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Eichler H.-G.,European Medicines Agency | Eichler H.-G.,Massachusetts Institute of Technology | Abadie E.,European Medicines Agency | Abadie E.,European Medicines Agency Committee for Medicinal Products for Human Use | And 11 more authors.
Nature Reviews Drug Discovery | Year: 2011

Drug regulatory agencies should ensure that the benefits of drugs outweigh their risks, but licensed medicines sometimes do not perform as expected in everyday clinical practice. Failure may relate to lower than anticipated efficacy or a higher than anticipated incidence or severity of adverse effects. Here we show that the problem of benefitgrisk is to a considerable degree a problem of variability in drug response. We describe biological and behavioural sources of variability and how these contribute to the long-known efficacy-effectiveness gap. In this context, efficacy describes how a drug performs under conditions of clinical trials, whereas effectiveness describes how it performs under conditions of everyday clinical practice. We argue that a broad range of pre- and post-licensing technologies will need to be harnessed to bridge the efficacy-effectiveness gap. Successful approaches will not be limited to the current notion of pharmacogenomics-based personalized medicines, but will also entail the wider use of electronic health-care tools to improve drug prescribing and patient adherence. © 2011 Macmillan Publishers Limited. All rights reserved.


Brabers A.E.M.,Netherlands Institute for Health Services Research | Van Dijk L.,Netherlands Institute for Health Services Research | Bouvy M.L.,Utrecht Institute for Pharmaceutical science UIPS | Bouvy M.L.,SIR Institute for Pharmacy Practice and Policy | De Jong J.D.,Netherlands Institute for Health Services Research
BMJ Open | Year: 2013

Objective: To examine consumers' confidence in their own, and also in other people's, over-the-counter (OTC) skills and to describe their attitude towards the availability of OTC painkillers. Moreover we examined the association between confidence in OTC skills and attitudes. Design: Cross-sectional survey. Mixed methods (postal and electronic) self-administered questionnaire. Participants: Members of the Dutch Health Care Consumer Panel. Main outcome measures: Consumers' confidence in their own, and in other people's, OTC skills was examined. Confidence was measured by three questions regarding obtaining information on, choosing and using OTC medication. Consumers' attitudes towards availability were assessed using six safety profiles, by asking which channel consumers prefer for each profile. Results: The response rate was 68% (n=972). Consumers feel confident about their own OTC skills (mean 3.74; 95% CI 3.69 to 3.79, on a 5-point Likert scale), but have less confidence in OTC skills of others (mean 2.92; 95% CI 2.88 to 2.96). Consumers are conservative in their attitudes towards the availability of OTC painkillers. Most consumers prefer painkillers to be available exclusively in pharmacies (41-71% per profile indicated pharmacy only). Moreover, there is an association between confidence in OTC skills and attitudes (p=0.005; β=-0.114). Consumers who are more confident about their own OTC skills prefer OTC painkillers to be more generally available. Conclusions: Consumers feel confident about their own OTC skills. However, they would prefer painkillers with safety profiles resembling those currently available OTC, to be available as OTC in pharmacies exclusively. Consumers' confidence in the OTC skills of others is more consistent with their attitudes towards availability of OTC painkillers. Until consumers themselves realise that they are also one of the others, they may overestimate their own OTC skills, which may entail health risks.


Galarraga O.,Brown University | Galarraga O.,National Institute of Public Health INSP | Wirtz V.J.,National Institute of Public Health INSP | Wirtz V.J.,Boston University | And 3 more authors.
PLoS ONE | Year: 2013

Global HIV control funding falls short of need. To maximize health outcomes, it is critical that national governments sustain reasonable commitments, and that international donor assistance be distributed according to country needs and funding gaps. We develop a country classification framework in terms of actual versus expected national domestic funding, considering resource needs and donor financing. With UNAIDS and World Bank data, we examine domestic and donor HIV program funding in relation to need in 84 low- and middle-income countries. We estimate expected domestic contributions per person living with HIV (PLWH) as a function of per capita income, relative size of the health sector, and per capita foreign debt service. Countries are categorized according to levels of actual versus expected domestic contributions, and resource gap. Compared to national resource needs (UNAIDS Investment Framework), we identify imbalances among countries in actual versus expected domestic and donor contributions: 17 countries, with relatively high HIV prevalence and GNI per capita, have domestic funding below expected (median per PLWH $143 and $376, respectively), yet total available funding including from donors would exceed the need ($368 and $305, respectively) if domestic contribution equaled expected. Conversely, 27 countries have actual domestic funding above the expected (medians $294 and $149) but total (domestic+donor) funding does not meet estimated need ($685 and $1,173). Across the 84 countries, in 2009, estimated resource need totaled $10.3 billion, actual domestic contributions $5.1 billion and actual donor contributions $3.7 billion. If domestic contributions would increase to the expected level in countries where the actual was below expected, total domestic contributions would increase to $7.4 billion, turning a funding gap of $1.5 billion into a surplus of $0.8 billion. Even with imperfect funding and resource-need data, the proposed country classification could help improve coherence and efficiency in domestic and international allocations. © 2013 Galárraga et al.


Santa-Ana-Tellez Y.,Utrecht Institute for Pharmaceutical science UIPS | Mantel-Teeuwisse A.K.,Utrecht Institute for Pharmaceutical science UIPS | Dreser A.,National Health Research Institute | Leufkens H.G.M.,Utrecht Institute for Pharmaceutical science UIPS | And 2 more authors.
PLoS ONE | Year: 2013

Background:In Latin American countries over-the-counter (OTC) dispensing of antibiotics is common. In 2010, both Mexico and Brazil implemented policies to enforce existing laws of restricting consumption of antibiotics only to patients presenting a prescription. The objective of the present study is therefore to evaluate the impact of OTC restrictions (2010) on antibiotics consumption in Brazil and Mexico.Methods and Findings:Retail quarterly sales data in kilograms of oral and injectable antibiotics between January 2007 and June 2012 for Brazil and Mexico were obtained from IMS Health. The unit of analysis for antibiotics consumption was the defined daily dose per 1,000 inhabitants per day (DDD/TID) according to the WHO ATC classification system. Interrupted time series analysis was conducted using antihypertensives as reference group to account for changes occurring independently of the OTC restrictions directed at antibiotics. To reduce the effect of (a) seasonality and (b) autocorrelation, dummy variables and Prais-Winsten regression were used respectively.Between 2007 and 2012 total antibiotic usage increased in Brazil (from 5.7 to 8.5 DDD/TID, +49.3%) and decreased in Mexico (10.5 to 7.5 DDD/TID, -29.2%). Interrupted time series analysis showed a change in level of consumption of -1.35 DDD/TID (p<0.01) for Brazil and -1.17 DDD/TID (p<0.00) for Mexico. In Brazil the penicillins, sulfonamides and macrolides consumption had a decrease in level after the intervention of 0.64 DDD/TID (p = 0.02), 0.41 (p = 0.02) and 0.47 (p = 0.01) respectively. While in Mexico it was found that only penicillins and sulfonamides had significant changes in level of -0.86 DDD/TID (p<0.00) and -0.17 DDD/TID (p = 0.07).Conclusions:Despite different overall usage patterns of antibiotics in Brazil and Mexico, the effect of the OTC restrictions on antibiotics usage was similar. In Brazil the trend of increased usage of antibiotics was tempered after the OTC restrictions; in Mexico the trend of decreased usage was boosted. © 2013 Santa-Ana-Tellez et al.


Kwint H.F.,SIR Institute for Pharmacy Practice and Policy | Kwint H.F.,Utrecht Institute for Pharmaceutical science UIPS | Faber A.,SIR Institute for Pharmacy Practice and Policy | Gussekloo J.,Leiden University | And 2 more authors.
Drugs and Aging | Year: 2011

Background: There are concerns that automated drug dispensing may increase inappropriate drug use. Automated dispensing could lead to perpetual repeating of drug therapies without the necessary re-evaluation. Objective: The aim of this study was to examine the effect of a pharmacist-led medication review on drug-related problems (DRPs) in older patients receiving their drugs via automated dispensing. Methods: This was a pragmatic randomized controlled study conducted in primary care. Patients were recruited from six Dutch community pharmacies. They were eligible if they lived at home, were aged ≥65 years, and used five or more different drugs, of which at least one had to be dispensed via an automated system. Patients were randomly allocated to receive a medication review at the start of the study (intervention group) or after 6 months (waiting-list group). Each patient was independently reviewed by two pharmacist reviewers. The results of these medication reviews were sent to the community pharmacist to be discussed with the patients general practitioner (GP). The primary outcome measure was the number of DRPs leading to a recommendation for drug change. Secondary outcomes were the total number of drug changes and the number of drug changes related to a recommendation. In order to analyse drug changes, medication records were collected 6 months after the medication review or index date in the waiting-list group. Potential DRPs were classified using the DOCUMENT classification. Results: There were no baseline differences between the 63 patients in the intervention group and the 55 patients in the waiting-list group with respect to age, sex, number of drugs per patient and type of drug prescribed. The mean number of DRPs per patient at baseline in the intervention group and waiting list combined was 8.5, with no difference between the groups. At baseline, the mean number of DRPs leading to a recommendation for drug change was 4.5 per patient and did not differ between the two groups. After 6 months, the number of DRPs leading to a recommendation for drug change decreased by 29% in the intervention group versus 5% in the waiting-list group (p<0.01). Recommendations for cessation of a drug were more frequently accepted than recommendations to add a new drug (82% vs 44%, p = 0.01). Conclusions: This study shows that patients using automated drug dispensing have a high number of DRPs. Medication review decreases the number of DRPs among these patients. We recommend that all patients with automatic drug dispensing should have a thorough medication review by pharmacists and prescribers.


Kwint H.F.,Utrecht Institute for Pharmaceutical science UIPS | Kwint H.F.,SIR Institute for Pharmacy Practice and Policy | Faber A.,SIR Institute for Pharmacy Practice and Policy | Gussekloo J.,Leiden University | And 2 more authors.
Journal of Clinical Pharmacy and Therapeutics | Year: 2012

What is known and Objective: To determine to what extent patient interviews contribute to the identification of drug-related problems (DRPs) in home medication reviews, in terms of number, type and clinical relevance. Methods: We performed a cross-sectional study within the intervention arm of a randomized controlled trial. Patients were recruited from 10 Dutch community pharmacies. Patients were eligible if they were home-dwelling, aged 65 years and over and used five or more different drugs, including at least one cardiovascular or antidiabetic drug. The community pharmacist interviewed the patient at home about the medicines and identified potential DRPs in combination with medication and clinical records. This medication review was assessed and modified by an independent pharmacist reviewers' panel. Outcomes were the number and type of DRPs and recommendations and percentage of clinical relevant DRPs. Clinical relevance of DRPs was assessed by DRPs assigned a high priority, DRPs followed by recommendations for drug change and DRPs followed by implemented recommendations for drug change. Results: A total of 1565 potential DRPs and recommendations (10 per patient).were identified for 155 patients (median age, 76 years; 54% women). Fifty-eight per cent of all recommendations involved a drug change; 27% of all DRPs were identified during patient interviews and 74% from medication and clinical records. Compared to DRPs identified from patient medication and clinical records, DRPs identified during patient interviews were more frequently assigned a high priority (OR = 1·8 [1·4- 2·2]), were more frequently associated with recommendations for drug change (OR = 2·4 [1·9-3·1]) and were implemented recommendations for drug change (OR = 2·8 [2·1-3·7]). What is new and Conclusion: This study shows that more than a quarter of all DRPs were identified during patient interviews. DRPs identified during patient interviews were more frequently assigned a higher clinical relevance. © 2012 Blackwell Publishing Ltd.


Kaplan W.A.,Boston University | Kaplan W.A.,World Health Organization | Wirtz V.J.,Boston University | Wirtz V.J.,World Health Organization | And 2 more authors.
PLoS ONE | Year: 2013

This observational study investigates the private sector, retail pharmaceutical market of 19 low and middle income countries (LMICs) in Latin America, Asia and the Middle East/South Africa analyzing the relationships between volume market share of generic and originator medicines over a time series from 2001 to 2011. Over 5000 individual pharmaceutical substances were divided into generic (unbranded generic, branded generic medicines) and originator categories for each country, including the United States as a comparator. In 9 selected LMICs, the market share of those originator substances with the largest decrease over time was compared to the market share of their counterpart generic versions. Generic medicines (branded generic plus unbranded generic) represent between 70 and 80% of market share in the private sector of these LMICs which exceeds that of most European countries. Branded generic medicine market share is higher than that of unbranded generics in all three regions and this is in contrast to the U.S. Although switching from an originator to its generic counterpart can save money, this narrative in reality is complex at the level of individual medicines. In some countries, the market behavior of some originator medicines that showed the most temporal decrease, showed switching to their generic counterpart. In other countries such as in the Middle East/South Africa and Asia, the loss of these originators was not accompanied by any change at all in market share of the equivalent generic version. For those countries with a significant increase in generic medicines market share and/or with evidence of comprehensive "switching" to generic versions, notably in Latin America, it would be worthwhile to establish cause-effect relationships between pharmaceutical policies and uptake of generic medicines. The absence of change in the generic medicines market share in other countries suggests that, at a minimum, generic medicines have not been strongly promoted. © 2013 Kaplan et al.


Hoebert J.M.,Utrecht Institute for Pharmaceutical science UIPS | van Dijk L.,Netherlands Institute for Health Services Research NIVEL | Mantel-Teeuwisse A.K.,Utrecht Institute for Pharmaceutical science UIPS | Leufkens H.G.M.,Utrecht Institute for Pharmaceutical science UIPS | Laing R.O.,World Health Organization
Journal of Pharmaceutical Policy and Practice | Year: 2013

Objectives: Continuous provision of appropriate medicines of assured quality, in adequate quantities, and at reasonable prices is a concern for all national governments. A national medicines policy (NMP) developed in a collaborative fashion identifies strategies needed to meet these objectives and provides a comprehensive framework to develop all components of a national pharmaceutical sector. To meet the health needs of the population, there is a general need for medicine policies based on universal principles, but nevertheless adapted to the national situation. This review aims to provide a quantitative and qualitative (describing the historical development) study of the development process and evolution of NMPs.Methods: The number of NMPs and their current status has been obtained from the results of the assessment of WHO Level I indicators. The policy formulation process is examined in more detail with case studies from four countries: Sri Lanka, Australia, former Yugoslav Republic of Macedonia and South Africa.Results: The number of NMPs worldwide has increased in the last 25 years with the highest proportional increase in the last 5-10 years in high-income countries. Higher income countries seem to have more NMP implementation plans available and have updated their NMP more recently. The four case studies show that the development of a NMP is a complex process that is country specific. In addition, it demonstrates that an appropriate political window is needed for the policy to be passed (for South Africa and the FYR Macedonia, a major political event acted as a trigger for initiating the policy development). Policy-making does not stop with the official adoption of a policy but should create mechanisms for implementation and monitoring. The NMPs of the FYR Macedonia and Australia provide indicators for monitoring.Conclusions: To date, not all countries have a NMP since political pressure by national experts or non-governmental organizations is generally needed to establish a NMP. Case studies in four countries showed that the policy process is just as important as the policy document since the process must create a mechanism by which all stakeholders are brought together and a sense of collective ownership of the final policy may be achieved. © 2013 Hoebert et al.


Stephens P.,IMS Health | Stephens P.,Utrecht Institute for Pharmaceutical science UIPS
Vaccine | Year: 2014

Vaccines offer the most cost-effective solution to prevent both communicable and non-communicable disease in poor countries. Published studies suggest that vaccine research is seeing declining success. This study updates the latest analyses on success rates in vaccine research, and examines the potential causes of decline and their ongoing impact. Success rates are shown to decline, the observed probability of market entry being just 1.8%, almost a fourfold decline over 5 years, but in the context of a very different product portfolio from that seen in earlier studies. DNA vaccines see high Phase I failures as expected, and therapeutic vaccines have lower success rates than prophylactic vaccines. The changing scientific challenge, lack of investment and lack of co-operation are highlighted as potential causes of the decline. Many issues have now been resolved, but co-operation between academia, regulators and industry remains a significant challenge, requiring links across new disciplines and technologies. © 2014 Elsevier Ltd.


Koster E.S.,Utrecht Institute for Pharmaceutical science UIPS | Maitland-Van Der Zee A.-H.,Utrecht Institute for Pharmaceutical science UIPS | Tavendale R.,University of Dundee | Mukhopadhyay S.,University of Dundee | And 5 more authors.
Allergy: European Journal of Allergy and Clinical Immunology | Year: 2011

Background: The T2206C FCER2 variant was found previously to be associated with IgE levels, exacerbation rates and decreased FCER2 expression in children on inhaled corticosteroids (ICS) participating in a clinical trial. This finding has not been replicated. We sought to replicate the association between the FCER2 gene and exacerbations in children with asthma. In addition, we tested the hypothesis that the T2206C variant may be associated with other markers of steroid resistance such as asthma symptom scores and asthma medication use. Methods: The influence of the T2206C variant on asthma exacerbations (emergency department visits or hospitalization), symptoms scores and medication use was explored using data from two populations of asthmatic children using ICS: Pharmacogenetics of Asthma medication in Children: Medication with ANti-inflammatory effects study (n = 386) and BREATHE study (n = 939). Results: The T2206C variant was associated with increased risk of asthma-related hospital visits in both cohorts (OR: 1.91, 95%CI: 1.08-3.40), and meta-analysis with previously published results was highly significant (OR: 2.38, 95%CI: 1.47-3.85, P = 0.0004). The FCER2 variant was also associated with increased risk of uncontrolled asthma measured by Asthma Control Questionnaire (OR: 2.64, 95%CI: 1.00-6.98) and was associated with increased daily steroid dose (OR: 2.46, 95%CI: 1.38-4.39). Conclusion: The association between the FCER2 T2206C variant and asthmarelated hospitalizations in steroid-treated asthma appears robust and may also be associated with other indicators of lack of ICS efficacy such as asthma symptoms and a requirement for higher daily doses of ICS. Our results suggest that the FCER2 T2206C variant might be a useful pharmacogenetic predictor of steroid refractory patients. © 2011 John Wiley & Sons A/S.

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