Evaluation of rule effectiveness and positive predictive value of clinical rules in a Dutch clinical decision support system in daily hospital pharmacy practice.

INTRODUCTION: Our advanced clinical decision support (CDS) system, entitled 'adverse drug event alerting system' (ADEAS), is in daily use in our hospital pharmacy. It is used by hospital pharmacists to select patients at risk of possible adverse drug events (ADEs). The system retrieves data from several information systems, and uses clinical rules to select the patients at risk of ADEs. The clinical rules are all medication related and are formulated using seven risk categories. OBJECTIVE: This studies objectives are to 1) evaluate the use of the CDS system ADEAS in daily hospital pharmacy practice, and 2) assess the rule effectiveness and positive predictive value (PPV) of the clinical rules incorporated in the system. SETTING: Leiden University Medical Center, The Netherlands. All patients admitted on six different internal medicine and cardiology wards were included. MEASURES: Outcome measures were total number of alerts, number of patients with alerts and the outcome of these alerts: whether the hospital pharmacist gave advice to prevent a possible ADE or not. Both overall rule effectiveness and PPV and rule effectiveness and PPV per clinical rule risk category were scored. STUDY DESIGN: During a 5 month study period safety alerts were generated daily by means of ADEAS. All alerts were evaluated by a hospital pharmacist and if necessary, healthcare professionals were subsequently contacted and advice was given in order to prevent possible ADEs. RESULTS: During the study period ADEAS generated 2650 safety alerts in 931 patients. In 270 alerts (10%) the hospital pharmacist contacted the physician or nurse and in 204 (76%) cases this led to an advice to prevent a possible ADE. The remaining 2380 alerts (90%) were scored as non-relevant. Most alerts were generated with clinical rules linking pharmacy and laboratory data (1685 alerts). The overall rule effectiveness was 0.10 and the overall PPV was 0.08. Combination of rule effectiveness and PPV was highest for clinical rules based upon the risk category "basic computerized physician order entry (CPOE) medication safety alerts fine-tuned to high risk patients" (rule efficiency=0.17; PPV=0.14). CONCLUSION: ADEAS can effectively be used in daily hospital pharmacy practice to select patients at risk of potential ADEs, but to increase the benefits for routine patient care and to increase efficiency, both rule effectiveness and PPV for the clinical rules should be improved. Furthermore, clinical rules would have to be refined and restricted to those categories that are potentially most promising for clinical relevance, i.e. "clinical rules with a combination of pharmacy and laboratory data" and "clinical rules based upon the basic CPOE medication safety alerts fine-tuned to high risk patients".

A computerized adverse drug event alerting system using clinical rules: a retrospective and prospective comparison with conventional medication surveillance in the Netherlands.

BACKGROUND: Adverse drug events (ADEs) are an important problem in hospital practice. Computerized physician order entry (CPOE) and clinical decision support systems (CDSS) are useful tools in the prevention of ADEs. In the Netherlands there are some basic CDSS within CPOE systems, but there is not much experience with sophisticated systems. We have recently developed a more advanced CDSS, a computerized adverse drug event alerting system (ADEAS). OBJECTIVE: The aim of the study was to compare the newly developed ADEAS, which uses a set of clinical rules, with the conventional medication surveillance, a basic CDSS within a CPOE, to assess its additional value in detecting patients with a potential ADE. SETTING: Leiden University Medical Center (LUMC), a university hospital in Leiden, the Netherlands. DESIGN: Two studies were carried out; one retrospective and one prospective. The retrospective comparison of ADEAS with conventional medication surveillance was conducted on all patients admitted to the hospital (except intensive care unit patients) during a 1-month period (15 November-15 December 2006). A prospective comparison of both systems was performed during a 6-month period (May-October 2007) on one general internal medicine ward. MEASUREMENTS: The endpoint was the total number of alerts and content of alerts generated by both methods. In the prospective study we also focused on the number of unique alerts and interventions by the hospital pharmacist following the alerts. RESULTS: In the retrospective study, ADEAS generated 2010 alerts compared with 2322 generated by the conventional method. In the prospective study, 248 and 177 alerts were generated by ADEAS and the conventional method, respectively. The number of unique alerts was 85 (of which 72 were considered true positive alerts) and 136, respectively. The hospital pharmacist made 14 (19.4%) interventions following a true positive alert with ADEAS and 5 (3.7%) with the conventional method. The contents of alerts generated by ADEAS were different to the safety alerts generated by conventional medication surveillance. The conventional medication surveillance generated safety alerts regarding drug-drug interactions and drug-overdosing. ADEAS generated alerts regarding declined renal function or other laboratory abnormalities and absence of essential concurrent medication. CONCLUSIONS: Compared with our conventional medication surveillance, the computerized alert system ADEAS selected different patients at risk for an ADE. This makes ADEAS in our hospital of additional value to the hospital pharmacist as a suitable tool in reducing the number of preventable ADEs.

Comparison of methods for identifying patients at risk of medication-related harm.

BACKGROUND: With the introduction of Computerised Physician Order Entry (CPOE) in routine hospital care, a great deal of effort has been put into refining Clinical Decision Support Systems (CDSS) to identify patients at risk of preventable medication-related harm. OBJECTIVES: This study compared a CPOE with basic CDSS and 16 clinical rules with a manual pharmacist medication review to detect overdose and drug-drug interactions that actually required a change in medication. METHODS: The study involved the review of 313 patients admitted over 5 months at an internal medicine ward where a change in medication as a result of dosing of therapeutic errors was detected by a manual medication review by a trained pharmacist. Subsequently, all these patients' medication orders (MOs) were entered into the authors' CPOE with basic CDSS. Medication orders with a safety alert indicating overdose and drug-drug interactions generated by the authors' CPOE with basic CDSS were compared with the same type of medication errors identified through manual review. The positive predictive value (PPV), sensitivity and specificity compared with manual review were determined. Second, a set of 16 clinical rules was applied to the patient and prescribing data. The overlap between the clinical rules and manual review was determined by comparing patients triggered by the clinical rule with patients with a corresponding error in the manual medication review. RESULTS: Manual medication review identified 57 medication errors involving overdose and 143 therapeutic errors of which 46 were drug-drug interactions. The CPOE with basic CDDS generated 297 safety alerts involving overdose (PPV 0.06, sensitivity 0.32, specificity 0.92) and 365 safety alerts involving drug-drug interactions (PPV 0.12, sensitivity 0.96, specificity 0.91). The clinical rules generated 313 safety alerts identifying 39% of all the overdoses and therapeutic errors found in the manual review at which they were targeted. In 23% of the alerts generated by a clinical rule, the patients actually required a change of medication as indicated by the manual review. When CPOE with basic CDSS and the rules were combined, 66% of the overdoses and therapeutic errors were identified. CONCLUSIONS: The authors' CPOE with basic CDSS and the clinical rules are useful early strategies for preventing medication-related harm. They could be a first step towards more advanced decision support. These computerised systems will be even more useful in daily practice, once they are further fine-tuned to decrease the number of alerts that need no clinical action.

Efficacy and safety of a single intrathecal methylprednisolone bolus in chronic complex regional pain syndrome.

Activated immune cells in the spinal cord may play an important role in the development and maintenance of neuropathic pain, such as occurs in response to peripheral inflammation or tissue injury. Immune activation may therefore serve as a therapeutic target for immune modulating drugs like corticosteroids. This double-blind randomized placebo-controlled parallel-group trial aimed to investigate the efficacy and safety of a single intrathecal administration of 60 mg methylprednisolone (ITM) in chronic patients with complex regional pain syndrome (CRPS). The primary outcome measure was change in pain (pain intensity numeric rating scale; range 0-10) after 6 weeks. With 21 subjects per group the study had a 90% power to detect a clinically relevant difference (> or = 2 points). After 21 patients (10 on ITM) were included, the trial was stopped prematurely after the interim analysis had shown that ITM had no effect on pain (difference in mean pain intensity numeric rating scale at 6 weeks 0.3, 95% confidence interval -0.7 to 1.3) or any other outcome measure. We did not find any difference in treatment-emergent adverse events between the ITM and placebo group. We conclude that a single bolus administration of ITM is not efficacious in chronic CRPS patients, which may indicate that spinal immune activation does not play an important role in this phase of the syndrome.

Intrathecal glycine for pain and dystonia in complex regional pain syndrome.

Since glycinergic neurotransmission plays an important inhibitory role in the processing of sensory and motor information, intrathecal glycine (ITG) administration may be a potential therapy for both pain and movement disorders in patients with complex regional pain syndrome (CRPS). Aims of the current study, which is the first report on ITG in humans, were to evaluate its safety and efficacy. ITG treatment during 4 weeks was studied in CRPS patients with dystonia in the period before they received intrathecal baclofen treatment. Twenty patients were assessed and after exclusion of one patient, the remaining 19 patients were randomized in a double-blind placebo-controlled crossover study. Safety was assessed by clinical evaluation, blood examinations and electrocardiograms. Efficacy measures involved pain (numeric rating scale, McGill pain questionnaire), movement disorders (Burke-Fahn-Marsden dystonia rating scale, unified myoclonus rating scale, tremor research group rating scale), activity (Radboud skills questionnaire, walking ability questionnaire), and a clinical global impression (CGI) and patient's global impression score (PGI). Treatment-emergent adverse events were generally mild to moderate and not different from placebo treatment. During ITG treatment growth hormone levels were slightly increased. Although there was a trend to worsening on the CGI and PGI during ITG treatment, there were no significant differences between ITG and placebo treatment in any of the outcomes. ITG given over 4 weeks was ineffective for pain or dystonia in CRPS. Although no serious adverse events occurred, further studies are required to rule out potential neurotoxicity of ITG.

Preventing adverse drug events in hospital practice: an overview.

Adverse drug events (ADEs) are a considerable cause of morbidity and mortality in hospital practice. The precise frequency is unknown, but studies give an incidence number ranging from 2 until 52 ADEs per 100 patients. There are many different methods for definition, causality assessment, severity classification and detection which make it difficult to compare the different studies. A substantial part (in some studies up to 70%) of ADEs can be prevented and it is important to, besides their detection, focus on the prevention of these ADEs. In this literature review we give an overview of methods for preventing ADEs. There are many different tools with different impact on a particular part of the distribution system which has the potential to prevent ADEs. A multifaceted approach is needed. Two interesting strategies of prevention, pharmacist participation on ward rounds and computerised physician order entry with clinical decision support systems (CDSS), are highlighted. Moreover, two promising CDSS are discussed in more detail, namely computer-based monitoring systems and information systems which link laboratory and pharmacy data.

Medication errors: hospital pharmacist perspective.

In recent years medication error has justly received considerable attention, as it causes substantial mortality, morbidity and additional healthcare costs. Risk assessment models, adapted from commercial aviation and the oil and gas industries, are currently being developed for use in clinical pharmacy. The hospital pharmacist is best placed to oversee the quality of the entire drug distribution chain, from prescribing, drug choice, dispensing and preparation to the administration of drugs, and can fulfil a vital role in improving medication safety. Most elements of the drug distribution chain can be optimised; however, because comparative intervention studies are scarce, there is little scientific evidence available demonstrating improvements in medication safety through such interventions. Possible interventions aimed at reducing medication errors, such as developing methods for detection of patients with increased risk of adverse drug events, performing risk assessment in clinical pharmacy and optimising the drug distribution chain are discussed. Moreover, the specific role of the clinical pharmacist in improving medication safety is highlighted, both at an organisational level and in individual patient care.