Juurlink 2004.

Methods	Study design: ITS
Participants	Physicians Clinical speciality: not clear Level of training: fully trained Setting/country: mixed/Canada
Interventions	The PEM consisted of the RALES published in September 1999, which demonstrated that treatment with spironolactone substantially reduced morbidity and mortality in patients with severe heart failure
Outcomes	1 process outcome: rate of spironolactone prescription for patients with heart failure 2 patient outcomes: rate of hospital admission for hyperkalaemia for patients with heart failure rate of in‐hospital death owing to hyperkalaemia for heart failure patients
Notes	‐
Risk of bias
Bias	Authors' judgement	Support for judgement
Intervention independent of other changes ‐ ITS	Unclear risk	No information was provided
Shape of Intervention effect pre‐specified ‐ ITS	Unclear risk	Quote, pg. 543: "the Randomized Aldactone Evaluation Study (RALES) demonstrated that spironolactone significantly improves outcomes in patients with severe heart failure. Use of angiotensin‐converting–enzyme (ACE) inhibitors is also indicated in these patients. However, life‐threatening hyperkalemia can occur when these drugs are used together..."
Intervention unlikely to affect data collection ‐ ITS	Low risk	The intervention (RALES)  did not affect either the source or method of data collection
Blinding of outcome assessors (detection bias) ‐ ITS All outcomes	Low risk	The outcome was objective
Incomplete outcome data (attrition bias) ‐ ITS All outcomes	Low risk	Quote, pg. 544: "we examined the computerized prescription records of the Ontario Drug Benefit Program, which records prescription drugs dispensed to all Ontario residents 65 years of age or older. The overall error rate in this database is less than 1 percent. Hospitalization records were obtained from the Canadian Institute for Health Information Discharge Abstract Database, which contains a record of all hospitalizations, including up to 16 diagnoses for each admission. Although the accuracy of coding in this database has not been established for all diagnoses, one recent study showed a positive predictive value of 90 to 96 percent for the diagnosis of heart failure." COMMENT: the authors establish that the databases used as sources are accurate and complete
Selective reporting (reporting bias) ‐ ITS	Low risk	All relevant outcomes in the methods section were reported in results section
Other bias ‐ ITS	High risk	Quote, pg. 550: "indeed, many of the patients hospitalized for hyperkalemia may have died of another illness. The diagnostic coding for hyperkalemia has not been validated; moreover, many patients hospitalized for hyperkalemia may have also had volume contraction or renal insufficiency related to spironolactone therapy. In addition, we were unable to identify adverse outcomes that occurred before admission"