Introduction
After pre-clinical research, the tests or treatments undergo a series of clinical trials. The aim is to determine if these treatments are safe and effective in humans. In this section, we will discuss the clinical trial design for different types of drugs. First, we will focus on the general study design, which is mostly applicable for small molecule drugs or new biologics. Thereafter, we will dive into the differences in trial design for biologics and biosimilars.
The classic form of clinical trial design can be subdivided into mainly four phases. Here we will take a closer look at these phases.
This video will give a short introduction to the different clinical trial phases:
Phase I
Phase 1 studies are first in human studies aimed at monitoring and gathering information about how a drug interacts with the human body. Here dose range will be investigated to determine the safest dosage to continue further off into phase 2. Furthermore, the pharmacokinetics (PK) and pharmacodynamics (PD) are assessed together with the short-term safety/toxicity of the drug. The length of phase 1 trials is usually several months.
These studies usually have non-therapeutic objectives and may be conducted in 20-80 healthy volunteers or certain types of patients. Drugs with significant potential toxicity e.g., cytotoxic drugs are usually studied in patients
Typical studies performed in phase 1 are, for example:
- Single ascending dose test (SAD)
- Multiple ascending doses (MAD)
- Food-drug interaction
- Drug-drug interaction
The probability of success in phase 1 trials are estimated to be 73%.
Phase II: Therapeutic exploratory
Phase 2 studies are aimed at exploring the therapeutic efficacy of the drug in a larger population consisting of 100-300 patients with the underlying disease that the drug is aimed to treat. The aims in this study are mostly dose refining, PK, short term efficacy and safety. Dose refining studies are important to determine phase 3 trials. The length of phase 2 trials may take up to two years.
Drug developments are mostly abandoned in this phase due to failure to demonstrate efficacy or safety. A good clinical trial design with proper sensitivity to certain biomarkers early in the trial phases is therefore essential to prevent late phase 2 or phase 3 abandonment.
The probability of success in the transition from phase 2 to phase 3 trials are estimated to be 27,3%.
Phase III: Therapeutic confirmatory or comparative efficacy
Phase 3 studies are studies usually aimed at demonstrating or confirming the therapeutic efficacy of the drug. The studies are designed to confirm the preliminary evidence obtained in phase 2 showing that a drug is safe and effective for use. The side effects are monitored, and the drug or treatment is compared to the current golden standard treatment. These studies also provide an adequate first basis for marketing approval. In this phase the subjects consist of a large population with more than 1000 patients with the underlying condition. The trials usually take place in different multicenter. The length of phase 3 can take up to 5 years.
The overall probability of success from phase 3 to applying for submitting a New drug application (NDA) or New Biological application (NBA) is 63.6%.
Phase IV: Therapeutic use
Phase 4 consists of post-marketing studies to observe the long term (side) effects that the drug may have. These studies were not considered necessary for approval but are often important for optimizing the drug’s use. Here pharmacovigilance (*external link to the pharmacovigilance section*) is implemented.
Commonly conducted studies in this phase include:
- Additional drug-drug interaction
- Dose-response
- Safety studies
- Studies designed to support use under the approved indication
