Drug switching in the Netherlands: a cohort study of 20 active substances.

BACKGROUND: For a patient, drug switches are not desirable (either between a brand-name drug and a generic drug, or between two generic drugs of the same active substance). Research into the causes of drug switches, and related adverse drug reactions, is hampered by the absence of quantitative data on drug switches. METHODS: We describe the frequency of drug switches in the Netherlands for a selection of active substances. A retrospective cohort study was conducted using the Drug Information System of the National Health Care Institute in the Netherlands. We studied the Dutch patient population from mid-2009 to 2016. The selection of active substances (n = 20) was made based on a report by Lareb, the Netherlands Pharmacovigilance Centre, on adverse drug reactions related to drug switching, and we used qualitative and quantitative descriptive analyses. A drug switch is defined as the replacement of a patient's prescribed drug with a similar drug from a different manufacturer. RESULTS: We identified 23.8 million drug switches on a total of 206 million (11.6%) similar drug dispenses. The frequency of drug switches demonstrated a yearly peak in the period from January to March. In some months, for atorvastatin, losartan, pantoprazole, and irbesartan, more than 60% of similar drug dispenses were drug switches. Most drug switches (80.3%) were between two generic drugs, and 0.12% of these involved a drug from a European parallel import. The proportion of drug switches between two brand-name drugs decreased from 14.5 to 5.53% during our study period, and of these, 86.5% involved a drug from a European parallel import. CONCLUSIONS: Drug switching is common in the Netherlands, and most of the drug switches we studied are between generic drugs. The observed annual peak of drug switches is most likely explained by a specific Dutch reimbursement policy. Not only are the data valuable as is, but they also serve as a first step towards elucidating the reasons for the occurrence of these drug switches. In addition, these data can be used to put into perspective the adverse drug reactions associated with drug switching.

Potential approaches for the pricing of cancer medicines across Europe to enhance the sustainability of healthcare systems and the implications.

Introduction: There are growing concerns among European health authorities regarding increasing prices for new cancer medicines, prices not necessarily linked to health gain and the implications for the sustainability of their healthcare systems.Areas covered: Narrative discussion principally among payers and their advisers regarding potential approaches to the pricing of new cancer medicines.Expert opinion: A number of potential pricing approaches are discussed including minimum effectiveness levels for new cancer medicines, managed entry agreements, multicriteria decision analyses (MCDAs), differential/tiered pricing, fair pricing models, amortization models as well as de-linkage models. We are likely to see a growth in alternative pricing deliberations in view of ongoing challenges. These include the considerable number of new oncology medicines in development including new gene therapies, new oncology medicines being launched with uncertainty regarding their value, and continued high prices coupled with the extent of confidential discounts for reimbursement. However, balanced against the need for new cancer medicines. This will lead to greater scrutiny over the prices of patent oncology medicines as more standard medicines lose their patent, calls for greater transparency as well as new models including amortization models. We will be monitoring these developments.

Quantification of Adverse Drug Reactions Related to Drug Switches in The Netherlands.

We performed a retrospective cohort study in the Dutch patient population to identify active substances with a relatively high number of adverse drug reactions (ADRs) potentially related to drug switching. For this, we analyzed drug switches and reported ADRs related to switching between June 1, 2009, and December 31, 2016, for a selection of 20 active substances. We also compared pharmacovigilance analyses based on the absolute, switch-corrected, and user-corrected numbers of ADRs. In total, 1,348 reported ADRs and over 23.8 million drug switches were obtained from the National Health Care Institute in The Netherlands and from Lareb, which is The Netherlands Pharmacovigilance Centre. There was no correlation between the number of ADRs and the number of switches, but, on average, we found 5.7 reported ADRs per 100,000 switches. The number was relatively high for rivastigmine, levothyroxine, methylphenidate, and salbutamol, with 74.9, 50.9, 47.6, and 26.1 ADRs per 100,000 switches, respectively. When comparing analyses using the absolute number and the switch-corrected number of ADRs, we demonstrate that different active substances would be identified as having a relatively high number of ADRs, and different time periods of increased numbers of ADRs would be observed. We also demonstrate similar results when using the user-corrected number of ADRs instead of the switch-corrected number of ADRs, allowing for a more feasible approach in pharmacovigilance practice. This study demonstrates that pharmacovigilance analyses of switch-related ADRs leads to different results when the number of reported ADRs is corrected for the actual number of drug switches.

The effect of completeness of revascularization on event-free survival at one year in the ARTS trial.

OBJECTIVES: We sought to assess the relationship between completeness of revascularization and adverse events at one year in the ARTS (Arterial Revascularization Therapies Study) trial. BACKGROUND: There is uncertainty to what extent degree of completeness of revascularization, using up-to-date techniques, influences medium-term outcome. METHODS: After consensus between surgeon and cardiologist regarding the potential for equivalence in the completeness of revascularization, 1,205 patients with multivessel disease were randomly assigned to either bypass surgery or stent implantation. All baseline and procedural angiograms and surgical case-record forms were centrally assessed for completeness of revascularization. RESULTS: Of 1,205 patients randomized, 1,172 underwent the assigned treatment. Complete data for review were available in 1,143 patients (97.5%). Complete revascularization was achieved in 84.1% of the surgically treated patients and 70.5% of the angioplasty patients (p < 0.001). After one year, the stented angioplasty patients with incomplete revascularization showed a significantly lower event-free survival than stented patients with complete revascularization (i.e., freedom from death, myocardial infarction, cerebrovascular accident and repeat revascularization) (69.4% vs. 76.6%; p < 0.05). This difference was due to a higher incidence of subsequent bypass procedures (10.0% vs. 2.0%; p < 0.05). Conversely, at one year, bypass surgery patients with incomplete revascularization showed only a marginally lower event-free survival rate than those with complete revascularization (87.8% vs. 89.9%). CONCLUSIONS: Complete revascularization was more frequently accomplished by bypass surgery than by stent implantation. One year after bypass, there was no significant difference in event-free survival between surgically treated patients with complete revascularization and those with incomplete revascularization, but patients randomized to stenting with incomplete revascularization had a greater need for subsequent bypass surgery.

A 10-year analysis of the effects of media coverage of regulatory warnings on antidepressant use in The Netherlands and UK.

BACKGROUND: In 2003-2004 and 2007-2008, the regulatory banning of SSRI use in pediatrics and young adults due to concerns regarding suicidality risk coincided with negative media coverage. SSRI use trends were analyzed from 2000-2010 in the Netherlands (NL) and the UK, and whether trend changes might be associated with media coverage of regulatory warnings. METHODS: Monthly SSRIs sales were presented as DDDs/1000 inhabitants/day. SSRI-use trends were studied using time-series segmented regression analyses. Timing of trend changes was compared with two periods of media coverage of warnings. Annual Dutch SSRI prescription data were analyzed by age group. RESULTS: Trend changes in SSRI use largely corroborated with the periods of media coverage of warnings. British SSRI use declined from 3.9 to 0.7 DDDs/month (95%CI 3.3;4.5 & 0.5;0.9, respectively) before the first warning period (2003-2004). A small decrease of -0.6 DDDs/month (-1.2; -0.05) was observed in Dutch SSRI use shortly after 2003-2004. From 2007-2008, British SSRI use stabilized, whilst Dutch SSRI use diminished to -0.04 DDDs/month (-0.4;0.3). Stratified analyses showed a rapid decrease of -1.2 DDDs/month (-2.1; -1.7) in UK paroxetine use before 2003-2004, but only a minimal change in Dutch paroxetine use (-0.3 DDDs/month -0.8;0.2). Other SSRI use, especially (es)citalopram, increased during 2003-2004 in both countries. Significant reductions in Dutch paroxetine use were observed in pediatrics, adolescents, and young adults after 2003-2004. CONCLUSION: Changes in SSRI use (NL & UK) were associated with the timing of the combined effect of media coverage and regulatory warnings. Our long-term assessment illustrates that changes in SSRI use were temporal, drug-specific and more pronounced in pediatrics and young adults. The twofold increase in SSRI use over one decade indicates that regulatory warnings and media coverage may come and go, but they do not have a significant impact on the overall upward trend of SSRI use as a class in both countries.

[Cardiovascular polypill in high risk patients]. / De cardiovasculaire polypil voor hoogrisicopatiënten.

The initial theoretical concept of a polypill was a fixed-dosed combination pill containing an antiplatelet agent, a cholesterol-lowering agent and multiple blood pressure-lowering agents aimed at the prevention of atherosclerotic vascular disease in the population aged 55 years and up. The reduction in the risk of cardiovascular disease does not depend on the cholesterol level and blood pressure at the start of treatment. The pharmacological reduction in risk factors in individuals with a high risk of atherosclerotic vascular disease is often suboptimal, partly due to the complexity of the guidelines and low adherence to the therapy. A polypill may offer opportunities for improvement. Research has shown that the use of combination products leads to a greater reduction in risk factors than the use of separate substances, possibly through improved adherence to the therapy. The use of a polypill in the prevention of vascular disease in high-risk patients may lead to a more effective reduction in risk, a decrease in costs and a reduction in pharmacological expenditure.

Determinants of potential drug-drug interaction associated dispensing in community pharmacies in the Netherlands.

OBJECTIVE: There are many drug-drug interactions (D-DI) of which some may cause severe adverse patient outcomes. Dispensing interacting drug combinations should be avoided when the risks are higher than the benefits. The objective of this study was to identify determinants of dispensing undesirable interacting drug combinations by community pharmacies in the Netherlands. METHODS: A total of 256 Dutch community pharmacies were selected, based on the dispensing of 11 undesirable interacting drug combinations between January 1st, 2001 and October 31st, 2002. These pharmacies were sent a questionnaire by the Inspectorate for Health Care (IHC) concerning their process and structure characteristics. MAIN OUTCOME MEASURE: The number of times the 11 undesirable interacting drug combinations were dispensed. RESULTS: Two hundred and forty-six questionnaires (response rate 96.1%) were completed. Dispensing determinants were only found for the D-DI between macrolide antibiotics and digoxin but not for the other 10 D-DIs. Pharmacies using different medication surveillance systems differed in the dispensing of this interacting drug combination, and pharmacies, which were part of a health care centre dispensed this interacting drug combination more often. CONCLUSION: Medication surveillance in Dutch community pharmacies seems to be effective. Although for most D-DIs no determinants were found, process and structure characteristics may have consequences for the dispensing of undesirable interacting drug combinations.