Access to Orphan Drugs: A Comprehensive Review of Legislations, Regulations and Policies in 35 Countries

Abstract

ObjectiveTo review existing regulations and policies utilised by countries to enable patient access to orphan drugs.MethodsA review of the literature (1998 to 2014) was performed to identify relevant, peer-reviewed articles. Using content analysis, we synthesised regulations and policies for access to orphan drugs by type and by country.ResultsFifty seven articles and 35 countries were included in this review. Six broad categories of regulation and policy instruments were identified: national orphan drug policies, orphan drug designation, marketing authorization, incentives, marketing exclusivity, and pricing and reimbursement. The availability of orphan drugs depends on individual country’s legislation and regulations including national orphan drug policies, orphan drug designation, marketing authorization, marketing exclusivity and incentives such as tax credits to ensure research, development and marketing. The majority of countries (27/35) had in place orphan drug legislation. Access to orphan drugs depends on individual country’s pricing and reimbursement policies, which varied widely between countries. High prices and insufficient evidence often limit orphan drugs from meeting the traditional health technology assessment criteria, especially cost-effectiveness, which may influence access.ConclusionsOverall many countries have implemented a combination of legislations, regulations and policies for orphan drugs in the last two decades. While these may enable the availability and access to orphan drugs, there are critical differences between countries in terms of range and types of legislations, regulations and policies implemented. Importantly, China and India, two of the largest countries by population size, both lack national legislation for orphan medicines and rare diseases, which could have substantial negative impacts on their patient populations with rare diseases.

Orphan drug policies and use in pediatric nephrology

“…Product development is initiated when an application for orphan drug designation is approved, allowing the company to proceed with certain benefits and fiscal incentives, including reduction of regulatory fees, tax credit for the costs of studies, fee waivers, priority review for authorization, and 7 (USA) or 10 (Europe) years of market exclusivity per indication [3,13,14]. A recent comprehensive review showed that most European, Asian, and North American countries (27/35) had adopted orphan drug legislation [3] and that these regulations have promoted the development of orphan products [15][16][17] although some issues, pertaining to pricing, have arisen, regarding incentives given to companies that later reap huge profits [18].…”

“…If the price is excessively high, availability will depend on coverage and reimbursement policies and regulations, imposed by society as well as by insurance companies. Health technology assessment (HTA), the systematic appraisal of a novel therapy and its consequences, is usually applied [3]. Governmental agencies may rely on incremental cost-effectiveness ratios (ICERs) for evaluation of drug price in relation to health benefits.…”

“…QALY ratios utilized for assessment of orphan drugs may have certain shortcomings [3,5]. In the calculation of QALYs, an inherent assumption is that the quality of life scale (Y-axis) and the time scale (X-axis) are linear, which is seldom the case in clinical practice.…”

“…There is an estimate of close to 7000 rare diseases altogether [1,2], and the cumulative prevalence is estimated to affect up to 6-8 % of the world's population [3]. Ultra-rare diseases have a prevalence of 1 in 50,000 individuals or less in Europe (EU regulation 536/2014).…”

Proposed changes to the reimbursement of pharmaceuticals and medical devices in Poland and their impact on market access and the pharmaceutical industry

“…Thus, orphan and ultra-orphan products (targeting diseases that affect <5 in 10,000 people [24], and ≤1 in 50,000 people [2], respectively) are required to demonstrate cost-effectiveness at the current willingness-to-pay (WTP) threshold of three times the gross domestic product (GDP) per capita per quality-adjusted life year (QALY) gained [5] (in 2015, GDP per capita was PLN46,764, or approximately €11,000 [22,25], which would translate into a WTP threshold of approximately PLN140,000 or €33,000 per QALY). This threshold appears rather stringent, given that reimbursement decisions based on clinical value and measures of innovation – rather than a formal cost-effectiveness analysis – may lead to broader coverage for orphan drugs [26], thus improving patient access. The proposed changes exempt ultra-orphan drugs from the aforementioned cost-effectiveness requirements, and focus reimbursement decisions in ultra-orphan indications on factors that may justify the drug’s price, such as clinical effectiveness [27].…”