How drugs are developed and tested
And why are some drugs so expensive
Finding a new remedy for the treatment of a particular disease is a colossal task: to develop a drug, many years of research and clinical trials are needed, and at each stage it may turn out that the expectations of scientists have not been confirmed, and the new development is ineffective. Pharmacologist Yuri Kiselyov, Ph.D., associate professor at Oslo Metropolitan University, tells about the methods by which scientists are looking for new drugs and how they check their safety.
There are several principal ways to develop new drugs. The first of them is the principle of kinship, or similarity: if we have a bronchodilator that works in a matter of minutes, and we need a longer effect, then we refine the molecule of the original drug and get a new drug with the properties we need — for example, with a longer half-life.
The second principal way is bioprospecting. We know that many molecules with interesting structures and properties can be found in animal and plant organisms, especially if these organisms live in extreme conditions — for example, in the northern seas. Bioprospecting implies that we identify various molecules in a certain tissue sample, and then select some of them according to certain parameters and test them on cell cultures in the laboratory to establish their effects and principle of action. If it turns out that one of these molecules kills a tumor cell, but does not act on a healthy one, then this molecule can potentially be used as an anti-cancer agent.
The third option is the development of medicines based on the study of folk traditions. For example, if different peoples independently use the same medicinal plant as an anti-inflammatory agent for arthritis, it is worth studying this plant: to prove that it works, and to find the compound that has a pharmacological effect.
Finally, a fourth option is possible — this is the development of a drug by target. If we know the structure of some molecular target in the cells of our body - for example, a receptor for growth factors on a cancer cell — we can try to create a molecule that would block this receptor to stop the growth of a tumor.
Stages of drug development
During the development of the drug , three stages can be distinguished: in silico, that is, computer modeling; in vitro1, that is, testing on cell cultures in the laboratory; and in vivo, that is, testing on living organisms, animal models. Then comes the stage of clinical trials already in humans, since not all molecules that work on mice, pigs or even primates will work well and safely in the human body.
In clinical trials, three phases can also be distinguished. In the first phase of the trials, a small number of healthy volunteers take part — a couple dozen people, most often men. At this stage, researchers test how the human body reacts to the developed drug, starting with very small doses and gradually increasing the concentration.
If the drug is well tolerated, the second stage comes when researchers check its effectiveness. This phase of research involves several hundred people with a specific disease or problem — for example, with high blood pressure. Researchers give them the drug in different doses or in different dosage regimens and monitor the body's response, while continuing to collect data on the tolerability and undesirable effects of the drug.
Thousands of people are already participating in the third phase, which is ideally carried out in several research centers in different countries. At this stage, for example, placebo-controlled studies using the blinding method occur, when neither the patient nor the researcher knows exactly what the patient is receiving: this allows for more objective results.
Due to the fact that drugs are more often tested on healthy men, the effect of many drugs on women, children and elderly patients is poorly studied. They try not to involve children in clinical trials, because it can be dangerous for them; older people have a slightly worse state of health, and pharmaceutical companies are afraid that their test results will not be as positive as they could be in young subjects. If women are examined, then their menstrual cycle may affect the results of the studies: certain changes in the patient's health status may be associated not with the effect of the drug, but with monthly fluctuations in the physiological functions of the body, and this may be difficult to take into account in the tests. Thus, pharmaceutical companies prefer to test their drugs on men — but because of this, the effect of such drugs on other groups of patients is poorly studied, which can lead to problems in therapy. Today, many health authorities are working to fix this problem.
At the end of clinical trials, all collected documents are sent to the appropriate regulator — for example, the Ministry of Health of the Russian Federation, the European Medicines Agency or the FDA in the USA. After analyzing the data obtained, the regulator either permits the use of the drug, or requires additional information, or refuses registration if the data on its effectiveness is not convincing or if it is not safe enough.
Sometimes there is a fourth phase — post-registration. Suppose our drug has proved itself in pre-registration trials, and there is evidence that it works, but there is no complete certainty; in this case, we are talking about a life-threatening disease against which medicines are urgently needed. In such cases, the regulator may issue conditional registration and oblige the company to conduct additional studies after the start of clinical use of the drug in order to collect data on the effectiveness and safety of the drug in real practice.
How much does drug development cost
Why are some drugs so expensive? There are both objective and subjective reasons for this. The objective reasons are that it is very difficult and costly to create drugs: according to various estimates, the development of one drug costs a pharmaceutical company in the range of 500-1200 million US dollars. So, the development cycle of a drug from a candidate molecule to registration can take about 7-10 years, and a huge team of specialists is working on this molecule. There are costs associated with each stage of development: for example, clinical trials are very expensive, partly due to the need for insurance, especially for participants in the first phase of trials who take a special risk. It is also expensive, for example, to keep laboratory animals: the requirements for the level of sterility in vivariums for laboratory animals are the most severe, and compliance with such requirements requires very large investments. In addition, legal problems are possible already at the stage of clinical use of the drug. As a result, the company is trying to set a price for the drug so that the proceeds from its sales cover not only the development costs, but also the potential amounts of risks.
On the other hand, medicines are developed by companies that usually take the form of joint—stock companies, and their main task is to make a profit for shareholders. At the same time, pricing in pharmaceuticals is very opaque, and sometimes even regulators do not understand what the gigantic, exorbitant price of a particular drug is based on. Thus, the development of a drug can be extremely costly — but if the medicine is really good, then you can make good money on it.
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