The proportion of trials that are classed as high participant burden in this small sample of prostate cancer clinical trials should give the trial community pause for thought. That only one trial had a low participant burden is very significant. We know that trials collect a lot of data, and much of this goes unused. We don't know why trial teams collect so much data that is not subsequently used but anecdotally we know that investigators think that if they are going to the trouble of collecting data, they might as well get as much as possible – the information might get used some time. Prior studies have given some thought to the effort and cost trial teams go to collect this data (22) but it's now time to consider the effort of the participant, and the potential impact on their experience of participating in a trial with a high or medium participant burden.
The variation of participant age appeared to have a slight effect on the burden score with 58.8% (10/17) of trials in the over 70’s being identified as high burden. This coincided with a high perceived familial burden, which supports the idea of perceived negative effect of trial participation on caregivers of elderly participants. Physical burden had the strongest correlation with trial burden, the lowest physical burden score was recorded for the trial that had the lowest overall TBS score. On the corollary, all trials considered high burden had higher than the average (>10.5) physical burden scores.
Recruitment and retention have been widely documented as one of the most difficult aspects in clinical research, where slow recruitments and high loss to follow up rates often affect a trial’s financial and logistical feasibility and its external validity (10),(15),(23). In this review over 65% (20/30) of the trials met their recruitment targets or had less than 5% (acceptable variance) between the pre-determined sample size and actual recruitment, while 70% (21/30) of trials maintained 90% retention. While we did not statistically show any trend associated with recruitment or retention difficulties and high medium or low participant burden, most likely because recruitment and retention was in relative terms pretty high in these trials, our sample consisted of the people that consented to participate in the RCTs. We have no way of knowing if the burden of the trial dissuaded any other potential participants. This would need further investigation, and could be done effectively in a SWAT (Study Within A Trial).
Participants in trials with diseases such as cancer, which can be life-limiting and have limited treatment options, may have a higher tolerance for higher burden in trials, as their perception of risk of a trial could be outweighed by their motivation to receive potentially life-saving treatments and may account for the higher-than-average recruitment and retention rates. This was seen to be a relative trait at all stages of diagnosis, as there was no variance between diagnosis stage and recruitment or retention rates. As this was a retrospective study with limited knowledge of the inner workings of each trial other than the reported methodologies, the potential use of strategies to reduce/mitigate attrition rates such as undocumented conversations between caregivers/trialists with participants to encourage and support them during the trial process may also have been applied to some or all trials in this sample and these strategy benefits cannot be understated, as both frequency and quality of patient contact have previously been identified as a workable retention strategy(24),(25). It is possible that this was even more important in high participant burden trials.
The concept of participant burden has yet to be fully defined. The data categories identified for this review are not by any means definitive. If the methodology outlined in this study were to be applied to trials that are currently in progress and a survey to participants was an available option, information such as marital status, number of children, employment status and financial situations (availability of pensions or savings) could all have been introduced to the categories previously identified to give a more comprehensive view of the potential burdens placed on participants and their families during trial participation. Further research, using a mixed-methods approach, should be conducted to quantify the level of participation burden on cancer patients during clinical trials.
Due to the retrospective nature of this study, access to information was restricted to that reported in a sample of prostate cancer clinical trials in peer reviewed journals. This confined the amount of extractable information that could be utilised to create the burden sub-categories. For example, data was not available for distance to clinic visit for all studies and this has previously identified as a major barrier to initial participant recruitment (26),(27). Societal and economic burden both had the lowest burden scores, which on observation can be associated with the inconsistency of the number of sub-categories per data category. Due to restricted data availability, these burden categories could not be expanded or developed, which lead to an under-representation of the potential burden effect of each category within each trial.