Which of the following trials can be performed to determine the maximal tolerated dose of a drug?
Ans. c. Phase I trial (Ref: KDT 7/e p79, 6/e p77)Phase I: Human Pharmacology and safetyThe emphasis is on safety and tolerability, while the purpose is to observe the pharmacodynamic effects in man, and to characterize absorption, distribution, metabolism and excretion.New Drug DevelopmentStandards for the design, ethics, conduct, monitoring, auditing, recording and analyzing data and reporting of clinical trials have been laid down in the form of 'Good Clinical Practice' guidelines by an International Conference on Hormonization.Adherence to these provides assurance that the data and reported results are credible and accurate, and that the rights, integrity and confidentiality of trial subjects are protected.The clinical studies are conventionally divided into 4 phasesPhase I: Human Pharmacology and safetyThe emphasis is on safety and tolerability, while the purpose is to observe the pharmacodynamic effects in man, and to characterize absorption, distribution, metabolism and excretion.Phase II: Therapeutic exploration and dose rangingThe primary aim is to establishment of therapeutic efficacy, dose range and ceiling effect in a controlled setting.Tolerability and pharmacokinetics are studied as extension of phase I.Phase III: Therapeutic confirmation/comparisonThe aim is to establish the value of the drug in relation to existing therapy.Safety, tolerability and possible drug interactions are accessed on a wider scale, while additional pharmacokinetic data may be obtained.Indications are finalized and guidelines for therapeutic use are formulated.A 'new drug application' is submitted to the licensing authority, who if convinced give marketing permission.Phase IV: Post marketing surveillance/studiesUncommon/ idiosyncratic adverse effects, or those that occur only after long-term use and unsuspected drug interactions are detected at this stage.Pattern of drug utilization and additional information may emerge from the surveillance data.
Case control study
Phase II Randomized control trial (RCT)
Phase I trial
Phase IV Randomized control trial (RCT)
Clinical Trials