Practices, patients and (im)perfect data - feasibility of a randomised controlled clinical drug trial in German general practices

<p>Abstract</p> <p>Background</p> <p>Randomised controlled clinical (drug) trials supply high quality evidence for therapeutic strategies in primary care. Until now, experience with drug trials in German general practice has been sparse. In 2007/2008, the authors conducted an investigator-initiated, non-commercial, double-blind, randomised controlled pilot trial (HWI-01) to assess the clinical equivalence of ibuprofen and ciprofloxacin in the treatment of uncomplicated urinary tract infection (UTI). Here, we report the feasibility of this trial in German general practices and the implementation of Good Clinical Practice (GCP) standards as defined by the International Conference on Harmonisation (ICH) in mainly inexperienced general practices.</p> <p>Methods</p> <p>This report is based on the experience of the HWI-01 study conducted in 29 German general practices. Feasibility was defined by 1) successful practice recruitment, 2) sufficient patient recruitment, 3) complete and accurate data collection and 4) appropriate protection of patient safety.</p> <p>Results</p> <p>The final practice recruitment rate was 18%. In these practices, 79 of 195 screened UTI patients were enrolled. Recruitment differed strongly between practices (range 0-12, mean 2.8 patients per practice) and was below the recruitment goal of approximately 100 patients. As anticipated, practice nurses became the key figures in the screening und recruitment of patients. Clinical trial demands, in particular for completing symptom questionnaires, documentation of source data and reporting of adverse events, did not agree well with GPs' documentation habits and required support from study nurses. In many cases, GPs and practice staff seemed to be overwhelmed by the amount of information and regulations. No sudden unexpected serious adverse reactions (SUSARs) were observed during the trial.</p> <p>Conclusions</p> <p>To enable drug trials in general practice, it is necessary to adapt the setup of clinical research infrastructure to the needs of GPs and their practice staff. Risk adaption of clinical trial regulations is necessary to facilitate non-commercial comparative effectiveness trials in primary health care.</p> <p>Trial Registration</p> <p>Trial registration number: <a href="http://www.controlled-trials.com/ISRCTN00470468">ISRCTN00470468</a></p

Typical investigational medicinal products follow relatively uniform regulations in 10 European Clinical Research Infrastructures Network (ECRIN) countries

<p>Abstract</p> <p>Background</p> <p>In order to facilitate multinational clinical research, regulatory requirements need to become international and harmonised. The EU introduced the Directive 2001/20/EC in 2004, regulating investigational medicinal products in Europe.</p> <p>Methods</p> <p>We conducted a survey in order to identify the national regulatory requirements for major categories of clinical research in ten European Clinical Research Infrastructures Network (ECRIN) countries-Austria, Denmark, France, Germany, Hungary, Ireland, Italy, Spain, Sweden, and United Kingdom-covering approximately 70% of the EU population. Here we describe the results for regulatory requirements for typical investigational medicinal products, in the ten countries.</p> <p>Results</p> <p>Our results show that the ten countries have fairly harmonised definitions of typical investigational medicinal products. Clinical trials assessing typical investigational medicinal products require authorisation from a national competent authority in each of the countries surveyed. The opinion of the competent authorities is communicated to the trial sponsor within the same timelines, i.e., no more than 60 days, in all ten countries. The authority to which the application has to be sent to in the different countries is not fully harmonised.</p> <p>Conclusion</p> <p>The Directive 2001/20/EC defined the term 'investigational medicinal product' and all regulatory requirements described therein are applicable to investigational medicinal products. Our survey showed, however, that those requirements had been adopted in ten European countries, not for investigational medicinal products overall, but rather a narrower category which we term 'typical' investigational medicinal products. The result is partial EU harmonisation of requirements and a relatively navigable landscape for the sponsor regarding typical investigational medicinal products.</p

Comparison of early and late results of a Carbofilm-coated stent versus a pure high-grade stainless steel stent (the Carbostent-Trial).

Contains fulltext : 57936.pdf (publisher's version ) (Closed access)The long-term success of coronary interventions with stents is largely determined by the development of restenosis. The aim of this study was to compare a Carbofilm-coated and a pure stainless steel stent with regard to early and late adverse events. In this prospective, randomized trial, the Carbofilm-coated Carbostent and Sirius stent (same stent design, newly developed delivery system) were compared with the stainless steel stents S660, S670, and S7 (newly developed delivery system, same principal stent design with a few changes). The primary end point was relative late luminal loss, and secondary end points were diameter stenosis at 6 months, rate of restenosis, and major adverse cardiac events (MACEs) (myocardial infarction, reintervention, and death). From March 2000 to June 2002 at 18 centers in Canada and Europe, 420 patients were randomized. Relative late luminal loss (Carbofilm 28.9 +/- 23.0% vs stainless steel 26.7 +/- 20.2%, p = 0.95) as the primary end point, absolute late luminal loss (1.00 +/- 0.72 vs 0.93 +/- 0.62 mm, p = 0.95), net gain (1.32 +/- 0.82 vs 1.40 +/- 0.74 mm, p = 0.75), and the degree of stenosis (40.7 +/- 22.9% vs 38.0 +/- 20.1%, p = 0.92), as well as restenosis rates (23.5% vs 15.9%, p = 0.09) and MACEs (20.1% vs 13.7%, p = 0.11) were not significantly different. Thus, the Carbofilm coating of stents does not lead to an improvement in angiographic results or a reduction of restenosis rate and MACEs. These results agree with other trials using inactive coatings on stents, which also could not demonstrate any advantage over pure stainless steel stents