Outcome prioritisation tool for medication review in older patients with multimorbidity: a pilot study in general practice.

BACKGROUND: Several methods have been developed to conduct and support medication reviews in older persons with multimorbidity. Assessing the patient's priorities for achieving specific health outcomes can guide the medication review process. Little is known about the impact of conducting such assessments. AIM: This pilot study aimed to determine proposed and observed medication changes when using an outcome prioritisation tool (OPT) during a medication review in general practice. DESIGN AND SETTING: Participants were older patients with multimorbidity (aged ≥69 years) with polypharmacy (five or more chronic medications) from the practices of 14 GPs. METHOD: Patients were asked to prioritise four universal health outcomes - remaining alive, maintaining independence, reducing pain, and reducing other symptoms - using an OPT. GPs used this prioritisation to review the medication and to propose and discuss medication changes with the patient. The outcomes included the proposed medication change as documented by the GP, and the observed medication change in the electronic health record at follow-up. Descriptive analyses were conducted to determine medication changes according to the prioritised health outcomes. RESULTS: A total of 59 patients using 486 medications prioritised the four health outcomes. GPs proposed 34 changes of medication, mainly stopping, for 20 patients. At follow-up, 14 medication changes were observed for 10 patients. The stopping of medication (mostly preventive) was particularly observed in patients who prioritised 'reducing other symptoms' as most important. CONCLUSION: Using an OPT leads mainly to the stopping of medication. Medication changes appeared to be easiest for patients who prioritised 'reducing other symptoms' as most important.

Eliciting Preferences of Multimorbid Elderly Adults in Family Practice Using an Outcome Prioritization Tool.

OBJECTIVES: To explore an outcome prioritization tool (OPT) in eliciting individuals' preferred health outcomes (remaining alive, maintaining independence, reducing pain, reducing other symptoms) in the context of medication review in family practice. DESIGN: Cross-sectional pilot study with mixed-methods design. SETTING: Family practice. PARTICIPANTS: Multimorbid individuals (N = 60; aged ≥69) with polypharmacy (≥5 chronic medications) derived from the practice lists of a purposive sample of 13 family physicians (FPs). MEASUREMENTS: Participants were asked to prioritize each health outcome according the trade-off principle, and FPs used this prioritization for medication review. The acceptability and practicality were measured using a questionnaire for FPs and participants and semistructured interviews with FPs. RESULTS: Ninety-two percent of participants found the OPT understandable, and 55% could easily prioritize between health outcomes. Working with the OPT (mean duration 31 minutes) was a new approach for FPs, but they became more adept at using it. For FPs, the OPT provides better understanding of their patients. Participants and FPs thought that there should be a specific reason to discuss preferences, such as (expected) decline in health status. CONCLUSION: The OPT appears to be promising in eliciting patient preferences but is not suitable for routine medication review at present. Further optimization before actual use is needed (e.g., knowledge in which clinical situations the OPT is useful). More information is needed on how individuals and their families perceive the tool.

Using primary care electronic health record data for comparative effectiveness research: experience of data quality assessment and preprocessing in The Netherlands.

AIM: Details of data quality and how quality issues were solved have not been reported in published comparative effectiveness studies using electronic health record data. METHODS: We developed a conceptual framework of data quality assessment and preprocessing and apply it to a study comparing angiotensin-converting enzyme inhibitors with angiotensin receptor blockerss on renal function decline in diabetes patients. RESULTS: The framework establishes a line of thought to identify and act on data issues. The core concept is to evaluate whether data are fit-for-use for research tasks. Possible quality problems are listed through specific signal detections, and verified whether they are true problems. Optimal solutions are selected for the identified problems. CONCLUSION: This framework can be used in observational studies to improve validity of results.

Economic evaluations of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers in type 2 diabetic nephropathy: a systematic review.

BACKGROUND: Structured comparison of pharmacoeconomic analyses for ACEIs and ARBs in patients with type 2 diabetic nephropathy is still lacking. This review aims to systematically review the cost-effectiveness of both ACEIs and ARBs in type 2 diabetic patients with nephropathy. METHODS: A systematic literature search was performed in MEDLINE and EMBASE for the period from November 1, 1999 to Oct 31, 2011. Two reviewers independently assessed the quality of the articles included and extracted data. All cost-effectiveness results were converted to 2011 Euros. RESULTS: Up to October 2011, 434 articles were identified. After full-text checking and quality assessment, 30 articles were finally included in this review involving 39 study settings. All 6 ACEIs studies were literature-based evaluations which synthesized data from different sources. Other 33 studies were directed at ARBs and were designed based on specific trials. The Markov model was the most common decision analytic method used in the evaluations. From the cost-effectiveness results, 37 out of 39 studies indicated either ACEIs or ARBs were cost-saving comparing with placebo/conventional treatment, such as amlodipine. A lack of evidence was assessed for valid direct comparison of cost-effectiveness between ACEIs and ARBs. CONCLUSION: There is a lack of direct comparisons of ACEIs and ARBs in existing economic evaluations. Considering the current evidence, both ACEIs and ARBs are likely cost-saving comparing with conventional therapy, excluding such RAAS inhibitors.

Do treatment quality indicators predict cardiovascular outcomes in patients with diabetes?

BACKGROUND: Landmark clinical trials have led to optimal treatment recommendations for patients with diabetes. Whether optimal treatment is actually delivered in practice is even more important than the efficacy of the drugs tested in trials. To this end, treatment quality indicators have been developed and tested against intermediate outcomes. No studies have tested whether these treatment quality indicators also predict hard patient outcomes. METHODS: A cohort study was conducted using data collected from >10.000 diabetes patients in the Groningen Initiative to Analyze Type 2 Treatment (GIANTT) database and Dutch Hospital Data register. Included quality indicators measured glucose-, lipid-, blood pressure- and albuminuria-lowering treatment status and treatment intensification. Hard patient outcome was the composite of cardiovascular events and all-cause death. Associations were tested using Cox regression adjusting for confounding, reporting hazard ratios (HR) with 95% confidence intervals. RESULTS: Lipid and albuminuria treatment status, but not blood pressure lowering treatment status, were associated with the composite outcome (HR = 0.77, 0.67-0.88; HR = 0.75, 0.59-0.94). Glucose lowering treatment status was associated with the composite outcome only in patients with an elevated HbA1c level (HR = 0.72, 0.56-0.93). Treatment intensification with glucose-lowering but not with lipid-, blood pressure- and albuminuria-lowering drugs was associated with the outcome (HR = 0.73, 0.60-0.89). CONCLUSION: Treatment quality indicators measuring lipid- and albuminuria-lowering treatment status are valid quality measures, since they predict a lower risk of cardiovascular events and mortality in patients with diabetes. The quality indicators for glucose-lowering treatment should only be used for restricted populations with elevated HbA1c levels. Intriguingly, the tested indicators for blood pressure-lowering treatment did not predict patient outcomes. These results question whether all treatment indicators are valid measures to judge quality of health care and its economics.

A pilot qualitative study to explore stakeholder opinions regarding prescribing quality indicators.

BACKGROUND: Information on prescribing quality of diabetes care is required by health care providers, insurance companies, policy makers, and the public. Knowledge regarding the opinions and preferences of all involved parties regarding prescribing quality information is important for effective use of prescribing quality indicators. METHODS: Between June and December 2009 we conducted semi structured interviews with 16 key-informants representing eight different organizations in the Netherlands involved in healthcare quality measurement and improvement. The interview guide included topics on participants' opinions and preferences regarding existing types of prescribing quality indicators in relation to their aim of using quality information. Content analysis methods were used to process the resulting transcripts following the framework of predetermined themes. RESULTS: Findings from this qualitative study of stakeholder preferences showed that indicators focusing on undertreatment are found important by all participants. Furthermore, health care providers and policy makers valued prescribing safety indicators, insurance companies prioritized indicators focusing on prescribing costs, and patients' organization representatives valued indicators focusing on interpersonal side of prescribing. Representatives of all stakeholders preferred positive formulation of the indicators to motivate health care providers to participate in health improvement programs. A composite score was found to be most useful by all participants as a starting point of prescribing quality assessment. Lack of information on reasons for deviating from guidelines recommendations appeared to be the most important barrier for using prescribing quality indicators. According to the health care providers, there are many legitimate reasons for not prescribing the recommended treatment and these reasons are not always taken into account by external evaluators. The latter may cause mistrust of health care providers towards external stakeholders and limit the use of PQI in external quality improvement programs. CONCLUSION: Prescribing quality indicators are considered to be an important tool for assessing quality of provided diabetes care by all participants, although the preferences for specific types of indicators may differ by stakeholder depending on their user aim. Introduction of information systems to register the reasons for deviating from the recommended drug treatment may contribute to a more widespread use of PQI for assessment of provided health care quality to diabetic patents. This study identified the potential preferences regarding quality indicators for diabetes care, and this could be used for development of questionnaires to conduct a survey among a larger group of participants.

Development of a minimal set of prescribing quality indicators for diabetes management on a general practice level.

OBJECTIVE: To identify the relevant prescribing quality domains of type 2 diabetes mellitus care as a basis for the selection of a minimal set of prescribing quality indicators from a set of previously validated indicators. METHODS: We used the principal factor analysis to identify the underlying dimensions or domains of prescribing quality for 76 general practitioners participating to the Groningen Initiative to Analyse Type 2 Diabetes Treatment project in the Netherlands. From a set of 10 prescribing quality indicators covering various aspects of cardiovascular and metabolic management, we selected a subset of indicators with the highest loading within each identified domain. Next, we evaluated the effect of using this subset on the quintile ranking of practices on their prescribing quality scores. RESULTS: We identified five prescribing quality domains in our data set: two assessing initiation of pharmacotherapy for different risk factors in diabetic patients, two on stepwise intensification of treatment, and one on treatment of patients with cardiovascular disease. A composite score comprising the indicators selected from each of the domains showed good agreement with the composite score comprising all indicators with 82% of general practitioners either not changing their position or shifting their ranking by only one quintile. CONCLUSIONS: We showed that a minimal set of prescribing quality indicators for type 2 diabetes mellitus care should not just focus on the management of different clinical risk factors but also reflect different steps of treatment intensification. The results of our study are relevant for stakeholders when selecting quality indicators to assess the quality of prescribing in diabetic patients.

Effect of safety issues with HIV drugs on the approval process of other drugs in the same class: an analysis of European Public Assessment Reports.

BACKGROUND: Knowledge on the safety of new medicines is limited at the time of market entry. Nearly half of all drugs used to treat HIV registered in the EU required ≥1 Direct Healthcare Professional Communication (DHPC) in the past 10 years for safety issues identified post-approval. OBJECTIVE: The aim was to evaluate the extent to which regulators and industry have addressed the risk of safety issues for HIV drugs based on prior experience with other drugs in the same class and whether doing so impacts development time of these drugs. METHODS: HIV drugs receiving ≥1 DHPC in the Netherlands between January 1999 and December 2008 were identified. Each drug with a DHPC ('index' drug) was paired with subsequently approved HIV drug(s) in the same class (Anatomical Therapeutic Chemical [ATC] 4th level) ['follow-on' drugs]. Characteristics of safety issues were extracted from the DHPCs of the 'index' drugs. European Public Assessment Reports (EPARs) were reviewed regarding whether the safety issues had been considered during development and approval. Consideration of previously identified safety issues in 'follow-on' drug applications was assessed regarding attention paid to adverse drug reaction (ADR) symptoms in pre-marketing studies, Summary of Product Characteristics (SmPC) and postmarketing commitments, and whether size of the safety population was in accordance with Regulatory guidelines. 'Index' drugs were also paired with drugs in the same class already on the market ('older' drugs). For 'older' drugs, we identified whether the safety issue led to appropriate changes in the current SmPC (January 2011) compared with the SmPC at the time of marketing authorization. Clinical development time was assessed using time from first patent application to market authorization as proxy, and comparison was made between 'index' and 'follow-on' drugs. RESULTS: For 9 (43%) of the 21 centrally authorized HIV drugs, 11 serious safety issues that required a DHPC were identified. Two drugs were excluded from our analysis (DHPCs related to contamination/medication error). Six 'index' drugs were paired, each with one to six 'follow-on' drugs. Three concerned drug-drug interactions (DDIs); the other three were intracranial haemorrhage, neuromuscular weakness and severe skin/hepatic reactions. All but one 'follow-on' drug had information in the EPAR on that specific ADR (i.e. attention was paid to the ADR). The DDIs were addressed in pre-marketing studies and/or the SmPC. Two of the other ADRs were addressed by postmarketing surveillance commitments; intracranial haemorrhage was not addressed. Three safety issues for two 'index' drugs could not be paired with a 'follow-on' drug as no drug in the same class was approved after the corresponding DHPCs were issued. Five of the nine safety issues were added to at least one of the current SmPCs for the 'older' drugs already on the market at the time of DHPC issue. Two safety issues were already in the SmPC of the 'older' drugs at time of market approval and two were not introduced into the SmPC of 'older' drugs. Population size to assess short-term safety complied with the guidelines for four 'index', seven 'follow-on' and three 'older' drugs; population size to assess long-term safety complied for one, three and two drugs, respectively. For five drugs, EPARs did not provide adequate information on population size. No statistically significant difference in development time between 'index' and 'follow-on' drugs was found. CONCLUSION: Generally, safety issues were taken into account in the approval process of other drugs in the class. The approaches were different and determined by the nature of the ADR. Taking safety issues into account in the approval process did not seem to impact on the time taken to perform the pre-approval clinical programme.

Soft regulations in pharmaceutical policy making: an overview of current approaches and their consequences.

It is a challenge to improve public health within limited resources. Pharmaceutical policy making is a greater challenge due to conflicting interests between key stakeholder groups. This paper reviews current and future strategies to help improve the quality and efficiency of care, with special emphasis on demand-side controls for pharmaceutical prescribing. A large number of different educational, organizational, financial and regulatory strategies have been applied in pharmaceutical policy making. However, the effectiveness of most strategies has not been thoroughly evaluated and there is evidence that the behaviour of healthcare professionals is difficult to influence with traditional methods. During the last decades, new modes of governing and new governing constellations have also appeared in healthcare. However, relationships between those who regulate and those regulated are often unclear. New approaches have recently been introduced, including extensive dissemination strategies for guidelines and extensive quality assessment programmes where physicians' performances are measured against agreed standards or against each other. The main components of these 'soft regulations' are standardization, monitoring and agenda setting. However, the impact of these new modes on health provision and overall costs is often unknown, and the increased focus on monitoring may result in a higher conformity and uniformity that may not always benefit all key stakeholders. Alongside this, a substantial growth of auditing associations controlling a diminishing minority of people actually performing the tasks may be costly and counter-productive. As a result, new effective strategies are urgently needed to help maintain comprehensive healthcare without prohibitively raising taxes or insurance premiums. This is especially important where countries are faced with extreme financial problems. Healthcare researchers may benefit from researching other areas of society. However, any potential strategies initiated must be adequately researched, debated and evaluated to enhance implementation. We hope this opinion paper is the first step in the process to develop and implement new demand-side initiatives building on existing 'soft regulations'.

Reliability of the assessment of preventable adverse drug events in daily clinical practice.

PURPOSE: To determine the reliability of the assessment of preventable adverse drug events (ADEs) in daily practice and to explore the impact of the assessors' professional background and the case characteristics on reliability. METHODS: We used a combination of the simplified Yale algorithm and the National Coordinating Council for Medication Error Reporting and Prevention (NCC MERP) scheme to assess on the one hand the causal relationship between medication errors (MEs) and adverse events in hospitalised patients and on the other hand the severity of the clinical consequence of MEs. Five pharmacists and five physicians applied this algorithm to 30 potential MEs. After individual assessment, the pharmacists reached consensus and so did the physicians. Outcome was both MEs' severity (ordinal scale, NCC MERP categories A-I) and the occurrence of preventable harm (binary outcome, NCC MERP categories A-D vs. E-I). Kappa statistics was used to assess agreement. RESULTS: The overall agreement on MEs' severity was fair for the pharmacists (kappa = 0.34) as well as for the physicians (kappa = 0.25). Overall agreement for the 10 raters was fair (kappa = 0.25) as well as the agreement between both consensus outcomes (kappa = 0.30). Agreement on the occurrence of preventable harm was higher, ranging from kappa = 0.36 for the physicians through kappa = 0.49 for the pharmacists. Overall agreement for the 10 raters was fair (kappa = 0.36). The agreement between both consensus outcomes was moderate (kappa = 0.47). None of the included case characteristics had a significant impact on agreement. CONCLUSIONS: Individual assessment of preventable ADEs in real patients is difficult, possibly because of the difficult assessment of contextual information. Best approach seems to be a consensus method including both pharmacists and physicians.

Determinants of self-medication with antibiotics in Europe: the impact of beliefs, country wealth and the healthcare system.

BACKGROUND: Self-medication with antibiotics occurs among the population in Europe, particularly in southern and eastern countries. We studied the impact of predisposing factors (e.g. attitudes and knowledge concerning antibiotic use and self-medication) and enabling factors (country wealth and healthcare system factors) on self-medication with antibiotics in Europe. METHODS: In this follow-up of a previous European survey, we interviewed a subsample of 1101 respondents. A multilevel analysis with two levels (respondent and country) was performed. Variables that were statistically significantly different between users and non-users of self-medication were considered for inclusion into the multilevel regression analyses. RESULTS: Predisposing factors included individual-level characteristics. High perceived appropriateness of self-medication with antibiotics for bronchitis and an attitude favouring antibiotic use for minor ailments were related to a higher likelihood of self-medication. Enabling factors included individual and country data. At the individual level, perceived availability of antibiotics without a prescription was related to increased probability of self-medication. At the country level, higher gross domestic product (wealth) and exact dispensation of prescribed tablet quantities by pharmacies were independently associated with lower likelihood of self-medication. CONCLUSIONS: Interventions aimed at preventing self-medication should include public education, enforcing regulations regarding the sale of antibiotics, and implementing laws for dispensing exact prescribed tablet quantities in pharmacies. With the included determinants, we explained almost all the variance at the country level, but not at the individual level. Future studies to increase our understanding of determinants of self-medication with antibiotics should focus on individual-level factors such as doctor-patient relationships and patient satisfaction.

European Surveillance of Antimicrobial Consumption (ESAC): quality indicators for outpatient antibiotic use in Europe.

BACKGROUND AND OBJECTIVE: Indicators to measure the quality of healthcare are increasingly used by healthcare professionals and policy makers. In the context of increasing antimicrobial resistance, this study aimed to develop valid drug-specific quality indicators for outpatient antibiotic use in Europe, derived from European Surveillance of Antimicrobial Consumption (ESAC) data. METHODS: 27 experts (15 countries), in a European Science Foundation workshop, built on the expertise within the European Drug Utilisation Research Group, the General Practice Respiratory Infections Network, the ESCMID Study Group on Primary Care Topics, the Belgian Antibiotic Policy Coordination Committee, the World Health Organization, ESAC, and other experts. A set of proposed indicators was developed using 1997-2003 ESAC data. Participants scored the relevance of each indicator to reducing antimicrobial resistance, patient health benefit, cost effectiveness and public health policy makers (scale: 1 (completely disagree) to 9 (completely agree)). The scores were processed according to the UCLA-RAND appropriateness method. Indicators were judged relevant if the median score was not in the 1-6 interval and if there was consensus (number of scores within the 1-3 interval was fewer than one third of the panel). From the relevant indicators providing overlapping information, the one with the highest scores was selected for the final set of quality indicators-values were updated with 2004 ESAC data. RESULTS: 22 participants (12 countries) completed scoring of a set of 22 proposed indicators. Nine were rated as relevant antibiotic prescribing indicators on all four dimensions; five were rated as relevant if only relevance to reducing antimicrobial resistance and public health policy makers was taken into account. A final set of 12 indicators was selected. CONCLUSION: 12 of the proposed ESAC-based quality indicators for outpatient antibiotic use in Europe have face validity and are potentially applicable. These indicators could be used to better describe antibiotic use in ambulatory care and assess the quality of national antibiotic prescribing patterns in Europe.

Claims in advertisements for antihypertensive drugs in a Dutch medical journal.

BACKGROUND: Advertising claims must not conflict with the official summary of product characteristics. After a drug has been approved, new clinical evidence may become available. AIMS: To determine how the pharmaceutical industry deals with evolving clinical evidence in advertising claims for antihypertensive drugs, and whether such pharmaceutical promotion is up to standard. METHODS: We examined all advertisements from the Dutch Journal of Medicine published between 1996 and 2004. We judged whether claims were in agreement with the information available from the summary of product characteristics or evidence from cited clinical trials. Subsequently, we reviewed whether these claims had been assessed by the Code of Practice authority. RESULTS: We identified 50 unique advertisements with, in total, 492 appearances for 16 antihypertensive drugs. Claims of blood pressure lowering and convenient use were all judged to be sufficiently substantiated. For calcium-channel blockers, insufficiently supported safety claims had been made in three cases (41 appearances). Claims suggesting effects on long-term outcomes started in 1999 for angiotensin II receptor blockers, and were made during the whole period for several other antihypertensive drugs. In 16 cases (135 appearances), such claims were not supported by the available information. Some claims were premature, others transferred results from a specific patient group to the general population of hypertensive patients. Only two cases were reviewed by the Code of Practice authority. CONCLUSIONS: Overall, 35% of the advertisements for antihypertensive drugs contained suggestive claims not supported by the offered evidence. The current system of self-regulation cannot ensure that pharmaceutical promotion is always accurate, balanced and evidence-based.

Self-medication with antibiotics by a population in northern Israel.

BACKGROUND: The current study is part of a larger study--Self-Medication with Antibiotics and Resistance Levels in Europe (SAR project)--coordinated by the University of Groningen in the Netherlands and run in 19 European countries and Israel. OBJECTIVES: To estimate self-medication with antibiotics by a population in northern Israel. METHODS: We sent by post a questionnaire on antibiotic usage to 2,615 adults, both Jewish and Arab, living in northern Israel. RESULTS: The overall response rate was low (17.9%), particularly among the Arab population (9.4% of respondents). Among the 467 respondents, 169 (36.2%) reported 215 antibiotic courses within the last year. Amoxicillin was the antibiotic most commonly used (32.7% of courses); 89.4% of antibiotics were obtained via a physician's prescription; 114 respondents (24.4%) stored leftover antibiotics at home, and 81 (18.7%) would consider self-medication with antibiotics without a medical consultation. CONCLUSIONS: Over-the-counter acquisition of antibiotics is rare in Israel. However, the storage of leftover antibiotics in the home constitutes an alternative potential source of self-medication that can have untoward consequences, not only for the individual patient but also for the general population since inappropriate antibiotic usage contributes to the increasing rates of antimicrobial resistance.

Improving compliance with hospital antibiotic guidelines: a time-series intervention analysis.

OBJECTIVES: This study investigated the impact of a combined intervention strategy to improve antimicrobial prescribing at University Hospital Groningen. For the intervention, the antimicrobial treatment guidelines were updated and disseminated in paperback and electronic format. The credibility of the guidelines was improved by consultation with users. In a second phase, academic detailing (AD) was used to improve specific areas of low compliance with the guidelines. MATERIALS AND METHODS: Prescribing data were prospectively collected for 2869 patients receiving 7471 prescriptions for an antimicrobial for an infection covered by the guidelines between July 2001 and September 2003. After collection of baseline data, the guidelines were actively disseminated in February 2002. Next, after a 5 month interval, a second intervention, i.e. an AD approach, addressed suboptimal prescribing of ciprofloxacin and co-amoxiclav. Segmented regression analysis was used to analyse the interrupted time-series data. RESULTS: At baseline, compliance with the drug choice guidelines was 67%. The first intervention showed a significant change in the level of compliance of +15.5% (95% CI: 8%; 23%). AD did not lead to statistically significant additional changes in already high levels +12.5% (95% CI:-3%; 28%) of compliance. Post-intervention compliance was stable at 86%. CONCLUSIONS: Updating the guidelines in close collaboration with the specialists involved followed by active dissemination proved to be an efficient way to improve compliance with guideline recommendations. An 86% compliance level was achieved in this study without compulsory measures. A ceiling effect may have limited the added value of AD.

Self-medication with antibiotics in a Swedish general population.

To assess the extent of antibiotic self-medication in a Swedish population, a postal questionnaire was distributed to 1000 randomly selected subjects. The antibiotics used were in all but 3 cases reported to have been obtained with a prescription. Thus, prescribers are the primary target for interventions to optimize antibiotic use.