RESUMEN
OBJECTIVE: The objective of this project was to evaluate the quality and quantity of initial applications for a clinical trial according to § 7 of the German Good Clinical Practice (GCP) ordinance (German: GCP-Verordnung, GCP-V), the quality of evaluations of those applications by Ethics Committees (ECs)/Investigational Review Boards (IRBs) in Germany as well as the pattern of EC objections in their reasoned opinions (vote). In order to identify a change over time, the results of the present survey were also compared with a survey performed in 2008. METHODS: Based on reasoned opinions issued by the respective EC in charge of the coordinating principle investigator (coordinating EC) in 2011, a written survey among members of the German Association of Research-Based Pharmaceutical Companies (vfa) was conducted in 2012. The answers to the questionnaire were analyzed descriptively. Since the data set collected in 2011 was structurally identical with the data set gained in 2007 both surveys were compared. RESULTS: Of the 24 companies represented on the vfa Clinical Research/Quality Assurance Subcommittee, 75% (18) took part in the survey. Survey evaluation was based on a total of 251 applications of these 18 companies submitted to 43 ECs. These account for about 21% of 1,214 applications for authorization of commercial and non-commercial phase I-IV clinical trials submitted to the regulatory authorities (BfArM and PEI) in 2011. In comparison to 2007, a lower amount of applications (n=251 in 2011 vs. n=288 in 2007) was submitted to a slightly higher number of ECs (43 in 2011 vs. 40 in 2007). The amount of objections increased by 21% from 1,299 (2007) to 1,574 (2011) resulting in an average of 4.5 (2007) vs. 6.3 (2011) objections per application. Overall, the analysis of both formal and content related objections revealed almost the same pattern as in the previous survey. In total, the most frequent objections applied to the patient information and consent form followed in descending order by trial protocol content, miscellaneous, other application documents pursuant to § 7 (2) and (3) GCP-V, formal deficiencies pursuant to § 8 (1) GCP-V, and investigator and site qualifications. A trend towards a slightly increased rate of objections concerning patient information and consent form (+4%) and a minimal decrease in objections concerning investigator and site qualifications (-2%) was observed. As in 2007, about 1 in 6 applications was still incomplete with formal objections. Whilst the proportion of study applications with objections related to the patient information and consent form (+7.2%), the trial protocol content (+11.6%), and documents according to § 7 (2) and (3) GCP-V (+11.8%) increased in 2011 compared to 2007, the amount of study applications with objections related to the investigator and site qualifications decreased by 6.3%. CONCLUSIONS: The majority of findings with respect to quantity, quality and main focus of objections reported in the first survey in 2008 were also found in 2012, indicating a shared understanding of applicable measures and criteria by sponsors and ECs on how to ensure patient rights and well-being, data integrity, and high quality documentation in clinical trials.
Asunto(s)
Investigación Biomédica/normas , Ensayos Clínicos como Asunto/normas , Industria Farmacéutica , Comités de Ética en Investigación/tendencias , Investigación Biomédica/tendencias , Competencia Clínica/normas , Protocolos Clínicos/normas , Ensayos Clínicos como Asunto/estadística & datos numéricos , Ensayos Clínicos como Asunto/tendencias , Alemania , Humanos , Consentimiento Informado/normas , Educación del Paciente como Asunto/normas , SociedadesRESUMEN
The review of requests for a positive opinion of the ethics committees (application procedure) as a requirement to start a clinical trial in Germany has been completely redesigned with the transposition of EU Directive 2001/20/EC in the 12(th) Amendment of the German Medicines Act in August 2004. The experience of applicants (sponsors, legal representatives of sponsors in the EU and persons or organizations authorized by the sponsors to make the application, respectively) in terms of interactions with the ethics committees in Germany has been positive overall, especially with respect to ethics committee adherence to the statutory timelines applicable for review of requests. However, inconsistencies between ethics committees exist in terms of the form and content of the requirements for application documents and their evaluation. With the objective of further improving both the quality of applications and the evaluation of those applications by ethics committees, a survey among members of the German Association of Research-Based Pharmaceutical Companies (VFA) was conducted from January to April 2008. Based on reasoned opinions issued by the respective ethics committee in charge of the coordinating principal investigator (coordinating ethics committee), the type and frequency of formal and content-related objections to applications according to section sign 7 of the German Good Clinical Practice (GCP) Regulation were systematically documented, and qualitative and quantitative analyses performed. 21 out of 44 members of the VFA participated in the survey. 288 applications for Phase I-IV studies submitted between January and December 2007 to 40 ethics committees were evaluated. This survey shows that about one in six applications is incomplete and has formal and/or content objections, respectively, especially those that pertain to documents demonstrating the qualification of the investigator and/or suitability of the facilities. These objections are attributable to some extent to the differing and/or unclear requirements of the individual ethics committees on the content and comprehension of the submission documents. However, applicants also need to pay more attention to the completeness and validity of the submission documents. The majority of content-related objections apply to the patient information and consent documents and study protocols submitted. Applicants on average acted upon only 3 out of 4 objections, for various reasons: the relevant information was already given in the submitted documents, but had not been taken into consideration by the ethics committees; objections were not applicable; objections lacked a legal basis. In such cases the applicants made reference to the specific information already submitted or gave reasons for not acting on the objection. This course of action was accepted by the ethics committees, with few exceptions. The survey sheds light on the existing inconsistencies in the evaluations of applications by the various ethics committees and suggests ways in which the existing constructive dialogue between applicants and ethics committees may provide a basis to further harmonize both the requirements regarding form and content of application documents, and the criteria for evaluation of applications by ethics committees within the legal framework.