All over the world and across different nations and cultures, the standardisation in managing and providing clinical research is not a dream anymore, but it’s a reality with still growing awareness of the importance of international clarity and harmony in the clinical trials’ environment. Guidelines designating the direction of efforts in clinical regulatory and ethics standards were prepared almost 20 years ago by the International Conference on Harmonisation (ICH). The clinical research environment is dynamic, and is continuously growing in experience. As the basic principles ruling the course of the undertaken research are not precise, they leave a place for individual interpretation. The new European Medicines Agency (EMA) policy on publication of clinical data for medicinal products for human use, which is effective from 1st of January 2015, strengthens transparency in the publication of trials’ results by requiring public disclosure of the data submitted under the centralised marketing authorisation procedure in the European Union (EU). In addition, a new EU clinical trials regulation, that will harmonise administrative aspects of providing clinical research outlines a list of items that should be included in publicly posted summaries of the results. The implementation of these items in the clinical study reports (CSRs), will result in higher quality reports. The open-minded and flexible attitude should drive tailoring even the perfect guideline to each individual case, so the final CSR presents an effective and clear summary that is not overloaded with inapplicable details.
The regulatory and ethical basis of CSRs is grounded in the Section 5.22 of the ICH Guideline for Good Clinical Practice (ICH E6 Guideline), while the detailed guidelines for writing CSRs are given in the ICH Guideline for Structure and Content of Clinical Study Reports (ICH E3 Guideline). The European Medical Writers Association (EMWA) in co-operation with the American Medical Writers Association (AMWA) assembled a group of experts, named the EMWA Budapest Working Group (BWG), who is responsible for reviewing both documents and preparing verified reference for good practices in reporting clinical trials. The main objective of this reference is to ensure clarity and ease in preparing CSRs. It is planned to be an open-access, end-user resource that will complement the ICH E3 Guideline and its consecutive updates. It is almost certain that the whole pharmaceutical industry and its co-operators including medical writers, regulators, and at last but not least – patients, will benefit from this initiative.
Actually, the main problem observed in preparing CSRs in accordance with the ICH E3 Guideline is that the need for reporting certain information is not taken into consideration during the study start-up. The researchers usually pay attention to the CSRs’ guidelines at the end of the trial, when it is too late to fill the gaps in the collected data.
For those who take part in creating study documents, especially medical writers, the clarity of guidelines is of high importance. A de novo review of the ICH E3 guideline should provide recommendations minimising the existing ambiguity. The effort should be made to include rationale at the point of designing the study, in order to improve accuracy, transparency, and quality. It is often observed that study objectives are unclearly linked to study endpoints.
The important issue is that the section of the ICH E3 Guideline relating to adverse events reporting may be misinterpreted as only requiring the number of reported adverse events to be included, without detailing the actual nature of the experienced health disadvantages or/and life-threats. This fact shall be clarified and the basis for proper reporting shall be created. Summary of the adverse events that occurred during the study must be considered as an important component of the CSRs.
- Hamilton S., Seiler W., Gertel A. 2014. The EMWA Budapest Working Group: A 2-year collaboration to make recommendations for aligning the ICH E3 guideline with current practice and developing clinical study protocol guidance. Medical Writing. 23(4): 281-288.