A clinical trial is a research study conducted on human beings to determine whether new drugs, diagnostics, or treatments are both safe and effective. It is an integral part of the drug and diagnostics discovery and development process. Before a new medicine or diagnostic marketing, it must be carefully monitored clinical studies in volunteers to provide enough evidence of its safety and effectiveness. Clinical trials are broken down into different phases and categorized as Phase I to IV trials. Each phase is designed to answer certain questions and the trials should be conducted according to Good Clinical Practice (GCP) guidelines. Based on the clinical study, more information is gained about the potential treatment, its risks, and therapeutic effect.
Fig1. Clinical phase trials (Mahan, 2014)
The clinical trial methodology comprises the methods necessary to provide a valid inference about the objective of the trial and the methods required for the protection of participants in a clinical trial. A well-designed clinical research study would be able to derive a valid and meaningful scientific conclusion. There are two major types of clinical study designs, namely observational and experimental. It is important to choose a design and clinical trial methodology that will most appropriately answer the question and provide the most valuable information.
Before a clinical trial can be started, an investigational new drug (IND) application must be filed with the FDA. After approval, clinical trials are usually conducted in phases. Phase I studies of a new drug are to find the highest safe dose and usually include a small number of people. If the new drug is safe, a phase II clinical trial is done to see its efficacy in larger numbers of patients. Phase III clinical trials further investigate the safety and effectiveness of the new treatment. After phase III clinical trials, a new drug application (NDA) is submitted to FDA for approval. Finally, the new drug approved by the FDA is watched over a long period in phase IV studies.
Ethics is important in clinical research because ethical strategies can the safety of patients who volunteer to participate in the trials. On the other hand, ethics ensure the integrity of the research results. All proposed clinical trials should be approved by an institutional review board. Before participants can give their consent, they need to be fully informed about the risks of the trial. Some formal documents and ethical frameworks are in place to provide ethical guidance to clinical researchers.
When a new drug is tested on humans, the sponsor needs to submit an IND to the FDA for approval. The IND application must contain certain information including the results from studies, the parameters of the drugs, and details about the clinical trial team. Based on the IND file, FDA can decide whether the treatment is safe for testing in people. The research sponsor must commit to following all the rules required for studying investigational new drugs.
Clinical Data Management (CDM) is a critical phase in clinical research, helping to dramatically reduce the time from drug development to market. The team members of CDM should have adequate process knowledge that helps generate high-quality, reliable, and statistically sound data from clinical trials. Quality assessment for CDM includes Case Report Form (CRF) designing, CRF annotation, database designing, data entry and validation, discrepancy management, medical coding, data extraction, and database locking.
Adaptive designs make clinical trials more flexible and can make better use of resources such as time and money. Traditional clinical trials are straightforward and inflexible and do not include options for changes that may become desirable or necessary during the trial. In contrast, adaptive design can use accumulated results from experiments to modify the process according to predefined rules. Adaptive design can be applied at all stages of clinical research.
Clinical Supply Chain is defined as the chain from raw materials right through to worldwide distribution to customers. It is often worldwide and distribute to hundreds of study sites. The clinical trial supply chains ensure the supply and quality assurance of products so that the implementation of trials is not interfered with. Clinical supply chain management is the process of designing, planning, executing, and monitoring supply chain activities.
Drug formulation is the multistep process to develop a preparation of the drug that is both stable and acceptable to the patient. The formulation types vary with the route of administration, including capsules, tablets, pills, etc. The drug can enter the body through various means and common routes of administration include oral, sublingual, topical, transdermal, inhaled, etc.
Mahan, V., 2014. Clinical Trial Phases. International Journal of Clinical Medicine, 5, 1374-1383.