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BACKGROUND: Volunteer infection studies have become a standard model for evaluating drug efficacy against Plasmodium infections. Molecular techniques such as qPCR are used in these studies due to their ability to provide robust and accurate estimates of parasitaemia at increased sensitivity compared to microscopy. The validity and reliability of assays need to be ensured when used to evaluate the efficacy of candidate drugs in clinical trials. METHODS: A previously described 18S rRNA gene qPCR assay for quantifying Plasmodium falciparum in blood samples was evaluated. Assay performance characteristics including analytical sensitivity, reportable range, precision, accuracy and specificity were assessed using experimental data and data compiled from phase 1 volunteer infection studies conducted between 2013 and 2019. Guidelines for validation of laboratory-developed molecular assays were followed. RESULTS: The reportable range was 1.50 to 6.50 log10 parasites/mL with a limit of detection of 2.045 log10 parasites/mL of whole blood based on a parasite diluted standard series over this range. The assay was highly reproducible with minimal intra-assay (SD = 0.456 quantification cycle (Cq) units [0.137 log10 parasites/mL] over 21 replicates) and inter-assay (SD = 0.604 Cq units [0.182 log10 parasites/mL] over 786 qPCR runs) variability. Through an external quality assurance program, the QIMR assay was shown to generate accurate results (quantitative bias + 0.019 log10 parasites/mL against nominal values). Specificity was 100% after assessing 164 parasite-free human blood samples. CONCLUSIONS: The 18S rRNA gene qPCR assay is specific and highly reproducible and can provide reliable and accurate parasite quantification. The assay is considered fit for use in evaluating drug efficacy in malaria clinical trials.

© 2019 John Wiley & Sons Ltd Aims and objectives: To extract, examine and report the highest available levels of evidence from healthcare disciplines in the use of simulation-based education as substitution for clinical placement in prelicensure programmes. Background: Simulation is widely employed across prelicensure health professional education to create safe, realistic clinical learning experiences for students. Whether simulation can be employed to substitute for actual clinical placement, and if so, in what proportion, replacement ratio and duration, is unclear. Methods: A systematic review and quality appraisal of primary studies related to prelicensure students in all health disciplines, guided by the PRISMA checklist. Results: Ten primary studies were included, representing 2,370 students from three health disciplines in four countries. Nine studies were experimental and quasi-experimental and methodological quality was assessed as moderate to high with good to very good inter-rater agreement. Direct substitution of simulation for clinical practice ranged from 5% to 50%. With one exception, replacement ratios were 1:1 and duration of replacement ranged from 21 hr–2 years. Levels of evaluation included measures of reaction, knowledge and behaviour transfer; no negative outcomes were reported. We appraised practicalities for design of substitution, design limitations and knowledge transfer to accreditation standards for prelicensure programmes. Conclusions: This review synthesised highest levels and quality of available evidence for substitution of simulation for clinical placement in health professional education. Included studies were heterogenous in simulation interventions (proportion, ratio and duration) and in the evaluation of outcomes. Future studies should incorporate standardised simulation curricula, widen the health professions represented and strengthen experimental designs. Relevance to clinical practice: Current evidence for clinical educationa

© 2019 John Wiley & Sons Ltd Aims and objectives: To extract, examine and report the highest available levels of evidence from healthcare disciplines in the use of simulation-based education as substitution for clinical placement in prelicensure programmes. Background: Simulation is widely employed across prelicensure health professional education to create safe, realistic clinical learning experiences for students. Whether simulation can be employed to substitute for actual clinical placement, and if so, in what proportion, replacement ratio and duration, is unclear. Methods: A systematic review and quality appraisal of primary studies related to prelicensure students in all health disciplines, guided by the PRISMA checklist. Results: Ten primary studies were included, representing 2,370 students from three health disciplines in four countries. Nine studies were experimental and quasi-experimental and methodological quality was assessed as moderate to high with good to very good inter-rater agreement. Direct substitution of simulation for clinical practice ranged from 5% to 50%. With one exception, replacement ratios were 1:1 and duration of replacement ranged from 21 hr–2 years. Levels of evaluation included measures of reaction, knowledge and behaviour transfer; no negative outcomes were reported. We appraised practicalities for design of substitution, design limitations and knowledge transfer to accreditation standards for prelicensure programmes. Conclusions: This review synthesised highest levels and quality of available evidence for substitution of simulation for clinical placement in health professional education. Included studies were heterogenous in simulation interventions (proportion, ratio and duration) and in the evaluation of outcomes. Future studies should incorporate standardised simulation curricula, widen the health professions represented and strengthen experimental designs. Relevance to clinical practice: Current evidence for clinical educationa