New rules bring faster approval of clinical trials, greater availability of innovative therapies in Croatia

The Ministry of Health will amend the rules for clinical trials of drugs in Croatia to expedite the approval and contracting procedures and increase the number of clinical trials in healthcare institutions, ensuring greater availability of innovative therapies for patients.

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Health Minister Milan Kujundžić confirmed to Hina that models from neighboring countries that successfully implement this, such as Hungary, Slovakia, and Slovenia, are currently being studied. The issue of clinical trials has been brought back to the forefront with the announcement by Prime Minister Andrej Plenković that 23 Croatian patients with spinal muscular atrophy will be included in a clinical trial of a new drug for this disease, conducted by Roche.

Clinical trials are particularly important for oncology patients and those with rare diseases

Changes are also advocated by the Innovative Pharmaceutical Initiative (iF!), an association that brings together 23 innovative drug manufacturers in Croatia. They warn that the approval and contracting process for clinical trials in Croatia is excessively long compared to other European countries – it takes an average of eight months, which is twice as long as in Hungary.

Clinical trials are direct investments in Croatia and its healthcare system, providing patients with quick and direct access to the latest drugs, and offering doctors new scientific insights and therapeutic options.

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“Patients participating in clinical trials have access to the latest innovative drugs that are otherwise not available on the Croatian market. This is particularly important for oncology patients for whom clinical trials are often the last option for continuing treatment and prolonging life, as well as for those suffering from rare diseases,” emphasizes iF!.

The healthcare system also benefits as savings are realized since the cost of treatment and diagnostic procedures is fully covered by the trial sponsor.

Therefore, the association recently presented solutions to the Ministry of Health that they claim could shorten the approval process to 28 days and make Croatia significantly more attractive for clinical trials.

In Croatia, an investment of only 9.2 euros per capita

Currently, there are 200,000 clinical trials being conducted worldwide, with an annual investment of 16 billion euros, so it is concerning that only 40 million euros or 9.2 euros per capita is invested annually in Croatia, points out iF!.

In Slovenia, for example, 161 million euros are invested annually in clinical trials, or 81 euros per capita, in Hungary 158 million euros annually, or 16 euros per capita, while Belgium invests 2.4 and Denmark 1.4 billion euros annually.

According to the Ministry of Health, there are currently 193 clinical trials being conducted in Croatia, with several in the approval process. Last year, 69 new clinical trials were approved, and in the first few months of this year, seven.

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Since 2009, an average of 65 trials have been approved annually. The largest number pertains to trials for oncological diseases, chronic inflammatory diseases such as Crohn’s disease and rheumatoid arthritis, cardiovascular diseases, multiple sclerosis, diabetes, etc.

For example, in the largest Croatian hospital, KBC Zagreb, 61 new clinical trials of drugs and medical products were contracted last year. The most are conducted in the Clinic for Internal Diseases (26), the Clinic for Heart and Blood Vessel Diseases (11), the Jordanovac Clinic for Lung Diseases (9), and the Oncology Clinic (5), with five to ten patients included in each study.

At KBC Rijeka, 49 trials are currently being conducted, and for most, the patient inclusion process is still ongoing. Over 350 individuals are included in studies across all three hospital locations. Among larger projects, the effectiveness and safety results of the drug roxadustat in treating patients with kidney diseases, and the drug LCZ696 intended for patients with heart complications, are highlighted by the hospital.

The trial is approved by the Ministry based on the opinion of the Central Ethics Committee

According to the current regulations, for a clinical trial of a drug to begin, the Central Ethics Committee (CEP) must provide an opinion within 30 days based on the extensive documentation that the research conductor is required to submit. However, this deadline is often exceeded due to requests for additional clarifications and documentation, as well as the fact that this body meets once a month.

Based on the positive opinion of the CEP, the trial must then be approved by the Ministry of Health within 30 days. After that, the contracting process begins with each healthcare institution where the trial is to be conducted, and since there is no deadline for concluding these contracts, this process can also be prolonged.

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While the pharmaceutical industry claims that the entire process takes an average of eight months, the Ministry of Health states that, in their case, this procedure was shortened to an average of 17 days last year.

At KBC Zagreb, they state that the contracting process with clinical trial conductors takes an average of one to two months, while at KBC Rijeka it takes 30 to 40 days, noting that this hospital is currently in the process of adopting a procedure that should reduce this timeframe to a maximum of 10 working days.

Croatian researchers are paid less than their colleagues abroad

Regarding funding, under current rules, 20 percent of the money from the clinical trial goes to the healthcare institution, while 80 percent goes to the principal investigator and other doctors, nurses, and staff conducting it.

The compensation for work, which includes patient inclusion in the study, their monitoring, and maintaining extensive documentation, is paid through the salaries they receive as employees of the institution, meaning that the compensation is additionally taxed, and often due to this, the salary falls into a higher tax bracket.

Since this involves additional engagement alongside regular work, Croatian researchers are paid less than their colleagues abroad, which is a reason for demotivation that can reflect on lower patient inclusion in the study, which ultimately affects the success of a study.

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Therefore, iF! believes that Croatia needs to take a clear stance and strategy to become a desirable country for conducting clinical trials. This includes systematic education of the medical professional community, timely information for patients about clinical trials, and the establishment of a National Register of Clinical Trials.

Since there are still prejudices in Croatia regarding clinical trials of drugs as a form of experimentation on humans, the pharmaceutical industry emphasizes that these are strictly controlled processes led by the best healthcare professionals who are in daily contact with patients with the aim of improving treatment outcomes.

The president of the Coalition of Health Associations, Ivica Belina, states that patient associations support initiatives that would lead to a greater number of clinical trials and their greater availability to Croatian patients.

Patients included in the study have advantages over other patients

“Patients are often not sufficiently informed about the possibilities of participating in clinical studies, which is especially important for patients for whom there are no other available therapies. Patients included in a clinical study are usually at an advantage over other patients because they are treated according to precisely prescribed procedures and receive better healthcare, and in case of any side effects, the trial is halted,” says Belina.

Additionally, Belina adds, clinical trials that come to us are mainly in the third and fourth phases, when the effectiveness of a drug has already been proven.

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Clinical drug research is conducted in four phases and lasts an average of 10 years, with an average research cost of 1.6 billion euros.

Drugs enter the clinical trial phase only after there is sufficient evidence that a new drug could outperform the effectiveness of existing drugs or be safer for use.

Thanks to innovative drugs that have passed the clinical trial process, mortality rates for many diseases have decreased – cancer mortality has fallen by 20 percent, from HIV complications by up to 80 percent, and hepatitis C is curable within 12 weeks.

written by: Tamara Marinković