Where do the medicines we take from chemists come from? How do doctors know which medicine is good for which disease? How can medicines really cure a particular ailment for which they have been prescribed? Do these questions come to mind every time you buy a medicine?
Come let us know 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 experimenting with a health intervention in an attempt to find sufficient evidence for a process that scientists believe would be useful in medical treatment.
Pharmaceutical study begins its journey from drug design and drug molecule discovery, moving towards animal testing and then human studies to see the efficacy of the drug.
The drug undergoes many trials: preclinical, phase 0, phase I, II, III and IV. Combined trials are also sometimes done to reduce development time, such as Phase I/II and II/III.
preclinical study
When the drug molecule is identified, it is subjected to many in vitro (test tube or cell culture) and in vivo (animal) experiments. These experiments are performed to determine the preliminary efficacy, toxicity, and pharmacokinetics of different doses of the drug. Many drug molecules are designed at once, and these preclinical studies allow pharmaceutical companies to decide which molecule has the greatest potential in further studies.
Study Design:
Trials are always carried out following a set of steps, called a protocol, developed by researchers to address 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 Attendees
- 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 administered to collect pharmacokinetics (KP) drug data. This allows the company to decide whether or not to continue further development of the drug, based on more relevant human data rather than animal data.
Such trials outpace the development of promising drugs by establishing whether or not the drug works in humans as expected in preclinical studies.
After the company decides to move the drug molecule forward in development, it must submit data from its preliminary studies to the FDA called Investigational New Drug (INDIANA) submission of applications.
Phase I Study
Also called First-in-man studies, since they are the first stage of human testing studies. These are 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 2-100 healthy subjects enrolled for the study and collect the data.
These studies determine the safety (pharmacovigilance), tolerability, pharmacokinetics (KP) and pharmacodynamics (database) of the drug. The design of Phase I studies is dose-ranging, 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: ascending multiple dose
phase II study
More than 100 diseased subjects are enrolled in a longer study to learn the benefits of the drug along with its safety, which includes genetic testing. These studies are also called “Proof of Concept or Pilot” studies.
This is the phase in which drug development can fail due to toxicity or subpar results.
Two divisions of this phase are:
Phase IIa: Pilot study, to determine clinical efficacy or biological activity.
Phase IIb: Dose-finding study, to verify biological activity with minimal side effects.
A combined trial that determines efficacy and toxicity are 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 via the New Drug Application (NDA) for registration. Also called premarket or pivotal trials.
These studies are multicenter, randomized, in a large diseased population (more than 500) with a much longer duration of treatment and a short follow-up period, to determine the long-term safety and efficacy of the drug.
Even if regulatory submission is pending, patients receive the drug in the event that it is a life-saving drug until the drug can be purchased.
‘Label expansion’, meaning that the drug can treat an additional disease, other than the disease for which the drug is already approved, may 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 Healthcare Products Regulatory Agency) needs at least two trials of successful trial data to register the drug.
After these trials, the drug is approved for sale in the market.
phase IV study
These are post-marketing safety monitoring studies conducted after the drug is registered. Also called late-phase or confirmatory trials.
This type of study determines long-term adverse effects in a much larger 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 off the market because it can no longer be sold.
The complete journey of the drug from a molecule to a product for sale on the market takes about 15 to 20 years.
