In January 2022 the European Medicines Agency (EMA) introduced the new Clinical Trials Information System (CTIS). Alongside new Clinical Trials regulation, from February 2023 this now means that EU member states must adhere to an initial timeline of 60-108 days from initial application, evaluation, and decision – with a few exceptions. Previous to this, study start up timelines widely varied per EU country.

With EU member states now aligned on clinical trial regulation as well as application and evaluation procedures, I spoke with Dana Leff Niedzielska, CEO & Co-Founder of August Research, a European-focused CRO with offices across the region on the opportunities to conduct trials in Bulgaria.

David (PBC Group): Can you provide an overview of the regulatory landscape for conducting clinical research in Bulgaria? What are the key requirements and processes that researchers and sponsors need to be aware of?

Dana (August Research): Some people may not know it, but Bulgaria is part of the European Union and follows all EU regulations for the conduct of clinical trials. Therefore, as of February 2023, all submissions for studies to be conducted in Bulgaria must be submitted according to the Clinical Trial Regulation (CTR) through the CTIS portal. It's the same portal that is used for submissions for Germany, France, Spain, etc.

The benefit for sponsors is that they only need to make one submission for all countries in the European Union but the challenge is that there are more documents to collect for the initial submission.

According to the regulations, the approval timelines for submissions range from 60-106 days. Submissions for studies with advanced therapies may have the review period extended by an additional 50 days.

David: What are the advantages and potential challenges of operating clinical trials in Bulgaria compared to other countries? How does the local healthcare infrastructure and expertise contribute to the successful execution of trials?

Dana: As a former Soviet Bloc country, Bulgaria has a very centralized health care system that allows for easier identification of specific patient populations and speeds enrolment via large treatment centres. Bulgaria has a lower standard of care and underfinanced health care system which makes clinical trial protocols attractive treatment options for patients and investigators.

As the trial sponsor is required to cover all protocol treatments, the burden on local health funds is decreased, which is also an advantage for the State. Well-trained medical personnel ensure the quality of the care and protocol compliance, at lower per-patient costs compared to other parts of Europe.

The main challenges of working in Bulgaria is the relatively small size of the country (~7 million people), limited site potential for advanced therapy trials and the lack of cutting-edge technologies which limits the ability to perform some trials.

David: How do you ensure patient recruitment and retention in clinical trials conducted in Bulgaria? Are there any unique strategies or considerations specific to the Bulgarian population that researchers should be aware of?

Dana: As mentioned earlier, the centralized health system in Bulgaria facilitates the identification of potential patients for clinical trials. It is not common to rely on direct outreach or campaigns for patients. The investigators can identify eligible patients through their databases and referrals from other doctors.

Since the standard of care in Bulgaria is lower than in most European countries, clinical trials are very attractive treatment option for patients who are in need of advanced medical care.

Patient retention is supported through our local CRAs who are very experienced, motivated and keep in close contact with sites to support them as needed. Regular calls with sites keep them engaged with the trial and committed to completing all visits, data entry, etc.

David: Could you discuss any recent developments or initiatives in Bulgaria that have aimed to improve the efficiency and quality of clinical trial operations? How have these initiatives impacted the research landscape in the country?

Dana: The large majority of clinical trials in Bulgaria have traditionally been conducted in the public hospital system. However, over the past few years there is an increase in the number of experienced investigators moving to privately owned medical centres or hospitals for their clinical trial activities. Generally, the private centres can deliver better overall quality with faster start-up, dedicated study coordinators, newer equipment, and a better physical infrastructure for the conduct of clinical trials.

David: Are there any specific therapeutic areas or research areas where Bulgaria has shown particular strength or expertise in conducting clinical trials? How has this expertise contributed to advancements in those fields?

Dana: As the prices have been increasing for cutting edge therapies, the Bulgarian health fund is not able to keep up with the costs and demand for these products. Patients with diseases treated with these medications are often put on waiting lists and must delay treatments. BioPharma developing competitive products in these categories can quickly identify motivated patients and investigators for their trials.

Overall, Bulgaria contributes to FDA clinical trials with higher per capita enrolment than many other countries of Europe. This was documented in an FDA publication, "Global Participation in FDA Trials Report" from July 2017 and the same trends continue today.

In conclusion, Bulgaria's participation in clinical research aligns with EU regulations and offers advantages such as centralized healthcare, attractive treatment options, and lower per-patient costs. While challenges exist, the country's expertise, experienced investigators, and recent developments contribute to the growth and success of clinical trials conducted in Bulgaria.

August Research will be exhibiting at COG Europe, taking place on the 10th & 11th October 2023, in Milan, Italy. More information can be found here: https://www.thepbcgroup.com/cog-europe

** Disclaimer: the views shared here are the author’s alone, and not of the Pharmaceutical Business Conference Group, August Research or any other organisations **