This study examined the application, feasibility, and validity of supervised learning models for text classification in appraisals for rare disease treatments (RDTs) in relation to uncertainty, and analyzed differences between appraisals based on the classification results.

We analyzed appraisals for RDTs (n = 94) published by the National Institute for Health and Care Excellence (NICE) between January 2011 and May 2023. We used Naïve Bayes, Lasso, and Support Vector Machine models in a binary text classification task (classifying paragraphs as either referencing uncertainty in the evidence base or not). To illustrate the results, we tested hypotheses in relation to the appraisal guidance, advanced therapy medicinal product (ATMP) status, disease area, and age group.

The best performing (Lasso) model achieved 83.6 percent classification accuracy (sensitivity = 74.4 percent, specificity = 92.6 percent). Paragraphs classified as referencing uncertainty were significantly more likely to arise in highly specialized technology (HST) appraisals compared to appraisals from the technology appraisal (TA) guidance (adjusted odds ratio = 1.44, 95 percent CI 1.09, 1.90, p = 0.004). There was no significant association between paragraphs classified as referencing uncertainty and appraisals for ATMPs, non-oncology RDTs, and RDTs indicated for children only or adults and children. These results were robust to the threshold value used for classifying paragraphs but were sensitive to the choice of classification model.

Using supervised learning models for text classification in NICE appraisals for RDTs is feasible, but the results of downstream analyses may be sensitive to the choice of classification model.

Out of 185 orphan medicinal products (OMPs) registered in 2015–2021, a mere 110 (59 percent) were available to Czech patients, and only 54 (29 percent) were officially reimbursed. Moreover, this proportion has steadily decreased over time. After years of public debate induced by this unsatisfactory OMP patient access, the national viewpoint shifted toward creating a special pathway for the reimbursement of OMP. Thus, a rigorous pricing and reimbursement procedure with strict timelines and elaborated methodology has been recently adopted in Czechia.

The innovative legislation follows the recommendations for value assessment and funding processes for rare diseases and incorporates additional elements of value, such as the societal perspective. First, the application with clinical evidence, cost-effectiveness, and budget impact analyses is submitted to the governmental health technology assessment (HTA) agency by the Marketing Authorization Holder or a Health Insurance Fund. Moreover, professional associations and patients’ organizations are rightful participants in the proceeding, providing evidence and comments. Then, the HTA agency performs the assessment/appraisal of the evidence. It subsequently publishes the assessment report summarizing available information. The report is then forwarded to the Ministry of Health and its advisory body consisting of patients, clinical experts, health insurance funds, and the State. They critically evaluate the documents and issue a binding opinion following prespecified decision-making criteria. Based on this binding opinion, the decision is issued by the HTA agency. Thus, the role of the advisory body in this process is crucial.

We believe that this novel approach may offer satisfactory patient access to orphan drugs. Moreover, it serves as a real-world example of “value-based” decision making.

Cochlear implantation candidacy criteria have continued to evolve over the years, and cochlear implantation is possible with many inner-ear and brain anomalies with good hearing and linguistic outcomes. Cystic leukoencephalopathy without megalencephaly is a rare disease in children, with only 30 cases reported in the literature, but it is associated with hearing loss in only three cases. Radiological investigations can help in diagnosing this rare entity before proceeding with cochlear implantation.

A four-year-old female child born out of consanguinity with normal psychomotor development, bilateral sensorineural hearing loss and an incidental magnetic resonance imaging finding of cystic leukoencephalopathy without megalencephaly underwent successful cochlear implantation. Her post-operative period was uneventful with successful mapping of the cochlear implant.

This is the first reported case of cystic leukoencephalopathy without megalencephaly and with sensorineural hearing loss in which cochlear implantation was performed successfully. White matter and temporal lobe abnormalities should not deter paediatric cochlear implantation.

This study aimed to identify different criteria for priority setting of rare diseases to help policy makers in making evidence-informed decisions.

A scoping review was conducted to comprehensively examine the existing various methods and criteria for prioritizing orphan drugs and rare diseases. We performed searching in Scopus, PubMed, Embase, and websites of health technology assessment (HTA) agencies, 2000–21, and data were extracted.

From the 1,580 identified publications, eleven articles were included. Multicriteria decision analysis was the most frequent method (seven out of eleven studies) used for priority setting. The extracted criteria for priority setting of orphan products were analyzed based on six main categories as follows: health outcomes and clinical implications (six subsets which showed clinical implications), economic aspects (four subsets that indicated the economic effects of orphan drugs and rare diseases), disease and population characteristics (six subsets that included the characteristics of the rare diseases), therapeutic alternatives and uniqueness of orphan technologies (two subsets which discussed the alternatives and uniqueness of orphan technologies), evidence (three subsets which regarded the quality and availability of evidence), and other criteria (three subsets dealing with social and organizational criteria). Cost-effectiveness, budget impact, and disease severity were the most frequent criteria in the studies.

Because of the high price of orphan drugs and limitations of using HTA for reimbursement of them, it is critical to explore them by precise technical methods like multiple criteria decision making in priority setting.

By studying the odds of developing idiopathic subglottic stenosis in the isolated and genetically unique Hutterite population, this study sought to strengthen the hypothesis that an underlying genetic predisposition may exist for its development.

A retrospective chart review examined the medical records of all adult patients treated for idiopathic subglottic stenosis in Saskatchewan between 2008 and 2018. Cases were segregated into Hutterite and non-Hutterite.

Four out of 36 cases of idiopathic subglottic stenosis occurred among Hutterites. The odds of a Hutterite developing idiopathic subglottic stenosis are 21.89 times higher than for non-Hutterites. Positive family history was only observed in the Hutterite population.

The study strengthens the hypothesis that genetics may play a role in the aetiology of idiopathic subglottic stenosis by demonstrating that the genetically and socially unique Hutterites are more likely to develop this rare disease. This study is the first to demonstrate that a specific subpopulation is at a higher risk for developing idiopathic subglottic stenosis.

No significant relationships.

Recognition of faces of family members, friends, and colleagues is an important skill essential for everyday life. Individuals affected by prosopagnosia (face blindness) have difficulty recognizing familiar individuals. The prevalence of prosopagnosia has been estimated to be as high as 3%. Prosopagnosia can severely impact the quality of life of those affected, and it has been suggested to co-occur with conditions such as depression and anxiety.

To determine real-world diagnostic frequency of prosopagnosia and the spectrum of its comorbidities, we utilized a large database of more than 7.5 million de-identified electronic health records (EHRs) from patients who received care at major academic health centers and Federally Qualified Health Centers in New York City. We designed a computable phenotype to search the database for diagnosed cases of prosopagnosia, revealing a total of n = 902 cases. In addition, data from a randomly sampled matched control population (n = 100,973) were drawn from the database for comparative analyses to study the condition’s comorbidity landscape. Diagnostic frequency of prosopagnosia, epidemiological characteristics, and comorbidity landscape were assessed.

We observed prosopagnosia diagnoses at a rate of 0.012% (12 per 100,000 individuals). We discovered elevated frequency of prosopagnosia diagnosis for individuals who carried certain comorbid conditions, such as personality disorder, depression, epilepsy, and anxiety. Moreover, prosopagnosia diagnoses increased with the number of comorbid conditions.

Results from this study show a wide range of comorbidities and suggest that prosopagnosia is vastly underdiagnosed. Findings imply important clinical consequences for the diagnosis and management of prosopagnosia as well as its comorbid conditions.

Health-related quality of life (HRQoL) data generated by generic, preference-based instruments (i.e., EQ-5D) are highly demanded in health policy decision making, because they allow for direct comparisons of HRQoL outcomes between disease areas. We aimed to quantify HRQoL outcomes in breast cancer (BC), rheumatoid arthritis (RA), multiple sclerosis (MS), rare cancers (RC), and rare disease (RD) patients and understand the patterns that differentiate HRQoL outcomes between these disease areas, and more specifically between rare and more common disease population groups.

An international, Web survey of patients measured HRQoL (EQ-5D-5L), self-perceived health (EQ-5D-5L Visual Analogue Scale), and additional QoL dimensions, such as patient disability level.

We received 675 completed responses. Average utility loss was 53.5 percent, 32.5 percent, and 33.3 percent for RD, RA, and MS patients, respectively, in contrast to 18.6 percent for BC and RC patients. Statistically significant differences (p < .05) were observed between disease groups in all EQ-5D-5L domain outcomes, apart from that of “Anxiety/Depression.” Severe and/or extreme problems were reported in performing usual activities for RD and RC (34 percent and 13 percent of overall problems reported respectively), mobility for MS (18 percent), pain/discomfort for RA (13 percent), and anxiety/depression for BC (7 percent) patients.

We demonstrated significant differences in the dimensions that drive HRQoL outcomes between rare and more common diseases and showcased that the same EQ-5D utility may reflect very different severities depending on the patient population under investigation. Future research should examine whether outcomes in other, critical HRQoL domains not included in generic measures also highlight significant differences across disease areas.