Design and study area

An observational and descriptive design study was carried out, using data from Peru between the years 2014 and 2019.

Population and sample

The population corresponds to people affected by rare and orphan diseases in Peru, obtained from a database of administrative records of the health sector, the Intangible Solidarity Health Fund (FISSAL). In addition, a survey validated by Orphanet was carried out on an intentional sample of 20 people or relatives of people affected by rare and orphan diseases. For the economic part, the Ministry of Economy and Finance was consulted. People affected by diseases that do not appear in the list of 399 rare diseases identified in the country or that do not coincide with the respective ICD-10 were excluded.

Variable and instruments

The variables proposed were the sociodemographic characteristics of the patients (age, gender, origin, and comprehensive health insurance regime). As well as the time elapsed between the first symptom and the moment of diagnosis, how many doctors did they consult between the first manifestation of the disease and the diagnosis, if they gave you wrong diagnoses before the final diagnosis, if looking for the diagnosis required personal expense, if they received complete information on their illness, and if the patient or family received psychological support and if their origin was from the city of Lima or another (classified as "province"). Those inherent to the economic aspect of these diseases were total budget, budget execution, and unit cost.

The information was obtained from the database of administrative records of the health sector, FISSAL; A questionnaire validated by Orphanet was also taken into account. For the economic data, a review was made of the public budget of the Ministry of Economy and Finance, the Integrated Financial Administration System - Budget Monitoring (SIAF), available at: https://apps5.mineco.gob.pe/transparencia/Navegador/ default.aspx.

Procedures

The information on the economic aspect was obtained through the Modified Institutional Budget of the FISSAL-MINSA per year between 2014 and 2019. The figures shown in this budget are used to cover high-cost diseases such as Chronic Kidney Failure on dialysis, cancers, and rare and orphan diseases. For the first, approximately 60% is allocated, approximately 40% to the problem of cancer and only 2.25% to ROD (this is calculated with the data that for the year 2017 the allocation of resources for ROD was 5.8 million soles, that is, 2.25% of the total). Therefore, the ROD budget for each year was considered as 2.25% of the total budget for the same year.

On the other hand, the data collection of the Orphanet questionnaire was carried out through contact with the ESPERANTRA organization, which facilitated the meeting with patients to conduct interviews with them or their relatives in different hospital centers in Lima with different pathologies anonymously.

Statistical analysis

A descriptive analysis of the variables studied was carried out, using central tendency and dispersion measures for the quantitative variables and frequencies and percentages for the qualitative ones. Inferential analysis was carried out to compare the budget for ROD in 2015 against that of 2019; for this, the non-parametric Mann Whitney U test was used. SPSS version 25 and Microsoft Excel were used to process the database.

Ethical aspects

The study was approved by the Research Ethics Committee of the Ricardo Palma University.

Sociodemographic data

The findings obtained show that 49 ROD of the 399 listed. In contrast to these figures, in the United States, they estimate that between 25 and 30 million patients have a ROD. In the European Union, it reaches approximately 27 to 36 million.⁹Few of the Latin American countries report accurate data, one of them is Colombia, which estimates in 2013 a total of 13,173 patients.¹⁰On the other hand, if we consider that 5 to 7% of the world's population suffers from some rare or orphan disease, when transferred to Peru, between 1.5 to 2 million would be affected¹¹hypothetically, so the road is still long to have an accurate figure in the country.

Schoolchildren and young adults are the majority of patients, with 18% each. Still, if evaluated together, between newborns and all children, they add up to 60%, so these are diseases that occur more frequently in pediatric age. This agrees in part with the authors Carbajal and Navarrete,⁴who affirm that approximately 50% appears in pediatric age. Still, the highest prevalence is seen in adults due to excessive infant mortality due to these diseases.

54% were male. Similar to Colombia in a study on mortality due to ROD, it was found that 51.4% were men of all ages,¹²although with this it cannot be affirmed that the frequency of appearance is higher in them, since another study also in Colombia,¹⁰found that 53.96% of patients with ROD were women.

The origin of more than half of the patients is from the capital, Lima. The other departments have a very low percentage, but this may be due to their under-registration because it is difficult to diagnose and identify them even more outside the capital.

71% of patients are cared for in health facilities with a subsidized regime, which is the mechanism by which the population without the ability to pay access health services; in other words, it is the most impoverished population in the country.

In the literature, it is found that 72% of ROD are genetic and 70% of them begin in childhood,⁶the finding of the present study is close to this figure since 67% or 33 diseases are genetic such as hemophilia A and osteogenesis imperfecta , but if the distribution among the patients is seen, they only constitute 39% (177 patients), the other 277 suffer from congenital, acquired, multifactorial diseases or still of unknown etiology.

A study in China¹³chooses to study 7 rare diseases of their country, of which only Gaucher disease matches our list. Carbajal and Navarrete⁴list "the rarest and most curious diseases in the world," and only one coincides (Moebius syndrome). In the study of mortality due to orphan diseases in Colombia¹²cited above, gastroschisis is the only one that matches our list. It was a frequent cause of death in men and women; in still lack this data in our country. Of the most frequent pathologies according to the research of María Pareja,¹⁰two coincide with the findings of this study: Hemophilia A and Von Willebrand's disease, which occupy the fourth and fourteenth place in our results. In addition, his research includes the percentage of people with ROD with disabilities, which was 10.74% of the total, data that is not required in Peru either.

Several RODs can be diagnosed prenatally, which is important because it facilitates delivery and newborn care, ensures their well-being as much as possible, and suggests a better future prognosis.¹⁴Based on what was found in this study, of the 49 diseases, 13 can be diagnosed or at least suspected in utero (tetralogy of Fallot, gastroschisis, among others), by means of routine prenatal ultrasounds that refer to more specific tests, another 12 can be diagnosed prenatally if family history is known (hemophilia, primary agammaglobulinemia, cystic fibrosis, phenylketonuria, for example).

Neonatal screening is another way to detect ROD, in 2012 the law established interest for the screening of 6 pathologies in Peru¹⁵, of which phenylketonuria and cystic fibrosis are ROD on the list. Just for comparison, the United States has 32 diseases for newborn screening,¹⁶including the 2 diseases mentioned.

Based on the questionnaire, data were obtained that may or may not reflect the reality of rare and orphan diseases in the country, but it gives us a general idea.

First, it is obtained that the delay in diagnosis was up to 7 months for half of the patients, a fact that does not agree with the information collected in the bibliography; for the other half, it took from 1 to 6.5 years for the final diagnosis. Regarding the number of doctors who were seen, a marked majority is seen in the range of 3 to 5, without obtaining results greater than this. Regarding the impoverishment of the families, 12 people affirmed that reaching the diagnosis represented a moderate, high and very high expense, while for the other 8 it was little or none. At this point, it should be taken into account that the question only refers to the direct expenditure of the families to reach the diagnosis, without considering other expenses such as follow-up of the pathology, the price of medicines in some cases for life, rehabilitation, other products health and necessary care in addition to the high level of dependency that most of these patients have. In addition, the health insurance scheme they have was not included.

It is very important to provide complete information to the patient and/or relatives about the disease so that they take care of themselves and know what to expect from the disease in terms of complications and prognosis to make the quality of life the best possible, in addition to identifying the nature of the pathology so that, if it is the case of having genetic inheritance, that data can be known within the family, 85% of the people surveyed did receive this information; it was different in the case of psychological support since only half received it. Psychological support for the patient and their families is important, as in other cases as well, due to the high emotional impact, doubts, and fears that these diagnoses carry.

70% of the people surveyed came from the province, and in their entirety, they agreed that their stay in Lima was for some reason related to their illness or that of their relative, such as diagnosis, treatment or better conditions in terms of follow-up of their illness.

Budget

Regarding the budget, there is mostly an increasing trend as the years go by, and the highest amount assigned to ROD was that of 2018 with 9.4 million if we compare this figure with the 53.4 million soles that are required to pay for at least the first 8 diseases on the list, reflecting that it only covers 17.6%. Therefore, the insufficient budget allocated to ROD is evident.

Cost

Similar cases that denote the high cost of ROD can be found in the literature, for example, in Germany, in a study it is calculated that the cost of Annual treatment per patient with ROD is between € 27,811 and € 1,647,627 (S/. 104,013 and S/. 6,162,124), they also analyze the impact on the annual budget of ROD and ultra-rare in Europe, which it was on average € 677,975,264 (S/. 2,535,627,487) but of this amount, pharmaceutical spending only constituted 2.7% (0.7-7.8)¹⁷. Another study carried out a literature review (mostly European) that facilitated the prices of medicines for ROD, from which they concluded that the annual cost ranged from € 1,474 to € 912,000 (S/. 1,772 to 3,410,880) per patient, that is, an average of € 96,518 (S/. 360,977).¹⁸

The study has certain limitations since, being based on secondary sources, there could be errors regarding the diagnoses or underreporting. The comparison with other countries is minimal since the prevalence of the diseases can vary in different populations, thus being rare in some and more frequent in others, and there are few data worldwide. Its most significant strength is that it gives a broader vision of the reality that was had in Peru regarding ROD, which is a great step for public health.