Good practice is of the essence in clinical trials, and the data they produce – the result of major investment – is a highly sensitive and highly valuable long-term asset. As they gather it, trial sponsors and CROs must follow trusted protocols and processes. It stands to reason that, both during and after the trial, the exchange and storage of that data should be conducted with similar rigour. The scientific, regulatory and commercial implications of clinical trial data are enormous, and it deserves to have a long and highly productive life. If stewarded in line with good practice – emphasising security, integrity, accessibility and usability – it can continue to provide value for decades, or even indefinitely.

As a structured repository for clinical trial data, the trial master file (TMF) provides evidence of the diverse forms of good practice followed by the various stakeholders in the trial. In managing the TMF, sponsors and CROs strive for constant readiness for regulatory inspection while responding to evolving requirements for the safety, efficacy and reproducibility of trials. Inspectors from official bodies will wish to verify that the clinical trial has complied with regulatory requirements and the principle standards of Good Clinical Practice (GCP), and that the clinical trial data has been validated and stored correctly. If it has not, the TMF can fail the inspection, causing drug approval to be denied.

Over the past ten years, the paper TMF has been largely superseded by the electronic TMF or eTMF, which is better suited to the demands of a digitised world and ever-growing volumes of data – not least in data-heavy areas such as gene therapy, which are setting the pace for the future.

Arkivum’s particular interest is in the archiving of TMF data, which the EMA requires to remain secure and inspection-ready for 25 years. The TMF Futures report places archived data in the context of digital transformation and broader corporate objectives.

The 2021 survey found that 90% of life sciences organisations face challenges in the conduct of clinical trials, but as much as 80% plan to reduce the cost and duration of trials – and increase their chances of success – with the help of significant investment in technology, such as artificial intelligence, machine learning and cloud computing. In accelerating digital transformation, they are seeking to increase efficiencies, enhance collaboration, and modernise and improve the entire clinical trial process. Their priorities are now to:

• Improve the way the life sciences sector identifies and communicates with healthcare professionals and patient populations (50% of survey respondents cited this)
• Improve archiving and integration of the eTMF and other data on a large scale (38%)
• Further the adoption of decentralised clinical trials (34%).

Behind every TMF archive is the regulatory imperative of long-term inspection-readiness. Traditionally, that inspection has taken the form of a visit but thanks to digital technology remote inspections have gained ground during the pandemic. Beyond its regulatory role, TMF data can prove its value time and time again: in facilitating scientific discovery, pharmacovigilance, new formulations and marketing approvals, and in expediting corporate processes such as licensing, the establishment of partnerships, and due diligence for mergers and acquisitions. This presupposes that the data is ‘kept alive’ in the archive in accordance with good practice as defined by the FAIR principles, which undertake to keep data Findable, Accessible, Interoperable and Re-usable. These core principles are complemented by ALCOA+, originally established by the FDA with the aim of ensuring data integrity in areas such as pharmaceutical research: Attributable, Legible, Contemporaneous, Original, Accurate + Complete, Consistent, Enduring and Available.

In the context of digital transformation and technological acceleration, the eTMF’s strategic potential is becoming strikingly evident. TMF Futures 2021 reports that the vast majority (90%) of life sciences companies maintain a digital archive, and that living archive data is playing an increasingly important role in extending the applications of treatments. By definition, trial master files represent a much richer and more detailed source of data than published literature. Over the last year a total of four in ten life sciences organisations have accessed the TMF archive in order to locate data to support new submissions (34%), new indications (31%) and repurposing (7%). This compares to the 26% that accessed the archive in the context of a regulatory inspection.

Despite these opportunities, many life sciences and biopharma companies still struggle to protect, access and interrogate the data in their TMF archive. Just half (48%) of TMF Futures respondents said that, if they were inspected tomorrow by a regulator, they would be confident that their eTMF would pass an inspection. Indeed, 30% of all respondents and 80% of regulatory and compliance specialists went so far as to describe their TMF archive as very or extremely inadequate. Most confirmed that they are currently unable to use their archives to:

• Keep their data secure, accessible and inspection-ready for 25 years (59%)
• Conduct searches in real time to locate files in seconds (66%)
• Handle large volumes of data (75%)
• Upload data from multiple sources (81%)
• Provide a clear audit trail (83%).

The life sciences sector is hoping to ‘come back stronger’ after COVID-19. In the quarter century that the world has been online, data has given consistent proof of its power to drive discovery and the economy, and to shape our society. As digital transformation is achieved in life sciences, data will play a central and multifaceted role in innovation, in streamlining the development of new therapies at lower cost and – once marketing approval has been obtained for a drug – in maximising commercial and societal benefits.

Good data, and good management of data, will be key to success at every stage of the product life cycle. When it comes to extending and enriching that life cycle to the full, skilfully preserved data has a major contribution to make. As we have all seen, a period of 25 years – as stipulated by the EMA for archiving of the TMF – can hold all kinds of new possibilities.

Chris Sigley is CEO of Arkivum