Managing clinical risk in Eastern Europe

Running clinical trials in Eastern Europe has its pros and cons - two industry veterans from Parexel discuss how best to manage the risks.

The advantages of Eastern Europe include a high patient population of over 200m with a high number of treatment naïve patients and a high incidence of diseases, leading to higher recruitment rates, good patient retention and compliance and ultimately valuable time and cost savings.

In addition, Eastern Europe has a good number of experienced investigators and a positive regulatory environment with ICH GCP already adopted and a new EU Directive currently being implemented.

However, despite the advantages, companies conducting clinical trials in Eastern Europe are facing the same challenges that were faced in Western Europe 20 years ago.

Dr Albertas Valavicius and Dr Aleksei Zhmuro, managers of Clinical Operations for Parexel in Lithuania and Ukraine respectively, spoke at the Association of Clinical Research Professionals (ACRP) conference held recently in Brussels to address some of these challenges.

"When operating in Eastern Europe sponsors must have an effective risk management program," stressed Dr Valavicius.

"This helps to control project time, cost, scope, and quality and allows sponsors to adequately identify risks and reduce their probability and the negative impact on project objectives."

In order to minimise risk, Drs Valavicius and Zhmuro suggest that identifying and managing the different types of risk at each of four clinical trial phases: planning; set up; monitoring and close out is the best way to proceed.

At the planning stage, assessing site suitability is crucial - it is wise to steer clear of sites that are inexperienced, are experienced but overloaded with other studies or those that have English language problems, said Dr Valavicius.

Equipment is also an important consideration as it is not uncommon to find sites without basics such as a computer, email, fax, freezer, cupboards and touch phones, he warned.

"Even when equipment is provided by the sponsor, it often has a nasty habit of disappearing during the course of the study."

Sponsors should therefore allocate additional expenses for equipment as well as general or study-specific training which is often required.

"Local staff members often need education, particularly on how to work effectively as a team as motivation inside a team can often be lacking."

"Culturally, Eastern European investigators can often be quite proud and prefer to work alone, or fail to keep others informed of what is going on, and may need education in this regard also."

Moving on to the set up phase, Dr Zhmuro advised sponsors to make sure they have a good knowledge of local requirements and timelines in order to submit documents, obtain licenses and finalise contracts etc. in accordance with the different laws of the different countries.

During the monitoring stage, risks to watch out for are those related to sites, such as the data quality, adherence to protocol, adverse event reporting, adequate laboratory test evaluation and filing and appropriate drug accountability.

At this stage sites can often fail to recruit once activated, due to initial overestimation of the patient pool, Dr Zhmuro warned.

Lack of experienced clinical research associates (CRAs) on the market can also cause problems during this stage.

During the close out phase, sponsors are advised to make sure that standards don't slip and that documents are correctly archived according to local business requirements, and that study documents do not go missing from files "as they have a habit of doing," said Zhmuro.

Last but not least, general cultural and psychological aspects of working in Eastern European countries should not be overlooked.

"Language issues can be problematic and paperwork needs to always be checked carefully, as well as the level of understanding of protocol etc. that staff members have," Dr Valavicius.

"Communication differences also need to be considered - Eastern Europeans are often introverted. Also the investigator and CRA may tend to become too friendly and may cross professional boundaries and this should be monitored."

The news in Eastern European-run trials is not all doom and gloom, however.

In a recent study, trials conducted in Eastern Europe did have nearly double the number of inadequately/incorrectly completed clinical records compared to those in Western Europe.

But on all other aspects measured, including failure to adhere to protocol, inadequate patient content, failure to report adverse events and inadequate drug accountability, Eastern European trials fared slightly better than those run by their neighbours to the West.