Drivers of bias in diagnostic test accuracy estimates when using expert panels as a reference standard

Objectives To assess the impact of study and expert panel characteristics on index test diagnostic accuracy estimates. Study Design and Setting Simulations were performed in which an expert panel was used as reference standard to estimate the sensitivity and specificity of an index diagnostic test. Diagnostic accuracy was determined by combining probability estimates of target condition presence, as provided by experts using four component reference tests, through a predefined threshold. Study and panel characteristics were varied in several scenarios: target condition prevalence (20%, 40%, 50%), accuracy of component reference tests (70%, 80%, mixed), expert panel size (2, 3, 10), study population size (360, 1000), and random or systematic differences between expert’s probability estimates. Bias in accuracy estimates across all possible true index test values was quantified for all scenarios. The total bias in each scenario was quantified using the mean squared error (MSE). Results When estimating an index test with 80% sensitivity and 70% specificity, bias in these estimates was hardly affected by the study population size or the number of experts. When one expert was systematically biased, bias in sensitivity and specificity estimates increased, but this effect lessened when the number of experts in the panel was higher. Prevalence had a large effect on bias, scenarios with a prevalence of 0.5 estimated sensitivity between 63.3% and 76.7% and specificity between 56.1% and 68.7%, whereas scenarios with a prevalence of 0.2 estimated sensitivity between 48.5% and 73.3% and specificity between 65.5% and 68.7%. Random and systematic differences between experts also increased bias, with estimated sensitivity between 48.6% and 77.4% and specificity between 59.1% and 69.1% as opposed to scenarios without random or systematic differences, which estimated sensitivity between 58.0% and 77.4% and specificity between 56.1% and 69.1%. More accurate component reference tests also reduced bias. Scenarios with four component tests of 80% sensitivity and specificity estimated index test sensitivity between 60.1% and 77.4% and specificity between 62.9% and 69.1%, whereas scenarios with four component tests of 70% sensitivity and specificity estimated index test sensitivity between 48.5% and 73.4% and specificity between 56.1% and 67.0%. Conclusion Bias in accuracy estimates when using an expert panel will increase if the component reference tests (combined) are less accurate. Prevalence, the true value of the index test accuracy, and random or systematic differences between experts can also impact the amount of bias, but the amount and even direction will vary between scenarios. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This study did not receive any funding. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present study are available upon request to the authors.