Disrupted research journeys: Exploring the experience of premature clinical trial termination.

: (Alternative Format Thesis)

Abstract

Background: Premature trial termination is a potential ending for all clinical trials and occurs when the Investigational Medicinal Product (IMP) is ineffective or unsafe, or when the trial will not be able to demonstrate efficacy. When a clinical trial prematurely terminates participants need to transition onto a new care pathway which may be a return to the previous standard care they were receiving. The healthcare professionals (HCPs) delivering the trial are responsible for managing the situation including immediate participant care. There is little known about the phenomenon of prematurely terminated clinical trials in relation to those who experience this or how to manage the situation, resulting in HCPs working without an evidence-base. This can lead to poor outcomes and experiences for patients, participants, families and HCPs.

Aim: The aim of this doctoral research was to answer the following research question: ‘What strategies can HCPs delivering clinical research utilise to support paediatric patients and their families when a clinical trial prematurely terminates?’.

Methods: A mixed methods approach was adopted and three studies were conducted. In study one a systematic review of clinical trial protocols registered onClinicalTrials.gov was conducted to a) quantify the proportion of clinical trial protocols that included premature trial termination and instructions related to participant management and care, and b) review the context in which premature termination was included and the detail of any instructions for participant management and care. Data were summarised descriptively. Study two was a national e-survey of HCPs delivering clinical research to identify how many UK healthcare professionals delivering clinical research have experienced premature trial termination, the challenges experienced and resources available for managing this situation. Data were analysed with descriptive statistics and content analysis. Study three was qualitative study exploring how UK HCPs and parents had experienced a premature trial termination, and its data were analysed using reflexive thematic analysis.

Main findings: Study one: Nearly all protocols (95.9%) identified the possibility of premature trial termination. The majority identified that the sponsor had the right to terminate the trial (82.7%) and provided reasons why the trial could be stopped (65.5%). Only forty-two percent provided guidance for participant management and care, most commonly this was only to contact/inform the participant of the termination. Directions varied in the quantity and level of detail but did not include sufficient information to enable HCPs to explain the decision for termination or confidently understand which research procedures and data were required. Study two: 65% of responding UK HCPs professionals had experienced ≥ one premature trial termination. Challenges around premature trial termination included communicating with research participants and/or families and emotional distress for participants and/or families. 48 healthcare professionals identified resources they used for advice. Of those available for review (n=2), only one provided guidance relating to the management of research participants. Study three: UK HCPs and parents (n=10) involved with a prematurely terminated paediatric clinical trial found this to be a difficult experience, reflected in the three themes: 1. Upset, unaware, unprepared, 2. Caught in the middle, and 3. “What now?”. This doctoral research provides insights into the phenomenon, showing it to be challenging and without resources that HCPs could consult to support them in managing the situation.

Conclusions: In the UK professional regulators require HCPs to engage with research, and the government expect clinical research to be usual business within the NHS. As progress is made to meet these ambitions there will be greater numbers of HCPs, participants and families engaging with clinical research and therefore potentially more experiencing premature trial terminations. Based on the findings of this8research recommendations have been made for clinical and research practice to improve the experience of prematurely terminating trials for HCPs, participants and families. This has focused on improving the awareness of the potential trial ending and preparing for this ending, clear communication when the decision has been made to prematurely terminate a trial, and emotional support for participants and families. Future research recommendations from this doctoral research focus on a)including other groups involved in this experience such as children and young people, trial sponsors and members of Research Ethics Committees, and b)implementation and evaluation of the recommendations for clinical practice

Date of Award	20 May 2026
Original language	English
Awarding Institution	University of Bath
Supervisor	Abbie Jordan (Supervisor), Paula Smith (Supervisor) & Julie Menzies (Supervisor)