Masterstudiengang "Drug Regulatory Affairs"

Master-Thesis

Clinical trials in Central America: an analysis of the low MRCT allocation to this region by comparing the regulatory requirements in Cuba, Dominican Republic and Puerto Rico with EU standards

Elizabeth Klemm (Abschlußjahr: 2018)

Summary
Language: English

Introduction and objectives:
The most recent information about clinical studies in drug development and other health care issues provided by Human Research Protections (OHRP), National Institutes of Health (NIH), and Food and Drug Administration (FDA) web sites dated 10 December, 2017 shows a low percentage of clinical trials conducted in Central America compared with other areas in the world. While 261,364 studies were registered with locations in 201 countries, only 2592 were conducted in Central America, which represents 1 % of the total number of clinical trials registered. The aim of this thesis was to exhibit an analysis of different factors that could have led to the low participation in clinical trials, with a focus on three countries in Central America: Cuba, the Dominican Republic and Puerto Rico. The analysis is divided into two parts: first, it focuses on each country´s regulatory environment and second, it compares the allocations of trials in the three countries.

Issues under examination and methods:
Following the objective of identifying possible gaps in the regulatory framework of the three concerned countries: Cuba, the Dominican Republic and Puerto Rico by comparison of their regulatory requirements with the EU regulatory requirements including the requirements recommended by the WHO, the following clinical trial fundamental elements were established for comparing the standards of the countries: 1) Authorisation procedure, 2) Application dossier, 3) Protection of subjects in clinical trials, 4) Duration of a clinical trial, 5) Safety reporting and monitoring, 6) Compliance, good practice, 7) Manufacturing and import of investigational medicinal products, 8) Labelling and 9) Supervision, Inspections.
The regulatory effectiveness of the regulations in the three different countries was analysed by review of the structure of regulatory authorities and whether the regulations are founded on government’s laws.
In additional, records from the clinical trial registry ClinicalTrials.gov were taken as a basis for analysis. From the list of recorded trials, eight "cancer" diseases were selected per country to limit the number of records to be analysed.

Results:
Part I: Puerto Rico´s clinical trial requirements had the highest adherence to the EU requirements for all requirements analysed. By contrast, clinical trial requirements are not regulated in the Dominican Republic. There are no regulations on clinical trials fixed by law in the regulatory framework of the Dominican Republic.
Conformity with EU requirements was identified for Cuba for 7 of 9 selected clinical trials elements analysed. The following clinical trial key elements selected were regulated with similar strength: Authorisation procedure (including submission, assessment, establishment of timeline and procedure for modifying a protocol), protection of subjects in clinical trials, safety reporting and monitoring, compliance, good practice and supervision, inspections. By contrast, the Dominican Republic did not conform in all of the 9 elements analysed.
Part II: Requirements for site allocation similar to the EU were only found in the FDA regulation applicable in Puerto Rico. Different to the EU and Puerto Rico, Cuba’s clinical trial regulation scope does not consider closely the requirements and procedure for conducting multi-region trials that involve various countries.
Within the Central America region, Puerto Rico had the highest number of clinical trials registered (940) from all cancer trials allocated (1,172). By contrast, considerably fewer clinical trial records were found in Cuba (28) and the Dominican Republic (26).

Discussion:
Cuba´s current regulatory requirements, constituted by national laws and supported by the competent authority CECMED, are similar to EU Regulation 536/2014 in 7 of 9 requirements selected. However this does not have a significant influence on attracting international trial participation. Causes for the low participation of Cuba in clinical trials may be related to the aspects concerning requirement implementation but not the requirements themselves.
The Dominican Republic regulatory framework for medicinal drugs does not regulate the conduct of clinical trials; nevertheless 161 trials were registered for this country. This number represents three times more than the trials recorded for Cuba, which has a regulatory framework for clinical trials with ICH standards. As a result, on the one hand the 161 trials conducted in the Dominican Republic demonstrate that the availability of regulation does not have an impact on trial allocation for sponsors who do not follow the principles established in the EU, ICH and WHO. On the other hand, the 161 studies show a low allocation of clinical trials compared with the total number of trials allocated in Central America (2,592), probably due to the lack of regulatory requirements in this country.
Puerto Rico’s current regulatory requirements, constituted by US federal laws and supported by the competent authority FDA, are similar to EU Regulation 536/2014 in 9 of 9 requirements selected including the requirements for site allocation. This has a significant influence on attracting international trial participation. The high adherence to the requirements analysed between Puerto Rico (FDA) and the EU requirements is associated with the applicability of US requirements (FDA) in this country.

Conclusions:
Availability of regulatory requirements in accordance with the EU requirements leads to trial allocation only when these can be implemented, as demonstrated in the analysis for Cuba and Puerto Rico.
Adherence to the EU requirements leads to trial allocations when pharmaceutical companies/sponsors are interested in conducting trials with high quality standards in order to obtain acceptance of clinical data by the regulatory authorities. The low clinical trial participation of the three countries analysed is not associated with the current regulatory requirements, except the Dominican Republic, which does have regulations on clinical trials.
Clinical trial requirements in Central America are not harmonised regarding the conduct of multi-regional trials.

Pages: 102
Annexes: 8, Pages: 83