WE SPEAK A LOT ABOUT EVIDENCE MEDICINE built on the results of clinical trials – but few people understand how these studies are conducted and what they mean for the participants themselves. Some people think of a futuristic laboratory with many sensors, while others think that the research is unethical or dangerous, because you can get a placebo instead of a cure for cancer. We will tell you what mechanisms protect patients in clinical trials and why people choose to participate in them.
Who is doing the research and why
Large studies of drugs are most often carried out by pharmaceutical companies that create them – this is a must, because without studying the effectiveness and safety, no one will allow the drug to be registered. It takes about fifteen years from the moment of the creation of a new molecule to successful registration , and at various stages tens of thousands of other substances are eliminated that will not become drugs. After a long work in the laboratory, preclinical studies begin – on animals and “in vitro”, for example, on cell cultures. The standard set is the study of toxicity, effects on various organs and tissues, effects on fertility, teratogenicity, carcinogenicity and other parameters. Finally, after collecting enough data, the company begins to conduct clinical research, that is, study how a potential drug works in the human body.
This is an exciting moment for a pharmaceutical company: you can rely on theoretical data as much as you like, but no one knows how the human body will react to the introduction of a new substance. Phase I clinical trials (the earliest, including first-in-human, the very first in humans) are usually conducted with healthy volunteers. At this stage, not yet before determining the activity in the treatment of the disease, it is a question of establishing the basic safety. Phase 1 studies are the only ones that participants are paid for. Most often, young healthy men are selected for them – and for some of them, participation in research becomes an important source of income (we can talk about amounts of $ 200-300 per day).
The next phases, the second and the third, are already close to real life. The third phase of research is aimed at collecting data on the effectiveness of the drug so that it can finally be registered, therefore, patients with specific diseases participate in it. When it comes to common diseases such as asthma, the number of participants can be in the tens of thousands around the world. At the same time, to participate in the study, you do not need to be in a special laboratory – this can be suggested by the attending physician in an ordinary clinic or hospital; in Russia, studies are carried out in hundreds of medical institutions in different cities.
How to achieve ideal conditions
It’s hard to believe, but even if the research is carried out in hundreds of clinics around the world, in countries where they speak different languages and sometimes use different standards of treatment and diagnostics, all processes, procedures, data registration in the study are as standardized as possible. For this, the protocol – the main document of the study – describes the finest details; if it is necessary to measure pressure and pulse after a person has taken the medicine, then the protocol will indicate the exact time of measurement – for example, after one, three or five minutes. All this does not mean that there are no violations – but constant checks allow you to minimize the risk, and when analyzing the data, the risk of errors is also taken into account.
In clinical trials, absolutely everything that happens to the patient is recorded, regardless of whether the events seem to be “side effects” of the drug under study. A cut while shaving can be attributed to a rush, and a fracture from a fall on the street – to an unfortunate accident; but if all incidents are recorded, it may turn out that the cuts have become frequent, because the drug causes hand tremors, and fractures will be associated with increased fragility of the bones.
This is how it was found that sildenafil (a drug now used to treat erectile dysfunction) helps maintain an erection – a drug that was developed to treat angina. The cardiac effects were not very good, but patients reported an improvement in sexual function so often that it was impossible to ignore this fact. The company took on the development of sildenafil in a completely different profile – and it was a revolution in the pharmaceutical world, when everyone started talking about the industry of “lifestyle drugs.” A similar story happened with minoxidil: it was studied in hypertensive patients when it was found to stimulate hair growth; as a result, the drug was registered for the treatment of baldness.
Ethics and design
Perhaps the main myths about clinical trials are “the doctor has no idea what the patient is getting”, “you can get a placebo instead of a vital drug”, “a person may not even know that something is being tested on him.” But in reality this is not so – and if violations do occur, they do not remain hidden. The key point of any research is the informed consent of the patient; usually a person receives a multi-page document, where the study is described in simple and understandable words, and can calmly study it at home, discussing the situation with loved ones, and then ask any remaining questions to the doctor. Until the consent form is signed, no research procedures can be carried out.
As for doctors who do not know what the patient is getting, double-blind treatment really means that neither the participants nor the researchers know what kind of therapy is being given. But at the same time, all possible options are known; there may be two or more of these, and may include a placebo, investigational drug in different doses, or other known medications. It is known in advance what effects and reactions are likely to be expected. There are criteria, upon reaching which the treatment can and should be canceled, and for emergency situations it is possible to find out what exactly was used by a particular participant.
Placebo is not always used: in situations where there is an effective registered therapy, it would be simply unethical to leave the patient untreated. If no such therapy exists, but early research reveals that a new drug is clearly effective, the course of the study may be changed so that all participants receive the necessary treatment. Research is also a lot of checks: the quality of the collected data, the presence or absence of violations, and ethics are constantly monitored. If there are any important new data, they are reported to all researchers in the world, at the same time notifying the ethics committees. If changes are made to the study, patients will surely find out about them, who must again give written consent for further participation (or refuse it). Any participant can leave the study at any time without giving a reason.
Benefit and harm
All possible risks are explained to patients in advance – including the risk of unexpected adverse reactions that have never been observed before, or complications such as bruising or pain after taking blood from a vein. Each participant must receive insurance that will cover any damage caused if it occurs. Research participation fees are not paid (except for the first phase in healthy volunteers), but often compensate for, for example, transportation or food expenses while in the clinic.
Sometimes no benefit is foreseen for the patient personally – and this is also written in the form of informed consent, offering to contribute to science and, possibly, to do a useful thing for the medicine of the future. And yet, the benefits are often obvious, and not only because of the effectiveness of the new drug. Research participants receive increased attention, more regular examinations, blood and urine tests in international laboratories (blood samples from all over Europe, including Russia, can be sent, for example, to Switzerland or Belgium).
Where to look for suitable research
The main database of clinical trials around the world is clinicaltrials.gov , where you can filter your search by disease name and country; research conducted in Russia is also collected at clinical-trials.ru . Other options are websites of large pharmaceutical companies, most of which have Russian pages and the ability to search for clinical trials for specific diseases.