Increasing impact of non-industry drug clinical trials through experience with regulatory submission

Late-phase clinical trials are run with a view to impacting clinical practice & improving outcomes for patients. For industry-led trials of drugs & devices, the pathway to impact is clear: develop & run trials of healthcare interventions that can be submitted for regulatory review leading, if successful, to a new or extended license.

Industry cannot and will not do all needed trials of healthcare interventions; non--industry groups (academia, charities, government agencies) seek to bridge these gaps. However, industry-led trials cost 1-2orders of magnitude more to deliver.

A current MSc student's exploration of cancer CTIMPs in 2022/23 by sponsor type, & our pilot, wider scoping review of clinicaltrials.gov both show that a large proportion of late-phase RCTs involve collaboration between industry & non-industry. Yet, as shown by our previous PhD student, few trials with major non-industry involvement are used in regulatory submissions.

The objective is to enhance the "pathway to impact" by analysing factors in non-industry-led trials' design, conduct, and analysis that may hinder their delivery or the use of their results, for example by impeding the appropriate prescription of repurposed agents.

The ultimate aim is to extract valuable insights from these experiences, which can then be applied to trials, primarily those led by non-industry, to increase their use in decision-making by regulatory bodies & guideline committees, all while minimizing any additional delivery costs.

The distillation of lessons from recent experiences has the potential for widespread impact on the execution of clinical trials. The project plan consists of:

1. Scoping the scale of the problem: [a] Conduct detailed review of sponsorship & collaboration between industry & non-industry in recent late-phase CTIMP RCTs using a major international trial (meta-)registry. [b] Review summary European Public Assessment Reports (EPARs) available on the EMA website for successful & unsuccessful applications, categorized by extent of non-industry

involvement, & compare these findings to public-facing documents from selected regulators. [c] Identify examples of drugs with positive trial results not widely-available for prescribing.

2. Lessons: [a] Secure access to comments from inspectors/rapporteurs/reviewers from regulatory partners on trials submitted for review. (EMA previously made Rapporteur comments available from selected trials.) Distil key insights, without disclosure of confidential information. This may involve secondment to appropriate partner. [b] Perform in-depth, semi-structured interviews with trials teams that have published positive findings in industry-led & non-industry-led CTIMP RCTs completed since 2020 that underwent, or were excluded from, regulatory submissions.

3. Guidance: Extract, summarise & disseminate practical guidance tailored for teams working on RCTs with non-industry involvement that may be used in a regulatory submission. Investigate how these guidelines could have impacted the design, conduct or analysis plans of recently-initiated trials at UCL's clinical trials units.