A pilot test of the new Swiss regulatory procedure for categorizing clinical trials by risk: A randomized controlled trial

BACKGROUND/AIMS Several countries are working to adapt clinical trial regulations to align the approval process to the level of risk for trial participants. The optimal framework to categorize clinical trials according to risk remains unclear, however. Switzerland is the first European country to adopt a risk-based categorization procedure in January 2014. We assessed how accurately and consistently clinical trials are categorized using two different approaches: an approach using criteria set forth in the new law (concept) or an intuitive approach (ad hoc). METHODS This was a randomized controlled trial with a method-comparison study nested in each arm. We used clinical trial protocols from eight Swiss ethics committees approved between 2010 and 2011. Protocols were randomly assigned to be categorized in one of three risk categories using the concept or the ad hoc approach. Each protocol was independently categorized by the trial's sponsor, a group of experts and the approving ethics committee. The primary outcome was the difference in categorization agreement between the expert group and sponsors across arms. Linear weighted kappa was used to quantify agreements, with the difference between kappas being the primary effect measure. RESULTS We included 142 of 231 protocols in the final analysis (concept = 78; ad hoc = 64). Raw agreement between the expert group and sponsors was 0.74 in the concept and 0.78 in the ad hoc arm. Chance-corrected agreement was higher in the ad hoc (kappa: 0.34 (95% confidence interval = 0.10-0.58)) than in the concept arm (0.27 (0.06-0.50)), but the difference was not significant (p = 0.67). LIMITATIONS The main limitation was the large number of protocols excluded from the analysis mostly because they did not fit with the clinical trial definition of the new law. CONCLUSION A structured risk categorization approach was not better than an ad hoc approach. Laws introducing risk-based approaches should provide guidelines, examples and templates to ensure correct application.

Detecting dementia in patients with normal neuropsychological screening by Short Smell Test and Palmo-Mental Reflex Test: an observational study

BACKGROUND General practitioners (GPs) are in best position to suspect dementia. Mini-Mental State Examination (MMSE) and Clock Drawing Test (CDT) are widely used. Additional neurological tests may increase the accuracy of diagnosis. We aimed to evaluate diagnostic ability to detect dementia with a Short Smell Test (SST) and Palmo-Mental Reflex (PMR) in patients whose MMSE and CDT are normal, but who show signs of cognitive dysfunction. METHODS This was a 3.5-year cross-sectional observational study in the Memory Clinic of the University Department of Geriatrics in Bern, Switzerland. Participating patients with normal MMSE (>26 points) and CDT (>5 points) were referred by GPs because they suspected dementia. All were examined according to a standardized protocol. Diagnosis of dementia was based on DSM-IV TR criteria. We used SST and PMR to determine if they accurately detected dementia. RESULTS In our cohort, 154 patients suspected of dementia had normal MMSE and CDT test results. Of these, 17 (11 %) were demented. If SST or PMR were abnormal, sensitivity was 71 % (95 % CI 44-90 %), and specificity 64 % (95 % CI 55-72 %) for detecting dementia. If both tests were abnormal, sensitivity was 24 % (95 % CI 7-50 %), but specificity increased to 93 % (95 % CI 88-97 %). CONCLUSION Patients suspected of dementia, but with normal MMSE and CDT results, may benefit if SST and PMR are added as diagnostic tools. If both SST and PMR are abnormal, this is a red flag to investigate these patients further, even though their negative neuropsychological screening results.

Developing an alternative response format for the script concordance test

Introduction: Clinical reasoning is essential for the practice of medicine. In theory of development of medical expertise it is stated, that clinical reasoning starts from analytical processes namely the storage of isolated facts and the logical application of the ‘rules’ of diagnosis. Then the learners successively develop so called semantic networks and illness-scripts which finally are used in an intuitive non-analytic fashion [1], [2]. The script concordance test (SCT) is an example for assessing clinical reasoning [3]. However the aggregate scoring [3] of the SCT is recognized as problematic [4]. The SCT`s scoring leads to logical inconsistencies and is likely to reflect construct-irrelevant differences in examinees’ response styles [4]. Also the expert panel judgments might lead to an unintended error of measurement [4]. In this PhD project the following research questions will be addressed: 1. How does a format look like to assess clinical reasoning (similar to the SCT but) with multiple true-false questions or other formats with unambiguous correct answers, and by this address the above mentioned pitfalls in traditional scoring of the SCT? 2. How well does this format fulfill the Ottawa criteria for good assessment, with special regards to educational and catalytic effects [5]? Methods: 1. In a first study it shall be assessed whether designing a new format using multiple true-false items to assess clinical reasoning similar to the SCT-format is arguable in a theoretically and practically sound fashion. For this study focus groups or interviews with assessment experts and students will be undertaken. 2. In an study using focus groups and psychometric data Norcini`s and colleagues Criteria for Good Assessment [5] shall be determined for the new format in a real assessment. Furthermore the scoring method for this new format shall be optimized using real and simulated data.

Do multiple true-false items beat the commonly used one-best-answers questions regarding to the Ottawa Criteria for Good Assessment? Results of a literature review

Background: Multiple True-False-Items (MTF-Items) might offer some advantages compared to one-best-answer-questions (TypeA) as they allow more than one correct answer and may better represent clinical decisions. However, in medical education assessment MTF-Items are seldom used. Summary of Work: With this literature review existing findings on MTF-items and on TypeA were compared along the Ottawa Criteria for Good Assessment, i.e. (1) reproducibility, (2) feasibility, (3) validity, (4) acceptance, (5) educational effect, (6) catalytic effects, and (7) equivalence. We conducted a literature research on ERIC and Google Scholar including papers from the years 1935 to 2014. We used the search terms “multiple true-false”, “true-false”, “true/false”, and “Kprim” combined with “exam”, “test”, and “assessment”. Summary of Results: We included 29 out of 33 studies. Four of them were carried out in the medical field Compared to TypeA, MTF-Items are associated with (1) higher reproducibility (2) lower feasibility (3) similar validity (4) higher acceptance (5) higher educational effect (6) no studies on catalytic effects or (7) equivalence. Discussion and Conclusions: While studies show overall good characteristics of MTF items according to the Ottawa criteria, this type of question seems to be rather seldom used. One reason might be the reported lower feasibility. Overall the literature base is still weak. Furthermore, only 14 % of literature is from the medical domain. Further studies to better understand the characteristics of MTF-Items in the medical domain are warranted. Take-home messages: Overall the literature base is weak and therefore further studies are needed. Existing studies show that: MTF-Items show higher reliability, acceptance and educational effect; MTF-Items are more difficult to produce

Criteria for Ballast Flight Initiation Induced by High Speed Trains

One of the phenomena that limit the velocity of trains in high speed lines is the so- called “ballast pick-up”. It is a ballast train-induced-wind erosion (or BATIWE) that can produce damage to the train under body and the infrastructure surrounding the tracks. The analysis of the measurements taken during several passes of the train allows for a criterion of ballast flight initiation to be obtained. The first rotation of a ballast stone occurs when the impulse given to the stone (arising from the aerodynamic loading produced by the wind gust genera ted by the passing train) overpasses a critical impulse. This impulse depends on the physical properties of the stone (mass, shape, moment of inertia, etc. ...) and its posture on the track bed. The aim of this paper is to report on the experimental results obtained in the ADIF’S Brihuega (Guadalajara) test station, in the Madrid to Barcelona high speed line, and the way they can be used to support the feasibility of the definition of a criterion to evaluate the BA TIWE capability of trains. The results obtained show the feasibility of the proposed method, and contribute to a method of BATIWE characterization, which can be relevant for the development of train interoperability standardization.

Criteria for mathematical model selection for satellite vibro-acoustic analysis depending on frequency range

Satellites and space equipment are exposed to diffuse acoustic fields during the launch process. The use of adequate techniques to model the response to the acoustic loads is a fundamental task during the design and verification phases. Considering the modal density of each element is necessary to identify the correct methodology. In this report selection criteria are presented in order to choose the correct modelling technique depending on the frequency ranges. A model satellite’s response to acoustic loads is presented, determining the modal densities of each component in different frequency ranges. The paper proposes to select the mathematical method in each modal density range and the differences in the response estimation due to the different used techniques. In addition, the methodologies to analyse the intermediate range of the system are discussed. The results are compared with experimental testing data obtained in an experimental modal test.

Screening for Language Disorders in Stroke: German Validation of the Language Screening Test (LAST)

BACKGROUND Screening of aphasia in acute stroke is crucial for directing patients to early language therapy. The Language Screening Test (LAST), originally developed in French, is a validated language screening test that allows detection of a language deficit within a few minutes. The aim of the present study was to develop and validate two parallel German versions of the LAST. METHODS The LAST includes subtests for naming, repetition, automatic speech, and comprehension. For the translation into German, task constructs and psycholinguistic criteria for item selection were identical to the French LAST. A cohort of 101 stroke patients were tested, all of whom were native German speakers. Validation of the LAST was based on (1) analysis of equivalence of the German versions, which was established by administering both versions successively in a subset of patients, (2) internal validity by means of internal consistency analysis, and (3) external validity by comparison with the short version of the Token Test in another subset of patients. RESULTS The two German versions were equivalent as demonstrated by a high intraclass correlation coefficient of 0.91. Furthermore, an acceptable internal structure of the LAST was found (Cronbach's α = 0.74). A highly significant correlation (r = 0.74, p < 0.0001) between the LAST and the short version of the Token Test indicated good external validity of the scale. CONCLUSION The German version of the LAST, available in two parallel versions, is a new and valid language screening test in stroke.

An analysis of motorcycle side impact. Interim report of test results.

National Highway Traffic Safety Administration, Washington, D.C.

CRASH III model improvements: vehicle categorization for stiffness parameters. Volume 1. Final report.

Mode of access: Internet.

Yielding barrier test data base--a study of side impact cases in the multi-disciplinary accident investigation (MAI) file. Final report.

National Highway Traffic Safety Administration, Washington, D.C.

Final report of 270 degree contoured moving barrier impact into a 1985 Chrysler LeBaron 5-door hatchback in support of CRASH III damage algorithm reformation.

Mode of access: Internet.

Final report of 180 degree fixed flat barrier impacts of a 1983 Ford Thunderbird 2-door coupe in support of CRASH III damage algorithm reformation.

Mode of access: Internet.

Final report of 270 degree contoured moving barrier impact into a 1985 Chevrolet Celebrity 4-door sedan in support of CRASH III damage algorithm reformation.

Mode of access: Internet.

Final report of 270 degree contoured moving barrier impact into a 1983 Honda Prelude 2-door coupe in support of CRASH III damage algorithm reformation.

Mode of access: Internet.

Final report of 270 degree contoured moving barrier impact into a 1985 Nissan Sentra 2-door coupe in support of CRASH III damage algorithm reformation.

Mode of access: Internet.