Clinical Trials in Eastern Europe: Although clinical sites in Eastern Europe have been proven as excellent contributors in delivering timely, high-quality data, and have been known for high recruitment, sponsors still have a lot of concerns when making a decision whether to select this region for conducting their clinical trial. Besides the expertise of its principal investigators, Eastern Europe offers willing participants, who are showing high interest in participating in clinical trials. On top of that, the centralized healthcare systems common throughout Eastern Europe funnel patients into a few specialized centers, making it easier to identify patients who meet protocol criteria and to treat a large number of patients at one site. As a result, recruitment in Eastern Europe is almost always higher compared to the one in Western Europe or North America. High patient motivation and compliance can be accredited to the fact that, in spite of the negative picture clinical research may have in media, patients in this region still have a high level of trust in their physicians and are open to their suggestions. Clinical trials very often may represent a unique opportunity for patients to get access to novel, costly or otherwise unavailable medications. In many instances, the drugs undergoing clinical trials in Eastern Europe may not be considered novel in Western Europe and North America markets and may even be commercially available.
Nevertheless, we often hear that sponsors have questions and are unsure about whether Eastern Europe is the right location for their trial. In this article, we would like to address six typical misconceptions about clinical trials in Eastern Europe.
1. The quality of data in clinical trials in Eastern Europe is poor
A concern with the quality of data has been often raised by the clients in the past, especially for Russia, although our experience speaks in favor of good quality data obtained from this country, as the results of three sponsor’s audits revealed no major
findings. Eastern Europe, Russia, and Ukraine have attracted a number of FDA and EMA inspections during global clinical trials. Many of these audits show the same if not better results in these sites than those in the US or Western European countries, as
investigators often demonstrate a high adherence to ethical standards. They provide adequate ICFs, appropriate monetary compensation for volunteers, full accuracy of records and strict adherence to initial investigational plans. This is also still a common apprehension that Eastern Europe and Russia are falling behind in the development and application of the latest procedures and technology. This is not the case. Implementation of ICH-GCP standards at sites is obligatory and regulated by local authorities. The relevant principle investigators are all certified, with the necessary experience and specialization to be approved.
2. There is too much unfamiliar bureaucracy
Every country naturally has its own set of rules and procedures, with expected variations from country to country. Eastern Europe can be divided into nations that adhere to the European Medicines Agency (EMA) guidelines and those with their
own internal standards. However, these days there are well-structured written procedures required for clinical trial initiation in each Eastern European country. Any bureaucratic burden can be eased for a sponsor with the help of a local clinical research partner who understands the varying systems and landscapes.
3. Regulatory approvals in Eastern Europe take too long
The complexity of regulatory approval procedures and start-up timelines play an important role in the strategic country-selection decision-making process. Some of our clients have raised concerns that some approvals were more than 7 months in Eastern Europe. However, our experience is showing that, with the help of a local CRO that has the flexibility to be adaptable to the local legislation environment, this is rarely the case. Eastern European countries are aware of the damage that long start-up timelines may have on the clinical research market and have been working to shorten them and bring them into reasonable timeframes. Study phase, study design and the overall rationale for the study will play an important role in the decision-making process conducted by Regulatory Authorities, who may raise questions or ask for additional information, which would have an impact on the overall timelines. However, many countries that were known by their long start-up timelines, such as Serbia whose official start-up timelines were almost 8 months, now require between 3.5 and 4.5 months. For other Eastern European countries, including Russia, our experience is that start-up timelines are between 3.5 and 5.5 months. It is highly likely that the extended timelines might be a drawback resulting from using global CROs’ services, which are often less flexible and adaptive to the local legislation environment. It’s essential that you have a local CRO who can advise you on the most predictable and fastest timelines to help you meet the required deadlines.
4. There are too many hidden costs
When working in Eastern Europe and Russia, some sponsors worry that the project budget they receive will eventually increase due to hidden costs that are not immediately apparent. However, most increases in cost are often due to a CRO’s specific manner of doing business. To win an initial bid a CRO may underprice its services or not include all expenses the sponsor will face. Extra costs may also arise due to poor planning of the full study or miscalculations. Transparency with a CRO is a cornerstone to avoiding hidden costs. We believe that using a transparent budgeting policy and making sure all aspects are negotiated and
agreed in advance with all risks disclosed and discussed, will help to avoid unnecessary surprises. The use of a local CRO, familiar with ongoing changes that may be beyond control, such as national legislation changes, taxation or custom fee
changes, might be beneficial. It is a fact that clinical trials in Eastern Europe and Russia are more cost-efficient than running the same study in the US or Western Europe. This is not only due to the investigator fees that can be even up to 5 times lower compared to the US, but also due to lower vendor costs and high concentration of patients in therapeutically aligned medical centers.
5. Regulatory submissions and filing procedures are risky and complex
Regulatory submissions should not be a complicated process if you are working with a CRO with adequate regional experience. The necessary procedure and document requirements, along with the timelines and fees, can all be found through each country’s regulatory authority and Local Ethical Committee. The most crucial aspect is that a sponsor has an Investigational Medicinal Product Dossier for an Investigational Medicinal Product and a GMP certificate of the manufacturer. These documents are obligatory for Clinical Trial Authorization in all countries. There are also assumptions that the filing procedure can be risky. However, these days all procedures are clear and well-structured. Your local CRO should know the intricacies of any local regulatory authority’s demands and be able to respond swiftly to any changes. It is recommended to have a regional partner with a local legal representative entity so certain activities can be completed. For example, in Russian law only local legal entities are capable of signing contracts directly with clinical sites in Russia. In this instance, a local partner is necessary, and therefore a Sponsor can issue the power of attorney to complete the action on their behalf.
6. Importing drugs is expensive and complicated
There are always costs arising from an import of anything new to a non-EU country from the EU or the US, ranging from customs fees to brokerage services, etc. However, custom fees often depend on the declared value of a product, while brokerage fees are usually minor given all aspects of an average clinical trial budget. The complexity of importing really does depend on what exactly needs to be imported into a country. If a sponsor’s IMP is pills or injections, the import can be quite simple and easy. When there is a need to import specific devices, custom procedures can become a bit more complicated. However, in the majority of cases, your regional partner should be able to complete adequate research and give you detailed instructions on how to proceed to minimize the cost impact.
In Conclusion
To sum up, there may be some pre-conceived challenges about clinical research in Easter Europe and Russia. While some are false beliefs, others can be easily surpassed with the right knowledge and experience from a reliable research partner. Ensure your partners have not just the medical and logistics skills needed to run a trial smoothly, but that they speak the local language fluently and know how the clinical trials bureaucracy works in the country in question. Only then all the pieces of
running a successful clinical trial can fit together. There are clear advantages to exploring clinical trials in Eastern Europe and Russia such as greater access to patient pools, extremely fast recruitment speeds and lower costs per patient. If you would like to explore the region further, Hygeia Research will be happy to assist.
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