from a rare disease in order to identify objectives for optimal care in the health care received by these patients. Methods. A cross-sectional study was conducted in Spain involving patients associated with the Spanish Rare Diseases Federation [Federación Española de Enfermedades Raras] (FEDER). A modified version of the PREM IEXPAC instrument was used (IEXPAC-rare-diseases). Scores ranged between 0 (worst experience) and 10 (best experience). Results A total of 261 caregivers (in the case of paediatric population) and patients with rare diseases (response rate 54.4%) replied. Most males, 227 (87%), with an average age of 38 (SD 13.6) years. The mean time since confirmation of diagnosis was 7.8 (SD 8.0) years. The score in this PREM was 3.5 points out to 10 (95%CI 3.2-3.8, SD 2.0). Caregivers of paediatric patients scored higher, except for coordination of social and healthcare services. Conclusions There are wide and important areas for improvement in the care of patients with rare diseases. This study involves a first assesment of the experience of patients with rare diseases in Spain.

Results A total of 261 caregivers (in the case of paediatric population) and patients with rare diseases (response rate 54.4%) replied. Most males, 227 (87%), with an average age of 38 (SD 13.6) years. The mean time since confirmation of diagnosis was 7.8 (SD 8.0) years. The score in this PREM was 3.5 points out to 10 (95%CI 3.2-3.8, SD 2.0). Caregivers of paediatric patients scored higher, except for coordination of social and healthcare services.
Conclusions There are wide and important areas for improvement in the care of patients with rare diseases. This study involves a first assesment of the experience of patients with rare diseases in Spain.

Background
Diseases with a lower prevalence of 0.65% are known as rare. Most of the approximately 7.000 of rare diseases which are known have a genetic cause and are diagnosed in childhood , . The paradox of rare diseases lies in the fact that, although each of the pathologies classified as rare affects a very small number of people, the total number of people suffering from a rare disease is high , .
People suffering from a rare disease share a long journey through the set of assistive devices until diagnosis ,,, . Rare diseases test the capacity of health systems as these people (particularly in the case of childhood) need different responses to meet their physical, social, and psychological needs in a cocherent, integrated, and effective way4 ,, .
Health organizations that pursue to a person-centered care systematically measure the experiences of their patients in the course of the care they receive. However, the problem of people suffering from a rare disease has been little studied so far , and less in Spain. The limited research results have applied methods based on surveys or qualitative techniques. These results are similar and highlight the delays in diagnosis, the demand for information, and the burden of the family compared to other chronic processes. This last one is due to the uncertainty of low frequency, that relatives normally have more information about the disease than most professionals, that there is no adequate coordination between care levels as this role is exercised by relatives and that the care received is fragmented1 ,, .
Patient-Reported-Experience-Measure (PREM) is a methodological approach little applied in the case of patients with rare diseases, despite its extensive application in patients with chronic diseases. This is a measure of a patient's perception of their personal experience of the healthcare they have received , . The PREMs are instruments that have been designed with the opinion and perspective of patients.
Moreover, the PREMs have demonstrated its positive associations with health outcomes4 , .
As far as we know, in our country no studies have been carried out using standardised instruments (PREM instruments) to evaluate the experience of patients who suffer from a rare disease or their caregivers, analysing the response capacity and the degree of integration of healthcare provision at different levels of care. The aim of this study was to measure the experience of the person suffering from a rare disease in order to identify objectives for optimal care in the health care received by these patients. Four questions of this instrument were modified to adjust to the rare diseases context (reinforcing the measure of patient-centered-care, support for engagement, and integrate care) and four specific items were added to explore the experience with care in case of emergency care, homecare, being receiving support from social services and information received about diagnosis. Adaptation was done by a selection of specialist working on rare diseases and the research team applying consensus technique. Responses were transformed in scores following criteria applied by Orozco et al[ii] using the IEXPAC considering always (score 10), mostly (7.5), sometimes (5), seldom (2.5) or never (0). The overall score was calculated as the sum of individual scores for the 11 common items divided by 11 between 0 (worst experience) and 10 (best experience). This procedure allowed to compare data with the national study conducted by Orozco et al including 1618 chronic patients suffering diabetes mellitus, human immunodeficiency virus infection, inflammatory bowel disease, or rheumatic diseases. Additionally, percentages of subjects who answered with the always option was calculated. These percentages allows identification of range in which improvement is needed and compare data with the Spanish studies conducted asking chronic patients9 and caregivers of chronic patients (relatives suffering Alzheimer, mental illness, and Chronic

Method
Obstructive Pulmonary Disease)[iii] using the same scale.
This version of the IEXPAC was assessed by a set of patients representatives and their wording changes suggested were introduced to assure content validity and legibility. Additionally, metric properties of this instrument was assessed to assure the validity (applying exploratory factorial analysis) and reliability (using Cronbach's Alpha and Rho coefficient) of the measurement conducted in this study.
The reliability measures using Cronbach's Alpha of this version of the IEXPAC instrument for rare diseases was 0.87 and coefficient Rho was 0.86 (for the 11 elements applied in all cases). Items converged in two factors explaining 59.4 of total variance (Appendix I).

Statistical analysis
Only subjects replaying all items were included. Descriptive information (mean, standard deviation, SD) were displayed for each item, and the overall score. The distribution of responses to individual items was also displayed, as is the percent of "always" responses to each item. Frequencies or percent for qualitative variables were also used. Student's t test or analysis of variance (ANOVA) were used to compare continuous variables. Time to diagnosis was grouped into categories (0 to 3 years, 4 to 6, 7 to 15, and 16 or more). Chi-Square was used to compare qualitative and continuous variables. Given the overall descriptive nature of the results, no multiplicity adjustments were made. Lineal regression was calculated to establish the relation of age, number of drugs they are taking, number of times they have been admitted to the hospital in the last year, length of time in years that they have been diagnosed with the main illness (overall score on the PREM).   (Table 1).
Overall, 39 (14.9%) participants confirmed the patient has received support from Social Services in the last six months, meanwhile 73 (28%) needed hospitalization, 153 (58.6%) had been seen in the emergency department and 21 (8%) were in the home care programme. Table 1. Description of the sample of subjects who answered to PREM The score on the IEXPAC scale (11 elements) was 3.5 points (95%CI 3.2-3.8, SD 2.0).
The systematic review of medication in each consultation was the element of care with the lowest range of improvement (Table 3). After hospital discharge, only 3 (4.1% of the total number of patients requiring hospitalization) said they had called or visited them at home to see how they were doing and what care they needed.
Twenty out to 153 who had gone to the emergency department (13.1%) had been informed of which telephone number to call if they had an emergency again. Of the patients in home care, 6 (28.6%) considered that the professionals of the different health resources in which they received care were coordinated. Only 6 (16.8%) of the persons who had received care in the Social Services considered that there was adequate coordination of these professionals with those of the health services.
Neither the time of diagnosis, nor the number of hospital admissions, nor the number of medications they were taking influenced the patient's experience. As age increased, the patient's experience became more negative (Table 2).  Score range 0 to 10 % = 5 + Percentage of subjects who answered with the always response option (score = 10).

Discussion
There are wide and important areas for improvement in the care of rare disease patients. This Spanish study confirms the results found in other countries4 , 6 , 7 , 8 , 9 , 10. There is no positive experience with the organization of the assistance process in any of the aspects evaluated through the PREM IEXPAC-rarediseases scale. In view of these results, and from the perspective of these patients, it cannot be considered that they receive integrated care and what is most striking, they do not have the perception that they receive enough support to manage their disease autonomously. These results highlight that the objective of empowering patients who suffer from a rare disease to face the social, psychological, occupational, etc. challenges of their illness and who go beyond their medical and health care needs are far from being met.
As far as we have been able to find out, this PREM instrument is the first in Spain focused on the experience of patients with rare diseases. The results are similar to the findings obtained in other countries and, compared to the results of similar studies conducted in Spain with another patient profile, they show that the experience of rare disease patients is even less positive.
Patients who are routinely seen in health centers, by primary care teams, described a more negative experience than those followed in hospitals. These results seem to suggest that the proposal that this patient profile should have reference services, with staff sensitised to the psychological and social problems that accompany these disease processes9, may contribute to a better experience in the course of the health care received. On the other hand, they also suggest that action plans, even if they arise from the health environment, should not forget the social care needs that some families may need. In this sense and according to these results, moving forward in the coordination between the two systems seems to be an objective for the action plans of the health organisations.
The following limitations should be considered when interpreting these results.

Availability of data and materials
The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Competing interests
The design, planning and execution of the study and the analysis and interpretation All authors read and approved the final manuscript.