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Answering Questions about Clinical Trials in Eastern Europe (FAQ)
When exploring Eastern European and CIS countries as a destination for clinical trials, we receive a number of typical questions and stereotypical concerns from Sponsors. So, our team has decided to make a compilation of answers to frequently asked questions about clinical trials in Eastern Europe, Russia, and Commonwealth of Independent States (CIS). This is an attempt to clarify the decision-making process to consider tapping into our region or not.
The most common concerns Sponsors face are:
1. Lack of knowledge about clinical trials in Eastern Europe and Russia.
It is good to know that essential clinical trials procedures in Russia/Ukraine and Eastern Europe do not differ much from the European or American ones. National standards of clinical trials are a direct translation of ICH-GCP. However, there are some minor deviations present to meet regional regulations that your local clinical research partner has to be aware of and provide needed guidance to glide smoothly through these minor alterations.
It is noteworthy that Eastern Europe, Russia, and Ukraine have attracted many FDA and EMA inspections during global clinical trials. When studying the outcomes of those inspections one can notice that, for instance, audits of Russian research sites demonstrated better results than sites of commonly known as ‘leading’ Western European countries. Consequently, it is possible to positively affirm that Russia has a high number of sites with no deficiencies.
Normally Russian research sites demonstrate high adherence to the ethical standards. They provide adequate ICFs and an appropriate monetary compensation to volunteers. What is more, clinical research at Russian and Eastern European sites demonstrates the full accuracy of records and strict adherence to initial investigational plans.
To sum up the answer, we strongly recommend partnering with a trustworthy CRO with the local knowledge and regional presence. This will help Sponsor to avoid any unnecessary confusion and to benefit from the advantages of our region of operation to its fullest potential.
2. The data is of poor quality. The sites are below GCP standards.
This is one of common questions about clinical trials in Eastern Europe that arises when communicating for the first time with our clients. There is still a belief that Eastern Europe and Russia are somewhere behind in development and adaptation of the latest procedures and technologies. In fact, this is not correct.
First and foremost, implementation of ICH-GCP standards at sites is obligatory and regulated by local authorities. Thus, all sites adhere fully to international standards of Good Clinical Practice (GCP). Besides, all Principle Investigators (PIs) are extensively trained in GCP and have experience in clinical trials. In accordance with the law, all PIs should obtain a GCP certification, have at least 3 years of experience in clinical research, and specialize in the therapeutic area they wish to qualify for in clinical trials in order to be approved by local regulatory authorities. All these terms clearly demonstrate the implementation of the highest standards to maintain a high level of professionalism and to, consequently, provide the best quality of data.
In addition to these regulations, Accell’s monitors meticulously control accuracy of data receipt from the sites and adherence to the standards. Moreover, results of inspections could also provide a valuable insight on unfounded concerns about the quality of data and deviations from following international regulations.
As a real-life example, going through Accell’s past metrics reveals that Russian sites received a smaller number of Data Clarification Forms (DCFs) per dosed patient than the sites in the USA (88 in Russia versus 241 in the USA), as well as a fewer number of Data Management (DM) queries per patient visit (1,2 in Russia vs. 2,8 in the USA). In Accell’s current oncology trial, an independent auditor recently highlighted an exceptional accuracy of data and precision in documentation management at the sites that we work with.
Another way to verify the quality of data is to check the information on the FDA’s website. So, it will become quite clear that there is plenty of Russian and Eastern European sites taking part in global clinical trials with the data accepted by the regulatory agency.
By and large, it is primarily a preconception of poor quality and non-following GCP standards that keeps many Sponsors away from a recruitment goldmine that Eastern European and CIS countries nowadays are. Having a trusted partner will ease Sponsor’s navigation in the region making sure that only time-tested and well-performing sites and truly qualified PIs are selected to guarantee timely and reliable results.
3. There is too much of unfamiliar bureaucracy and red tape involved.
It is common that every country has their own regulations, set of rules and procedures, and it varies from region to region, 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 and CIS country.
It is essential for your local clinical research partner to be an ‘insider’ and have a clear system of dealing with all necessary paperwork in every country of operation. This would undeniably take away much of ‘bureaucratic’ burden from Sponsor’s shoulders and help them to concentrate more on product research and development. What is more, a comprehensive Sponsor’s instruction in advance on all documents required to get necessary approvals is a big bonus from research partner’s side. If the Sponsor precisely follows given instructions, no problems or delays will arise.
To learn more about the regulatory submission process and timelines within Eastern Europe and CIS countries see ‘Regulatory Approval’ part of this FAQ.
4. There are many hidden extra costs.
When receiving a project budget some clients are worried that it might eventually increase greatly after the initiation of the work. Mostly increases in costs are due to CROs specific manner of doing business. Often, it is based on a CRO’s attempt to win an initial bid by either underpricing the services or not including all expenses that the Sponsor will still inevitably face. Also, extra costs can arise due to the inability to properly plan the study in advance caused either by CRO’s or Sponsor’s miscalculations. With some CROs, hidden costs might become an unexpected issue, but not with Accell Clinical Research.
Principally, transparency is an essential part of Accell’s policy and a solid business rule of conduct. This is why the company adheres to transparent budgeting making sure there are no CRO-initiated change orders after the contract signing. Accell also makes sure all aspects are well negotiated and agreed on in advance and all risks have been disclosed and discussed with the Sponsor.
Nevertheless, we always warn our partners that there might be some alterations in pricing due to aspects that Accell cannot directly control. This could include national legislation changes, taxation changes, custom fee changes, etc.; and it is obvious that such shifts can occur within any country in the world at any given time. However, Accell Clinical Research constantly tries to optimize a trial budget and find possible solutions to solve a problem on a win-win basis. For instance, VAT changed recently in Russia from 18% to 22%, yet Accell made sure well in advance that due to its legal form the company worked without VAT. Thus, the change did not affect the Sponsor’s budget.
On the contrary to the belief that having a clinical trial in Eastern Europe and Russia might produce hidden extra costs, it can actually become more cost-efficient than running the same study in the USA or Western Europe. In fact, an average per patient cost in Accell’s region can be up to 30-40% lower than in the USA due to regionally differentiated costs (for example, more reasonable investigators’ fees) and a high concentration of patients in therapeutically aligned medical centers. Yet, of course, each clinical trial needs to be assessed separately to give a better picture of overall savings since the complexity and specific demands vary greatly from study to study.
In case you have any particular questions about clinical trials in Eastern Europe and their costs, do not hesitate to contact us. We will provide you with individual information concerning your specific research needs.
5. Regulatory approval in Eastern Europe takes too long.
The complexity of regulatory approval procedures and time to the first-site initiation play a vital role in strategic country-selection decision-making process. Now and then our team has heard some scare stories that approvals are taking too long (up to 6 months) in Eastern Europe. In fact, extended timelines in regions might become a reality as a drawback of using global CROs’ services which often lack flexibility and adaptability to the local legislation environment. However, at Accell, we normally get regulatory approvals within approximately 60 days depending on the selected countries and their regulatory landscape.
Having a real-life experience in regulatory submissions in all countries that the company covers, we can always advise on the countries with the most predictable and fast timelines to make sure Sponsor meets required deadlines. More detailed information on each country’s regulatory timelines is available in ‘Our Locations’ section of the website.
In short, we summarized timelines in a brief table below:
|Country||Timeframes||Submission to EC
|Belarus||60 days||Consecutive (LECs > RA)|
|Georgia||28-56 days||Consecutive (LECs > RA)|
|Hungary||60 days||Joint submission (dossier is submitted to RA)|
|Kazakhstan||10 business days||Simultaneous|
|Russia||60 days||Consecutive (RA + CEC (joint submission) > LECs)|
It is important to note, though, that not all countries always precisely adhere to declared timelines. Assuredly Russia, Georgia, Latvia, and Lithuania consistently follow stated deadlines. So, it is essential that a local research partner knows well if there are any potential ‘pitfalls’ and instructs its Sponsor accordingly suggesting an optimal solution for a clinical trial on a case by case basis.
6. Regulatory submission and filing procedures are risky and complicated.
Regulatory submission is not a complicated procedure if a Sponsor partners with a regional CRO with a vast experience at managing this task. Each country’s regulatory authorities and Local Ethical Committees (LECs) clearly describe procedures and document requirements along with timelines and fees. However, we always remind our clients that it is their responsibility to accurately provide us with all the required documents.
Specifically, it is crucial that a Sponsor has an Investigational Medicinal Product Dossier (IMPD) for an Investigational Medicinal Product (FDA IND Module 3) and a GMP certificate of the manufacturer. These documents are obligatory for Clinical Trial Authorization in all countries. Without these 2 documents, it is not possible to obtain a permit for clinical trial conduct. Apart from that, a Sponsor has no need to be troubled: the rest of the procedures will be your clinical research partner’s responsibility to complete.
There is also a prejudice that filing procedure can be risky since they are unknown to most pharmaceutical/biotechnology industry representatives overseas. Yet, these days all procedures are clear and well-structured. Your local partner has to know all intricacies of local regulatory authorities demands and should react swiftly if there are any changes.
Besides, it is recommended to have a regional partner with a local legal representative entity in order to be able to do certain activities. For instance, sometimes a Sponsor wishes to sign contracts directly with the clinical sites in Russia; however, in accordance with the Russian law only local legal entities have a capacity of doing so. That is why in such case the Sponsor just needs to issue a power of attorney to their local partner and the latter will do the rest of the job.
By and large, a question about regulatory procedures for clinical trials in Eastern Europe and CIS countries should not impede any extra problems if your local research partner knows well regional ‘landscape’ and has a local presence in order to take full care of all processes required for a swift and successful clinical trial initiation.
7. Importing drug is expensive and complicated.
It is obvious that there are costs arising when one imports something to a non-EU country from EU or the USA. These costs consist of a customs fee and of broker’s services for a custom’s clearance procedure.
Custom fee depends on the declared value of a product and comprises circa 30% of the value. Yet, it is crucial to consider each project individually to provide more accurate estimates. However, these are average numbers that would happen in any other part of the world and the situation is not exclusive to Russia or any other CIS country.
Secondly, broker’s services fees are usually a minor expense given all aspects of an average clinical trial budget. Besides, these costs can be easily disregarded due to overall savings on using local CRO’s services and lower investigators’ fees in comparison with Western Europe or the USA.
The complexity of importing really depends on what exactly is needed to be imported into a country. If Sponsor’s IMP is pills or injections, import is actually quite simple and easy. If there is a need to import specific devices, customs procedures can become just a bit more complicated. Yet, in the majority of cases it is achievable and any case, your regional partner is expected to take all burden in making sure an optimal solution is provided.
Here, at Accell we take seriously every aspect of the clinical research process, always do a feasibility research prior to making any promises and give a detailed instruction on how to proceed in every single case and at every single step of the clinical research to make sure your clinical trial is truly taken care of.
To sum up, there might be some preconceived challenges about clinical research in Eastern Europe and CIS countries, but, hopefully, the answers and details above make it clear that some of the issues are false beliefs, others are easily surpassed if a Sponsor works with a reliable research partner. However, numerous published studies obviously demonstrate that advantages of the region outnumber any ‘cons’ of having a clinical trial conducted in Eastern Europe, Russia, and CIS. Most obvious advantages are access to the patient pool and extreme recruitment speed as well as lower costs per patient in comparison with the USA or Western Europe.
Do you still have questions about clinical trials in Eastern Europe?
In case of any other questions or concerns, do not hesitate to get in touch with us: our team will be happy to discuss each specific clinical trial need and provide an optimal solution.
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