Table 2.

Details of clinical decision rules undergoing prospective validation and key differences between derivation and validation datasets.

Rule	High risk variables	High risk outcome	Key differences in derivation and validation dataset
Rules predicting microbiologically defined infection
PICNICC [8]	Weighted variables for malignancy type, maximum temperature, clinically unwell, WCC, haemoglobin and AMC	Microbiologically defined infection	Developed from IPD meta-analysis from 22 studies with variable inclusion and exclusion criteria
Rules predicting adverse outcome
SPOG-AE [21]	Applied after 24 h. Total score ≥ 9 = high risk	Adverse outcome defined as a serious medical complication (death, ICU or other life-threatening complication) as a result of infection, MDI and radiologically confirmed pneumonia	-Excluded inpatient onset FN.
			-Fever: ≥ 38·5 °C once or ≥38·0 °C during ≥2 h
	Score for preceding chemotherapy more intensive than ALL maintenance =4; haemoglobin ≥ 90=5; WCC < 300 cells/mm3 = 3; platelet <50 G/L=3		-Neutropenia: ANC ≤ 500cells/mm3
			-Bacteraemia not defined*
Hakim [22]	Total score ≥ 24 = high risk	Proven invasive bacterial infection defined as isolation of a pathogen from a sterile body site or as proven by histology or culture-negative sepsis defined as a systemic response to a possible infection because of hemodynamic instability, focal or multiple organ involvement or altered mental status or lethargy	-Excluded inpatient onset FN
	Score for cancer diagnosis: AML=20, ALL/lymphoma = 7, solids = 0 points; Seriously unwell⁎⁎ = 14 points; temperature ≥39 °C = 11 points; ANC <100 cells/mm3 = 10 points	Bacteraemia defined as a recognized pathogen cultured from one or more blood cultures or common commensals cultured from two or more blood cultures	-Fever: ≥38·3 °C or ≥ 38·0 °C for ≥1 h
Alexander [23]	Any of following = high risk	Adverse outcome defined as identification of a pathogen or where there was a serious medical complication or death	-Excluded inpatient onset FN.
	AML, Burkitt lymphoma, ALL in induction, progressive or relapsed disease; Hypotension, tachypnea/hypoxia 94%; new CXR changes; altered mental status; severe mucositis; vomiting or abdominal pain; focal infection; other clinical reason for in-patient treatment		-Fever: >38·5 °C at presentation or within 6h
			-Neutropenia: ANC ≤ 500cells/mm3
			-Bacteraemia,* serious medical complication,* hypotension⁎⁎⁎ and focal infection# not defined
Klaassen [24]	AMC < 100 cells/mm3	Significant bacterial infection defined as blood or urine culture positive for bacteria, interstitial or lobar consolidation on CXR, or unexpected death from infection (patient not palliative)	-Excluded comorbidity on presentation inc. severe mucositis and pneumonia
			-Fever: > 38·5 °C once or > 38·0 °C or within 12h
Rules predicting bacteraemia
SPOG-bacteraemia [28]	Applied after 24 h	Bacteraemia defined as at least 1x positive blood culture	-Excluded inpatient onset FN.
	Score for shaking or chills = 5; Hb ≥90 = 3; platelet <50 G/L = 3; Other need for inpatient care = 3		-Fever: ≥ 38·5 °C once or ≥ 38·0 °C for ≥2h
			-Neutropenia: ANC ≤ 500cells/mm3
			-Definition of bacteraemia different
Ammann [27]	High risk: any of temperature >39·7 °C, comorbidity requiring inpatient care, WCC≤1000 cells/mm3, not in remission	Bacteraemia defined as at least 1x positive blood culture	-As for SPOG bacteraemia CDR
Baorto [25]	AMC<155 cells/mm3	Bacteraemia (not defined)*	-Excluded age <1y
			-Neutropenia – ANC < 500cells/mm3
Rackoff [26]	High risk: AMC < 100 cells/m3 and temperature ≥39 °C	Bacteraemia defined as a positive blood culture	-Excluded inpatient onset FN.
	Low risk = AMC ≥ 100 cells/mm3; intermediate risk = AMC < 100 cells/mm3 and temperature <39 °C		-Fever: ≥ 38·5 °C once or ≥ 38·0 °C 3x within 24h
			-Neutropenia: ANC < 500cells/mm3
			-Definition of bacteraemia different

PICNICC, Predicting Infectious ComplicatioNs In Children with Cancer; WCC, white cell count; AMC, absolute monocyte count; IPD, individual participant data; SPOG, Swiss Paediatric Oncology Group; AE, adverse event; ANC, absolute neutrophil count; ALL, acute lymphoblastic leukaemia; ICU, intensive care unit; MDI, microbiologically defined infection; AML, acute myeloid leukaemia; HSCT, haematopoietic stem cell transplant; SMC, serious medical complication; ICU, intensive care unit; PCR, polymerase chain reaction.

^⁎international consensus definition used for validation.⁵²

^⁎⁎defined as severe sepsis or septic shock (as per Goldstein et al.), ¹⁵ altered conscious state (Glasgow Coma Score <15 or only responsive to voice or pain), documented as ‘severely unwell’ or equivalent in the patient record or either the blood pressure or respiratory rate in the mandatory emergency call range.¹⁶

^⁎⁎⁎Hypotension defined according to VICTOR chart.¹⁶

^#Focal infection includes defined as upper respiratory tract infection (URTI), lower respiratory tract infection (LRTI), anorectal infection or central venous catheter (CVC) infection.