Clinical trial designs of new medicinal products for treating schizophrenia: discussion of EMA's Guideline and a Better Long Term Trial Design

Background and Objectives: Schizophrenia is a severe chronic disease. Endpoint variables lack objectivity and the diagnostic criteria have evolved with time. In order to guide the development of new drugs, European Medicines Agency (EMA) issued a guideline on the clinical investigation of medicinal products for the treatment of schizophrenia. Methods: Authors reviewed and discussed the efficacy trial part of the Guideline. Results: The Guideline divides clinical efficacy trials into short-term trials and long-term trials. The short-term three-arm trial is recommended to replace the short-term two-arm active-controlled non-inferiority trial because the latter has sensitivity issues. The Guideline ultimately makes that three-arm trial a superiority trial. The Guideline discusses four types of long-term trial designs. The randomized withdrawal trial design has some disadvantages. Long-term two-arm active-controlled non-inferiority trial is not recommended due to the sensitivity issue. Extension of the short-term trial is only suitable for extension of the short-term two-arm active-controlled superiority trial. The Guideline suggests that a hybrid design of a randomized withdrawal trial incorporated into a long-term parallel trial might be optimal. However, such a design has some disadvantages and might be too complex to be carried out. Authors suggest instead a three-group long-term trial design, which could provide comparison between test drug and active comparator along with comparison between the test drug and placebo. This alternative could arguably be much easier to carry out compared with the hybrid design. Conclusions: The three-group long-term design merits further discussion and evaluation.

Effect of a weight loss program in obese adolescents: a long-term follow-up

Objectives: Obesity during adolescence is an increasing health problem in industrial countries. The comorbidities associated with obesity include important metabolic diseases. Methods: To analyze the effect of a weight-loss program, we recruited 12 obese, male adolescents before entering this program. We determined body weight measures at baseline, 6-week and 36-month follow-up. Also, the long-term changes of blood pressure, HbAlc, and CRP were evaluated. Twenty healthy age-matched adolescents served as controls. Results: Within the intervention group ((body mass index [BMI, kg/m²] > 95th percentile for age and sex, age 13-17 years) the BMI and BMI-standard deviation score [SDS] were significantly reduced in the 6-week follow-up after completing the weight loss program. However, the significant weight-reduction effect was not persistent until the 36-month follow-up. Conclusion: The 6-week weight-loss program had beneficial short-term effects on body weight, BMI, and BMI-SDS in obese adolescents, but these effects could not be maintained until the 36-month follow-up.

Non-institutionalized nonagenarians health-related quality of life and nutritional status: is there a link between them?

Introduction: Nonagenarian population, clearly increasing, shows different characteristics from the rest of elderly people. Health-related quality of life is a way to study population health in physical, psychological and social dimensions. Objectives: To examine the relationship between nutritional status and health-related quality of life in a group of free-living nonagenarians. Differences with octogenarians were also studied. Methods: Within Villanueva Older Health Study, 20 non-institutionalised people (92.5±3.5 years; 80% women) make the nonagenarian subsample. Nutritional risk was assessed by Mininutritional Assessment questionnaire, dietary intake by a 24-hour dietary recall and health-related quality of life by EuroQoL-5D questionnaire. SPSS was used for statistical analysis. Results: 40% nonagenarians were at risk of malnutrition. Dietary assessment showed magnesium, zinc, potassium, folic acid, vitamin D and vitamin E deficiencies. Problems in mobility were more frequently reported (80%). EQ-5Dindex was associated with MNA (p<0.05). Self-care dimension was associated with calcium and niacin (p<0.05), retinol and cholesterol (p<0.01) intake. Usual activities dimension was associated with niacin (p<0.01) and cholesterol(p<0.05) intake. Pain/discomfort dimension was associated with protein (p<0.01), energy, selenium and niacin (p<0.05) intake. Anxiety/depression was associated with protein(p<0.01) and selenium (p<0.05) intake. Conclusions: Risk of malnutrition is a factor associated to health-related quality of life. Results suggest that energy and some nutrient intakes could be possibly associated to health-related quality of life but further research on this influence is required.

Compliance in food consumption of young and long-lived elderly of a city in southern Brazil

Introduction: Life expectancy is increasing and becoming a characteristic phenomenon of developed countries and, increasingly, of developing countries, such as Brazil. The aging process causes changes of some physiological functions such as loss of smell, taste, loss of appetite, among other things that end up changing the food intake of these individuals. Objectives: This study aimed to assess food consumption of the young and long-lived elderly in a city in southern Brazil. Methods: A cross-sectional survey conducted through home visits in Palmeira das Missões - RS, Brazil. The sociodemographic, anthropometrical and dietary data were collected through questionnaires and 24-hour recall. The adequacy of nutrients was assessed according to the Dietary Reference Intakes. Data were analyzed using SPSS 18.0 software. Results: The study included 424 older adults, 84,4% (n = 358) aged less than 80 years old and 15,6% (n = 66) older than 80. The intake of energy and protein was insufficient for both young elderly and the oldest. The consumption of vitamins and minerals has been insufficient in all seniors except for iron, which presented an excessive intake. There was a statistically significant difference between the elderly and oldest only for the consumption of lipids and vitamin B12. Conclusion: The majority of studies with elderly corroborate the results found in this article. An inadequate intake of nutrients can develop nutritional deficiencies, and consequently it can result in physiological and pathological changes which would compromise the functional capacity of the elderly. Energy consumption was insufficient and macronutrients were inadequate, both for the young elderly as for the oldest. Additionally, the consumption of vitamins and minerals was insufficient to everyone except the iron, which presented excessive intake for young and oldest elderly.