Abstract
BackgroundIn cancer screening trials where the primary outcome is target cancer-specific mortality, the unbiased determination of underlying cause of death (UCD) is crucial. To minimise bias, the UCD should be independently verified by expert reviewers, blinded to death certificate data and trial arm. We investigated whether standardising the information submitted for UCD assignment in a population-based randomised controlled trial of prostate-specific antigen (PSA) testing for prostate cancer reduced the reviewers’ ability to correctly guess the trial arm.MethodsOver 550 General Practitioner (GP) practices (>415,000 men aged 50–69 years) were cluster-randomised to PSA testing (intervention arm) or the National Health Service (NHS) prostate cancer risk management programme (control arm) between 2001 and 2007. Assignment of UCD was by independent reviews of researcher-written clinical vignettes that masked trial arm and death certificate information. A period of time after the process began (the initial phase), we analysed whether the reviewers could correctly identify trial arm from the vignettes, and the reasons for their choice. This feedback led to further standardisation of information (second phase), after which we re-assessed the extent of correct identification of trial arm.Results1099 assessments of 509 vignettes were completed by January 2014. In the initial phase (n = 510 assessments), reviewers were unsure of trial arm in 33% of intervention and 30% of control arm assessments and were influenced by symptoms at diagnosis, PSA test result and study-specific criteria. In the second phase (n = 589), the respective proportions of uncertainty were 45% and 48%. The percentage of cases whereby reviewers were unable to determine the trial arm was greater following the standardisation of information provided in the vignettes. The chances of a correct guess and an incorrect guess were equalised in each arm, following further standardisation.ConclusionsIt is possible to mask trial arm from cause of death reviewers, by using their feedback to standardise the information submitted to them.Trial registrationISRCTN92187251Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2288-15-6) contains supplementary material, which is available to authorized users.
Highlights
In cancer screening trials where the primary outcome is target cancer-specific mortality, the unbiased determination of underlying cause of death (UCD) is crucial
This paper investigated whether the standardisation of information submitted to an endpoint committee for UCD ascertainment in the ongoing Cluster randomised triAl of prostate-specific antigen (PSA) testing for Prostate cancer (CAP) (ISRCTN92187251) successfully reduced the ability of reviewers in correctly guessing the trial arm, thereby minimising any potential biases arising from such guesses
59% of intervention arm men did not respond to the PSA testing invitation or were not invited for a PSA test because they did not fulfil the Protect inclusion criteria (Figure 1), and so followed standard National Health Service (NHS) prostate cancer risk management
Summary
In cancer screening trials where the primary outcome is target cancer-specific mortality, the unbiased determination of underlying cause of death (UCD) is crucial. The use of an independent panel of experts to assign underlying cause of death (UCD) following a review of medical notes is usually regarded, with the exception of autopsy, as the gold standard [1,2,3,4] and in most countries is preferable to the use of death certificates alone, where doubt may exist about the overall quality of cause of death certification [5,6,7] This is especially true in trials where the population is elderly with multiple, competing co-morbidities or malignancies [8,9,10]. Differential misclassification may be avoided by blinding panel experts to the trial arm a participant was in
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