Section 2 - Patients’needs/epidemiology

2.1 Epidemiological profile of selected countries

2.1.1 OECD Countries

According to the World Health Organization’s estimates, around 5 000 rare diseases affect human beings on a worldwide scale. Some analysts estimate that these figures may evolve according to our knowledge of diseases.

For example, in the United States, it is believed that 20 million Americans are affected by rare diseases.

There is a difference between the prevalence (the percentage of population which is affected by a disease) and the incidence (the number of new patients affected by the disease per annum).

Some diseases affect very few patients, like Floating Harbor syndrome (20 cases have been reported), Freeman-Sheldon Syndrome (65 reported cases), Hallermann Streiff Syndrome (150 cases have been reported)....

Others affect a larger part of OECD countries’ populations like Malignant Hyperthermia (1/50 000 anesthezied patients), Narcolepsy (260 000 individuals in Europe)...

Some rare diseases, under patient associations’ pressures, are better known than others:

We could add to this list some cancers (lymphoma, eyes’ melanoma, sarcoma, kidney cancer, nasopharingeal cancer, childhood cancer...) and opportunistic diseases related to AIDS (cryptosporidies diarrhoea, progressive multifocal leucoencephalopathy...).

The previous examples of some rare diseases show that, taken as a whole, rare diseases are affecting a far from negligible part of developed countries’ populations.

2.1.2 Developing countries and less developed countries

Contrary to orphan diseases, tropical diseases are affecting millions of people, but likewise are not well treated mainly because of problem of economic profitability.

Paludism

It is affecting one billion people in the world according to the World Health Organization. Three million patients die every year from paludism. It remains uncertain whether an efficacious vaccine will be available.

Trypanosomiasis

The sleeping sickness is affecting fifty million people in thirty-six African countries.

Chagas disease is affecting 10 to 20 million people. Some efficacious drugs exist for sleeping sickness but are toxic like suramin, pentamidin or melarsoprol.

Nifurtimox indicated for Chagas disease is not well supported as a continued treatment and its efficacy is not admitted by all physicians.

Leishmaniosis

It is a parasitic disease which affects 12 million people every year according to WHO. Two treatments exist but are not fully satisfactory. There is some research concerning the epidemiology of the disease aiming to diminish the level of the transmission.

Filiarosis

Filiarosis affects over 100 million patients worlwide. Some treatments exist which are not satisfactory.

Schistosomiasis or bilharziosis

Those diseases have contaminated 200 to 300 million people worldwide.

Leprosy

It is affecting 15 million people.

Another acute problem in the developing countries is the distribution of safe and efficacious drugs. Often in these countries, the infrastructures are too weak to distribute the drugs which are needed by patients properly: lack of distribution channels, poor functioning of the existing distribution networks, diversion of drugs distribution...

The level of safety and efficacy of drugs is also an issue, because there is a lack of control by the Authorities, including cases of corruption which lead to the distribution of poor quality, or even dangerous, products.

 

2.2 Rare disease definitions

2.2.1 Criteria to identify rare diseases

Rare diseases affect a restricted number of people, hence the main criterion to identify rare disease is a prevalence level.

The single most criterion used to identify rare disease is a prevalence below 7.5 affected individuals per ten thousand people. This threshold was included in the US Orphan Drug Act (1983).

2.2.2 List of potential rare diseases in line with prevalence criteria

The European Commission’s DG V has established a list of rare diseases.

Some other rare disease lists are also available, providing additional information concerning disease diagnosis and treatment recommendations. One of the most complete list of rare disease was set up by NORD (National Organization for Rare Disorders) in the USA and is continuously updated with the assistance of affiliated patient associations.

Another attempt to broaden the knowledge concerning rare diseases and orphan drugs is made on a European scale through the Orphanet network. It provides information concerning rare diseases, their diagnosis and their characteristics.

This list aims also to monitor the inclusion of rare diseases with respect to prevalence criteria. This monitoring could lead to the exclusion of some diseases according to the evolution of their epidemiology.

For example, HIV infection at the beginning of the epidemy was a rare disease. As the medical knowledge about HIV increased, and also as the epidemy grew, it became less rare.

 

2.3 Patients’needs/health-care delivery

2.3.1 Health-care in the EU with regard to rare diseases and medicines

For the time being, it is within the marketing authorization procedure that orphan drugs are able to receive some support. But orphan drugs are not explicitly designated in the European Union with a specific status.

If the term "Orphan Drugs" is used in some European texts, no European policy explicitly designed to enhance orphan drugs development has been set up yet.

Orphan drugs were only partially and implicitely considered in the 91/507/EEC Directive which aimed to facilitate their registration process.

The centralized or decentralized procedures make it possible to reckon orphan drugs under exceptional circumstances as it is quoted in a recommendation from DG XII. There are some administrative support and low registration fees for orphan drugs, but there is no specific policy designed for orphan drugs in the European Union. For the moment, only the general status and the possibility of a ad-hoc legislation are mentioned in the 91/507/EEC directive.

Some European countries have already partially designed a status for orphan drugs:

France

The Health Ministry introduced the mention of drugs dedicated to patients affected by rare diseases through the December 8, 1992 law (Art L 601-2). The Health Ministry has also allowed the use of specific drugs in hospitals before they obtained their marketing authorization.

Spain

Like in France, orphan drugs are specified in the article N°34 of the drugs bill. It contains the mention "drugs without commercial interest".

Sweden

There is not a specific status for orphan drugs, but a particular process is allowed for a drug with a great medical value for which sales forecasts are weak: below 250 000-300 000 Skr or only 10 000-20 000 persons eligible for this drug.

Denmark

In Denmark, the Health Ministry has established a Research Centre for Rare Diseases and Handicapped People. To complement this measure, the National Health Council suggested an appropriate organization for hospitals including diagnosis and treatment.

In the United Kingdom and Germany, initiatives concerning Orphan drugs policy are still limited:

United Kingdom

In the field of research, there is a collaboration between Academic Authorities and the Pharmaceutical Industry. In some instances, requirements for marketing authorization are limited, subject to commercialization to a small number of patients and availability or additional data.

Germany

In the early ‘90s, the Pharmaceutical Industry Association proposed to the German Parliament that the possibilities for promoting R&D of orphan drugs be studied. The Parliament requested that this question should be dealt with at the European level

2.3.2 Review of unsatisfied patients’ needs in terms of caring for rare diseases, social protection and public health policies

The main unmet needs of patients affected with rare diseases are:

Lack of accurate diagnosis to quickly identify the disease

Deficiency of treatments

Insufficient lobbying

Patients are waiting for safe, efficacious and cost-effective treatments for rare diseases. The lack of orphan drugs status in Europe lead patients affected by rare diseases to wait that the drugs already sold in the USA or in Japan, become available in their countries, or that a European company develops such products.

There is also a lack of information concerning rare diseases. Some patient associations’ members have difficulties to find updated and relevant information concerning their conditions and the available treatments for their specific disease.

Some observers believe that it may be interesting to set up a European network on clinical trials for rare diseases in order to foster patients’ knowledge on therapies in development.

There is also a lack of clarity as to which specialists patients should visit. Patients need clarification concerning their disease management in order to improve their access to proper care.

Affording available treatments could also be a crucial issue. As there is no harmonization concerning European health-care systems, financing is still a national issue for each Member State. It may be crucial if drugs, especially issued from genetic therapies are expensive. But treating rare diseases, under the pressure of Patient Associations or the public opinion, is generally considered by health-care systems as a public health priority.

Physicians’ knowledge of rare diseases is also fragmented. This weakness leads to belated diagnosis which may be an obstacle for good patient management. Because of this lack of information, treatments are frequently inappropriate or ineffective and may even be harmful in some cases.

In summary, several studies have shown that professionals and patients face five main challenges concerning rare disease management:

substantial lack of information about the ongoing clinical research;

limited knowledge of experts and support services;

limited access to specialized health services and to approved therapies;

greater cost of providing advice, diagnosis and health interventions for rare diseases;

lack of financial resources.

 

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