A dose-ranging study is a clinical trial where different doses of an agent (e.g. a drug) are tested against each other to establish which dose works best and/or is least harmful.
Clinical trials are experiments or observations done in clinical research. Such prospective biomedical or behavioral research studies on human participants are designed to answer specific questions about biomedical or behavioral interventions, including new treatments and known interventions that warrant further study and comparison. Clinical trials generate data on safety and efficacy. They are conducted only after they have received health authority/ethics committee approval in the country where approval of the therapy is sought. These authorities are responsible for vetting the risk/benefit ratio of the trial – their approval does not mean that the therapy is 'safe' or effective, only that the trial may be conducted.
A biological agent—also called bio-agent, biological threat agent, biological warfare agent, biological weapon, or bioweapon—is a bacterium, virus, protozoan, parasite, or fungus that can be used purposefully as a weapon in bioterrorism or biological warfare (BW). In addition to these living and/or replicating pathogens, toxins and biotoxins are also included among the bio-agents. More than 1,200 different kinds of potentially weaponizable bio-agents have been described and studied to date.
A drug is any substance that, when inhaled, injected, smoked, consumed, absorbed via a patch on the skin, or dissolved under the tongue causes a physiological change in the body.
Dose-ranging is usually a phase I or early phase II clinical trial. Typically a dose ranging study will include a placebo group of subjects, and a few groups that receive different doses of the test drug. For instance, a typical dose-ranging study may include four groups: a placebo group, low-dose group, medium-dose group and a high-dose group. The maximum tolerable dose (MTD) information is necessary to be able to design such groups and therefore dose-ranging studies are usually designed after the availability of MTD information. [1]
A placebo is a substance or treatment of no intended therapeutic value. Common placebos include inert tablets, inert injections, sham surgery, and other procedures.
The main goal of a dose-ranging study is to estimate the response vs. dose given, so as to analyze the efficacy and safety of the drug. Although such a response will nevertheless be available from phase III or phase IV trials, it is important to carry out dose-ranging studies in the earlier phase I or phase II stages. There are some advantages by using healthy volunteers. They are in a steady-state condition showing no different stages of disease and no variation due to disease. In addition, it is easy to recruit and select volunteers among varying age, sex, race etc. under identical conditions in which the test can be repeated. The main reasons for this is to avoid trials in the later phases using doses that are significantly different from those that will subsequently be recommended for clinical use and also to avoid the need for modification of dosing schedules at later stages where a large amount of data has already been accumulated for a different dose range. [2] The duration of action should be determined during dose-ranging study, as it will allow definition of the dosage schedule. Because it is hard to measure reliable pharmacodynamic parameter, it is difficult to determine the duration of action during early clinical trials. Other parameters instead are suggested as a tentative dosage, such as half-lives in plasma and urine in various test species and human, receptor binding in vitro, or pharmacodynamic data in vivo in animals. [3]
Efficacy is the ability to get a job done satisfactorily. The word comes from the same roots as effectiveness, and it has often been used synonymously, although in pharmacology a distinction is now often made between efficacy and effectiveness. The word efficacy is used in pharmacology and medicine to refer both to the maximum response achievable from a pharmaceutical drug in research settings, and to the capacity for sufficient therapeutic effect or beneficial change in clinical settings.
Safety is the state of being "safe", the condition of being protected from harm or other non-desirable outcomes. Safety can also refer to the control of recognized hazards in order to achieve an acceptable level of risk.
