Danish Health and Medicines Authority

Copenhagen, Denmark

Danish Health and Medicines Authority

Copenhagen, Denmark
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Abou-El-Enein M.,Charité - Medical University of Berlin | Bauer G.,University of California at Davis | Reinke P.,Charité - Medical University of Berlin | Renner M.,Paul Ehrlich Institute | And 3 more authors.
Trends in Molecular Medicine | Year: 2014

During the past decade, successful gene therapies for immunodeficiencies were finally brought to the clinic. This was accomplished through new gene therapy vectors and improved procedures for genetic modification of autologous hematopoietic stem cells. For HIV, autologous hematopoietic stem cell (HSC) gene therapy with 'anti-HIV genes' promises a functional cure for the disease. However, to develop such a therapy and translate it into a clinical application is rather challenging. The risks and benefits of such a therapy have to be understood, and regulatory hurdles need to be overcome. In this joint paper by academic researchers and regulators, we are, therefore, outlining a high level roadmap for the early stage development of HSC gene therapy as a potential functional cure for HIV. © 2014 Elsevier Ltd.


Olofsson P.,Skåne University Hospital | Ayres-De-Campos D.,University of Porto | Kessler J.,University of Bergen | Tendal B.,Danish Health and Medicines Authority | And 2 more authors.
Acta Obstetricia et Gynecologica Scandinavica | Year: 2014

We appraised the methodology, execution and quality of the five published meta-analyses that are based on the five randomized controlled trials which compared cardiotocography (CTG)+ST analysis to cardiotocography. The meta-analyses contained errors, either created de novo in handling of original data or from a failure to recognize essential differences among the randomized controlled trials, particularly in their inclusion criteria and outcome parameters. No meta-analysis contained complete and relevant data from all five randomized controlled trials. We believe that one randomized controlled trial excluded in two of the meta-analyses should have been included, whereas one randomized controlled trial that was included in all meta-analyses, should have been excluded. After correction of the uncovered errors and exclusion of the randomized controlled trial that we deemed inappropriate, our new meta-analysis showed that CTG+ST monitoring significantly reduces the fetal scalp blood sampling usage (risk ratio 0.64; 95% confidence interval 0.47-0.88), total operative delivery rate (0.93; 0.88-0.99) and metabolic acidosis rate (0.61; 0.41-0.91). © 2014 The Authors. Acta Obstetricia et Gynecologica Scandinavica published by John Wiley & Sons on behalf of Nordic Federation of Societies of Obstetrics and Gynecology.


Larsen T.B.,University of Aalborg | Rasmussen L.H.,University of Aalborg | Skjoth F.,University of Aalborg | Due K.M.,University of Aalborg | And 4 more authors.
Journal of the American College of Cardiology | Year: 2013

Objectives The aim of this study was to assess the efficacy and safety in an "everyday clinical practice" population of anticoagulant-naïve patients with atrial fibrillation (AF) treated with dabigatran etexilate after its post-approval availability in Denmark, compared with warfarin. Background Concerns have been raised about an excess of bleeding events or myocardial infarction (MI) among patients treated with the new oral direct thrombin inhibitor, dabigatran etexilate. Methods From the Danish Registry of Medicinal Product Statistics, we identified a dabigatran-treated group and a 1:2 propensity-matched warfarin-treated group of 4,978 and 8,936, respectively. Comparisons on efficacy and safety outcomes were made on the basis of Cox-proportional hazards models stratified on propensity-matched groups. Results Stroke and systemic embolism were not significantly different between warfarin- and dabigatran-treated patients. Adjusted mortality was significantly lower with both dabigatran doses (110 mg b.i.d., propensity-match group stratified hazard ratio [aHR]: 0.79, 95% confidence interval [CI]: 0.65 to 0.95; 150 mg b.i.d., aHR: 0.57, 95% CI: 0.40 to 0.80), when compared with warfarin. Pulmonary embolism was lower compared with warfarin for both doses of dabigatran. Less intracranial bleeding was seen with both dabigatran doses (110 mg b.i.d., aHR: 0.24, 95% CI: 0.08 to 0.56; 150 mg b.i.d., aHR: 0.08, 95% CI: 0.01 to 0.40). The incidence of MI was lower with both dabigatran doses (110 mg b.i.d., aHR: 0.30, 95% CI: 0.18 to 0.49; 150 mg b.i.d., aHR: 0.40, 95% CI: 0.21 to 0.70). Gastrointestinal bleeding was lower with dabigatran 110 mg b.i.d. (aHR: 0.60, 95% CI: 0.37 to 0.93) compared with warfarin but not dabigatran 150 mg b.i.d. The main findings were broadly consistent in a subgroup analysis of dabigatran users with ≥1-year follow-up (median follow-up 13.9 months [interquartile range: 12.6 to 15.3 months]). Conclusions In this "everyday clinical practice" post-approval nationwide clinical cohort, there were similar stroke/systemic embolism and major bleeding rates with dabigatran (both doses) compared with warfarin. Mortality, intracranial bleeding, pulmonary embolism, and MI were lower with dabigatran, compared with warfarin. We found no evidence of an excess of bleeding events or MI among dabigatran-treated patients in this propensity-matched comparison against warfarin, even in the subgroup with ≥1-year follow-up. © 2013 by the American College of Cardiology Foundation.


Olofsson P.,Skåne University Hospital | Ayres-De-Campos D.,University of Porto | Kessler J.,University of Bergen | Tendal B.,Danish Health and Medicines Authority | And 2 more authors.
Acta Obstetricia et Gynecologica Scandinavica | Year: 2014

We reappraised the five randomized controlled trials that compared cardiotocography plus ECG ST interval analysis (CTG+ST) vs. cardiotocography. The numbers enrolled ranged from 5681 (Dutch randomized controlled trial) to 799 (French randomized controlled trial). The Swedish randomized controlled trial (n = 5049) was the only trial adequately powered to show a difference in metabolic acidosis, and the Plymouth randomized controlled trial (n = 2434) was only powered to show a difference in operative delivery for fetal distress. There were considerable differences in study design: the French randomized controlled trial used different inclusion criteria, and the Finnish randomized controlled trial (n = 1483) used a different metabolic acidosis definition. In the CTG+ST study arms, the larger Plymouth, Swedish and Dutch trials showed lower operative delivery and metabolic acidosis rates, whereas the smaller Finnish and French trials showed minor differences in operative delivery and higher metabolic acidosis rates. We conclude that the differences in outcomes are likely due to the considerable differences in study design and size. This will enhance heterogeneity effects in any subsequent meta-analysis. © 2014 The Authors. Acta Obstetricia et Gynecologica Scandinavica published by John Wiley & Sons on behalf of Nordic Federation of Societies of Obstetrics and Gynecology.


Nordahl H.,Copenhagen University | Lange T.,Copenhagen University | Osler M.,Glostrup University Hospital | Diderichsen F.,Copenhagen University | And 5 more authors.
Epidemiology | Year: 2014

Background: Differential exposures to behavioral risk factors have been shown to play an important mediating role on the education-mortality relation. However, little is known about the extent to which educational attainment interacts with health behavior, possibly through differential vulnerability. Methods: In a cohort study of 76,294 participants 30 to 70 years of age, we estimated educational differences in cause-specific mortality from 1980 through 2009 and the mediating role of behavioral risk factors (smoking, alcohol intake, physical activity, and body mass index). With the use of marginal structural models and three-way effect decomposition, we simultaneously regarded the behavioral risk factors as intermediates and clarified the role of their interaction with educational exposure. Results: Rate differences in mortality comparing participants with low to high education were 1,277 (95% confidence interval = 1,062 to 1,492) per 100,000 person-years for men and 746 (598 to 894) per 100,000 person-years for women. Smoking was the strongest mediator for cardiovascular disease, cancer, and respiratory disease mortality when conditioning on sex, age, and cohort. The proportion mediated through smoking was most pronounced in cancer mortality as a combination of the pure indirect effect, owing to differential exposure (men, 42% [25% to 75%]; women, 36% [17% to 74%]) and the mediated interactive effect, owing to differential vulnerability (men, 18% [2% to 35%], women, 26% [8% to 50%]). The mediating effects through body mass index, alcohol intake, or physical activity were partial and varied for the causes of deaths. Conclusion: Differential exposure and vulnerability should be addressed simultaneously, as these mechanisms are not mutually exclusive and may operate at the same time. Copyright © 2014 by Lippincott Williams & Wilkins.


Weise M.,Federal Institute for Drugs and Medical Devices | Kurki P.,Finnish Medicines Agency | Wolff-Holz E.,Paul Ehrlich Institute | Bielsky M.-C.,Medicines and Healthcare Products Regulatory Agency | And 2 more authors.
Blood | Year: 2014

Despite the establishment of a specific approval pathway, the issuance of detailed scientific guidelines for the development of similar biological medicinal products (so-called "biosimilars") and the approval of several biosimilars in the European Union, acceptance of biosimilars in the medical community continues to be low. This is especially true in therapeutic indications for which no specific clinical trials with the biosimilar have been performed and that have been licensed based on extrapolation of efficacy and safety data from other indications. This article addresses the concerns frequently raised in the medical community about the use of biosimilars in such extrapolated indications and explains the underlying scientific and regulatory decision making including some real-life examples from recently licensed biosimilars. © 2014 by The American Society of Hematology.


Kessel L.,Copenhagen University | Kessel L.,Danish Health and Medicines Authority | Tendal B.,Danish Health and Medicines Authority | Jorgensen K.J.,Danish Health and Medicines Authority | And 5 more authors.
Ophthalmology | Year: 2014

Purpose: Favorable outcome after cataract surgery depends on proper control of the inflammatory response induced by cataract surgery. Pseudophakic cystoid macular edema is an important cause of visual decline after uncomplicated cataract surgery.Methods: We performed a systematic literature search in Medline, CINAHL, Cochrane, and EMBASE databases to identify randomized trials published from 1996 onward comparing topical steroids with topical NSAIDs in controlling inflammation and preventing PCME in patients undergoing phacoemulsification with posterior chamber intraocular lens implantation for age-related cataract.Design: We compared the efficacy of topical steroids with topical nonsteroidal anti-inflammatory drugs (NSAIDs) in controlling inflammation and preventing pseudophakic cystoid macular edema (PCME) after uncomplicated cataract surgery.Participants: Patients undergoing uncomplicated surgery for age-related cataract.Main Outcome Measures: Postoperative inflammation and pseudophakic cystoid macular edema.Results: Fifteen randomized trials were identified. Postoperative inflammation was less in patients randomized to NSAIDs. The prevalence of PCME was significantly higher in the steroid group than in the NSAID group: 3.8% versus 25.3% of patients, risk ratio 5.35 (95% confidence interval, 2.94-9.76). There was no statistically significant difference in the number of adverse events in the 2 treatment groups.Conclusions: We found low to moderate quality of evidence that topical NSAIDs are more effective in controlling postoperative inflammation after cataract surgery. We found high-quality evidence that topical NSAIDs are more effective than topical steroids in preventing PCME. The use of topical NSAIDs was not associated with an increased events. We recommend using topical NSAIDs to prevent inflammation and PCME after routine cataract surgery. © 2014 by the American Academy of Ophthalmology.


Hansen S.,Copenhagen University | Baptiste K.E.,Danish Health and Medicines Authority | Fjeldborg J.,Copenhagen University | Horohov D.W.,University of Kentucky
Ageing Research Reviews | Year: 2015

The equine aging process involves many changes to the immune system that may be related to genetics, the level of nutrition, the environment and/or an underlying subclinical disease. Geriatric horses defined as horses above the age of 20, exhibit a decline in body condition, muscle tone and general well-being. It is not known whether these changes contribute to decreased immune function or are the result of declining immune function. Geriatric years are characterized by increased susceptibility to infections and a reduced antibody response to vaccination as a result of changes in the immune system. Humans and horses share many of these age-related changes, with only a few differences. Thus, inflamm-aging and immunosenescence are well-described phenomena in both human and equine research, particularly in relation to the peripheral blood and especially the T-cell compartment. However, the lung is faced with unique challenges because of its constant interaction with the external environment and thus may not share similarities to peripheral blood when considering age-related changes in immune function. Indeed, recent studies have shown discrepancies in cytokine mRNA and protein expression between the peripheral blood and bronchoalveolar lavage immune cells. These results provide important evidence that age-related immune changes or 'dys-functions' are organ-specific. © 2014 Elsevier B.V.


Folkvardsen D.B.,Statens Serum Institute | Svensson E.,Statens Serum Institute | Thomsen V.O.,Statens Serum Institute | Thomsen V.O.,Danish Health and Medicines Authority | And 6 more authors.
Journal of Clinical Microbiology | Year: 2013

Patients may harbor both drug-susceptible and -resistant bacteria, representing heteroresistance. We studied mixtures of isoniazid- resistant and -susceptible Mycobacterium tuberculosis strains. Conventional drug susceptibility testing was the most sensitive method of detection, whereas the line probe assay and sequencing were not able to detect the clinically relevant 1% proportion of resistant bacteria. Copyright © 2013, American Society for Microbiology.


Callreus T.,Danish Health and Medicines Authority
Pharmaceutical Medicine | Year: 2013

Traditionally, bioethics has focused on the obligations of healthcare professionals and the rights of individual patients as well as participants in clinical research. However, in recent years, this center of attention has been questioned and a new "Public Health Ethics" has emerged. It argues that when dealing with ethical issues related to research or interventions, the health of groups and populations should be considered and not only that of individuals. This article reviews the background to the current debate on Public Health Ethics as well as some ethical theories and principles guiding its development. Following a discussion of issues in pharmacovigilance with an ethical dimension, the article explores the potential implications of the emergence of a Public Health Ethics perspective for regulatory pharmacovigilance as a public health activity. In summary it appears that this new perspective may offer a new take on ethical issues in pharmacovigilance and provide guidance as to when public health paternalism is justified or when the public good should take precedence over rights of individuals. © 2013 Springer International Publishing Switzerland. Reference:.

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