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Clinical Research and Its Different Phases

While preclinical research answers basic questions about a drug’s safety, it is not a substitute for studies of ways the drug will interact with the human body. “Clinical research” refers to studies, or trials, that are done in people. As the developers design the clinical study, they will consider what they want to accomplish for each of the different Clinical Research Phases and begin the Investigational New Drug Process (IND), a process they must go through before clinical research begins.

Clinical trials are designed to answer specific research questions related to an investigational drug. The trials must follow a study protocol – a document that describes exactly how the clinical trial will be conducted. It details key study objectives, study design, and statistical considerations, to ensure the safety of participants and the integrity of the data collected during the study.

Designing Clinical Trials

Researchers design clinical trials to answer specific research questions related to a medical product. These trials follow a specific study plan, called a protocol, that is developed by the researcher or manufacturer. Before a clinical trial begins, researchers review prior information about the drug to develop research questions and objectives.

Then, they decide:

  1. Who qualifies to participate (selection criteria)
  2. How many people will be part of the study
  3. How long the study will last
  4. Whether there will be a control group and other ways to limit research bias
  5. How the drug will be given to patients and at what dosage
  6. What assessments will be conducted, when, and what data will be collected?
  7. How the data will be reviewed and analyzed

Clinical trials follow a typical series from early, small-scale, Phase 1 studies to late-stage, large scale, Phase 3 studies.

Phase I

Number of participants: 20–100. These can either be “healthy” people or people diagnosed with the specific condition/disease you are developing the drug to treat.

Study length: Typically, several months.

Primary purpose: To determine safety in humans, and to gather information on dosage. Phase I studies also guide how best to administer the drug to limit toxicity and enhance therapeutic effect.

Phase II

Number of participants: Several hundred. The participants will be diagnosed with the condition/ disease you are developing the drug to treat.

Study length: Spans from several months to two years.

Primary purpose: To acquire additional safety data – to determine efficacy and adverse effects. This information is used to optimize the design of the larger Phase III study.

Phase III

Number of participants: 300–3000. The participants will be diagnosed with the condition/disease you are developing the drug to treat.

Study length: Spans from one to four years in length.

Primary purpose: To determine the drug’s efficacy and to monitor adverse reactions. Due to the increased number of participants during Phase III, long-term or rarer side effects that may have gone undetected in Phase I and Phase II are usually detected. The greatest proportion of safety information is collected during Phase III.

Phase IV

Number of Participants: Several thousand Volunteers who have the disease condition

Primary purpose: To determine the safety profile and efficacy of the drug

The Investigational New Drug Process

Drug developers, or sponsors, must submit an Investigational New Drug (IND) application to FDA before beginning clinical research.

In the IND application, developers must include:

  1. Animal study data and toxicity (side effects that cause great harm) data
  2. Manufacturing information
  3. Clinical protocols (study plans) for studies to be conducted
  4. Data from any prior human research
  5. Information about the investigator

Asking for FDA Assistance

Drug developers are free to ask for help from FDA at any point in the drug development process, including:

  • Pre-IND application, to review FDA guidance documents and get answers to questions that may help enhance their research
  • After Phase 2, to obtain guidance on the design of large Phase 3 studies
  • Any time during the process, to obtain an assessment of the IND application

Even though FDA offers extensive technical assistance, drug developers are not required to take FDA’s suggestions. If clinical trials are thoughtfully designed, reflect what developers know about a product, safeguard participants, and otherwise meet Federal standards, FDA allows wide latitude in clinical trial design.

FDA IND Review Team

The review team consists of a group of specialists in different scientific fields. Each member has different responsibilities.

  • Project Manager: Coordinates the team’s activities throughout the review process and is the primary contact for the sponsor.
  • Medical Officer: Reviews all clinical study information and data before, during, and after the trial is complete.
  • Statistician: Interprets clinical trial designs and data and works closely with the medical officer to evaluate protocols and safety and efficacy data.
  • Pharmacologist: Reviews preclinical studies.
  • Pharmakineticist: Focuses on the drug’s absorption, distribution, metabolism, and excretion processes. Interprets blood-level data at different time intervals from clinical trials, as a way to assess drug dosages and administration schedules.
  • Chemist: Evaluates a drug’s chemical compounds. Analyzes how a drug was made and its stability, quality control, continuity, the presence of impurities, etc
  • Microbiologist: Reviews the data submitted, if the product is an antimicrobial product, to assess response across different classes of microbes.

Approval

The FDA review team has 30 days to review the original IND submission. The process protects volunteers who participate in clinical trials from unreasonable and significant risk in clinical trials.

Source:

  1. https://www.fda.gov/patients/drug-development-process/step-3-clinical-research
  2. https://www.technologynetworks.com/drug-discovery/articles/exploring-the-drug-development-process-331894

Author

Dr Shilpa Subramanian

Dr. Shilpa Subramanian is a Periodontist and currently manages Global Pharmacovigilance Operations at Indegene Pvt Ltd. She is passionate about staying ahead of the curve in clinical and non-clinical advances in the field of pharma and healthcare.

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