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Introduction Overdiagnosis is the diagnosis of a disease that would never have caused any symptom or problem. It is a harmful side effect of screening and may lead to unnecessary treatment, costs and emotional drawbacks. Doctors and other healthcare professionals (HCPs) have the opportunity to mitigate these consequences, not only by informing their patients or the public but also by adjusting screening methods or even by refraining from screening. However, it is unclear to what extent HCPs are fully aware of overdiagnosis and whether it affects their screening decisions. With this systematic review, we aim to synthesise all available research about what HCPs know and think about overdiagnosis, how it affects their position on screening policy and whether they think patients and the public should be informed about it.Methods and analysis We will systematically search several databases (MEDLINE, Embase, Web of Science, Scopus, CINAHL and PsycArticles) for studies that directly examine HCPs' knowledge and subjective perceptions of overdiagnosis due to health screening, both qualitatively and quantitatively. We will optimise our search by scanning reference and citation lists, contacting experts in the field and hand searching abstracts from the annual conference on 'Preventing Overdiagnosis'. After selection and quality appraisal, we will analyse qualitative and quantitative findings separately in a segregated design for mixed-method reviews. The data will be examined and presented descriptively. If the retrieved studies allow it, we will review them from a constructivist perspective through a critical interpretive synthesis.Ethics and dissemination For this type of research, no ethical approval is required. Findings from this systematic review will be published in a peer-reviewed journal and presented at the annual congress of 'Preventing Overdiagnosis'. In addition, the results will serve as guidance for further research on this topic.PROSPERO registration number CRD42021244513.

Objective To estimate the rate and type of downstream activities (DAs) after laboratory testing in primary care, with a specific focus on check-up laboratory panels, and to explore the effect of a clinical decision support system (CDSS) for laboratory ordering on these DAs.Design Cluster randomised clinical trial.Setting 72 primary care practices in Belgium, with 272 general practitioners (GPs), randomly assigned to the intervention arm or the control arm.Participants The study included 10 270 lab panels from 9683 primary care patients (women 55.1%, mean age 56.5). All adult patients who consulted one of the participating GPs during the trial period and needed a laboratory exam were eligible for participation.Interventions GPs in the intervention group used a CDSS integrated into their online laboratory ordering system, while GPs in the control arm used their lab ordering system as usual. The trial duration was 6 months, with another 6 months follow-up.Main outcome measures This publication reports on the exploratory outcome of DAs after an initial laboratory exam and the effect of the CDSS on these DAs.Results 19.7% of all laboratory panels resulted in further diagnostic procedures (95% CI 18.9% to 20.5%) and 19% (95% CI 18.2% to 19.7%) in treatment changes. Check-up laboratory exams showed similar rates of DAs, with 17.5% (95% CI 13.8% to 21.2%) diagnostic DAs and 18.9% (95% CI 13.9% to 23.9%) treatment changes. Using the CDSS resulted in a significant reduction in downstream referrals (−2.4%; 95% CI −4.2% to −0.6%; p=0008), imaging and endoscopies (−0.9%; 95% CI −1.6% to −0.1%; p=0026) and treatment changes (−5.4%; 95% CI −9.5% to −1.2%; p=0.01).Conclusion This is the largest study so far to examine DAs after laboratory testing. It shows that almost one in three laboratory exams leads to further DAs, even in check-up panels. Using a CDSS for laboratory orders may reduce the rate of some DAs.Trial registration number NCT02950142.