Section for Rheumatology, Department of Neurology,Rheumatology, and Physical Medicine, Førde Central Hospital, Førde, Norway
The article describes functioning of drug procurement cooperation. A Norwegian organisation which main goal is to reduce costs of expensive treatments
Increasing cost of pharmacological treatment is a growing problem all over the world. This is partly caused by high prices of the original, patent protected medicines. The price must compensate costs of development of a new drug in the limited time of patent protection. Most of the new drugs bring about significant progress in therapy of many diseases.
One of the best example are so-called “biologics” drugs used in rheumatology. The “biologics” are heterogeneous group with different mechanism of action. All of them are biologically active proteins. The history of “biologics” in rheumatic diseases dates back to the 1990s. It began with infliximabnand etanercept, two anti tumor necrosis factor (anti-TNF) agents. Infliximab is a monoclonal, human-mouse antibody against TNF while etanercept is a soluble TNF receptor connected to Fc fragment of IgG .
A range of other anti-TNF agents as well as drugs with another mechanism of action was developed later. The group includes but is not limited to: adalimumab (fully human monoclonal anti-TNF antibody), rituximab (monoclonal anti-CD20 antibody, depleting B-cells), tocilizumab (monoclonal antibody against interleukin 6 receptor), golimumab (anti-TNF monoclonal antibody), certolizumab pegol (PEGylated monoclonal Fab fragment of antibody against TNF). Both anti-TNF therapy and rest of “biologics” brought significant improvement in outcome and prognosis of rheumatoid arthritis and other inflammatory joint diseases. The disadvantage is a high direct treatment cost, which may be difficult to bear for health insurance system also in countries with good macroeconomic results such as Norway.
Drug procurement cooperation (nor. Legemiddleinnkjøpssamarbeid – LIS)is an organisation which main goal is to reduce costs of expensive treatments .
It is necessary to overview Norwegian healthcare system to understand LIS role. Norway is a country with high role of public funds in the healthcare system. The system is tax-based and covers all inhabitants. The public expenditure on health was 7.6% of global domestic product (GDP) in 2007 when private was only 1.5% of GDP . The primary health services are managed and financed municipally/communally. The public specialist services are organised in four regional health enterprises. The health regional enterprises are divided in smaller units – local health enterprises, which manage hospitals and outpatient clinics for patients with somatic and psychiatric disorders. There are a small number of private hospitals and private practitioners that participate in the public specialist service. They are obliged to cover the same requirements as the state health institution. Those hospitals are mainly managed by non-profit organisations.
In rheumatology all patients who need intensive treatment for inflammatory joint diseases are treated and followed up at the specialist policlinics/hospitals in cooperation with general practitioners. It means that “biologics” are important for of the healthcare providers.
LIS is an effect of cooperation agreement between all four regional health enterprises. All public hospitals/policlinic participate in agreement via their regional institution. LIS organises the yearly tender and makes its results public. LIS publishes yearly recommendations for use of medicines that are subject of the tender. The recommendations list the medicines from the least to the most expensive. All suppliers are obliged to maintain price during adequate period (one year) after the offer was approved.
Per the LIS recommendations it is advised to choose the least expensive medicine from the list if there is no medical reason to use another one . It is endorsed to take into consideration:
- Ease of use, including injection frequency and storage conditions
- Particular disease manifestations, for example iridocyclitis and inflammatory bowel diseases in patients with ankylosing spondylitis
- Infusion cost, including local capability for treatment with infusions
- Travel cost
- Known response predictors, such as positivity for anti-CCP antibodies in rheumatoid arthritis and rituximab use or contraindications for traditional disease modifying drugs that are indicated to use with “biologics” (for example methotrexate and anti-TNF agents)
- Safety profile and comorbidities.
All medicines included in agreement are free of charge for patients and covered by the hospitals/policlinics that participate in the LIS system. All economical and medical liability lies with the local health enterprises or the independent hospital/clinic. The LIS recommendations are not superior to the clinical judgment. In practice a physician can choose any medicine from the list if it can be documented that it is beneficial for the patient. The recommendations are valid at the time of an introduction of a new treatment or at the time of any change of the treatment. The treatment change is made only due to medical reasons, not due to financial reasons.
In rheumatology all decisions regarding treatment introduction and change are made collectively by at least 2 specialists. The patient is assessed with validated clinical tools, according to the recommendations of relevant professional associations.
LIS made possible the control of expenses for expensive medicines despite growing number of patients treated with them . Some disadvantage is a short validity period of the recommendations. It can cause domination of one provider/producer that can increase price after achieving a desirable market share.
In resent years European Medicine Agency (EMA) approved 2 infliximab substitutions . Original infliximab patent run to 2015 in most of European countries and to 2018 in USA, but in some European countries it is no longer valid since 2013. One of those countries is Norway and these two infliximab substitutions were matter of the tender in 2014.
“Biologics” substitutions due to their complicate structure cannot be considered as generic medicines. Despite chemical similarity, including identical or almost identical amino acid sequence, post-transactional reactions can lead to different protein configuration. It can theoretically produce different biological effect. Therefore EMA uses term – “similar biological medicinal products”, short “biosimilars”. EMA has special registration procedure for that kind of product . For example it is accepted to expand registration to all original product indications even if a producer provides data for safety and efficacy only for same of these indications. Biosimilars are not subject of this article but it is worth to mention that they are widely discussed in professional community. Some concerns have been raised not only about the indication extension but also about possible immunogenetical issues occurring at possible switch between original medicine and its biosimilar. In Norway it was decided that biosimilars are not object to automatic switch. In LIS recommendation for 2014 one of infliximab biosimilar is the first choice for all indications, but it is not recommended to change between original infliximab and its biosimilars.
In conclusion: the LIS system, despite of its limitation, is a well functioning mechanism to control raising costs of medical treatment.
- Smolen JS., Landewé R., Breedveld FC., et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2013 update. Ann Rheum Dis 2013; 0:1–18
- Available from: www.lisnorway.no;
- Røed Dahl S., Manavado L., Monsen Ø., Siem H., et al. Norway and Health. An introduction. Apr 2009. Booklet of Norwegian Directorate of Health
- Available from: www.lisnorway.no; LIS-TNF/BIO Avtaler 2014
- Sparte 168 millioner på samarbeid om legemiddelinnkjøp i Hele Midt-Norge. 2014 [Cited 18.04.2014] From http://www.sykehusapoteket.no/no/Aktuelt/Aktuelt-fra-Sykehusapoteket/Sparte-168-millioner-pa-samarbeid-om-legemiddelinnkjop-i-Helse-Midt-Norge/122274/;
- European Medicines Agency. Guideline on similar biological medicinal products. Oct 2005