Petrus Mol

Impact of Safety-Related Regulatory Action on Clinical Practice A Systematic Review

AbstractBackground: After market approval, new serious safety issues are regularly identified for drugs that lead to regulatory action to inform healthcare professionals. However, the effectiveness of these safety-related regulatory actions is under question. We currently lack a comprehensive overview of the effects of these drug safety warnings on clinical practice to resolve the debate about their effectiveness. Objective: The aim of this systematic review is to provide an overview of studies that assessed the impact of safety warnings. Study Selection: A systematic search was performed for articles assessing the impact of Direct Healthcare Professional Communications or ‘Dear Doctor’ letters, Black Box Warnings and Public Health Advisories on clinical behaviour published between January 1996 and January 2010. The following variables were extracted: publication year, country, name of the drug, safety issue, specific safety warning (Direct Healthcare Professional Communication/Black Box Warning/Public Health Advisory), effect (intended/unintended) of the safety warning, outcome measure and study design. Papers were checked for several quality aspects. Study data were summarized using descriptive analyses. Results: A total of 50 articles were identified. Two articles assessed two different drugs and were therefore counted twice (n = 52). Thirty-three articles described the impact of safety warnings issued for three drugs and drug groups, i.e. third-generation oral contraceptives, cisapride and selective serotonin reuptake inhibitors. The remaining 19 articles described a broad variety of 14 drugs and drug groups. Twenty-five studies applied an interrupted time series design, 23 a controlled or uncontrolled before/after design, and four articles applied both. None of the articles could rule out the influence of confounding factors. The intended effects were reported in 18 (72%) of the 25 before/after analyses, whereas only 11 (41%) of the 27 interrupted time series analyses reported an impact. Only two (8%) of the before/after analyses against 11 (41%) of the interrupted time series analyses reported mixed impacts. When unintended effects were assessed in case of selective serotonin reuptake inhibitors and third-generation oral contraceptives, these were almost always present: in 19 of 22 and 4 of 5 articles, respectively. Our review shows that safety-related regulatory action can have some impact on clinical practice but firm conclusions are difficult to draw. Evidence is primarily based on three drugs and drug groups. Almost half of the studies had inadequate before/after designs and the heterogeneity in analyses and outcome measures hampered the reporting of overall effect sizes. Studies with adequate interrupted time series design reported a more mixed impact of safety warnings than before/after studies. Furthermore, this review shows the relevance of considering not only the intended but also the unintended effects of safety warnings. Conclusions: There is a clear need for further research with appropriate study designs and statistical analyses, with more attention to confounding factors such as media coverage, to understand the impact of safety-related regulatory action.

Medication errors: the impact of prescribing and transcribing errors on preventable harm in hospitalised patients

Background: Medication errors (MEs) affect patient safety to a significant extent. Because these errors can lead to preventable adverse drug events (pADEs), it is important to know what type of ME is the most prevalent cause of these pADEs. This study determined the impact of the various types of prescribing (administrative, dosing and therapeutic) and transcribing errors on pADEs in hospitalised patients. Methods: During a 5-month period, data for patients admitted to a total of five internal medicine wards of one university and one teaching hospital in The Netherlands were prospectively collected by chart review. In each hospital, MEs were detected and classified by the same pharmacist, using the classification scheme for MEs developed by The Netherlands Association of Hospital Pharmacists. The primary outcome measure was the prevalence of pADEs during hospital stay. In consensus meetings, five pharmacists assessed the causal relationship between MEs and pADEs. The association between type of ME and pADEs was determined by a multivariate regression analysis taking into account potential confounders. Results: The study included 592 hospital admissions with 7286 medication orders (MOs), of which 60% contained at least one prescribing or transcribing error. 1.4% of all MOs led to pADEs, concerning 14.8% of all admitted patients. The total number of pADEs was 103, and in 92 of these cases patients experienced temporary harm, in eight cases hospital admission was prolongued, two cases were life-threatening, and one was fatal. Therapeutic errors were most strongly associated with pADEs (OR 1.98; 95% CI 1.53 to 2.56). Conclusions: Although many prescribing and transcribing errors occur in the process of medication use of hospitalised patients, a minority lead to pADEs. In particular, therapeutic errors are the cause of these pADEs and are therefore clinically relevant. Intervention and prevention programmes should primarily focus on this type of medication error.

Impact of Safety-Related Regulatory Action on Drug Use in Ambulatory Care in the Netherlands

The effect of Direct Healthcare Professional Communications (DHPCs) informing health‐care providers of serious drug safety issues has been questioned. The aim of this study was to evaluate the impact of DHPCs on drug use. Nationwide dispensing data for the period 2000–2008 for new users of 46 drugs with one or more DHPCs were assessed. Impact on short‐term volume of use was evaluated with regression models, and the presence of long‐term changes in use was evaluated with interrupted time series analyses incorporating preexisting trends. The short‐term prescription level was lower post‐DHPC in 28 (48.3%) of 58 cases. Twenty (34.5%) DHPCs resulted in long‐term changes in use. A long‐term mean reduction in use was observed in 26.7% of cases (95% confidence interval, −15.2 to −38.2%). Long‐term changes in use were not significantly related to preexisting trends in use. Although short‐ and long‐term decreases in use were observed after only half and a third of DHPCs, respectively, the decrease was substantial.

Cost-effectiveness of an electronic medication ordering system (CPOE/CDSS) in hospitalized patients

INTRODUCTION Prescribing medication is an important aspect of almost all in-hospital treatment regimes. Besides their obviously beneficial effects, medicines can also cause adverse drug events (ADE), which increase morbidity, mortality and health care costs. Partially, these ADEs arise from medication errors, e.g. at the prescribing stage. ADEs caused by medication errors are preventable ADEs. Until now, medication ordering was primarily a paper-based process and consequently, it was error prone. Computerized Physician Order Entry, combined with basic Clinical Decision Support System (CPOE/CDSS) is considered to enhance patient safety. Limited information is available on the balance between the health gains and the costs that need to be invested in order to achieve these positive effects. Aim of this study was to study the balance between the effects and costs of CPOE/CDSS compared to the traditional paper-based medication ordering. METHODS The economic evaluation was performed alongside a clinical study (interrupted time series design) on the effectiveness of CPOE/CDSS, including a cost minimization and a cost-effectiveness analysis. Data collection took place between 2005 and 2008. Analyses were performed from a hospital perspective. The study was performed in a general teaching hospital and a University Medical Centre on general internal medicine, gastroenterology and geriatric wards. Computerized Physician Order Entry, combined with basic Clinical Decision Support System (CPOE/CDSS) was compared to a traditional paper based system. All costs of both medication ordering systems are based on resources used and time invested. Prices were expressed in Euros (price level 2009). Effectiveness outcomes were medication errors and preventable adverse drug events. RESULTS During the paper-based prescribing period 592 patients were included, and during the CPOE/CDSS period 603. Total costs of the paper-based system and CPOE/CDSS amounted to €12.37 and €14.91 per patient/day respectively. The Incremental Cost-Effectiveness Ratio (ICER) for medication errors was 3.54 and for preventable adverse drug events 322.70, indicating the extra amount (€) that has to be invested in order to prevent one medication error or one pADE. CONCLUSIONS CPOE with basic CDSS contributes to a decreased risk of preventable harm. Overall, the extra costs of CPOE/CDSS needed to prevent one ME or one pADE seem to be acceptable.