Additional File 3, Table S3. Study Characteristics for Trials of Acute Care Managementa

Additional file 3, Table S3. Study characteristics for trials of acute care managementa Study Methods Funding Indication Settingc CCDSS Intervention Comparison (Country) Scoreb Source (No. of clinics / sites) Management Assistants – Alerts and Reminders Terrell, 9 Public Reduction of prescription of •Academic CCDSS data was only provided Usual care 2009[48], potentially inappropriate medications centre when a physician in the USA to older adults discharged from •Emergency intervention group attempted to emergency departments. Department prescribe 1 of the 9 targeted (1/1) potentially inappropriate medications in patients ≥ 65 years old who were being discharged from the emergency department. The system provides either an option to order a recommended alternative therapy or to reject the recommendation. When the latter option was chosen, a second menu was displayed to query the most important reason for rejecting the CCDSS recommendation. Peterson, 4 Private Drug dosing for patients ≥ 65 years •Academic CCDSS provided initial dose Control group not 2007[36]d, in a tertiary care academic health centre advice for sedatives, neuroleptics, specified (probably USA centre. (1/...) anti-emetics, and skeletal muscle usual care with no relaxants and discouraged CCDSS prescription of contraindicated recommendations) drugs for patients ≥ 65 years old in emergency rooms, intensive care units, and subacute units. Practitioners were not prevented from selecting higher doses than recommended.

1 Study Methods Funding Indication Settingc CCDSS Intervention Comparison (Country) Scoreb Source (No. of clinics / sites) Kroth, 7 Public Improve accuracy of temperature •Other CCDSS identified patients’ low Usual care 2006[39], capture by nurses at the bedside of •Academic temperature values and USA non-critical care hospital patients. centre generated prompts for nurses to •Hospital repeat the measurement. Nurses inpatients could take or override the (.../...) recommendation. Rood, 8 ... Management of glucose regulation •Other CCDSS monitored the interval Paper-based 2005[34], in critically ill inpatients. •Hospital between glucose measurements guideline for timing The inpatients and made guideline-based between glucose Netherlands (1/1) recommendations for timing measurements and between glucose measurements administration of and administration of insulin insulin doses in ICU doses in ICU patients. patients Recommendations were displayed electronically in pop-up windows when patient records were activated. Zanetti, 8 Public Redosing of prophylactic antibiotics •Academic CCDSS provided an automated Usual care 2003[47], during prolonged cardiac surgery. centre audible alarm and visual USA •Hospital intraoperative alert on the inpatients operating room computer console (1/1) for physicians to redose prophylactic antibiotics during cardiac surgery at 225 minutes after administration of preoperative antibiotics. A reply was required to clear the display. If planned redosing was indicated, a new alarm and alert were issued after 30 minutes and the circulating nurse was required to indicate whether a follow-up dose of antibiotics had been administered. Selker, 8 Public Management of thrombolytic and •Academic Thrombolytic Predictive Usual care 2002[29], overall reperfusion therapy in acute centre Instrument (TPI) is an

2 Study Methods Funding Indication Settingc CCDSS Intervention Comparison (Country) Scoreb Source (No. of clinics / sites) USA myocardial infarction. •Hospital electrocardiograph-based inpatients CCDSS. When there is an ST •Primary care segment elevation on the (28/28) electrocardiogram (ECG), TPI prints on ECG text header its prediction of five key outcomes of thrombolytic therapy for acute myocardial infarction patients. Dexter, 10 Public Preventive therapies in hospital •Academic CCDSS provided guideline-based Usual care 2001[19], inpatients. centre reminders for preventative care USA •Hospital procedures (pneumococcal inpatients vaccination, influenza (.../...) vaccination, prophylactic entericoated aspirin for cardiovascular disease, and prophylactic subcutaneous heparin for thromboembolic events) to physicians and medical students. Kuperman, 4 Public Detection of critical laboratory •Academic The CCDSS was used to detect Usual care 1999[23], results in hospital inpatients. centre critical laboratory results for all USA •Hospital medical and surgical inpatients inpatients and page the health provider that (1/1) the results were ready. The intervention signalled single laboratory results, changes in laboratory results and detection of drug-laboratory interaction. Overhage, 8 Public Identification of corollary orders to •Academic A rule-based reminder CCDSS Physicians used 1997[26], prevent errors of omission for tests centre determined corollary orders for 87 CPOE system but did USA and treatments in hospital inpatients •Hospital target orders and displayed these not receive on-line on a general medicine ward. inpatients on-line to physicians using the corollary orders. (1/1) CPOE system. Corollary orders could be accepted or rejected by physicians.

3 Study Methods Funding Indication Settingc CCDSS Intervention Comparison (Country) Scoreb Source (No. of clinics / sites) Overhage, 10 Public Compliance with 22 US Preventive •Academic CCDSS was incorporated into the Usual care 1996[25], Services Task Force preventive care centre electronic medical record and USA measures for hospital inpatients, •Hospital order-entry system and used data including cancer screening, inpatients from these sources to generate preventive screening and (1/1) reminders for 22 preventive care medications, diabetes care measures. CCDSS ran overnight reminders, and vaccinations. and provided reminders to physicians in 2 ways: printed at the top of daily patient reports, and displayed at the bottom of the workstation screen in red when physicians entered orders for patients. Physicians could accept or reject orders generated by the reminder program. White, 4 ... Monitoring signs and risk factors for •Academic CCDSS (Health Evaluation Usual care 1984[31], digoxin intoxication in inpatients. centre through Logical Processing USA •Hospital [HELP]) accessed a clinical inpatients patient database nightly and used (1/1) expert-determined decision criteria to identify concerns (drug interactions or signs of potential digoxin intoxication) for patients taking digoxin. Concerns were summarized in alert reports placed in patient charts. Management Assistants – Guidelines and Algorithms Helder, 6 ... Management of incubator settings in •Other CCDSS used infant birth weight, Nurse-determined 2008[43], neonatal ICU. •Academic gestational and postnatal ages, incubator humidity The centre room air temperature, incubator levels Netherlands •Hospital design, and use of phototherapy inpatients to suggest incubator air (1/1) temperature and humidity levels for premature, low birth weight neonates.

4 Study Methods Funding Indication Settingc CCDSS Intervention Comparison (Country) Scoreb Source (No. of clinics / sites) Davis, 9 Public Electronic prescribing for paediatric •Hospital Physicians used an electronic Usual care 2007[42], care (conditions included acute otitis outpatients prescription writer on 1 of several USA media, allergic rhinitis, sinusitis, •Primary care computer work stations or constipation, pharyngitis, croup, (2/2) wireless hand-held computers to urticaria, and bronchiolitis) in prescribe antibiotics (including outpatient and primary care settings. selection of indication and treatment duration). CCDSS then displayed evidence-based data relating to the prescription. Full articles or article abstracts were available if requested. Rothschild, 7 Public Decision support for non-emergent •Academic CCDSS suggested new orders if Usual care 2007[37, inpatient transfusion orders. centre blood products (red blood cells, 38], USA •Hospital platelets, and fresh frozen inpatients plasma) ordered through CPOE (1/1) were inconsistent with guidelines. Recommendations could be overridden. Kuilboer, 10 Public Monitoring and treatment of asthma •Primary care CCDSS uses data in electronic Usual care 2006[41], and COPD in daily practice in •Solo practice health records and clinical The primary care. (32/32) guidelines to provide feedback on Netherlands treatment to physicians for patients with asthma or COPD. Paul, 10 Public Management of antibiotic treatment •Academic By imputing variables that In control wards only, 2006[40], in hospital inpatients. centre significantly influence the observation and data Italy, •Hospital probability of pathogens, collection was Germany & inpatients physicians used the TREAT conducted and Israel (15/3) CCDSS to assess the probability physicians could not of infection, pathogen distribution, access the CCDSS. mortality and antibiotic coverage, and prescribe empirical antibiotic treatment for microbiologically documented infections.

5 Study Methods Funding Indication Settingc CCDSS Intervention Comparison (Country) Scoreb Source (No. of clinics / sites) Brothers, 6 Public Surgical management of patients •Academic Markov surgical decision analysis Standard decision- 2004[46], with peripheral arterial disease. centre CCDSS predicted quality- making USA •Hospital adjusted life years for each of 4 outpatients therapeutic interventions and •Subspecialty recommended optimal clinic treatments. Analysis was based (2/2) on patient data (e.g., utility assessment) and surgeon data (e.g., surgeon surgical results). Hamilton, 8 ... Evaluating labour progress and •Academic CCDSS used data from clinical Labour progress was 2004[44], need for caesarean sections. centre examination and obstetrical evaluated by plotting Canada & •Hospital monitor to create a reference cervical dilation USA inpatients range of women in the same against time. •Hospital labour conditions. System outpatients assigned a percentile ranking of (7/7) the labour progress of that particular mother against the reference population. This information was used by physicians to determine whether to deliver the baby by caesarean section. Hales, 4 ... Computer system for hospital •Other A personal CCDSS (Review Nurses had access to 1995[20], admission screening. •Academic Criteria) used data from the expert system output USA centre (Health Evaluation through but did not contact (1/1) Logical Processing, [HELP]) physicians about hospital information system and admissions identified data input by nurses to prescreen as unnecessary. patients and identify unnecessary hospital admissions. Nurses consulted with physicians about unnecessary admissions. Physicians had the final decision.

6 Study Methods Funding Indication Settingc CCDSS Intervention Comparison (Country) Scoreb Source (No. of clinics / sites) Wyatt, 5 Public Identification of high-cardiac risk •Academic CCDSS, (Admitted to the CCU A questionnaire with 1989[33], patients among patients with chest centre OR Not, [ACORN]), used 24 questions was UK pain attending the emergency •Hospital questionnaire data manually administered but data department. outpatients entered by a nurse to identify the were not entered into •Emergency cardiac risk of emergency CCDSS. Department department patients with chest (1/1) pain. For those patients identified as high-risk, a nurse took the record to the doctor for urgent consideration. Diagnostic Assistants Roukema, 6 Public Diagnostic management for children •Emergency CCDSS used prediction rules to Same as intervention 2008[35], with fever without apparent source Department generate a serious bacterial except that users of The in emergency department. (1/1) infection risk score for children < CCDSS were not Netherlands 17 years of age presenting to the given “order emergency department with a laboratory tests” fever without apparent source. instruction for For patients with high-risk: Users children in control of CCDSS were given advice to group. (This is not “order laboratory tests” for explicitly stated in patients randomized to CCDSS article.) intervention. Stengel, 8 ... Diagnosis in patients admitted to •Academic Handheld CCDSS guides entry of Usual, handwritten, 2004[45], orthopaedic ward. Purpose of study centre patient signs and symptoms and documentation on Germany was to compare thoroughness of •Hospital offers clinically reasonable standard paper forms documentation of clinical findings. inpatients diagnoses for physician selection •Hospital in orthopaedic hospital ward. outpatients Data were transferred to desktop •Subspecialty unit daily. clinic (1/1) Boguseviciu 7 ... Diagnosis of acute small bowel •Academic CCDSS used a Bayesian Contrast radiography s, 2002[15], obstruction in surgical inpatients. centre posterior probability formula and used for diagnosis Lithuania •Hospital 36 significant historical, clinical, inpatients and laboratory test results (1/1) together with plain abdominal

7 Study Methods Funding Indication Settingc CCDSS Intervention Comparison (Country) Scoreb Source (No. of clinics / sites) radiography to diagnose type of mechanical acute small bowel obstruction (complete or partial). Physicians determined appropriate treatment based on diagnosis. Medication Dosing Assistants Cavalcanti, 8 Public, Glucose measurement and insulin •Academic CCDSS (Computer Assisted Leuven: A strict 2009[49], Private dosing for glucose control for ICU centre Insulin Protocol, [CAIP]) used glycaemic control Brazil patients •Hospital patient data including current protocol for inpatients infusion rate, glucose level and intravenous insulin (5/5) time between previous glucose infusion with target measurements to make blood glucose recommendations for intravenous between 80 and 110 insulin dosing and glucose mg/dL. All insulin monitoring to maintain a blood adjustments were glucose between 100 and 130 made by nurses. mg/dL. The CCDSS was Conventional: available via desktop or handheld Subcutaneous insulin computers for nursing staff at was administered for hospital based ICUs. The nurses blood glucose levels input patient data and followed > 150 mg/dL the recommendations provided. according to a sliding Recommendations were scale. All insulin determined by the authors who adjustments were created the algorithms. made by nurses. Saager, 6 Public Glucose management in diabetic •Academic CCDSS (EndoTool Glucose Standard locally- 2008[50], patients in cardiothoracic ICUs. centre Management System) developed paper- USA •Hospital recommended insulin dose, based ICU insulin inpatients glucose determination frequency, protocol with target (1/1) and a 50% dextrose dose (when blood sugar levels appropriate) for hypoglycaemia, between 90 and 150 based on blood glucose readings mg/dL from a point-of-care device. It used the previous 4 dose responses to regulate the dosing

8 Study Methods Funding Indication Settingc CCDSS Intervention Comparison (Country) Scoreb Source (No. of clinics / sites) relationship, and is designed to be used by trained health care professionals. Peterson, 4 Private Drug dosing for patients ≥ 65 years •Academic CCDSS provided initial dose Control group not 2007[36]d, of age in a tertiary care academic centre advice for sedatives, neuroleptics, specified (probably USA health centre. (1/...) anti-emetics, and skeletal muscle usual care with no relaxants and discouraged CCDSS prescription of contraindicated recommendations) drugs for patients ≥ 65 years old in emergency rooms, intensive care units, and subacute units. Practitioners were not prevented from selecting higher doses than recommended. Poller, 3 Public Anticoagulation therapy initiation •Academic CCDSS (DAWN AC) generated Usual care 1998[28], and maintenance for outpatients. centre anticoagulant dosing schedules UK, •Hospital and time to next INR test using 2 Denmark, outpatients main modules. The induction Portugal, (5/5) module was for dosing initial Norway warfarin therapy over the first 4 days to reach a dose within 1 mg of eventual maintenance dose. The maintenance module adjusted the dose to reach and sustain the therapeutic range. Vadher, 6 Public Warfarin initiation and maintenance •Academic CCDSS used simple proportional- Usual care plus 1997[30], for inpatients and outpatients with centre derivative control methods to guidelines for UK deep vein thrombosis, pulmonary •Hospital provide recommendations for anticoagulation embolus or systemic embolus, atrial inpatients initial and maintenance dosing of fibrillation, valve disease, or mural (1/1) oral anticoagulation. Maintenance thrombus, or who needed dosing was based on previous prophylaxis. dose and difference between target and actual INR. Physicians could choose to accept or reject dosing recommendations, and also received guidelines on anticoagulation.

9 Study Methods Funding Indication Settingc CCDSS Intervention Comparison (Country) Scoreb Source (No. of clinics / sites)

Casner, 3 ... Theophylline dosing for inpatients •Hospital Pharmacokinetic CCDSS (linear Physician-directed 1993[18], with asthma or COPD. inpatients one-compartment model) was theophylline infusion USA (1/1) used to predict theophylline adjustments to infusion rates to achieve a target achieve a target serum level of 15 mg/L. The serum level of 15 CCDSS was run on hand-held mg/L based on 2 computers and adjusted dosing early serum based on 2 early measures of measures serum theophylline levels. Burton, 6 Public Aminoglycoside dosing for inpatients •Academic CCDSS with Bayesian-based Physician-directed 1991[16], with clinical infections. centre algorithm used serum aminoglycoside USA •Hospital aminoglycoside level data to dosing using serum inpatients predict aminoglycoside dosage level data (1/1) needed to achieve peak (gentamicin and tobramycin, 5-10 mg/L; amikacin, 20-30 mg/L) and trough (gentamicin and tobramicin, <2mg/L; amikacin, <5mg/L) target levels. Begg, 4 ... Individualized aminoglycoside •Hospital CCDSS used pharmacokinetic Routine clinical 1989[14], dosing for inpatients receiving inpatients analysis (one-compartment practice used to New gentamicin or tobramycin. (.../...) model) to predict individualized achieve peak plasma Zealand aminoglycoside doses and dose aminoglycoside levels intervals needed to achieve a of 6-10 mg/L and peak level at end of infusion of 8 trough levels of 1-2 mg/L and trough level of 1.5 mg/L mg/L. Gonzalez, 5 Private Drug-dosing of aminophylline in the •Academic CCDSS used Bayesian Dosing nomogram 1989[22], emergency department. centre pharmacokinetic model to based on emergency USA •Hospital estimate aminophylline loading department asthma inpatients and maintenance dosing for guidelines and (.../...) individual patients to achieve theophylline level 4 serum theophylline levels of 15 hours after initial mg/L (12 mg/L if oral theophylline bolus were used to given within 6 hours). determine aminophylline dosing

10 Study Methods Funding Indication Settingc CCDSS Intervention Comparison (Country) Scoreb Source (No. of clinics / sites) needed to maintain a serum theophylline level of 10-20 mg/L Hickling, 3 Private Pharmacokinetic dosage prediction •Hospital CCDSS pharmacokinetic model Nomogram was used 1989[21], for aminoglycosides based on inpatients was used to predict early to determine the New estimated creatinine clearance in (1/1) therapeutic dose and dose aminoglycoside dose Zealand critically ill patients. interval of aminoglycoside to and dose interval achieve any desired peak and based on estimated trough concentration in critically ill creatinine clearance. patients, based on 3 post- distributional plasma concentrations after the initial dose. Carter, 2 Public Warfarin initiation dosing for hospital •Academic CCDSS suggested warfarin Usual care 1987[17] inpatients. centre dosages (analog-computer USA •Hospital method) or a single dosage inpatients prediction was made using a (1/1) formula (linear-regression method) for adult inpatients. White, 6 ... Warfarin initiation and dosing for •Academic CCDSS (Warfcalc) used Usual care. 1987[32], patients hospitalized with deep vein centre Bayesian forecasting methods to Physicians selected USA thrombosis, cerebrovascular •Hospital determine appropriate warfarin target prothrombin accident, transient ischemic attack, inpatients dosing based on patient data ratio. pulmonary embolus or atrial (2/...) including response to warfarin fibrillation. therapy. Warfarin therapy was managed by a physician or pharmacist familiar with the CCDSS but who were not experts in management of warfarin therapy. Primary physicians selected target prothrombin ratio. Hurley, 8 Public, Theophylline dosing for inpatients •Hospital Initial loading and infusion doses Physicians selected 1986[24], Private with acute air-flow obstruction. inpatients of theophylline were based on a IV and oral doses of Australia (1/1) nomogram; subsequent infusion theophylline based on and oral doses were adjusted drug serum levels based on CCDSS without use of formal pharmacokinetic analysis of pharmacokinetic

11 Study Methods Funding Indication Settingc CCDSS Intervention Comparison (Country) Scoreb Source (No. of clinics / sites) theophylline serum levels. analysis. Rodman, 6 Public Lidocaine dosing for patients in •Academic CCDSS recommended lidocaine Usual care 1984[27], ICUs or coronary care units. centre infusion regimen based on USA •Hospital patient’s age, sex, height, weight, inpatients cardiac index, past lidocaine (1/1) therapy, and desired lidocaine concentration for ICU and coronary care unit patients. Abbreviations: CCDSS, computerized clinical decision support system; COPD, chronic obstructive pulmonary disease; CPOE, computerized physician order entry system; ICU, intensive care unit; INR, international normalized ratio. a Ellipses (…) indicate item was not assessed. b Based on 5 individual items (score 2 = yes, 1 = partly, and 0 = no) and a summed total score (range 0 to 10). Because this review update included only randomized, controlled trials, the total score differs from that reported in the previous version of this review[3]: the item evaluating study type (randomized, quasi-randomized, or concurrent controls) has been replaced by one that evaluates use of concealed allocation (concealed, unclear, not concealed). c Diabetes clinic is an example of a subspecialty clinic. dStudy included in 2 categories.