Masterstudiengang "Drug Regulatory Affairs"

Master-Thesis

Clinical Studies in Eastern Europe: critical assessment of the regulatory requirements ***

Anna Volodina (Abschlußjahr: 2010)

Language: English

For the last fifteen years Eastern Europe has become one of the dynamic and attractive markets in clinical research. This region offers a perfect solution to the shortage in patient recruitment and high study costs in the established markets such as the US and Western Europe. Despite of political, geographical and socio-economical similarities this region is far from being homogenous. The purpose of this study is to take a closer look at Eastern Europe and to analyze the regulatory requirements for clinical research in four countries: Russia, Belarus, Moldova and Kazakhstan. The focus of the assessment is put on the clinical study approval procedure, notification of amendments, structure and procedures of the ethics committees, requirements to clinical research in vulnerable populations and customs regulations on human biological material and medicinal products. In addition, this study provides the outcome of the survey carried out with the representatives of competent authorities and research industry, where they share opinions on the regulatory frameworks and experience in these countries.
The study approval procedure in the reviewed countries consists of the ethical evaluation by the ethics committee and scientific evaluation by the competent authority. Submission of the application is done either in parallel (Belarus, Moldova) or sequentially (Russia, Kazakhstan). Duration of the study approval is laid down in the legislation of Russia and Kazakhstan and corresponds to 7 weeks and 33 weeks respectively. In Moldova and Belarus duration of the approval procedure is not fixed by the legislation, however according to the industry reports Moldova has the shortest approval times (4 weeks on average), and in Belarus it takes from 4 to 12 weeks to approve the study.

Ethics Committees (EC) in the reviewed countries are organized in the similar way and include central EC within the Ministry of Health and local ECs at the health facilities and higher educational institutions. Establishment of the ECs has been supported by the international organizations (WHO, UNESCO). Structure and operations of the ECs are in line with the ICH GCP standards. Ethical evaluation of the study is carried out by the central EC in Russia and Moldova; in Belarus it is always done by the local EC; in Kazakhstan the central EC reviews applications only for the international multicenter studies. Centralized ethical review system in Russia, Moldova and partly in Kazakhstan allows better control over clinical research, uniformity of procedures, consistency in adopted decisions and ability to deal with complicated issues due to the large application flow and therefore accumulated experience of assessors. Shift of the responsibilities on the local committees, on the other hand, ensures closer monitoring of the study, allows identifying and resolving ethical issues much quicker and facilitates direct and active communication with the investigator and the sponsor.

The reviewed legislations differ remarkably in their requirements to the investigator, conduct of the studies in vulnerable populations and definitions of the study types. The common provision between the countries is the requirement to carry out the clinical study in accredited medical facilities. This regulatory restriction is necessary considering the current state of the healthcare systems in the whole region. There are a lot of medical facilities, especially in the remote areas, that require substantial renovation, do not meet international standards and therefore can not be used as study sites. Accreditation, therefore, confirms compliance of the health facility to the GCP standards and adequate resources availability. Currently there are 946 accredited health facilities in Russia, about 50 in Belarus, 26 in Kazakhstan and their number increases annually.

The reviewed legislations of all four countries lacks proper description of the procedures carried out after the study approval, such as notification of amendments, submission of progress and final study reports, notification of adverse events and the end of the study. A number of regulatory concepts are not defined in the legislation: orphan drug (absent in Moldova, Belarus), observational study (absent all countries), post-marketing study (absent in Belarus, Kazakhstan, Moldova), substantial and non-substantial amendment (absent in Belarus, Kazakhstan, Moldova), etc.

In the conducted survey the industry representatives have identified two main challenges true for all countries: customs regulations hampering the study logistics and cultural perceptions to clinical research. The best strategy to overcome these hurdles is to seek assistance form local and international service providers and to empower local investigators in order to gain trust of the communities and overcome cultural issues. Areas of improvements in the national regulatory systems, identified by the representatives of the competent authorities, included poor requirements to health insurance for study subjects (Moldova, Belarus), non-harmonized standards on training of investigators and attestation of the ECs (Kazakhstan, Moldova) and poor quality of the study site inspections (Kazakhstan). All respondents share the opinion that although national legislations include clear regulatory provisions and procedures, a number of them do not work in practice and therefore a strong law enforcement mechanism is needed.

Pages: 62,
Annexes: 9, pages: 13