Phases of drug development

The development of a pharmaceutical drug can begin in many ways, from a layperson's observation about the effect of a plant on a symptom or disease, to molecular pharmacology processes, using CADD (computer-aided drug design), when a receptor for a chemical messenger is identified, sequenced, and its active site used as a template for the development of a new drug. This is a long path until the drug candidate ("medicine" is an incorrect term for pharmaceutical) reaches the laboratory bench.

Something that must be made clear is that the entire process only begins if the chemical compound or plant has some potentially profitable pharmacological effect, can be transformed into a pharmacy shelf product and gives a return on investment, as well as a lot of profit. It involves the isolation and identification of the drug, efficacy and safety tests with animals, pharmacogenetic tests, in which the effects on pregnancy (animal pregnancy), breastfeeding, development of the offspring whose mothers were exposed to the drug under test are studied, and must be performed on mice, rats, guinea pigs, dogs, pigs and primates (monkeys).

The major problem with thalidomide was precisely that they did not perform pharmacogenetic testing on monkeys, resulting in the phocomelia that affected thousands of newborns.

The pharmacogenetic phase is the most time-consuming, taking between 6 and 10 years until the drug is released to the clinical phase because the appearance of abnormalities and syndromes produced by chromosomal alterations or mutations in the offspring must be evaluated, up to at least the third generation.

Once approved for the clinical phase, the drug, which is now a test drug, will go through three controlled phases and enter a final, uncontrolled one:

• Phase I: trial with a small group of young and healthy adult men to test safety and identify potential adverse effects. In this phase, the subjects of the sample are rigorously selected, discarding those who may develop strong and dangerous "side" reactions;
• Phase II: clinical trial involving a small cohort of patients diagnosed with the disease targeted by the investigational pharmaceutical agent. The subjects in this cohort are rigorously selected, with exclusion criteria applied to individuals presenting with concomitant comorbidities.
• Phase III: multicenter clinical trial (several research centers around the world), randomized (groups with or without the disease), double-blind (when the doctor does not know if the patient is taking placebo/standard drug or the test drug) with use of placebo or standard drug (in the case of comparative efficacy trials, a drug already established in the treatment of the target disease is used - see an example here, evaluating the safety and efficacy in large groups and diverse ethnicities;
• Phase IV: Pharmacovigilance. This is the post-marketing phase of a drug, when adverse effects not observed in the previous phases usually appear because before there was a control and a selection of the subjects of the sample, whereas once placed on the market and being prescribed, anyone can receive the drug, regardless of whether or not they have a predisposition to serious effects resulting from its use.