EUPATI and Patients in Medicines Research and Development: Guidance for Patient Involvement in Ethical Review of Clinical Trials.

Involvement of patients in the research and development process (R&D) of new medicines-in all areas of indications-today is a widely accepted strategy in pharmaceutical industry to ensure relevance and suitability of the treatment under development. This may consist in, but is not limited to, patient input to achieve more patient-friendly protocol design, endpoint, and comparator selection as well as disease-adapted study conditions in a pre- or post-marketing clinical trial. Ethical aspects and especially the balance of benefit and risk in a clinical trial are frequently judged differently by clinical researchers, regulators, ethics committees, and patients due to their different focus. The final assessment of the ethical aspects of a planned clinical trial is provided by an independent ethics committee consisting of physicians and other experts in healthcare and clinical trial methodology as well as of lay persons. The participation of patients in ethics committees is a much-discussed concept, its suitability disputed in many countries, and only limited experience on best practices is available. In order to be effective and yield the best results for all stakeholders, integration of patients into the medicines development process needs to be structured and governed by clear, mutually agreed rules and modes of operation. Communication and collaboration processes need to be systematically implemented to establish transparency, trust and respect between those developing new medicines and their users, respectively between those involved in design and approval of clinical trials and participants. In particular agreement on the ethical aspects of a clinical trial and/or its overall ethical acceptability is a prerequisite before the start of a clinical trial. Existing codes of practice for patient involvement with various stakeholders do not comprehensively cover the full scope of R&D, with the exception of more general statements on interaction. Overarching guidance on meaningful and ethical interaction is missing. One specific aim of the European Patients' Academy on Therapeutic Innovation (EUPATI) was to close this gap through the development of guidance documents for ethics committees, pharmaceutical industry-led medicines R&D, regulatory authorities, and health technology assessment (HTA). This EUPATI "Guidance for patient involvement in ethical review of clinical trials" gives practical recommendations for ground rules and lists options for conditions and practices for involving patients in the work of ethics committees to enable trustful and constructive collaboration whatever the national (legal) framework for patient involvement in ethics committees might be. The guidance sets the collaboration of patients in ethics committees in the broader context of relevance and opportunities for patient input on ethics in the overall medicines R&D and specifically the overall clinical trial process from concept development to trial result reporting in lay summaries. In addition to a presentation of the full text of the Guidance, this article aims at providing additional background information on the development process of the Guidance, as well as insight into the current debate on this topic.

Gender aspects in medical publication - the Wiener klinische Wochenschrift.

OBJECTIVE: Medicine is a discipline where there are still pronounced gender imbalances. Whereas worldwide about 50% of beginners in medical schools are female, only few of them reach leading positions. Our aim was to analyze how this situation is reflected in a peer-reviewed general medical-scientific journal. METHODS: We screened all papers submitted to the Wiener klinische Wochenschrift - The Middle European Journal of Medicine between January 2001 and September 2009, analyzing the percentage of female first authors of submitted papers and accepted papers, the contribution of female authors depending on the type of article and medical specialty, and the percentage of invited female peer reviewers as well as the quality of their reviews. MAJOR RESULTS: During the period studied, a total of 2507 manuscripts were submitted to Wiener klinische Wochenschrift. 26% of these papers had female first authors, and this proportion increased continuously from 16% in 2001 to 32% in 2007, whereafter it remained constant. The proportion of papers submitted by female first authors was dependent on the medical subspecialty (e.g. 48% female first authors of pediatric papers, 12% female first authors of cardiology papers). There was no difference in the acceptance rate of papers by male and female first authors; however, a somewhat higher rate of papers with female first authors was subject to rapid rejection (21% vs. 16%). Papers with female first authors more often named a different corresponding author than papers with male first authors, and in most of these cases the corresponding author was a man. More than 40% of all submitted original papers, 24% of the review articles, but only 10% of the editorials had female first authors. During the years studied only 5-11% of reviewers were women, despite that the quality of their reviews was generally better than those by men. Among the 21 members of the editorial board only one is a woman. CONCLUSION: Between 2001 and 2007 the percentage of manuscripts submitted to Wiener klinische Wochenschrift by female authors constantly increased and is now around 30%, reaching almost 50% in some specialties such as pediatrics. Nevertheless, there remains a massive gender imbalance in Wiener klinische Wochenschrift: review papers or invited editorials are only rarely authored by female researchers, a very low percentage of peer reviewers is female - although the quality of their reviews is generally better - and only one member of the editorial board is female. Even though this is mostly a reflection of the general situation in academic medicine, medical journals can and must take action and contribute to the elimination of these gender inequalities.

Determination of amino acids in cell culture and fermentation broth media using anion-exchange chromatography with integrated pulsed amperometric detection.

Anion-exchange chromatography with integrated pulsed amperometric detection (AE-IPAD) separates and directly detects amino acids, carbohydrates, alditols, and glycols in the same injection without pre- or post-column derivatization. These separations use a combination of NaOH and NaOH/sodium acetate eluents. We previously published the successful use of this technique, also known as AAA-Direct, to determine free amino acids in cell culture and fermentation broth media. We showed that retention of carbohydrates varies with eluent NaOH concentration differently than amino acids, and thus separations can be optimized by varying the initial NaOH concentration and its duration. Unfortunately, some amino acids eluting in the acetate gradient portion of the method were not completely resolved from system-related peaks and from unknown peaks in complex cell culture and fermentation media. In this article, we present changes in method that improve amino acid resolution and system ruggedness. The success of these changes and their compatibility with the separations previously designed for fermentation and cell culture are demonstrated with yeast extract-peptone-dextrose broth, M199, Dulbecco's modified Eagle's (with F-12), L-15 (Leibovitz), and McCoy's 5A cell culture media.