Table 1 Results for CCDSS trials of therapeutic drug monitoring and dosing^a

Vitamin K antagonist Dosing

Poller, 2008 [35–37]

5

1 of 2 CCDSSs (DAWN-AC or PARMA) provided dosing for warfarin/acenocoumarol/phenprocoumon in outpatients with AF, DVT or PE, mechanical heart valves, or other indications.

32/69/13,219*

Time INR in range (clinic-determined).

+

Adjudicated clinical events.

0

Claes, 2005 [27, 28]

6

CCDSS (DAWN-AC) provided dosing for warfarin/acenocoumarol/phenprocoumon in outpatients with AF, DVT or PE, mechanical heart valves, or other indications.

66*/96/834

Duration of INR values within 0.5 or 0.75 INR-units of target range (2.5 or 3.5 depending on indication).

0

Thromboembolic complications and hemorrhagic events.

0

Mitra, 2005 [29]

5

CCDSS (DAWN-AC) provided dosing for warfarin in hospitalised rehabilitation patients,

1/.../30*

Time in therapeutic INR range (2.0 to 3.0) and number of blood draws during hospitalization.

+

Incident deep vein thrombosis or pulmonary embolism during hospitalization and length of hospital stay.

...

Manotti, 2001 [26]

4

CCDSS (PARMA) provided dosing for warfarin/acenocoumarol in outpatients with VTE, non-ischemic heart disease, heart-valve prosthesis, or other indications.

5/.../1,251*

Time long term therapy group spent in therapeutic INR range (2.0 to 3.0 or 3.0 to 4.5) and proportion of starting treatment group reaching a stable condition (three consecutive INRs within therapeutic range, 2.0 to 3.0, at least one week from each other].

+

...

...

Fitzmauric, 2000 [25]

6

CCDSS provided warfarin dosing for outpatients with venous or arterial thromboembolic disorders.

12*/.../367

Proportion of patients achieving therapeutic INR target, and time in target INR range (target range varied by clinical indication for treatment: 2.0 to 3.0 or 3.0 to 4.5).

0

Deaths, serious adverse events, and patient satisfaction.

0

Ageno, 1998 [23]

6

CCDSS (DAWN-AC) provided dosing for warfarin maintenance in outpatients with mechanical heart valves.

1/.../101*

INR within therapeutic range, >5.0, or <2.0;% dose adjustments; number of INR tests; time within INR range 2.5 to 3.5; mean INR; test interval; proportion interventions manually overridden in CCDSS group.

...

...

...

Poller, 1998 [24]

3

CCDSS (DAWN-AC) provided dosing for warfarin initiation and maintenance in outpatients.

5/.../285*

Time in INR target range (2 to 3 or 2.5 to 3.5, or 3 to -0.5).

+

...

...

Vadher, 1997 [22]

6

CCDSS provided dosing for warfarin initiation and maintenance in inpatients with venous or arterial thromboembolic disorders.

1/49/148*

Time to reach therapeutic range and stable dose, time to pseudoevent (INR ≤1.5 or ≥5 after therapeutic range is reached), and time within INR range 2 to 3.

0

Deaths, thrombotic events, and hemorrhagic events.

...

Fitzmauric, 1996 [20]

4

CCDSS provided dosing for warfarin maintenance in outpatients with venous or arterial thromboembolic disorders.

2/.../49*

INR control.

...

Deaths, thrombotic or hemorrhagic episodes, and patient satisfaction.

...

Fihn, 1994 [19]

3

CCDSS scheduled follow-up visits for outpatients receiving warfarin at anticoagulation clinics.

5/.../849*

Ability to increase visit intervals and deviation of measured prothrombin times and INRs from target values.

+

Deaths, clinically important bleeding, and thromboembolic complications.

0

Poller, 1993 [18]

5

CCDSS provided dosing for warfarin therapy in outpatients with venous or arterial thromboembolic disorders.

1/.../186*

Proportion of visits spent in or out of target range and time between visits.

0

Death, major bleeding events, and other clinical events

0

White, 1991 [15]

6

CCDSS predicted steady-state warfarin dosing in outpatients on long-term warfarin therapy.

1/.../50*

Difference between achieved and target PT, patients with final PT within 2 seconds of target, and follow-up interval.

0

...

...

Carter, 1987 [9]

2

CCDSS provided dosing for warfarin initiation in hospital inpatients.

1/.../54*

Time from administration of first warfarin dose to stabilization dosage in patients with stable PT ratio pre-discharge

0

...

...

White, 1987 [10]

6

CCDSS (Warfcalc) provided dosing for warfarin therapy in patients hospitalised with DVT, cerebrovascular accident, transient ischemic attack, PE, or AF.

2/.../75*

Time to reach stable therapeutic dose or therapeutic PR, patients with PR above therapeutic range during hospital stay, predicted vs observed PR, and absolute PR error.

+

Length of hospital stay and in-hospital bleeding complications.

+

Aminophylline and Theophylline Dosing

Tierney, 2005 [31]

9

CCDSS generated care suggestions for physicians and pharmacists managing asthma and chronic obstructive pulmonary disease in adults in primary care.

4/266*/706

Proportion of care suggestions to change theophylline dose adhered to by physicians and pharmacists; medication compliance; and patient satisfaction with physicians and pharmacists.

0

Short-form 36 (physical function, role physical, pain, general health, vitality, social function, role emotional, mental health), asthma-related and chronic respiratory disease-related quality of life, emergency department visits, and hospitalizations.

0

Casner, 1993 [17]

3

CCDSS predicted theophylline infusion rates for inpatients with asthma or chronic obstructive pulmonary disease.

1/.../47*

Mean serum theophylline levels, absolute and mean difference between final and target (15 mg/L) theophylline levels, patients with subtherapeutic (<10 mg/L) final theophylline levels, and patients with toxic (>20 mg/L) final theophylline levels.

0

Theophylline-associated toxicity (nausea, vomiting, tremor, tachycardia, and seizures), length of hospital stay, treatment duration.

0

Gonzalez, 1989 [12]

5

CCDSS estimated aminophylline loading and maintenance dosing for patients in the emergency department.

.../.../67*

Mean theophylline level.

+

Discharge from emergency department within 8 hours,

adverse effects in emergency department, and peak flow rate.

0

Hurley, 1986 [8]

8

CCDSS provided dosing for theophylline in inpatients with acute air-flow obstruction.

1/.../96*

Patients with theophylline levels above or below therapeutic range (10 to 20 μg/mL) on days 1 and 2 or trough theophylline levels in therapeutic range during oral therapy, mean serum theophylline levels, mean 1st serum level and trough levels during oral therapy.

0

In first 3 days: peak expiratory flow rate, air flow obstruction symptoms (severe breathlessness, wheeziness, night wheeze, or cough during hospitalization), side effects (severe palpitations, nausea, tremulousness, agitation, blurred vision, or diarrhoea during hospitalization), and deaths.

0

Insulin Dosing and Glucose Glycaemic Regulation

Cavalcanti

2009 [39]

8

CCDSS (computer assisted insulin protocol, [CAIP]) recommended insulin dosing and glucose monitoring to achieve glucose control in patients in intensive care units.

5/60/168*

Number of blood glucose measurements and proportion of time blood glucose controlled (60 to 140 mg/dL).

+

Blood glucose levels in ICU and rates of hypoglycaemia.

+/-

Saager, 2008 [38]

6

CCDSS (EndoTool Glucose Management System) recommended insulin dosing and glucose assessment frequency for diabetic patients in cardiothoracic intensive care units.

1/.../40*

Proportion of blood glucose measures in range and time in range in operating rooms or intensive care units.

+

Blood glucose levels and time to reach blood glucose level <150 mg/dL in operating rooms or intensive care units.

+

Albisser, 2007 [33]

8

CCDSS predicted glycaemia and risk for hypoglycaemia in insulin-dependent patients in primary care.

.../2/22*

Mean daily insulin dose.

+

Hypoglycaemia episodes.

+

Rood, 2005 [30]

8

CCDSS recommended timing for glucose measurements and administration of insulin in critically ill patients.

1/104/484*

Proportion of time that glucose measurements were early or late, proportion of time that glucose levels were within target range (4.0 to 7.0 mmol/L), adherence to guideline for timing of glucose measurement, and proportion of samples taken on time.

+

...

...

Ryff-de Léche, 1992 [16]

3

CCDSS (Camit S1) analyzed and summarized blood glucose data for Insulin dosing in outpatients with diabetes.

1/.../38*

Proportion of blood glucose levels in low range (<4.0 mmol/L), at <2.9 mmol/L level, and in target range (4.0 to 10.0 mmol/L).

...

Change in haemoglobin A1c levels.

...

McDonald, 1976 [5]

2

CCDSS generated recommendations for repeat laboratory tests to detect potential medication-related events and treatment changes in adults attending a diabetes clinic.

1/.../226*

Provider adherence to recommendations to change therapy or order tests for monitoring drug effects.

+

...

...

Aminoglycoside Dosing

Burton, 1991 [14]

6

CCDSS provided aminoglycoside dosing for inpatients with clinical infections.

1*/.../147

Proportion, of patients with peak aminoglycoside level >4 mg/L or trough levels ≥2 mg/L.

0

Deaths, cures, therapy response, treatment failure, indeterminate therapy response, nephrotoxicity, length of hospital stay overall and after start of antibiotics, and length of aminoglycoside therapy.

0

Begg, 1989 [11]

4

CCDSS provided individualised aminoglycoside dosing for inpatients receiving gentamicin or tobramycin.

.../.../50*

Number of patients achieving either or both peak (6 to 10 mg/L) and trough (1 to 2 mg/L) aminoglycoside levels.

+

Deaths and change in creatinine clearance during therapy.

0

Hickling, 1989 [13]

3

CCDSS provided dosing and dose intervals aminoglycoside in critically ill patients.

1/.../32*

Proportion of patients outside of therapeutic range (6 to 10 mg/L for peak and <2 mg/L for trough) or with peak plasma levels >6 mg/L., and mean peak and trough plasma aminoglycoside levels.

+

Increase in creatinine clearance during recovery.

0

Digoxin Dosing/Monitoring

White, 1984 [7]

4

CCDSS (Health Evaluation through Logical Processing [HELP]) identified concerns (drug interactions or signs of potential digoxin intoxication) in inpatients taking digoxin.

1/.../396*

Physician compliance with alerts.

+

...

...

Peck, 1973 [4]

6

CCDSS provided a digoxin dosing scheme for outpatients with congestive heart failure.

1/4/42*

Errors for prediction of serum digoxin level.

+

Digoxin toxicity and congestive heart failure index.

0

Lidocaine Dosing

Rodman, 1984 [6]

6

CCDSS recommended lidocaine dosing for patients in intensive or coronary care units.

1/.../20*

Plasma lidocaine levels in therapeutic range (1.5 to 5.0 μg/mL).

+

Toxic response requiring lidocaine discontinuation or dosage reduction.

0

Miscellaneous

Matheny, 2008 [34]

8

CCDSS generated reminders for routine laboratory testing in primary care patients taking specified medications.

20*/303/1,922

Physician compliance with reminders.

0

...

...

Judge, 2006 [32]

8

CCDSS provided real-time alerts when ordered drugs posed potential risks, required monitoring, or needed action to prevent adverse events in a long-term care setting.

1*/27/445

Physician compliance with alerts.

0

...

...

Overhage, 1997 [21]

8

CCDSS determined corollary orders for 87 target orders and displayed these on-line to physicians using the CPOE. CCDSS identified corollary orders to prevent errors of omission for any of 87 target tests and treatments in hospital inpatients.

1*/92/2,181

Compliance with corollary orders and pharmacists interventions with physicians for significant errors.

+

Hospital length of stay and maximum serum creatinine level during hospital stay.

0