Lisa M. Kalisch

Prevalence of potentially hazardous drug interactions amongst Australian veterans

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT * Up to 21% of adverse drug event related hospital admissions are due to drug interactions. Clinical significance of drug interactions varies. * Studies which only identified drug interactions of potentially major clinical significance found lower prevalence, of between 2 and 16%. * Prevalence of drug interactions defined potentially hazardous has had limited study, with no publications identified for the Australian population. WHAT THIS STUDY ADDS * In the study population of 287 074, 1.5% of subjects were dispensed potentially hazardous interacting drug pairs. * However, limited to populations on specific medicines, it was found that for patients dispensed verapamil, methotrexate, amiodarone, lithium, warfarin, cyclosporin and itraconazole, potentially hazardous interactions occurred at a rate greater than 5%. * These patients should be the focus of medication review programmes to avoid potentially serious adverse drug events. BACKGROUND Up to 21% of adverse drug event-related hospital admissions are due to drug interactions. Clinical significance of drug interactions varies, and drug interactions defined potentially hazardous are more likely to contribute to morbidity and mortality. AIM The aim of this study was to assess the prevalence of potentially hazardous drug interactions in an elderly Australian veteran population. METHODS This study assessed the prevalence of potentially hazardous drug interactions, where hazardous was defined in three or more international drug interaction references, using Repatriation Pharmaceutical Benefits Scheme pharmacy claims data. Analysis was limited to patients who received regular concurrent dispensings of potentially hazardous interacting medicines. RESULTS Of the 287 074 subjects included in the study, 1.5% were dispensed potentially hazardous interacting drug pairs. For patients dispensed cyclosporin, concomitant use of a statin was common (47%); as was statin use with those dispensed itraconazole (31%). Of those dispensed methotrexate, 24% also received a non-steroidal anti-inflammatory drug; of those on lithium, 18% also received an ACE inhibitor or angiotensin 2 receptor blocker; of those on warfarin, 7.2% and 5.9% were co-dispensed an non-steroidal anti-inflammatory drugs or antiplatelets respectively; for those on verapamil, 5.3% were co-dispensed a beta-blocker, while for those on amiodarone 6.2% were co-dispensed digoxin. CONCLUSIONS Overall prevalence of potentially serious drug interactions appears to be low in the Australian veteran population. However, patients taking cyclosporine, itraconazole, methotrexate, lithium, warfarin, verapamil and amiodarone appear to be most at risk and their medicine use should be regularly reviewed to prevent potentially hazardous drug interactions.

Prevalence of preventable medication-related hospitalizations in Australia: an opportunity to reduce harm.

OBJECTIVEnTo identify the prevalence of potentially preventable medication-related hospitalizations amongst elderly Australian veterans by applying clinical indicators to administrative claims data.nnnDESIGN AND SETTINGnRetrospective cohort study in the Australian veteran population from 1 January 2004 to 31 December 2008.nnnPARTICIPANTSnA total of 109 044 veterans with one or more hospitalizations defined by the medication-related clinical indicator set, during the 5-year study period.nnnMAIN OUTCOME MEASUREnThe prevalence of potentially preventable medication-related hospitalizations as a proportion of all hospitalizations defined by the clinical indicator set.nnnRESULTSnDuring the 5-year study period, there were a total of 1 630 008 hospital admissions of which 216 527 (13.3%) were for conditions defined by the medication-related clinical indicator set for 109 044 veterans. The overall proportion of potentially preventable medication-related hospitalizations was 20.3% (n= 43 963). Of the 109 044 veterans included in the study, 28 044 (25.7%) had at least one potentially preventable medication-related hospitalization and 7245 (6.6%) veterans had two or more potentially preventable admissions. Conditions with both a high prevalence of hospitalization and preventability included asthma/chronic obstructive pulmonary disorder, depression and thromboembolic cerebrovascular event (23.3, 18.5 and 18.3%, respectively, were potentially preventable). Other hospitalizations that were less common but had a high level of preventability (at least 20%) included hip fracture, impaction, renal failure, acute confusion, bipolar disorder and hyperkalaemia.nnnCONCLUSIONSnThe results of this study highlight those conditions where hospitalizations could potentially be avoided through improved medication management. Strategies to increase the awareness, identification and resolution of these medication-related problems contributing to these hospitalizations are required in Australia.

The validity of sequence symmetry analysis (SSA) for adverse drug reaction signal detection

To determine the validity of sequence symmetry analysis (SSA) method to detect adverse drug reactions from an administrative claims database.

Continuity of care: when do patients visit community healthcare providers after leaving hospital?

Background/Aims:u2002 Enhanced communication and transfer of information between healthcare providers and healthcare settings can reduce medication and healthcare errors post‐hospital discharge. The timeframes within which patients access community healthcare providers post‐hospital discharge are not well studied. This study aimed to determine length of time from hospital discharge until a general practice, pharmacy or specialist visit, or care planning service.

Managing Glaucoma in those with Co-morbidity: Not as Easy as it Seems

Purpose: To identify the extent of use of medicines recommended to be used with caution in glaucoma patients with specified comorbidities and to determine evidence of associated harm. Methods: Retrospective cohort analysis from administrative claims data and prescription/event sequence symmetry analysis. Participants: Australian Government Department of Veterans’ Affairs treatment card holders dispensed glaucoma eye-drops. Main outcome measures: Proportion of veterans with glaucoma and diabetes, airways disease, heart failure, ischemic heart disease or depression, dispensed glaucoma eye drops which should be used with caution. For harms, outcome measures were hospitalizations for airways disease and heart disease. Results: The cohort analysis included 25,984 veterans. Of these, 88% with airways disease were dispensed glaucoma eye drops with the potential to aggravate airways disease, 43% with heart failure were dispensed topical beta-blockers and 49% with depression received glaucoma eye drops which should be used cautiously in those with depression. We found increased risk of initiation of inhaled beta-agonist following timolol (adjusted sequence ratio (ASR) 1.48, 99% CI 1.22–1.78) and latanoprost (ASR 1.24, 99% CI 1.11–1.38) initiation. We found increased risk of inhaled corticosteroid initiation following initiation of timolol (ASR 1.43, 99% CI 1.13–1.81). There was increased risk of antidepressant initiation following timolol initiation (ASR 1.24, 99% CI 1.07–1.43), and latanoprost (ASR 1.16, 99% CI 1.03–1.31). There was also increased risk of hospitalization for bradycardia following timolol initiation (ASR 2.22,99% CI 1.15–4.31). Conclusion: Use of glaucoma eye drops recommended to be used with caution in co-morbidities is common and was associated with adverse outcomes. Awareness of co-morbidities is required in the selection and prescription of glaucoma eye drops.

Comparing Time to Adverse Drug Reaction Signals in a Spontaneous Reporting Database and a Claims Database: A Case Study of Rofecoxib-Induced Myocardial Infarction and Rosiglitazone-Induced Heart Failure Signals in Australia

IntroductionThe objective of post-marketing surveillance of medicines is to rapidly detect adverse drug reactions (ADRs). Early ADR detection will enable policy makers and health professionals to recognise adverse events that may not have been identified in pre-marketing clinical trials. Multiple methods exist for ADR signal detection. Traditional quantitative methods employed in spontaneous reports data have include reporting odds ratio (ROR), proportional reporting ratio (PRR) and Bayesian techniques. With the development of administrative health claims databases, additional methods such as sequence symmetry analysis (SSA) may be able to be employed routinely to confirm ADR signals.Objective and MethodWe tested the time to signal detection of quantitative ADR signalling methods in a health claims database (SSA) and in a spontaneous reporting database (ROR, PRR, Bayesian confidence propagation neural network) for rofecoxib-induced myocardial infarction and rosiglitazone-induced heart failure.ResultsThis study demonstrated that all four signalling methods detected safety signals within 1–3xa0years of market entry or subsidisation of the medicines, and for both cases the signals were detected before post-marketing clinical trial results. By contrast, the trial results and subsequent warning or withdrawal were published 5–7xa0years after first marketing of these medicines.ConclusionThis case study highlights that a post-marketing quantitative method utilising administrative claims data can be a complementary tool to traditional quantitative methods employed in spontaneous reports that may help to verify safety signals detected in spontaneous reporting data.

Brand substitution or multiple switches per patient? An analysis of pharmaceutical brand substitution in Australia†‡

To determine the number of times patients have brand and generic products substituted under Australias Pharmaceutical Benefits Scheme (PBS) brand substitution policy.

Improving heart failure outcomes with pharmacist–physician collaboration: how close are we?

Improved management of chronic disease can improve health outcomes and has the potential to reduce health service costs. Heart failure is one of the chronic diseases in which improved management involving multidisciplinary care leads to improved health outcomes. Numerous studies have shown that multidisciplinary teams involving a doctor, pharmacist, nurse, health educator and/or a social worker can improve health outcomes for heart failure patients. Fewer studies have examined the effect of collaborative interventions that specifically involve pharmacists and physicians. This review focuses on the efficacy of pharmacist-physician collaborative medicines reviews in improving health outcomes for heart failure patients. The translation of results from randomized controlled trials to the practice setting is discussed, and barriers to the implementation of collaborative medicines reviews in practice are described.

The Detection of Adverse Events in Randomized Clinical Trials: Can we Really Say New Medicines are Safe?

BACKGROUNDnWhile it is well known that randomized controlled trials (RCTs) are usually designed with sufficient sample size and power to detect the efficacy but not safety of a medicine, the extent to which RCTs quantify safety has not been well ascertained.nnnPURPOSEnThe aim of this study was to assess the safety data available for five commonly prescribed medicines at the time of marketing.nnnMETHODSnPublished RCTs for five medicines risperidone, sertraline, donepezil, strontium ranelate and tramadol extended release were identified. All adverse events (AEs) in the trials were independently extracted by two clinical researchers. Using the sample size in the trials, the power to detect the observed difference in AEs rates between the treatment and placebo groups was calculated. A power of 80% or more was deemed adequate to detect AEs; studies with power of < 80% were deemed insufficiently powered to detect AEs.nnnRESULTSn12 RCTs were identified. Six trials were insufficiently powered to detect any of the potential AEs reported. Of the 150 evaluated AEs, the trials were insufficiently powered to detect 81% (122/150) of the AEs reported. For the adverse events that were detected with adequate powered clinical trials, only 53% (10/19) of potentially very common AEs (≥10%) and 17% (18/106) of potentially common AEs (1%-<10%) were identified.nnnCONCLUSIONnTrials are insufficiently powered to detect the majority of adverse events that are reported in clinical trials, even for common adverse events. Observations other than primary efficacy endpoints such as AEs that are not prespecified with adequate power should be treated as hypothesis generating only and not justification of evidence. Claims of safety based on trial evidence not designed for the safety endpoint are often premature.

Sequence Symmetry Analysis and Disproportionality Analyses: WhatPercentage of Adverse Drug Reaction do they Signal?

Background: Sequence Symmetry Analysis (SSA) is a method to detect Adverse Event (AE) signals using administrative claims data. Proportional Reporting Ratio (PRR), Reporting Odds Ratio (ROR) and Bayesian Confidence Propagation Neural Network (BCPNN) are methods to detect AE signals using spontaneous reporting data. The proportion of AEs detected by all four methods is unknown. Objective: To determine sensitivity, specificity and predictive values of SSA, PRR, ROR and BCPNN for a set of medicine-AE pairs. Methods: All AEs identified in published Randomised Controlled Trials (RCTs) and Product Information (PI) were extracted for 19 medicines. Gold standard positive AEs were events identified in powered RCTs and gold standard negative AEs were events not listed in the PI for that medicine or any other medicines in the class. SSA was performed for each medicine-AE pairs using Australian Goverrnment Department of Veterans Affairs’ data, while the PRR, ROR and BCPNN, was calculated using the Food and Drug Administration Adverse Events Reporting System data. Results: A total of 157 medicine-AE pairs (43 positive and 114 negative) were identified and tested. SSA, PRR, ROR and BCPNN had a sensitivity of 65%, 1 9%, 49% and 51% respectively. Specificities across all methods were similar; 89%-97%. Thirty percent of true positive pairs were detected by all methods. SSA detected an additional 35% different true positive pairs while PRR, ROR and BCPNN methods detected an additional 21% different true positive pairs. Conclusions: Using the combination of signalling methods and data sources, more adverse drug reactions can be detected and could potentially strengthen the safety surveillance of post-marketing medicine.