Data analysis of medicines aimed at health technology assessment within the activities of the “Circle of Kindness” Foundation from 2021 to 2024

Background. In 2021, the Russian Foundation “Circle of Kindness” was established to provide additional financial support for children with severe life-threatening and chronic diseases (including rare and orphan ones) requiring essential treatment, particularly expensive medicines. At the same time, the predominant part of the provided medicines is intended for the treatment of rare diseases. Methodological support for decision-making regarding the inclusion of diseases in the list of diseases and medicines in the procurement lists of the “Circle of Kindness” Foundation is provided by health technology assessment conducted in the Center for Healthcare Quality Assessment and Control. Objective: To analyze the characteristics of medicines that underwent assessment during the four years of operation of the “Circle of Kindness” Foundation, depending on their inclusion status in the procurement lists, as well as to review the evidence base confirming the clinical effectiveness of the analyzed medicines. Material and methods. A total of 187 pairs of “medicine – disease” that underwent assessment were analyzed based on the following characteristics: registration status of the medicines in the Russian Federation, the United States of America (USA), and the European Union (EU), and data on orphan status for registered technologies; the presence of unmet therapeutic needs for the given medicine (absence of alternative therapy options); and data on the availability of generic medicines. Characteristics of published studies on the clinical efficacy of the medicines included in the analysis contained information on study design, used endpoints (surrogate or clinical outcomes), median follow-up duration, control group, as well as the presence of comparative studies for each “medicine – disease” pair. Results. It was found that medicines included in the procurement lists, compared to the analyzed non-included medicines, were characterized by a higher frequency of obtaining orphan status in the USA (84.6% vs. 67.8%) and the EU (65.7% vs. 38.8%) as well as by the absence of alternative therapy options (50.6% vs. 32.0%). Use of surrogate endpoints only was reported in 56% of published studies on the clinical efficacy of the medicines; the median time follow-up for outcome assessment was 12.00 months (interquartile range 5.52–35.94). Among study designs, randomized controlled trials and single-arm studies predominated (36.7% and 30.9%, respectively). Published data on the results of comparative studies were absent for 36.8% of all analyzed “medicine – disease” pairs. Conclusion. Pairs of “medicine – disease” included in the “Circle of Kindness” Foundation lists are characterized by a high unmet medical need (absence of alternative treatment options) and, in more than half of the cases, by the corresponding orphan status in the EU and/or USA. The obtained results also correspond to data from domestic and international authors regarding the predominant use of surrogate endpoints and the prevalence of single-arm study designs justifying the efficacy of orphan medicines. These findings highlight the relevance of conducting health technology assessments of medicines with high uncertainty regarding their effectiveness, which, on the one hand, allows for consideration of the limitations of evidence from their clinical studies, and on the other hand, summarizes data on other significant characteristics of the medicines and rare diseases.