UK paediatric clinical trial protocols: A review of guidance for participant management and care in the event of premature termination.

Abstract

Background/aims: Clinical trials provide an opportunity to identify new treatments and can offer patients access to treatments otherwise unavailable. However, approximately 10% of paediatric clinical trials discontinue before the trial has completed. If this premature termination is because the trial treatment(s) being investigated are identified to be ineffective or unsafe, it results in the abrupt discontinuation of the investigational medicinal product for participants. For some participants, there may not be other treatment options to pursue at the trial-end. Trials prematurely terminating can be a distressing experience for all involved and currently there is little published evidence about the guidance provided to healthcare professionals in the event of premature trial termination. The study protocol is the source of guidance for healthcare professionals delivering clinical research, detailing how to conduct all aspects of the trial. The aim was to quantify the proportion of clinical trial protocols that included premature trial termination and subsequently those that provided instructions related to participant management and care. In addition, to analyse the context in which premature termination was included and the detail of any instructions for participant management and care.

Methods: The ClinicalTrials.gov database was searched by a single reviewer for UK interventional drug trials enrolling children with an available study protocol. Protocols were searched to assess if the risk of premature trial termination was identified, the context for premature termination being included, if information was provided to support the management and care of participants should this situation occur and the detail of those instructions. Data were summarised descriptively.

Results: Of 245 clinical trial protocols, 235 (95.9%) identified the possibility of premature trial termination, the majority within the context of the sponsor asserting their right to terminate the trial (82.7%, 115/235) and providing reasons why the trial could be stopped (65.5%, 91/235). Forty-two percent (98/235) provided guidance for participant management and care, most commonly to contact/inform the participant (45.9%, 45/98). Directions varied in the quantity and level of detail.

Conclusions: This review of UK clinical trial protocol highlights that information surrounding premature termination is lacking, with only 42% providing guidance on the care of trial participants. While this ensures regulatory compliance, it fails to consider the challenge for healthcare professionals in managing participants on-going care or the duty of care owed to participants. Further research is required to understand if additional documents are being used in practice, and if these meet the needs of healthcare professionals in supporting research participants and families during premature trial termination.