Common Clinical Trial Amendments, why they are submitted and how they can be avoided: a mixed methods study on NHS UK Sponsored Research (Amendments Assemble).

BACKGROUND

Amendments are changes made to a clinical trial after it has received regulatory approval. An amendment can take a significant amount of time and resources to develop, review and implement at participating sites. This can affect the efficient delivery of clinical trials and potentially contribute to research waste. This study aimed to establish what the most common amendments are, why they are submitted, and what, if anything, can be done to avoid them.

METHODS

An explanatory sequential mixed methods design was employed. The first strand involved a content analysis on a sample of amendments, submitted in trials sponsored by a University Hospital NHS Trust between September 2009 and March 2020, to establish the most common changes and reasons for amendments. The second strand involved thematically analysing semi-structured interviews with trial stakeholders to explore their views on the reasons underpinning the submission of amendments, and the potential for efficiencies that could prevent avoidable amendments.

RESULTS

Two hundred forty-two approved amendments were examined from 53 clinical research studies. The 'Addition of sites' was the most common amendment change, and the most common reason for amendments was 'To achieve the trial's recruitment target'. The root causes for avoidable amendments identified by the 11 interviewees included the following: 'Rushing the initial application knowing an amendment will be needed later', 'Not involving all the right people to input' at the start of the trial, and 'Realising it's not feasible in practice when delivering the trial'. Missing regulatory checks following an onerous and error-prone application process were also identified as the cause of some amendments.

CONCLUSIONS

Trials need to be critically reviewed by various stakeholders and have sufficient time allocated to planning and feasibility assessments to avoid some amendments. This may improve clinical trial efficiency, to benefit the trial participants, researchers, funders, sponsors, and regulatory bodies, and potentially bring new treatments to patients faster.