Recommendations for the conduct of clinical trials for drugs to treat or prevent sarcopenia

PURPOSE: Sarcopenia is an age-related muscle condition which is frequently a precursor of frailty, mobility disability and premature death. It has a high prevalence in older populations and presents a considerable social and economic burden. Potential treatments are under development but, as yet, no guidelines support regulatory studies for new drugs to manage sarcopenia. The objective of this position paper is therefore to suggest a set of potential endpoints and target population definitions to stimulate debate and progress within the medico-scientific and regulatory communities. METHODS: A multidisciplinary expert working group was hosted by the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis, which reviewed and discussed the recent literature from a perspective of clinical experience and guideline development. Relevant parallels were drawn from the development of definition of osteoporosis as a disease and clinical assessment of pharmaceutical treatments for that indication. RESULTS: A case-finding decision tree is briefly reviewed with a discussion of recent prevalence estimations of different relevant threshold values. The selection criteria for patients in regulatory studies are discussed according to the aims of the investigation (sarcopenia prevention or treatment) and the stage of project development. The possible endpoints of such studies are reviewed and a plea is made for the establishment of a core outcome set to be used in all clinical trials of sarcopenia. CONCLUSIONS: The current lack of guidelines for the assessment of new therapeutic treatments for sarcopenia could potentially hinder the delivery of effective medicines to patients at risk

Genes, environment and responsibility for violent behaviour:‘Whatever genes one has it is preferable that you are prevented from going around stabbing people’

For the legal system to function effectively people are generally viewed as autonomous actors able to exercise choice and responsible for their actions. It is conceivable that genetic traits associated with violent and antisocial behaviour could call into question an affected individual’s responsibility for acts of criminal violence. Evidence concerning genes associated with violent and antisocial behaviour has been introduced in criminal courts in USA and Italy, either alone or with associated environmental factors. One example of a ‘genetic defence’ is based on low levels of monoamine oxidase A (MAOA) activity, with a prevalence of around thirty percent in Caucasian males. In countries with trial by jury it is particularly relevant to consider the views of publics on criminal liability and the significance they assign to evidence citing genetic influences on behaviour. This article draws on largely qualitative research looking at participants’ explanations of, and assigning of responsibility for, violent and antisocial behaviour where environmental or genetic influences are claimed. Genetic factors were not viewed deterministically by participants but were considered by most to be irrelevant to personal responsibility. Notions of human agency, free will and choice were crucial to explanations of problem behaviours and ensured that offenders could be held responsible despite evidence on environmental and genetic factors

Biomarkers and personalised medicine in rheumatoid arthritis: a proposal for interactions between academia, industry and regulatory bodies.

Rheumatoid arthritis (RA) is one of the most appropriate conditions for the application of personalised medicine as a high degree of heterogeneity has been recognised, which remains to be explained. Such heterogeneity is also reflected in the large number of treatment targets and options. A growing number of biologics as well as small molecules are already in use and there are promising new drugs in development. In order to make the best use of treatment options, both targeted and non-targeted biomarkers have to be identified and validated. To this aim, new rules are needed for the interaction between academia and industry under regulatory control. Setting up multi-centre biosample collections with clear definition of access, organising early, possibly non-committing discussions with regulatory authorities, and defining a clear route for the validation, qualification and registration of the biomarker-drug combination are some of the more critical areas where effective collaboration between the drug industry, academia and regulators is needed

Tools in the assessment of sarcopenia

Objective We aimed to test the fetal overnutrition hypothesis by comparing the associations of maternal and paternal adiposity (sum of skinfolds) with adiposity and cardiovascular risk factors in children.Design Children from a prospective birth cohort had anthropometry, fat percentage (bio-impedance), plasma glucose, insulin and lipid concentrations and blood pressure measured at 9·5 years of age. Detailed anthropometric measurements were recorded for mothers (at 30 ± 2 weeks’ gestation) and fathers (5 years following the index pregnancy).Setting Holdsworth Memorial Hospital, Mysore, India.Subjects Children (n 504), born to mothers with normal glucose tolerance during pregnancy.Results Twenty-eight per cent of mothers and 38 % of fathers were overweight/obese (BMI ? 25·0 kg/m2), but only 4 % of the children were overweight/obese (WHO age- and sex-specific BMI ? 18·2 kg/m2). The children's adiposity (BMI, sum of skinfolds, fat percentage and waist circumference), fasting insulin concentration and insulin resistance increased with increasing maternal and paternal sum of skinfolds adjusted for the child's sex, age and socio-economic status. Maternal and paternal effects were similar. The associations with fasting insulin and insulin resistance were attenuated after adjusting for the child's current adiposity.Conclusions In this population, both maternal and paternal adiposity equally predict adiposity and insulin resistance in the children. This suggests that shared family environment and lifestyle, or genetic/epigenetic factors, influence child adiposity. Our findings do not support the hypothesis that there is an intra-uterine overnutrition effect of maternal adiposity in non-diabetic pregnancies, although we cannot rule out such an effect in cases of extreme maternal obesity, which is rare in our population.<br/

Health claims assessment in the field of joint and cartilage: a consensus viewpoint of the Group for the Respect of Ethics and Excellence in Science

Abstract Introduction: In 2006, the European Parliament and Council issued a regulation (No. 1924/2006) for the nutrition and health claims made on foods, including food supplements. According to the regulation, the use of nutrition and health claims shall only be permitted if the substance in respect of which the claim is made has been shown to have a beneficial nutritional or physiological effect. In the field of joint and cartilage health, there is no clear scientific-based definition of the nature of such a beneficial nutritional or physiological effect. The objective of this paper is to scientifically define the possible content of health claims related to joint and cartilage health and to provide scientific guidelines for the design of clinical studies which need to be adopted to substantiate such health claims. Methods: Literature review up to September 2011 followed by a consensus expert discussion organized by the Group for the Respect of Ethics and Excellence in Science (GREES). Results: In line with the general principles of the PASSCLAIM and the Codex recommendations, the GREES identified four acceptable health claims related to joint and cartilage health based on the effects on discomfort, joint and cartilage structural integrity or risk factors for joint and cartilage diseases. The GREES considers that randomized controlled trials on a relevant outcome is the best design to assess health claims. Moreover, animal studies could also be of interest to substantiate some health claims, to assess the clinical relevance of endpoints used in human studies or to extrapolate data obtained in patients to the target (apparently) healthy population. Conclusion: According to the methodology and biomarkers used in the study and whether or not additional animal studies are provided to support the claim, various health claims can be acceptable in the field of joint and cartilage health