Informational continuity of medication management in transitions of care: Qualitative interviews with stakeholders from the HYPERION-TransCare study.

BACKGROUND: The transition of patients between inpatient and outpatient care can lead to adverse events and medication-related problems due to medication and communication errors, such as medication discontinuation, the frequency of (re-)hospitalizations, and increased morbidity and mortality. Older patients with multimorbidity and polypharmacy are particularly at high risk during transitions of care. Previous research highlighted the need for interventions to improve transitions of care in order to support information continuity, coordination, and communication. The HYPERION-TransCare project aims to improve the continuity of medication management for older patients during transitions of care. METHODS AND FINDINGS: Using a qualitative design, 32 expert interviews were conducted to explore the perspectives of key stakeholders, which included healthcare professionals, patients and one informal caregiver, on transitions of care. Interviews were conducted between October 2020 and January 2021, transcribed verbatim and analyzed using content analysis. We narratively summarized four main topics (stakeholders' tasks, challenges, ideas for solutions and best practice examples, and patient-related factors) and mapped them in a patient journey map. Lacking or incomplete information on patients' medication and health conditions, inappropriate communication and collaboration between healthcare providers within and across settings, and insufficient digital support limit the continuity of medication management. CONCLUSIONS: The study confirms that medication management during transitions of care is a complex process that can be compromised by a variety of factors. Legal requirements and standardized processes are urgently needed to ensure adequate exchange of information and organization of medication management before, during and after hospital admissions. Despite the numerous barriers identified, the findings indicate that involved healthcare professionals from both the inpatient and outpatient care settings have a common understanding.

[General practice care for patients with chronic non-cancer pain: A rapid review as part of the RELIEF project]. / Hausärztliche Versorgung von Patient:innen mit chronischen nicht-tumorbedingten Schmerzen: ein Rapid Review im Rahmen des RELIEF-Projekts.

INTRODUCTION: Approximately one fifth of the German population suffers from chronic pain, which is often associated with limitations in coping with everyday life, social isolation and psychological comorbidities such as anxiety and depression. The importance of a treatment approach that considers biological, psychological, and social factors (bio-psycho-social model) as well as non-drug interventions is emphasized in current guidelines, but presents challenges for primary care practices. To support the implementation of evidence-based best practice recommendations, the RELIEF project (Resource-oriented case management to implement recommendations for patients with chronic pain and frequent use of analgesics in general practices) aims to develop a case management program for the primary care of patients with chronic non-tumor pain. METHODS: Prior to intervention development, a rapid review was conducted to identify best practice recommendations for the care of patients with chronic non-tumor pain, barriers and strategies to their implementation, and gaps in care in current guidelines and literature. Selective searches of guidelines, PubMed, the Cochrane Library, bibliographies of relevant publications, and the gray literature focused on assessment and monitoring, education, promotion of self-care, and rational pharmacotherapy. RESULTS: Numerous recommendations on assessment and monitoring were identified, but only a few studies examined their feasibility in primary care practices. Guidelines contained few specific recommendations on content and format of patient education on chronic pain. Recommendations for non-drug self-care measures were mainly related to physical activity, relaxation techniques, behavioral therapy techniques and external applications. Especially for the area of physical activity, numerous barriers but also strategies for a successful implementation could be identified. DISCUSSION: In a potential primary care model for patients with chronic non-tumor pain, pain assessment should aim to identify patients who need support in implementing medication and non-medication interventions in the primary care setting and/or could benefit from specialized care. To implement recommendations for pain education, primary care physicians need educational materials in a variety of formats and levels of detail that ideally could be processed by patients at home and then get addressed in practices using simple key questions. Non-drug measures should be an explicit part of the treatment plan. CONCLUSION: Many of the identified recommendations for the treatment of patients with chronic non-tumor pain can also be considered relevant for the primary care setting. Specific guidelines and concepts for primary care physicians that include setting-specific characteristics at the physician, patient, and system levels would be desirable for a successful implementation of these recommendations.

Implementation and evaluation of a complex intervention to improve information availability at the interface between inpatient and outpatient care in older patients with multimorbidity and polypharmacy (HYPERION-TransCare) - study protocol for a pilot and feasibility cluster-randomized controlled trial in general practice in Germany.

BACKGROUND: Despite attempts to improve the cross-sectoral flow of information, difficulties remain in routine healthcare. The resulting negative impact on continuity of care is often associated with poor health outcomes, especially in older patients. Our intervention aims to increase information availability with respect to medications and health conditions at the interface between inpatient and outpatient care and to contribute towards improving the quality of care in older patients. This pilot study focuses on feasibility and implementability. METHODS: The idea of the complex intervention has been developed in a previous study. This intervention will be tested in a prospective, multicenter, cluster-randomized (via web tool), controlled pilot trial with two parallel study arms (intervention and control group). The pilot study will be conducted in 20 general practices in Hesse and Saxony (Germany) and include 200 patients (≥ 65 years of age with multimorbidity and polypharmacy) recruited by the practices. Practice staff and patients will be blinded. We will use qualitative and quantitative methods to assess the feasibility and implementability of the intervention and the study design in a process evaluation covering topics ranging from expectations to experiences. In addition, the feasibility of proposed outcome parameters for the future definitive trial will be explored. The composite endpoint will include health-related patient outcomes (hospitalization, falls, and mortality using, e.g., the FIMA questionnaire), and we will assess information on medications (SIMS questionnaire), symptoms and side effects of the medication (pro-CTCAE questionnaire), and health literacy (HLQ questionnaire). Data will be collected at study begin (baseline) and after 6 months. Furthermore, the study will include surveys and interviews with patients, general practitioners, and healthcare assistants. DISCUSSION: The intervention was developed using a participatory approach involving stakeholders and patients. It aims to empower general practice teams as they provide patient-centered care and play a key role in the coordination and continuity of care. We aim to encourage patients to adopt an active role in their health care. Overall, we want to increase the availability of health-related information for patients and healthcare providers. The results of the pilot study will be used in the design and implementation of the future definitive trial. TRIAL REGISTRATION: The study was registered in DRKS-German Clinical Trials Register: registration number DRKS00027649 (date: 19 January 2022). Date and version identifier 10.07.2023; Version 1.3.

Development of an Electronic Tool to Assess Patient Preferences in Geriatric Polypharmacy (PolyPref).

Purpose: Medical decision-making in older adults with multiple chronic conditions and polypharmacy should include the individual patient's treatment preferences. We developed and pilot-tested an electronic instrument (PolyPref) to elicit patient preferences in geriatric polypharmacy. Patients and Methods: PolyPref follows a two-stage direct approach to preference assessment. Stage 1 generates an individual preselection of relevant health outcomes and medication regimen characteristics, followed by stage 2, in which their importance is assessed using the Q-sort methodology. The feasibility of the instrument was tested in adults aged ≥70 years with ≥2 chronic conditions and regular intake of ≥5 medicines. After the assessment with PolyPref, the patients rated the tool with regard to its comprehensibility and usability and assessed the accuracy of the personal result. Evaluators rated the patients' understanding of the task. Results: Eighteen short-term health outcomes, 3 long-term health outcomes, and 8 medication regimen characteristics were included in the instrument. The final population for the pilot study comprised 15 inpatients at a clinic for geriatric rehabilitation with a mean age of 80.6 (± 6.0) years, a median score of 28 (range 25-30) points on the Mini-Mental State Examination, and a mean of 11.6 (± 3.6) regularly taken medicines. Feedback by the patients and the evaluators revealed ratings in favor of understanding and comprehensibility of 86.7% to 100%. The majority of the patients stated that their final result summarized the most important aspects of their pharmacotherapy (93.3%) and that its ranking order reflected their personal opinion (100%). Preference assessment took an average of 35 (± 8.5) min, with the instrument being handled by the evaluator in 14 of the 15 participants. Conclusion: Preference assessment with PolyPref was feasible in older adults with multiple chronic conditions and polypharmacy, offering a new strategy for the standardized evaluation of patient priorities in geriatric pharmacotherapy.

Prevalence and patient-rated relevance of complexity factors in medication regimens of community-dwelling patients with polypharmacy.

PURPOSE: To describe the prevalence of complexity factors in the medication regimens of community-dwelling patients with more than five drugs and to evaluate the relevance of these factors for individual patients. METHODS: Data were derived from the HIOPP-6 trial, a controlled study conducted in 9 general practices which evaluated an electronic tool to detect and reduce complexity of drug treatment. The prevalence of complexity factors was based on the results of the automated analysis of 139 patients' medication data. The relevance assessment was based on the patients' rating of each factor in an interview (48 patients included for analysis). RESULTS: A median of 5 (range 0-21) complexity factors per medication regimen were detected and at least one factor was observed in 131 of 139 patients. Almost half of these patients found no complexity factor in their medication regimen relevant. CONCLUSION: In most medication regimens, complexity factors could be identified automatically, yet less than 15% of factors were indeed relevant for patients as judged by themselves. When assessing complexity of medication regimens, one should especially consider factors that are both particularly frequent and often challenging for patients, such as use of inhalers or tablet splitting. TRIAL REGISTRATION: The HIOPP-6 trial was registered retrospectively on May 17, 2021, in the German Clinical Trials register under DRKS-ID DRKS00025257.

Development of an algorithm to detect and reduce complexity of drug treatment and its technical realisation.

BACKGROUND: The increasing complexity of current drug therapies jeopardizes patient adherence. While individual needs to simplify a medication regimen vary from patient to patient, a straightforward approach to integrate the patients' perspective into decision making for complexity reduction is still lacking. We therefore aimed to develop an electronic, algorithm-based tool that analyses complexity of drug treatment and supports the assessment and consideration of patient preferences and needs regarding the reduction of complexity of drug treatment. METHODS: Complexity factors were selected based on literature and expert rating and specified for integration in the automated assessment. Subsequently, distinct key questions were phrased and allocated to each complexity factor to guide conversation with the patient and personalize the results of the automated assessment. Furthermore, each complexity factor was complemented with a potential optimisation measure to facilitate drug treatment (e.g. a patient leaflet). Complexity factors, key questions, and optimisation strategies were technically realized as tablet computer-based application, tested, and adapted iteratively until no further technical or content-related errors occurred. RESULTS: In total, 61 complexity factors referring to the dosage form, the dosage scheme, additional instructions, the patient, the product, and the process were considered relevant for inclusion in the tool; 38 of them allowed for automated detection. In total, 52 complexity factors were complemented with at least one key question for preference assessment and at least one optimisation measure. These measures included 29 recommendations for action for the health care provider (e.g. to suggest a dosage aid), 27 training videos, 44 patient leaflets, and 5 algorithms to select and suggest alternative drugs. CONCLUSIONS: Both the set-up of an algorithm and its technical realisation as computer-based app was successful. The electronic tool covers a wide range of different factors that potentially increase the complexity of drug treatment. For the majority of factors, simple key questions could be phrased to include the patients' perspective, and, even more important, for each complexity factor, specific measures to mitigate or reduce complexity could be defined.

Medication beliefs and use of medication lists - is there a connection? Results from a before-and-after study in Germany.

BACKGROUND: Despite increasing digitalisation the paper-based medication list remains one of the most important instruments for the documentation and exchange of medication-related information. However, even elderly patients with polypharmacy who are at high risk for medication errors and adverse drug events, frequently do not receive or use a complete and comprehensible medication list. Increasing the use of medication lists would be a great contribution to medication safety and facilitate the work of health care providers. METHODS: This study is related to the project MeinPlan (MyPlan) which comprised an information campaign on safe drug administration in the Rhine-Neckar region in South Germany. The campaign was evaluated in a before-and-after study based on a survey among two independent, representative samples of citizens over 65 years. In total, 5034 questionnaires were analysed. While the effects of the primary outcome (the percentage of citizens using a medication list) have been reported elsewhere, this analysis focusses on the effects of the campaign on citizens' medication beliefs and assesses whether medication beliefs are associated with the use of medication lists, the use of over-the-counter drugs and the use of the tools offered by the campaign. Medication beliefs were assessed with the German version of the General Beliefs About Medicines Questionnaire (BMQ) which results in subscales for "General Overuse", "General Usefulness" and "General Harm". The use of medication lists and over-the-counter drugs was assessed with self-developed questionnaire items. RESULTS: No statistically significant change in citizens' medication beliefs before and after the campaign could be detected. Likewise, no association between medication beliefs and the use of medication lists, the use of over-the-counter drugs or the use of the tools offered by the campaign could be shown. CONCLUSIONS: A campaign focussing on the risks of drug administration did not change the medication beliefs of the targeted population. Moreover, citizens' general medication beliefs do not seem to be crucial for their decision to use a medication list or over-the-counter drugs. Strategies to improve the use of medication lists by patients should focus on other influential factors, such as individual benefits and barriers and socio-psychological factors.

Individual factors increasing complexity of drug treatment-a narrative review.

PURPOSE: Complexity of drug treatment is known to be a risk factor for administration errors and nonadherence promoting higher healthcare costs, hospital admissions and increased mortality. Number of drugs and dose frequency are parameters often used to assess complexity related to the medication regimen. However, factors resulting from complex processes of care or arising from patient characteristics are only sporadically analyzed. Hence, the objective of this review is to give a comprehensive overview of relevant, patient-centered factors influencing complexity of drug treatment. METHODS: A purposeful literature search was performed in MEDLINE to identify potential complexity factors relating to the prescribed drug (i.e. dosage forms or other product characteristics), the specific medication regimen (i.e. dosage schemes or additional instructions), specific patient characteristics and process characteristics. Factors were included if they were associated to administration errors, nonadherence and related adverse drug events detected in community dwelling adult patients. RESULTS: Ninety-one influencing factors were identified: fourteen in "dosage forms", five in "product characteristics", twelve in "dosage schemes", nine in "additional instructions", thirty-one in "patient characteristics" and twenty in "process characteristics". CONCLUSIONS: Although the findings are limited by the non-systematic search process and the heterogeneous results, the search shows the influence of many factors on the complexity of drug treatment. However, to evaluate their relevance for individual patients, prospective studies are necessary.

Methods to Assess Patient Preferences in Old Age Pharmacotherapy - A Systematic Review.

PURPOSE: The aim of this systematic review was to identify methods used to assess medication preferences in older adults and evaluate their advantages and disadvantages with respect to their applicability to the context of multimorbidity and polypharmacy. MATERIAL AND METHODS: Three electronic databases (PubMed, Web of Science, PsycINFO) were searched. Eligible studies elicited individual treatment or outcome preferences in a context that involved long-term pharmacological treatment options. We included studies with a study population aged ≥ 65 years and/or with a mean or median age of ≥ 75 years. Qualitative studies, studies assessing preferences for only two different treatments, and studies targeting preferences for life-sustaining treatments were excluded. The identified preference measurement methods were evaluated based on four criteria (time budget, cognitive demand, variety of pharmacological aspects, and link with treatment strategies) judged to be relevant for the elicitation of patient preferences in polypharmacy. RESULTS: Sixty articles met the eligibility criteria and were included in the narrative synthesis. Fifty-five different instruments to assess patient preferences, based on 24 different elicitation methods, were identified. The most commonly applied preference measurement techniques were "medication willingness" (description of a specific medication with inquiry of the participant's willingness to take it), discrete choice experiments, Likert scale-based questionnaires, and rank prioritization. The majority of the instruments were created for disease-specific or context-specific settings. Only three instruments (Outcome Prioritization Tool, a complex intervention, "MediMol" questionnaire) dealt with the broader issue of geriatric multimorbidity. Only seven of the identified tools showed somewhat favorable characteristics for a potential use of the respective method in the context of polypharmacy. CONCLUSION: Up to now, few instruments have been specifically designed for the assessment of medication preferences in older patients with multimorbidity. To facilitate valid preference elicitation in the context of geriatric polypharmacy, future research should focus on suitable characteristics of existing techniques to develop new measurement approaches for this increasingly relevant population.

[Simplifying complex drug therapies : Challenges and solutions]. / Komplexe Arzneimitteltherapien vereinfachen : Herausforderungen und Lösungsansätze.

The difficulties of managing a complex medication regimen are often underestimated in outpatient care. A large number of drugs (polypharmacy) and complicated dosage schemes or dosage forms may overstrain patients. Indeed, wrong drug administration can impair treatment success or cause adverse drug events.Patients are often unaware of the medication administration errors. Furthermore they do not voice administration problems, often because they are not aware of the potential to optimize their drug therapy. Medication regimen complexity can often be reduced by simple measures. However, feasible concepts for reducing medication regimen complexity in a structured way have been lacking in routine care so far.Electronic decision support facilitates systematic and efficient identification of factors that increase the complexity of a medication regimen. Furthermore, electronic decision aids may enable physicians and pharmacists to take appropriate measures in order to reduce medication regimen complexity. Personalizing the analysis and resulting measures to reduce medication regimen complexity might increase readiness of patients to implement changes in treatment and, thus, probably increase adherence. The first results of a prospective trial that is supported by the Federal Joint Committee (G-BA) Innovationsfonds (HIOPP-6, Komplexitätsreduktion in der Polypharmazie unter Beachtung von Patientenpräferenzen) will be available in autumn 2018 and answer these questions.

Risk factors of adverse health outcomes after hospital discharge modifiable by clinical pharmacist interventions: a review with a systematic approach.

The present review assessed the evidence on risk factors for the occurrence of adverse health outcomes after discharge (i.e. unplanned readmission or adverse drug event after discharge) that are potentially modifiable by clinical pharmacist interventions. The findings were compared with patient characteristics reported in guidelines that supposedly indicate a high risk of drug-related problems. First, guidelines and risk assessment tools were searched for patient characteristics indicating a high risk of drug-related problems. Second, a systematic PubMed search was conducted to identify risk factors significantly associated with adverse health outcomes after discharge that are potentially modifiable by a clinical pharmacist intervention. After the PubMed search, 37 studies were included, reporting 16 risk factors. Only seven of 34 patient characteristics mentioned in pertinent guidelines corresponded to one of these risk factors. Diabetes mellitus (n = 11), chronic obstructive lung disease (n = 9), obesity (n = 7), smoking (n = 5) and polypharmacy (n = 5) were the risk factors reported most frequently in the studies. Additionally, single studies also found associations of adverse health outcomes with different drug classes {e.g. warfarin [hazard ratio 1.50; odds ratio (OR) 3.52], furosemide [OR 2.25] or high beta-blocker starting doses [OR 3.10]}. Although several modifiable risk factors were found, many patient characteristics supposedly indicating a high risk of drug-related problems were not part of the assessed risk factors in the context of an increased risk of adverse health outcomes after discharge. Therefore, an obligatory set of modifiable patient characteristics should be created and implemented in future studies investigating the risk for adverse health outcomes after discharge.

[Good prescribing practice]. / Gute Verordnungspraxis.

Drug prescription is the very first step initiating a cascade of events in the medication process. It is, hence, decisive for success or failure of any pharmacologic treatment. A good prescription must therefore consider (1) relevant patient factors and co-morbidities, (2) evidence-based knowledge on medically sound prescribing practices, and (3) the setting in which a prescription is issued. The setting will determine which partners will participate, contribute, and safeguard the ongoing medication process and how much responsibility can be shared. Partners in the medication process refer to other healthcare professionals dispensing the drug, teaching the patient, or administering the medicines. It also involves the patients or their relatives with their information needs and often variable motivation and conviction to use a drug. By issuing a prescription, the physician must provide the partners with sufficient and appropriate information, must ensure that they understand the meaning of the prescription and are able to perform their assigned tasks during the medication process. Lastly, medication prescription is also subject to formal constraints and must meet legal criteria that are relevant for reimbursement by health insurance companies.

[Good prescription practice for out-patients-quality requirements of prescriptions in Germany]. / Gute Verordnungspraxis im ambulanten Sektor - Qualitätsanforderungen an die Rezeptschreibung in Deutschland.

Because the written prescription is a central communication medium between the prescribing physician and the dispensing pharmacist measures to improve the prescription quality are top priorities. While most primary care physicians in Germany use electronic systems, in outpatient clinics and nursing homes and on special occasions such as emergency services and home visits, many prescriptions are still handwritten. Incorrectly and illegibly issued prescriptions impair the physician-pharmacist-patient relationship and thus represent a risk factor in the context of medication safety. Well issued prescriptions expedite the dispensing and thus the continuity of treatment of the patients and spare human resources by avoiding queries and unnecessary steps in the care process. At the same time, legible and unequivocal prescriptions facilitate measures for quality assurance by the dispensing pharmacists and are essential preconditions needed for insurance reimbursement. Probably the most important step to high quality prescriptions is the consistent use of suitable electronic prescription software. This is only possible if physicians are willing to cooperate and understand the significance and benefits of an electronic prescription system.

Inappropriate crushing information on ward lists: cytotoxic drugs, capsules, and modified release formulations are gravely neglected.

PURPOSE: The aim of this study was to assess the quality of the information sources on the modification of solid medication dosage forms (crushing, suspending) used on the wards of a large university hospital in Germany. METHODS: We performed on-site visits of all 79 wards of the hospital and collected available sources of information on the modification of solid medication dosage forms. To evaluate the quality of such information, we gathered reference information for each listed brand from the respective pharmaceutical company, transferred this information to a knowledge base, and classified it into three categories, i.e., modification not allowed, modification allowed, and modification allowed under certain circumstances. RESULTS: Twenty-two lists of information on drug modification were identified in the 79 wards. Each list contained errors, and on average 17.0 % (range 8.0-32.3 %) of the brands listed had been withdrawn from the market or the information on crushing and/or suspending was inappropriate. Most of the incorrect information either concerned brands containing ingredients that were potentially hazardous to the staff members who prepared the drugs or referred to special dosage forms such as capsules and modified release formulations (e.g., cytotoxic drugs). CONCLUSION: We found that the lists posted on the wards were often outdated and did not take into account the limitations/problems of preparing drugs on the ward. Our results emphasize that lists posted in wards need to be checked regularly and that "ready-to-use" lists from third parties might require adaptation to site-specific conditions in order to protect healthcare staff from exposure to potentially hazardous drugs during drug preparation and ensure safe drug application to the patient.

Opportunities to reduce medication regimen complexity: a retrospective analysis of patients discharged from a university hospital in Germany.

BACKGROUND: Numerous characteristics of a medication regimen can weaken patient adherence to drug therapy and thus impair clinical outcomes of drug therapy. OBJECTIVE: The aim of the study was to investigate the prevalence of medication regimen characteristics that are known to reduce patient adherence to drug therapy. Furthermore, we assessed to what extent complex medication regimens can possibly be simplified through different strategies. METHODS: We retrospectively evaluated the medication regimens of 500 consecutive patients discharged from the University Hospital of Heidelberg, Germany, in whom the dosages of all drugs were specified. The medication regimens were extracted from the discharge letters issued between 1 January 2007 and 29 December 2007. Each medication regimen was checked for the presence of seven regimen characteristics that are known to reduce patient adherence, and theoretical viable strategies to avoid four of the respective characteristics were identified. The extent of possible simplification through the identified strategies was evaluated for the overall study population and the subgroup of elderly patients (≥65 years) with polypharmacy (≥5 drugs). RESULTS: On average, every medication regimen in the overall study population had 2.9±1.7 (standard deviation) characteristics (range 0-7) known to impair patient adherence. In contrast, the medication regimens of elderly patients with polypharmacy contained 3.7±1.6 characteristics (range 0-7) known to impair patient adherence. The most prevalent complexity characteristics in the overall study population were prescription of ≥1 drug with multiple doses per day (441 patients), ≥3 drugs with different dosing intervals (349 patients), tablet splitting (223 patients), followed by ≥12 daily drug administrations (190 patients). Almost half of the prescribed tablet splitting could be prevented. Moreover, 17.9% of the multi-dose prescriptions could be switched to once-daily dosing, and thus reduced the number of drugs with different dosing intervals and the number of daily drug administrations. The combined intervention reduced the total number of potentially preventable complexity characteristics by 18.3% (from 2283 to 1865 characteristics) without reducing prescription quality. CONCLUSION: Almost one-fifth of all regimen complexity characteristics relevant for patient adherence were avoidable by simple modifications of the medication scheme, stressing the need for targeted interventions.

Pharmacokinetic predictions for patients with renal impairment: focus on peptides and protein drugs.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: • Renal impairment may affect the pharmacokinetics of peptide and protein drugs. • Molecular size is a predictor. Small molecules are eliminated by the kidneys, whereas large molecules (>67 kDa) are not. • Urinary recovery of peptide and protein drugs in healthy volunteers is not predictive for pharmacokinetic changes in patients with renal impairment. WHAT THIS STUDY ADDS: • An apparently continuous non-linear relationship between molecular weight and pharmacokinetic alterations as observed in patients with severe renal impairment or end-stage renal disease is described. • Potentially relevant pharmacokinetic changes were found for drugs with a molecular weight below 50 kDa. • Analysis of observed pharmacokinetics in patients with severe renal impairment may be a useful approach, especially when urinary recovery in healthy volunteers is not predictive. AIM: Drug dosage adjustments in renal impairment are usually based on estimated individual pharmacokinetics. The extent of pharmacokinetic changes in patients with renal impairment must be known for this estimation. If measured data are not available, an estimate based on drug elimination in urine of healthy subjects or patients with normal renal function is commonly made. This is not reliable, however, if renal drug metabolism is involved, as is presumably the case for many peptide and protein drugs. In the present study a new method to predict pharmacokinetic changes for such drugs based on molecular weight was derived. METHODS: Articles reporting measured pharmacokinetics of peptide and protein drugs in patients with severe renal impairment or end-stage renal disease were identified from the scientific literature, the pharmacokinetic parameter values were extracted and a statistical data synthesis was performed. A sigmoid E(max) model was applied and fitted to the data and the prediction error was analyzed. RESULTS: Overall, 98 peptide and protein drugs were identified. Relevant pharmacokinetic data in patients with renal impairment were found for 21 of these drugs. The average drug clearance was 30% and the average prolongation in half-life was 3.1-fold for low molecular weight peptides or proteins. The median root squared percentage of the prediction error was 18% (drug clearance) and 12% (half-life). CONCLUSION: An apparently continuous non-linear relationship between molecular weight and pharmacokinetic alterations in patients with severe renal impairment was found. The derived equations could be used as a rough guide for decisions on drug dosage adjustments in such patients.