International Day of Rare (Orphan) Diseases

Every year on the last day of February, the world celebrates the International Day of Rare (Orphan) Diseases. The term “orphan diseases” includes rare diseases, the frequency of which does not exceed two cases per 10,000 people. 80% of rare diseases are due to genetic causes. Patients require expensive, continuous and lifelong treatment.

“My goal is to defend the interests of not one, but all patients with orphan diseases at the state and regional levels.” – Tetyana Kulesha, head of the board of the public union “Orphan diseases of Ukraine”

The national legislation of Ukraine consists of important legal acts that regulate that orphan patients are guaranteed and provided with the necessary treatment:

• Law of Ukraine “Basics of the legislation of Ukraine on health care”.
• Resolution of the CMU “On Approval of the Procedure for Providing Citizens Suffering from Rare (Orphan) Diseases with Medicinal Products and Appropriate Food Products for Special Dietary Consumption” dated March 31, 2015 No. 160.
• Decree of the CMU “On the approval of the Concept for the development of the system of providing medical care to citizens suffering from rare (orphan) diseases for 2021-2026” dated April 28, 2021 No. 377.
• Decree of the CMU “On approval of the plan of measures for the implementation of the Concept of development of the system of providing medical care to patients suffering from rare (orphan) diseases for 2021-2026” dated October 11, 2021 No. 1235.
• Order of the Ministry of Health “On the introduction of extended neonatal screening in Ukraine” dated August 4, 2022 No. 1396. Extended neonatal screening in Ukraine became operational on October 1, 2022. Neonatal screening is a comprehensive examination of newborns aimed at detecting hereditary (genetic) and congenital diseases (including screening for some orphan diseases as well).
• Resolution of the CMU “Some issues regarding managed access contracts and suspension of the first paragraph of clauses 1-2 of the Resolution of the Cabinet of Ministers of Ukraine dated March 25, 2009 No. 333” dated January 27, 2021 No. 61.

The “Medical Designer” team met with Tetyana Kulesha, the head of the board of the public union “Orphan diseases of Ukraine”, to find out the latest news in the direction of “Orphan diseases” and what changes await patients already in 2023.

In your opinion, is the neonatal screening of newborn babies in Ukraine fully operational?

Considering the state of war in Ukraine, unfortunately, we have two fully functioning neonatal centers and expect the launch of two more centers (Kryvyi Rih and Kharkiv). In my opinion, when four neonatal centers are already operational, then we can already talk about full-fledged work. If we talk about the subject of full-fledged screening studies, it will take approximately six months, so that we can already evaluate the work of the centers and the number of screening studies. After all, the main purpose of neonatal screening is to detect diseases in a newborn child, including orphan diseases for effective treatment, in case of detection of diseases.

Creation of a registry of patients with orphan diseases in Ukraine, what advantages does it provide for the medical system of Ukraine?

We have been talking about the register of patients with orphan diseases for five or six years. We, as the GS “Orphan Diseases of Ukraine”, proposed to create a separate register. When the question arises of how many patients with orphan diseases are in Ukraine, no state institution (MOH, National Health Service, etc.) has an answer to this question, because no official statistical information is kept on the number of such patients. Currently, in the process of implementation of the “Concept for the development of the system of providing medical care to citizens suffering from rare (orphan) diseases for 2021-2026”, the ORPHANET National Classifier will be adopted. Each patient, according to the available nosology, will be included in such a classifier and the number of patients with SMA[1], epidermolysis bullosa, cystic fibrosis, etc. will already be known. Currently, NGOs, health care facilities, health departments/offices maintain tentative registers of orphan patients, but such numbers are not reliable. Therefore, the introduction of ORPHANET will solve this problem and provide answers to many questions in this direction. Unfortunately, the International Classification of Diseases (ICD) does not include an extensive list of nosologies in the orphan field, and this is also a problem not only in Ukraine, but also in the whole world. In Ukraine, we expect that ORPHANET will be an addendum to the International Medical Center and integrated into the E-Health system, and all information will be accumulated on patients with orphan nosologies.

That is, the integrated ORPHANET system will be a separate column in the E-Health system?

Yes, it will be a separate column. Thus, the doctor will see in the E-Health system that the patient has the main disease – an orphan disease according to the corresponding ORPHANET code. In this regard, if we are talking about children, the pediatrician sees information on the patient, the ORPHANET code, and this is already a signal to the doctor that such a patient needs appropriate therapy.

Will reference orphan centers bring medical care to patients with orphan diseases?

Creation of a network of reference orphan centers is one of the tasks of the “Concept for the development of the system of providing medical assistance to citizens suffering from rare (orphan) diseases for 2021-2026”. Already in 2023, such a network is being created, health care institutions submit applications that they are ready to join such a network and provide qualified medical care to patients at the regional level. Patients will be registered in such centers, and it will already be known how many patients there are in the regions of Ukraine. In the future, such centers will create a need for the Ministry of Health to provide medicines for orphan diseases. Such actions will significantly bring medical care to patients with orphan diseases, both in the adult population and in children.

What is the position of the NSZU regarding the financing of reference orphan centers?

The centers will function on the basis of health care institutions and will be financed by the National Health Service in accordance with the medical guarantee program at a certain ratio. After all, patients with orphan diseases require a multidisciplinary approach to treatment, more specialized knowledge of doctors and medical personnel, more time must be spent during the reception of patients. Therefore, given that almost every medical guarantor program package contains a list of services that the patient will potentially need, the idea is to apply the ratio specifically for orphan patients (ie, the doctor will receive a premium for orphan patients according to the ORPHANET code).

When do we expect ORPHANET to be integrated into the medical system of Ukraine?

We strongly believe that it will happen in the near future, maybe even in the summer or from the third quarter of this year.

For 2022, what is the trend in terms of the number of appeals by parents who have encountered orphan diseases to your public union? What kind of support do you provide to parents?

We have official statistics, according to which the public union helped 150 families move abroad. The main questions we had were the following:

• If you have gone abroad, where can you get treatment there?

• Internally displaced persons in the middle of the country, where can they get the necessary treatment on the territory of Ukraine?

According to our statistics, 30% of orphan patients left abroad, and 70% of orphan patients remained in Ukraine, whom we help with further treatment.

Are there any obstacles to treatment for Ukrainian patients who went abroad after February 24, 2022?

There are different situations depending on the country and the human factor. Some patients did not receive treatment abroad at all and returned to Ukraine, because not all European countries purchase expensive drugs for the treatment of orphaned patients with state funds. Inability to see a doctor on the day of seeking medical help or the next day, because patients with orphan diseases cannot wait 2-3 weeks or months. These are the main reasons why patients with orphan diseases return to Ukraine. In Poland, patients with SMA received appropriate expensive treatment, we also have such cases. Ukraine has already started the procedure of purchasing expensive medicines under managed access contracts, we hope that such steps will bring patients even closer to a high-quality treatment strategy and our patients who are abroad will return to Ukraine for further treatment in Ukraine.

Are parents already aware of what orphan SMA disease is and what the treatment strategy is? Does the pediatrician explain it or do they figure it out themselves?

Currently, there is a lot of information in the public domain, public organizations also provide informational support to parents. Unfortunately, not all family doctors (therapists, pediatricians) have special knowledge of what SMA is, where to refer the patient for specialized medical care, and the subsequent treatment tactics. Usually, parents turn to public organizations, we provide all necessary informational support to parents or patients with orphan diseases. This should not be the case, because doctors, first of all, should know what to do with such a patient and where to refer them. We hope that the introduced orphan centers will solve this problem, we will see.

In your opinion, since the beginning of the medical reform, in particular in the primary care, has the awareness of doctors regarding orphan patients increased?

Unfortunately, doctors’ awareness of orphan patients has not increased, not all family doctors know what orphan diseases are and what to do with such patients. Some doctors became knowledgeable not at the expense of the reform, but at the expense of acquiring knowledge on their own initiative or during communication with colleagues who already had professional experience in managing such patients.

Will the introduction of a must have short course (as part of continuing professional development) on educating primary care physicians about orphan diseases improve the situation?

So! It would be easier for patients and doctors, because such patients need more attention from a family doctor, regardless of whether they are a child or an adult. A family doctor must know where to refer such a patient, and not refer to just where without knowing for sure whether the doctor is referring correctly. We are as ready as possible to participate in the development of such a course and are open to cooperation in this direction.

Martial law and procurement of medicines by the Ministry of Health in 2022. Did the patients (adults and children) receive the necessary medicines from the state?

Yes, indeed, in 2022, Ukraine received medicines through purchases and humanitarian aid. There are no complaints, because the Ministry of Health and State Enterprise “Medical Procurement of Ukraine” made all the necessary purchases and the patients received appropriate treatment.

Are managed access contracts for “Orphan diseases” the only solution for speeding up the delivery of medicines to patients?

Managed access contracts are not about speeding up, but one of the opportunities to get expensive drugs to patients at a price that is lower for the state than the market value of such a drug. The price under managed access contracts is confidential, but the principle of such contracts is that the Ministry of Health concludes direct contracts with drug manufacturers on favorable terms for both parties for a period of three years, then the price is revised.

Can we already say that the “Concept for the development of the system of providing medical assistance to citizens suffering from rare (orphan) diseases for 2021-2026” is gradually being implemented? (If we take into account the period 2021-2023)

We can definitely say that the “Concept for the development of the system of providing medical assistance to citizens suffering from rare (orphan) diseases for 2021-2026” is being implemented. Neonatal screening is already operational, ORPHANET is on the way to implementation, reference orphan centers are on the way to implementation – these are the most important pillars of the Concept.

We understand that it is difficult to plan for 2023 now, but still, what priority changes should society expect in terms of medical care for patients with orphan diseases?

We will continue to expand the list of nosologies in the orphan direction for managed access contracts. I am confident that we will be able to add Duchenne to procurement of medicines through managed access contracts. We will introduce ORPHANET and the introduction of reference orphan centers this year. That is, changes will take place in the coming months, and it is certainly encouraging that precisely because of such changes, the number of patients who will receive treatment will increase.

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[1] Spinal muscular atrophy (SMA) is a rare (orphan) genetic disease. Patients with SMA lack the SMN1 gene, which encodes the SMN protein, which is necessary for the operation of motoneurons. In patients with SMA, the motor neurons of the spinal cord gradually die, which leads to the death of neuronal connections with muscles and muscle atrophy – a complete stop of muscle activity over time. This is a gradual, but irreversible process, which means the loss of the ability to move and, over time, to breathe.