Study:Goldman 2004. Outcome: relapse of histoplasmosis
Confounding domains	Measured variable(s)	Is there evidence that controlling for this variable was unnecessary?	Is the confounding domain measured validly and reliably?	OPTIONAL Is failure to adjust for this variable expected to favour intervention or comparator
Severity of PDH	Evidence of histoplasmosis infection AND remission with antigen concentrations < 4.1 units and negative blood culture.	No	Yes	—
Severity of HIV	CD4 – required to have > 150 cells/μL for study entry.	No	Yes	—
Comorbidities and comedications	Required to have received both antifungal and ART treatment for ≥ 12 months prior to starting trial.	No	Yes	—
Cointerventions	Is there evidence that controlling for this cointervention was unnecessary?		Is presence of this cointervention likely to favour outcomes in the intervention or comparator?
ART at time of PDH diagnosis	All participants were required to be on ART at time of initiation into trial.		—
Supportive therapy	Not reported		—
Bias domain	Signalling questions	Comments		Risk of bias judgement
Bias due to confounding	1.1–1.8	Protocol stipulated eligibility criteria for all the confounding domains cited above.		Low
Bias in participant selection	2.1–2.5	Start of intervention varied – participants enrolled after a range of 14–81 months of antifungal therapy. Unclear how many eligible patients not enrolled.		Serious
Bias in classification of intervention	3.1–3.3	Intervention was well‐defined – discontinuation of antifungal treatment		Low
Bias due to deviations from intended intervention	4.1–4.6	Regular monitoring of participants ensured that intervention was delivered as intended.		Low
Bias due to missing data	5.1–5.5	Details on missing data were reported.		Low
Bias in measurement of outcomes	6.1–6.4	Relapse of histoplasmosis was clearly defined in the protocol.		Low
Bias in selection of reported result	7.1–7.3	Outcome of interest was determined in the protocol and reported.		Low
Overall bias				Serious