Impact of medicine shortages on patients - a framework and application in the Netherlands.

BACKGROUND: Medicine shortages are often described in plain numbers, suggesting all shortages have a uniform impact. However, some shortages have a direct and serious effect on patients and need a prompt reaction from stakeholders. This study aims to create a broad framework to assess the impact of a shortage. METHOD: We identified high impact shortages and selected exemplary shortages which we considered our learning cases. From five learning cases, we identified elements that had a potentially profound impact on one or more of these cases. We tested data saturation on the elements with another five test cases. Based on these elements, we created a framework to assess impact of shortages on patients and presented practical examples how to rate these different elements. Subsequently, we visualised the impact of these five learning cases on patients in radar charts. RESULTS: The five elements which we identified as potentially having a large impact were 1) alternative product, 2) disease, 3) susceptibility, 4) costs and 5) number of patients affected. The five learning cases rated high on different elements, leading to diverse and sometimes even opposite patterns of impact. CONCLUSION: We created a framework for assessing the impact of a medicine shortage on patients by means of five key elements. By rating these elements, an indication of the impact can be obtained.

No Evidence for an Association Between Renal Function and Serious Bleeding Events in Patients Treated With Coumarins: A Population-Based Study.

BACKGROUND: Although anticoagulation therapy is closely monitored in the Netherlands, coumarin-induced serious bleeding events are still observed. Current literature suggests that renal impairment may contribute to this. OBJECTIVE: To explore the association between renal function and bleeding events during coumarin treatment. METHODS: A nested case-control study was conducted using data from the PHARMO Database Network. Patients hospitalized for a bleeding event during coumarin treatment were selected as cases and matched on sex, birth year, and geographic region to up to 2 controls using coumarins without hospitalization for bleeding. All values of estimated glomerular filtration rates (eGFRs) were selected in the year before index date (case hospitalization date) and compared between cases and controls using logistic regression analyses. RESULTS: In total, 2224 cases were matched to 4398 controls (61% male; mean ± SD age 75 ± 11 and 78 ± 11 years among cases and controls, respectively). Availability of eGFR values was higher among cases compared with controls (mean ± SD eGFR values 4.5 ± 7.1 vs 3.2 ± 5.5), reflected in the significantly shorter time since last eGFR value (at index date, mean ± SD = 2.7 ± 3.0 vs 3.8 ± 3.1 months; odds ratio [OR] = 0.91, 95%CI = 0.89-0.92). No statistically significant difference was found for the mean eGFR value in the year before index date (mean ± SD 65.7 ± 22.8 vs 64.6 ± 20.9 mL/min/1.73 m2; OR per 10 units [95%CI] = 0.99 [0.96-1.02]). CONCLUSIONS: No association between renal function and serious bleeding events during coumarin treatment was observed.

The effect of prescriber education on medication-related patient harm in the hospital: a systematic review.

AIMS: Educating prescribers is a strategy to reduce prescription errors in hospitals. The present systematic review gives an overview of original research papers on the education of prescribers and reporting outcomes on (potential) patient harm. METHODS: A search of the databases Embase and Medline, using the Ovid interface, was performed. Research on the effect of physician education in order to prevent medication-related problems in inpatients, and on reporting original data and outcomes on prescribing errors and/or (potential) patient harm, was included. The assessment of methodological quality and risk of bias was performed using the Methodological Index for Non-Randomized studies (MINORS) checklist and the suggested risk of bias criteria for Effective Practice and Organization of Care (EPOC) reviews. RESULTS: Eight studies investigated an intervention on education alone, and in seven studies education was the main part of a multifaceted intervention. All studies were small and had short follow-up periods. The educational programmes varied and were given to physicians of different specialties and levels of experience. Most studies reported intermediate process parameters as the outcome. The risk of performance and reporting bias were high. CONCLUSION: All included studies suffered from poor methodology. The majority, especially studies in which education was part of a multifaceted intervention, reported effectiveness on intermediate outcome markers as prescription errors and potential adverse drug events. However, we found no firm evidence that educating prescribers in the hospital leads to a decrease in patient harm. Further work is needed to develop educational programmes, accompanied by more high-quality research with outcomes on the improvement of patient care.

A multifaceted intervention to reduce drug-related complications in surgical patients.

AIM: The P-REVIEW study was a prospective, multicenter, open intervention study, designed to determine whether a multifaceted intervention of educating the prescriber combined with medication review and pharmaceutical visits to the ward by the hospital pharmacist could lead to a reduction in drug-related complications among surgical patients. METHODS: A total of 6780 admissions of 5940 patients to surgical, urological and orthopaedic wards during the usual care period and 6484 admissions of 5711 patients during the intervention period were included. An educational programme covering pain management, antithrombotics, fluid and electrolyte management, prescription in case of renal insufficiency and antibiotics was developed. National and local hospital guidelines were included. Hospital pharmacists performed medication safety consultations, combining medication review of high-risk patients and a visit to the physician on the ward. RESULTS: A significantly lower proportion of admissions with one or more clinically relevant, potentially preventable, drug-related problems (including death, temporary or sustained disability, increased length of hospital stay or readmission within 30 days) occurred in the intervention period (1.1% (73/6484) compared to the usual care period [1.6% (106/6780)] (P = 0.029). The relative risk (RR) was 0.72 (95% CI 0.53-0.97). Several types of drug-related problems occurred less frequently. Costs incurred as result of time spent on study-related activities were not different before and after the intervention. CONCLUSIONS: The P-REVIEW study shows that education and support of the prescribing physician with respect to high-risk patients in surgical departments leads to a significant, clinically relevant benefit for patients without generating additional costs.

Use of pharmacy dispensing data to measure adherence and identify nonadherence with oral hypoglycemic agents.

PURPOSE: A framework for calculation of adherence for oral hypoglycemic agents (OHAs) based on data from health-insurance claims is available. Pharmacy dispensing data aid identification of nonadherent patients in pharmacy practices. However, use of these data for calculation of OHA adherence requires additional methodological categories. We examined the impact of different methodological choices on estimation of OHA adherence using pharmacy dispensing data. METHODS: Four methodological categories were added to the framework available to be used for adherence calculation with pharmacy dispensing data. Three adherence measures were defined to supply pharmacists with significant information on OHA use of their patients: (i) percentage of days covered by use periods of dispensed medication (PDC), (ii) mean rate of adherent patients with a PDC ≥80 % (MRAP80), and (iii) mean number of nonadherent patients (MNNP80) per pharmacy with a PDC <80 %. A basic scenario was developed from 16 methodological categories. Consequences of choices for different parameters within these categories on the scores of the three adherence measures were calculated from dispensing data between July 2013 and July 2014. RESULTS: Data were available for 604,500 OHA users in 1737 community pharmacies in the Netherlands. For the basic scenario, mean PDC for OHA was 88.3 %. MRAP80 was 80.3 %, which corresponded to an average of 69 nonadherent patients per pharmacy. Different choices for parameter values resulted in score variations for PDC of 85.0-91.8 %, for MRAP80 of 75.3-86.1 %, and between 49 and 92 MNNP80 per pharmacy. CONCLUSION: Sixteen methodological categories specified calculation of OHA adherence based on pharmacy dispensing data. Adherence scores expressed as percentages were relatively robust to variation in parameter values, but differed substantially for the absolute numbers of nonadherent patients per pharmacy.

Drug therapy management in patients with renal impairment: how to use creatinine-based formulas in clinical practice.

PURPOSE: The use of estimated glomerular filtration rate (eGFR) in daily clinical practice. METHODS: eGFR is a key component in drug therapy management (DTM) in patients with renal impairment. eGFR is routinely reported by laboratories whenever a serum creatinine testing is ordered. In this paper, we will discuss how to use eGFR knowing the limitations of serum creatinine-based formulas. RESULTS: Before starting a renally excreted drug, an equally effective drug which can be used more safely in patients with renal impairment should be considered. If a renally excreted drug is needed, the reliability of the eGFR should be assessed and when needed, a 24-h urine creatinine clearance collection should be performed. After achieving the best approximation of the true GFR, we suggest a gradual drug dose adaptation according to the renal function. A different approach for drugs with a narrow therapeutic window (NTW) is recommended compared to drugs with a broad therapeutic window. For practical purposes, a therapeutic window of 5 or less was defined as a NTW and a list of NTW drugs is presented. Considerations about the drug dose may be different at the start of the therapy or during the therapy and depending on the indication. Monitoring effectiveness and adverse drug reactions are important, especially for NTW drugs. Dose adjustment should be based on an ongoing assessment of clinical status and risk versus the benefit of the used regimen. CONCLUSION: When determining the most appropriate dosing regimen serum creatinine-based formulas should never be used naively but always in combination with clinical and pharmacological assessment of the individual patient.

Beliefs about inhaled corticosteroids: Comparison of community pharmacists, pharmacy technicians and patients with asthma.

OBJECTIVES: To compare pharmacists' and pharmacy technicians' perceptions of patients' beliefs regarding inhaled corticosteroids (ICS) with those of patients and to compare the ICS beliefs of pharmacists and technicians with those of patients with asthma. METHODS: 1269 community pharmacies were approached to fill out an online questionnaire; 1952 patients were sent a questionnaire by post. Beliefs (i.e., necessity and concerns) regarding ICS were measured using (an adapted version of) the Beliefs about Medicines Questionnaire (BMQ-specific). Pharmacists and technicians were instructed to fill out the BMQ for themselves, and to fill it out in the way they thought most of their patients would complete it. RESULTS: 136 pharmacists, 90 pharmacy technicians and 161 patients with asthma completed the questionnaire. Pharmacists and technicians thought patients had more concerns about ICS than patients themselves reported (p < 0.0001). They also thought that patients had stronger beliefs in their personal need for ICS than patients reported (p < 0.01). Pharmacists reported lower levels of concerns than patients (p < 0.05) and both providers attributed a higher level of necessity to ICS than patients did (p < 0.0001). CONCLUSION: Pharmacists and technicians overestimate the personal need for treatment as well as the concerns patients with asthma have regarding ICS. They also have, to some extent, stronger positive beliefs about ICS than patients. If pharmacists and technicians expect that patients share their positive views about ICS, they might be less likely to elicit and address patients' doubts and concerns about ICS, which might be relevant for effective ICS treatment and subsequent patient outcomes.

Nature and frequency of drug therapy alerts generated by clinical decision support in community pharmacy.

PURPOSE: The purpose of this study is to investigate the nature, frequency, and determinants of drug therapy alerts generated by a clinical decision support system (CDSS) in community pharmacy in order to propose CDSS improvement strategies. METHODS: This is a retrospective analysis of dispensed drugs and drug therapy alerts generated by a CDSS in community pharmacies. RESULTS: Data were extracted from the CDSS of 123 community pharmacies. After taking a 10% random sample of patients with a prescription in the period August 2013-July 2014, 1,672,169 dispensed prescriptions from 81,742 patients were included in the analysis. Of all processed prescriptions, 43% led to one or more drug safety alerts, most frequently drug-drug interaction alerts (15% of all prescriptions), drug-disease interaction alerts (14%), duplicate medication alerts (13%), and dosing alerts (7%). The majority of prescriptions with alerts (80%) were clustered in a minority of patients (16%). The therapeutic drug group of the prescribed drug was the most important determinant of alert generation. Prescriptions for antithrombotic agents accounted for 9.4% of all prescriptions with an alert, beta-blocking agents for 7.5% and angiotensin-converting-enzyme inhibitors for 6.1%. DISCUSSION AND CONCLUSION: The investigated CDSS in Dutch community pharmacy generated one or more drug therapy alerts in nearly half of the processed prescriptions. The majority of alerts were concentrated in a minority of therapeutic drug groups and patients. To decrease the alert burden, CDSS improvements should be directed at the prioritization and integration of drug therapy alerts for these therapeutic groups within patients.

Cue-Responding Behaviors During Pharmacy Counseling Sessions With Patients With Asthma About Inhaled Corticosteroids: Potential Relations With Medication Beliefs and Self-Reported Adherence.

The aim of this study was to examine cue-responding behavior at the pharmacy while counseling about inhaled corticosteroids (ICS) in relation to medication adherence and medication beliefs. Patients with asthma aged ≥18 years using ICS were recruited from 12 pharmacies. Counseling sessions were video-recorded. Patients' emotional and informational cues and pharmacists' and pharmacy technicians' cue-responding behaviors were coded using an expanded version of the Medical Interview Aural Rating Scale. The Beliefs about Medicines Questionnaire assessed patients' ICS concern and necessity beliefs. Self-reported ICS adherence was measured by four questions. During the 86 sessions, patients expressed on average 2.3, mostly informational, cues (70.8%). In 26.7% of the sessions, no cues were expressed. Pharmacists' and technicians' responses to emotional cues (59.3%) were mostly inadequate, and to informational cues mostly appropriate (63.6%). Providing inappropriate information (20.3%) was related to higher concerns post session (p < .05), and cue exploration to higher self-reported adherence at 3 months (p < .05). Apparently, providers' responses to patients' cues might have therapeutic value. In addition, patients might need to be encouraged to ask questions and express their concerns.

Time-trends in the prescribing of gastroprotective agents to primary care patients initiating low-dose aspirin or non-steroidal anti-inflammatory drugs: a population-based cohort study.

AIMS: Low-dose aspirin (LDA) and non-steroidal-anti-inflammatory drugs (NSAIDs) both increase the risk of upper gastrointestinal events (UGIEs). In the Netherlands, recommendations regarding the prescription of gastroprotective agents (GPAs) in LDA users were first issued in 2009 in the HARM-Wrestling consensus. National guidelines on gastroprotective strategies (GPSs) in NSAID users were issued in the first part of the preceding. The aim of the present study was to examine time-trends in GPSs in patients initiating LDA and those initiating NSAIDs between 2000 and 2012. METHODS: Within a large electronic primary healthcare database, two cohorts were selected: (i) patients newly prescribed LDA and (ii) patients newly prescribed NSAIDs between 2000 and 2012. Patients who had been prescribed a GPA in the previous six months were excluded. For both cohorts, patients' risk of a UGIE was classified as low, moderate or high, based on the HARM-Wrestling consensus, and the presence of an adequate GPSwas determined. RESULTS: A total of 37 578 patients were included in the LDA cohort and 352 025 patients in the NSAID cohort. In both cohorts, an increase in GPSs was observed over time, but prescription of GPAs was lower in the LDA cohort. By 2012, an adequate GPS was present in 31.8% of high-risk LDA initiators, vs. 48.0% of high-risk NSAID initiators. CONCLUSIONS: Despite a comparable risk of UGIEs, GPSs are prescribed less in high-risk LDA initiators than in high-risk NSAID initiators. For both groups of patients, there is still room for improvement in guideline adherence.

Quick assessment of drug-related admissions over time (QUADRAT study).

PURPOSE: To develop a computerized prescreening procedure for the identification of possible/probably Hospital Admissions potential Related to Medications (HARMs). METHOD: Pairs of drugs and reasons for hospitalization (generated automatically from the PHARMO record linkage database by using two data mining techniques) were assessed manually to determine whether they represented pharmacologically plausible adverse drug events (PP-ADEs). Two crude samples of these PP-ADEs (from 2005 and 2008) were examined manually to establish causality and preventability on the basis of hospital discharge letters plus medication dispensing data. The results were used to calculate the positive predictive value (PPV) of the crude causality PP-ADEs, the net percentage of possible/probably HARMs, and their potential preventability. RESULTS: Data mining by Gamma Poisson Shrinkage and trend analysis produced 1330 and 2941 significant drug-event pairs, respectively. After manual assessment, 307 different PP-ADEs remained. The annual prevalence of these PP-ADEs was stable at approximately 8% throughout 2000-2009. Manual assessment of two samples of crude PP-ADEs showed that their causality PPV was 53.7% (95%CI: 52.7%-54.7%) in 2005 and 47.9% (95%CI: 46.9%-49.0%) in 2008. The net contribution of possible/probably HARMs to all acute admissions was 4.6% (95%CI: 4.5%-4.8%) in 2005 and 3.9% (95%CI: 3.8%-4.0%) in 2008. The potential preventability of all possible/probably HARMs in the two samples was 19.3% (95%CI: 18.5-20.1). CONCLUSION: Automated pre-selection of PP-ADEs is an efficient way to monitor crude trends. Further validation and manual assessment of the automatically selected hospitalizations is necessary to get a more detailed and precise picture.

Fluctuation of the renal function after discharge from hospital and its effects on drug dosing in elderly patients--study protocol.

BACKGROUND: Chronic kidney disease (CKD) is associated with an increased mortality rate, risk of cardiovascular events and morbidity. Impaired renal function is common in elderly patients, and their glomerular filtration rate (GFR) should be taken into account when prescribing renally excreted drugs. In a hospital care setting the GFR may fluctuate substantially, so that the renal function group and therefore the recommended dose, can change within a few days. The magnitude and prevalence of the fluctuation of renal function in daily clinical practice and its potential effects on appropriateness of drug prescriptions after discharge from the hospital is unknown. METHODS/DESIGN: This is a prospective observational study. Patients ≥ 70 years with renal impairment (eGFR < 60 ml/min/1.73 m(2)) admitted to a geriatric ward are eligible to participate. Participants undergo blood sample collection to measure serum creatinine level at three time points: at discharge from hospital, 14 days, and 2 months after discharge. At these time points the actual medication of the participants is assessed and the number of incorrect prescriptions according to the Dutch guidelines in relation to their estimated renal function is measured. In addition, for a hypothetical selection of drugs, the need for drug dose adaptation in relation to renal function is measured. The outcome of interest is the percentage of patients that changes from renal function group after discharge from hospital compared to the renal function at discharge. In addition, the percentages of patients whose actual medications are incorrectly prescribed and for the hypothetical selection of drugs that would have required dose adaptation will be determined at discharge, 14 days and 2 months after discharge. For each outcome, risk factors which may lead to increased risk for fluctuation of renal function and/or incorrect drug prescribing will also be identified and analysed. DISCUSSION: This study will provide data on changes in renal function in elderly patients after discharge from the hospital with a focus on the medications used. The benefits for healthcare professionals comprise of the creation, adjustment or confirmation of recommendations for the monitoring of the renal function after discharge from hospital of elderly patients.

Checklist for standardized reporting of drug-drug interaction management guidelines.

PURPOSE: Inconsistencies and omissions in drug-drug interaction (DDI) management guidelines may lead to harm and suboptimal therapy. The purpose of this study was to define a checklist for DDI management guidelines to help developers produce high-quality guidelines that will support healthcare providers in clinical practice. METHODS: We carried out a two-round Delphi process with an international panel of healthcare providers, most of whom are pharmacists involved in providing DDI information, in order to select those items that should be addressed in DDI management guidelines (including grading systems that could be used). RESULTS: Twenty-three panellists reached consensus on 19 items in two main domains. These were consolidated into a checklist of 15 elements for standardized reporting in management guidelines. For each element a description is provided to specify what information should be documented in that specific element. CONCLUSIONS: It was possible to reach a broad consensus on which relevant items should be included in a checklist for the development of DDI management guidelines.

Effectiveness of interventions by community pharmacists to reduce risk of gastrointestinal side effects in nonselective nonsteroidal anti-inflammatory drug users.

PURPOSE: Upper gastrointestinal (UGI) complications in elderly users of nonselective nonsteroidal anti-inflammatory drugs (ns-NSAIDs) without concomitant use of gastroprotective agents (GPAs) were a leading cause of potentially avoidable drug-related hospital admissions in the Netherlands. We aimed to determine the effectiveness of community pharmacists' interventions to improve safety in ns-NSAID use in patients at UGI risk. METHODS: In this prospective cohort study, pharmacists in participating pharmacies (intervention group, IG) received feedback on drug dispensing in ns-NSAID users of ≥60 years of age at risk for UGI damage and were instructed to select patients to improve ns-NSAID prescribing, in collaboration with primary care physicians. Ns-NSAID users from other pharmacies without concomitant GPA use were followed in parallel as a control group (CG). Changes in the UGI risk of ns-NSAID users between baseline and follow-up measurement, assessed either by the addition of GPAs or the cessation of ns-NSAIDs, were compared between the two study arms. RESULTS: At baseline, 14% of ns-NSAID users at UGI risk did not receive GPAs. Persistent ns-NSAID users from the selected IG patients had an additional 7% likelihood of reduced UGI risk at follow-up (odds ratio 0.93, 95% confidence interval 0.89-0.97) compared with CG patients. In the IG, 91% of selected IG patients at UGI risk from ns-NSAIDs at baseline were no longer at increased risk at follow-up because of cessation of ns-NSAIDS or to concomitant GPA use. CONCLUSION: Although concomitant gastroprotection use in susceptible ns-NSAID users in the Netherlands is high, pharmacist-led interventions could further improve prescribing of ns-NSAIDs.

Missed drug therapy alerts as a consequence of incomplete electronic patient records in Dutch community pharmacies.

BACKGROUND: Complete and up-to-date medical and pharmaceutical information in the electronic patient record (EPR) is a prerequisite for risk management in community pharmacy. OBJECTIVES: To analyze which information is missing in the EPR and which drug therapy alerts, therefore, fail to appear. METHODS: Pharmacy students selected patients who were dispensed a prescription drug and enlisted for >3 months in the participating pharmacies. Patients received a questionnaire in which they were asked to verify their medication history, and to provide additional patient information. For each enrolled patient, the students collected all relevant information from the EPR. Self-reported data from the patient were compared with data retrieved from the EPR. Missed information in the EPR was evaluated based on national professional guidelines. RESULTS: Questionnaires were received from 67% of the selected patients (442/660). Prescription drugs were missing in the EPR of 14% of the 442 patients, nonprescription drugs in 44%, diseases in 83%, and intolerabilities in 16%. In 38% of the patients (166/442), drug therapy alerts failed to appear because of missing information: drug-disease interactions in 34% of the patients, duplicate medications in 4%, drug-drug interactions (DDIs) in 4%, and drug intolerabilities in 2%. Among the (non-)prescription drugs missing, NSAIDs were most frequently responsible for the missed alerts. Diseases most frequently associated with missed alerts were gastroesophageal reflux disease, renal insufficiency, asthma/chronic obstructive pulmonary disease, and heart failure. CONCLUSIONS: Relevant patient information was frequently missing in the EPRs. The nonappearance of drug therapy alerts may have had clinical consequences for patients.

Ineffectiveness and adverse events of nitrofurantoin in women with urinary tract infection and renal impairment in primary care.

PURPOSE: To determine whether treatment with nitrofurantoin in women with urinary tract infection (UTI) and renal impairment in primary care is associated with a higher risk of ineffectiveness and/or serious adverse events than in women without renal impairment. METHODS: A cohort of 21,317 women treated with nitrofurantoin and a cohort of 7,926 women treated with trimethoprim, identified from the Pharmo Record Linkage System, were analysed. The primary outcome was ineffectiveness of treatment of nitrofurantoin defined as the start of a second antibacterial within 1 month after the start of nitrofurantoin. The secondary outcome was the occurrence of serious adverse events of nitrofurantoin leading to hospitalization within 90 days. A cohort of trimethoprim users was used to determine if the associations found for nitrofurantoin were mainly related to nitrofurantoin itself. The association between renal impairment and the risk of these outcomes was determined with Cox regression and expressed as hazard ratios (HRs). RESULTS: Overall, the incidence density for ineffectiveness was 5.4 per 1,000 person-days, and moderate renal impairment was not associated with ineffective treatment [HR 1.1, 95 % confidence interval (CI) 0.74-1.51]. The overall incidence density for adverse events was 0.02 per 1,000 person-days. In patients with renal impairment (<50 ml/min/1.73 m²) the risk of pulmonary adverse events leading to hospitalization was significantly increased (HR 4.1, 95 % CI 1.31-13.09) CONCLUSIONS: Nitrofurantoin treatment was not associated with a higher risk of ineffectiveness in women with UTI and moderate renal impairment (30-50 ml/min/1.73 m²). However, we did find a significant association between renal impairment (<50 ml/min/1.73 m²) and pulmonary adverse events leading to hospitalization.

[Medicines from nature: old fashioned concept or promise for the future?] / Geneesmiddelen uit de natuur.

Scientific research into natural products has substantially contributed to our current drug armamentarium. This research has yielded numerous novel molecular structures and it has also increased our knowledge of pharmacological mechanisms of action. Moreover, ethnopharmacological studies have regularly shown that the traditional use of a natural product may correlate with the pharmacological action of its components and their derivatives. Nature still has much more in store for healthcare than a bunch of flowers for the bedridden patient. To secure that future generations can fully reap these benefits, it is essential to conserve the biodiversity of natural resources and the indigenous knowledge about their bioactivity.

Medicine shortages: impact behind numbers.

INTRODUCTION: Current research to assess the impact that medicine shortages have on patients is limited to general aspects, such as the prevalence of shortages and product characteristics. The aim of this study is to assess the overall impact that medicine shortages have on economic, clinical, and humanistic outcomes. METHODS: A cohort of all known products in shortage in the Netherlands between 2012 and 2015 were characterized by their route of administration, anatomical therapeutic chemical class, and whether they were originator or generic products. A representative sample of 324 shortages (18% of all shortages) was rated as having low, medium, or high impact on the five elements that determine the impact of shortages on patients: availability of an alternative product, underlying disease, susceptibility of the patient, costs (for patients and society at large), and number of patients affected. Ratings were converted into numerical scores per element and multiplied to obtain an overall impact score. RESULTS: Two elements were most frequently rated as having a high impact: disease (29%) and costs (20%). Nearly half of the shortages (47%) rated high on at least one element, while nearly 10% rated high on multiple elements. Thirty percent of the shortages rated high on direct impact, which is represented by these elements: alternative product and disease. An additional 17% of the shortages rated high on indirect impact, which is represented by these elements: costs, susceptibility, and number of patients. High impact scores could not significantly be attributed to characteristics of the products in shortage. CONCLUSIONS: An assessment of the medicine shortages' impact using a framework based on economic, clinical, and economic outcomes showed that all three outcomes affect the overall impact that medicine shortages have on patients.

Information comparison of the effects of drugs on laboratory tests in drug labels and Young's book.

BACKGROUND: The effects of drugs on laboratory tests may lead to misinterpretation of laboratory data, unnecessary tests, higher costs and missed diagnoses. This study compared the information on drug-laboratory effects (DLE) described in 200 drug labels with that in Young's book. METHODS: Information on DLE was searched in the drug labels of 200 frequently prescribed drugs using the keywords 'interfer*', 'influence', and 'laborator*'. This information was compared with the information in Young's book. Each item of information scored 1 point if it was specific and exactly the same. Primary outcome was the percentage of DLE with completely the same information. RESULTS: In 23 (11.5%) of the 200 drug labels 83 DLE were described. Most DLE were described in drug labels of contraceptives (71%) and antibacterials (15%). The most frequently affected laboratory tests were adrenal gland (17%), urine tests (15%), liver tests (10%) and renal function tests (10%). Comparison of six DLE with Young's book was not possible because the information was not described in the book. Twelve (14.5%) DLE of the information in the drug label was identical to that in Young's book. Detailed information about nature of the effect, strength of the effect and body fluid was not described in the drug labels. CONCLUSIONS: In a limited number of DLE in the drug labels the information was the same as in Young's book. Overall, the information on DLE provided in drug labels is unclear, inconsistent and incomplete and does not support healthcare professionals in making evidence-based monitoring decisions.

Instructions on laboratory monitoring in 200 drug labels.

BACKGROUND: Monitoring drug treatment is important to assess the therapeutic effects and to prevent adverse drug reactions. Unfortunately, the clinical evidence for monitoring is often missing. To attain evidence-based laboratory monitoring and to improve patient safety it is mandatory for the clinical chemist to develop effective and rational methods for monitoring. The legal source for this evidence-based information is the drug label. We analysed frequency, nature, and applicability of instructions on laboratory monitoring described in 200 drug labels. METHODS: The applicability of instructions was assessed with an adapted Systematic Information for Monitoring score. Seven items of information were evaluated: why to monitor, what to monitor (essential), when to start or stop monitoring, how frequently to monitor, critical value (essential) and how to respond (essential). Each item scored one point when information was described specifically, otherwise the score was zero. Instructions were applicable if all three essential items scored. RESULTS: In 131 drug labels, 566 instructions on laboratory monitoring were identified, an average of 2.8 per drug label. Kidney, liver, electrolyte, and drug monitoring were important biomarker categories (71%). The median applicability score was 2.1 (0-6) and 95 (17%) instructions were applicable. Six determinants were associated with applicable instructions: kidney (OR 7.0; 95% CI 4.4-11.3), creatine phosphokinase (4.5; 1.5-13.6), drug selection (6.8; 4.0-11.7), dose adjustments (2.4; 1.5-3.7), year on the market 2000-2007 (2.6; 1.1-6.1) and statins (4.8; 2.5-9.0). CONCLUSIONS: Drug labels frequently describe instructions on laboratory monitoring, but these are ambiguous and incomplete and clinical applicability for the professional is limited.