Is a controlled randomised trial the non-plus-ultra design? A contribution to discussion on comparative, controlled, non-randomised trials

AbstractBackgroundClinical studies provide formalised experience for evidence-based medicine (EBM). Many people consider a controlled randomised trial (CRT, identical to a randomised controlled trial RCT) to be the non-plus-ultra design. However, CRTs also have limitations. The problem is not randomisation itself but informed consent for randomisation and masking of therapies according to today's legal and ethical standards. We do not want to de-rate CRTs, but we would like to contribute to the discussion on clinical research methodology.SituationInformed consent to a CRT and masking of therapies plainly select patients. The excellent internal validity of CRTs can be counterbalanced by poor external validity, because internal and external validity act as antagonists. In a CRT, patients may feel like guinea pigs, this can decrease compliance, cause protocol violations, reduce self-healing properties, suppress unspecific therapeutic effects and possibly even modify specific efficacy.DiscussionA control group (comparative study) is most important for the degree of evidence achieved by a trial. Study control by detailed protocol and good clinical practice (controlled study) is second in importance and randomisation and masking is third (thus the sequence CRT instead of RCT). Controlled non-randomised trials are just as ambitious and detailed as CRTs.RecommendationWe recommend clinicians and biometricians to take high quality controlled non-randomised trials into consideration more often. They combine good internal and external validity, better suit daily medical practice, show better patient compliance and fewer protocol violations, deliver estimators unbiased by alienated patients, and perhaps provide a clearer explanation of the achieved success

Разработка измерительного преобразователя радиационного измерителя поверхностной плотности экранного покрытия

Работа направлена на разработку преобразователя радиационного измерителя, позволяющего осуществлять технологический контроль нанесения защитного покрытия при наличии доступа только с одной стороны.The work is aimed at the development of a radiation meter converter, which allows the technological control of the application of protective coatings in the presence of access only on one side

IgG Antibodies against Measles, Rubella, and Varicella Zoster Virus Predict Conversion to Multiple Sclerosis in Clinically Isolated Syndrome

BACKGROUND:Multiple sclerosis (MS) is characterized by a polyspecific B-cell response to neurotropic viruses such as measles, rubella and varicella zoster, with the corresponding antibodies measurable in CSF as the so-called "MRZ reaction" (MRZR). We aimed to evaluate the relevance of MRZR to predict conversion of patients with clinically isolated syndrome (CIS) to MS, and to compare it to oligoclonal bands (OCB) and MRI. METHODOLOGY/PRINCIPAL FINDINGS:MRZR was determined in a prospective study over 2 years including 40 patients that remained CIS over follow-up (CIS-CIS) and 49 patients that developed MS (CIS-RRMS) using ELISA. Using logistic regression, a score (MRZS) balancing the predictive value of the antibody indices included in MRZR was defined (9 points measles, 8 points rubella, 1 point varicella zoster, cutpoint: sum of scores greater 10). MRZR and MRZS were significantly more frequent in CIS-RRMS as compared to CIS-CIS (p=0.04 and p=0.02). MRZS showed the best positive predictive value (PPV) of all parameters investigated (79%, 95%-CI: 54-94%), which could be further increased by combination with MRI (91%, 95%-CI: 59-99%). CONCLUSIONS/SIGNIFICANCE:Our data indicate the relevance of MRZR to predict conversion to MS. It furthermore shows the importance of weighting the different antibody indices included in MRZR and suggest that patients with positive MRZR are candidates for an early begin of immunomodulatory therapy

A language-based sum score for the course and therapeutic intervention in primary progressive aphasia

Background: With upcoming therapeutic interventions for patients with primary progressive aphasia (PPA), instruments for the follow-up of patients are needed to describe disease progression and to evaluate potential therapeutic effects. So far, volumetric brain changes have been proposed as clinical endpoints in the literature, but cognitive scores are still lacking. This study followed disease progression predominantly in language-based performance within 1 year and defined a PPA sum score which can be used in therapeutic interventions. Methods: We assessed 28 patients with nonfluent variant PPA, 17 with semantic variant PPA, 13 with logopenic variant PPA, and 28 healthy controls in detail for 1 year. The most informative neuropsychological assessments were combined to a sum score, and associations between brain atrophy were investigated followed by a sample size calculation for clinical trials. Results: Significant absolute changes up to 20% in cognitive tests were found after 1 year. Semantic and phonemic word fluency, Boston Naming Test, Digit Span, Token Test, AAT Written language, and Cookie Test were identified as the best markers for disease progression. These tasks provide the basis of a new PPA sum score. Assuming a therapeutic effect of 50% reduction in cognitive decline for sample size calculations, a number of 56 cases is needed to find a significant treatment effect. Correlations between cognitive decline and atrophy showed a correlation up to r = 0.7 between the sum score and frontal structures, namely the superior and inferior frontal gyrus, as well as with left-sided subcortical structures. Conclusion: Our findings support the high performance of the proposed sum score in the follow-up of PPA and recommend it as an outcome measure in intervention studies

Needs-oriented discharge planning and monitoring for high utilisers of psychiatric services (NODPAM): Design and methods

<p>Abstract</p> <p>Background</p> <p>Attempts to reduce high utilisation of psychiatric inpatient care by targeting the critical time of hospital discharge have been rare.</p> <p>Methods</p> <p>This paper presents design and methods of the study "Effectiveness and Cost-Effectiveness of Needs-Oriented Discharge Planning and Monitoring for High Utilisers of Psychiatric Services" (NODPAM), a multicentre RCT conducted in five psychiatric hospitals in Germany. Inclusion criteria are receipt of inpatient psychiatric care, adult age, diagnosis of schizophrenia or affective disorder, defined high utilisation of psychiatric care during two years prior to the current admission, and given informed consent. Consecutive recruitment started in April 2006. Since then, during a period of 18 months, comprehensive outcome data of 490 participants is being collected at baseline and during three follow-up measurement points.</p> <p>The manualised intervention applies principles of needs-led care and focuses on the inpatient-outpatient transition. A trained intervention worker provides two intervention sessions: (a) Discharge planning: Just before discharge with the patient and responsible clinician at the inpatient service; (b) Monitoring: Three months after discharge with the patient and outpatient clinician. A written treatment plan is signed by all participants after each session.</p> <p>Primary endpoints are whether participants in the intervention group will show fewer hospital days and readmissions to hospital. Secondary endpoints are better compliance with aftercare, better clinical outcome and quality of life, as well as cost-effectiveness and cost-utility.</p> <p>Discussion</p> <p>If a needs-oriented discharge planning and monitoring proves to be successful in this RCT, a tool will be at hand to improve patient outcome and reduce costs via harmonising fragmented mental health service provision.</p> <p>Trial Registration</p> <p>ISRCTN59603527</p

Evaluation of a health promotion program in children: Study protocol and design of the cluster-randomized Baden-Württemberg primary school study [DRKS-ID: DRKS00000494]

<p>Abstract</p> <p>Background</p> <p>Increasing prevalences of overweight and obesity in children are known problems in industrialized countries. Early prevention is important as overweight and obesity persist over time and are related with health problems later in adulthood. "Komm mit in das gesunde Boot - Grundschule" is a school-based program to promote a healthier lifestyle. Main goals of the intervention are to increase physical activity, decrease the consumption of sugar-sweetened beverages, and to decrease time spent sedentary by promoting active choices for healthy lifestyle. The program to date is distributed by 34 project delivery consultants in the state of Baden-Württemberg and is currently implemented in 427 primary schools. The efficacy of this large scale intervention is examined via the Baden-Württemberg Study.</p> <p>Methods/Design</p> <p>The Baden-Württemberg Study is a prospective, stratified, cluster-randomized, and longitudinal study with two groups (intervention group and control group). Measurements were taken at the beginning of the academic years 2010/2011 and 2011/2012. Efficacy of the intervention is being assessed using three main outcomes: changes in waist circumference, skinfold thickness and 6 minutes run. Stratified cluster-randomization (according to class grade level) was performed for primary schools; pupils, teachers/principals, and parents were investigated. An approximately balanced number of classes in intervention group and control group could be reached by stratified randomization and was maintained at follow-up.</p> <p>Discussion</p> <p>At present, "Komm mit in das Gesunde Boot - Grundschule" is the largest school-based health promotion program in Germany. Comparative objective main outcomes are used for the evaluation of efficacy. Simulations showed sufficient power with the existing sample size. Therefore, the results will show whether the promotion of a healthier lifestyle in primary school children is possible using a relatively low effort within a school-based program involving children, teachers and parents. The research team anticipates that not only efficacy will be proven in this study but also expects many other positive effects of the program.</p> <p>Trial registration</p> <p>German Clinical Trials Register (DRKS), DRKS-ID: DRKS00000494</p

Computereinsatz und &quot;E-Learning&quot; im Lehrprojekt Biometrie []

[english] Starting from the necessity for a change in teaching practice as required by new regulations for registration to practice medicine, in the teaching project biometry teaching will be brought closer to "new media" in this subject, and at the same time the attempt will be made to raise the level of motivation amongst students. In doing so, present-day learning will be approached through the use of a computer-assisted teaching system. A comprehensible sustainability of acquired knowledge and thus a rise in motivation should result in the learning of a statistic software programme. Integration in a complex medical model should also effect this rise in motivation. The project will be implemented for the first time in this semester (SS 2005), and thus so far few experience values and other data are available. [german] Ausgehend von der Notwendigkeit einer Veränderung der Lehre nach neuer ÄAppO wird in dem Lehrprojekt Biometrie die Lehre in dem Fach näher herangebracht an die "neuen Medien" und gleichzeitig versucht, die Motivation bei den Studierenden zu erhöhen. Dabei wird durch den Einsatz eines computergestützten Lehrsystems dem heutigen Lernen näher gekommen. Eine nachvollziehbare Nachhaltigkeit des Erlernten und demnach eine Motivationssteigerung soll das Erlernen eines Statistiksoftwareprogrammes erbringen. Eine Einbindung in ein komplexeres medizinisches Beispiel soll ebenfalls diese Motivationssteigerung bewirken. Das Projekt wird in diesem Semester (SS 2005) zum ersten Mal umgesetzt so dass bisher wenige Erfahrungswerte und keine Daten für einen Vergleich vorliegen

Selection of a statistical software in the

Based on the major revision of the regulation for the licence to practice medicine (ÄAppO) we adapted teaching in medical biometry. The so-called “teaching project Biometry” is intended to give basics of biometry to the students by using computer methods. For this purpose an E-Learning system is established and a statistical software is introduced. Methods of statistics are inducted using a real medical patient data set. First of all the new project is intended to increase the students’ motivation for the subsidiary subject of medical biometry, secondly to improve the sustainability for future medical research and for dissertation writing. This field report mainly describes the selection process and the applicability of a statistical software. Additionally the implementation of the course will be presented

STATISTICAL CONSIDERATIONS FOR LOT-BY-LOT ACCEPTANCE/REJECTION SAMPLING WITH AN ATTRIBUTE

The standard procedure for lot-by-lot acceptance/rejection sampling described in literature makes always a decision. If there are more invalid items in the sample than specified, then the lot is rejected, otherwise the lot is accepted. However, if the actual proportion of invalid items in the lot is close to the accepted quality level then it is - in principle - impossible to control the customer's and the producer's risk with a reasonable sample size. The published standard procedure can result in acceptance of the lot even if there is insufficient information. We think this is unfair to the customer. Three statistical methods with a common acceptable quality limit are proposed and discussed: A simple procedure, confidence intervals, and finally a statistical test. The idea of a statistical test, its application in lot-by-lot acceptance/rejection sampling, and the proposed statistical test are described in detail and with examples. Additionally, determination of sample size and multiple step sampling plans are characterized