Where do the drugs we take come from from chemicals? How do doctors know which drug is good for which disease? How can medications really cure a particular ailment for which they have been prescribed? Do these questions come to mind every time you buy a medicine?
Come, tell us today about the development of medicine from the beginning …
The development of medicine is called Clinical Research and has different Phases. The phases of clinical research are the steps of experiments with a health intervention in an attempt to find sufficient evidence for a process that scientists believe would be useful in medical treatment.
The pharmaceutical study begins its journey from a drug design and the discovery of a drug molecule that progresses further in animal tests and then human studies to see the drug’s efficacy.
The drug undergoes many trials: preclinical, phase 0, phase I, II, III and IV. Sometimes combined trials are also performed to reduce development time, such as Phase I / II and II / III.
Preclinical study
When the drug molecule is identified, it undergoes many in vitro tests (test tube or cell culture) and in vivo (animal) experiments. These experiments are performed to learn the preliminary efficacy, toxicity, and pharmacokinetics of various doses of the drug. Many drug molecules are designed at the same time, and these preclinical studies allow pharmaceutical companies to decide which molecule has the greatest potential in subsequent studies.
Study design:
The trials are always carried out following the set of steps, called a protocol, developed by the researchers to find the specific questions related to the medical product. Information from previous studies becomes the basis for researchers to develop the questionnaire and research objectives:
- Selection of participants
- Number of participants
- Study duration
- Controlled or not
- How and what dose will be administered
- What and when the data will be collected
- Review and analysis time
Phase 0 study
Also called microdosing trials, 10-15 human subjects are taken and single subtherapeutic doses are given to collect pharmacokinetics (package) drug data. This allows the company to decide whether or not to accept further development of the drug, based on more relevant human data rather than animal data.
Such trials exceed the speed of promising drug development by establishing whether or not the drug works in humans as expected in preclinical studies.
Once the company decides to go ahead with the development of the drug molecule, it will have to send the data from its preliminary studies to the FDA called Investigational New Drug (INDIANA) submission of applications.
Phase I Study
They are also called first-man studies, as they are the first stage of human testing studies. These are the studies that are designed to determine the maximum dose that can be administered without showing adverse effects.
Contract research organizations (CRO) conduct such studies in clinical trial clinics where medical staff provide full-time care to between 2 and 100 healthy subjects enrolled for the study and collect the data.
These studies determine the safety (pharmacovigilance), tolerability, pharmacokinetics (package) and pharmacodynamics (P.S.) of the drug. The design of Phase I studies is dose range also called dose escalation studies conducted in controlled clinics called Central Pharmacological Units (CPU).
Usually healthy subjects are recruited, but sometimes patients with terminal illnesses such as cancer and HIV and also those who have already tried and failed to improve existing drugs.
There are two divisions for the Phase I study:
Phase Ia: single ascending dose
Phase Ib: multiple ascending dose
Phase II study
More than 100 sick subjects are enrolled for a longer-term study to learn about the drug’s benefits along with its safety, which includes genetic testing. These studies are also called “proof of concept or pilot” studies.
This is the phase where drug development may fail due to toxicity or lower than expected results.
Two divisions of this phase are:
Phase IIa: Pilot study, to determine the clinical efficacy or biological activity.
Phase IIb: Dose search study, to verify biological activity with minimal side effects.
A combined trial that determines efficacy and toxicity is phase I / II trials.
Phase III study
These are pre-registration trials, which means that the data from this study is submitted to the regulatory agency through the New Drug Application (NDA) for registration. They are also called pre-marketing trials or pivotal trials.
These studies are multicenter, randomized, in a large diseased population (more than 500) with a much longer treatment duration and a short follow-up period, to determine the long-term safety and efficacy of the drug.
Even if regulatory filing is pending, patients receive the drug in the event that it is a life-saving drug until the drug can be purchased.
The “expansion of the label”, which is a drug, can treat an additional disease, other than the disease for which the drug is already approved, it can also be the reason for conducting the phase III trial.
It is said that for the FDA (United States Food and Drug Administration) and MHRA (UK Medicines and Health Products Regulatory Agency) needs at least two trials with data from successful trials to register the drug.
After these trials, the drug is approved for sale on the market.
Phase IV study
These are Post-Marketing Safety Monitoring studies that take place after the drug is registered. They are also called late-phase or confirmatory trials.
This type of study determines long-term adverse effects in a much older population over a very long period (at least 2 years). If harmful effects are found in this study, the drug is disapproved and the company has to take the drug back from the market, as it can no longer be sold.
The entire drug journey from a molecule to a commercial product takes 15-20 years.