Last Updated on April 23, 2020 by Sagar Aryal
- In clinical research, clinical trials are a type of research experiment done on people aiming at finding a solution to a disease. These trials include studies of diagnostic tests, treatments, and monitoring and evaluation of the human health outcomes.
- The interventions of clinical trials include:
- Biological products
- Surgical and radiation procedures
- Medical devices
- Preventive treatment (vaccines)
- Behavioral treatment.
- Clinical trials normally begin in the laboratories experimenting on animals and some human cell experiments.
- When the first experiment is successful using both animal and human cell models, then the facility/company/laboratory involved sends their data to the Food and Drug Administration (FDA) for approval for clinical research and testing directly on humans.
- Major interventions that require human research experimentations are drug testing and Vaccine development and testing. Once the FDA approves human experimentation, the testing of the drug or vaccine or medical device can begin.
- These experiments are done in four to five phases and each phase is a completely separate trial. After completion of a phase trial, the investigators must present their data for FDA approval before they continue to the next phase. Each phase builds on the previous phase.
- The clinical trials can involve people of all age groups including children on a voluntary basis, involving healthy and sick individuals depending on the type of clinical interventions of investigation and the type of disease or infection. For example, cancer clinical trials are long (take long periods of time) and they can be done in three phases according to the FDA, while those of novel emerging infections take 4 to five phases of short periods of time of about several months at most a year.
Preparation for a Clinical Trials
Before clinical trials, the investigators must prepare a research design, citing the research questions and research objectives, similar to a study plan. The steps that are involved in a clinical trial are known as a protocol. The FDA recommends that before a phase trial, the research design is presented for approval before beginning the clinical trials.
These protocols include:
- Choosing the selection criteria of participants who qualify for the study
- The number of participants to involve in the study
- Duration of the study
- Inclusion of a control group and how to limit research bias
- The dosage and duration of administrating the drug
- The assessment of the research trial should answer what? when? and what data is to be collected
- How to review and analyze the data
Participants in Clinical Trials
- To participate in a clinical trial, a participant must qualify for the study to be considered for volunteering. The investigator must inform the participant on all possible guidelines to participate in the study. The factors that allow a volunteer to participate in a clinical trial are called inclusion criteria and the factors that do not allow volunteers from participating in the trials is called exclusion criteria. These criteria include age, gender, the type and stage of the disease, previous treatment history, and any other medical conditions.
- Depending on the clinical trial, some research investigators seek for participants who are already sick with the condition of study while some seek for healthy participants. the exclusion and inclusion criteria are meant to identify appropriate participants, promote participants’ safety, and to ensure the researchers get the required information at the end of the study.
Phases of Human Clinical Trials
- Phase 0
- This is a clinical trial that is done on a very small population of people normally less than 15 persons. The investigators will use a very small dosage of the medication ensuring that it is not harmful before adding a higher dosage for the next phase. The experimentation outcomes of each individual are closely monitored and their outcomes reported and documented accordingly.
- If the individuals react to the medication differently, another preclinical research is done before making a decision on whether to continue or terminate the trial.
- Phase 0 is not mandatory in most trials and therefore they move directly to phase one after preclinical research trials and approval.
- Phase I
- After a positive result outcome of phase 0, the investigators move to phase I where the investigators use a larger population of 20-80 people with no underlying health conditions, spending more time, running up to several months.
- This phase investigates using a larger dose of the drug, basically the largest dose a human being can take without serious side effects, with close monitoring of the participants and reporting and documenting their body reactions in this phase.
- In this phase, investigators decide the route of administration of the dug which can be more effective. Administration can be Intravenous, oral, or topical also depending on the type of infection or disease of investigation.
- If the medication is from trusted sources, of approximately 70%, according to the FDA, it can then move to the next phase, phase II.
- Phase II
- This phase which is a continuation of phase 1, studies test treatments that have been found to be safe in phase I but now need a larger group of human subjects to monitor for any adverse effects.
- The population need in this phase is normally above 100, who have the condition of investigation. The dosage of treatment is the same as the one given at phase I.
- However, the population use for the trial is still not enough for demonstrating the overall safety of the medication but the data collected in this phase broadens the prospects of phase III.
- According to the FDA, about 30% of the drugs found to be safe in phase II move to phase III.
- Phase III
- Studies are conducted on larger populations and in different regions and countries and are often they are the step right before a new treatment is approved.
- It involves 300- 3000 participants with the condition the medication are meant to treat and this phase trials can last as long as several years. It is a long phased clinical trial because it involves a large group of participants in different regions.
- This phase trials aim at evaluating how the new medication works in comparison to other existing drugs treating the same condition, and therefore, the investigators must demonstrate the efficacy, safety, and effectiveness of the medication against that of the existing drugs, if any.
- Randomized studies are used whereby participants are randomly selected to receive the new medication while another set of participants is administered with another drug, with the same objective of treating the underlying condition.
- Phase III trials are usually double-blind, which means that neither the participant nor the investigator knows which medication the participant is taking, which eliminates bias during result interpretation.
- Due to the larger number of participants and longer duration of phase III, rare and long-term side effects are more likely to show up during this phase. And if the investigators can be able to show that the medication is safe and effective, the FDA can approve it for use.
- At least 25-30% of drugs from trusted sources by the FDA move to phase IV.
- Phase IV
- These are studies that take place after country approval and there is a need for further testing in a wide population over a longer timeframe.
- Investigators use this phase to get more information about the medication’s long-term safety, effectiveness, and any other benefits.
Clinical Trials Review Team
According to the Food and Drug Administration (FDA), a complete clinical trial review team consists of these professionals with their 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.
(Adapted from the US FDA website)
References and Sources
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