(BSPOT36) Assessing Clinical Evidence for the Incorporation of Technologies in Ultra-rare Diseases in Brazil: A Decade of CONITEC Reports

Background: The decision-making process for health technology assessment (HTA) in ultra-rare diseases faces a significant challenge for agencies worldwide.

Objectives: The objective of this study was to describe the clinical evidence reported in the reports of recommendations for the incorporation of technologies for the treatment of ultra-rare diseases from the National Commission for the Incorporation of Technologies (CONITEC) of Brazil.

Methods: Data were extracted from recommendation reports for the ultra-rare diseases evaluated between 2012 and 2022. To classify a disease as ultra-rare, the epidemiological criterion or a consultation with the ORPHANET platform was used (prevalence of ≤ 1/50,000 inhabitants). The extracted variables included the type of evidence synthesis, type of studies, instrument, the result of the assessment of the methodological quality of the studies, the format of evidence synthesis presentation, whether the evidence was graded, and the result.

Results: Of the 53 reports analyzed, 70% were based on randomized clinical trials, followed by systematic reviews and, finally, observational studies. Positive recommendations (incorporating technology into Brazil's healthcare system) were based on Systematic Reviews representing 63% of reports. The GRADE tool was applied to 27 recommendation reports, presenting the quality of evidence as low level (62%) or very low level for the two main outcomes studied. However, of the 53 reports evaluated, no clear link was observed between the quality of the evidence and the final recommendation (for or against the incorporation of the technology). Reports containing meta-analysis had a higher rate of recommendation in favor of incorporating the technology (83%), compared to reports that did not perform meta-analysis (55%). Surrogate clinical outcomes were the majority in evaluations of ultra-rare diseases. The characteristics of the clinical evidence influenced the final decision (incorporation or not of technology), especially when new evidence was shown in public consultation or had the potential to change disease progression, such as reducing serious events or increasing survival.

Conclusions: Ultra-rare diseases represent a challenge, both in quantity and quality of evidence. Traditional HTA frameworks applied in the context of ultra-rare diseases are apparently inadequate to account for the difficulties associated with a lack of robust evidence. As a limitation of the analyses presented here, the heterogeneity in the structure of older reports compared to more recent ones is noted, reflecting methodological advancements in HTA in Brazil.