Making trials as efficient and effective as possible protect trial participants better, ensure reliable results and mean that new treatments can reach the general public more quickly. The TEMPER study was one of the largest every pre-planned studies into how best to run trials. It has provided important evidence on a key clinical trial process.
"Monitoring" in clinical trials is a broad term referring to the activities trial sponsors (those responsible for running trials) undertake in order to make sure trial participants are protected and trial results are robust. Often, monitoring takes the form of frequent visits by sponsor representatives to the healthcare centres where trials are taking place. This has the advantage of giving monitors direct access to medical notes and other documentation that can show whether or not a trial is being run correctly. However, it is expensive and may not always be justified, particularly in lower-risk trials.
As part of a wider drive to get new developments in healthcare more quickly and more affordably to the wider public, trial monitoring has come under scrutiny as a particularly costly and inefficient process in drug development. Researchers are therefore looking for alternatives to the frequent site visit model that will still adequately protect patient safety and ensure trial data are reliable.
One alternative approach is triggered monitoring. This uses information reported to the sponsor from the trial centre to calculate an overall risk score for each, based on factors such as whether the centre is sending in trial data on time, whether the centre is sending all required information about participant safety, or whether the centre is correctly following the trial procedures. Each factor has an associated "trigger", and the more triggers fire at any time, the higher the centre's risk score. Centres with highest overall risk scores are prioritised for the next "monitoring visits". This should be both more efficient, as some visits are avoided, and effective, as the high risk centres are still looked at in more detail.
In the TEMPER study, centres in three large clinical trials running in the UK were examined. Any centre triggered for a visit was paired with a centre that was similar in important respects - number of participants and time since the first participant joined the trial - but as different as possible in terms of risk (i.e. currently with a low overall risk score). Both centres were visited at a similar point in time, and the results were compared. If the approach worked, we would expect more "serious" findings from the visit to the higher risk centre in each pair.
The paired visits - 84 in total - took place between 2013 and 2016. Overall, there was no statistically significant difference between the amount of important findings at the higher and lower risk centres, indicating that the triggered monitoring approach, as currently used, is not effective enough.
The results of the TEMPER study were published in Clinical Trials journal. They showed that "triggered monitoring" may not be as effective in current practice as expected, but they also provided evidence about how the approach could be optimised and improved.
The study was funded by CRUK with support from the Medical Research Council.