Clinical-Functional and Pharmacoeconomic Effectiveness of Modern Therapy for Cystic Fibrosis in Children

The dissertation is devoted to a comprehensive evaluation of the clinical-functional and pharmacoeconomic effectiveness of modern therapy for cystic fibrosis in children. The research is based on a comparative analysis of the condition of patients with cystic fibrosis and the cost of their treatment in three time periods (1993–1994, 1998–1999, and 2003–2004) in Moscow, as well as on a comparison of data from patients in Moscow and other regions of Russia. The study evaluates the impact of the introduction of microspheric pancreatic enzymes, the mucolytic drug dorzolamide-alpha, and anti-pseudomonal antibiotics (ceftazidime, cefepime, meropenem) on the clinical course of the disease, life expectancy, and the economic costs of treatment. Special attention is devoted to the evidence base for the implementation of inpatient-replacing technologies in the practice of cystic fibrosis treatment.

RELEVANCE OF THE PROBLEM

Cystic fibrosis (CF) is the most prevalent hereditary pathology at the present stage. This is a monogenic disease caused by a mutation in the CFTR (cystic fibrosis transmembrane conductance regulator) gene, characterized by damage to the exocrine glands of vital organs and typically having a severe course and prognosis. For a long time, cystic fibrosis was classified as a prognostically unfavorable disease leading to a fatal outcome in the early years of a child's life. At present, achievements in the elucidation of the disease, new possibilities for early diagnosis, and the improvement of treatment and rehabilitation measures lead to a significant increase in the duration and improvement of the quality of life of patients [3, 33, 129]. Being an important medical and social problem associated with considerable moral, physical, and financial costs incurred by families, healthcare authorities, and society as a whole for diagnosis, treatment, rehabilitation, and social adaptation of patients, cystic fibrosis dictates the necessity of constant search and improvement of the most acceptable methods of treatment under the conditions of the modern economy for the preservation of lung structure and function by the time genetic methods of treatment become applicable and accessible [22, 52].

Modern treatment of cystic fibrosis is complex and costly, encompassing medicinal preparations such as pancreatic enzymes, mucolytics, bronchodilators, antibiotics, hepatoprotectors, and vitamins. As demonstrated previously, effective outpatient treatment (day hospital, hospital at home) with the use of modern preparations often makes it possible to avoid inpatient treatment without reducing the volume and quality of medical care and to improve the quality of life of patients with cystic fibrosis.

The cost of treatment of one patient with cystic fibrosis amounts to 15,000 US dollars in the United States, 31,000 US dollars in the United Kingdom, and 29,200 euros in Germany [52, 87]. However, standards ensuring the optimal ratio of quality of medical care to treatment cost have not been developed.

Thus, the comprehensive determination of clinical-functional and pharmacoeconomic effectiveness of the therapy conducted at the present stage is highly relevant, as it will make it possible to identify the most rational approaches in treatment and rehabilitation programs for patients with cystic fibrosis.

OBJECTIVE OF THE RESEARCH

To study the clinical effectiveness and economic feasibility of the inclusion of certain modern preparations and medical technologies in the complex therapy of cystic fibrosis in children.

TASKS OF THE RESEARCH

1. To conduct a comparative analysis of the clinical-functional state and life expectancy of patients with cystic fibrosis residing in Moscow in various time periods of 1993, 1998, and 2003.

2. To compare the clinical-functional characteristics of patients with cystic fibrosis from Moscow and those residing in other regions of Russia (2003).

3. To determine the total cost and pharmacoeconomic effectiveness of treatment of a patient with cystic fibrosis in Moscow in 1993, 1998, and 2003 with expensive preparations (microspheric pH-sensitive coated pancreatic enzymes, dorzolamide-alpha, anti-pseudomonal antibiotics (ceftazidime, cefepime, meropenem)) included in the therapy of cystic fibrosis in the given periods.

4. To investigate the pharmacoeconomic feasibility of the inclusion of inpatient-replacing technologies in the treatment of cystic fibrosis at the present stage.

SCIENTIFIC NOVELTY

For the first time in the Russian Federation, the effectiveness of the inclusion of microspheric pancreatic enzymes with pH-sensitive coating, modern parenteral antibacterial preparations of the anti-pseudomonal group, and the mucolytic drug Dorzolamide-alpha into the standards of complex therapy of cystic fibrosis in children in Russia at the stages of their introduction was clinically and pharmacoeconomically evaluated.

The pharmacoeconomic feasibility of the implementation of inpatient-replacing technologies for the treatment of patients with cystic fibrosis has been demonstrated.

For the first time, a direct relationship between the cost of treatment and the life expectancy of patients with cystic fibrosis was established and proven.

PRACTICAL SIGNIFICANCE

High clinical-functional and pharmacoeconomic effectiveness of microspheric enzymes (Creon), Dorzolamide-alpha (Pulmozyme), and certain antibiotics (ceftazidime (Fortum), cefepime (Maxipime), and meropenem (Meroneem)) in the treatment of children with cystic fibrosis has been demonstrated. A comparative clinical-functional characterization of the course of cystic fibrosis in different periods made it possible to develop formularies and standards of treatment for cystic fibrosis in children in the Russian Federation. The clinical and economic evaluation of inpatient-replacing technologies demonstrated the feasibility of their further implementation in the practice of regional cystic fibrosis centers in the Russian Federation.

IMPLEMENTATION OF THE RESULTS

The results of the research have been implemented in the practice of the Russian and Moscow Cystic Fibrosis Centers of the Federal State Unitary Enterprise "Federal Medical and Biological Center" of the Russian Academy of Medical Sciences, the departments of medical genetics of the Russian Children's Clinical Hospital of the Ministry of Health of the Russian Federation (Moscow), the cystic fibrosis departments of the City Clinical Hospital No. 13 named after N.F. Filatov (Moscow), and a number of regional cystic fibrosis centers.

DEFENSE OF THE DISSERTATION

The defense of the work took place on September 29, 2005, at the scientific-practical conference of the scientific-clinical department of cystic fibrosis of the Federal State Unitary Enterprise "Federal Medical and Biological Center" of the Russian Academy of Medical Sciences, with the participation of employees of the Department of Pediatric Diseases No. 2 of the pediatric faculty of the Russian State Medical University of the Ministry of Health of the Russian Federation, the Department of Social Medicine of the Russian Medical Academy of Postgraduate Education, and physicians of the Russian Children's Clinical Hospital.

The main provisions of the dissertation were presented at: 1) the V Congress of the Russian Genetic Society, Ufa, 2005; 2) the 7th International Slavic-Baltic Forum "Saint Petersburg — Gastro — 2005", Saint Petersburg, 2005; 3) the 28th European Conference on Cystic Fibrosis, Crete, Greece, 2005; 4) the IV Congress "Modern Technologies in Pediatrics and Pediatric Surgery", Moscow, 2005.

PUBLICATIONS

Eleven scientific works have been published on the topic of the dissertation.

VOLUME AND STRUCTURE OF THE WORK

The dissertation is presented on 140 pages of typed text. The work includes the following sections: introduction, literature review, materials and methods of research, 3 chapters of own observations, conclusion, conclusions, practical recommendations. The bibliography includes 169 sources, of which 85 are domestic and 84 are foreign. The work is illustrated with 42 tables and 6 figures.