Abstract
Introduction
Suboptimal compliance with the protocol is a very common problem in Randomised Clinical Trials (RCTs) that can distort the generalisability and validity of the results. Monitoring compliance is crucial within the conduct of RCTs to tackle arising issues, data quality problems, and recruitment and retention figures. Nevertheless, sole reliance on CONSORT diagram and summary figures might not be adequate to uncover masked patterns in noncompliance. We developed a comprehensive visualisation method that can aid trialists to monitor adherence and identify unanticipated issues.
Methods
The scheme was developed and critically appraised within the STAR clinical trial to assess the impact of COVID-19 pandemic on the trial. STAR recruited patients with age-related macular degeneration to investigate the effect of baseline treatment with stereotactic radiotherapy (SRT) on the number of as needed intravitreal ranibizumab injections during the subsequent two years (evaluated on monthly basis). The following steps are used to construct the plot: (1) define compliance rules (for STAR trial we used a priori set window to categorise visits), (2) assign a colour-coded label for each rule, and (3) the colour-coded visit timelines for all participants are stacked above each other from the first to last recruited patient. We labelled visits as: red (to indicate unattendance), amber (attended but out of the planned window), green (completed per protocol), back (death), and white (withdrawal).
Results
The plot allowed graphical comparison of the overall compliance, death rate, and withdrawals in the trial. Moreover, the impact of COVID-19 pandemic could be viewed and compared before and after the lockdown. The plot showed higher rates of noncompliance during the first few months of the pandemic, however, the preceding pattern was re-established afterwards. The plot informed an ad-hoc sensitivity analysis proposed by the trial management group to weigh the possible impact of the pandemic on the trial results.
Discussion
Future studies can adopt this compliance plot to examine protocol adherence and participant retention within the conduct of clinical trials. Furthermore, the plot provides a simple and more transparent method to report compliance issues in clinical trials.
Suboptimal compliance with the protocol is a very common problem in Randomised Clinical Trials (RCTs) that can distort the generalisability and validity of the results. Monitoring compliance is crucial within the conduct of RCTs to tackle arising issues, data quality problems, and recruitment and retention figures. Nevertheless, sole reliance on CONSORT diagram and summary figures might not be adequate to uncover masked patterns in noncompliance. We developed a comprehensive visualisation method that can aid trialists to monitor adherence and identify unanticipated issues.
Methods
The scheme was developed and critically appraised within the STAR clinical trial to assess the impact of COVID-19 pandemic on the trial. STAR recruited patients with age-related macular degeneration to investigate the effect of baseline treatment with stereotactic radiotherapy (SRT) on the number of as needed intravitreal ranibizumab injections during the subsequent two years (evaluated on monthly basis). The following steps are used to construct the plot: (1) define compliance rules (for STAR trial we used a priori set window to categorise visits), (2) assign a colour-coded label for each rule, and (3) the colour-coded visit timelines for all participants are stacked above each other from the first to last recruited patient. We labelled visits as: red (to indicate unattendance), amber (attended but out of the planned window), green (completed per protocol), back (death), and white (withdrawal).
Results
The plot allowed graphical comparison of the overall compliance, death rate, and withdrawals in the trial. Moreover, the impact of COVID-19 pandemic could be viewed and compared before and after the lockdown. The plot showed higher rates of noncompliance during the first few months of the pandemic, however, the preceding pattern was re-established afterwards. The plot informed an ad-hoc sensitivity analysis proposed by the trial management group to weigh the possible impact of the pandemic on the trial results.
Discussion
Future studies can adopt this compliance plot to examine protocol adherence and participant retention within the conduct of clinical trials. Furthermore, the plot provides a simple and more transparent method to report compliance issues in clinical trials.
| Original language | English |
|---|---|
| Title of host publication | 6th International Clinical Trials Methodology Conference, 3rd – 6th October 2022, Harrogate, UK |
| Pages | 72-72 |
| Number of pages | 1 |
| DOIs | |
| Publication status | Published - 16 Mar 2023 |