Placebo Controlled Trial

Osteoporosis imposes a tremendous burden on Australia: 1.2 million Australians have osteoporosis and 6.3 million have osteopenia. In the 2007–08 financial year, 82 000 Australians suffered fragility fractures, of which > 17 000 were hip fractures. In the 2000–01 financial year, direct costs were estimated at $1.9 billion per year and an additional $5.6 billion on indirect costs. Osteoporosis was designated a National Health Priority Area in 2002; however, implementation of national plans has not yet matched the rhetoric in terms of urgency. Building healthy bones throughout life, the Osteoporosis Australia strategy to prevent osteoporosis throughout the life cycle, presents an evidence-informed set of recommendations for consumers, health care professionals and policymakers. The strategy was adopted by consensus at the Osteoporosis Australia Summit in Sydney, 20 October 2011. Primary objectives throughout the life cycle are: to maximise peak bone mass during childhood and adolesc...

Beyond placebo: Alternative options to the randomized control trial design in rare disease studies. ABSTRACT Unique difficulties and challenges can arise for rare diseases and orphan disease indications within a clinical trial. Some of the challenges encountered by trials that are working on rare diseases can include recruitment and enrollment. One of the explanations for the challenges that are encountered in rare disease trials is because of the trial design of study, where the investigational product is being compared to the placebo. This review paper discusses the usage of placebo and when other options could be taken into consideration while creating the protocol, specifically with consideration to rare disease studies. It is essential for the investigators and those designing the protocol to consider alternative options from the standard randomized controlled trial. The aim of this paper is to review alternative trial design options. The trial designs discussed in this review paper include crossover trials, single arm studies and historical data, and n-of-1 trials.

In this investigation, the hypothesis was tested whether the selective dopamine D2/D3 receptor antagonist tiapride is effective in maintaining abstinence after detoxification in alcohol-dependent patients. The rationale of the study was based on the relevance of the dopaminergic system for addictive behaviour as well as some preliminary studies. A multi-centre, randomized, double-blind, placebo-controlled, parallel-group study was conducted. A total of 299 detoxified alcohol-dependent patients (ICD-10: F10.2) received either tiapride (300 mg/d) or placebo over a 24-wk study period. Subjects with severe comorbid psychiatric disorder such as schizophrenia or Wernicke-Korsakoff syndrome were excluded. Primary outcome variable was the time to first relapse with relapse defined as any alcohol consumption after detoxification. Data analysis was done with Kaplan-Meier estimates with log-rank test (one-sided, p<0.05). Tiapride was not superior to placebo in maintaining abstinence. The ti...

BackgroundLithium and quetiapine are considered standard maintenance agents for bipolar disorder yet it is unclear how their efficacy compares with each other.AimsTo investigate the differential effect of lithium and quetiapine on symptoms of depression, mania, general functioning, global illness severity and quality of life in patients with recently stabilised first-episode mania.MethodMaintenance trial of patients with first-episode mania stabilised on a combination of lithium and quetiapine, subsequently randomised to lithium or quetiapine monotherapy (up to 800 mg/day) and followed up for 1 year. (Trial registration: Australian and New Zealand Clinical Trials Registry - ACTRN12607000639426.)ResultsIn total, 61 individuals were randomised. Within mixed-model repeated measures analyses, significant omnibus treatment × visit interactions were observed for measures of overall psychopathology (Brief Psychotic Rating Scale (BPRS), P = 0.005, Clinical Global Impressions - Bipolar, seve...

Objective: The use of placebos is a necessary,
if controversial, part of determining
the efficacy of new antidepressants in
randomized clinical trials. Such studies
need to convey accurate and useful riskbenefit
information to subjects since effective
treatments are withheld. The authors
assessed the cost-effectiveness of
entering such a trial from the perspective
of potential subjects.
Method: The choice between individualized
psychiatric treatment and an 8-week
placebo-controlled, randomized clinical
trial was modeled by using a static model.
The analysis was conducted from the perspective
of a potential subject who has
moderate depression, is at low risk for suicide,
has no comorbid conditions, and
lacks adequate insurance to pay for mental
health services. The trial was assumed
to be free for subjects, except for indirect
costs. Model outcomes included the probability
of treatment response at 8 weeks
and “decremental” cost-effectiveness. Data
were based on reviews of published and
some unpublished clinical trials of novel
antidepressants that were eventually
shown to be efficacious.
Results: A participant in a typical antidepressant
efficacy trial has a chance of
treatment response almost 25% less than
that with individualized treatment. An
uninsured participant can expect to save
just over $164 for every 10% chance of response
sacrificed by entering the placebocontrolled
trial.
Conclusions: For placebo-controlled antidepressant
trials, it is possible to derive
systematic and evidence-based estimates
of the burdens and potential benefits to
subjects. Such information may be more
useful for institutional review boards and
potential subjects than an unstructured
enumeration of risks and benefits.

The management of type 2 diabetes mellitus is complicated by the presence of risk factors related to overweight and obesity, particularly visceral adiposity. However, weight loss and weight maintenance are difficult for patients with diabetes, and the benefits of dietary modifications are typically modest. Sibutramine is a serotonin- and norepinephrine-reuptake inhibitor that reduces food intake by inducing early satiety and attenuates the decrease in basal energy expenditure associated with weight loss. Previous trials of sibutramine in overweight and obese patients with type 2 diabetes have shown significant weight loss accompanied by better glycemic control. The goal of this study was to assess the effect on body weight and glycemic control of sibutramine in combination with glibenclamide in obese Hispanic patients with type 2 diabetes. This was a 12-month, randomized, double-blind, placebo-controlled clinical trial conducted at the Endocrinology Service, General Hospital of Mexico, Mexico City. Included were overweight or obese (body mass index [BMI] >27 kg/M2) patients with type 2 diabetes between the ages of 24 and 65 years who had been receiving glibenclamide monotherapy for at least 2 weeks and whose glucose concentrations were stable. Patients were randomized to receive sibutramine 10 mg or placebo once daily. The primary efficacy measures were change in body weight, waist circumference, and glycosylated hemoglobin (HbA1c). Anthropometrics and fasting glucose concentrations were measured monthly. HbA1c was determined at baseline and at 6 and 12 months. Laboratory parameters were measured at baseline and at the end of the study. Forty-four patients were randomized to receive sibutramine (28 women, 16 men; mean [SD] age, 47.6 [9.0] years), and 42 were randomized to receive placebo (31 women, 11 men; mean age, 45.8 [8.1] years). Twenty-four patients in the sibutramine group and 23 in the placebo group completed the trial. In the sibutramine group, body weight was reduced from a mean (SD) of 73.9 (10.3) kg at baseline to 69.8 (10.6) kg at month 12; BMI decreased from 29.9 (2.6) to 28.2 (2.9) kg/M2; waist circumference was reduced from 94.9 (8.4) to 90.8 (8.4) cm; the plasma fasting glucose concentration decreased from 140.4 (29.4) to 114.2 (32.0) mg/dL; and the HbA1c value was reduced from 8.9% (1.2) to 8.3% (1.2) (all, P < 0.001). In the placebo group, the corresponding changes were from 74.5 (10.3) kg at baseline to 73.1 (11.2) kg at month 12; from 30.1 (2.5) to 29.5 (2.9) kg/M2; from 94.4 (7.3) to 93.1 (8.3) cm (P < 0.05); from 140.7 (25.2) to 123.9 (38.3) mg/dL (P < 0.05); and from 9.0% (1.2) to 9.1% (1.3). In the sibutramine group, weight loss continued for up to 12 months. In this population of obese Hispanic patients with type 2 diabetes, sibutramine combined with glibenclamide therapy achieved weight loss for up to 12 months and was associated with better glycemic control than placebo.

The objective of this study was to determine whether a nonabsorbable antibiotic lozenge could alleviate radiation-induced oral mucositis. Patients scheduled to receive radiation therapy to more than one-third of the oral cavity mucosa were selected for the study. After stratification, patients were randomized to receive either a nonabsorbable antibiotic lozenge or a placebo. Both groups were then evaluated for mucositis by health care providers and self-report instruments. Fifty-four patients were randomized to receive the antibiotic lozenge and 58 to receive the placebo. There were no substantial differences or trends in mucositis scores between the two study arms as measured by the health care providers. However, the mean patient-reported mucositis score and the duration of patient-reported Grade 3-4 mucositis were both lower in the patients randomized to the antibiotic lozenge arm (P = 0.02 and 0.007, respectively). This prospective, controlled trial provides evidence to suggest that a nonabsorbable antibiotic lozenge can decrease patient-reported radiation-induced oral mucositis to a modest degree. Nonetheless, this evidence does not appear to be compelling enough to recommend this treatment as part of standard practice.

Approximately 70% of the immune system is localized in the gastrointestinal tract. The saliva and gastrointestinal secretions, as well as flora (probiotics) and supplied fibres (prebiotics), are important for optimal function. Probiotic bacteria have been shown to influence the immune system through several molecular mechanisms. Pre-, pro- and synbiotics (products produced by fermentation) offer both protection against and cure of a variety of endemic and acute diseases. This review summarizes the present experience in various forms of diarrhoea, inflammatory bowel disease, and Helicobacter infections, in intensive care patients and in connection with extensive surgery.