Publication date: October 10, 2024
There were attempts to introduce into the Polish legal system the compassionate use procedure, when implementing the amendments to the Polish Clinical Trial Act and Pharmaceutical Law. The changes were to enter into force in 2022, however, ultimately, the Act did not include any mention of the so-called compassionate use procedure. This procedure, also known as the use of medicines in exceptional situations, allows patients to access therapies that have not yet been registered on the market. This is particularly important in the context of rare and serious diseases, where available treatments are insufficient or ineffective. In many European countries, including in EU law, compassionate use is regulated and is an important tool in protecting public health. Unfortunately, in Poland, the implementation of this procedure encounters numerous obstacles, which is a serious problem for patients and doctors.
Compassionate use allows for the use of new, unapproved drugs in patients who have no other treatment options. It is a humanitarian action, aimed at people suffering from serious, life-threatening diseases for which available treatments are ineffective or non-existent. Compassionate use provides the opportunity to use innovative therapies that are in clinical trials but have not yet been officially registered.
The European Union regulates the compassionate use procedure within the framework of Directive 2001/83/EC and Regulation 726/2004 (Article 83). This procedure is coordinated and implemented by the Member States, which establish their own rules for its application and financing of such programs. Coverage of the costs of therapy is usually carried out by both pharmaceutical companies and health services. According to the regulations, a medicinal product not authorized for marketing can be made available for individual use. This means making the medicine available to a specific group of patients due to a chronic, serious, debilitating or life-threatening disease, provided that this group cannot be effectively treated with available medicinal products. A medicine covered by the compassionate use procedure must be the subject of an application for a marketing authorization or be subject to clinical trials. The European Medicines Agency (EMA) can authorize the use of medicines on a compassionate use basis throughout the European Union, ensuring a uniform approach to this procedure. Member States also have the possibility to introduce their own regulations regarding the use of these medicines at national level, which allows for greater flexibility in responding to the specific needs of patients. The European Medicines Agency (EMA) defines COMPASSIONATE USE as “the use of an unapproved medicine outside a clinical trial in individual patients under strictly controlled conditions” or as “a treatment option that allows the use of an unapproved medicine”. The implementation of the compassionate use principle is at the discretion of each Member State, which must also take into account the EMA guidelines on compassionate use of medicinal products. There is considerable diversity in the requirements and characteristics of compassionate use programmes across the EU. The last decade has seen rapid development of new medicines and biological therapeutics. Marketing authorisation for new therapies is often time-consuming and stressful for patients. Additional programmes have been developed to address previous clinical trials that were the only way to access new medicines in development. However, not every patient meets the inclusion criteria, and participation in a trial is difficult for patients with life-threatening, long-term or severely debilitating diseases, such as rare diseases. Early access programmes such as the Compassionate Use Programme (CUP) have provided alternative channels for such patients. The European Medical Agency provides regulations and recommendations on compassionate use, on the basis of which each European Union (EU) member state has developed its own rules and regulations.
In Poland, the compassionate use procedure is not formally regulated, which is a significant problem for patients and doctors. In recent years, attempts have been made to introduce appropriate legal regulations, but none of them have been successful. On 17 January 2022, a version of the draft act on clinical trials of medicinal products for human use was published and was to ensure the application of Regulation (EU) No 536/2014 of the European Parliament and of the Council of 16 April 2014. Detailed information about the changes can be found in legislation Print No. 2843.[1] According to the plan to introduce the changes, the most important element was to be the application of “compassionate use”.
Due to this planned change there was aimed a new provision of the Pharmaceutical Law, Article 4da, according to which the President of the Office of the Medicinal Products and Medical Devices in Poland could issue consent to the use of a medicinal product under a program of individual use, however, a clinical trial would have to be conducted, there would have to be a completed clinical trial or an application for marketing authorization would have to be submitted, for a specific group of patients suffering from chronic or serious debilitating or life-threatening diseases, who cannot be effectively treated with a medicinal product authorized for marketing in the territory of Poland. The most important aspect, however, would be the fact that this person participated in a clinical trial of this medicinal product and gained a therapeutic benefit. Thanks to this change, the President of the Office would approve the use and issue a permit for the use of the drug under a program of individual use for a specific group of patients. The application process would consist of submitting an application by the responsible entity (“MAH”), sponsor or attending physician.
However, the changes have not been introduced and the clinical research sector and patients have been waiting for years for the introduction of the possibility of compassionate use, which is allowed by the Member States under Regulation (EC) 726/2004. Already in 2016, we could notice mentions in interpellation no. 2260[2], we can find in it the following fragment: “With regard to other indicated solutions, it should be noted that Compassionate use (i.e. financing of medicines by their manufacturers) and financing of benefits in connection with clinical trials will be the subject of assessment by a team that will be appointed by the Minister of Health in the near future. This team will be tasked with analyzing the currently applicable regulations and proposing solutions that could regulate these issues within the framework of the Clinical Trials Act”. The early stages of work related to the Clinical Trials Act included a certain change to the pharmaceutical law. It was to add provisions on an individual use program corresponding to compassionate use.
An exception to the principle of prescribing medicines approved for marketing in the country is established by art. 45 sec. 3 of the Medical Regulations, which allows a doctor to prescribe medicines approved for marketing in other countries. An example of the use of compassionate use in Poland is the use of remdesivir (an antiviral drug originally developed to treat patients with hemorrhagic fever, Ebola) in the treatment of COVID-19 patients in 2020. The specific one-time use by the Minister of Health still arouses surprise.
The lack of regulations on compassionate use in Poland can be attributed to several factors. First, there is a concern about the potential risk associated with patient safety. The use of unapproved drugs is associated with uncertainty about their effectiveness and possible side effects, which raises concerns among decision-makers. Additionally, introducing such a procedure would require the creation of appropriate supervision and monitoring mechanisms to minimize patient risk.
Second, the legislative process in Poland is complicated and time-consuming. The introduction of new regulations requires extensive cooperation between various institutions and administrative bodies, which often leads to delays and difficulties in reaching consensus. In fact, this argument cannot be considered a good one, due to the previously mentioned plans, as well as frequent changes to regulations in Polish law.
Third, the lack of appropriate regulations may result from budget constraints. Financing compassionate use programs requires significant financial outlays, which may be a barrier to the introduction of such regulations in Poland. The costs associated with research, production, and monitoring patient safety can be high.
The lack of regulations on compassionate use in Polish law is a significant problem that requires an urgent solution. Patients suffering from serious, life-threatening diseases for which there are no effective treatments should have the opportunity to benefit from innovative therapies that can save their lives. The introduction of appropriate legal regulations would ensure access to such therapies in a safe and controlled manner. The introduction of such regulations would increase the availability of innovative therapies for Polish patients and improve the quality of healthcare.
In the current legal status in Poland, there are no precise regulations regarding access to the so-called expanded access programs dedicated to clinical trial participants who respond positively to treatment with the product being studied. In practice, there are several options to provide treatment after the trial for those participants who benefit therapeutically:
– Further treatment with the investigated product.
Such a situation may occur if the clinical trial concerned a drug already registered in Poland for a given indication, then after the trial, treatment with the same drug can be continued if it is reimbursed or if the patient is able to bear the costs of treatment. If a given drug is registered in Poland for another indication, the possibility of treatment may be considered, although in such a situation there is usually no possibility of reimbursement of costs by the National Health Fund or they are very limited.
– Further treatment with another registered drug with a similar effect or the same active substances.
Such a situation may occur, for example, in the case of a clinical trial of a biosimilar drug if the reference biological drug is reimbursed in Poland or if the patient is able to bear the costs of treatment.
– Further treatment with an unregistered product tested as part of another clinical trial.
Various types of “follow up studies” or “open label studies” are often conducted for this purpose to enable the continuation of treatment and at the same time collect additional medical data on the tested drug.
Sources
[1] https://orka.sejm.gov.pl/Druki9ka.nsf/0/5D58C3895C6FC899C125890C004EEF90/%24File/2843.pdf
[2] Response to interpellation no. 2260 on taking action as soon as possible for patients with breast cancer overexpressing the HER2 receptor.