From the Randomized AMBORA Trial to Clinical Practice: Comparison of Medication Errors in Oral Antitumor Therapy.

The randomized AMBORA trial showed that medication errors are frequent in patients treated with oral antitumor therapeutics and that they can be substantially reduced by an intensified clinical pharmacological/pharmaceutical care program. While randomized controlled trials are essential to generate clinical evidence, their generalizability in real-world is not always given. The AMBORA care program was implemented in clinical routine within the AMBORA Competence and Consultation Center (AMBORA Center) at the Comprehensive Cancer Center Erlangen-EMN, allowing a thorough comparison of medication error frequencies and characteristics. Our primary analysis compared data at therapy initiation of new oral antitumor therapeutics from the AMBORA trial intervention group (n = 98) and the AMBORA Center (n = 142). Medication errors involving the oral antitumor therapeutics were twofold higher in real-world compared to the randomized controlled trial (mean 0.83 ± 0.80 per patient vs. 0.41 ± 0.53, P < 0.001). We observed more complex oral antitumor therapeutic regimens, a higher median number of medications, and a higher ECOG status in clinical routine vs. the randomized trial. A high percentage of medication errors was completely solved in both groups (85.7% vs. 88.3%, ns). Medication error characteristics within the complete medication (oral antitumor therapeutics and concomitant medication) were similar in both groups (e.g., patient-related causes, drug-drug/drug-food interactions). Taken together, medication errors were even more frequent in clinical routine than in the randomized controlled trial and a high rate was solved in clinical routine by a clinical pharmacological/pharmaceutical care program.

Clinical Pharmacist Counselling Improves Long-term Medication Safety and Patient-reported Outcomes in Anti-TNF-treated Patients With Inflammatory Bowel Diseases: The Prospective, Randomized AdPhaNCED Trial.

BACKGROUND: Antitumor necrosis factor (anti-TNF) antibody treatment has led to marked improvements in the management of patients with inflammatory bowel diseases (IBDs). Nevertheless, anti-TNF therapy is associated with potential adverse drug reactions (ADRs). Our prospective, randomized trial investigated the effect of intensified clinical pharmacist counselling in a multidisciplinary team on medication safety in anti-TNF-treated IBD patients. METHODS: Patients with IBD with ongoing anti-TNF treatment were enrolled in our tertiary center AdPhaNCED trial and randomized to either receive conventional standard of care (control group) or additional clinical pharmacist counselling (intervention group) over 12 months. The primary end point consisted of the number and severity of ADRs associated with anti-TNF therapy. Secondary end points included patient satisfaction with medication information and medication safety. RESULTS: One hundred twenty-seven IBD patients were included in this study. Anti-TNF-related ADRs were significantly lower in the intervention compared with the control group (0.20 vs 0.32 [mean] ADR/patient/month, P = .006) after 12 months. The risk of more severe ADRs (Common Terminology Criteria for Adverse Events [CTCAE] grade ≥2) was significantly higher in the control compared with the intervention group (hazard ratio, 0.34; P = .001). The probability of ADR resolution (hazard ratio, 2.02; P < .001) and patient satisfaction with medication information (14.82 vs 11.60; P < .001) were significantly higher in the intervention group compared with the control group. CONCLUSIONS: Our study results demonstrate that intensified pharmacist counselling significantly reduces the occurrence and severity of therapy-related ADRs and improves patient satisfaction. Clinical pharmacists should therefore be part of a holistic approach to IBD care delivered by a multidisciplinary team.

The prospective, randomized AdPhaNCED trial demonstrated that anti-TNF-treated IBD patients had diminished and less severe drug-related adverse reactions and higher patient satisfaction when they received intensified pharmacist counselling in comparison with conventional standard of care over 12 months.

Sobetirome rescues α-synuclein-mediated demyelination in an in vitro model of multiple system atrophy.

Multiple system atrophy (MSA) is a rare and rapidly progressive atypical parkinsonian disorder characterized by oligodendroglial cytoplasmic inclusions containing α-synuclein (α-syn), demyelination, inflammation and neuronal loss. To date, no disease-modifying therapy is available. Targeting α-syn-driven oligodendroglial dysfunction and demyelination presents a potential therapeutic approach for restricting axonal dysfunction, neuronal loss and disease progression. The present study investigated the promyelinogenic potential of sobetirome, a blood-brain barrier permeable and central nervous system selective thyromimetic in the context of an in vitro MSA model. Oligodendrocyte precursor cells (OPCs) were obtained from transgenic mice overexpressing human α-syn specifically in oligodendrocytes (MBP29 mouse line), a well-described MSA model, and non-transgenic littermates. mRNA and protein expression analyses revealed a substantial rescue effect of sobetirome on myelin-specific proteins in control and α-syn overexpressing oligodendrocytes. Furthermore, myelination analysis using nanofibres confirmed that sobetirome increases both the length and number of myelinated segments per oligodendrocyte in primary murine α-syn overexpressing oligodendrocytes and their respective control. These results suggest that sobetirome may be a promising thyromimetic compound targeting an important neuropathological hallmark of MSA.

Optimizing Medication Safety with Oral Antitumor Therapy: A Methodological Approach for the Real-World Implementation of the AMBORA Competence and Consultation Center.

Generating evidence for the efficacy of an intervention is not sufficient to guarantee its implementation in real-world settings. The randomized AMBORA trial (Medication Safety with Oral Antitumor Therapy) demonstrated that an intensified clinical pharmacological/pharmaceutical care program has substantial benefits for patients, treatment teams, and the healthcare system. Thus, we are now investigating its implementation into routine care within the AMBORA Competence and Consultation Center (AMBORA Center). We perform a multicenter type III hybrid trial following the RE-AIM framework to assess the clinical effectiveness of this care program under real-world conditions, while evaluating the implementation outcomes. Semi-structured stakeholder interviews based on the Consolidated Framework for Implementation Research (CFIR) have been conducted to identify barriers and facilitators. So far, 332 patients treated with oral antitumor drugs have been referred to the AMBORA Center by 66 physicians from 13 independent clinical units. In 20 stakeholder interviews (e.g., with clinic directors), 30% (6/20) of the interviewees anticipated possible barriers which may partly hinder sustainable implementation (e.g., unavailable consultation rooms). Furthermore, important facilitators (e.g., operational processes) were identified. This methodological description adds knowledge on how to structure a hybrid effectiveness-implementation trial and proposes multilevel implementation strategies to improve the medication safety of oral antitumor therapy.

[Drug therapy safety supported by interprofessional collaboration between ICU physicians and clinical pharmacists in critical care units in Germany : Results of a survey]. / Arzneimitteltherapiesicherheit gefördert durch die interprofessionelle Zusammenarbeit von Arzt und Apotheker auf Intensivstationen in Deutschland : Erkenntnisse einer Umfrage.

BACKGROUND: Critically ill patients are particularly susceptible to adverse drug events. International studies show that pharmaceutical care has a positive impact on patient and drug therapy safety. Nationally, the integration of pharmacists into the multidisciplinary team and participation in ward rounds is required. The aim of this work is to assess the scope and extent of pharmaceutical care in intensive care units (ICU) in Germany. METHOD: In a literature and database search, 13 relevant pharmaceutical activities were identified. Based on this, an online survey with 27 questions on the implementation of pharmaceutical care in ICU was prepared by a panel of experts. The survey was sent to heads of German ICUs. RESULTS: Of the participants, 35.3% (59/167) have established regular pharmaceutical care. Drug information (89.7% [52/58]), pharmaceutical interventions with change of therapy (e.g., ward rounds; 67,2% [39/58]), regular evaluation of prescriptions (medication analysis; 65.5% [38/58]) as well as the monitoring of medication (e.g., side effects, effectiveness, costs; 63.8% [37/58]) were most frequently mentioned. The participants with pharmaceutical care (58/168) graded 7 of 13 but those without (104/168) only two  activities as 'essential/indispensable'. CONCLUSION: Only a few ICU in Germany have already integrated ward pharmacists into the multidisciplinary team. Once a pharmaceutical service has been established, a greater role/importance is assigned to several pharmaceutical activities.

Characteristics and Cost of Unscheduled Hospitalizations in Patients Treated with New Oral Anticancer Drugs in Germany: Evidence from the Randomized AMBORA Trial.

Drug-related problems (e.g., adverse drug reactions, ADR) are serious safety issues in patients treated with oral anticancer therapeutics (OAT). The previously published randomized AMBORA trial showed that an intensified clinical pharmacological/pharmaceutical care program within the first 12 weeks of treatment reduces the number and severity of ADR as well as hospitalization rates in 202 patients. The present investigation focused on unscheduled hospitalizations detected within AMBORA and analyzed the characteristics (e.g., frequency, involved OAT) and cost of each hospital stay. To estimate the potential savings of an intensified care program in a larger group, the absolute risk for OAT-related hospitalizations was extrapolated to all insureds of a leading German statutory health insurance company (AOK Bayern). Within 12 weeks, 45 of 202 patients were hospitalized. 50% of all unscheduled hospital admissions were OAT-related (20 of 40) and occurred in 18 patients. The mean cost per inpatient stay was EUR 5873. The intensified AMBORA care program reduced the patients' absolute risk for OAT-related hospitalization by 11.36%. If this care program would have been implemented in the AOK Bayern collective (3,862,017 insureds) it has the potential to reduce hospitalization rates and thereby cost by a maximum of EUR 4.745 million within 12 weeks after therapy initiation.

New Oral Antitumor Drugs and Medication Safety in Uro-Oncology: Implications for Clinical Practice Based on a Subgroup Analysis of the AMBORA Trial.

Oral antitumor therapeutics (OAT) bear a high risk for medication errors, e.g., due to drug-drug or drug-food interactions or incorrect drug intake. Advanced age, organ insufficiencies, and polymedication are putting uro-oncological patients at an even larger risk. This analysis sets out to (1) investigate the frequency and relevance of medication errors in patients with prostate cancer or renal cell carcinoma treated with OAT and (2) compile recommendations for clinical practice. This post-hoc subgroup analysis used data collected in the randomized AMBORA trial (2017-2020; DRKS00013271). Clinical pharmacologists/pharmacists conducted advanced medication reviews over 12 weeks after initiation of a new oral regimen and assessed the complete medication process for drug-related problems. Medication errors related to either the OAT, prescribed or prescription-free concomitant medication, or food were classified regarding cause and severity. We identified 67 medication errors in 38 patients within the complete medication within 12 weeks. Thereof, 55% were detected at therapy initiation, 27% were caused by the patients, and 25% were drug-drug or drug-food interactions. Problem-prone issues are summarized in a 'medication safety table' to provide recommendations for clinical practice in uro-oncology. Tailored strategies including intensified care by clinical pharmacologists/pharmacists should be implemented in clinical practice to improve medication safety.

[Pilot survey on continuing education for pharmacists in Germany]. / Piloterhebung zur Fortbildungssituation der Apotheker*innen in Deutschland.

INTRODUCTION: Continuing education (CE) for pharmacists is mandatory in Germany. However, the findings on CE activities of pharmacists are limited. The aim of this study was to conduct a pilot survey on the CE situation of pharmacists in Germany, including licensed and future pharmacists, to determine the commitment to CE, the attitude towards CE and an obligation to provide evidence, the extent of CE considered necessary and the application of CE content in professional practice. METHODS: A cross-sectional study was conducted in the form of an online survey using SoSci survey, which was addressed to licensed pharmacists, pre-registration pharmacists, and pharmacy students. The online survey was promoted by pharmaceutical professional societies, trade media and interest groups. RESULTS: In total, 880 participants were included in the study: 695 pharmacists, 136 pharmacy students and 49 pre-registration pharmacists. Only 50.0% of the participants were aware of their CE obligations. Among the pharmacists, 44.9% reported that they held the voluntary advanced training certificate issued by the Chambers of Pharmacists. 551 participants reported the CE points of the past twelve month. On average, 56.2 ±â€¯50.2 CE points were collected (x̅ = 210.8 CE minutes per month). Pharmacists not holding the voluntary advanced training certificate of the Chamber of Pharmacists collected significantly fewer (p < 0.001) CE points (39.5 ±â€¯32.0 points; x̅ = 148.1 CE minutes per month). On average, the study population considered a minimum number of 33.9 ±â€¯20.9 CE points per year (x̅ = 127.1 CE minutes per month) to be adequate to meet the CE requirements. DISCUSSION: Although the majority participated in CE, the introduction of nationwide CE commitment monitoring was rejected. On the one hand, this may be linked to a lack of willingness to engage in lifelong learning. On the other hand, it should be borne in mind that, despite the same common nationwide legal basis, the different Chambers of Pharmacists districts have set up different rules concerning the minimum yearly CE commitment, the proof of compliance with CE requirements and fines for non-compliance. Therefore, the introduction of nationwide standard regulations may result in a greater acceptance of CE commitment checks. CONCLUSION: Pharmacists' willingness to CE participation has so far been dependent on intrinsic motivation. Although many licensed pharmacists were in possession of the advanced training certificate issued by the Chambers of Pharmacists, the majority of participants did not support the introduction of a nationwide CE commitment monitoring. 127.1 CE minutes per month were considered appropriate to fulfill the CE obligations, which is significantly less than the 187.5 CE minutes per month which are required to obtain the advanced training certificate of the Chambers of Pharmacists.

[Economic aspects in the care of patients with new oral anticancer drugs: findings from the AMBORA trial]. / Ökonomische Aspekte bei der Versorgung von Patient*innen mit neuen oralen Tumortherapeutika: Erkenntnisse aus der AMBORA-Studie.

INTRODUCTION: The number of prescriptions and costs of oral anticancer drugs are increasing. Therapy discontinuation due to, for example, side effects, progression, or death, often lead to medication wastage. While evidence exists for the economic value of wasted injectable chemotherapeutics, there is a lack of data for oral anticancer drugs in Germany. METHODS: The multicenter AMBORA trial investigated 202 patients, who had been newly started on new oral anticancer drugs, over 12 weeks and analyzed the outpatient prescription data of patients who discontinued treatment. The amount of medicines wasted and their costs were determined using the pharmacy retail price. Defined daily doses and prescription data from the AOK Bayern, a German statutory health care insurance company, were used to extrapolate these costs. RESULTS: Within 12 weeks, 24.8 % of the AMBORA patients discontinued oral anticancer treatment (50 of 202). Prescription data of 34 patients were evaluable. In total, 1,693 tablets/capsules with a value of 112,212 euros were wasted. The approximate extrapolation to the prescription volume of the AOK Bayern resulted in an estimated wastage of 3.49 million euros in 12 weeks. DISCUSSION: Medication wastage due to discontinuation of new oral anticancer drug therapy leads to a considerable financial burden. Regarding rising prescription numbers and therapy costs in oncology, measures to reduce wastage of oral anticancer drugs should be initiated. CONCLUSION: Clinical pharmacological / pharmaceutical care including medication reconciliation and review, side effect management and patient counseling to optimize adherence and medication intake behavior, contributes to a reduction of therapy discontinuations, thereby reducing drug wastage. To further reduce drug wastage small (initiation) packages, which are currently not always available for an economic prescription, play an important role. The practice of partial prescription fills, which is already practiced internationally, should also be further discussed in Germany.

An Easily Expandable Multi-Drug LC-MS Assay for the Simultaneous Quantification of 57 Oral Antitumor Drugs in Human Plasma.

Oral anticancer drugs have led to significant improvements in the treatment of multiple tumor entities. However, in patients undergoing oral antitumor therapy, plasma concentrations are highly variable, resulting in risks of reduced therapeutic effects or an increase in side effects. One important tool to reduce this variability is therapeutic drug monitoring. In this work we describe a method to simultaneously quantify the plasma concentrations of 57 oral antitumor agents. Quantification of these drugs was achieved using liquid chromatography coupled to an Orbitrap mass spectrometer. The method was fully validated according to the FDA guidelines and constitutes a simple and robust way for exposure monitoring of a wide variety of oral anticancer drugs. Applicability to clinical routine was demonstrated by the analysis of 71 plasma samples taken from 39 patients. In summary, this new multi-drug method allows simultaneous quantification of 57 oral antitumor drugs, which can be applied to exposure monitoring in clinical studies, taking into account the broad variety of oral antitumor drugs prescribed in clinical routine.

Clinical pharmacy services in Germany: a national survey.

OBJECTIVES: Clinical pharmacy services in German hospitals appear to be underdeveloped compared with other European countries. However, recent developments have increased the interest in expanding these services. Detailed data about the current state of clinical pharmacy services in Germany are lacking. This survey establishes the current level of pharmacy services in Germany and the barriers to implementation. METHODS: An online survey conducted in 2017 was distributed to directors of all 389 German hospital pharmacies. The survey contained 26 questions addressing hospital and pharmacy characteristics, clinical pharmacy services provided, the number of clinical pharmacists and the frequency as well as the quality assurance of these services. RESULTS: There were 133 responses (34%). Of these, 84 (63%) pharmacies provided some form of clinical pharmacy services. Based on the 389 contacted pharmacies, a clinical pharmacy service is available in at least 22% of hospital pharmacies in Germany. On average there are 2.4 full-time equivalent (FTE) clinical pharmacists per hospital employed, although there is a wide variation in numbers (0.3-22 FTE) and service provision between hospitals. Clinical pharmacy services are generally provided on a daily or weekly basis, with a principal focus on general surgery, critical care and general medicine wards. CONCLUSIONS: This is the first survey providing a detailed picture of clinical pharmacy services in Germany. There is wide variation in clinical service provision among hospitals, with some hospitals having developed a comprehensive range of clinical services. Compared with other countries, particularly the UK where the focus has shifted to provision of 7-day clinical services, the gap in clinical pharmacy services remains large. The focus should be turned to refining clinical pharmacy services in hospital admissions and discharge planning while also improving Health IT, the opportunities for specialisation and aligning education in accordance with the EAHP common training framework.

Medication Errors During Treatment with New Oral Anticancer Agents: Consequences for Clinical Practice Based on the AMBORA Study.

Patients treated with oral anticancer agents (e.g., kinase inhibitors) are a high-risk population for medication errors due to, for example, polymedication, age, and limited adherence. Systematic evaluations regarding frequencies and causes of medication errors and resulting harm are lacking. Our previously published multicenter randomized AMBORA trial revealed that an intensified support by clinical pharmacologists/pharmacists for patients and the treatment team considerably reduced drug-related problems and improved patient-reported outcomes. Using this database, we performed a comprehensive, additional analysis focusing on medication errors related to the patients' complete medication with consideration of the antitumor agents, concomitantly administered drugs, and herb/food intake. Two hundred two patients starting a new oral anticancer drug regardless of the tumor entity were included. Clinical pharmacologists/pharmacists performed advanced medication reviews for 12 weeks. Medication errors were characterized regarding type, cause, patient harm, and the involved medicines. We detected 1.7 medication errors per patient (335/202). Of the medication errors (216/335), 64.5% occurred within the concomitant medication. Patients caused 28.4% of the medication errors. There were 67.8% detected immediately after the start of the new oral regimen, and 14.9% resulted in temporary harm. Drug-drug or drug-food interactions accounted for 24.8% of the medication errors. Patients and physicians need to be addressed in strategies for systematic reduction of medication errors during treatment with new oral antitumor drugs. Clinical decision support systems focusing on drug-drug interactions capture only a minority of the medication errors. Specialists with expertise in clinical pharmacology/pharmacy should support both the treating physicians as well as the patients for improved patient safety.

The Randomized AMBORA Trial: Impact of Pharmacological/Pharmaceutical Care on Medication Safety and Patient-Reported Outcomes During Treatment With New Oral Anticancer Agents.

PURPOSE: Oral anticancer drugs (eg, kinase inhibitors) play an important role in cancer therapy. However, considerable challenges regarding medication safety of oral anticancer drugs have been reported. Randomized, controlled, multicenter studies on the impact of intensified clinical pharmacological/pharmaceutical care on patient safety and patient treatment perception are lacking. METHODS: Patients were eligible for the randomized, multicenter AMBORA study, if they were newly started on any of the oral anticancer drugs approved in 2001 or later without restriction to certain tumor entities. Patients were randomly assigned to receive either standard of care (control group) or an additional, intensified clinical pharmacological/pharmaceutical care, which included medication management and structured patient counseling, over a period of 12 weeks (intervention group). Primary end points were the number of antitumor drug-related problems (ie, side effects and unresolved medication errors) and patient treatment satisfaction with the oral anticancer therapy after 12 weeks measured with the Treatment Satisfaction Questionnaire for Medication, category convenience. RESULTS: Two hundred two patients were included. Antitumor drug-related problems were significantly lower in the intervention compared with the control group (3.85 v 5.81 [mean], P < .001). Patient treatment satisfaction was higher in the intervention group (Treatment Satisfaction Questionnaire for Medication, convenience; 91.6 v 74.4 [mean], P < .001). The hazard ratio for the combined end point of severe side effects (Common Terminology Criteria for Adverse Events ≥ 3), treatment discontinuation, unscheduled hospital admission, and death was 0.48 (95% CI, 0.32 to 0.71, P < .001) in favor of the intervention group. CONCLUSION: Treatment with oral anticancer drugs is associated with a broad range of medication errors and side effects. An intensified clinical pharmacological/pharmaceutical care has considerable, positive effects on the number of medication errors, patient treatment perception, and severe side effects.

Long-term effectiveness, safety and immunogenicity of the biosimilar SB2 in inflammatory bowel disease patients after switching from originator infliximab.

BACKGROUND: Long-term data on inflammatory bowel disease (IBD) patients switched from originator to biosimilar infliximab SB2 are lacking. The aim of the conducted study was to investigate the effectiveness, immunogenicity and safety of a large prospectively followed-up IBD patient cohort that was entirely switched from originator infliximab to biosimilar SB2 treatment. METHODS: This was a prospective, single-center, longitudinal, observational study describing clinical outcomes in IBD patients, over an 80-week period following switch from originator infliximab to SB2. Primary outcome measures were change of disease activity [Harvey-Bradshaw Index for Crohn's disease (CD), partial Mayo Score for ulcerative colitis (UC)], C-reactive protein (CRP), infliximab trough levels (TLs), anti-drug antibodies (ADAs) and adverse events. RESULTS: One hundred and forty-four IBD patients (94 CD, 50 UC), with median duration of 30.5 months' (range 2-110) treatment with originator infliximab were evaluated. Mean change of disease activity compared with baseline was -0.9 (SD 2.6), -0.4 (2.2) and -0.4 (2.0) in CD; 0.1 (1.1), 0.1 (1.1) and 0.1 (1.3) in UC patients at weeks 24, 48 and 72. Median infliximab TLs were 6.2 µg/ml (interquartile range 2.3-12.2), 5.0 µg/ml (2.7-10.0), 6.6 µg/ml (3.5-12.4) and 5.1 µg/ml (2.7-10.9) at baseline and weeks 24, 48 and 72. Median CRP levels were within normal ranges throughout the study. After the switch, 9.8% of the patients developed new ADAs. Persistence on SB2 was 90% (95% confidence interval 0.85-0.95), 79% (0.72-0.86), 72% (0.64-0.80) at weeks 26, 52 and 78. Serious adverse events occurred in 11 patients. CONCLUSION: Over the individual patient follow-up of 80 weeks, switch to biosimilar SB2 from originator infliximab does not result in increased disease activity or changed immunogenicity patterns. The switch to SB2 was well tolerated.

Medication Safety in Intravenous Therapy: A Compatibility Study of Clonidine with Drugs Frequently Used in Intensive Care.

The intravenous pharmacotherapy of critically ill patients is extremely challenging due to the high number of drugs administered. We therefore evaluated the physicochemical compatibility of combinations of clonidine with drugs frequently used in an intensive care unit setting. Amiodarone, dihydralazine, furosemide, levosimendan, metamizole, milrinone, urapidil, and verapamil were each prepared as binary combinations with clonidine at the standard low and high administration concentrations. Selected ternary combinations were also analyzed. Samples were examined for physical compatibility. To verify chemical compatibility in samples deemed either physically compatible or to exhibit uncertain results, the drug content was quantified using high-performance liquid chromatography. Admixtures of clonidine with amiodarone or furosemide proved to be physically incompatible, whereas mixtures with levosimendan and metamizole exhibited results, which were not clearly meeting the specification criteria for physical compatibility. Binary combinations of clonidine with dihydralazine, milrinone, urapidil, and verapamil were found to be physically compatible. Combinations with dihydralazine, levosimendan, metamizole, milrinon, urapidil, or verapamil were chemically compatible for the analyzed concentrations. Ternary admixtures of clonidine, metamizole, and urapidil; clonidine, metamizole, and verapamil; clonidine, urapidil, and verapamil were shown to be physicochemically compatible for the analyzed concentrations. These data suggest that clonidine can be coadministered with dihydralazine, levosimendan, metamizole, milrinone, urapidil, and verapamil. However, the concomitant administration of clonidine with amiodarone or furosemide is not recommended.

[Clinical pharmacists in palliative care: effects on drug therapy and drug expenses]. / Apotheker auf der Palliativstation: Auswirkung auf Arzneimitteltherapie und Therapiekosten.

BACKGROUND: The effect of integrating clinical pharmacists in German palliative care units with regard to the quality of drug therapy and drug costs has yet not been evaluated. OBJECTIVES: This work aims to assess the number of pharmaceutical interventions (PI) and the cost-benefit ratio of a clinical pharmacist taking part in the interprofessional patient care team on an inpatient palliative care unit in Germany. METHODS: The number of and underlying reasons for the pharmacist-led recommendations were recorded and analyzed over a 1-year period. In addition, the respective drugs and the acceptance rate of recommendations were assessed. To evaluate the cost-benefit ratio, the financial savings in the provision of drugs were recorded and compared with the expenses for the clinical pharmacy service. RESULTS: A total of 245 PI were performed. Most frequently, the pharmacist advised physicians on drug choices and drug dosages. The acceptance rate was 93%. The cost savings in the provision of drugs covered 83% of the expenses for the clinical pharmacy service. CONCLUSION: The results indicate that the integration of a clinical pharmacist is well suited to optimizing the interprofessional treatment of distressing symptoms with a beneficial economic outcome in palliative care. Consequently, the permanent integration of a clinical pharmacist on an inpatient palliative care unit seems to be beneficial and advisable.

New Oral Anti-Cancer Drugs and Medication Safety.

BACKGROUND: Many oral anti-cancer drugs have come onto the market in the past 20 years. For example, kinase inhibitors, such as the BCR-ABL and BRAF inhibitors, have markedly improved the treatment of chronic myeloid leukemia and melanoma. In this review, we discuss the special challenges posed by poor adherence, drug-drug interactions with other substances, and side effects, among other problems, and the ways in which these challenges can be met. METHODS: A selective search was carried out in PubMed for original and review articles on the safety of new oral anti-cancer drugs. Guidelines and current Summaries of Product Characteristics (SmPC) were also considered in the analysis. RESULTS: Review articles have pointed out numerous safety concerns with oral anti-cancer drugs. One of these is adherence, on which highly variable figures are available (with mean non-adherence rates ranging from 0 to 54%). The absorption of approximately half of these drugs is influenced by the patient's diet, and that of approximately 20% by gastric pH (Caution: proton-pump inhibitors may influence bioavailability). 70% of the active substances are metabolized primarily by CYP3A4, which means that their pharmacokinetics can be altered by grapefruit juice and CYP3A4 modulators. The prevention, detection, and treatment of side effects (which can be gastrointestinal, cutaneous, cardiovascular, or other) is a highly important matter. CONCLUSION: The increasing use of oral anti-cancer drugs confronts patients and treatment teams with special challenges. To optimize treatment outcomes, a multidisciplinary approach should be taken, involving physicians, pharmacists, and nurses. To improve medication safety, medication and side-effect management should be performed, and adherence should be regularly checked and systematically encouraged.

Dose adjustment of cisplatin, etoposide, and ifosfamide according to kidney function: a retrospective analysis and implications for medication safety.

Clearance of cisplatin, etoposide, and ifosfamide depends on kidney function and dosages should be adjusted in patients with renal impairment. However, there is still limited data on the adherence of physicians to dosing recommendations for these drugs in cancer patients with renal impairment. Three thousand four hundred forty-eight prescriptions to 369 patients, treated in the Comprehensive Cancer Center of a German university hospital, were retrospectively evaluated. The administered relative doses of cisplatin, etoposide, and ifosfamide were compared with relative doses recommended at the time of prescription according to the patients' creatinine clearance. Cisplatin is contraindicated according to two German summary of product characteristics (SmPC) in patients with a creatinine clearance < 60 mL/min. Nevertheless, 37 cisplatin prescriptions were made for this group of patients (i.e., 2.0% of all cisplatin prescriptions). According to one German SmPC (valid in the year of data analysis), etoposide dosage should be reduced in patients with a creatinine clearance from 15 to 50 mL/min, while it is contraindicated below 15 mL/min. Thirteen etoposide prescriptions were without dose reduction in patients with creatinine clearance from 15 to 50 mL/min (1.5% of all etoposide prescriptions); one patient received etoposide with creatinine clearance below 15 mL/min. In 8.9% of ifosfamide prescriptions, patients did not receive a reduced dose in spite of respective recommendations. Dosages of cisplatin, etoposide, and ifosfamide are not always adjusted as recommended in patients with renal impairment. Consistent international dosing recommendations (e.g., in SmPCs), preferentially included in clinical decision support systems, should be developed to tackle this problem.

Advances in clinical pharmacy education in Germany: a quasi-experimental single-blinded study to evaluate a patient-centred clinical pharmacy course in psychiatry.

BACKGROUND: The pharmacy profession has shifted towards patient-centred care. To meet the new challenges it is necessary to provide students with clinical competencies. A quasi-experimental single-blinded teaching and learning study was carried out using a parallel-group design to evaluate systematically the benefits of clinical teaching in pharmacy education in Germany. METHODS: A clinical pharmacy course on a psychiatric ward was developed and implemented for small student groups. The learning aims included: the improvement of patient and interdisciplinary communication skills and the identification and management of pharmaceutical care issues. The control group participated only in the preparation lecture, while the intervention group took part in the complete course. The effects were assessed by an objective structured clinical examination (OSCE) and a student satisfaction survey. RESULTS: The intervention group achieved significantly better overall results on the OSCE assessment (46.20 ± 10.01 vs. 26.58 ± 12.91 of a maximum of 90 points; p < 0.0001).The practical tasks had the greatest effect, as reflected in the outcomes of tasks 1-5 (34.94 ± 9.60 vs. 18.63 ± 10.24 of a maximum of 60 points; p < 0.0001). Students' performance on the theoretical tasks (tasks 6-10) was improved but unsatisfying in both groups considering the maximum score (11.50 ± 4.75 vs. 7.50 ± 4.00 of a maximum of 30 points; p < 0.0001). Of the students, 93% rated the course as practice-orientated, and 90% felt better prepared for patient contact. Many students suggested a permanent implementation and an extension of the course. CONCLUSIONS: The results suggest that the developed ward-based course provided learning benefits for clinical skills. Students' perception of the course was positive. Implementation into the regular clinical pharmacy curriculum is therefore advisable.

[HERA-QUEST: HTA evaluation of generic pharmaceutical products to improve quality, economic efficiency, patient safety and transparency in drug product changes in hospitals]. / HERA-QUEST: HTA-Evaluation generischer Arzneimittel zur Verbesserung von Qualität, Oekonomie, Patientensicherheit und Transparenz bei Produktumstellungen in Kliniken.

In view of the rising cost pressure and an increasing number of drug shortages, switches between generic drug preparations have become a daily routine in hospitals. To ensure consistently high treatment quality and best possible patient safety, the equivalence of the new and the previous drug preparation must be ensured before any change in the purchase of pharmaceutical products takes place. So far, no easily usable, transparent and standardized instrument for this kind of comparison between generic drug products has been available. A group of pharmaceutical experts has developed the drug HTA (health technology assessment) model "HERA" (HTA Evaluation of geneRic phArmaceutical products) through a multi-step process. The instrument is designed to perform both a qualitative and economic comparison of equivalent drug preparations ("aut idem" substitution) before switching products. The economic evaluation does not only consider unit prices and consumption quantity, but also the processing costs associated with a product change process. The qualitative comparison is based on the evaluation of 34 quality criteria belonging to six evaluation fields (e.g., approval status, practical handling, packaging design). The objective evaluation of the quality criteria is complemented by an assessment of special features of the individual hospital for complex drug switches, including the feedback of the physicians utilizing the drug preparation. Thus potentially problematic switches of pharmaceutical products can be avoided at the best possible rate, contributing to the improvement of patient safety. The novel drug HTA model HERA is a tool used in clinical practice that can add to an increase in quality, therapeutic safety and transparency of drug use while simultaneously contributing to the economic optimization of drug procurement in hospitals. Combining these two is essential for hospitals facing the tension between rising cost pressure and at the same time increasing demands on quality and transparency, triggered by, amongst others, current legislation (Hospital Structures Act, anti-corruption legislation).