| 1. |
- Malmström, Rickard E., et al.
(författare)
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Dabigatran - a case history demonstrating the need for comprehensive approaches to optimize the use of new drugs
- 2013
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Ingår i: Frontiers in Pharmacology. - : FRONTIERS RESEARCH FOUNDATION. - 1663-9812. ; 4
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Tidskriftsartikel (refereegranskat)abstract
- Background: There are potential conflicts between authorities and companies to fund new premium priced drugs especially where there are safety and/or budget concerns. Dabigatran, a new oral anticoagulant for the prevention of stroke in patients with non-valvular atrial fibrillation (AF), exemplifies this issue. Whilst new effective treatments are needed, there are issues in the elderly with dabigatran due to variable drug concentrations, no known antidote and dependence on renal elimination. Published studies have shown dabigatran to be cost-effective but there are budget concerns given the prevalence of AF. There are also issues with potentially re-designing anticoagulant services. This has resulted in activities across countries to better manage its use. Objective: To (i) review authority activities in over 30 countries and regions, (ii) use the findings to develop new models to better manage the entry of new drugs, and (iii) review the implications for all major stakeholder groups. Methodology: Descriptive review and appraisal of activities regarding dabigatran and the development of guidance for groups through an iterative process. Results: There has been a plethora of activities among authorities to manage the prescribing of dabigatran including extensive pre-launch activities, risk sharing arrangements, prescribing restrictions, and monitoring of prescribing post-launch. Reimbursement has been denied in some countries due to concerns with its budget impact and/or excessive bleeding. Development of a new model and future guidance is proposed to better manage the entry of new drugs, centering on three pillars of pre-, pen-, and post-launch activities. Conclusion: Models for introducing new drugs are essential to optimize their prescribing especially where there are concerns. Without such models, new drugs may be withdrawn prematurely and/or struggle for funding.
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| 2. |
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| 3. |
- Eriksen, Jaran, et al.
(författare)
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High adherence to the 'Wise List' treatment recommendations in Stockholm : a 15-year retrospective review of a multifaceted approach promoting rational use of medicines
- 2017
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Ingår i: BMJ Open. - London, UK : BMJ Publishing Group Ltd. - 2044-6055. ; 7:4
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: To present the 'Wise List' (a formulary of essential medicines for primary and specialised care in Stockholm Healthcare Region) and assess adherence to the recommendations over a 15-year period.DESIGN: Retrospective analysis of all prescription data in the Stockholm Healthcare Region between 2000 and 2015 in relation to the Wise List recommendations during the same time period.SETTING: All outpatient care in the Stockholm Healthcare Region.PARTICIPANTS: All prescribers in the Stockholm Healthcare Region.MAIN OUTCOME MEASURES: The number of core and complementary substances included in the Wise List, the adherence to recommendations by Anatomic Therapeutic Chemical (ATC) 1st level using defined daily doses (DDDs) adjusted to the DDD for 2015, adherence to recommendations over time measured by dispensed prescriptions yearly between 2002 and 2015.RESULTS: The number of recommended core substances was stable (175-212). Overall adherence to the recommendations for core medicines for all prescribers increased from 75% to 84% (2000 to 2015). The adherence to recommendations in primary care for core medicines increased from 80% to 90% (2005 to 2015) with decreasing range in practice variation (32% to 13%). Hospital prescriber adherence to core medicine recommendations was stable but increased for the combination core and complementary medicines from 77% to 88% (2007 to 2015). Adherence varied between the 4 therapeutic areas studied.CONCLUSIONS: High and increasing adherence to the Wise List recommendations was seen for all prescriber categories. The transparent process for developing recommendations involving respected experts and clinicians using strict criteria for handling potential conflicts of interests, feedback to prescribers, continuous medical education and financial incentives are possible contributing factors. High-quality evidence-based recommendations to prescribers, such as the Wise List, disseminated through a multifaceted approach, will become increasingly important and should be developed further to include recommendations and introduction protocols for new expensive medicines.
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| 4. |
- Eriksson, Irene, et al.
(författare)
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Did we see it Coming? : An Evaluation of the Swedish Early Awareness and Alert System
- 2019
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Ingår i: Applied Health Economics and Health Policy. - : Springer. - 1175-5652 .- 1179-1896. ; 17:1, s. 93-101
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Early awareness and alert systems have been established in many countries but evidence on their ability to accurately prioritize new medicines (for early assessment) is limited.OBJECTIVE: The purpose of this study was to assess whether the Swedish Early Awareness and Alert System identified and prioritized (i.e., produced early assessment reports for) new medicines that would go on to have substantial economic impact.METHODS: We adapted a study design commonly used in the assessment of diagnostic test accuracy. The prioritization made by the Swedish Early Awareness and Alert System prior to marketing authorization comprised the index test and the national drug sales data in the second year post-authorization served as the reference standard. All initial marketing authorization applications for medicinal products processed by the European Medicines Agency between 2010 and 2015 (study population) were classified using the index test and the reference standard.RESULTS: Two hundred and fifty-three new medicinal products processed by the European Medicines Agency comprised the study population. Of these, 71 were prioritized by the Swedish Early Awareness and Alert System and 21 were classified as having substantial economic impact. The sensitivity and positive predictive value were 76.2% and 22.5%, respectively. Subgroup analyses showed that the accuracy of prioritization, in terms of sensitivity, was 100% for antineoplastic/immunomodulating agents.CONCLUSIONS: The Swedish Early Awareness and Alert System identified all new medicines that would go on to have substantial economic impact and prioritized most of these medicines. Our findings provide reassurance to decision makers who rely on the outputs of the Swedish Early Awareness and Alert System to keep informed about new medicines. Moreover, this study also provides valuable insights to stakeholders willing to establish or evaluate their own early awareness and alert activities and systems.
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| 5. |
- Eriksson, Irene, et al.
(författare)
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Persistence with dimethyl fumarate in relapsing-remitting multiple sclerosis : a population-based cohort study
- 2018
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Ingår i: European Journal of Clinical Pharmacology. - Berling : Springer Berlin/Heidelberg. - 0031-6970 .- 1432-1041. ; 74:2, s. 219-226
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To describe patients initiating dimethyl fumarate (DMF) and measure persistence with DMF, discontinuation, and switching in treatment-naïve DMF patients and patients switching to DMF from other multiple sclerosis disease-modifying treatments (DMTs).METHODS: A population-based cohort study of all Stockholm County residents initiating DMF from 9 May 2014 until 31 May 2017. All data were derived from a regional database that collects individual-level data on healthcare and drug utilization of all residents. The study outcomes were persistence with DMF and DMF discontinuation and switching to other DMTs. Persistence was measured as the number of days until either DMF discontinuation (treatment gap ≥ 60 days) or switching to another DMT.RESULTS: The study included 400 patients (median follow-up = 2.5 years). The majority had previously been treated with other DMTs (61%). Throughout the follow-up period, 124 patients (31%) discontinued DMF and 114 patients (29%) switched treatment. Overall, 34% of patients initiating DMF stopped treatment within 1 year and only 43% of patients remained on DMF at 2 years from treatment initiation.CONCLUSIONS: DMF had a rapid market uptake likely due to high expectations held by both patients and clinicians. However, persistence with DMF in routine clinical practice was found to be low.
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| 6. |
- Eriksson, Irene, et al.
(författare)
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The changing multiple sclerosis treatment landscape : impact of new drugs and treatment recommendations
- 2018
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Ingår i: European Journal of Clinical Pharmacology. - Berlin, Germany : Springer. - 0031-6970 .- 1432-1041. ; 74:5, s. 663-670
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: The purpose of this study is to describe the utilization of disease-modifying treatments (DMTs) in relapsing-remitting multiple sclerosis (MS) and assess the impact of both the introduction of new drugs and treatment recommendations (local recommendation on rituximab use issued at the largest MS clinic in Stockholm and regional Drug and Therapeutics Committee (DTC) recommendation on how dimethyl fumarate should be used).METHODS: Interrupted time series analyses using monthly data on all MS patients treated with DMTs in the Stockholm County, Sweden, from January 2011 to December 2017.RESULTS: There were 4765 individuals diagnosed with MS residing in the Stockholm County from 2011 to 2017. Of these, 2934 (62%) were treated with an MS DMT. Since 2011, fingolimod, alemtuzumab, teriflunomide, dimethyl fumarate, peginterferon beta-1a, and daclizumab were introduced. Only fingolimod and dimethyl fumarate significantly impacted MS DMT utilization. In parallel, the use of rituximab off-label increased steadily, reaching 58% of all DMT-treated MS patients by the end of the study period. The local recommendation on rituximab was associated with an increase in rituximab use. The regional DTC recommendation on dimethyl fumarate was associated with a decrease in dimethyl fumarate use.CONCLUSIONS: Three MS DMTs-fingolimod, dimethyl fumarate, and rituximab off-label-impacted MS DMT utilization in the Stockholm County. The associations between the treatment recommendations and the subsequent changes in MS DMT utilization indicate that such interventions can influence the uptake and utilization of new drugs used in the specialized care setting.
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| 7. |
- Eriksson, Irene, et al.
(författare)
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The Early Awareness and Alert System in Sweden : History and Current Status
- 2017
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Ingår i: Frontiers in Pharmacology. - : Frontiers Media S.A.. - 1663-9812. ; 8
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Forskningsöversikt (refereegranskat)abstract
- The Swedish EAA System started as a regional initiative and rapidly grew to become a national level activity. An important feature of the system today is its complete integration into the national process for managed introduction and follow-up of new medicines. The system will continue to evolve as a response both to the changing landscape of health innovations and to new policy initiatives at the regional, national and international level.
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| 8. |
- Hesse, Ulrik, et al.
(författare)
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Impact of Delisting ARBs, Apart from Losartan, on ARB Utilisation Patterns in Denmark: Implications for Other Countries.
- 2013
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Ingår i: Applied health economics and health policy. - : Springer Science and Business Media LLC. - 1179-1896 .- 1175-5652. ; 11:6, s. 677-85
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Tidskriftsartikel (refereegranskat)abstract
- Renin-angiotensin inhibitor drugs have been a target for health authority initiatives across Europe with the potential for substantial savings once generic angiotensin-converting enzyme inhibitors (ACEIs) became available without compromising care. Recently, losartan was the first angiotensin receptor blocker (ARB) to lose its patent. In Denmark, the authorities removed all other ARBs from the reimbursement list, apart from losartan, as they were all seen as essentially similar for the management of hypertension or congestive heart failure at appropriate doses, but more expensive. Similarly, all other ARB fixed-dose combinations (FDCs), apart from losartan, were removed from the reimbursement list.
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| 9. |
- Malmström, Rickard E
(författare)
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Neuropeptide Y Y1 receptor mechanisms in sympathetic vascular control
- 1997
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- It was demonstrated that the Y1 receptor was the predominant vascular neuropeptide Y (NPY) receptor in pig kidney and hind limb as exogenous and endogenous NPY evoked vasoconstrictor responses that were almost or totally abolished by the selective non-peptide Y1 receptor antagonist, BIBP 3226. Furthermore, renal vasoconstriction was evoked by NPY and a peptide Y1 agonist, but not by a Y 2 agonist, and these responses were strongly reduced by another non-peptide Y, receptor antagonist, SR 120107A. Moreover, expression of Y1 receptors in pig kidney and renal arteries was indicated by reverse transcriptase-polymerase chain reaction (RT PCR) and mRNA for Y1 receptors was detected in small intrarenal arteries with in situ hybridization. The NPY receptor population in the pig spleen seems to consist of both Y1 and Y2 receptors, since peptide agonists with preference for either subtype evoked splenic vasoconstriction. Splenic vasoconstriction evoked by the Y1 agonist was markedly reduced by SR 120107A. RT-PCR indicated expression of both Y1 and Y2 receptors in pig spleen and the existence of splenic Y2 receptors was also demonstrated with membrane and autoradiograpbic receptor binding. The predominant NPY receptor in both dog spleen and kidney is the Y1 receptor as demonstrated by in vivo studies, RT-PCR and receptor binding. The Y1-selectivity of SR 120107A was demonstrated by the fact that the compound displaced binding of an iodinated Y1, but not Y2, receptor ligand from membranes and sections of pig and dog spleen. Moreover, both SR 120107A and BIBP 3226 potently displaced tritiated BIBP 3226 binding from Y1 receptors in dog spleen. Increasing concentrations of BIBP 3226 caused a rightward shift in the concentration-response curves to NPY without influencing the maximal NPY-evoked contraction in guinea-pig vena cava. The antagonism appeared competitive as the slope (0.84) of the Schild plot was not significantly different from unity, with a pA2 value of 8.0. SR 120107A appeared as effective as BIBP 3226 in antagonizing NPY-evoked contractions in this vessel. SR 120107A potently inhibited Y1 receptor mediated vasoconstriction in the pig in vivo, without influencing vascular responses exerted via Y2, a, P2X1 and angiotensin II receptors. In addition, the Y, receptor antagonism of SR 120107A was of long (>3h) duration in vivo. BIBP 3226 exerted dose-dependent and equal antagonism on vascular responses to both endogenous and exogenous NPY in the pig in vivo. The elimination of BIBP 3226 from plasma fit a two-compartment model with half-lives of 2 and 20 min for the A- and B- phase, respectively. The final pharmacological evidence for NPY as a mediator of sympathetic vasoconstriction was presented. Thus, neurogenically released NPY mediates long-lasting contraction of the guinea-pig caval vein in vitro, as shown by the inhibitory effects of both BIBP 3226 and SR 120107A. In the presence of either antagonist, only an initial rapid adrenergic phase of contraction remained upon high frequency transmural electrical field stimulation in this vessel. The neurogenic contractions were largely unaffected by the S-enantiomer to BIBP 3226, BIBP 3435, which is virtually inactive on Y1 receptors. Evidence was also presented for the involvement of NPY in nonadrenergic sympathetic vasoconstriction evoked in the reserpine-treated pig in vivo. Thus, SR 120107A strongly reduced the long-lasting phase of vasoconstriction evoked in nasal mucosa and hind limb by high frequency sympathetic nerve stimulation, leaving merely an initial rapid phase of constriction. Furthermore, the reserpine-resistant sympathetic vasoconstriction in pig kidney was almost abolished by SR 120107A, whereas both the peak and duration of this response were reduced in the spleen. In contrast, the role of NPY in sympathetic vascular control is less obvious in the control pig, in which noradrenaline (NA) levels are intact and the NPY release is smaller due to prejunctional a2-receptor regulation. Reperfusion after two h of renal ischaemia was associated with venous overflow of NA, but not of NPY-like immunoreactivty (Ll). In addition, the renal sympathetic nerve-evoked overflow of NA, but not of NPY-LI, was reduced in parallel with reduced renal vasoconstrictor responses to nerve activation and exogenous agonists. The vascular responses as well as the nerve-evoked overflow of NA were partially restored a further two h after reperfusion. No overflow of either NA or NPY-LI was seen upon reperfusion after 15 min of renal ischaemia but an enhanced overflow of NPY-LI, but not NA, was observed upon sympathetic nerve stimulation and this was paralleled by an augmented vasoconstnctor response that in turn was significantly inhibited by BIBP 3226. Furthermore, the renal vasoconstrictor response to Y, receptor activation by exogenous agonists was markedly prolonged after 15 min ischaemia and this prolonged response was nearly abolished by BIBP 3226. These results suggest that, presumably due to an impaired local degradation, the role of neurogenically released NPY in renal sympathetic vasoconstriction is enhanced after short-term ischaemia compared to control conditions. It is concluded that NPY may serve as a sympathetic mediator of vasoconstriction, preferentially acting on the Y1 receptor. The role of NPY in sympathetic vascular control is enhanced after reserpine treatment and short-term ischaemia, but is less obvious in the control situation. Furthermore, BIBP 3226 and SR 120107A are selective Y, receptor antagonists both in vitro and in vivo.
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