Rammell Consulting Limited

Proposed EU Clinical Trial Regulation – Update


Well, my optimism from our meeting with one of the UK MEPs a short while ago was misplaced! It appeared a possibility that the intention was to only retain the clinical study report indefinitely and not the whole of the TMF. This is NOT the case.

I have had it confirmed categorically by the rapporteur for the new Regulation that the intent of the proposes wording is to retain the whole of the trial master file – in electronic form only – for an indefinite period. The Committee on the Environment, Public Health and Food Safety (ENVI) are aware that there are concerns from industry on the practicality of these proposals and this will be something that will be on the table as negotiations continue with the European Council. The position of the Committee is that transparency and accountability are paramount and it is thought the trial master file would be invaluable should problems come to light a long time after the end of a clinical trial.

However, I have yet to hear a convincing argument to support this supposition. Suppose we have a drug that has recently completed its clinical programme, been given marketing approval and is then on the market for 30 years before serious side effects are identified. Given the vast quantities of post-marketing surveillance data that would have been collected over the coming 30 years and the existence of a huge amount of data available in the clinical study reports and their associated tables and listings (including individual case report forms for adverse events and deaths), I really have to question what additional value records in the trial master file would provide, other than to potentially protect the sponsor against accusations of improper conduct.

I’ve heard various “drug disaster scenarios” used as justification for the indefinite retention period (e.g. Stilbestrol) but these examples are all from the era when toxicology testing was fairly rudimentary compared to today’s regulatory environment. Since the 1950s, 1960s and 1970s, regulations governing pre-clinical safety testing have been significantly enhanced, including the requirement that “observations should be continued through one complete life cycle, i.e. from conception in one generation through conception in the following generation” [CPMP/ICH/386/95]. This does not completely eliminate any risk of teratological issues arising but it certainly makes it inappropriate to use examples such as Stilbestrol, Etretinate and Thalidomide as justification to retain records ad infinitum.

So where do we go from here? Industry really needs to start taking this issue seriously as it will undoubtedly have a significant impact on the conduct of clinical trials. Perhaps the biggest impact will be on academic and investigator-sponsored studies where a high proportion of trial records are still maintained and archived in paper format; these will all need to be maintained in a fully validated, electronic trial master file system (eTMF) and measures put in place to archive the electronic files indefinitely. Relevant industry bodies and companies need to lobby their MEPs and regulatory agencies with urgency to ensure common sense prevails on this issue. Parliament is due to begin debating this issue later this year.