Pharmacoepidemiologic and Pharmacoeconomic Latvian Study of Rare Diseases and Orphan Drugs. Summary of the Doctoral Thesis

Abstract

Rare diseases, also called orphan diseases, are life-threatening or chronically debilitating conditions of different origin. Majority of them are genetic disorders, others being rare cancers, congenital malformations, autoimmune, toxic and infectious diseases. Conducting clinical studies in small populations may be very challenging; therefore quality of clinical evidence may differ between rare and non-rare disease therapies. Nevertheless, number of orphan medicinal products on the market and number of rare disease patients, taking these usually expensive products, are increasing. As a result, budget impact of orphan drugs is growing. This factor, along with the cost-effectiveness of orphan drugs, is often considered in the reimbursement decisions, directly affecting accessibility of rare disease therapies. More than ten years have passed since Latvia became a Member State of the EU. Consequently, European regulations, including those related to rare diseases and orphan drugs, have been applied to Latvian legislative system. Orphan diseases have been recognized as a priority area for the European Community action in the public health system, though there are significant differences in the national healthcare services for rare disease patients among the EU States. The aim of the study was to determine situation in the field of rare diseases in Latvia, assess the impact of orphan drugs on the state budget and compare the findings with data from other European countries. The following sources of information were used: National plan for rare diseases, EUCERD reports, Orphanet data, Latvian and European regulations, publicly available data from the state and EU agencies and registers (SAM, NHS, EMA, Community register of designated orphan medicinal products and EU clinical trials register), as well as direct communication with drug manufacturers and wholesalers. Impact of orphan drugs on the state budget was estimated from the NHS perspective. It was calculated for the period of time from 2010 to 2014 in absolute values and relative to the total pharmaceutical market and total drug reimbursement budget. A literature review was performed for comparison with other European countries. Development and approval of the national plan might be an important step towards improving situation in the field of rare diseases in Latvia. Still, there are no official designated centers of expertise as well as no specific register for rare diseases in place. Newborns are screened for only two disorders: phenylketonuria and congenital hypothyroidism. 51 interventional clinical trials in rare diseases conducted in Latvia (all of which were multicenter and multinational trials) were identified through the EU clinical trials register. A total of 35 unique investigational medicinal products were studied in 29 different conditions. The majority of clinical trials were phase III trials, while oncology was the biggest therapeutic area. It has been found that clinical trials in rare diseases vary from those in non-rare conditions, with notable differences in trial randomization, blinding, enrollment and use of active comparators. However, no difference was found in trial duration and types of primary endpoints. Budget impact of orphan drugs in Latvia is very small in comparison with other European countries. It increased slightly over a period of five years, due to the slight increase in the number of patients and the number of orphan drugs reimbursed. Orphan drug annual expenditure ranged between EUR 2.065 and 3.065 million, with total 5-year expenditure EUR 12.467 million. It constituted, on average, 0.84 % of total pharmaceutical market and 2.14 % of total drug reimbursement budget, respectively. Anticancer drugs represented more than a half of the total orphan drug expenditure, followed by drugs for metabolic and endocrine conditions and medicines for cardiopulmonary diseases. Three indications: Ph+ CML, MPS II, and PAH accounted for nearly 90 % of the total orphan drug expenditure. Majority of orphan drugs authorized in the EU are not available in Latvia, moreover those drugs that are available are often not accessible because they are insufficiently reimbursed.