A randomised controlled trial is not a pilot trial simply because it uses a surrogate endpoint.

BACKGROUND: It has been argued that true endpoints (or 'hard' endpoints) for clinical trials, which are meaningful to clinicians, researchers and patients alike, are limited to those that measure health status, survival and cost. Other endpoints are termed 'surrogate' endpoints and are intended to substitute and predict the true endpoint.  A number of trials that describe using surrogate endpoints use the term 'pilot' in the title of the paper but the reason for this, as related by the authors, is the use of these surrogate endpoints in the trial. The conduct and reporting of such a trial may follow the traditional pattern for a conventional randomised controlled trial (RCT) as defined by the original CONSORT statement, with power-based sample size calculations, and significance tests of the results. However, this is contrary to the guidelines of the CONSORT extension for the reporting of pilot trials. MAIN BODY: We review the definition of a surrogate endpoint and the use of surrogate endpoints in clinical trials. We consider to what extent a trial could be considered a pilot trial if it uses a surrogate endpoint and discuss two examples that illustrate current practice. CONCLUSION: Trials which use surrogate endpoints should only be described as 'pilot' when a definitive trial is a distinct possibility and the authors consider conditions which would indicate whether the definitive main trial was worthwhile and feasible. Simply because a trial uses a surrogate endpoint is not justification for calling it a pilot trial.

Molecular composition of recycled organic wastes, as determined by solid-state 13C NMR and elemental analyses.

Using solid state (13)C NMR data and elemental composition in a molecular mixing model, we estimated the molecular components of the organic matter in 16 recycled organic (RO) wastes representative of the major materials generated in the Sydney basin area. Close correspondence was found between the measured NMR signal intensities and those predicted by the model for all RO wastes except for poultry manure char. Molecular nature of the organic matter differed widely between the RO wastes. As a proportion of organic C, carbohydrate C ranged from 0.07 to 0.63, protein C from <0.01 to 0.66, lignin C from <0.01 to 0.31, aliphatic C from 0.09 to 0.73, carbonyl C from 0.02 to 0.23, and char C from 0 to 0.45. This method is considered preferable to techniques involving imprecise extraction methods for RO wastes. Molecular composition data has great potential as a predictor of RO waste soil carbon and nutrient outcomes.

Influence of a single oral dose of vitamin D(2) on serum 25-hydroxyvitamin D concentrations in tuberculosis patients.

SETTING: Newham Chest Clinic, London, UK. OBJECTIVE: To determine the safety and efficacy of the administration of bolus-dose vitamin D(2) in elevating serum 25-hydroxyvitamin D (25[OH]D) concentrations in tuberculosis (TB) patients. DESIGN: A multi-ethnic cohort of TB patients was randomised to receive a single oral dose of 2.5 mg vitamin D(2) (n = 11) or placebo (n = 14). Serum 25(OH)D and corrected calcium concentrations were determined at baseline and 1 week and 8 weeks post-dose, and compared to those of a multi-ethnic cohort of 56 healthy adults receiving an identical dose of vitamin D(2). RESULTS: Hypovitaminosis D (serum 25[OH]D < 75 nmol/l) was present in all patients at baseline. A single oral dose of 2.5 mg vitamin D2 corrected hypovitaminosis D in all patients in the intervention arm of the study at 1 week post-dose, and induced a 109.5 nmol/l mean increase in their serum 25(OH)D concentration. Hypovitaminosis D recurred in 10/11 patients at 8 weeks post-dose. No patient receiving vitamin D(2) experienced hypercalcaemia. Patients receiving 2.5 mg vitamin D(2) experienced a greater mean increase in serum 25(OH)D at 1 week post-dose than healthy adults receiving 2.5 mg vitamin D(2). CONCLUSION: A single oral dose of 2.5 mg vitamin D(2) corrects hypovitaminosis D at 1 week but not at 8 weeks post-dose in TB patients.

Psychological disturbance in atopic eczema: the extent of the problem in school-aged children.

Although psychological factors are widely considered to be important in atopic eczema, there have been few controlled studies to assess the extent of disturbance in affected children and the problems experienced by their parents. This study was designed to find out the degree of psychological difficulty experienced by children with atopic eczema, whether their mothers show higher levels of mental distress than a comparison group, and whether the families of children with atopic eczema have less social support than the comparison group. We investigated 30 school-aged children with atopic eczema for psychological problems using the Rutter parent scale and compared them with 30 children with relatively minor skin lesions such as viral warts. Mental distress in mothers was assessed using the General Health Questionnaire. The Family Support Scale was used to get a measure of the social support experienced by the families. We found twice the rate of psychological disturbance in children in the eczema group compared with the control group. This difference was statistically significant for children with moderately severe eczema and severe eczema, but not for children with very mild eczema. Levels of mental distress were no greater in mothers of children with eczema than in parents of the control group and there was no difference in the degree of social support experienced by their families. These findings indicate that school-aged children with moderate and severe atopic eczema are at high risk of developing psychological difficulties, which may have implications for their academic and social development.