Commentary on the EMA reflection paper on the pharmaceutical development of medicines for use in the older population.

Older people are often affected by impaired organ and bodily functions resulting in multimorbidity and polypharmacy, turning them into the main user group of many medicines. Very often, medicines have not specifically been developed for older people, causing practical medication problems for them like limited availability of easy to swallow formulations, easy to open packaging and dosing instructions for enteral administration. In 2020, the European Medicines Agency (EMA) published a reflection paper 'Pharmaceutical development of medicines for use in the older population', which discusses how the emerging needs of an ageing European population can be addressed by medicines regulation. The paper intends to help industry to better consider the needs of older people during pharmaceutical/clinical medicines development by summarising data on the most relevant topics, providing early suggestions on how to move forward and prompting expert discussions and studies into knowledge gaps. Topics include patient acceptability, (dis)advantages of an administration route, formulation, dosage form, packaging, dosing device and user instruction. While the paper is directed at older people and the pharmaceutical industry, the reflections are also relevant to younger patients with similar disease-related needs and of value to other stakeholders parties, e.g., healthcare professionals, academics, patients and caregivers, as the paper makes clear what can be expected from industry and where collaborative work is needed. This commentary provides an overview of the different steps in the development of the reflection paper, discusses points considered most controversial and/or subject to (multidisciplinary) expert discussions and indicates their value for real world clinical practice.

Optimizing Therapy to Prevent Avoidable Hospital Admissions in Multimorbid Older Adults (OPERAM): cluster randomised controlled trial.

OBJECTIVE: To examine the effect of optimising drug treatment on drug related hospital admissions in older adults with multimorbidity and polypharmacy admitted to hospital. DESIGN: Cluster randomised controlled trial. SETTING: 110 clusters of inpatient wards within university based hospitals in four European countries (Switzerland, Netherlands, Belgium, and Republic of Ireland) defined by attending hospital doctors. PARTICIPANTS: 2008 older adults (≥70 years) with multimorbidity (≥3 chronic conditions) and polypharmacy (≥5 drugs used long term). INTERVENTION: Clinical staff clusters were randomised to usual care or a structured pharmacotherapy optimisation intervention performed at the individual level jointly by a doctor and a pharmacist, with the support of a clinical decision software system deploying the screening tool of older person's prescriptions and screening tool to alert to the right treatment (STOPP/START) criteria to identify potentially inappropriate prescribing. MAIN OUTCOME MEASURE: Primary outcome was first drug related hospital admission within 12 months. RESULTS: 2008 older adults (median nine drugs) were randomised and enrolled in 54 intervention clusters (963 participants) and 56 control clusters (1045 participants) receiving usual care. In the intervention arm, 86.1% of participants (n=789) had inappropriate prescribing, with a mean of 2.75 (SD 2.24) STOPP/START recommendations for each participant. 62.2% (n=491) had ≥1 recommendation successfully implemented at two months, predominantly discontinuation of potentially inappropriate drugs. In the intervention group, 211 participants (21.9%) experienced a first drug related hospital admission compared with 234 (22.4%) in the control group. In the intention-to-treat analysis censored for death as competing event (n=375, 18.7%), the hazard ratio for first drug related hospital admission was 0.95 (95% confidence interval 0.77 to 1.17). In the per protocol analysis, the hazard ratio for a drug related hospital admission was 0.91 (0.69 to 1.19). The hazard ratio for first fall was 0.96 (0.79 to 1.15; 237 v 263 first falls) and for death was 0.90 (0.71 to 1.13; 172 v 203 deaths). CONCLUSIONS: Inappropriate prescribing was common in older adults with multimorbidity and polypharmacy admitted to hospital and was reduced through an intervention to optimise pharmacotherapy, but without effect on drug related hospital admissions. Additional efforts are needed to identify pharmacotherapy optimisation interventions that reduce inappropriate prescribing and improve patient outcomes. TRIAL REGISTRATION: ClinicalTrials.gov NCT02986425.

Prescribing medicines to older people-How to consider the impact of ageing on human organ and body functions.

Ageing is associated with several changes in human organs, which result in altered medication pharmacokinetics and pharmacodynamics. Ageing is also associated with changes in human body functions, such as impaired vision, hearing, swallowing, motor and cognitive functions, which can affect the adequate intake and administration of drugs. As a consequence, older people, and especially patients older than 75 years, are the main users of many drugs and they frequently use 5 drugs or more long-term (i.e. polypharmacy). All this increases the complexity of adequate drug intake, administration and adherence. However, there is a lack of evidence on the considerations that should be taken into account to ensure appropriate drug prescribing to older people. This review article summarizes the most clinically relevant changes in human organ and body functions and the consequential changes in pharmacokinetics and pharmacodynamics in older people, along with possible dosing consequences or alternatives for drugs frequently prescribed to this patient population. Recommendations are given on how ageing could be considered in clinical drug development, drug authorization and appropriate prescribing.

Reducing Inappropriate Drug Use in Older Patients by Use of Clinical Decision Support in Community Pharmacy: A Mixed-Methods Evaluation.

INTRODUCTION: Older people are prone to drug-related harm. Clinical decision support systems (CDSSs) in community pharmacies may improve appropriate prescribing in this population. OBJECTIVE: This study investigated (persistent) drug therapy changes and its determinants to reduce potentially inappropriate medication (PIM) in older patients based on CDSS alerts and to investigate barriers and facilitators for implementation of drug therapy changes based on these CDSS alerts. METHODS: Five clinical decision rules based on national guidelines for inappropriate drugs in older patients were incorporated in a web-based CDSS in 31 community pharmacies between February and April 2017. The CDSS generated alerts for patients aged > 70 years who had prescriptions for one of the following drugs: alprazolam, amitriptyline, barnidipine, duloxetine, fluoxetine, trazodone, quetiapine and olanzapine. The registered alert management data and medication dispensing histories were analysed to find potential determinants of persistent drug therapy changes. Ten pharmacists were interviewed about the barriers and facilitators for implementing drug therapy changes based on CDSS alerts. An inductive thematic analysis of the transcripts was performed. RESULTS: The pharmacists recorded the management of 1810 of the 2589 generated alerts, and 158 (8.7%) alerts were associated with a persistent drug therapy change. A logistic regression analysis found that the drug triggering the alert and the type of prescription [first dispensing vs. repeat; odds ratio 2.1 (95% confidence interval 1.4-3.2)] were significantly associated with persistent drug therapy changes. No association was found between persistent changes and age, sex, number of medicines in use, or recent clinical medication review. Analysis of the interviews revealed nine barriers and facilitators associated with drug therapy change. CONCLUSION: When community pharmacists implemented CDSS alerts to reduce inappropriate drug use in older patients, they registered a persistent drug therapy change in 8.7% of the cases. Alerts triggered by a first prescription were two times more likely to be associated with a persistent drug therapy change than alerts triggered by repeat prescriptions. This study found that clinical rules can be used to detect inappropriate drug use in older patients and that drug therapy can change based on the alerts. This suggests that CDSS alerts are a useful tool for implementing guidelines on PIM in older patients in daily practice.

Effects of Pharmacogenetic Screening for CYP2D6 Among Elderly Starting Therapy With Nortriptyline or Venlafaxine: A Pragmatic Randomized Controlled Trial (CYSCE Trial).

PURPOSE/BACKGROUND: The duration of untreated depression is a predictor for poor future prognosis, making rapid dose finding essential. Genetic variation of the CYP2D6 isoenzyme can influence the optimal dosage needed for individual patients. The aim of this study was to determine the effectiveness of CYP2D6 pharmacogenetic screening to accelerate drug dosing in older patients with depression initiating nortriptyline or venlafaxine. METHODS/PROCEDURES: In this randomized controlled trial, patients were randomly allocated to one of the study arms. In the intervention arm (DG-I), the specific genotype accompanied by a standardized dosing recommendation based on the patients' genotype and the prescribed drug was directly communicated to the physician of the participant. In both the deviating genotype control arm (DG-C) and the nonrandomized control arm, the physician of the participants was not informed about the genotype and the associated dosing advise. The primary outcome was the time needed to reach adequate drug levels: (1) blood levels within the therapeutic range and (2) no dose adjustments within the previous 3 weeks. FINDINGS/RESULTS: No significant difference was observed in mean time to reach adequate dose or time to adequate dose between DG-I and DG-C. Compared with the nonrandomized control arm group, adequate drug levels were reached significantly faster in the DG-I group (log-rank test; P = 0.004), and there was a similar nonsignificant trend for the DG-C group (log-rank test; P = 0.087). IMPLICATIONS/CONCLUSIONS: The results of this study do not support pharmacogenetic CYP2D6 screening to accelerate dose adjustment for nortriptyline and venlafaxine in older patients with depression.

International core outcome set for clinical trials of medication review in multi-morbid older patients with polypharmacy.

BACKGROUND: Comparisons of clinical trial findings in systematic reviews can be hindered by the heterogeneity of the outcomes reported. Moreover, the outcomes that matter most to patients might be underreported. A core outcome set can address these issues, as it defines a minimum set of outcomes that should be reported in all clinical trials in a particular area of research. The objective in this study was to develop a core outcome set for clinical trials of medication review in multi-morbid older patients with polypharmacy. METHODS: Firstly, eligible outcomes were identified through a systematic review of trials of medication review in older patients (≥65 years) and interviews with 15 older patients. Secondly, an international three-round Delphi survey in four countries involving patients, healthcare professionals, and experts was conducted to validate outcomes to be included in the core outcome set. Consensus meetings were conducted to validate the results. RESULTS: Of the 164 participants invited to take part in the Delphi survey, 150 completed Round 1, including 55 patients or family caregivers, 55 healthcare professionals, and 40 experts. A total of 129 participants completed all three rounds. Sixty-four eligible outcomes were extracted from 47 articles, 32 clinical trial protocols, and patient interviews. Thirty outcomes were removed and one added after Round 1, 18 outcomes were removed after Round 2, and seven after Round 3. Results were discussed during consensus meetings. Consensus was reached on seven outcomes, which constitute the core outcome set: drug-related hospital admissions; drug overuse; drug underuse; potentially inappropriate medications; clinically significant drug-drug interactions; health-related quality of life; pain relief. CONCLUSIONS: We developed a core outcome set of seven outcomes which should be used in future trials of medication review in multi-morbid older patients with polypharmacy.

The Systematic Tool to Reduce Inappropriate Prescribing (STRIP): Combining implicit and explicit prescribing tools to improve appropriate prescribing.

Inappropriate prescribing is a major health care issue, especially regarding older patients on polypharmacy. Multiple implicit and explicit prescribing tools have been developed to improve prescribing, but these have hardly ever been used in combination. The Systematic Tool to Reduce Inappropriate Prescribing (STRIP) combines implicit prescribing tools with the explicit Screening Tool to Alert physicians to the Right Treatment and Screening Tool of Older People's potentially inappropriate Prescriptions criteria and has shared decision-making with the patient as a critical step. This article describes the STRIP and its ability to identify potentially inappropriate prescribing. The STRIP improved general practitioners' and final-year medical students' medication review skills. The Web-application STRIP Assistant was developed to enable health care providers to use the STRIP in daily practice and will be incorporated in clinical decision support systems. It is currently being used in the European Optimizing thERapy to prevent Avoidable hospital admissions in the Multimorbid elderly (OPERAM) project, a multicentre randomized controlled trial involving patients aged 75 years and older using multiple medications for multiple medical conditions. In conclusion, the STRIP helps health care providers to systematically identify potentially inappropriate prescriptions and medication-related problems and to change the patient's medication regimen in accordance with the patient's needs and wishes. This article describes the STRIP and the available evidence so far. The OPERAM study is investigating the effect of STRIP use on clinical and economic outcomes.

Efficiency of Clinical Decision Support Systems Improves with Experience.

Efficiency, or the resources spent while performing a specific task, is widely regarded as one the determinants of usability. In this study, the authors hypothesize that having a group of users perform a similar task over a prolonged period of time will lead to improvements in efficiency of that task. This study was performed in the domain of decision-supported medication reviews. Data was gathered during a randomized controlled trial. Three expert teams consisting of an independent physician and an independent pharmacist conducted 150 computerized medication reviews on patients in 13 general practices located in Amsterdam, the Netherlands. Results were analyzed with a linear mixed model. A fixed effects test on the linear mixed model showed a significant difference in the time required to conduct medication reviews over time; F(31.145) = 14.043, p < .001. The average time in minutes required to conduct medication reviews up to the first quartile was M = 20.42 (SD = 9.00), while the time from the third quartile up was M = 9.81 (SD = 6.13). This leads the authors to conclude that the amount of time users needed to perform similar tasks decreased significantly as they gained experience over time.

[Appropriate choice of drugs in older patients]. / De juiste keuze van geneesmiddelen bij ouderen.

Older patients use many drugs, while there is hardly any information about the effect and safety of these in elderly patients. It appears that only 56%, and 20% of the information required by the European Medicines Agency (EMA) concerning use of medication in the elderly is stated in the patient information leaflet and in the Dutch Pharmacotherapeutic Compass, respectively. The Expertise Centre PHarmacotherapy in Old Persons (Ephor) gathered all available information about drug prescribing in older patients for a number of drug groups from national and international literature, and provided prescribing advice. This information will be made available to users of the Dutch Pharmacotherapeutic Compass, for quick accessibility.

Adherence with Dosing Guideline in Patients with Impaired Renal Function at Hospital Discharge.

OBJECTIVES: To determine the prevalence, determinants, and potential clinical relevance of adherence with the Dutch dosing guideline in patients with impaired renal function at hospital discharge. DESIGN: Retrospective cohort study between January 2007 and July 2011. SETTING: Academic teaching hospital in the Netherlands. SUBJECTS: Patients with an estimated glomerular filtration rate (eGFR) between 10-50 ml/min/1.73 m(2) at discharge and prescribed one or more medicines of which the dose is renal function dependent. MAIN OUTCOME MEASURES: The prevalence of adherence with the Dutch renal dosing guideline was investigated, and the influence of possible determinants, such as reporting the eGFR and severity of renal impairment (severe: eGFR<30 and moderate: eGFR 30-50 ml/min/1.73 m(2)). Furthermore, the potential clinical relevance of non-adherence was assessed. RESULTS: 1327 patients were included, mean age 67 years, mean eGFR 38 ml/min/1.73 m(2). Adherence with the guideline was present in 53.9% (n=715) of patients. Reporting the eGFR, which was incorporated since April 2009, resulted in more adherence with the guideline: 50.7% vs. 57.0%, RR 1.12 (95% CI 1.02-1.25). Adherence was less in patients with severe renal impairment (46.0%), compared to patients with moderate renal impairment (58.1%, RR 0.79; 95% CI 0.70-0.89). 71.4% of the cases of non-adherence had the potential to cause moderate to severe harm. CONCLUSION: Required dosage adjustments in case of impaired renal function are often not performed at hospital discharge, which may cause harm to the majority of patients. Reporting the eGFR can be a small and simple first step to improve adherence with dosing guidelines.

Computerized Decision Support Improves Medication Review Effectiveness: An Experiment Evaluating the STRIP Assistant's Usability.

BACKGROUND: Polypharmacy poses threats to patients' health. The Systematic Tool to Reduce Inappropriate Prescribing (STRIP) is a drug optimization process for conducting medication reviews in primary care. To effectively and efficiently incorporate this method into daily practice, the STRIP Assistant--a decision support system that aims to assist physicians with the pharmacotherapeutic analysis of patients' medical records--has been developed. It generates context-specific advice based on clinical guidelines. OBJECTIVE: The aim of this study was to validate the STRIP Assistant's usability as a tool for physicians to optimize medical records for polypharmacy patients. METHODS: In an online experiment, 42 physicians were asked to optimize medical records for two comparable polypharmacy patients, one in their usual manner and one using the STRIP Assistant. Changes in effectiveness were measured by comparing respondents' optimized medicine prescriptions with medication prepared by an expert panel of two geriatrician-pharmacologists. Efficiency was operationalized by recording the time the respondents took to optimize the two cases. User satisfaction was measured with the System Usability Scale (SUS). Independent and paired t tests were used for analysis. RESULTS: Medication optimization significantly improved with the STRIP Assistant. Appropriate decisions increased from 58% without the STRIP Assistant to 76% with it (p < 0.0001). Inappropriate decisions decreased from 42% without the STRIP Assistant to 24% with it (p < 0.0001). Participants spent significantly more time optimizing medication with the STRIP Assistant (24 min) than without it (13 min; p < 0.0001). They assigned it a below-average SUS score of 63.25. CONCLUSION: The STRIP Assistant improves the effectiveness of medication reviews for polypharmacy patients.

[Detecting inappropriate medication in older people: the revised STOPP/START criteria]. / Onjuist geneesmiddelgebruik bij ouderen opsporen. De herziene STOPP- en START-criteria.

The use of potentially inappropriate medications (PIMs) by older people and potential prescribing omissions (PPOs) represent a serious problem. It increases the risk of adverse drug reactions (ADRs), however it is susceptible to influence in a substantial number of cases. Use of the STOPP/START criteria developed in Ireland to optimise pharmacotherapy of older people reduces the number of ADRs and medication errors. Licensing of new drugs, the increased number of potentially inappropriate drugs, and the availability of new literature were grounds for an update of the first version of the STOPP/START criteria which was published in 2008. In order to develop a screening tool with a broader application, a consensus panel of experts in the field of pharmacotherapy of older people was selected from 14 European countries for the second version of the STOPP/START criteria, including two from the Netherlands. The translation of the second version of the STOPP/START criteria has been adapted to the situation in the Netherlands, partly by omitting drugs that are not licensed in the Netherlands.

Pharmacists' and general practitioners' pharmacology knowledge and pharmacotherapy skills.

Understanding differences in the pharmacology knowledge and pharmacotherapy skills of pharmacists and physicians is vital to optimizing interprofessional collaboration and education. This study investigated these differences and the potential influence of work experience. The pharmacology knowledge and pharmacotherapy skills of pharmacists, general practitioners (GPs), and trainees were compared, using a written assessment; 294 participants were included. Overall scores (mean ± SD) ranged from 69.3% ± 6.5% to 76.5% ± 9.5% for basic knowledge, 70.3% ± 10.8% to 79.7% ± 8.4% for applied knowledge, and 66.3% ± 21.1% to 84.7% ± 20.7% for pharmacotherapy skills (analysis of variance all P < .05). The pharmacists had the highest scores for all domains (P < .05), with the exception of pharmacist trainees, who had comparable scores for basic knowledge and pharmacotherapy skills (both P > .05). The GPs scored the lowest for pharmacotherapy skills (P < .05). More work experience was associated with better knowledge of applied pharmacology among pharmacists (by 2% per 10 work-years), but with poorer pharmacotherapy skills among pharmacists and GPs (by 3% and 4% per 10 work-years, respectively). In conclusion, pharmacists and GPs differ in their knowledge and skills, and these differences become more pronounced with more work experience. In general, pharmacists outperform pharmacist trainees, whereas GP trainees outperform GPs. These differences could be important for interdisciplinary collaboration and education.

Education on prescribing for older patients in the Netherlands: a curriculum mapping.

PURPOSE: Pharmacology and pharmacotherapy education is being increasingly integrated in medical curricula, which might lead to a specific loss of knowledge in these subjects. This, in turn, could lead to harmful prescribing errors, especially in vulnerable older patients. METHODS: Teachers who coordinated education in Dutch medical schools completed a structured interview on (geriatric) pharmacology and pharmacotherapy education. A list of core learning goals was developed. Pharmacology and pharmacotherapy education in general was compared to geriatric pharmacology and pharmacotherapy education. RESULTS: All Dutch medical schools participated. Contact hours for education in pharmacology and pharmacotherapy ranged from 39 to 107 h; ECTSs (representing 28 study hours) ranged from 0 to 3. The various curricula covered, on average, 79% of all learning goals for these subjects: knowledge 85%, skills 76%, and attitudes 66%; the curricula also covered specific geriatric goals: knowledge 87% and skills 65%. All geriatric learning goals were met if a geriatrician was among the coordinators. Half (4 of 8) of the medical schools lacked appropriate assessment procedures. Evaluation was mostly based on students' opinions. Teachers rated students as being moderately well prepared for daily practice. CONCLUSIONS: There are large differences in the quantity and quality of (geriatric) pharmacology and pharmacotherapy education in Dutch medical schools. In general, more time should be devoted to skills and attitude, and the assessment procedures should be optimized with high priority. Other curricula with a problem-based approach might benefit from the points of improvement described in this article.

Effects and cost-effectiveness of pharmacogenetic screening for CYP2D6 among older adults starting therapy with nortriptyline or venlafaxine: study protocol for a pragmatic randomized controlled trial (CYSCEtrial).

BACKGROUND: Nortriptyline and venlafaxine are commonly used antidepressants for treatment of depression in older patients. Both drugs are metabolized by the polymorphic cytochrome P450-2D6 (CYP2D6) enzyme and guidelines for dose adaptations based on the CYP2D6 genotype have been developed. The CYP2D6 Screening Among Elderly (CYSCE) trial is designed to address the potential health and economic value of genotyping for CYP2D6 in optimizing dose-finding of nortriptyline and venlafaxine. METHODS/DESIGN: In a pragmatic randomized controlled trial, patients diagnosed with a major depressive disorder according to the DSM-IV and aged 60 years or older will be recruited from psychiatric centers across the Netherlands. After CYP2D6 genotyping determined in peripheral blood obtained by finger-prick, patients will be grouped into poor, intermediate, extensive, or ultrarapid metabolizers. Patients with deviant genotype (that is poor, intermediate or ultrarapid genotype) will be randomly allocated to an intervention group in which the genotype and dosing advice is communicated to the treating physician, or to a control group in which patients receive care as usual. Additionally, an external reference group of patients with the extensive metabolizer genotype is included. Primary outcome in all groups is time needed to obtain an adequate blood level of the antidepressant drug. Secondary outcomes include adverse drug reactions measured by a shortened Antidepressant Side-Effects Checklist (ASEC), and cost-effectiveness of the screening. DISCUSSION: Results of this trial will guide policy-making with regard to pharmacogenetic screening prior to treatment with nortriptyline or venlafaxine among older patients with depression. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01778907 ; registration date: 22 January 2013.

Implementation of the WHO-6-step method in the medical curriculum to improve pharmacology knowledge and pharmacotherapy skills.

AIM: The only validated tool for pharmacotherapy education for medical students is the 6-step method of the World Health Organization. It has proven effective in experimental studies with short term interventions. The generalizability of this effect after implementation in a contextual-rich medical curriculum was investigated. METHODS: The pharmacology knowledge and pharmacotherapy skills of cohorts of students, from years before, during and after implementation of a WHO-6-step-based integrated learning programme were tested using a standardized assessment containing 50 items covering knowledge of basic (n = 25) and clinical (n = 24) pharmacology, and pharmacotherapy skills (n = 1 open question). All scores are expressed as a percentage of the maximum score possible per (sub)domain. RESULTS: In total, 1652 students were included between September 2010 and July 2014 (participation rate 89%). The WHO-6-step-based learning programme improved students' knowledge of basic pharmacology (mean score ± SD, 60.6 ± 10.5% vs. 63.4 ± 10.9%, P < 0.01) and clinical or applied pharmacology (63.7 ± 10.4% vs. 67.4 ± 10.3%, P < 0.01), and improved their pharmacotherapy skills (68.8 ± 26.1% vs. 74.6% ± 22.9%, P 0.02). Moreover, satisfaction with education increased (5.7 ± 1.3 vs. 6.3 ± 1.0 on a 10-point scale, P < 0.01) and as did students' confidence in daily practice (from -0.81 ± 0.72 to -0.50 ± 0.79 on a -2 to +2 scale, P < 0.01). CONCLUSIONS: The WHO-6-step method was successfully implemented in a medical curriculum. In this observational study, the integrated learning programme had positive effects on students' knowledge of basic and applied pharmacology, improved their pharmacotherapy skills, and increased satisfaction with education and self-confidence in prescribing. Whether this training method leads to better patient care remains to be established.

[Need for improvement in education on appropriate prescribing in elderly patients]. / Onderwijs in het voorschrijven aan ouderen moet beter.

Prescribing errors can cause great harm to patients. In the Netherlands, it is estimated that 7000 preventable medication-related hospitals admissions occur annually, caused in many cases by prescribing errors. Elderly patients are at greatest risk, since this patient demographic is most likely to be prescribed multiple medications. Robust education on appropriate prescribing is essential for all clinicians with the authority to prescribe. Currently, some issues still require improvement in the Netherlands: a) education continues to focus heavily on basic pharmacology knowledge instead of patient related pharmacotherapy skills, b) an appropriate assessment procedure on pharmacotherapy knowledge and skills is often lacking, c) there is no mandatory requirement for physicians to maintain their knowledge and skills in the field of pharmacotherapy during their working career. In this article we discuss means to improve this situation, with the overall aim to ensure that all vulnerable elderly patients are in safe hands with each physician.

Practical problems with medication use that older people experience: a qualitative study.

OBJECTIVES: To identify the practical problems that older people experience with the daily use of their medicines and their management strategies to address these problems and to determine the potential clinical relevance thereof. DESIGN: Qualitative study with semistructured face-to-face interviews. SETTING: A community pharmacy and a geriatric outpatient ward. PARTICIPANTS: Community-dwelling people aged 70 and older (N = 59). MEASUREMENTS: Participants were interviewed at home. Two researchers coded the reported problems and management strategies independently according to a coding scheme. An expert panel classified the potential clinical relevance of every identified practical problem and associated management strategy using a 3-point scale. RESULTS: Two hundred eleven practical problems and 184 management strategies were identified. Ninety-five percent of the participants experienced one or more practical problems with the use of their medicines: problems reading and understanding the instructions for use, handling the outer packaging, handling the immediate packaging, completing preparation before use, and taking the medicine. For 10 participants, at least one of their problems, in combination with the applied management strategy, had potential clinical consequences and 11 cases (5% of the problems) had the potential to cause moderate or severe clinical deterioration. CONCLUSION: Older people experience a number of practical problems using their medicines, and their strategies to manage these problems are sometimes suboptimal. These problems can lead to incorrect medication use with clinically relevant consequences. The findings pose a challenge for healthcare professionals, drug developers, and regulators to diminish these problems.

Participation of older people in preauthorization trials of recently approved medicines.

OBJECTIVES: To investigate the inclusion of older people in clinical trials of recently authorized medicines, evaluating adherence to the 20-year-old International Conference of Harmonisation (ICH) guideline on geriatrics (E7). DESIGN: Observational. SETTING: European public assessment reports, published clinical trials, World Health Organization International Clinical Trials Registry Platform. PARTICIPANTS: Individuals aged 65 and older and 75 and older. MEASUREMENTS: Number and proportion of randomized participants and all exclusion criteria of studies involving diseases characteristically associated with aging (venous thromboembolism, osteoporosis, atrial fibrillation) and diseases not unique to older adults (type 2 diabetes mellitus, depression, bipolar disorder, epilepsy). RESULTS: In 114 Phase II and III trials of 12 medicines, 43.1% of participants were aged 65 and older, and 16.1% were aged 75 and older. In trials involving diseases characteristically associated with ageing, 57% were aged 65 and older; 22% were aged 75 and older. In trials involving diseases not unique to old age, 9% were aged 65 and older, and 1% were aged 75 and older. Upper age limits were applied in 30.7% of the trials; the frequency did not differ between larger (sample size ≥ 500) and smaller trials (P = .36), although it was significantly lower in trials involving diseases characteristically associated with aging (18.0%) than in trials of diseases not unique to old age (45.3%; P = .002). Age-sensitive exclusion criteria, based on comorbidity (75.4%), concomitant medication (71.9%), and other criteria correlated with age (60.5%) were applied more frequently in larger trials (P < .02). CONCLUSION: Studies of diseases not uniquely associated with old age included an unacceptably low proportion of older people, contrary to the recommendations of the ICH E7 guideline. Although the proportion of older participants in trials of diseases characteristically associated with aging was appropriate for certain medicines, the use of age-sensitive exclusion criteria limits the representativeness of the trial population for daily practice.

Structured pharmaceutical analysis of the Systematic Tool to Reduce Inappropriate Prescribing is an effective method for final-year medical students to improve polypharmacy skills: a randomized controlled trial.

Medical students may not be adequately trained to prescribe appropriately to older adults with polypharmacy. This study addressed how to teach students to minimize inappropriate polypharmacy. Final-year medical students (N = 106) from two Dutch schools of medicine participated in this randomized controlled trial with a pre/posttest design. The Systematic Tool to Reduce Inappropriate Prescribing (STRIP) was used as the intervention. This medication review tool consists of five steps and is part of the Dutch multidisciplinary guideline on polypharmacy. Step two is a structured pharmaceutical analysis of drug use, assessed using six questions regarding undertreatment, ineffective treatment, overtreatment, potential adverse effects, contraindications or interactions, and dose adjustments. It is used in combination with the Screening Tool to Alert doctors to Right Treatment and the Screening Tool of Older Person's Prescriptions checklists. Students were asked to optimize the medication lists of real people, making use, or not, of the STRIP. The number of correct or potentially harmful decisions that the students made when revising the lists was determined by comparison with expert consensus. Students who used the STRIP had better scores than control students; they made more correct decisions (9.3 vs 7.0, 34%; P < .001, correlation coefficient (r) = 0.365) and fewer potentially harmful decisions (3.9 vs 5.6, -30%; P < .001, r = 0.386). E-learning did not have a different effect from that of non-E-learning methods. Students were satisfied with the method. The STRIP method is effective in helping final-year medical students improve their prescribing skills.