Phases of Clinical Trials
Table 1: The phases, types, and nature of clinical trial studies
| Clinical trial phase | Type of the study | Nature of study |
|---|---|---|
| Phase 0 | Exploratory | Examines too low (1/100th) concentrations (micro-dosing) of the drug for less time. Study the pharmacokinetics and determine the dose for phase I studies. Previously done in animals but now it is carried out in humans. |
| Phase I, Phase Ia, Phase Ib | Nontherapeutic trial | Around <50 healthy subjects are recruited. Establishes a safe dose range, and the MTD. Examines the pharmacokinetic and pharmacodynamic effects. Usually single-center studies. Phase Ia: SAD, and MTD. Duration of one week to several months depending on the trial and includes 6-8 groups of 3-6 participants. Phase Ib: MAD and the dose is gradually narrowed down. Three groups of 8 individuals each. |
| Phase II, Phase IIa, Phase IIb | Exploratory trial | Recruiting around 5-100 patients of either sex. Examines the effective dosage and the therapeutic effects on patients. It decides the therapeutic regimen and drug-drug interactions. Usually, multi-centre studies. Phase IIa: Decides the drug dosage, includes 20-30 patients, and takes up to weeks/months. Phase IIb: Studies dose response relationship, drug-drug interactions, and comparison with a placebo. |
| Phase III | Therapeutic confirmatory trial | More than 300 patients (up to 3000) of either sex are recruited in this study and are multi-centric trials. Premarketing phase examines the efficacy and the safety of the drug. Comparison of the test drug with the placebo/standard drug. Adverse drug reactions/adverse events are noted. Initiate the process of NDA with appropriate regulatory agencies like the FDA. |
| Phase IV | Post-approval study | After approval/post-licensure and post-marketing studies/surveillance studies. Following up on the patients for an exceptionally long time for potential adverse reactions and drug-drug interactions. |
* MTD: maximum tolerated dose; SAD: single ascending dose; MAD: multiple ascending doses; NDA: new drug application; FDA: food and drug administration
There are two main categories of clinical research design: observational/non-interventional studies and interventional/experimental studies. Analytical studies such as case-control and cohort studies may include a comparator group, or the research may be descriptive and not. The experimental trial can be classified as non-randomized or randomized. There are various kind of designs for clinical trials, such as adaptive, non-inferiority, randomized withdrawal method, factorial, crossover, parallel, and adaptable designs.
Table 2: Clinical trial designs, their advantages, and disadvantages
| Trial design type | Type of the study | Nature of study | Advantages/disadvantages |
|---|---|---|---|
| Parallel | Randomized | This is the most frequent design wherein each arm of the study group is allocated a particular treatment (placebo (an inert substance)/therapeutic drug). | The placebo arm does not receive the trial drug, so may not get the benefit of it |
| Crossover | Randomized | The patient in this trial gets each drug and the patients serve as a control themselves | Avoids participant bias in treatment and requires a small sample size. This design is not suitable for research on acute diseases. |
| Factorial | Nonrandomized | Two or more interventions on the participants and the study can provide information on the interactions between the drugs | The study design is complex |
| Randomized withdrawal approach | Randomized | This study evaluates the time/duration of the drug therapy | The study uses a placebo to understand the efficacy of a drug in treating the disease |
| Matched pairs | Post-approval study | Recruit patients with the same characteristics | Less variability |
Clinical trials are carried out for a variety of purposes, such as diagnosis, early detection