Burkhardt 2010

Methods	Randomised clinical trial, multicentre in 15 primary care practices in the area of Hanover, Germany
Participants	Inclusion criteria: adult patients with upper or lower ARIs in primary care Exclusion criteria: treatment with antibiotics during the previous 2 weeks, chronic liver disease, major surgery that had required hospitalisation during the last 4 weeks, autoimmune or systemic disorders, dialysis, medullary C‐cell carcinoma and other inflammatory diseases Included in this analysis: 550 out of 571 randomised patients: 21 post randomisation exclusions (2 withdrew consent, 1 due to loss of sample, 15 with autoimmune, inflammatory or systemic disease, 2 with advanced liver disease, 1 with prior use of antibiotics)
Interventions	Guiding antibiotic decisions in primary care with initial measurement only Algorithm used in this study: procalcitonin value < 0.25 µg/l indicated that a relevant bacterial infection of the respiratory tract is unlikely
Outcomes	Days with impairment during everyday life and/or leisure activities due to the infection of the respiratory tract within the first 14 days according to self assessment Revisit to the physician's office with a respiratory tract infection within 28 days Number of days with antibiotic‐induced side effects Antibiotic use Change of antibiotics within 28 days Patients with any symptoms of ongoing or relapsing infection at 28 days All‐cause mortality Hospitalisation
Notes	Funding: Brahms AG, Germany Follow‐up: fixed period of 28 days Registration: NCT00827060 and NCT00688610
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Computer‐generated Quote: "Baseline adaptive randomisation was realised through a web‐based randomisation data bank (IOMTech GmbH, Berlin, Germany), which had been programmed specifically for that purpose."
Allocation concealment (selection bias)	Low risk	Central randomisation Quote: "In the central laboratory, the web‐based randomisation of the patient into the procalcitonin group or the control group took place."
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	Open‐label trial where physicians knew in which group patients were and where procalcitonin levels were only communicated in the intervention arm
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Structured interviews by blinded personnel
Incomplete outcome data (attrition bias) All outcomes	Low risk	Follow‐up for mortality: 546/550 (99%)
Selective reporting (reporting bias)	Low risk	Outcomes correspond to study protocol
Other bias	Low risk	87% adherence to procalcitonin algorithm in procalcitonin group