Clinical research is a branch of science that involves study of health and illness in people. It focuses on improving knowledge of diseases, prevention of diseases, developing diagnostic methods and new treatments or medical devices to ensure better patient care. Clinical research is very structured and adheres to precise protocols, which must be followed exactly so that the results are valid.
Clinical research must precisely:
- Be conducted with the purpose of expanding medical knowledge
- Be carried out by a qualified and skilled team
- Take all necessary precautions to ensure the safety of the candidates participating in the research
- Obtain consent from all the candidates participating in the research.
- Obtain necessary approvals from regulatory bodies and follow all legal and ethical protocols
There are two types of clinical research studies, and they are observational studies and interventional studies (also known as clinical trials).
An observational study is a type of study wherein the investigators assess health outcomes in groups of participants according to a specific protocol or research plan.
Participants may receive interventions, which can include medical products, such as drugs or devices, or procedures as part of their routine medical care, but participants are not assigned to specific interventions by the investigator (as in a clinical trial).
Interventional Studies or Clinical Trials:
Interventional Studies or Clinical trials are scientific experiments that help scientists test if a new therapeutic drug, a new medicine combination or even a new treatment approach works well and is safe for humans. In a clinical trial, participants receive specific interventions according to the research plan or protocol created by the investigators.
All new drugs and treatment approaches are subjected to clinical trials before they are pushed for approval by the US Food and Drug Administration (USFDA), European Medical Agency (EMA) and Central Drugs Standard Control Organization (CDSCO). The duration of each study varies – some take months, while some take years.
Before clinical trials, any new cancer drug or treatment method is subjected to pre-clinical studies or laboratory studies. This is to check if the new drug or treatment is safe and is likely to work in human subjects.
In most cases, pre-clinical studies involve one or both of the following studies:
- Cell Studies: These are one of the first tests done on a new drug or treatment method. Researchers study the effects of the new medication on cancer cells cultivated in a lab dish or a test tube to see if it works. These investigations could be carried out on human or animal cancer cells.
- Animal studies: If the results from cell studies look promising, the new treatment is then tested in live animals. This is for researchers to study if the new treatment is safe among living subjects.
Not all insights from animal studies are useful for researchers. Humans and animals absorb, process, and eliminate drugs and therapies in fundamentally different ways. A chemotherapeutic drug, for instance, may work well in animals but fail to show the desired effect in humans. There may also be side effects that don’t show up in animals but could show up in humans. Therefore, clinical trials become important where the efficacy and safety of the new treatment are tested on human subjects.
Once the preclinical studies are completed and if the results appear promising, the research team should get permission before studying the new drug or treatment in human subjects through various phases of clinical trials.
The study must be approved before a clinical trial may begin. When researchers want to examine a particular drug in humans, they must submit an investigational new drug (IND) application or request to the regulatory bodies like US Food and Drug Administration (USFDA), European Medical Agency (EMA) and Central Drugs Standard Control Organization (CDSCO).
The following data has to be submitted to regulatory bodies before carrying out clinical trials in order to obtain the necessary permission:
- Results of preclinical data – to check whether or not the treatment is safe to be tested in human subjects
- Ample data on the new drug – its composition, preparation, stability, etc.,
- A detailed review of study protocols – Study protocols, which are detailed descriptions for planned clinical research, are examined to check if participants are being exposed to unnecessary hazards
- Clinical research team details – to check if the researchers have the knowledge and skills that are necessary to carry out that particular study.
It is also important for the research team to get informed consent from the subjects (patients) participating in the trial.
Once the regulatory bodies grant permission, the clinical trial begins.
Clinical Trial Phases
Whether it is a new drug, combination or a new treatment method, it will be tested in various stages, called phases, during a clinical trial. If it is successful in the first phase, it will be pushed to the next phase for more tests and accordingly to further phases.
Usually, clinical trials are conducted in four phases:
- Phase 1: Conducted to determine a safe dose for a new cancer drug and assess its toxicity levels.
- Phase 2: Conducted to understand how well the new drug/treatment works.
- Phase 3: Conducted to compare the new drug or treatment with the existing standard of treatment for its safety and efficacy.
- Phase 4: Conducted to analyze the long-term safety and effectiveness of a new drug or new treatment and to check if it has any adverse effects that were not apparent during the initial phases of clinical trials.
Below is the brief information on the intent, subject population and duration of each phase:
- Also termed ‘first-in-human’ studies, phase 1 trials are primarily conducted to determine a safe dose, the right mode of administration (oral, intravenous, intramuscular, etc.), the overall efficacy of the treatment and side effects.
- During this phase, the new drug is administered in a very low dose and the group is monitored closely. If the side effects are negligible, the next group is administered with a slightly higher dose. This will go on until the researchers find a safe dose to work with.
- Although disease response is not the primary intent of phase 1, a few patients tend to benefit in phase 1 itself.
- Patients with different types of cancer are involved in Phase 1.
- Those patients who have exhausted/failed all existing standard treatment options are suggested to participate in clinical trials. This helps them explore treatment options that could potentially improve their health condition.
Subject Population: 15 – 30 nos.
Duration: a few months
- Phase 2 trials are carried out to check if the new treatment has desired effect (benefit) on a particular cancer type, to find the specific cancer types that this treatment works well on and to learn more about the side effects of the treatment.
- The benefit that the research team looks for could be tumour size shrinkage, delayed disease progression, improved quality of life, etc.
- Phase 2 trials are carried out on patients with certain cancer types only.
Subject Population: less than 100 nos.
Duration: 1 -2 years
- Phase 3 trials are carried out to compare the efficacy of the new treatment with that of the current standard treatment.
- Phase 3 study is carried out among a larger population of subjects, and it may also be carried out in multiple locations.
Subject Population: from 100 to several thousand
Duration: 1 -5 years
- Also referred to as post-marketing surveillance, phase 4 trials are carried out once the drug is approved by the regulatory body and is on the market.
- Phase 4 trials are used to evaluate a drug’s performance in real-world settings, investigate the drug’s long-term dangers and benefits, and find any unusual adverse effects.
- Phase 4 trials are carried out among varied populations across multiple geographies.
- If the researchers find anything alarming during this phase, the drug may be recalled from the market.
Subject Population: NA
Why Should Patients Take Part in Clinical Trials?
Not all patients are eligible for clinical trials. Before selecting patients, a series of tests are conducted in order to make sure they are the right candidates for a particular clinical study. Clinical trials benefit patients in multiple ways:
Access to Newer Treatment Options: Clinical trials can help patients access some of the most advanced treatment protocols even before they are on the market.
Close Monitoring by the Expert Research Team: Throughout clinical trials, the patients are closely observed by the research team, and if there is any undesirable reaction observed among the patients, they are immediately addressed. The study itself may involve numerous tests (blood tests, PET/CT scans, etc.) and appointments in order to ensure that the patient is doing okay.
An Opportunity to Help Other Patients Battling the Same Disease: By becoming a part of clinical studies, patients get an opportunity to help other future patients with similar conditions to understand and make use of new treatments that are approved through clinical trials.
Reduced Treatment Costs: The treatment expenses of patients participating in the clinical trials are borne by the clinical research sponsors.
For the first three phases, the expenses of the tests, drugs and hospitalization are borne by the sponsor of the study/pharmaceutical company.
During the fourth phase, drugs are given free of cost. The required tests and hospitalization expenses will also be borne by the sponsor during the specified duration of the study. Following completion of the study, the company will provide the drug free of cost to the patients that were part of the study but the investigation expenses (lab tests, radiology etc.) would not be paid. For more information, you can always get in touch with our research team.