The Problem

An oncology clinical trial hit disaster when a patient experienced a suspected, unexpected, serious adverse reaction (SUSAR) and the Investigator reacted very strongly. He insisted on unblinding the subject, and having previously led one of the top recruiting sites he refused to enrol any more patients into the study, even complaining to the local ethics committee. Pharmora had provided the personnel accountable for patient safety in this trial and jumped quickly into action.

The Solution

Pharmora reacted immediately and arranged a meeting with the Investigator to discuss the specific details of the SUSAR. In this particular case it was clear to see why the Investigator was so suspicious of the investigational product: the patient was young (in his 40s), having been previously fit and well prior to developing lung cancer, and had suddenly become confused and lost consciousness, falling into a coma within a matter of days. All investigations to identify a possible cause, including brain scans to look for metastasis and blood tests to identify viral causes, found nothing.

The Pharmora team went to work to conduct a signal evaluation. This included a literature search and review, analysis of the safety profiles of comparable products, and assessment of all available clinical and non-clinical trial data. The Pharmora team drafted a signal evaluation report to present to a Senior Governance meeting. At this meeting there was discussion of putting the clinical trial on hold, pending the outcome of this event. Pharmora safety staff confirmed their evaluation that there was insufficient evidence to attribute a causal relationship to the investigational product in this situation. The Pharmora staff supported continuing the study as planned and warned that an unnecessary clinical hold for safety reasons could severely impact the future of the trial.

This SUSAR was discussed in the Development Safety Update Report (DSUR) as having insufficient evidence of a causal relationship between this isolated report and the investigational product and the Pharmora safety team kept the event under review for the remainder of the trial.

For the next 6 months the Investigator continued to refuse to recruit any further patients and informed us that the patient remained in a coma, but the study continued as planned. After 6 months the patient sadly died and a post-mortem examination was performed, the results of which were made available to the study team 2 months later.

The Outcome

The post-mortem examination results revealed brain metastases. In particular, there was one tiny metastasis preventing fluid from flowing out of the ventricles, which had put pressure on the brain tissue. The site and size of this metastasis meant that it would not have been visible on the scans at first, but would have been capable of interfering with fluid outflow as soon as it developed. The opinion of the examiner was that this was the cause of the patient’s symptoms including the confusion, coma and eventual death.

Had the team agreed to put the trial on hold while waiting for this outcome, there would have been an 8-month clinical hold for safety reasons and the study would have probably never restarted.