If we consider a variety of legislation on the statute book in the UK for example, it is more often the case that citizens and corporations are left to define their own retention period that is consistent with both the statute of limitations (Limitations Act 1980 in the UK) and any inspection or audit requirements. There is, for example, no mandated minimum retention period for personal financial records within the Finance Act but the legislation does provide for the possibility of an inspection by HMRC within six years of the end of the financial year. There is no mandated minimum retention period for documents that demonstrate compliance with the Race Relations Act 1976 but action cannot be brought once a period of six years has expired. Similarly, there is no mandated minimum retention period for workplace health assessment records within the Management of Health and Safety at Work Regulations 1999, but action cannot be brought once a period of six years has expired. There are exceptions to these general rules but explicit retention periods in legislation are usually consistent with the relevant period described in the Limitations Act.
Why is this relevant? Well last week, the rapporteur for the new draft Clinical Trials Regulation in the European Union (Glenis Willmott firstname.lastname@example.org) published her draft report on the proposals. The report includes 74 amendments to the draft regulation text, including a suggested amendment regarding retention times for clinical trial records (the trial master file). The original draft regulation stated the following:
“Unless other Union legislation requires archiving for a longer period, the sponsor and the investigator shall archive the content of the clinical trial master file for at least five years after the end of the clinical trial. However, the medical files of subjects shall be archived in accordance with national legislation.”
This provides adequate time for regulatory agencies to conduct inspections of both the sponsor documents and investigator site documents. Clearly, if the sponsor’s timeline for marketing authorisation application extends beyond this five year period, the retention time would be extended in order to support the application. However, that is a decision for the sponsor.
The draft regulation has now been amended as follows:
“The sponsor and the investigator shall archive the content of the clinical trial master file for an indefinite period of time after concluding the clinical trial. However, the medical files of subjects shall be archived in accordance with national legislation. If the sponsor is unable to archive the master file, it may be archived in the EU database.”
The rationale for extending the retention period to indefinite is given as:
“Should a sponsor come under investigation for misconduct, the clinical trial master file would be vital. Therefore the master file should be archived indefinitely unless national legislation states otherwise. The master file can be stored in the EU database if necessary.”
I believe there are several significant problems with this new burden, not least of which is outlined in my introduction…. an indefinite retention period should not be mandated by legislation.
1. The existing retention period (minimum of 5 years after clinical trial completion and longer if the trial data supports a marketing application) should be sufficient to support the identification of misconduct.
2. If the reason for an indefinite retention is to help identify misconduct, it is questionable why the revised text permits reversion to national legislation with a shorter retention period be followed in preference to an indefinite period.
3. Given that a significant majority of clinical research misconduct is practiced by the clinical trial investigator site and not the sponsor, it is not understood why the sponsor’s retention period has been extended to indefinite but the subject files (source records) are only retained ih naccordance with national legislation, typically 5-10 years. It is usually the source records which help to confirm the presence of misconduct by the investigator.
4. The suggestion that the sponsor may archive the master file “in the EU database” is unworkable from a number of perspectives. Firstly, existing EU Directives and ICH GCP make it clear that the sponsor is responsible for retention of the sponsor trial master file. It is therefore inconsistent to suggest that if the sponsor cannot achieve this (or chooses not to), they may store the master file with the EMA in an EU database. The proposed wording suggests that it would be acceptable for the sponsor to transfer custodianship of the master file immediately a trial has closed. Secondly, it took several years for the development of a consistent content, structure and format for the clinical study report. Given the huge scope of the trial master file, it will take an age to agree the content, structure and format for master files to be submitted to the EU database. And finally, it is not clear what the “EU database” is that will be storing the trial master files. If it is the same database that is described in Recital 52, this significantly broadens the scope of this database and calls into question the requirement for its contents to be publicly available. This would open up the whole content of the trial master file to the general public.
5. No distinction is made between industry-sponsored clinical trials and investigator-sponsored clinical trials. The implication therefore is that the investigator site will similarly be required to retain their trial master files for an indefinite period. The implications of this burden cannot be under-estimated, both for industry and for investigators. Such a requirement may drive more clinical trials away from Europe.
And finally, this critique would not be complete without also commenting on Amendment 59, proposed text for Article 53, paragraph 1. The original text stated:
“All clinical trial information shall be recorded, processed, handled, and stored in such a way that it can be accurately reported, interpreted and verified while the confidentiality of records and the personal data of the subjects remain protected in accordance with the applicable legislation on personal data protection.”
This is now stated as:
“All clinical trial information shall be recorded, processed, handled, and stored in the format of a clinical study report, in such a way that it can be accurately reported, interpreted and verified while the confidentiality of records and the personal data of the subjects remain protected in accordance with the applicable legislation on personal data protection.”
The original wording referred to ALL clinical trial information in a wide variety of documents e.g. correspondence, monitoring reports, source data etc. However, the revised wording bizarrely suggests that all clinical trial information should be written in a clinical study report. Unless I’ve misinterpreted the text, this just doesn’t make sense.