Preventable and Non-Preventable Adverse Drug Events in Hospitalized Patients A Prospective Chart Review in the Netherlands

Background: Medication safety research and clinical pharmacy practice tc day is primarily focused on managing preventable adverse drug events (pADEs). Determinants of both pADEs and non-preventable adverse drug react ons (ADRs) have been identified. However, relatively little is known on the overlap between these determinants and the balance of preventable and non-preventable harm inpatients experience in modern computerized hospitals. Objective: The aim of this study was to analyse the prevalence of pADEs and non-preventable ADRs as well as the determinants, including multimorbidity, of these ADEs, i.e. both pADEs and ADRs. Methods: Adverse events experienced by patients admitted to two Dutch hospitals with functioning computerized physician order entry (CPOE) systems were prospectively identified through chart review. Adverse events were divided into pADEs (i.e. as a result of a medication error) and non-preventable ADRs. In both cases, a causal relationship between adverse events and patients' drugs was established using the simplified Yale algorithm. Study data were collected anytime between April 2006 and May 2008 over a 5-month period at each hospital ward included in the study, beginning from 8 weeks after CPOE was implemented at the ward. Results: pADEs and non-preventable ADRs were experienced by 349 (58%) patients, of whom 307 (88%) had non-preventable ADRs. Multimorbidity (adjusted odds ratio [OR(adj)] 1.90; 95% CI 1.44, 2.50; OR(adj) 1.28; 95% CI 1.14, 1.45, respectively), length of stay (OR(adj) 1.13; 95% CI 1.06, 1.21; OR(adj) 1.11; 95% CI 1.07, 1.16, respectively), admission to the geriatric ward (OR(adj) 7.78; 95% CI 2.15, 28.13; OR(adj) 3.82; 95% CI 1.73, 8.45, respectively) and number Of medication orders (OR(adj) 1.25; 95% CI 1.16, 1.35; OR(adj) 1.13; 95% CI 1.06, 1.21, respectively) were statistically significantly associated with pADEs and ADRs. Admission to the gastroenterology/rheumatology ward (OR(adj) 0.22; 95% CI 0.06, 0.77; OR(adj) 0.40; 95% CI 0.24, 0.65, respectively) was inversely related to both pADEs and ADRs. Other determinants for ADRs only were female sex (OR(adj) 1.77; 95% CI 1.12, 2.80) and use of drugs affecting the nervous system (OR(adj) 1.83; 95% CI 1.09, 3.07). Age was a significant determinant for pADEs only (OR(adj) 1.07; 95% CI 1.03, 1.11). Conclusions: In this study more than half of the patients admitted to the hospitals are harmed by drugs, of which most are non-serious, non-preventable ADRs (after the introduction of CPOE). Determinants of both pADEs and ADRs overlap to a large extent. Our results imply the need for signalling early potential adverse events that occur during the normal use of drugs in multimorbid patients or those in geriatric wards. Subsequent therapeutic interventions may improve the well-being of hospitalized patients to a greater extent than focusing on errors in the medication process only

Dissemination of Direct Healthcare Professional Communications on Medication Errors for Medicinal Products in the EU: An Explorative Study on Relevant Factors

Introduction: When serious medication errors (ME) are identified, communication to the field may be necessary. In the EU, communication of serious safety issues, such a

Evaluation of information in summaries of product characteristics (SMPCs) on the use of a medicine in patients with hepatic impairment

Background: In 2005, the European Medicines Agency (EMA) released guidance on pharmacokinetic studies in patients with hepatic impairment. This guidance describes the design of these studies and what information should be presented in the Summary of Product

Identificatie van risicopatiënten op grond van patiënt- En ziektekenmerken: Determinanten van ciprofloxacineresistentie

Objective: Primary objective was to identify patient and disease characteristics associated with ciprofloxacin resistance in a university hospital. Secondary objective was to explore the quality of microbial diagnostics in clinical practice. Design: Retrospective nested case control study. Methods: Subsequent individual culture results were linked for 551 internal medicine patients using ciprofloxacin. Cases were patients with a pathogen resistance shift from sensitive before start of ciprofloxacin to resistant after start. Controls were patients with persistent ciprofloxacin sensitive pathogens. Patient (e.g. age, co-morbidity, prior extramural ciprofloxacin use) and disease characteristics (e.g. fever, CRP level) as determinants for ciprofloxacin resistance were assessed. Results: Nearly 80% of the patients were excluded. A shift in resistance was not detectable because there were no culture results after start of ciprofloxacin or because no pathogens were cultured. Of the evaluable patients, 19 were classified as cases and 81 as controls. No patient or disease characteristics were associated with ciprofloxacin resistance although elevated serum creatinin (>130 μmol/L) and CRP (>100 mg/L) levels were more common among the cases. Community patient data of prior ciprofloxacin use and ciprofloxacin resistant pathogens were poorly documented in the hospital files, hindering assessment of these determinants. Conclusion: It is possible to analyse the occurrence of ciprofloxacin resistance and its determinants on a patient level. Due to the nature of routine culture data collection (e.g. no cultures are taken once a patient improves on initiated therapy) this study is limited by the low number of assessable patients. A prospective study with surveillance cultures and a more thorough community patient data collection needs to be conducted to address this limitation

Determinants of ciprofloxacin resistance. Identifying patients at risk on the basis of patient and disease characteristics

Objective: Primary objective was to identify patient and disease characteristics associated with ciprofloxacin resistance in a university hospital. Secondary objective was to explore the quality of microbial diagnostics in clinical practice. Design: Retrospective nested case control study. Methods: Subsequent individual culture results were linked for 551 internal medicine patients using ciprofloxacin. Cases were patients with a pathogen resistance shift from sensitive before start of ciprofloxacin to resistant after start. Controls were patients with persistent ciprofloxacin sensitive pathogens. Patient (e.g. age, co-morbidity, prior extramural ciprofloxacin use) and disease characteristics (e.g. fever, CRP level) as determinants for ciprofloxacin resistance were assessed. Results: Nearly 80% of the patients were excluded. A shift in resistance was not detectable because there were no culture results after start of ciprofloxacin or because no pathogens were cultured. Of the evaluable patients, 19 were classified as cases and 81 as controls. No patient or disease characteristics were associated with ciprofloxacin resistance although elevated serum creatinin (>130 μmol/L) and CRP (>100 mg/L) levels were more common among the cases. Community patient data of prior ciprofloxacin use and ciprofloxacin resistant pathogens were poorly documented in the hospital files, hindering assessment of these determinants. Conclusion: It is possible to analyse the occurrence of ciprofloxacin resistance and its determinants on a patient level. Due to the nature of routine culture data collection (e.g. no cultures are taken once a patient improves on initiated therapy) this study is limited by the low number of assessable patients. A prospective study with surveillance cultures and a more thorough community patient data collection needs to be conducted to address this limitation

Additional safety risk to exceptionally approved drugs in Europe?

AIMS Regulatory requirements for new drugs have increased. Special approval procedures with priority assessment are possible for drugs with clear 'unmet medical need'. We question whether these Exceptional Circumstances (EC) or Conditional Approval (CA) procedures have led to a higher probability of serious safety issues. METHODS A retrospective cohort study was performed of new drugs approved in Europe between 1999 and 2009. The determinant was EC/CA vs. standard procedure approval. Outcome variables were frequency and timing of a first Direct Healthcare Professional Communication (DHPC). An association between approval procedure and the time from market approval to DHPC was assessed using Kaplan-Meyer survival analysis and Cox-regression to correct for covariates. RESULTS In total 289 new drugs were approved. Forty-six (16.4%) were approved under EC or CA, of which seven received a DHPC (15%). This was similar to the standard approval drugs (243), of which 33 received one or more DHPC (14%, P = 0.77). The probability of acquiring a DHPC for standard approval drugs vs. EC/CA drugs during 11-year follow-up is 22% (95% CI 14%, 29%) and 26% (95% CI 8%, 44%), respectively (log-rank P = 0.726). This difference remained not significant in the Cox-regression model: hazard ratio 0.94 (95% CI 0.40, 2.20). Only drug type was identified as a confounding covariate. CONCLUSION The EC/CA procedure is not associated with a higher probability of DHPCs despite limited clinical development data. These data do not support the view that early drug approval increases the risk of serious safety issues emerging after market approval

Future of the drug label: perspectives from a multi stakeholder dialogue

'Regulating drugs does not end when market access has been granted. Monitoring drugs over the life-cycle has become state of the art, inherent to evolving legislation and societal need. Here, we explore how the drug label could move along in a changing playing-field, and become a sustainable label for the future. A dialogue between academia, government, the pharmaceutical industry, and patient/societal organizations was organized by the Regulatory Science Network Netherlands, RSNN. This is their view.