The LaLiMo Trial: lamotrigine compared with levetiracetam in the initial 26 weeks of monotherapy for focal and generalised epilepsy—an open-label, prospective, randomised controlled multicenter study

Background: Of the newer antiepileptic drugs, lamotrigine (LTG) and levetiracetam (LEV) are popular first choice drugs for epilepsy. The authors compared these drugs with regard to their efficacy and tolerability in the initial monotherapy for epilepsy. Methods: A randomised, open-label, controlled, parallel group, multicenter trial was conducted to test the superiority of the LEV arm over the LTG arm. The primary endpoint was the rate of seizure-free patients in the first 6 weeks (two-sided Fisher's exact test, α=0.05, intent-to-treat set). Furthermore, efficacy, tolerability and quality of life were evaluated. The authors included 409 patients aged ≥12 years with newly diagnosed focal or generalised epilepsy defined by either two or more unprovoked seizures or one first seizure with high risk for recurrence. Patients were titrated to 2000 mg/day of LEV or 200 mg/day of LTG reached on day 22 or 71, respectively. Two dose adjustments by 500/50 mg were allowed. Results: The proportions of seizure-free patients were 67.5% (LEV) versus 64.0% (LTG) 6 weeks after randomisation (p=0.47), and 45.2% (LEV) versus 47.8% (LTG) during the whole treatment period of 26 weeks. The HR (LEV vs LTG) for seizure-free time was 0.86 (95% CI, 0.61 to 1.22). Adverse events occurred in 74.5% (LEV) versus 70.6% (LTG) of the patients (p=0.38). Adverse events associated with study discontinuation occurred in 17/204 (LEV) versus 8/201 (LTG) patients (p=0.07). Conclusions: There were no significant differences with regard to efficacy and tolerability of LEV and LTG in newly diagnosed focal and generalised epilepsy despite more rapid titration in the LEV arm. Clinical trial registration number: ClinicalTrials.gov identifier NCT00242606

Protocol for an observational study to identify potential predictors of an acute exacerbation in patients with chronic obstructive pulmonary disease (the PACE Study).

INTRODUCTION: Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are the most critical events for patients with COPD that have a negative impact on patients' quality of life, accelerate disease progression, and can result in hospital admissions and death. Although there is no distinct definition or detailed knowledge about AECOPD, it is commonly used as primary outcome in clinical studies. Furthermore, it may be difficult in clinical practice to differentiate the worsening of symptoms due to an AECOPD or to the development of heart failure. Therefore, it is of major clinical importance to investigate the underlying pathophysiology, and if possible, predictors of an AECOPD and thus to identify patients who are at high risk for developing an acute exacerbation. METHODS AND ANALYSIS: In total, 355 patients with COPD will be included prospectively to this study during a 3-week inpatient pulmonary rehabilitation programme at the Schoen Klinik Berchtesgadener Land, Schoenau am Koenigssee (Germany). All patients will be closely monitored from admission to discharge. Lung function, exercise tests, clinical parameters, quality of life, physical activity and symptoms will be recorded, and blood samples and exhaled air will be collected. If a patient develops an AECOPD, there will be additional comprehensive diagnostic assessments to differentiate between cardiac, pulmonary or cardiopulmonary causes of worsening. Follow-up measures will be performed at 6, 12 and 24 months.Exploratory data analyses methods will be used for the primary research question (screening and identification of possible factors to predict an AECOPD). Regression analyses and a generalised linear model with a binomial outcome (AECOPD) will be applied to test if predictors are significant. ETHICS AND DISSEMINATION: This study has been approved by the Ethical Committee of the Philipps University Marburg, Germany (No. 61/19). The results will be presented in conferences and published in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: NCT04140097

Standard requirements for GCP-compliant data management in multinational clinical trials

<p>Abstract</p> <p>Background</p> <p>A recent survey has shown that data management in clinical trials performed by academic trial units still faces many difficulties (e.g. heterogeneity of software products, deficits in quality management, limited human and financial resources and the complexity of running a local computer centre). Unfortunately, no specific, practical and open standard for both GCP-compliant data management and the underlying IT-infrastructure is available to improve the situation. For that reason the "Working Group on Data Centres" of the European Clinical Research Infrastructures Network (ECRIN) has developed a standard specifying the requirements for high quality GCP-compliant data management in multinational clinical trials.</p> <p>Methods</p> <p>International, European and national regulations and guidelines relevant to GCP, data security and IT infrastructures, as well as ECRIN documents produced previously, were evaluated to provide a starting point for the development of standard requirements. The requirements were produced by expert consensus of the ECRIN Working group on Data Centres, using a structured and standardised process. The requirements were divided into two main parts: an IT part covering standards for the underlying IT infrastructure and computer systems in general, and a Data Management (DM) part covering requirements for data management applications in clinical trials.</p> <p>Results</p> <p>The standard developed includes 115 IT requirements, split into 15 separate sections, 107 DM requirements (in 12 sections) and 13 other requirements (2 sections). Sections IT01 to IT05 deal with the basic IT infrastructure while IT06 and IT07 cover validation and local software development. IT08 to IT015 concern the aspects of IT systems that directly support clinical trial management. Sections DM01 to DM03 cover the implementation of a specific clinical data management application, i.e. for a specific trial, whilst DM04 to DM12 address the data management of trials across the unit. Section IN01 is dedicated to international aspects and ST01 to the competence of a trials unit's staff.</p> <p>Conclusions</p> <p>The standard is intended to provide an open and widely used set of requirements for GCP-compliant data management, particularly in academic trial units. It is the intention that ECRIN will use these requirements as the basis for the certification of ECRIN data centres.</p

The ANTOP study: focal psychodynamic psychotherapy, cognitive-behavioural therapy, and treatment-as-usual in outpatients with anorexia nervosa - a randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Anorexia nervosa is a serious eating disorder leading to high morbidity and mortality as a result of both malnutrition and suicide. The seriousness of the disorder requires extensive knowledge of effective treatment options. However, evidence for treatment efficacy in this area is remarkably weak. A recent Cochrane review states that there is an urgent need for large, well-designed treatment studies for patients with anorexia nervosa. The aim of this particular multi-centre study is to evaluate the efficacy of two standardized outpatient treatments for patients with anorexia nervosa: focal psychodynamic (FPT) and cognitive behavioural therapy (CBT). Each therapeutic approach is compared to a "treatment-as-usual" control group.</p> <p>Methods/Design</p> <p>237 patients meeting eligibility criteria are randomly and evenly assigned to the three groups – two intervention groups (CBT and FPT) and one control group. The treatment period for each intervention group is 10 months, consisting of 40 sessions respectively. Body weight, eating disorder related symptoms, and variables of therapeutic alliance are measured during the course of treatment. Psychotherapy sessions are audiotaped for adherence monitoring. The treatment in the control group, both the dosage and type of therapy, is not regulated in the study protocol, but rather reflects the current practice of established outpatient care. The primary outcome measure is the body mass index (BMI) at the end of the treatment (10 months after randomization).</p> <p>Discussion</p> <p>The study design surmounts the disadvantages of previous studies in that it provides a randomized controlled design, a large sample size, adequate inclusion criteria, an adequate treatment protocol, and a clear separation of the treatment conditions in order to avoid contamination. Nevertheless, the study has to deal with difficulties specific to the psychopathology of anorexia nervosa. The treatment protocol allows for dealing with the typically occurring medical complications without dropping patients from the protocol. However, because patients are difficult to recruit and often ambivalent about treatment, a drop-out rate of 30% is assumed for sample size calculation. Due to the ethical problem of denying active treatment to patients with anorexia nervosa, the control group is defined as "treatment-as-usual".</p> <p>Trial registration</p> <p>Current Controlled Trials ISRCTN72809357</p

Gemeinsame Empfehlungen zur Gesamtleistungsrechnung als Baustein zur Vereinfachung der Vertragsgestaltung

The objective of clinical trials is to transfer findings gained from basic research to patients and to result in innovative treatment approaches. Along with basic research, results from clinical trials thus represent a core area of medical advances. As a location for clinical trials, Germany is currently well-positioned and internationally competitive. This is evident in its position as No. 2 in Europe and No. 3 worldwide - behind the US and UK - in clinical trials of pharmaceuticals . Maintaining and further improving this favorable positioning as a location for clinical trials is in the mutual interest of all parties involved in the field of clinical research, patients, trial sites and sponsors of clinical trials.For patients, clinical trials offer opportunities to gain early access to innovative therapy options. In addition to the scientific interest from medical faculties, clinical research is thereby an important aspect for university clinics in Germany as they fulfill their medical care mandate. Their involvement in clinical trials gives physicians the ability to gather experience with new treatment approaches at an early stage and to pass this know-how on to their patients. A location's clinical research is thus an important competitive factor in terms of international comparison as well. Industry likewise benefits from the favorable research infrastructure in Germany, which provides rapid patient recruitment and outstanding quality of results obtained and can thus contribute to the early approval of new drugs. From the perspective of the authors, it is therefore essential that Germany continues to remain competitive as a location for conducting clinical trials, precisely because the number of clinical trials is decreasing overall. Companies themselves are in international competition internally and externally, which often creates a certain pressure on trial preparation and thus on the start of a clinical trial. To ensure that a clinical trial can begin early, it is essential that contracts related to the trial are concluded quickly and simply, including remuneration for participants and full, transparent and comprehensible coverage of content for the business relationship. The swift agreement of key contractual and budgetary aspects is therefore in the interest of everyone involved.Against this backdrop, the German Association of Medical Faculties (MFT), the German Association of Academic Medical Centers (VUD), the Coordination Center for Clinical Studies (KKS-Netzwerk) and the German Association of Research-Based Pharmaceutical Companies (vfa) have held joint discussions regarding an important aspect of the contract negotiations - the cost consideration of clinical trials.As a result of these talks, these organizations have developed and published joint "Recommendations for the preparation of a total services calculation for remuneration related to the conduct of a clinical trial in a trial center" , . The parties concerned share the conviction that, against the backdrops described, it would be helpful if the potential contract partners had access to recommendations that offer examples of constantly recurring cost positions in order to more precisely determine remuneration related to the conduct of a clinical trial.This article explains how the "Recommendations for the preparation of a total services calculation for remuneration related to the conduct of a clinical trial in a trial center" , were developed and provides an overview of their content.Klinische Prüfungen haben zum Ziel, die in der Grundlagenforschung gewonnenen Erkenntnisse auf den Patienten zu übertragen und innovative Behandlungsansätze zu schaffen. Neben der Grundlagenforschung bilden die Ergebnisse klinischer Prüfungen damit einen Kernbereich medizinischen Fortschritts. Derzeit ist Deutschland als Standort für die Durchführung klinischer Prüfungen gut aufgestellt und international wettbewerbsfähig. Dies zeigt sich an seiner Position als Nummer 2 in Europa und Nummer 2 weltweit - hinter den USA bzw. UK - bei klinischen Prüfungen von Arzneimitteln . Diese gute Positionierung des Studienstandortes zu erhalten und weiter zu verbessern, liegt im gemeinsamen Interesse aller Beteiligten im Bereich der klinischen Forschung, der Patienten, der Studienzentren und der Sponsoren klinischer Prüfungen.Für Patienten bieten klinische Prüfungen die Möglichkeiten, frühzeitig Zugang zu innovativen Therapiemöglichkeiten zu erhalten. Neben dem wissenschaftlichen Interesse der medizinischen Fakultäten ist die klinische Forschung damit für die Universitätskliniken in Deutschland ein wichtiger Aspekt bei der Wahrnehmung ihres Auftrags der Krankenversorgung. Die Einbindung in klinische Prüfungen gibt den Ärzten frühzeitig die Möglichkeit, Erfahrungen mit neuen Behandlungsansätzen zu sammeln und an die Patienten weitergeben zu können. Klinische Forschung an einem Standort ist damit ein wichtiger Wettbewerbsfaktor auch im internationalen Vergleich. Die Industrie profitiert auf der anderen Seite von der guten Forschungsinfrastruktur in Deutschland, da diese einen schnellen Patienteneinschluss und eine sehr hohe Qualität der gewonnenen Ergebnisse gewährleisten und damit zu einer frühzeitigen Zulassung eines neuen Arzneimittels beiträgt. Aus Sicht der Verfasser ist es daher wichtig, dass der Standort Deutschland bei der Durchführung klinischer Prüfungen auch zukünftig wettbewerbsfähig bleibt, gerade weil die Zahlen klinischer Prüfungen insgesamt zurückgehen. Die Unternehmen stehen ihrerseits im internationalen Wettbewerb, so dass die Vorbereitung der Studiendurchführung und damit der Start einer klinischen Prüfung häufig einem gewissen zeitlichen Druck unterliegen. Um eine klinische Prüfung frühzeitig beginnen zu können, ist es unerlässlich, Studienverträge inklusive der darin enthaltenden Vergütung zwischen den Beteiligten schnell und einfach, dabei aber inhaltlich umfassend, transparent und nachvollziehbar in der Leistungsbeziehung abzuschließen. Die zügige Einigung der wesentlichen vertraglichen sowie budgetären Aspekte liegt damit im Interesse aller Beteiligten.Vor diesem Hintergrund haben der Medizinische Fakultätentag (MFT), der Verband der Universitätsklinika Deutschlands (VUD), die Koordinierungszentren für Klinische Studien (KKS-Netzwerk) und der Verband forschender Arzneimittelhersteller (vfa) gemeinsam einen wichtigen Aspekt im Hinblick auf die Vertragsverhandlungen diskutiert - die Kostenbetrachtung klinischer Prüfungen.Als Ergebnis dieser Diskussionen haben diese Organisationen "Gemeinsame Empfehlungen zur Erstellung einer Gesamtleistungsrechnung der Vergütung bei der Durchführung einer klinischen Prüfung in einem Prüfzentrum" erarbeitet und veröffentlicht , . Die Beteiligten sind gemeinsam der Überzeugung, dass es vor dem beschriebenen Hintergrund hilfreich erscheint, wenn die potentiellen Vertragspartner in ihren jeweiligen Verhandlungen über Empfehlungen verfügen, die stetig wiederkehrende Kostenpositionen zur näheren Bestimmung der Vergütung im Rahmen der Durchführung einer klinischen Prüfung beispielhaft benennen.Dieser Artikel erörtert die Hintergründe der "Gemeinsamen Empfehlungen zur Erstellung einer Gesamtleistungsrechnung der Vergütung bei der Durchführung einer klinischen Prüfung in einem Prüfzentrum" , und ermöglicht einen Überblick über deren Inhalt