Life sciences professionals believe that COVID-19 must trigger a change in the way clinical trials are conducted and trial data is managed

As a consequence of the coronavirus pandemic, 41% of global clinical trials in fields other than COVID-19 (c.4,500¹) have been delayed or put on permanent hold. Looking ahead, 74% of life science organisations say that COVID-19 will continue to compromise their ability to deliver on clinical trial objectives for the next six to 12 months.

 That is just one of the findings of a major new report, TMF Futures: Keeping Data Alive², published today by Arkivum, which specialises in the archiving and digital preservation of valuable data, in collaboration with clinical and regulatory software specialists Phlexglobal, the Ethical Medicines Industry Group (EMIG) and Survey Goo. 

 As the life sciences industry takes the conduct of clinical trials beyond the first wave of the crisis, 70% of survey respondents identify a crucial opportunity for changing the way clinical trials are conducted in the future – with technology as an empowering factor.

 More than 200 life science professionals were surveyed, all of them directly or indirectly involved with the management of clinical trial data and the trial master file (TMF). More than half (51%) say that there needs to be more diversification of patient enrolment for clinical trials – e.g. that trials cannot focus on just one city, country or even continent. 37% say that more patients need to be enrolled to counteract possible future disruption, and 56% say there is a need for more virtual trials, incorporating telemedicine, remote monitoring of patients, wearable technologies, and mobile apps and devices.

 ► Challenges lie in the interoperability of eClinical applications and archiving of clinical data – potentially undermining good clinical practice and engendering regulatory risk.

 While the life sciences industry continues to embrace new technologies enthusiastically, the survey findings point to major deficiencies in:

·       interoperability between eClinical applications (39% of total respondents and 50% of CRO respondents are unable to convert documents from multiple eClinical applications);

·       the collection and archiving of clinical trial data (65% of compliance, legal and regulatory professionals describe their ability to access archived data as ‘extremely inadequate’ or ‘very inadequate’.

Unless addressed, these deficiencies could:

·      undermine any progress made in re-starting clinical trials;

·      compromise the benefits of technologies being used to transform the TMF into an eTMF;

·      engender regulatory risk, potentially causing delays to marketing authorisations;

·      hinder future access to TMF data, whether for pharmacovigilance purposes or in the cause of scientific discovery (new indications and formulations) and commercial growth (licensing, pricing and reimbursement, mergers and acquisitions).  

All in all, these current deficiencies could stand to cost the life sciences industry billions.

 

► The management and archiving of clinical trial data has moved beyond paper, but fit-for-purpose technology will open the way to further gains in productivity.

 

The trial master file (TMF)

Over the last 10 years the life science industry has moved to transform the conduct of clinical trials through the application of technology. The quest to eliminate paper from clinical research – and thus increase efficiency, enhance collaboration and improve trial performance – has transformed the primarily paper trial master file (TMF) into an electronic trial master file (eTMF).

 Over 90% of life science organisations (sponsors and CROs) have adopted eClinical applications, and 36% of sponsors and 48% of CROs now use purpose-built eTMF applications to manage clinical documents. Despite that, the survey finds that 45% of CROs continue to struggle to manage, locate and report data, while 50% are unable to convert documents from multiple software applications in order to make them usable. 

 When it comes to transferring valuable data from CRO to sponsor in clinical trials, many life science organisations use cumbersome and sometimes non-secure methods: 52% use email, 14% CDs, 12% data sticks and 25% paper files.

 The TMF archive

FDA and EMA directives require the data of completed trials to be maintained in an archive – in a continuous state of inspection-readiness – for at least 25 years. Nearly two-thirds (70%) of new sponsors use a digital archive.  That being said, the survey suggests that just 31% of life sciences organisations have a digital archive which facilitates good practice in long-term data management and can functionally ensure that archived data:

i)    continues to conform with the data management standards originally defined by the FDA with ALCOA+*, and that it remains Findable, Accessible, Interoperable, Reusable (FAIR), and

ii)   can meet the EMA’s stipulation in its 2018 TMF guidance that “The dynamic character of the audit trail should be preserved, when applicable.”

* ALCOA+ data integrity principles

ALCOA   Attributable / Legible / Contemporaneous / Original / Accurate

     +  Complete / Consistent / Enduring / Available

 

The survey also reveals that currently just 15% of organisations make plans for TMF archiving at the study start-up. 34% do so at phase 1, in accordance with GCP (good clinical practice).

 ► The life sciences industry stands to gain long-term commercial benefits from keeping clinical trial data alive in the archive.

 For all that life sciences organisations recognise the long-term value of TMF/archived data, many would stand to benefit from enhancing its accessibility: 38% of clinical trial sponsors currently find it very or extremely difficult to access, a proportion which rises to 65% amongst QA, compliance, legal and regulatory professionals.

 The survey found that 64% of life sciences organisations have experienced an inspection of an archived TMF, but the archive’s importance extends well beyond regulatory and compliance concerns. As organisations make further use of technology and data to extend the lifecycle and commercial potential of approved medicines, the digital archive must be increasingly responsive to broader objectives for innovation and commercial growth.

 Pharmaceutical companies (sponsors) say they need to access the TMF archive:

·      to support new indications and formulations   (45%)

·      in licensing and partnership opportunities       (34%)

·      to determine pricing and reimbursement        (22%)

·      to respond to legal challenges                       (28%)

·      for the purposes due diligence                       (19%)

·      in the context of mergers and acquisitions       (9%)

  Commenting on the report, Chris Sigley, CEO of Arkivum said:

 “In so many aspects of our professional and personal lives, COVID-19 has highlighted the practical value and transformational power of digital technology. Yet this report endorses a view expressed before the pandemic by influential voices: that in certain respects the life sciences industry has been outpaced by other highly regulated industries, such as banking and insurance, when it comes to digitisation. Now, as we all embark on shaping ‘the new normal’, is the time for the industry to overcome the digitization challenges it still faces.  

 “In the case of clinical trials, successful digitization presupposes efficiency and agility in collecting and managing data, and reliable interoperability between clinical applications. The electronic trial master file, or eTMF, has already become the norm, though our survey suggests that full interoperability often remains elusive.  The crucial and valuable data in the TMF merits special treatment – and specialist technology – when it comes to being archived. This is not just in the interests of regulatory compliance, but also of future scientific discovery and commercial growth. Clinical data has a life far beyond the clinical trial.”

References

1. 25,560 new clinical trials were registered in 2019. Statista: https://www.statista.com/statistics/732997/number-of-registered-clinical-studies-worldwide/

2. TMF Futures, Keeping Data Alive, September 2020