Gold-standard trials

The first issue lies in the whole realm of the human disease process itself. Many adverse drug events mimic diseases and vice versa. Is an adverse event really an adverse event, or is it merely a natural occurrence of a disease process that is entirely independent of drug exposure The science of drug safety is often complicated by the lack of objective markers of drug toxicity that can systematically separate a disease process from an adverse drug event process [2]. Clinical trials, often viewed as the gold standard to assess efficacy, are simply too limited in scope to answer safety questions in a systematic way. 

For any intervention intended to impact favorably upon human health, it is important to evaluate its safety and efficacy in order to demonstrate that it does not cause harm and it does provide the expected benefit. The gold standard method for evaluating any intervention, whether it be a botanical product, dietary supplement, drug, medical device or medical procedure, is the randomized, clinical trial (RCT). A clinical trial is a type of experiment conducted in human subjects where the effects of at least two interventions are compared. Often, the clinical trial takes the form of an active treatment compared to an inactive control or placebo. 

The gold-standard assay used for all chemokine receptor inhibitors that reach clinical-phase trials is the chemotaxis functional assay. This assay relies on the ability of chemokines to recruit cells expressing their respective receptor to areas of inflammation. In vitro, this assay was first described in detail by Taub et al. (16) for 24/48-well plates currently, this can be achieved by using 96-well plates. Cells are incubated in the upper chamber with an antagonist for a particular receptor (at different concentrations or with buffer) and challenged to migrate to the lower chamber, which has the relevant chemokine. After 2 to 4 hours of incubation at 37°C, the upper chamber inlet is removed and the cells in the lower chamber quantified by fluorescence with, for example, Calcein AM (Invitrogen, Carlsbad, CA). 

Until recently tamoxifen has been the gold standard for adjuvant therapy in ER(+) early breast cancer. Recent information from controlled trials comparing tamoxifen to aromatase inhibitors has challenged this idea. More research is needed to establish the respective roles of the two families of substances in the hormonal management of breast cancer (Chlebowski et al. 2002). 

The gold standard for human studies is called the randomized, controlled clinical trial. Such trials are close to experimental animal studies, but for obvious ethical reasons, they cannot be conducted to identify toxicity. They are, instead, designed to determine whether certain pharmaceutical or nutritional regimens, for example, reduce the risks of disease. They may provide information about adverse side effects, but they are not designed for studying toxicity. 

Long the treatments of choice for depression, the TCAs have in recent years been snpplanted by newer agents that are safer and more easily tolerated. Nonetheless, these medications are effective treatments for depression and a variety of other disorders and remain a gold standard for comparative research trials. 

The debate about quality of evidence most frequently ranks large randomised controlled trials as the gold standard, at least for efficacy, with controlled observational studies in the middle, and imcontrolled studies and opinions at the bottom. The evaluation of therapeutic benefit and risk is, in fact, never ending because clinicians will subject marketed medicines to comparison with other existing or new medicines, and they will experiment with alternative dosage schedules and combined use with other treatments. 

Active comparators are included to act as a benchmark or gold standard against which the new drug is to be compared. The selection of comparator depends on the specific objectives of the trial. The main considerations are as follows. 

S.5.5.2.3 Historical controls Since many clinical trials are conducted in the same diseases, with the same control treatments there is an obvious desire to make the most use of this potentially valuable information. Can we compare the results of a new treatment in a group of patients with a group of control patients extracted from a historical database For example, suppose we are testing a new treatment for migraine headache and 60% of patients improve in the first 2 h post-treatment, compared to 30% in a group of historical control patients treated who had been treated with the current gold standard. Are we able to conclude that the new treatment is preferable to the gold standard ... 

Numerous clinical trials have been done to determine the optimal regimen for H. pylori eradication, but there remains no gold standard of therapy to date. When selecting a regimen, take into account efficacy, tolerability, compliance, and cost. H. pylori is easily suppressed but, to ensure successful eradication, requires the use of... 

The current gold standard for evidence of drug efficacy is the randomized, adequate and well-controlled clinical trial. As mentioned previously, the number of phase-3 trials that fail to meet their prespecified acceptance criteria is around 50% as reported by PhRMA. So clearly, the current practice of controlled clinical trials is inadequate. Even when a study demonstrates an overall significant (p < 0.05) clinical effect, the efficacy signal often arises from a subset of patients, with other patients, in effect, being non-responders. 

Are there different gold standards in different countries If so, which one should be chosen in multicenter trials being conducted in countries with differing views ... 

While preapproval clinical trials are crucial in drug development, even the gold standard double-blind, randomized, concurrently controlled clinical trials are limited in their ability to provide information that truly represents the safety and effectiveness of the drug once it has been widely prescribed and is being taken by many more individuals than participated in the preapproval clinical trials. 

Kaptchuk, T. J. 2001, The double-blind, randomized, placebo-controlled trial gold standard or golden calf , J.Clin.Epidemiol., vol. 54, no. 6, pp. 541-549. 

Since clozapine may be the gold standard and the last resort in the treatment of refractory schizophrenia, the authors of a review aimed to discover whether a trial with clozapine is adequate (15). The results favored the approach of increasing the clozapine plasma concentration in treatment-refractory schizophrenic patients who do not respond to an initial low-to-medium dose. Some patients, especially young male smokers, will need dosages over 900 mg/day, and the addition of low-dose fluvoxamine while closely monitoring clozapine concentrations can help to reduce the large number of tablets required, since fluvoxamine increases the clozapine plasma concentration 2- to 3-fold, maximally 5-fold, and reduces N-desmethylclozapine concentrations the combination can lead to non-linear kinetics of clozapine. 

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